American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

A J CONFERENCE T M Proceedings of st 2 1 International Conference of Translational Medicine 0 1 You-Ping Deng1, JIanxin Gao2, Zhiqian Hu3, Zhong Li4, Guo-Tong Xu5, Gang-Ming Zou6 9 1University of Hawaii School of Medicine, Honolulu, USA 2Shanghai Jiao Tong University, Shanghai, China. 3Shanghai Changzheng Hospital, Shanghai, China 4Shanghai Cell Therapy Institute, Shanghai, China 5Tongji University, Shanghai, China 6American Journal of Translational Medicine. Honolulu, USA *Correspondence: G.M.Z. (email: [email protected])

Conference Chair: Gang-Ming Zou, MD, PhD

Conference Co-Chair: Guo-Tong Xu, PhD

Conference General Secretary: You-Ping Deng, PhD

Programs: Program A Translational Oncology (Abstract A001-A019) Program leader: Zhi-qian Hu, MD

Program B Stem cell and Regenerative medicine (Abstract B001-B012) Program leader Guo-Tong Xu, PhD

Program C Medicine and Health (Abstract C001-C013) Program leader: Gang-Ming Zou, MD, PhD

Scientific Advisors: Zhong-Chao Han (China). Zhi-Qian Hu (China), Victor Lobanenkov, PhD (USA), Organizing Committee: You-Ping Deng, PhD (USA), Cunyi Fan (China), Jian-Xin Gao, PhD (China), Zhi-Quan Hu, MD (China), Wen-Yang Hu, MD (USA), Zhong LI (China), Daniel Scherman, PhD, (France), Georges Uzan, PhD (France), Liaonan Zou, MD, PhD (China), Guo-Tong Xu (China), Gang-Ming Zou (USA),

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

Conference Committee: You-Ping Deng, PhD, Guo-Tong Xu, MD, Gang-Ming Zou, MD, PhD Finance Chair and Treasurer: You-Ping Deng PhD, Finance and Treasure Committee: You-Ping Deng PhD, Gang-Ming Zou, MD, PhD. Program Chair: Zhong Li, PhD Program Committee: Cunyi Fan, MD, PhD, Zhi-Qian Hu, MD Publication Chair: Liaonan Zou, MD, PhD Publication Committee: Daniela Capdepon, MD (Argentina), Gang-Ming Zou, MD, PhD (USA). Publicity & Public Relations Chair: Wen-Yang Hu, MD Publicity & Public Relations Committee: Jian-Xin Gao, PhD. Wen-Yang Hu, Cunyi Fan Special Guest: Joseph Green, MD, Jerris Hedges. MD Joseph Green, MD. Lt Governor. Hawaii State. USA Jerris Hedges. MD, Professor and Dean. University of Hawaii School of Medicine. Hawaii. USA Keynote Speaker: Loic Le Marchand, Professor, University of Hawaii School of Medicine Conference venue: University of Hawaii School of Medicine. Honolulu, Hawaii, USA Conference date: January 11-13, 2019 Supporting publication: American Journal of Translational Medicine Sponsor: Hawaii Gangze Inc., Publisher, Honolulu, USA

Introduction of Conference Chair

Gang-Ming Zou, MD, PhD. Professor, Editor-in-chief of American Journal of Translational Medicine

Prof. Zou is Editor-in-chief of American Journal of Translational Medicine published in Hawaii Gangze Inc (Publisher) since 2017. He has completed his medical degree (MD) from Gannan Medical University in 1985 in China, and his Ph.D. from Paris VI University in France in 2001. He also finished his postdoctoral studies from University of Chicago and Johns Hopkins University School of Medicine in USA. He once served as a Scientific Review Officer (SRO) in NIH before he moved to Shanghai in 2009. He has been listed in “Who's Who in the World, Marquis” Since 2010. He was the professor and principal investigator (PI) in Shanghai Cancer Institute, and Shanghai Institute for Pediatrics Research, Shanghai Jiao Tong University in China. He was the Chief of Section of Stem Cell Biology in the National laboratory of Oncogene and Related Genes in Shanghai Cancer Institute from 2009 to 2012. He has published more than 40 papers in reputed journals, including PNAS, Blood, Oncogene, and Stem Cells etc, His accomplishment include that he identified the relevance between Pu.1 level and early B cell development, and Redox factor Ape1 in stem cell differentiation etc. Currently, his funded research is focusing on stem cell in hearing loss repairing; and secreted Ape1 protein as a biomarker in cancer. He once served as a chair for session of stem cell therapy for liver disease (Track 4-7) in 3rd Annual World Congress of Regenerative Medicine & Stem Cells 2010 (Shanghai, China). In 2014, he returned to USA to found “American Journal of Translational Medicine” for publication through Hawaii Gangze Inc. a publisher located in Honolulu. Current he is a president and CEO in Hawaii Gangze Inc in Honolulu, USA. He was also a Professor in Nanchang University Hospital since 2015. He is the Professor, Physician, and Director of International Center of Translational

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

Medicine in Gannan Medical University in China since 2018.

Introduction of Conference Co-Chair

Guo-Tong Xu, M.D., Ph.D. Professor.

Prof. Xu is Associate Editor of American Journal of Translational Medicine published in Hawaii since 2017. He is a Professor of Ophthalmology and Pharmacology, Tongji University School of Medicine. He graduated from Harbin Medical University, and then studied in Peking Union Medical College (PUMC) Hospital in Beijing, China, where he obtained his Master and M.D. degrees. He also obtained a PhD in Pharmacology from University of North Texas Health Science Center (UNT-HSC) at Fort Wroth, Texas, US. Starting in 1994, he served, as a Research Assistant Professor, in the Dept. of Anatomy and Cell Biology, UNT-HSC. In 2001, he was appointed as research Professor in Shanghai Key Lab of Developmental Biology, Shanghai, China. Two years later, he joined the Institute of Health Sciences, Chinese Academy of Sciences, where he served as a professor, Assistant Director, Associate Director and Executive Deputy Director. Since 2008, Prof. Xu was appointed as the Executive Deputy Dean and then as the Dean of Tongji University School of Medicine (TUSM), Director of Tongji Eye Institute, TUSM, Chief PI, Department of Ophthalmology of Shanghai Tenth People’s Hospital and Principal Lecturer of Pharmacology Teaching Group. His research focuses on age-related eye diseases and stem cell-based regenerative medicine. As the PI of two Key National Basic Research “973” Projects, he plays an important role in the establishment of the stem cell bank network in China. He also served as the founding president of China Stem Cell Biology Society. Prof Xu has published over 100 research papers which have been cited more than 1000 times.

Introduction of Conference General Secretary

Youping Deng, Ph. D., Professor Prof. Deng is currently tenured professor, Director of Bioinformatics Core at University of Hawaii John A. Burns School of Medicine, as well as the Co-Director, Genomics and Bioinformatics Shared Resource, at University of Hawaii Cancer Center. Before he joined University of Hawaii in 2016, he was the Director of Bioinformatics and Biostatistics, Associate Professor, at Rush University of Medical Center in Chicago. He used to be Associate Director of Bioinformatics, Mississippi Functional Genomics Network as well as adjunct Associate Professor in the Department of Computer Sciences of Georgia State University. From 2004 to 2008, he was a tenure track assistant professor at the University of Southern Mississippi. Dr. Deng received his Ph.D. from Peking Union Medical College in 1998. He also received bioinformatics certificates in both IT and bioinformatics science from National Bioinformatics Institute and had computer science courses learning from Wayne State University. He finished his Postdoctoral training in 2002 at Wayne State University. He has published more than 200 papers in peer-reviewed

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) journals and is serving as editorial board members of 5 international journals.

Introduction of Special Guests

Josh Green, MD. Lt Governor, Hawaii State, USA Dr. Joshua B. Green (born February 11, 1970) is an American politician of the Democratic Party, who is the 14th and current lieutenant governor of Hawaii, since December 2018. He was a Hawaii State Senator 2009 to 2018, representing the 3rd district. He previously was a member of the Hawaii House of Representatives from 2005 to 2009, representing the 6th district. In 2018, Green won the Democratic primary as his party's nominee for lieutenant governor of Hawaii and was the running mate of incumbent Democratic Governor David Ige. He and Ige won the general election on November 6, 2018. Born in Kingston, New York, he was raised in Pittsburgh, Pennsylvania. He received his undergraduate degree at Swarthmore College and in 1997 received his medical degree from Penn State University. Green was elected to the Hawaii State House of Representatives on November 2, 2004 and served two terms before being elected to the Hawaii State Senate in 2008 where he previously chaired the Committee on Health and currently serves as the Majority Floor Leader, and continues to provide a leadership role statewide as Hawaii's Voice for Healthcare. Green championed the initiative to create an insurance mandate for children with Autism Spectrum Disorder and the legislation known as "Luke's Law" went into effect on January 1, 2016. He also led the charge in raising the legal age to obtain tobacco products and electronic cigarettes from 18 to 21, making Hawaii the first state to do so. In addition to his work in the State Legislature, Green is also an emergency department physician at Kohala Hospital on Hawaii Island

Jerris Hedges, MD, Professor and Dean University of Hawaii School of Medicine Prof. Hedges is Dean of the John A. Burns School of Medicine (JABSOM) since March 2008, is known nationally as co-author of one of the leading texts in patient care, Roberts and Hedges’ Clinical Procedures in Emergency Medicine, now in its sixth edition. In Hawaiʻi, he is also recognized as a leader who has strengthened the medical school by building vital bridges between JABSOM’s community partners and collaborators. In 2013, he was named “Physician of the Year” by the Hawaiʻi Medical Association. From his modest roots, Dr. Jerris Hedges personally understands how important it is that Hawaiʻi’s young people have opportunities to succeed, and how critical is the need to provide physicians and other health care workers in our rural, under-served communities. Dean Hedges and colleagues are expanding the medical school’s research focus on addressing disparities in both access to care and treatment outcomes that disproportionately affect Hawaiʻi’s citizens from certain cultural and ethnic backgrounds, especially the rural, the poor and those of Native Hawaiian, other Pacific Island and Filipino ancestry. Dr. Hedges earned his bachelor’s degree in aeronautics and astronautics, his master’s degree in chemical engineering, and his medical degree at the University of Washington. He completed his residency at the Medical College of Pennsylvania and served on the faculty of the University of Cincinnati - School of Medicine before joining OHSU. Dr. Hedges also holds a Master of Medical Management from the Marshall School of Business at the University of Southern California.

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

Introduction of Keynote speakers

Loic Le Marchand, PhD, Professor, University of Hawaii Cancer Center Dr. Le Marchand is Professor of Epidemiology and Associate Director for Ethnic Diversity at the University of Hawaii Cancer Center. He has published over 700 peer-reviewed articles mostly in cancer epidemiology and prevention. After graduating from medical school in France, he served two years as a volunteer physician in West Africa and the South Pacific before resuming his training in public health and epidemiology in Hawaii. He obtained an MPH and a PhD from the University of Hawaii School of Public Health; then, obtained a First Independent Research Support & Transition (FIRST) Award from the National Cancer Institute in 1987. Since then, he has been funded by NCI to conduct research on lifestyle and genetic risk factors for cancer at the University of Hawaii Cancer Center. His particular focus of research has been the role of biological and lifestyle factors in the etiology and progression of cancer, especially in regard to explaining ethnic/racial differences in cancer risk. He has conducted cross-sectional, case-control, cohort and intervention studies among various minority populations. He directed the Epidemiology Program at the University of Hawaii Cancer Center between 2008 and 2011. Since 2012, he has been the PI of two major projects: The Multiethnic Cohort (MEC) Study and a Program Project Grant on obesity and cancer. He is a Senior Editor for the American Association for Cancer Research journal Cancer Epidemiology, Biomarkers and Prevention since 2011. For the past three years, he has been included on the Thomson Reuters list of Highly Cited Researchers.

Introduction of Invited Speakers:

Zhiqian Hu, MD, Professor Prof. Hu is Vice President of anorectal physician branch of Chinese physician association and chairman of the professional committee of minimally invasive endoscopy. Chief and Professor of General surgery, Shanghai Changzheng Hospital. Prof. Hu is Section Editor of Translational Oncology of American Journal of Translational Medicine published in Hawaii. He has been working in clinical diagnosis and treatment of gastrointestinal tumors for more than 30 years, and is good at minimally invasive operations of gastrointestinal tumors and comprehensive treatment of complex gastrointestinal cancers. The average annual number of operations for gastrointestinal tumors (especially minimally invasive operations for gastric and colorectal cancers) was nearly 500. Taking concepts of functionalization, minimally invasive, and adhere to standardized and individualized treatment, Pro. Hu established the multidisciplinary team (MDT) of gastric and colorectal cancer in Changzheng hospital. He is one of the first surgeons performing laparoscopic total mesenterectomy (TME) plus pelvic fascia resection in the world, and in China is the first who performs nerve-guided laparoscopic radical resection of rectal cancer. His experience was published in the Ann Surg and Ann Surg Oncol. At present, Prof. Hu has a number of national and regional (Shanghai) projects with a total research funding of over 2 million yuan (RMB). As corresponding authors, he has published more than 50 articles and has 4 patents. Pro. Hu is the vice chairman of Chinese association of Chinese and western medicine perioperative professional committee, the member of committee of colorectal specialists of surgical branch of Chinese doctor association, and the chairman of Shanghai association of Chinese and western

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) medicine perioperative professional committee, etc. Meanwhile Prof. Hu is the deputy editor of the American journal of translational medicine, and the deputy editor of journal of hepatobiliary and pancreatic surgery in China.

Alex H. Chang, PhD Dr. Alex H. Chang is currently an Adjunct Professor in Tongji University School of Medicine and CEO of Shanghai YaKe Biotechnology Ltd., a R&D company dedicating to cancer cellular immunotherapy. Dr. Chang is also Associate Director of Shanghai Immunology Association Branch of Immunogenetics, Group Leader and Committee Member of the CAR-T19 Cell Research Group, Chinese Research Hospital Association Branch of Biotherapy, as well as Council Member of The Asia-Pacific Consortium of Gene and Cell Therapy. Dr. Chang obtained his Medical degree from Capital University of Medical Sciences, and his PhD degree from University of British Columbia, Canada. He worked as Postdoctoral Trainee and Senior Scientist thereafter in Weill Medical College of Cornell University and Memorial Sloan-Kettering Cancer Center, specializing in gene therapy and cancer cellular immunotherapy. Since coming back to China a few years ago, he was elected as a Member of the Pujiang Talent of Shanghai in 2012. His research has been supported by National Natural Science Foundation of China, Project 973 of National Science and Technology of China, as well as Prevention and Management of Major Chronic Non-Infectious Diseases Project of National Science and Technology of China. His research has been focused on cell-based cancer immunotherapy. His research group has established a platform technology for evaluation of chimeric antigen receptor-T cells against cancer, and is currently participating in clinical trials for the treatment of various hematological malignancies.

Huashun Li, MD, PhD Dr. Li is the founder of ATCG Corp. based in Suzhou, China. Dr. Huashun Li graduated from the Second Military Medical University in Shanghai, China in 1986. He got his master degree from the PLA General Hospital in Beijing in 1989. He was a visiting scholar in Johns Hopkins University School of Medicine, Baltimore, Maryland, USA from 1991 to 1994. He did the PhD dissertation in the laboratory of Dr. Yi Rao in the Department of Anatomy & Neurobiology from 1994 to 1999, and received his PhD from Washington University School of Medicine in St. Louis, Missouri, USA in 1999. He was a postdoctoral fellow in the laboratories of Drs. Yuh Nung Jan and Lily Jan in the Department of Physiology, Howard Hughes Medical Institute at the University of California San Francisco from 1999 to 2005. He has been an assistant professor in Developmental Neurobiology Program in the Institute of Molecular Medicine and Genetics at the Medical College of Georgia, Augusta, Georgia, USA since 2005. He was recruited to become a founding director of West China Developmental & Stem Cell Institute at Sichuan University in 2007 and has become the founding director of SARITE Center for Stem Cell Engineering Translational Medicine in Shanghai East Hospital, Tongji University School of Medicine. He found the ATCG Corp. Ltd, based in Biobay, Suzhou, China in 2013, focusing on developing “off-shelf” cell drug for cancer immunotherapy.

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

Fabin Han, MD, PhD Dr. Fabin Han is the professor and director, The Institute for Translational Medicine, Affiliated second hospital and Liaocheng Hospital in Shandong University of China. He graduated with his degrees of MD and MPH from School of Medicine, Shandong University, China. Then he got his PhD in human molecular genetics through University of Ottawa, Canada. In 1997-199, he worked as a postdoctoral fellow in molecular genetics at Texas A & M University, USA. In 2000-2006, he worked and studied as research assistant and PhD student in University of Ottawa, Canada. During the years of 2007-2010, he worked as research scientist in Stem cell program in University of Wisconsin at Madison, and Johns Hopkins University, USA. After that he moved back to China to set up his stem cell and translational research labs in Shandong University and Shandong First Medical University. He is currently working on generating induced pluripotent stem cells (iPS cells) from patients with neurodegenerative diseases and investigating the neural regeneration and autologous iPS cell-based therapy for these diseases. He has published many research papers in Peer-reviewed Journals of Stem cells, Cytotherapy, Neurology, Movement disorders, and Journal of Human Genetics. He is the committee members of Chinese neuroscience society, Chinese Society for cell biology, Chinese Neurorestoratology, Chinese Medical Doctor Association and Chinese Stem cell Engineering, Chinese Medical Association. He is the Reviewer for several SCI journals including Cell transplantation, Cyto-therapy, Scientific Reports, Clinical endocrinology and Journal of Neurorestoratology.

Changchun Cai, MD Dr. Cai graduated from the medical school of Nanchang University with a Master of Science in Medicine in 2008, specialized in gastroenterology. From 2013 to 2014, he was a visiting scholar at Johns Hopkins University School of Medicine and continued his research in gastroenterology. From 2014 to 2018, he has devoted his energy to the multidisciplinary research that incorporates clinical science, biomedical research, and AI technology. By far, he has successfully developed ten portable AI-powered diagnostic devices through collaboration with Shanghai Artificial Intelligence Research Institute, nine of which has been approved and certified by CFDA.

Yan Lei, PhD Dr. Lei received her Ph.D. in Internal Medicine from Sun-Yat Sen University in 2011. Since July 2013, she had been working as a thoracic oncologist in traditional Chinese medicine (TCM)-integrated Hospital in Southern Medical University. During these years, she has been dedicated in the clinical diagnosis and treatment of thoracic cancer, including lung, esophagus as well as breast cancer. She has begun to work in the 7th Affiliated Hospital of Sun-Yat Sen University (Shenzhen) since this August. It is worth mentioning that with the direction of Professor Yuandong Wang (pioneer of hyperthermic intrapleural perfusion in southern China), she has been devoted herself to the study of hyperthermic intrapleural perfusion on malignant pleural metastasis. In the preliminary study, her team found that hyperthermic intrapleural perfusion using 48℃ DW is as effective as but even safer than perfusion using 45℃ normal salines plus cisplatin in alleviating malignant pleural effusion. Furthermore, she established a human intrapleural hyperthermic perfusion model and analyzed the pleural malignancy treatment depth.

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

Shougang Zhuang，MD/PhD Professor, Brown University School of Medicine, USA Professor, Director, Department of Nephrology at Shanghai East Hospital, Tongji University, Shanghai, China Chair, Department of Physiology and Pharmacology, Tongji University School of Medicine; President, Former Chinese American Society of Nephrology; Vice President, World Chinese Association of Nephrologists; Vice President, Chinese Society of Renal Pharmacology; Vice President, Asia-Pacific Society of Medicine and Bio-Immunology-Nephrology; Board Member, International Association of Chinese Nephrologists. Research directions: Mechanisms of acute kidney injury and renal fibrosis and therapeutic intervention. Achievements: He has published 136 articles in peer-reviewed journals. His research has been supported by the grants from the US National Institutes of Health, the National Nature Science Foundation of China grants and the Key Discipline Construction Project of Pudong Health Bureau of Shanghai.

Chunqiao Liu, MD, PhD, Professor, Zhongshan Ophthalmic Center (ZOC), Sun Yat-Sen University, China Chunqiao Liu is a Professor of Developmental Neuroscience at Zhongshan Ophthalmic Center (ZOC), Sun Yat-Sen University, China (since 2015). Prior to joining ZOC, he held a senior staff scientist position at National Eye Institute in USA, conducting independent research sponsored by Intramural Research Program at National Institutes of Health. One of his research interests is to elucidate the role of Wnt-Frizzled signaling in retinal development and diseases. He is among scientists who first demonstrated Wnt signaling being essential for ocular development and diseases including microphthalmia and coloboma. His lab is also interested in brain development and diseases, as well as in stem cell-based neuronal regeneration. He owned his PhD in Chinese Academy of Sciences, accomplished his postdoc training at Carnegie Science and John Hopkins University and won many awards including Fogarty International Center Training Award for visiting scholars, Carnegie fellowship, NIH travel award and Graduate Student Merit Award. He is also a senior investigator of ‘Hundred People Program’ at Sun Yat-Sen University.

Joel Isaias Osorio Garcia. MD, CEO and Founder of Biotechnology and Regenerative Medicine at RegenerAge™ (www.regenerage.clinic). Vice President of International Clinical Development for Bioquark, Inc.(www.bioquark.com) and Founder and president for the Dr. Jois A.C initiative (www.drjois.com) Advance Fellow by the American Board of Anti-Aging and Regenerative Medicine (A4M), Visiting Scholar at University of North Carolina at Chapel Hill (Dermatology). Fellow in Stem Cell Medicine by the American Academy of Anti-Aging Medicine and University of South Florida. Presenting author details

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

Conference venue 1

Ala Moana Hotel, Honolulu, Hawaii

Conference venue 2

University of Hawaii School of Medicine Campus

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

ABSTRACTS

study among 1,861 healthy MEC participants Program A: Translational Oncology (median age: 69 years) who underwent a whole-body DXA and abdominal MRI to Program Chair: Zhi-Qian Hu, MD characterize overall and regional adiposity. Visceral (VAT) and liver fat, adjusted for total adiposity, A001 showed major differences by race: they were highest Using a Multiethnic Population to Characterize among Japanese Americans, lowest among African and Address Ethnic Disparities in Obesity and Americans, and intermediate among Hawaiians, Cancer Latinos, and whites. These findings are significant Loïc Le Marchand, MD, PhD since VAT and liver fat carry a higher metabolic risk University of Hawaii Cancer Center. Honolulu. USA than sub-cutaneous fat and peripheral fat. We have Abstract developed a set of blood biomarkers, which, when In addition to being key to characterizing health added to a model with age, sex, race and BMI, disparities, multiethnic studies allow the formulation significantly improves the prediction of ectopic fat, of research questions that would not originate from with AUROC of 0.93-0.97 for visceral obesity studies conducted in a single ethnic/racial group. (≥150 cm2) and 0.83-0.93 for non-alcoholic fatty Because findings from these studies are relevant to liver disease (NAFLD; ≥5% liver fat) across the five multiple populations, they are more robust and can ethnic groups. By applying the VAT prediction score be readily translated into risk stratification tools and by measuring these biomarkers in a case-control interventions. A research program on obesity and study nested in MEC, we confirmed our hypothesis, cancer based on the Multiethnic Cohort (MEC) as the score was associated with risks of breast and Study will be presented to illustrate these points. colorectal cancers, independently of BMI and other The MEC is a prospective study that has followed risk factors. 215,000 Hawaii and California residents, aged 45-75 No validated treatments exist for visceral obesity year in 1993, for development of cancer and other and NAFLD. As a first step to address the chronic diseases. It includes five main ethnic groups: propensity of Asians in our population to Japanese Americans, Latinos, whites, African accumulate fat intra-abdominally, we developed a Americans and Native Hawaiians. We showed in the lifestyle intervention to specifically reduce VAT and MEC that the association of body mass index (BMI) liver fat. Sixty volunteers of Asian descent with with cancer varies significantly across ethnic/racial DXA VAT ≥ 90 cm2 for men and ≥80 cm2 for groups. For example, the effect of BMI on breast women were randomized to either a combined cancer risk was stronger and observed at a lower intermittent energy restriction (ER) and level of body fatness in Japanese than the other Mediterranean-style (MED) diet, or to the Dietary ethnic groups. This observation led us to Approaches to Stop Hypertension (DASH) diet, for hypothesize that visceral fat carries a greater risk for three months. The IER-MED diet was superior to certain cancers than sub-cutaneous fat. This and the DASH diet in reducing both total adiposity (p = similar observations for colorectal and liver cancers 0.005) and VAT (p=0.02). Efforts to expand this were the premise for a program project grant on intervention to other ethnic groups are under way. obesity and cancer that included a cross-sectional Category: Keynote speaker

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

A002 the prediction of tumor recurrence and the selection Application of ctDNA-NGS in the assessment of of adjuvant therapy after surgery. minimal residual disease (MRD) for colorectal Category: Invited speaker cancer after surgery Zhiqian Hu, MD, PhD A003 Department of General Surgery, Changzheng The Application of Portable AI-powered Medical Hospital. the Second Military Medical University, Diagnostic Devices in China 415 S. Fengyang Road Shanghai. 200003, China Dr. Changchun Cai, MD. Email: [email protected] Professor and Director, The Institute of Digestive Abstract diseases University of Jiujiang The recurrence and metastasis of stage II and stage Jiangxi China Email: [email protected] III colorectal cancer (CRC) patients after operation Abstract have always been a difficult clinical problem. Portable AI-powered medical diagnostic devices are Currently there is a lack of accurate and specific mobile diagnostic tools based on AI technology. prediction methods. This project aims to evaluate They can help detect and collect basic clinical data the clinical value of ctDNA-NGS in the assessment from patients of a large region in a fast, convenient, of minimal residual disease (MRD) after surgerical and mobile way. Currently their major applications treatment of CRC. In this study, 517 cases of CRC include monitoring basic vital signs and testing patients who received tumor resection were included blood biomedical indexes. Their applications in in Shanghai Changzheng hospital from October China can help resolve or alleviate the following 2015 to December 2016. Excluding criteria were problems in the medical system, which include the neoadjuvant treatment or follow-up time less than12 difficulty and high cost of receiving care for patients months. 85 cases were finally included. All sample from underdeveloped regions of China, insufficient was sequenced by using Firefly-NGS technology. supply of medical devices to community and Our results showed that: (1) The mutation detection countryside hospitals and clinics, scarcity and rate and mutational map of ctDNA in preoperative disparity of medical resources to underprivileged venous blood were highly consistent with that in the patients. In addition, their application can also help database of TCGA, so as to verify the accuracy and with routine medical screening in the household and authenticity of Firefly-NGS technology. (2) contribute to the emerging internet-based medical Common clinical risk factors, such as CEA, could practices. Overall, our portable AI-powered not predict two-year recurrence. (3) ctDNA (+) and diagnostic devices can benefit individuals by abundance of postoperative ctDNA could accurately providing basic medical screenings and resolve predict the recurrence risk of patients with radical some of the current problems in the Chinese medical CRC within two years, and that abundance of system. postoperative ctDNA was an independent predictor Category: Invited speaker of tumor recurrence within two years after surgery. (4) For patients with ctDNA (-) after surgery, A004 adjuvant chemotherapy might not benefit to CRC A common pathway for the development of patients. In summary, Firefly-ctDNA-NGS can be tumor stem cells as the potential targets of cancer applied in the detection of MRD after surgery for therapy CRC, which is of clinical guiding significance for Jian-Xin Gao1,2, Lin-Feng Li1, Meng-Yao Liu 1,

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Hong-Min Lu1, Han-Yan Chen 1, Yu-Jie Fu1, Dynamic PET Imaging of Synchronous Multiple Yun-Ying Liu2 Primary Lung Cancer 1Laboratory of Tumorigenesis and Immunity, Renji Hongjun Jin, Ph.D. Hospital Clinical Stem Cell Research Center, Principal Investigator, Guangdong Provincial Shanghai Jiao Tong University School of Medicine, Engineering Research Center of Molecular Imaging, Shanghai 200217, China. The Fifth Affiliated Hospital of Sun Yat-sen 2Shanghai Evac Biotechnology Incorporation Ltd. University, Zhuhai, Guangdong Province, China Shanghai 201105, China Abstract Abstract Patients with lung cancer may present with more Whether there exist tumor stem cells (TSCs) than one primary lesion arising in the lung at the remains controversial, hampering the development same time or may develop a second, metachronous, of efficient therapeutic regimens for cancers. primary lung cancer after treatment of the initial Especially, the concept of cancer stem cell (CSCs) lesion. This is becoming a more common clinical currently used by most of the cancer researchers is issue and remains a challenge due to how these not typically represented for TSCs. Using cellular tumors are classified. Multiple primary lung cancers and molecular models established in our laboratory, (MPLC) pose a variety of clinically important we have identified a common cellular pathway and a diagnostic and therapeutic problems, which may common molecular pathway for TSC development differ from those in patients presenting with a single without limitation of cancer types. Our results have primary tumor. If tumors are determined revealed that TSC as a rare population of tumor cells simultaneously, they are called synchronous, but if represents a seed of tumorigenesis, which may the second tumor is determined after a certain time undergo at least three developmental stages, from the detection of the initial lesion, it is called including the tumor-initiating, precancerous and metachronous. In recent years, in parallel with the cancerous. However, TSC at the cancerous stage, i.e. usage of multislice computed tomography (CT) and CSC, may develop into the cancer progenitor cells positron emission tomography (PET) with (CPCs), which represent most of the proliferating 18F-fluorodeoxyglucose (18F-FDG), the incidence of cells in the tumors. These cells have probably been synchronous MPCL has increased. It is highly mistaken as “CSC”, which has caused debates important to distinguish synchronous MPLS from rigorously. In the coordination with the development both lung metastases of primary tumors and multiple of TSC from tumor-initiating stem cells (TISCs) to lung metastases of non-lung tumors. Previous PET precancerous stem cells (pCSCs), CSCs and imaging study suggested thatΔSUVmax results eventually to CPCs, a common molecular pathway obtained using 18F-FDG-PET could be used in the has been identified. A tumor-specific protein differentiation of metastasis and synchronous MPLC PL2L60, which is resulted from alienation activation from 21 lung cancer patient retrospective study, it by intragenic promotor within the host gene PIWIL2. was detected that theΔSUV results were greater in Targeting of PL2L60 significantly blocked primary synchronous tumor cases than in the tumorigenesis, suggesting a novel therapeutic target metastatic group. However, others found thatΔSUV for various type of cancers. results were not reliable to differ synchronous Category: Invited speaker MPLS from metastasis cases. Contrary to these regular static PET scans, we developed PET A005 dynamic scan protocol, which provides entire

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) cardiopulmonary organs of a full range of Abstract quantitative data, and leverages in tumor Early detection of lung cancer to allow curative metabolism and dynamic distribution of PET tracers. treatment remains challenging. Circulating tumor The purpose of this study was to investigate whether DNA (ctDNA) analysis may aid in malignancy this dynamic modeling of 18F-FDG PET/CT can assessment of lung nodules from screening imagery differ synchronous MPLS from metastasis cases. and in early diagnosis of lung cancers. Our study We have performed 0-60 min dynamic 18F-FDG enrolled 192 patients with operable occupying lung PET/CT of 7 primary lung carcinomas lesions of 4 diseases. Routine pathology revealed that 136 of MPLC and 12 regional lymph node metastasis from these lesions were cancerous and 56 benign. The 6 patients of lung cancer. The time-activity curves plasma ctDNA, white blood cell genomic DNA and (TAC) were picked up from the drawn region of tumor tissue genomic DNA of each patient were interest (ROI) in each patient regarding different analyzed by ultra-deep sequencing of the coding lesions and the reference regions. The radioactivity regions of 65 lung cancer-related genes including 29 calculated by averaging the whole voxel’s values lung-cancer-driven genes. Against the routine clinic within the ROI were used to estimate the parameter diagnosis, we conducted genetic profiling and of the model. The dynamic modeling including mutation burden analysis in ctDNA detection, 3-compartment (3TCM) and Patlak from the patients finding that the overall mutation detection were performed for parameter estimation. These sensitivity in 136 lung cancer patients by the ctDNA studies found that Ki values from Patlak modeling assay was 59%, 79%, 88% and 100%, for Stage I, II, for differentiation of synchronous (3.02 ± 0.24) III and IV, respectively. I will demonstrate the MPLC and lung metastasis (0.631±0.34) were details about the concordance between ctDNA and significant (p < 0.05). In all cases, there were tumor tissue gDNA detection, comparison of different histopathological diagnoses for those positive prediction value of ctDNA with serum MPLC. These findings suggest that in the context of protein biomarkers, and a combined model of identical background, different lung cancers in the ctDNA mutations and serum biomarkers which same individual may have distinct imaging profiles improved the sensitivity (to be 80%) and specificity and can be applied for staging, therapeutic strategies (to be 99%) of lung nodules malignancy assessment. and long-term survival analysis of lung cancer. Our study implies potential utility of plasma ctDNA test for determining lung nodule malignancy and A006 early-stage lung cancers. Assess of Benign and Malignant Lung Nodules by Ultra-Deep Sequencing of Targeted Genes in A007 Plasma Cell-Free DNA The safety, feasibility and short-term effects of Yuancai Xie, MD 1, Da Wu, MD1, Xiaohua Li, laparoscopic bursectomy and D2 radical Ph.D2, Muyun Peng, MD3, Chuanbo Xu, Ph.D2 gastrectomy outside bursa omentalis approach 1Thoracic Department, Peking University Shenzhen for advanced gastric cancer Hospital, Shenzhen, 518036, China 2Vienomics Liao-Nan Zou 1, M.D., Yaobin He 1, M.D., Guobin Biotech Co., Ltd., Shenzhen, 518053, China Chen1, M.D., Guowei Li1, M.D. 3Department of Thoracic Surgery, No.2 Xiangya 1 Department of Minimally Invasive Surgery, Zhuhai Hospital, Central South University, Changsha, Hospital of Guangdong Province Hospital of 410011, China Email: [email protected] Chinese Medicine, The second Affiliated Hospital of

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

Guang-dong University of Chinese Medicine, oncology effects equal to the LDRG. But the Zhuhai, Guangdong, China E-mail: 13423663496 procedure can obtain more lymph nodes, it may help @163.com to improve survival rate of patients with advanced Abstract gastric cancer. Keywords: Laparoscopic D2 radical Background: laparoscopic bursectomy and D2 gastrectomy (LDRG); Laparoscopic bursectomy and radical gastrectomy is technically challenging and D2 radical gastrectomy (LBDRG); Outside bursa its clinical proof is rare. This study aimed to omentalis approach (OBOA); Advanced gastric compare the safety, feasibility and short-term effects cancer (AGC). of laparoscopic bursectomy and D2 radical Category: Invited speaker gastrectomy (LBDRG) versus laparoscopic D2 radical gastrectomy (LDRG) in advanced gastric A008 cancer (AGC). Methods: Using data from a clinical Primary tumor resection in combination with database in our department, we retrospectively hyperthermic intrapleural perfusion (HIP) using analyzed the data of 68 consecutive cases 48℃ distilled water (DW) under video-assisted undergoing LBDRG in an outside bursa omentalis thoracoscopic surgery (VATS) for unexpected approach (OBOA) from August 2012 to December malignant pleural nodules in NSCLC patients: an 2016. Surgical outcomes of LBDRG were matched exploratory study and compared with those of patients who underwent Yan Lei 1, Ph.D. Weihua Huang2, MSc. Li Zhao2, classic LDRG in our department at the same time. MSc., Hongguang Liang2, MSc. , Qimeng Jin2, The Characteristic consisted of sex, gender, age, MSc., Mutao Guo2, MSc., Zelong Lin2, BSc., ASA score, BMI, tumor size, style of gastrectomy, Yuandong Wang 2, MSc. reconstruction method and histologic type. Data 1The 7th Affiliated Hospital of Sun-Yat Sen were compared between two groups. Results: The University Shenzhen, Guangdong Province, China clinic- pathological characteristics were similar in Email: [email protected] . both groups by matching. No conversion was 2Fuda Cancer hospital, Jinan University Guangzhou, recorded. Although the mean operative time was Guangdong Province, China longer in the LBDRG group than that in the LDRG Email: [email protected]. group (323.4 ± 20.70 min vs. 288.5 ± 21.76 min; p < Abstract 0.05), the number of lymph nodes dissected was Background: The treatment of NSCLC with pleural significantly more than that in the LDRG group dissemination remains controversial due to the (30.49 ± 5.41 vs. 23.2±4.87; p < 0.05), and there is unpredictable natural history of this tumor. Our no statistically difference in the rate of local preliminary study showed that hyperthermic recurrence or metastases within median two- year intrapleural perfusion using 48℃ DW is a feasible follow-up between the LBDRG group (5.9% [4/68]) and relatively safe method to control pleural and the LDRG group (8.8% [6/68]]). There is no effusion. It is reported that primary tumor resection statistically difference in the estimated blood loss, had survival benefits for patients with unexpected the average time of ground activities, the time to intraoperatively proven malignant pleural nodules. flatus, the hospital-stay and postoperative Our study is aimed to evaluate the safety and complication between two groups. Conclusions: efficacy of combining primary tumor resection with LBDRG by OBOA is technically safe and feasible HIP using 48℃ DW to treat NSCLC with for advanced gastric cancer patients, the short-term intraoperatively proven pleural dissemination.

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Methods: From February 2014 to August 2017, Yongchen Guo 1 Ph.D., Wancai Yang1,2 MD there were ten patients with unexpected 1Department of Pathology and Institute of Precision intraoperatively proven malignant pleural nodules Medicine, Jining Medical University, Jining 272067, enrolled in the trial which was approved by the China； Ethics Committee of the hospital. Primary tumor 2Department of Pathology, University of Illinois at resection in combination with hyperthermic Chicago, Chicago, IL 60612, USA intrapleural perfusion using 48℃ distilled water Email: [email protected] was performed in the participants. After primary Abstract tumor resection and tube (perfusion and drainage The serine protease PRSS8 has shown important tube) dwelling under VATS, the hyperthermic physiological and pathological functions, but its perfusion system was initiated. The thoracic cavity roles in cancer initiation and progression are unclear. was perfused at a speed of approximately 300- 400 We developed and dynamically characterized a ml/min using 48℃ DW. The perfusion process conditional knockout Prss8fl/fl, p-Villin-Cre+ lasted for 1-2 hours. Then all patients received mouse model. We found that genetic deficiency of standard adjuvant treatment based on NCCN the Prss8 gene caused spontaneous colitis and an guideline. Results: There were no perioperative inflamed rectum at an early age and caused deaths. During the hyperthermic perfusion, the intestinal tumors at a late age, which were linked to temperature of perfusion tube is preset to 48.0 ± increased intestinal cell proliferation and migration 0.2°C, and the temperature of drainage tube is 45.3 but decreased cell differentiation. Increased PRSS8 ± 0.7°C. The pulse rates before and after perfusion expression inhibited cancer cell growth and are 75±3.2 beats/min (68-126 beats/min) and metastasis in nude mice and inhibited cancer cell 114±8.5 beats/min (68-126 beats/min) respectively. migration, invasion, colony formation and tumor No severe adverse events such as lung edema, sphere formation in vitro, but decreased PRSS8 pneumonia, malignant arrhythmia was observed expression facilitated malignancies in vivo and in during the procedure and within 1 week after vitro. Gene profiling on manipulated cancer cells surgery. The median follow-up time is 38 months and intestinal epithelial cells of Prss8 mouse models, (14-56 months). The median progression- free gene set enrichment analysis and mechanistic survival time is 31 months (14-56 months). Except studies revealed that PRSS8 targeted the for one elderly patient died of heart failure 1 year Wnt/β-catenin, epithelial-mesenchymal transition, after surgery, the rest patients are still alive. and stem cell signaling pathways, which were Conclusions: Primary tumor resection in further supported by the results from the TCGA data combination with 48℃ DW may be an effective mining and validated by immunohistochemical treatment for NSCLC patients with unexpected staining on colorectal cancer tissue microarrays. In proven pleural dissemination and have an conclusion, PRSS8 is a novel tumor suppressor that encouraging impact on the patients’ long-term plays critical roles in the suppression of colorectal survival. More evidence is needed to verify the carcinogenesis and metastasis. results. Category: Oral presentation A010 A009 Identification of Key Candidate Genes and PRSS8 suppresses colorectal carcinogenesis and Pathways in Colorectal Cancer metastasis Jianjun Li1 MD, Yongchen Guo2 Ph.D., Wancai

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

Yang 2 MD, Yonghua Bao2 Ph.D. in the therapeutic effects of 5-Azacytidine on 1Department of Breast Surgery, Affiliated Hospital, AML Jining Medical University, Jining 272067, China; Wenyang Hu, PhD 2Department of Pathology and Institute of Precision University of Illonois at Chicago, Chicago. USA Medicine, Jining Medical University, Jining 272067, Abstract China；Email: [email protected] Background: P15 protein induced by TGF- Abstract negatively regulates cell cycle by inhibiting the Colorectal cancer (CRC) is one of the most common activity of Cyclin D/CDK4,6 complexes. p15 gene malignant diseases worldwide, but the involved can be inactivated by 5’ CpG island methylation in signaling pathways and driven-genes are largely their promoter regions in several hematopoietic unclear. This study integrated four cohorts profile malignancies such as AML. Inactivation of p15 gene datasets to elucidate the potential key candidate by 5’CpG island methylation blocks the negative genes and pathways in CRC. Expression profiles regulation of cell cycle by p15 gene which may play GSE28000, GSE21815, GSE44076 and GSE75970, important role in the AML. Demethylation of p15 including 319 CRC and 103 normal mucosa, were gene may therefore provide a new target for the integrated and deeply analyzed. Differentially therapies of AML. The chemotherapy agent expressed genes (DEGs) were sorted and candidate 5-Azacytidine is one of the analogs of the genes and pathways enrichment were analyzed. pyrimidine nucleotide cytosine. It interfered with the DEGs-associated protein–protein interaction process of DNA methylation, induced cell network (PPI) was performed. Firstly, 292 shared differentiation and demonstrated its clinical activity DEGs (165 up- regulated and 127 down-regulated) as a second line antileukemic agent. In this study, we were identified from the four GSE datasets. treated one AML patient with 5-Azacytidine for Secondly, the DEGs were clustered based on chemotherapy to investigate if this agent can functions and signaling pathways with significant actually demethylate and reactivate p15 gene. enrichment analysis. Thirdly, 180 nodes/DEGs were Methods: First we evaluated p15 gene methylation identified from DEGs PPI network complex. Lastly, by Eco52I enzyme digestion based-PCR. DNA the most significant 2 modules were filtered from samples from HL60 (negative control) and KG1A PPI, 31 central node genes were identified and most (positive control) cell lines, AML bone marrow of the corresponding genes are involved in cell cycle before and after 5-Azacytidine treatment were split process, chemokines and G protein-coupled receptor into two tubes. 50 ng each of Eco52I treated or signaling pathways. Taken above, using integrated untreated DNA were applied for PCR. PCR forward bioinformatical analysis, we have identified DEGs primer F1 and reverse primer R1 encompassing the candidate genes and pathways in CRC, which could Eco52I cleavage site in 5’ promoter region of human improve our understanding of the cause and p15 gene were used for PCR amplification. DNA underlying molecular events, and these candidate methylation levels were evaluated by calculating the genes and pathways could be therapeutic targets for percentage ratios of PCR product density with or CRC. without Eco52I digestion. Next, we investigated p15 Category: Poster mRNA expression by RT-PCR analysis. 1 µg each of total RNA from HL60 (positive control) cell lines A011 and AML bone marrow before and after Role of p15 gene demethylation and reactivation 5-Azacytidine treatment was reverse transcripted

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) into cDNA and 50 ng each of cDNA were applied fibers such as asbestos. Mesothelioma causes about for PCR reaction. Human beta-actin mRNA 3,000 deaths per year in the U.S. and over 100,000 expression served as internal control. p15 gene deaths per year worldwide. In the US it is estimated expression levels were evaluated by calculating the that more than 20 million people have been exposed mRNA ratios of p15 to -actin. Results: p15 gene is to asbestos and are at risk of developing MM during not methylated in HL60 cell line and almost 100% the next decades. With the lack of effective methylated in KG1A. In HL60 cell line p15 DNA strategies to diagnose, prevent and treat was completely digested by Eco52I, however, in mesothelioma, median survival is only about 12 KG1A, p15 DNA was not digested. In AML bone months from diagnosis. Therefore, novel approaches marrow, p15 DNA was not digested by Eco52I that target the onset and progression of this before 5-Azacytidine treatment indicating that the devastating malignancy are urgently needed. Recent hypermethylation of p15 gene in AML. The studies have demonstrated the importance of methylation levels of p15 gene were markedly asbestos-induced inflammation in the development decreased after 5-Azacytidine treatment. p15 mRNA and growth of mesothelioma. We identified HMGB1 expression was low in AML bone marrow before as the key initiator of this process. We discovered 5-Azacytidine treatment. Interestingly, 5- that asbestos induces cell necrosis, causing the Azacytidine treatment greatly increased p15 mRNA release of HMGB1. HMGB1 functions as the expression. Conclusion: These results indicated that “master switch” that when turned on, kick starts a in AML patient DNA hypermethylation silenced p15 series of inflammatory responses that over time may gene expression and blocked the negative regulation lead to malignant transformation of mesothelial cells of cell cycle which may trigger the pathogenesis of and mesothelioma development. We found HMGB1 AML. 5- Azacytidine treatment demethylated p15 to be significantly elevated in the sera of DNA and reactivated p15 gene expression asbestos-exposed individuals and in the sera of subsequently retarded G1/S transition of cell cycle mesothelioma patients, which suggest that HMGB1 by the combination of p15 to Cyclin D/CDK4,6 may be a biomarker for asbestos exposure or even complexes. Therefore, we conclude that for mesothelioma early detection. Moreover, demethylation and reactivation of p15 gene may mesothelioma cells are “addicted” to HMGB1 even play important role in the therapeutic effects of after the cells get transformed, and that HMGB1 5-Azacytidine on AML. contributes to mesothelioma growth and progression. Novel strategies that interfere with HMGB1- A012 mediated inflammation might prevent or delay the Gene and environment interaction in causing onset of mesothelioma in high-risk cohorts, cancer – what we have learned by studying including individuals genetically predisposed, mesothelioma and/or inhibit tumor growth. Besides the studies on Hailing Yang HMGB1, I am part of a research team lead by Dr. University of Hawaii Cancer Center. Honolulu. Carbone. We discovered that heterozygous germline Hawaii. USA BAP1 mutations predispose to malignant Abstract mesothelioma. These findings opened a new Malignant mesothelioma is a very aggressive tumor research field studying the mechanisms of and has been linked to occupational and gene-environment interaction in mesothelioma, and environmental exposure to carcinogenic mineral led to the discovery of a new cancer syndrome that

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) was named the “BAP1 cancer syndrome”. More CONCLUSIONS: Thus, the ratio-based method recently, we discovered the mechanisms of how can solve the difficult normalization problem for BAP1 mutations cause cancer development (Bononi circuiting ncRNA data to identify reliable A. et al, Nature 2017; Cell Death & Differentiation biomarkers to meet real clinical practice. 2017). A014 A013 The prognostic significance of minimal residual Early detection of cancer using innovative disease after first induction treatment in patients bioinformatics methods with adult acute lymphoblastic leukemia treated Youping Deng 1, Vedbar S. Khadka1, Junmei Ai2, with autologous stem cell transplantation Yan Li 2 Zoufang Huang, MD, Lugui Qiu, MD. 1Bioinformatics Core, Department of Department of Lymphoma Center, State Key Complementary & Integrative Medicine, University Laboratory of Experimental Hematology, Institute of of Hawaii John A. Burns School of Medicine, Hematology and Blood Diseases Hospital, Peking Honolulu, Hawaii 96813, USA Union Medical College and Chinese Academy of 2Department of Internal Medicine, Rush University Medical Sciences, China Medical Center, Chicago, IL 60612, USA Email: [email protected] Abstract Abstract Background: Recent studies have indicated that Acute lymphoblastic leukemia (ALL) is a malignant circulating noncoding RNAs (ncRNAs) such as proliferation of lymphoid progenitor cells in the miRNAs are stable biomarkers for the diagnosis and bone marrow, blood and extramedullary sites. prognosis of human diseases. However, due to low Autologous stem cell transplantation (auto-SCT) is a concentration of circulating ncRNAs in blood, data selectable approach to cure ALL. We investigated normalization in plasma/serum ncRNA experiments the prognostic significance of minimal residual using next-generation sequencing and quantitative disease (MRD) after first induction treatment in real time RT-qPCR is a challenge. Results: We patients with ALL treated with auto-SCT. ALL found that the current normalization methods based patients with minimal residual disease (MRD) by on synthetic external spiked-in controls or published flow cytometry after first induction treatment were endogenous miRNA controls are not appropriate as analyzed retrospectively. We found the proportion of they are not stably expressed and therefore, fails to high-risk immunophenotype (proB, proT, preT, reliably detect differentially expressed ncRNAs. As mature T) was higher in MRD-positive (≥10-4) an alternative of using individual ncRNAs as patients (34.6% vs. 14.5% in MRD-negative/<10-4, p biomarkers, we considered a ratio-based = 0.038). MRD positivity after induction treatment normalization method calculated as the ratio of any was associated with significantly shorter overall two ncRNAs in the same sample and used the survival and leukemia-free survival (5-year overall resulting ratios as biomarkers. We mathematically survival 72.7% vs. 47.3% in MRD- negative /<10-4, verified the method to be independent of spiked-in p = 0.004; 5-year leukemia- free survival 75.7% vs. and internal controls, and robust than existing 29.6% in MRD-negative /< 10-4, p < 0.001). reference control-based normalization methods to Multivariate analysis showed that MRD positivity identify differentially expressed ncRNAs as after induction treatment was associated with poor potential biomarkers for human diseases. outcomes. We conclude that auto-SCT could not

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) abrogates the poor prognosis of MRD positivity such therapies from Novartis and Kite having after induction treatment. received a milestone FDA approval last year. In addition, more CAR-T cell therapies have been A015 tested in clinical trials of ALL, lymphoma and CAR-T Translational and Clinical Challenges multiple myeloma with excellent results, as reported Yu Lei, M.D. / Ph.D., in recent 2018 ASH conference. We are one of the “Zijiang” Distinguish Professor, Director of the pioneer labs in China in terms of CAR-T cell Institute of the Biomedical Engineering and therapy research and have treated our first patient Technology (iBET), East China Normal University, who suffered from B cell mantle cell lymphoma in China July 2015. So far, this patient has achieved complete Abstract： remission for more than three years. In this CAR-T is a revolutionary new class of immune cell conference, we are going to present our clinical medicine for cancer immunotherapy. However, studies using CD19, CD22, BCMA targeting, as there are several clinical challenges that limited well as CD19/CD22 dual targeting CAR-T cell promotion of CAR-T applications in clinical, such therapies for various hematological malignancies. as CRS/CRES side effects, relapse, and tumor The future directions of research in CAR-T cell microenvironments. The new CAR-T technologies therapy will also be discussed. are necessary and urgent to be developed to solve Category: Invited speaker these issues. We developed several new CAR-T technologies (CAR-T2.0) that showed significantly A017 reduced CRS/CRES side effects and improved the In Situ Vaccination of monoclonal CAR-NK Cells solid tumor therapeutic effects. Translational Activates Systemic Immunity Against Tumors oncology of CAR-T is different from traditional Huashun Li, MD & PhD. medicines of small molecule, peptide, antibody, ATCG Corp. Ltd., Suzhou, China. siRNA drug and even nano-medicines, CAR-T is an Abstract individualized medicine because the T cell that Chimeric antigen receptor T lymphocyte (CAR-T) make CAR-T is from patients. Thus, there are lots technology has made remarkable success in the of challenges for making the proper formulation for treatment of hematological malignancies. However, CAR-T new drugs. In this presentation, the above its intrinsic character of the technology unlikely issues will be discussed. leads to a large-scale production of standardized and homogenous cell drugs for cancer treatment. The A016 ATCG Corp. has been pioneered on developing Progress of CAR-T cell therapy in hematological innovative “off-the-shelf” CAR-NK cell drugs for malignancies cancer immunotherapy. The ATCG research team, Alex H. Chang, PhD led by Dr. Huashun Li, has been based on natural Tongji University School of Medicine, and killer cell line NK-92 as a platform to develop over Shanghai YaKe Biotechnology Ltd., 15 CAR stably expressing NK cell lines (CAR-NK) Shanghai, China to treat different types of solid tumors. The Abstract preliminary clinical research studies have shown CD19 CAR-T cells has greatly advanced therapies that ATCG427 CAR-NK therapy yields a for relapsed/refractory B cell malignancies, with two remarkable response rate and partly persistent

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) remission in the treatment of over 80% solid tumors by fusing a PSCA-recognizing single chain antibody including but not limited to breast cancer, lung fragment, obtained through reversed genetics with cancer, renal cancer, and pancreatic cancer. In the signaling moieties of CD28, CD137 and CD3ζ addition, ATCG427 CAR-NK cells only directly kill chain. The third-generation chimeric antigen target tumor cells but also engage host NK cells and receptor PSCA-CAR was cloned in the pUC57 lymphocytes, leading to systemic activation of vector. The purpose gene PSCA-CAR was immunity against tumors. Thus, ATCG has been transferred to the parental minicircle plasmid by well positioned in the fast-growing tumor gene engineering technique, and the PSCA-CAR- immunotherapy field with the proprietary CAR-NK mcDNA carrier vector was extracted by means of technology. cultivation of ZYCY10P3S2T E. coli cells (SBI, Category: Invited speaker USA) carrying the respective parental plasmids on LB medium for approximately 15 hours, and an A018 extra 5.5 hours after adjusting the OD600 and PH PSCA targeting CAR-T cells engineered by using value within a proper range. Autologous T minicircle DNA vector inhibited growth of lymphocytes were prepared from PBMC culturing. prostate cancer in NOD/SCID mice PSCA-CAR-T effectors were produced by using Jinsheng Han1,2,3, Xueshuai Ye1,3, Pingping Du3, electroporation (LONZA) to transfer the PSCA- Ziqi Cai3, Long Shi3, Zexian Fu3, and Jianhui CAR-mcDNA plasmid into autologous T Cai1,2,3* lymphocytes. RT4 cancer cell line was used as 1Department of Surgery, Hebei Medical University, targets in the in vitro studies, and NOD/SCID mice 361 West Zhongshan Road, Shijiazhuang 050017, were used to establish the human prostate cancer China models by inoculation the RT4 cells subcutaneously 2Department of Surgery & Oncology, Hebei General for in vivo studies. Results: A significant higher Hospital, 348 West Heping Road, Shijiazhuang transfection efficiency of PSCA-CAR-mcDNA 050051, China vector was detected by FCM by means of 3Hebei NOFOY Biotech Corporation Ltd., electroporation with the efficiency of 58.69%, Hongchang Science Park of High-Tech Zone, 238 54.56%, and 59.23% respectively (triplicate). The Changjiang Avenue, Shijiazhuang 050000, China expression of CAR molecules on surface of T cells Abstract was reach up to 86.26%, 86.79%, and 82.87% Introductions: Chimeric antigen receptor (CAR) respectively (triplicate), detected by FCM, and in -engineered T cells (CAR-T) targeting prostate addition, persistent CAR expression could be cancer has emerged exciting results in preclinical persisted to the 14th day after the transfection. studies. Most of the CAR-T enrolled into clinical PSCA-CAR-T effectors have a stronger ability to trials was engineered by suing viral vectors which produce large amount of IL-2 and INF-γ cytokines might inevitably lead to several clinical safety risks when cocultured with PSCA-positive RT4 cells with such as replication of virus, bacteria reproduce, or comparison of DC induced CTLs (P<0.05). The secondary tumors. In the present study, we reported antigen-specific cytotoxicity of PSCA-CAR-T a novel technology platform for engineering of effectors was significantly higher than the normal T clinical grade CAR-T by suing non-viral minicircle cells and CTLs (p < 0.05, respectively). In vivo DNA vector aided by electroporation. Methods: An study indicated that PSCA-CAR-T effectors have a anti-PSCA CAR expressing plasmid was generated favorable capability to migrate into tumors and to

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) inhibit the tumor growth and metastasis. with advanced-stage hepatocellular carcinoma who Conclusions: Non-viral mcDNA vector technology received tumor resection or tumor resection plus platform has a significant benefit in preparation of pa-TACE as an initial therapy, was conducted to clinical grade CAR-T in view of its clinical safety, assess the effects of microRNA-4651 on pa-TACE higher transfection efficiency, higher and persistent treatment. MicroRNA -4651 expression in tumor CAR expression, and valuable antigen specific tissues was tested using TaqMan-PCR technique. cytotoxicity of CAR-T produced by using the The sensitivity of tumor cells to doxorubicin (an platform. anti-cancer drug used in pa-TACE procedure) was analyzed by the half- maximal inhibitory A019 concentration (IC50). Results: Upregulated MicroRNA-4651 (miR-4651) serves as a microRNA-4651 expression in tumor tissues can biomarker for selecting post-operative adjuvant improve the therapeutic response of patients with transarterial chemoembolization therapy hepatocellular carcinoma on pa-TACE [hazard ratios (pa-TACE) for hepatocellular carcinoma patients (95% confidence intervals) = 0.32 (0.22-0.46) for (HCCs) death risk and 0.39 (0.28-0.56) for tumor-recurrence Tian-Qi Zhang1, Qun-Qing Su1, Xiao-Ying risk, respectively], but down- regulated expression Huang1, Jin-Guang Yao1, Chao Wang2 Qiang Xia3, cannot. Functional analyses displayed microRNA- Xi-Dai Long1,3 4651 mimics decreased while its inhibitor increased 1Department of Pathology, the Affiliated Hospital of the IC50 of tumor cells to doxorubicin [0.65 Youjiang Medical University for Nationalities, Baise (0.61-0.69) vs. 2.17 (1.98-2.37) µM]. Cytochrome 533000, China. P450 2W1 was shown as a possible target of 2Department of Medicine, the Affiliated Hospital of microRNA-4651. Additionally, dysregulation of Youjiang Medical University for Nationalities, Baise microRNA-4651 also affected the clinical 533000, China. pathological features of hepatocellular carcinoma 3Department of Liver Surgery, Ren Ji Hospital, and was an independent prognostic factor for this School of Medicine, Shanghai Jiao Tong University, cancer. Conclusion: These results indicate that Shanghai 200127, China. increasing microRNA- 4651 expression may be Corresponding author: Xi-Dai Long, Department beneficial for pa-TACE improving hepatocellular of Liver Surgery, Ren Ji Hospital, School of carcinoma prognosis. Keywords: microRNA-4651; Medicine, Shanghai Jiao Tong University. No. 1270, pa-TACE; hepatocellular carcinoma; prognosis Dongfang Rd., Shanghai 200127, China. Email: [email protected]. Program B: Stem cell research and Abstract Aims: Previous reports have shown that microRNA Regenerative medicine -4651 is a potential early diagnostic and prognostic marker for hepatocellular carcinoma. We aimed to investigate whether microRNA-4651 modified Program chairs: Guo-Tong Xu post-operative adjuvant transarterial chemo- embolization (pa-TACE) improving the prognosis of B001 hepatocellular carcinoma. Methods: A hospital- Treatment of retinal degeneration with more based retrospective study, including 302 patients precise stem cell-based approaches

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

Haibin Tian, Qingjian Ou, Caixia Jin, Furong tested for their effects in the intervention of retinal Gao, Lixia Lv* and Guo-Tong Xu* degeneration in rats. They protected the retinal Shanghai Tongji University. Shanghai. China. structure and function but the mechanisms were Abstract significantly different from those of MSCs. It is Dept. of Ophthalmology of Shanghai Tenth People’s clear that, in order to achieve better treatment effects, Hospital, and Lab of Clinical Visual Science of more precise approached for stem cell therapy Tongji Eye Institute, and Dept. of Pharmacology should be taken in treating retinal degeneration and Tongji University School of Medicine, Shanghai, other diseases in similar nature. China * Co-corresponding authors Retinal degeneration is the leading cause of Category: Invited speaker blindness in the world and lacking of effective treatment. Stem cells or stem cell-derived donor B002 cells are expected to protect or rescue the visual Transplantation of adipose-derived stem cells function in such patients. However, the outcomes of preconditioned with mechanical stretch the reports varied even when the same type of stem accelerates impaired wound healing cells was tested. We thought that the inconsistency Qingfeng Li, M.D., Ph.D. Bin Fang, M.D. could be associated with the heterogeneity of donor Department of Plastic and Reconstructive Surgery, stem cells and examined such hypothesis by Shanghai Ninth People's Hospital, Shanghai Jiao comparing different stem cell subsets in both Royal Tong University School of Medicine, Shanghai College of Surgeons (RCS) rats and sodium iodate 200011, People’s Republic of China (SI)-treated rats. The results showed that Email: [email protected] subpopulations existed in both bone marrow Abstract mesenchymal stem cells (MSCs) and umbilical cord Previous studies have shown the therapeutic MSCs of rat and human. The subsets of MSCs potential of adipose-derived stem cells (ADSCs) in showed different biological behavior and therapeutic wound healing. However, poor viability and high effects. Expected treatment effects were obtained mortality of transplanted stem cells have restricted only when the proper subsets were transplanted. We the wide application of ADSCs. Mechanical stretch propose that different subpopulations of MSCs are is a known modulator of self-renewal and not the same type of cells and some subsets may not differentiation for many kinds of cells. In this study, be really stem cells. Therefore, it is probably true we found that mechanical stretch promoted the that only the proper subtypes of these MSCs could cellular viability, proliferation and migration, but effectively treat the diseases like retinal inhibited apoptosis of ADSCs. And the effects of degeneration. In addition, we combined gene mechanical stretch were maintained under static therapy with stem cell therapy in treating SI-induced conditions after the cessation of the stretch stimulus. rat retinal degeneration, and found that the Importantly, preconditioning with mechanical combination of MSCs and the EPO they expressed stretch allows better therapeutic efficiency of demonstrated improved therapeutic effects. The ADSCs in diabetes wound environment of db/db expression of EPO gene could be controlled by a mice and thus accelerates the wound healing process. Tet-Off/Tet-On system so that the EPO could be The molecular mechanisms that provide the released on demand. Other adult stem cells like beneficial effects of mechanical stretch were adipose-derived stem cells (ADSCs) were also connected with the upregulated expression of

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

PI3K/AKT and MAPK/ERK signal pathway and the disease modeling will also be discussed. Our next increased secretion of growth factors which can target is to generate reprogrammed kidney organoid promote skin regeneration and enhance wound through a more efficiency way and apply it to healing in vivo. Taken together, precondition by elucidate the renal disease researching and even mechanical stretch on ADSCs promotes survival, migration, and therapeutic efficiency, which will B004 bring new insights into the treatment of impaired Repair pathway of spermatogonial stem cells wound healing. DNA double strand break following X-ray irradiation: NHEJ or HR? B003 Lixin Qi, MD, Wei Le, MD, Jun Xu, Ph.D, Jinfu Sall1 is essential for cell reprogramming towards Zhang* Ph.D. embryonic nephron progenitor: a more effective *Department of Urology, Tongren Hospital, way for future application? Shanghai Jiaotong University School of Medicine, Qing Jiang, Ph.D. M.D. Shanghai, PR China. Nephrology Department, The 1st Affiliated Hospital Email: [email protected] of Nanchang University, Nanchang P.R. China Abstract Email: [email protected] DNA double strand break (DSB), can be caused by Abstract many factors in the nature. DNA DSB is very toxic Sall1 as a Zinc-finger transcriptional factor is to our genome, endangering the integrity of our considered essential for embryonic kidney genetic information. Spermatogonial stem cells development. Simultaneously, recent researches (SSCs) are the progenitor cells of sperm. DNA DSB further indicate its role in maintaining the nephron in SSC threats the capability of sperm generation in progenitor pools during embryogenesis. Our group males, subsequently affects the health of the is mainly working on demonstrating the Sall1’s role offspring. However, the precise DNA DSB repair in adult cell direct reprogramming towards nephron pathway in SSC is still not fully illustrated. In the progenitors, which includes: 1) The relationship of current study, it was designed that DNA DSB in Sall1 among those identified essential genes in murine SSC was induced with X-ray irradiation in induction of nephron progenitor. 2) The use of Sall1 vitro. Western blotting and immunofluorescence in directing adult cells to reprogram towards labeling were applied to determine the critical nephron progenitor in vivo. I would like to introduce proteins involved in DSB repair pathways. my previous works and results in understanding the Furthermore, NHEJ/HR pathway choice reporter mechanism of the embryonic kidney development. system was applied to confirm the activities of these Meanwhile, our present work and progress on cell two pathways, using flow cytometry. Our data reprogramming will also be discussed, which demonstrated NHEJ pathway was used during includes some unpublished data about efficiency mouse SSCs DNA DSB repair. Our data may improvement of nephron progenitor formation via provide some insight in understanding SSCs DNA Sall1 expression in HK2 cells and the relationship DSB repair, and might also provide some clues in between Sall1 and Six2, another key player in treatment for male fertility decrease and infertility nephron progenitor direct reprograming. At the end caused by DNA DSB. of my presentation, the future use of reprogrammed nephron progenitor in regenerative medicine and B005

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

Treatment of the patient in persist vegetative study, we developed a new method to increase the states (PVS) with hNSC conversion of neural stem cells and dopamine Mingwei Chen, PhD neurons from iPSCs of PD patients, by addition of Beijing Yulong Shenghi Biotechnology Ltd, China the growth factor cocktail containing noggin, Email: 1370157115qq.com CHIR99021, SHH, FGF8, TGFβ, GDNF and BDNF. Abstract In the presence of these growth factors, the iPSCs Here we report on the effective of the human neural showed a high-efficient DA neuronal conversion in stem cells for treating the patient in persist vitro. Then we transplanted the iPSCs-derived vegetative states (PVS), which is the one of the neural stem cells with the growth factor cocktail into world's rare diseases. The method we use was to the lesion side in the midbrain of 6-OHDA-treated accurately transplant the neural stem cells extracted rats as the model of PD. As a result, iPSC-derived from human tissue into specific parts of the patient's NSCs also showed a highly efficient DA neuronal brain by the non-frame stereotactic surgical robot. conversion in vivo. Both the grafted iPSC-NSCs and Over the past 3 years, we had been treating ten of the differentiated dopaminergic neurons survived PVS patients, and four of them were awakened. All and integrated into the host rat brains 16 weeks after of the four have restored their hearing and the transplantation. The iPSC-NSCs-derived neural cells response to voice, and the motor capacity of the displayed the same electrophysiological profile as limbs has been gradually restored. Age of the four DA neurons in vivo. More importantly, rats with wakened are 17, 19 and 64 years old. We will be transplanted iPSC-NSCs showed progressive further trying to restore the study of patients ' improvements in motor behaviors compared to language function. Our results showed that the controls from weeks 4 to 16 post-grafting. In neural stem cells extracted from human tissue have a addition, the GBA-mutated iPSCs are corrected with significant effect on the treatment of the rare disease CRISPR/Cas9 gene editing and induced to convert in the world, such as the PVS. to the dopaminergic precursors for transplantation study. These results demonstrated the efficacy and B006 clinical application of combined transplantation of Transplantation of Patient-specific Induced growth factor cocktail and iPSC-NSCs in Pluripotent stem cell-derived neural cells 6-OHDA-treated rats and provided experimental ameliorated motor defects of 6-OHDA-induced evidence for cell-based therapy of PD. Rat Model of Parkinson’s disease Category: Invited speaker Fabin Han，M.D., Ph.D. The Institute for Translational Medicine, Shandong B007 University/Liaocheng Peoples Hospital, Shandong, Human umbilical cord-derived mesenchymal China. stromal cells deliver systemic oncolytic reovirus Abstract to treat chronic myeloid leukemia Patient-specific induced pluripotent stem cells Yusi Liu, Chen Li, Jianwei Xu, Jiao Jin, Xing (iPSCs) have great therapeutic potential for Zhao, Zhixu He*, Liping Shu* neurodegenerative diseases such as Parkinson’s Department of Immunology, Guizhou Medical disease (PD). However, the therapeutic efficacy and University, Guiyang 550004, China; Tissue mechanisms of dopamine neuronal conversion from Engineering and Stem Cell Research Center, iPSCs have not been clearly determined. In this Guizhou Medical University, Guiyang 550004,

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

China; Laboratory Animal Center, Guizhou Medical Wang1, Jing-Ying Xu1,2, Weiye Li1,2,4, Haibin University, Guiyang 550004, China. Tian1,2, Caixia Jin1,2, Juan Wang1,2, Jieping *Email: [email protected] Zhang1,2, Jingfa Zhang1,2*, Lixia Lu1,2*, Guo- Abstract Tong Xu1,2* Oncolytic virus (OV) preferentially infects and lyse 1Dept. of Ophthalmology of Shanghai Tenth’s transformed cells, leaving normal cells relatively People Hospital and Tongji Eye Institute, Tongji unharmed. Oncolytic virotherapy may mediate University School of Medicine, Shanghai, China antitumor effects via direct oncolysis. Reovirus (Reo) 2Dept. of Regenerative Medicine and Stem Cell is under investigation as an oncolytic agent Research Center, and Dept. of Pharmacology, Tongji following observations that in tumor viral infection University School of Medicine, Shanghai, China leads to cell lysis. Despite this, the necessity to 3College of Medicine, Qingdao University, and shield Reo3 from neutralizing antibody during Qingdao Eye Hospital, Shandong Eye systemic delivery has not been appropriately Institute, Shandong Academy of Medical Sciences, addressed. Human umbilical cord-derived Qingdao, China mesenchymal stromal cells (hUC-MSCs) are 4Dept. of Ophthalmology, Drexel University College nonhematopoietic cells with the capacity to of Medicine, Philadelphia, USA. self-renew and differentiate into cell lineages of Abstract mesenchymal origin. Using a human in vitro system, PURPOSE. To study the effects of poly (ADP- this study investigates hUC-MSCs deliver systemic ribose) polymerase (PARP) activity on secondary oncolytic reovirus to treat chronic myeloid leukemia, photoreceptor (PR) death caused by RPE the innate immunological consequences of reovirus degeneration and develop a more effective strategy therapy and its potential to activate antitumor in cell-based therapy for treating retinal activity. hUC-MSCs were used to efficiently deliver degeneration (RD). METHODS. Antibody against Reo3 in a systemic xenograft model of CML. In the poly (ADP-ribose) (PAR) was used in Western blot presence of antibody, live cell imaging demonstrated (WB) and immunohistochemistry to examine the a viral hand off between hUC-MSCs and CML total PARP activity in retina and RPE of Royal K562 targets. In a murine model of carried K562 College of Surgeons (RCS) rats and SD rats. PBS. cells, with Reo treatment was abrogated by passive PARP inhibitor PJ34, ARPE-19 and ARPE-19 plus immunization with high-titer human anti-Reo3 PJ34 were separately injected into subretinal spaces antibody. Importantly, no such abrogation was seen of 3-week-old RCS rats. Electroretinography (ERG) in immunized mice receiving Reo3 delivered by was performed to test the retinal function. The hUC-MSCs. Our data support the use of hUC-MSCs amounts of apoptotic PRs were examined by as cellular carriers for Reo3 in patients with CML. TUNEL assay. Thicknesses of the retinal layers were Category: Invited speaker evaluated at 2 or 6 weeks after treatments. RESULTS. The PARP activity was found to B008 participate in secondary PR death, and subretinal Inhibition of PARP activity ameliorates injection of PJ34 delayed RD progress. Furthermore, photoreceptor death and improves therapeutic when PJ34 was given with ARPE-19 cell during the effect of ARPE-19 transplantation in RCS rats transplantation, they significantly reduced the Furong Gao1,2＃, Zongyi Li3＃, Peng Li1,2, Yiting amounts of apoptotic PRs and evidently improved Yang 1,2, Qingjian Ou1,2, Chunpin Lian1,2, Fang vision as represented by b-wave amplitudes on ERG.

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

Such therapeutic effects of the combined treatment AMSCs (AMSC-CM) were topically administered lasted longer as compared to ARPE-19 or PJ34 to mice with EAC, and symptoms and biological treatment alone. CONCLUSIONS. This study changes were evaluated. The cultured murine bone demonstrated that PARP was hyper-activated in PR marrow–derived mast cells (MCs) and conjunctival death secondary to RPE degeneration. Combined epithelial cells were used for mechanistic study. treatment of PARP inhibitor (like PJ34) and RPE Results: Topical instillation of AEC-CM cell (like ARPE-19) transplantation could achieve significantly attenuated the symptoms of EAC, significantly improved and prolonged therapeutic alone with a significant decrease in inflammatory effects, providing a new approach for treating RD cell frequency, in production of TNF-α, IL-1β and such as age-related macular degeneration (AMD). IL-4, in NF-κB expression, and IgE release. AEC-CM also decreased IL-4 and IgE production B009 and activation by MCs, and conjunctival vascular Conditioned Medium from Human Amniotic hyperpermeability. The AEC-CM-mediated Epithelial Cells Attenuates Allergic antiallergic effects in EAC were abrogated by Conjunctivitis through IL-1 RA/IL-1R/Th2 antibodies against IL-1 RA and IL-10. Topical Pathways instillation of IL-1 RA and IL-10 also significantly Binxin Wu1, Furong Gao1, Huiming Xu2, Lixia Lu1,3, attenuate EAC. These were confirmed by in vitro Guo-Tong Xu1,3* study that neutralized AEC-CM failed but IL-1 RA 1Department of Ophthalmology of Shanghai Tenth could decrease TNF-α, IL-1βand IL-4 production Hospital, Tongji Eye Institute, Tongji University and NF-κB expression in MCs and conjunctival School of Medicine (TUSM), Shanghai, China; epithelial cells in EAC. Conclusions: AEC-CM can 2Laboratory of Clinical Visual Science, Department inhibit EAC symptoms and pathology through IL-1 of Regenerative Medicine and Stem Cell Research RA-dependent antiallergic mechanisms and support Center, and Department of Pharmacology, TUSM, the instillation of AEC-CM as a potential strategy China; for treating allergic conjunctivitis. 3State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research B010 Center, Ren Ji Hospital, School of Medicine, Induction of hUC-MSCs into RPE like cells and Shanghai Jiao Tong University, Shanghai, China; evaluation of their therapeutic functions on RD Abstract animal model Background: Perinatal mesenchymal stem cells Haibin Tian, Qingjian Ou, Caixia Jin, Furong (MSCs), such as amniotic epithelial cell (AEC) and Gao, Lixia Lv* and Guo-Tong Xu* amniotic mesenchymal stromal cell (AMSC), show Dept. of Ophthalmology of Shanghai Tenth People’s vast potential in immunomodulatory and Hospital, and Lab of Clinical Visual Science of anti-inflammatory functions. Objective: To explore Tongji Eye Institute, and Dept. of Pharmacology the potential involvement and clinical application of Tongji University School of Medicine, Shanghai, perinatal MSC in treating experimental allergic China conjunctivitis (EAC) and its underlying mechanisms. Abstract Methods: The murine EAC models were generated The etiology of retinal degeneration (RD) involves with short ragweed (SRW) pollen. Conditioned the progressive and eventual death of photoreceptors medium from human AECs (AEC-CM) and human and retinal pigment epithelial (RPE) cells. Human

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) umbilical cord-derived mesenchymal stem cells Abstract (hUC-MSCs) possess great plasticity and are able to South Korea has achieved a significant progress in differentiate into a variety of cell types. This study commercializing Regenerative Medicine since the aimed to establish the method for differentiation of first cell therapy product approved by the Ministry hUC-MSCs into RPE cells, and clarify the functions of Food and Drug Safety (MFDS) - the Korean and mechanisms of hUC-MSC treatment of RD regulatory authority, in 2001. Currently, there are 16 diseases. hUC-MSCs were induced into RPE-like cell therapies and 1 gene therapy in the market cells by conditioned media from porcine RPE plus including 4 stem cell therapeutics, the first of which retinoic acid (RA), Activin-A and bone was market-approved by MFDS in 2011. morphogenetic protein-7 (BMP-7) or by MEDIPOST utilizes platform isolation and transcriptional factors. The functions of RPE-like expansion technology of human Umbilical Cord cells on RD were evaluated by transplantation of Blood-derived Mesenchymal Stem Cells (hUCB- cells into subretinal space of SD rats pretreated with MSCs) for manufacture of off-the-shelf allogeneic sodium iodate (SI). Results showed that RPE-like stem cell products. The world’s first, regulatory- cells could be obtained from hUC-MSCs when approved allogeneic stem cell product named cultured in RPE conditioned medium plus RA, CARTISTEM® for the treatment of knee Activin-A and BMP-7. RPE-like cells exhibited Osteoarthritis was market-approved in Korea in polygonal morphology. However, the expression 2012 following Phase 1/2 and Phase 3 clinical levels of RPE specific markers were lower in these studies conducted in Korea. Since the product differentiated cells. Induced by retina and RPE launch in 2012, over 10,000 commercial patients (as development related transcription factors, hUC- of December 2018) have received the treatment in MSCs could be transformed into RPE-like cells Korea with excellent safety and efficacy profile well (iRPE cells), which expressed RPE specific markers, established on the market including the 600-patient exhibited phagocytic functions and polarity. In Post Market Surveillance (PMS). CARTISTEM® addition, iRPE cells showed stronger vision rescue has also completed US FDA IND Phase 1/2 clinical function in SI-induced RD rat model, which may study with confirmation of safety and efficacy on provide proper cells for clinical treatment of patients U.S. patients. MEDIPOST’s commercialization with RD disease. experience with CARTISTEM® will be shared * Co-corresponding authors case-study on the second product PNEUMOSTEM® for the prevention of Bronchopulmonary-Dysplasia B011 (BPD) in premature infants including preclinical Commercialization of Allogeneic Cord proof-of-concept studies and the clinical study Blood-derived Mesenchymal Stem Cell Therapy design with outcomes. PNEUMOSTEM® has Products CARTISTEM® for Knee Osteoarthritis completed Phase 1 study in Korea and Phase 1/2 & PNEUMOSTEM® for Bronchopulmonary- study in the U.S. with confirmed safety profile with Dysplasia (BPD). strong efficacy signals. Currently double-blind Antonio Lee placebo-controlled Phase 2 clinical study is ongoing Global Head of Business Development at in Korea. MEDIPOST (KOSDAQ: 078160; Seoul, Korea) CEO and Managing Director at MEDIPOST B012 America Inc. The use of Bioquantine® and allogeneic

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Mesenchymal Stem Cells combined with a spinal inflammatory diseases because of their cord stimulation system in a No Option patient immunosuppressive and tissue repair properties. with ASIA-A classification. Moreover, their immunosuppressive properties and Joel Isaias Osorio Garcia, MD, Sergei Paylian low immunogenicity contribute to a reduced or PhD, Ale Ismael Gonzalez Cazares, MD weakened immune response elicited by the RegenerAge SAPI de CV - Bioquark, Inc. Mexico. implantation of allogeneic MSCs compared with Abstract other cell types, allogeneic MSCs are a promising In 1973 the American Spinal Injury Association option because of their low immunogenicity and made the International Standards for Neurological immunosuppressive and tissue repair capabilities. Classification of Spinal Cord Injury (ISNCSCI). In The positive findings throughout the evolution of this clinical review our patient was classified after our protocol for spinal cord injury with the obtained the vertebral fixation surgery with a ASIA-A scale results at this stage is a promising scientific based injury after suffering a fracture and luxation at and evidence-based medicine protocol that can be T-12-L1, having total spinal cord section. Based on offered in the near future as an option for severe SCI the research made by Sergei Paylian, PhD on animal patients. The functionality of the RestoreSensor® models and the safety use of allogeneic MSCs SureScan® by providing the electric stimulation demonstrated on multiple animal models fortifies the medical outcome and has given the applications, we decided to apply a experimental patient the confidence to perform his physical translational medical protocol based the research rehabilitation with more energy for a longer time by and the previous outcomes obtained by Hamid and the increase or decrease of the intensity of it MacEwan and decided to customize it exclusively to according to the type of exercise regulated by the our patient based on the clinical evidence and control-battery he handles. At this date, after 8 personalizing the therapy on evidence. The medical intrathecal applications of allogeneic MSCs and team designed an ambulatory method utilizing a Bioquantine® in situ combined together we have got C-arm to apply the allogeneic MSCs in situ and the following outcomes: an improvement in using a intrathecal (subdural) catheter using a slow sensitivity, strength in striated muscle and smooth pump release system for the rest of the biological muscle connection by increased muscle mass and material with an optimum tolerance and minor side sphincter control, at 23 months after the first effects (mild fever, miyalgias and headache) on the regenerative therapy and 12 months after the first 48hrs hour after application. The experimental placement of RestoreSensor® the patient is showing use of mRNA Bioquantine® was well tolerated with an evident improvement on his therapy of physical its purified form (intra and extra-oocyte liquid rehabilitation (legs movement and control of them) phases of electroporated oocytes showing to be well having the following movements reported by the tolerated by the patient without any anaphylactic physical therapist: a) hip: adduction and external reaction. The current clinical report is meant to rotation, extension, abduction, internal rotation; demonstrate the beneficial changes with the use of b)knee: flexion; c)toe: MP and IP extension, also Bioquantine® and its administration in a patient reporting an easier and functional crawling forward with a severe SCI offering a possible optional and backwards, and since 3 months ago the patient therapy and potential neuroregeneration in this is capable to stand on his knees for 2 or more clinical condition. Mesenchymal stem cells (MSCs) minutes without any support and taking small steps are ideal for cell-based therapy in various on his knees forward and backwards for the first

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) time in his process, showing a progressively hereas OCD genes enrich in adult and parietal cortex important functionality on both limbs, voluntary . In embryo brain, OCD genes show specific express movement at both feet and an increase in sensory ion in interneuron; but in adult brain, specific expres perception. Conclusion: As we are probing in the sion are observed in excitatory neuron. CNV genes o case, combinatorial biologics can be used safely f the two disorders show distinct PPI co-expression with other electronic disposals and bring a major patterns, both in period×region and in region×cell ty benefit to SCI patients. With this unique pe intervals. We demonstrated that genes associated combination we can give an option to those No with TS and OCD affect similar brain functions in di Option patients and create many more to improve fferent region and cell types at different period, thus patients’ quality of life. inducing distinct phenotypes.”

C002 Program C: Medicine and Health Chronic restraint stress-induced depression-like Program chairs: Gang-Ming Zou behavior is mediated by up-regulation of melanopsin expression in C57BL/6 mice retina C001 Yingmei Fu1, Shunying Yu1, Qingqing Xu1, Integrative Analysis Revealed Convergent and Di Xiaoyun Guo1, Yi Dong2 vergent Roles of Different Types of Mutations in 1Shanghai Key Laboratory of Psychotic Disorders, Obsessive Compulsory Disorder and Tourette Shanghai Mental Health Center, Shanghai Jiao Tong Syndrome University School of Medicine, Shanghai, 200030, SHUN YING YU, MD, China Professor, Shanghai Mental Health Center, Shanghai 2Key Laboratory of Adolescent Health Assessment Jiao Tong University School of Medicine, Shanghai, and Exercise Intervention of Ministry of Education, China East China Normal University, Shanghai 200241, Email: [email protected] China Abstract Email: [email protected] “Obsessive compulsory disorder (OCD) and Tourett Abstract e syndrome (TS) are severe neurodevelopmental dis Emerging evidence from both clinical data and orders with overlapping genetic factors, similar phen animal models suggests that depression is associated otypes and high comorbid rate. By applying integrati with circadian disturbances in which melanopsin ve bioinformatic approach on three types of mutatio was a key mechanism. Further studies have n genes (copy number variation, CNV; de novo muta demonstrated that melanopsin gene variations are tion, DNM; single nucleotide polymorphism, SNP) associated with some depressive disorders and of TS and OCD, we found that mutation rate and PP aberrant light can impair mood through I characteristic are varied among mutation types and melanopsin-expressing retinal ganglion cells the two kind disorders. Enrichment of TS and OCD (mRGCs). However, both the direct relationship genes in different brain function gene lists show stro between depression and melanopsin and the ng positive correlation. Moreover, the enriched GO- direction of causality are still unclear. Here, we BP terms of TS and OCD genes are largely overlap. show that the melanopsin expression up-regulate in TS genes are preferentially expressed in prenatal, do mRGCs of chronic restraint stress (CRS)-treating rsal thalamus, parietal cortex and occipital cortex, w mice which exhibit depression-like behavior and the

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) frequency of blue light-induced action potentials and overloaded cellular hepatic steatosis model, HCBP6 light-induced glutamate release mediated by gene and protein expression were significantly melanopsin also increase significantly. Moreover, induced by lipid overload in time- and we find that the apoptosis of the mRGCs blocks dose-dependent manners. Furthermore, we found CRS-induced depression-like behavior of mice that the level of TG is influenced by suggesting that melanopsin is the upstream of HCBP6-SREBP1c mediated fatty acid synthase depression-like behavior. Finally, we find that this (FASN) expression. We also able to demonstrated change of melanopsin is mediated by the that microRNA-122 (miR-122) participate such a CRS-induced glucocorticoid. These data suggest process by inhibiting both mRNA and protein that CRS may induce the depression-like behavior in expression of HCBP6. Taken together, we, for the mice via glucocorticoid-melanopsin pathway. Our first time, provide new evidence that miR-122 findings provide a novel mechanistic link between regulated HCBP6 working as a sensor protein CRS-induced depression and melanopsin. maintain intra-hepatocyte TG levels. Keywords: chronic restraint stress; depression; Keywords: TG sensor, TG down-regulator, Micro melanopsin; mRGCs; glucocorticoid RNA-122, TG metabolism, Promoter Category: Invited speaker C003 Hepatitis C virus core-binding protein 6 (HCBP6) C004 oscillates triglyceride homeostasis in hepatocyte FRIZZLED(FZD)-mediated WNT pathway in via SREBP1c/FASN pathway human microphthalmia and coloboma: From Jun Cheng, Lili Gao, Yu Zhang, Hongping Zhang, animal model to human patients Ming Han, Shunai Liu, Xiaoxue Yuan Chunqiao Liu Beijing Ditan Hospital, Capital Medical University, Professor of Developmental Neuroscience at Beijing 100015, China Zhongshan Ophthalmic Center (ZOC), Sun Yat-Sen Corresponding: Jun Cheng, MD, PhD, 8 East University, China Jingshun Street, Chaoyang District, Beijing 100015, Abstract China Ocular coloboma with microphthalmia (small eyes) E-mail: [email protected] and anophthalmia (absent eyes) represents a Abstract spectrum of malformations that account for up to Hypertriglyceridemia leads to liver steatosis, 11% of pediatric blindness. Often associated with cardiovascular diseases, type 2 diabetes. HCBP6 microphthalmia, coloboma results from a defect in was previously shown as an HCV (Hepatitis C virus) fusion of the optic fissure during development, and core-binding protein; however, its biological exhibits extensive locus heterogeneity with function is remained unclear. Here, we demonstrated mutations identified in transcription factors, that HCBP6 working as a negative regulator and a cytoskeletal proteins and signaling pathways. WNT sensor of intracellular triglyceride (TG) levels in pathway plays essential role in multiple aspects of hepatocyte. We found that bidirectional central nervous system development. Using genetic manipulation of HCBP6 expression in the engineered mouse model, we found that loss of Wnt hepatocyte by overexpression or silence, results in receptors, Fzd5 and/or Fzd8, leads to ocular decrease or increase of TG accumulation in hepatic microphthalmia and coloboma associated with cells, respectively. In addition, in the lipid retinal neurogenesis defect. We further identified a

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) heterozygous frameshift mutation in the single understood. Our data indicated that acute injury to coding exon of WNT receptor FZD5 (p.Ala219 the kidney resulted in reduced expression of Glufs*49), segregating in a large family with E-cadherin and ZO-1, whereas EZH2 inhibition dominant ocular coloboma. Expression of the largely preserved their expression. Moreover, resultant mutant protein causes microphthalmia and 3-DZNep was effective in counteracting the coloboma in zebrafish and disruption of apical increased expression of matrix metalloproteinase junction of the retinal neural epithelium in mouse, (MMP)-2 and MMP-9, as well as the consistent with phenotypes of Fzd5/8 compound phosphorylation of Raf-1 and ERK1/2 in the injured null mice. The mutant protein lacks transmembrane kidney. Conversely, blocking EZH2 reversed the domains, is secreted, and behaves as a dominant- decrease of tissue inhibitor of metalloproteinase negative FZD5 receptor antagonizing both canonical (TIMP)-2 and metalloproteinase (TIMP)-3, and Raf and non-canonical WNT signaling. Our studies kinase inhibitor protein (RKIP) in the kidney after directly implicate WNT-FZD pathway in the acute injury. Similarly, oxidant injury to cultured pathogenesis of human coloboma and suggest that kidney proximal tubular epithelial cells caused a WNT signaling components could be potential decrease in the expression of E-cadherin, ZO-1, targets for clinical treatment of coloboma disease. TIMP-2/-3 and RKIP, as well as an increase in the expression of MMP-2/9 and phosphorylation of C005 Raf-1 ERK1/2. Blocking EZH2 with 3-DZNep or Targeting histone methyltransferase EZH2 as SiRNA hindered these responses. These results the treatment of acute and chronic kidney disease suggest that targeting EZH2 protects against AKI Shougang Zhuang, M.D., Ph.D. through a mechanism associated with the Department of Medicine, Rhode Island Hospital and preservation of adhesion/junctions, reduction of Alpert Medical School, matrix metalloproteinases and attenuation of the Brown University, Providence, RI, 02903, USA Raf-1/ERK1/2 pathway. On the other hand, chronic Abstract injury to the kidney or cultured TKPT cells resulted Acute kidney injury (AKI) and chronic kidney in up-regulation of Snail-l family transcriptional disease (CKD) are common and costly global health repressor (Snail)-1 and Twist family basic problems. There is no effective therapy for AKI. We helix-loop-helix (BHLH) transcription factor found that EZH2 was highly expressed in the kidney (Twist)-1, which are 2 transcription factors, and after acute and chronic injury and that inhibition of down-regulation of phosphatase and tensin homolog, EZH2 with 3-DZNeP attenuated the development of a protein tyrosine phosphatase associated with renal fibrosis induced by unilateral ureteral inhibition of PI3K-protein kinase B (AKT) signaling; obstruction. This is associated with preservation of EZH2 inhibition or silencing reversed all those PTEN and Smad7 expression and inhibition of responses. 3-DZNeP was also effective in epithelial cell cycle arrest in G2/M phase. EZH2 suppressing epithelial arrest at the G2/M phase and inhibition also improves renal function and reduces dephosphorylating AKT and β-catenin in vivo and in renal tubular cell injury and apoptosis in vitro. These data indicate that EZH2 activation ischemia/reperfusion (I/R) induced AKI in mice. contributes to renal EMT and fibrosis through These data establish EZH2 activation as a critical activation of multiple signaling pathways. factor in the pathogenesis of acute and chronic renal Collectively, our data suggest that EZH2 is a injury, but the molecular basis remains poorly potential therapeutic target for treating acute and

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) chronic kidney disease. tuberculosis (Mtb). CD157 has a crucial role in Category: Invited speaker neutrophil and monocyte transendothelial migration and adhesion, but whether it has a role in protective C006 immunity against tuberculosis is unclear. Here, we CD157 confers host resistance to Mycobacterium hypothesized that CD157 might contribute to host tuberculosis via TLR2-CD157-PKCzeta- induced defense against Mtb infection. CD157 knockout ROS production mice infected with Mtb exhibited normal monocyte Qianting Yang1, Mingfeng Liao1, Wenfei Wang2, recruitment to sites of infection but macrophage Mingxia Zhang1, Qi Chen1, Jiubiao Guo2, Bin bactericidal ability was compromised. This defect Peng3, Jian Huang4, Haiying Liu5, Ayano Yahagi6, was due to impaired Mtb-induced macrophagic ROS Xingzhi Xu3, Katsuhiko Ishihara6, Andrea production, a biological process in which involves Cooper7, Yi Cai2, Xinchun Chen2 TLR2-CD157-PKCzeta interaction, but independent 1Guangdong Key Lab for Diagnosis &Treatment of of the ERK and NF-kB pathways. We also found Emerging Infectious Diseases, Shenzhen Third that membrane-bound and soluble CD157 People’s Hospital, Shenzhen University School of expression is significantly increased in human Medicine, Shenzhen, China, 518112 tuberculosis, and its expression gradually decreases 2Department of Pathogen Biology, Shenzhen after effective anti-tuberculosis chemotherapy. University School of Medicine, Shenzhen, China, Interestingly, the levels of soluble CD157 correlate 518060 with human peripheral monocyte derived 3Department of Cellular Biology, Shenzhen macrophage bactericidal activity. Exogeneous University School of Medicine, Shenzhen, China, application of soluble CD157 could compensate for 518060 macrophage bactericidal ability and restore ROS 4Key Laboratory of Systems Biomedicine (Ministry production. In conclusion, we have identified a of Education) and Collaborative Innovation Center novel protective immune function for CD157 during of Systems Biomedicine, Shanghai Center for Mtb infection via TLR2-dependent ROS production Systems Biomedicine, Shanghai Jiao Tong by macrophages. Application of soluble CD157 University, Shanghai, 200240, China. might be an effective strategy for host directed 5MOH Key Laboratory of Systems Biology of therapy against TB in those with insufficient CD157 Pathogens, Institute of Pathogen Biology, and production. Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical C007 College, Beijing 100176, China. The polymorphism rs17525495 of LTA4H is 6Department of Immunology and Molecular associated with susceptibility of Crohn’s disease Genetics, Kawasaki Medical School, 577 instead of intestinal tuberculosis in a Chinese Matsushima, Kurashiki, Okayama 701-0192, Japan Han population 7Leicester Tuberculosis Research Group, Zi-qi Yua,b＃, Wen-fei Wangc,d＃, Chuan-zhi Zhue, Department of Infection, Immunity and Ke-hong Zhangc,d, Xin-chun Chenc , Jian-yong Inflammation, University of Leicester,Leicester UK. Chena* Abstract aDepartment of Gastroenterology & Hepatology, Recruitment of monocyte to the site of infection is Jiangxi Provincial People's Hospital, Nanchang, critical for host resistance against Mycobacterium China.

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) bJiangxi Medical College, Nanchang University, 95%CI=1.01-1.82) and the differences are Nanchang, China. statistically significant. During treatment, the cDepartment of Microbiology and Immunology, presence of the T allele significantly increased the Shenzhen University Health Science Center, proportion of Crohn's patients requiring Shenzhen, China. Glucocorticoids (p < 0.05). CONCLUSION: The T d Friedrich Schiller University, Jena, Germany. allele of LTA4H gene SNP (rs17525495) is a risk e Laboratory of Molecular Biology, Beijing Chest factor for Crohn's disease instead of intestinal Hospital, Capital Medical University, Beijing tuberculosis. More importantly, there may be a Tuberculosis and Thoracic Tumor Research Institute, potential association of the different genotypes of Beijing, China. rs17525495 with the treatment efficacy of 5-ASA Correspondence to Jian-yong Chen, PhD, MD, and Glucocorticoids in patients with Crohn’s disease. Department of Gastroenterology & Hepatology, The association between LTA4H polymorphism and Jiangxi Provincial People's Hospital, Nanchang drugs therapeutic effects might contribute to the 330006, China. Tel/fax: +86 180 7008 8908; E-mail: practice of precision medicine and the prediction of [email protected] clinical outcomes. Abstract: BACKGROUND: Because of the similarity of C008 Intestinal tuberculosis and Crohn's disease in disease Tobacco use predicts poorer clinical outcomes phenotype, differential diagnosis has always been a and higher post-operative complication rates clinical problem. Arachidonic acid metabolites play after open elbow arthrolysis an important role in the inflammatory response of Ziyang Sun, M.D. intestinal tuberculosis and Crohn's disease. Recent Medical Student, Department of Orthopedics, studies have shown that rs17525495 polymorphism Shanghai Jiao Tong University Affiliated Sixth locus in the promoter region of LTA4H gene affects People’s Hospital, Shanghai, China LTB4 expression level and the susceptibility to Email: [email protected] extrapulmonary tuberculosis. Thus, we identified a Abstract total of 133 patients with intestinal tuberculosis,124 Tobacco use is a worldwide public health problem, Crohn's disease and 500 normal controls in this and has been found to be a predisposing factor for study. PATIENTS AND METHODS: All the Study adverse functional outcomes and increased participants were local Han people from Jiangxi post-operative complication rates after various province in the past ten years. DNA was extracted orthopedic operations. The purpose of this study was from the paraffin-embedded specimens or the whole to determine the potential impact of tobacco use on blood. The LTA4H promoter SNP (rs17525495) was open arthrolysis for post-traumatic elbow stiffness. genotyped with TaqMan assay. RESULTS: The A database search identified 145 patients with open T-alleles frequency of rs17525495 was increased in arthrolysis performed for post-traumatic elbow patients with intestinal tuberculosis compared with stiffness between January 2015 and December 2016; that of healthy control group (p = 0.23, OR=1.20, these were divided into three groups: current 95%CI=0.89-1.60), but there are no statistically tobacco users (37), former users (28), and nonusers significant differences. In contrast to healthy people, (80). All surgeries were performed using the same patient with Crohn's disease also has an increased technique by the same doctor. General patient data, T-alleles frequency (p = 0.04, OR=1.35, functional performance, and complications were

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) documented and analyzed. Demographic data and induced by injection of porcine cardiac disease characteristics were comparable at baseline. myosin-complete freud's adjuvance-emulsion, Postoperatively, significant differences were found animals of the control group were subcutaneously among the three groups in terms of range of motion injected with CFA alone. Rats were sacrificed (p < 0.001), Mayo Elbow Performance Score (p = respectively at 3 weeks and 8 weeks after 0.006), visual analog scale score for pain (p = 0.015), echocardiogram for the assessment of left Dellon classification for ulnar nerve symptoms ventricular cardiac function. Hematoxylin-eosin (P=.013), and total complication rates (p < .001). staining was performed to evaluate the The current tobacco users group had the poorest histopathological changes of myocardium and the clinical outcomes and highest complication rates, degree of inflammatory reaction with light while no significant differences were found between microscope. Enzyme-linked immunosorbent assays former users and nonusers. We conclude that current were performed to analyze the level of ET-1, Nitric tobacco users reported increased risk of poorer oxide (NO) in serum samples. The expression of clinical outcomes and higher postoperative ETAR and ETBR were detected by western blot. On complication rates after open arthrolysis. Former 3 and 8 weeks after the first immunization, cardiac users were found to have outcomes similar to those function decreased obviously in the experimental of nonusers. This study underlines the importance of group compared to the control group (p < 0.05). discontinuing tobacco use for patients with Histopathological examination showed an obvious post-traumatic elbow stiffness who are considering inflammatory cell infiltration with varying degrees open arthrolysis. Keywords: Post-traumatic elbow of myocardial cell degeneration and necrosis in the stiffness; Open arthrolysis; Tobacco use experimental group. The levels of ET-1, and NO in serum for the experimental group were higher than C009 the control group (p < 0.05). In addition, the ET-1/ETR axis activates in autoimmune expression of ETAR and ETBR proteins were myocarditis rats statistically significant in the experimental group Yu-Jing Wu 1,2, Zhen-Zhong Zheng1,2*, Xian-Tong when compared with control group (p < 0.05). The Cao1,2, Avner Adini3, Fang-Fei Li1,2, Guo-Rong results indicated that activation of ET-1/ETR is Cai1,2, Xiu-Juan Xiao1,2, Zhi-Chao Yang1,2, associated with immune damage in autoimmune Wen-Qiang Zhang1,2, Hao Wu3* myocarditis rats. Our findings will provide a new 1Department of Cardiology, The First Affiliated theoretical basis for the pathogenesis of myocarditis. Hospital of Nanchang University, Nanchang, Jiangxi, 330006, PR. China C010 2Jiangxi Hypertension Research Institute, Nanchang, Effects of KB-120, a microbe-derived Jiangxi, 330006, China antioxidant, on semen parameters of males with 3Vascular Biology Program, Boston Children’s asthenozoospermia Hospital Department of Surgery, Harvard Medical Huijuan Shi 1, Yan Li 2, Yihua Gu 1,2 School, Boston, MA 02115, USA 1Shanghai Institute of Parenthood Planning Abstract Research, China This study aimed to study whether ET-1/ETR axis is 2ProBiotiK Technologie Deutschland GmbH – associated with immune damage in autoimmune Frankfurt am Main, Germany myocarditis rats. Autoimmune myocarditis rats were Abstract

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

Objective: To evaluate effects of a microbe-derived 4.Shuguang Hospital Affiliated to Shanghai antioxidant, KB-120, on semen parameters of males University of TCM, Shanghai 200021 with asthenospermia. Method: Diagnosed according Abstract to WHO fourth edition semen analysis guideline, 40 Objective: The current study was designed to test males with asthenozoospermia were recruited, and the effect of acupuncture on weight and fertility of given 1 g of oral antioxidant daily for three months. Y123F leptin receptor knockout mice. Methods and Semen parameters were examined at the beginning Results: The obesity and infertility Y123F -/- mice and every one month of the treatment. Results: were randomly divided into acupuncture group and With one-month treatment, sperm concentration (p < the control group. After two weeks of stimulated on 0.01), ratio of progressive motility (PM) sperms (p < ST36 and RN12, the food intake, water intake, 0.01), and ratio of rapidly progressive motile (RP) weight, level of serum glu, serum cholesterol, serum sperms (p < 0.001) significantly increased. At the leptin, blood testosterone and IVF and sperm second month, ratios of PM and RP sperms were motility of both groups were compared. In higher than they were one month ago (p < 0.05). comparison with control group, the intakes of food Compared to those at the second month, the semen and water, weight level of serum glu, serum parameters were not statistically changed at the end cholesterol, serum leptin, serum testosterone were of treatment. And, during the treatment, there were 8 lower after acupuncture. And the level of IVF and natural pregnancies (20.0%). Conclusion: By sperm motility was significant increased compared significantly increasing the ratio of RP sperms, to control group (p < 0.05). Even more, one of treatment of KB-120 was capable to improve the acupuncture group made a female c57 mouse fertilizing capacity 43 of males with pregnant and gave birth to six mice. Conclusions: asthenozoospermia. These findings demonstrate that acupuncture can *Correspondence should be addressed to Yihua Gu, reduce weight, and also can improve male E-mail: [email protected] reproductive ability. Keywords: Needling, Metabolism, Fertility, Y123F-Gene-Knockin Mice C011 E-mail: [email protected] Effect of Needling Zusanli (ST36) and Zhongwan (RN12) on Metabolism and Fertility of C012 Y123F-Gene-Knockin Mice Effect of natural antioxidant KB-120 treatment Liang Chen1,2, Jianhui Li1,2, Lei Fan3, Miao Liu3, on men with asthenospermia Yihua Gu1, Huijuan Shi1, Weidong Shen4* Jufen Zheng1,2, Yao Yuan1 , Jianan Tang1 ,Miao 1.Shanghai Institute of Planned Parenthood Research Liu1, Bin Wu1, Xing Feng2, Jianhui Li2, Liang / WHO Collaborating Center for Research in Human Chen2, Yihua Gu1, Huijuan Shi1* Reproduction Department of Reproductive Biology / 1.Shanghai Institute of Planned Parenthood Research Department of Reproductive Pharmacology, NPFPC /WHO Collaborating Center for Research in Human Key Laboratory of Contraceptives and Devices, Reproduction Department of Reproductive Biology/ Shanghai 200032 Department of Reproductive Pharmacology, NPFPC 2.Shanghai Institute of Planned Parenthood Research Key Laboratory of Contraceptives and Devices， Hospital, Shanghai 200032 Shanghai 200032, China 3.Zhongshan Hospital, Fudan University, Shanghai 2.Shanghai Institute of Planned Parenthood Research 200032 Hospital

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O)

Abstract pregnancy rate was 20.5% (9/44) during the Purpose: To evaluate the effect of natural treatment periods. Conclusions: One-month antioxidant KB-120 treatment on men with antioxidant treatment could significantly improve asthenospermia. Methods: Forty-four men with sperm concentration, PR%, and A%. This asthenospermia were included to receive antioxidant significant improvement increased after 2-month treatment. The treatment duration ranged 1–3 antioxidant treatment. However, 3-month months, and the semen routine examination and antioxidant treatment did not have additional sample collection were conducted monthly. We beneficial effects on sperm concentration, PR%, and compared the changes in semen volume, sperm A% as compared with 2-months of antioxidant concentration, percentage of forward motility sperm treatment. Keywords: asthenospermia; infertility; (PR%), and percentage of rapidly forward motility KB-120; semen test; sperm sperm (A%) before and after intervention and assessed the pregnancy outcomes in men receiving C013 natural antioxidant KB-120. Results: The mean age Serum sex hormone-binding globulin and in men and women was 34.36 (6.69) and 32.20 bioavailable testosterone are associated to (5.60) years, respectively and the mean sterility late-onset hypogonadism symptoms complicated years was 2.74 (2.12) years. The baseline parameters with erectile dysfunction in aging males: a of the semen test between two examines did not community-based study have statistical significance (p > 0.05). Forty-two G.Q. Liang1*, J.H. Li2*, H.J. Shi2, Q.X. Zhu2, C. patients underwent the semen test after 1-month Liang2, Z.M. Xu2, J.B. Zheng3, R.H. Xu4, X.W. antioxidant treatment, and significant differences Zhou4, S.C. Zhang4, J.F. Zheng2 & X.H. Yu3. were observed in sperm concentration (37.05 vs 1Department of Andrology, Seventh People’s 48.64; p < 0.01), PR% (33.64 vs 44.12; p < 0.01), Hospital of Shanghai University of TCM, China; and A% (15.02 vs 20.86; P< 0.001) before versus 2Department of Reproductive Epidemiology and after antioxidant treatment. Two-month antioxidant Social Science, National Population and treatment was significantly associated with Family Planning Key Laboratory of Contraceptive increased PR% (47.54 vs 43.54; p < 0.05) and A% Drugs and Devices, Shanghai Institute of Planned (22.96 vs 20.61; p < 0.05) compared with 1-month Parenthood Research, Shanghai, China; antioxidant treatment; however, this significant 3Department of Urology, The First People’s Hospital difference was not observed for sperm concentration of Jiashan, Zhejiang, China; (39.54 vs 41.86; p > 0.05). Moreover, there were no 4Department of Cell Biology, National Research significant differences between 3- and 2-month Institute of Family Planning, Beijing, China; antioxidant treatment for sperm concentration (40.65 Abstract vs 37.29; p >0.05), PR% (45.35 vs 47.88; p >0.05), This study was to investigate the relationship and A% (21.94 vs 23.53; p > 0.05). Furthermore, we between serum levels of sex hormone-binding observed significant differences in PR% (45.33 vs globulin (SHBG), bioavailable testosterone (Bio-T) 34.09; p < 0.001) and A% (22.11 vs 15.78; p < 0.01) and Symptomatic late-onset hypogonadism (SLOH) after 3-month antioxidant therapy compared with complicated with erectile dysfunction (ED) in the baseline characteristics; however, no significant aging male population of eastern China. The aging difference was observed for sperm concentration male symptoms (AMS) scale forms and (51.72 vs 34.17; P>0.05). Finally, the natural International Index of Erectile Function (IIEF)

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American Journal of Translational Medicine Vol 3 Issue 1, 2019 ISSN 2474-7378 (P) & 2474-7386 (O) questionnaire were used to assess SLOH and erectile function (EF) instrument at the beginning of the investigation. Serum reproductive hormone levels of total testosterone (TT), free testosterone (fT), SHBG and luteinizing hormone (LH) were measured. Serum level of Bio-T was calculated from known values of TT, SHBG and serum albumin. All men filled out a health questionnaire and received a detailed physical examination. The final study population consisted of 2,588 men (range, 40 to 80 years) with a mean age of 57.95 years. SLOH (AMS ≥ 27) was observed in 930 (35.94%) males. Among which, 812 cases had positive ED (87.31%). There were 739 cases who had neither positive AMS nor ED. Pearson correlation analysis indicated that there were significant correlations between serum SHBG and AMS (r= 0.152, p < 0.0001) or IIEF scores (r = -0.303, p < 0.0001). Additional significant correlations were found between serum Bio-T and AMS (r= -0.247, p < 0.0001) or IIEF scores (r= 0.215, p < 0.0001), but there were no significant correlations between TT and AMS or age. Our study demonstrated that SHBG and Bio-T appear to have a strong link for SLOH and ED. Keywords: Aging Males’ Symptoms; Hypogonadism; Erectile dysfunction; testosterone; sex hormone-binding globulin; bioavailable testosterone *These authors contributed equally to this work.

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