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Exploratory Research for Pathogenesis of Papulopustular Rosacea and Skin Barrier Research in Besançon and Shanghai Chao Yuan

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Exploratory Research for Pathogenesis of Papulopustular Rosacea and Skin Barrier Research in Besançon and Shanghai Chao Yuan Exploratory research for pathogenesis of papulopustular rosacea and skin barrier research in Besançon and Shanghai Chao Yuan To cite this version: Chao Yuan. Exploratory research for pathogenesis of papulopustular rosacea and skin barrier research in Besançon and Shanghai. Dermatology. Université Bourgogne Franche-Comté, 2017. English. NNT : 2017UBFCE004. tel-01767270 HAL Id: tel-01767270 https://tel.archives-ouvertes.fr/tel-01767270 Submitted on 16 Apr 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITE BOURGOGNE- FRANCHE COMTE ECOLE DOCTORALE « ENVIRONNEMENTS-SANTE » Année 2017 THESE Pour obtenir le grade de Docteur de l’Université de Franche-Comté Spécialité : Sciences de la Vie et de la Santé Présentée et soutenue publiquement Le 12 Sept 2017 Par Chao YUAN Exploratory Research for Pathogenesis of Papulopustular Rosacea and Skin Barrier Research in Besancon and Shanghai Thesis directors : Philippe HUMBERT, Xiuli WANG Christos C. ZOUBOULIS, Professor, Dessau Medical Center, Germany Reviewer Li HE, Professor, Kunming Medical University, China Reviewer Philippe HUMBERT, Professor, University of Bourgogne Franche-Comté, France Thesis Co-director Xiuli WANG, Professor, University of Tongji, China Thesis Co-director Ferial FANIAN, Dermatologist, Laboratory Filorga, France Examinator 1 PhD Tutor Teams Pro. XiuLi WANG Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai. Pro. Li HE Department of Dermatology, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Pro. Qiang JU Department of Dermatology, RenJi Hospital, Shanghai. Dr. Ahmed ELKHYAT Research and Studies Center on the Integument (CERT), Department of Dermatology, Besançon University Hospital, University of Franche-Comté. PhD. Sophie MAC-MARY Skinexigence, Besançon. 2 CONTENT OF THESIS I –Introduction ............................................................................................ 6 II –Pathogenesis Study of Papulopustular Rosacea .................................... 14 A- Background of Rosacea Pathogenesis ......................................................... 15 A. 1 History of Rosacea ..................................................................................... 16 A. 2 Rosacea definition and subtypes ................................................................ 17 B- Pathogenesis of Rosacea from retrospect references.................................. 20 B.1 Controversy of Rosacea Pathogenesis ......................................................... 22 B.2 Augmented immune response .................................................................... 23 B.3 Microorganisms and demodex .................................................................... 25 B.4 Abnormalities in Cutaneous Vascular and Neurogenic dysregulation .......... 26 C – Non-invasive testing in Rosacea ................................................................ 28 C.1 Standardized Skin Surface Biopsy use in Acne ............................................. 28 C. 2 SSSB and Confocal Laser Scanning Microscopy use in rosacea.....................37 C. 3 CLSM and SSSB use in a pityriasis folliculorum patient ............................... 42 D- Skin flora situation in PPR patients ............................................................ 47 D.1 Materials and methods ............................................................................... 48 3 D.2 Results ........................................................................................................ 51 D.3 Discussion for the skin flora condition for rosacea .......................................57 E- Sensitive Skin and Rosacea ......................................................................... 62 E.1 Reflectance confocal microscopy for the evaluation of sensitive skin .......... 62 E.2 Sensitive Skin and Rosacea in Reflectance confocal microscopy .................. 77 F-Future ideas for the research of rosacea ...................................................... 83 Ⅲ–Skin Microbial distribution and Biophysical Parameters in Chinese female....................................................................................................... 86 A-Microbiology of Skin Surface ...................................................................... 87 A.1 Introduction .................................................................................................87 A.2 The Skin Flora ............................................................................................. 88 A.3 Diseased Skin .............................................................................................. 91 A.4 Skin Flora Influence by Skin Surface pH ..................................................... 100 B-Evaluation of Skin Surface Flora ................................................................ 102 B.1 Introduction ...............................................................................................102 B.2 Methods of Sampling ................................................................................ 103 B.3. Follicular Sampling Methods .................................................................... 108 C-Skin Microbial distribution and skin Biophysical Parameters in Chinese female .......................................................................................................... 113 4 C.1 Introduction .............................................................................................. 113 C.2 Methodology ............................................................................................ 115 C.3 Results....................................................................................................... 121 C.4 Discussion ................................................................................................. 126 C.5 Conclusion ................................................................................................ 130 C.6 Appendix ................................................................................................... 131 Ⅳ-Conclusions ........................................................................................ 146 Ⅴ- Acknowledgements ........................................................................... 150 Ⅵ- Reference .......................................................................................... 152 Ⅶ--Li st for the Published Papers in English ............................................. 167 Ⅷ--List for the Published Papers in Chinese ............................................ 170 Ⅸ--List for the Congress Presentation ..................................................... 172 Ⅹ--List for the Relevant Investigation Fund ............................................ 176 Ⅺ—Resume ............................................................................................ 178 5 I –Introduction 6 In 1975, Michaels et al. suggested a schematic model to explain the permeability of the stratum corneum (SC), which was called “brick & mortar” (1). The corneocytes are the bricks and the lipids are the mortar. Today this is viewed as the most appropriate model for the understanding of skin permeability (2). In the early point of view, skin barrier consisted of two important structures: one is the SC (corneocytes), which functions as a physical barrier against both percutaneous penetrations of harmful substances and excessive trans-epidermal water and salt loss (3); the other is the corneocytes-bound intercellular hydrophobic matrix, mainly composed of ceramides, fatty acids, and cholesterol, which functions as a chemical barrier against pathogens (4). In the past several years, advances in human measurement capabilities (5), in particular non-invasive methodologies, have not only reinforced the fact that the stratum corneum is incredibly responsive and adaptive, but also continue to provide new insights and opportunities for all the dermatologists (6). From 2013 to 2017, I devoted myself to the research of skin barrier, and paid more attention to the pathogenesis of rosacea (See fig.1). From 2013 to 2017, I published 9 SCI articles (among them, I am the first author or corresponding author for 6 articles), 7 articles in Chinese Core Journals, and 3 funded projects were awarded (among them, one is from the National Science Foundation of China). 7 Fig.1. the research lines and achievements from 2013 to 2017 The SC is under a constant barrage of environmental insults such as temperature, humidity, pathogens, pollution, and solar UV. First, many researches were focused on the different damaged skin from the environment. For example, we did the Human Repeated Insult Patch Test (HRIPT) testing in Shanghai and Mumbai and we found that meteorology and ethnicity are critical factors in skin reaction (published in RTP 2013)(7). I was also interested in UV-damaged skin, and we explored differences in phototest and photopatch test results, and in skin color⁃related parameters between healthy subjects and patients with chronic actinic dermatitis (CAD). Skin photobiological testing
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