REVIEW doi: 10.12032/TMRCR20200728016 TMR Clinical Research Meta-analysis of the clinical efficacy and safety of Urinary Kallidinogenase in the treatment of acute cerebral infarction Yuan Qin1, Qian Yi2, Hui-Hui Shi2, Ya-Lin Qi2*, Jing-Yue Hu2 1Chongqing Mental Health Center, Geleshan ward eight ward, Chongqing 400036, China. 2Military Army Medical University (Third Military Medical University) Daping Hospital Neurology, Chongqing 400010, China. *Corresponding to: Ya-Lin Qi. Daping Hospital, Army Medical University (Third Military Medical University. NO. 10, Changjiang branch road, Daping, Yuzhong district, Chongqing 400042, China. E-mail: [email protected]. Highlights The treatment of cerebral infarction by Urinary Kallidinogenase can improve the neurological defect symptoms, improve the quality of life, and the adverse reaction rate is low, and the safety is good, which provides evidence-based evidence for the treatment of cerebral infarction by Urinary Kallidinogenase. Submit a manuscript: https://www.tmrjournals.com/tcr TMR | November 2020 | vol. 3 | no. 4 | 131 doi: 10.12032/TMRCR20200728016 REVIEW Abstract Objective: To evaluate the clinical efficacy and safety of Urinary Kallidinogenase for Injection in the treatment of acute cerebral infarction. Methods: PubMed, The Cochrane Library, Embase, CNKI, VIP, Wan Fang and bibliographic database of Chinese medicine were searched by computer to collect randomized controlled trials of Urinary Kallidinogenase 's treatment of acute cerebral infarction. The time limit was set up until September 2019. At the same time, the references and grey literature in the literature were manually screened. Two independent researchers were screened, evaluated and extracted according to inclusion and exclusion criteria. Meta-analysis was carried out by RevMan 5.3 software. Results: A total of 17 randomized controlled trials involving 2,066 patients, including 1,033 in the experimental group, and 1,033 in the control group. meta-analysis results showed that compared with the conventional treatment, Urinary Kallidinogenase had better effect in the treatment of acute cerebral infarction [OR = 3.26, 95%CI (2.56, 4.16), P < 0.00001]; the national institule of Health Stroke Scale of the Urinary Kallidinogenase group was significantly better than that of the control group. Urinary Kallidinogenase group activity of daily living scale was better than the control group [OR = 21.33, 95%CI (6.64, 36.01), P = 0.004]; a total of 7 articles reported adverse reactions, including 19 cases in the trial group and 21 cases in the control group, the main adverse reactions were blood pressure drop, other symptoms were chest tightness, facial redness, dizziness fever, nausea and vomiting, arrhythmia, and no other serious adverse reactions. It can recover itself. Conclusion: the available evidence shows that Urinary Kallidinogenase can effectively improve the symptoms of neurological deficits and improve the ability of daily living in patients with acute cerebral infarction, and is safe. However, the quality of the study is limited. Keywords: Human urinary kallikrein, Urinary Kallidinogenase, Acute cerebral infarction, Randomized controlled trial, meta-analysis Abbreviations: rt-PA, recombinant tissue plasminogen activator; RCT, randomized controlled trial; CT, computed tomography; MRI, magnetic resonance Imaging; NIHSS, national institutes of health stroke scale; ADL, activity of daily living; OR, odds ratio; CI, confidence interval; PNA, pentose nucleic acid; ACEI, angiotension converting enzyme inhibitors; hk1, hexokinase 1. Competing interests: The authors declare that there is no conflict of interest. Citation: Yuan Qin, Qian Yi, Hui-Hui Shi, et al. Meta-analysis of the clinical efficacy and safety of Urinary Kallidinogenase in the treatment of acute cerebral infarction. TMR Clinical Research 2020, 3(4): 131–141. Executive Editor: Shan-Shan Lin. Submitted: 12 December 2019, Accepted: 12 May 2020, Online: 28 July 2020 TMR | November 2020 | vol. 3 | no. 4 | 132 Submit a manuscript: https://www.tmrjournals.com/tcr REVIEW doi: 10.12032/TMRCR20200728016 magnetic resonance Imaging (MRI) patients with a Background cute cerebral infarction within 72 hours had no ge nder or age. No strict gravity center, liver or kidn At present, stroke has become the first cause of death ey insufficiency, no systemic bleeding or bleeding in China. It is also an important cause of disability. Its tendency. main clinical manifestations are disturbance of (3) The intervention group adopted the same routine consciousness, dysfunction and other symptoms. It has treatment, including lowering blood fat, anti-platelet a high disability rate and mortality rate [1]. Cerebral aggregation, nourishing brain cells and improving the infarction, also known as ischemic stroke, is caused by cerebral circulation. The experimental group was local cerebral vascular supply disorders leading to additionally given Urinary Kallidinogenase, while the hypoxic degeneration and necrosis of the brain tissue, control group was given placebo, inactive or active resulting in a corresponding clinical neurological drugs on the routine treatment. Two groups were given deficit 80%, which accounts for all stroke types, is the same treatment. used in the treatment of acute cerebral infarction. In (4) Outcome measures: effective rate: the National addition to recombinant tissue plasminogen activator Institutes of Health Stroke Scale (NIHSS) was used to (rt-PA), an antiplatelet drug aspirin and thrombolytic evaluate the improvement of neurological deficits at drugs, has become an international guideline for grade the end of treatment. The following criteria were A and grade I recommendation. The evidence for other adopted to improve the degree of improvement: the drugs is not yet sufficient. Therefore, it is of great basic cure was: the neurological deficit score was significance to study new drugs for improving cerebral reduced by 90%–100%, the disability degree was 0 circulation and protecting brain function. grade; significant progress was achieved: the Urinary Kallidinogenase, also known as the human neurological impairment score was reduced by 46%– Urinary Kallidinogenase (trade name, Kai Likang), is a 89%, and the disability degree was 1–3; progress: serine proteinase composed of 238 amino acids neurological deficit score decreased by 18%–45%; no extracted from the urine of healthy men. It is a new change: neurological impairment score decreased or class I drug developed in recent years in China. It has increased by 18%; deterioration: neurological been shown that the drug has a certain dose under impairment score increased 18%. Improved conversion certain dose. It can expand the small artery in ischemic to classification variable effective and invalid, which area, increase blood flow in ischemic brain tissue, and will be effectively defined as basic cure, significant improve cerebral circulation in 10 years. In October progress and progress, Total Efficiency = (Basic Cure 2005, it was approved by The State Food and Drug + Significant Progress + Progression/Total Number) × Administration and widely used in clinical practice.In 100%; NIHSS score; 3 activity of daily living scale recent years, the drug has been more widely used in (ADL) score. China, and the corresponding clinical randomized (5) Adverse reactions were defined as intracranial controlled trials (RCT) are also increasing, but the hemorrhage, extracranial blood, allergies, and research quality is uneven, so it is necessary to carry unexplained organ dysfunction. out systematic evaluation to provide evidence-based medical evidence for it. Exclusion criteria (1) Non randomized controlled trials. Materials and methods (2) There is no clear diagnosis, inclusion and exclusion criteria. Search strategy Computer (3) The course of treatment is inconsistent and there is Search strategy retrieves databases such as PubMe d, no definite criteria for evaluating the therapeutic effect. The Cochrane Library, Embase, CNKI, VIP, Wa n (4) Repeated published studies. Fang and Chinese biomedical literature database. Registry from inception to September 2019. “Stro Data extraction ke” and Chinese search terms such as “Urinary K Extraction were carried out separately by two allidinogenase”, “human urinary kinase” and “cereb researchers, and the data were screened and extracted. ral infarction” were retrieved by combining themati If there were differences, reference was made to third c words and free words. people's opinions. The relevant documents were retrieved into the literature management software Inclusion criteria NoteExpress to read the titles and abstracts, and the (1) Study type: RCT, whether or not use blindness. articles that did not meet the inclusion criteria were Language is restricted to Chinese and English. carefully read out and screened again. Finally, the data (2) The subjects met the diagnostic criteria of cere included the first author or information provider, date bral infarction diagnosed by the Fourth National C of publication, age, time of entry, sample size, onference on cerebrovascular diseases, and confirm intervention measures, course of treatment, and ed by cranial computed tomography (CT) and/or outcome criteria. Submit a manuscript: https://www.tmrjournals.com/tcr TMR | November 2020 | vol. 3 | no. 4 | 133 doi: 10.12032/TMRCR20200728016 REVIEW analysis variables to draw funnel plots for publication Quality evaluation bias detection. According to the bias risk assessment method recommended in