1.Effect and Mechanism of Wulingsan Decoction in Protecting Blood Brain Barrier and Ameliorating Cerebral Edema after Intracerebral Hemorrhage in Mice
Damei TAO ; Huihong LI ; Xiaoqing ZHENG ; Yunfei DENG ; Wei WEI ; Xiehua XUE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):1-9
ObjectiveTo study the effect of Wulingsan on cerebral edema after intracerebral hemorrhage (ICH) in mice and explore the treatment mechanism. MethodsThe mouse model of ICH was established by injection of collagenase into the caudate nucleus. Mice were randomly assigned into the following groups: sham, ICH, intervention before modeling with low-dose and high-dose (3.69, 11.07 g·kg-1, respectively) Wulingsan, and intervention after modeling with high-dose Wulingsan. The modified neurological severity score (mNSS) was recorded, and the small animal MRI T2 sequential scanning was performed to measure the volume of cerebral hemorrhage after the modeling of ICH in each group. The Y-maze test, open field test, and Morris water maze test were conducted to evaluate the neurological behaviors of mice in each group. Hematoxylin-eosin staining was employed to observe the pathological changes in the brain tissue. Immunohistochemistry was employed to observe the expression of aquaporin 4 (AQP4), neuronal nuclei (NeuN), and glial fibrillary acidic protein (GFAP) in the brain tissue. Western blot was employed to determine the protein levels of AQP4, Claudin-5, and zonula occludens-1 (ZO-1) in the hematoma area. ResultsCompared with the sham group, the ICH group showed increases in the mNSS, the cerebral hemorrhage volume, and the escape latency in the Morris water maze test (P<0.01), decreases in the times of touching the platform and times of entering the quadrant where the platform was located in the Morris water maze test, and reductions in the spontaneous alternation rate in the Y-maze test and the ratio of distance of center travel to total travel distance in the open field test (P<0.01). Moreover, pathological changes such as cell disarrangement, cell space enlargement, and cell swelling were observed in the ICH group. Immunohistochemistry results showed that the ICH group had higher proportions of AQP4- and GFAP-positive cells and lower proportion of NeuN-positive cells than the sham group (P<0.01). Compared with the sham group, the ICH group showed an up-regulated protein level of AQP4 and down-regulated protein levels of Claudin-5 and ZO-1 (P<0.01). Compared with the ICH group, the intervention with Wulingsan decreased the mNSS, the volume of cerebral hemorrhage, and the escape latency in the Morris water maze test (P<0.05, P<0.01), while increasing the times of touching the platform and times of entering the quadrant where the platform was located in the Morris water maze test, the spontaneous alternation rate in the Y-maze test, and the ratio of distance of center travel to total travel distance in the open field test (P<0.05, P<0.01). Furthermore, the intervention with Wulingsan alleviated the pathological changes in the brain tissue after ICH, decreased the proportion of AQP4- and GFAP-positive cells (P<0.01), increased the proportion of NeuN-positive cells (P<0.01), down-regulated the protein level of AQP4 (P<0.01), and up-regulated the protein levels of Claudin-5 and ZO-1 (P<0.01). ConclusionThe intervention with Wulingsan could reduce the neural function score and the cerebral hemorrhage volume, up-regulate the expression of Claudin-5 and ZO-1, and down-regulate the expression of AQP4 to ameliorate the neurological function defect and cerebral edema after ICH, thereby protecting the brain.
2.Traditional Chinese Medicine Treats Diabetic Nephropathy via Pathways Related to Pyroptosis: A Review
Jintao SHI ; Zhiyi ZHANG ; Yunfei WEI ; Jiarui HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):290-300
Diabetic kidney disease (DKD), one of the leading causes of end-stage renal disease, shows increasing prevalence and mortality, seriously affecting the physical and mental health of patients. As a crucial link in the occurrence and development of DKD, pyroptosis can lead to kidney cell injury and inflammation through the abnormal activation of reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3), Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB)/NLRP3, nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), mitogen-activated protein kinase (MAPK)/NLRP3, and hypoxia-inducible factor-1α (HIF-1α)/NLRP3 signaling pathways, which accelerate the progression of DKD. In recent years, traditional Chinese medicine (TCM) has demonstrated definite efficacy in the treatment of DKD via multiple targets and pathways. Studies have shown that various TCM active components, including glycosides, flavonoids, polyphenols, terpenoids, and alkaloids, as well as TCM compound prescriptions for clearing heat and detoxifying, tonifying deficiency and consolidating root, and eliminating stasis and descending turbidity, can target relevant signaling pathways to inhibit pyroptosis and intervene in the development of DKD, providing new possibilities for precision treatment of DKD. This article systematically reviews the relevant pathways of pyroptosis and summarizes the research achievements and mechanisms of TCM active components and compound prescriptions in the treatment of DKD via pyroptosis in recent years. This review aims to provide new directions and ideas for the treatment and research of DKD with TCM and promote the modernization and development of TCM.
3.Construction of a competency evaluation indicator system for infection prevention and control nurses in Operating Rooms
Liqun SUN ; Zengmei ZHANG ; Haiyun ZHAO ; Ying ZHANG ; Zi JIN ; Yunfei NIE ; Wei WEI ; Yu WANG ; Shengyun LI ; Ruifang HUA
Chinese Journal of Modern Nursing 2024;30(13):1698-1705
Objective:To construct a competency evaluation indicator system for infection prevention and control nurses in Operating Rooms (hereinafter referred to as "IPC") and provide an objective basis for the management of IPC nurses.Methods:From June to November 2022, an initial competency evaluation indicator system for IPC nurses was developed through literature review and semi-structured interviews. The Delphi method was employed to consult 20 experts from 11 provinces and municipalities across the country. Analytical Hierarchy Process (AHP) and mean distribution method were applied to quantify and determine the weight of each level of indicators within the system.Results:Nineteen experts were finally included, with two rounds of questionnaire recovery rates of 95.00% (19/20) and 100.00% (19/19), respectively. The authority coefficients of the experts were 0.858 and 0.861, familiarity coefficients were 0.850 and 0.853, and coefficients of judgment basis were 0.865 and 0.868, respectively. The Kendall's W coefficient of concordance for the two rounds of inquiries were 0.139 and 0.202 ( P<0.05), respectively. The final IPC nurse competency evaluation indicator system included six primary indicators, 22 secondary indicators, and 66 tertiary indicators. Conclusions:The constructed IPC nurse competency evaluation indicator system is scientific, reasonable, objective, and comprehensive, providing a valuable reference for the capability training, assessment, entry standards, and qualification certification of IPC nurses.
4.Synthesis of 18F-labeled glucagon-like peptide-1 receptor agonist targeting probe and its preliminary evaluation in diagnosis of insulinoma with PET/CT
Yunfei XIE ; Nan LIU ; Zhaohui LIU ; Limeng HE ; Huan MA ; Hao LIU ; Hao WANG ; Haiyan GAO ; Weiwei ZHANG ; Wei ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(11):673-677
Objective:To explore the automated synthesis of glucagon-like peptide-1 receptor agonist 18F-AlF-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-maleimide (Mal)-cysteine (Cys) 39-exendin-4 ( 18F-exendin-4), and verify its diagnostic efficacy on insulinoma with PET/CT. Methods:Using NOTA-Mal-Cys 39-exendin-4 as the labeled precursor, 18F-exendin-4 was obtained by constructing Al 18F one-step reaction sequence and using All in one multifunctional chemical synthesizer for radiolabelling, purification and preparation. After the quality control, 18F-exendin-4 PET/CT imaging was performed on 1 patient (female, 55 years old) with clinical suspicion of insulinoma. Results:Radiolabelling of 18F-exendin-4 took about 40 min, with the non-decay corrected radiochemical yield of (18.03±2.67)% ( n=3), the molar activity>39.74 GBq/μmol, and the radioactivity concentration>390.00 MBq/ml. The injection was a colorless transparent liquid with pH value of 6.5, and the radiochemical purity>96%. Results of bacteria and endotoxins testing met the standards of Pharmacopoeia of the People′ s Republic of China (2020). PET/CT image analysis showed a nodular high uptake of 18F-exendin-4 in the pancreatic body. The pathological and immunohistochemical results were consistent with the characteristics of neuroendocrine neoplasm (G2). Conclusions:The automatic radiolabelling of 18F-exendin-4 is successfully realized by All in one multifunctional chemical synthesizer. 18F-exendin-4 has been proved to be of clinical value in diagnosis of insulinoma, and is suitable for promotion in medical institutions equipped with medical cyclotrons.
5.Mechanism of astrocyte derived exosome miR-193b-3p targeting TRPM2 in improving oxygen-glucose deprivation/reoxygenation injury in cerebral microvascular endothelial cells
Yunfei DENG ; Huihong LI ; Wei WEI ; Damei TAO ; Xiaoqing ZHENG ; Xiehua XUE
Chinese Journal of Neuromedicine 2024;23(9):874-885
Objective:To investigate the role and mechanism of astrocyte (AS) derived exosomes in protecting brain microvascular endothelial cells (bEnd. 3) from cerebral ischemia reperfusion injury by establishing an oxygen-glucose deprivation/re-oxygenation (OGD/R) model in vitro. Methods:(1) Dual-luciferase reporter gene assay was used to confirm the regulating effect of miR-193b-3p on transient receptor potential cation channel, subfamily M, member 2 (TRPM2). OGD/R model was established by OGD 8 h followed by reoxygenation 24 h in bEnd. 3 cells after being transfected miR-193b-3p mimics/negative sequence (OGD/R+miR-193b-3p mimics group or OGD/R+miR-193b-3p negative sequence group); real-time quantitative PCR (RT-qPCR) was used to detect the miR-193b-3p expression, Western blotting (WB) was used to detect the expressions of TRPM2, cleaved caspase-3, Bax, Bcl-2, ZO-1 and Claudin-5, and flow cytometry was used to detect the apoptosis. (2) AS was extracted from the cerebral cortex of C57BL/6 suckling mice and identified; modeling time was determined by CCK-8 and AS-derived exosomes were extracted by ultracentrifugation from cell supernatant and identified by electron microscopy, particle size analysis, and WB for marker proteins. RT-qPCR was used to detect the miR-193b-3p expression in AS and AS-derived exosomes. Low-expressed miR-193b-3p exosomes were extracted from AS after being transfected miR-193b-3p inhibitory sequence and co-incubated with OGD/R bEnd. 3 cells (group of OGD/R+AS-derived inhibitory sequence exosomes); exosomes were extracted from AS transfecting with miR-193b-3p negative sequence, and co-incubated with OGD/R bEnd.3 cells (group of OGD/R+AS-derived negative sequence exosomes); and normal exosomes were co-incubated with OGD/R bEnd. 3 cells (group of OGD/R+AS-derived exosomes). The miR-193b-3p expression in these 3 groups was detected by RT-qPCR, expressions of TRPM2, cleaved-caspase-3, Bax, Bcl-2, ZO-1, and Claudin-5 were detected by WB, cell apoptosis was detected by flow cytometry, and cell migration ability was detected by scratch test.Results:(1) Dual-luciferase reporter gene assay showed that miR-193b-3p could bind to TRPM2 mRNA. The miR-193b-3p can improve the TRPM2-mediated apoptosis and tight junction reduction in bEnd.3 cells during OGD/R: compared with OGD/R group, OGD/R+miR-193b-3p mimics group had significantly decreased TRPM2, cleaved-caspase-3, and Bax protein expressions, and statistically increased Bcl-2, ZO-1 and Claudin-5 protein expressions ( P<0.05). Flow cytometry further verified the above results: compared with OGD/R group, OGD/R+miR-193b-3p mimics group had significantly decreased cell apoptosis rate (21.34% vs. 13.93%, P<0.05). (2) The extracted exosomes exhibited lipid bilayer cup-like structure with particle size of 126.5 nm (exosome marker proteins: negative Cal and positive CD81 and SG101), indicating successful exosome extraction. After modeling, miR-193b-3p expression in AS and AS-derived exosomes was significantly decreased compared with that in the Control goup ( P<0.05). Compared with the OGD/R group, the group of OGD/R+AS-derived exosomes and group of OGD/R+AS-derived negative sequence exosomes had significantly increased miR-193b-3p expression, statistically decreased TRPM2, cleaved-caspase-3 and Bax protein expressions, and significantly increased ZO-1, Claudin-5 and Bcl-2 expressions ( P<0.05); while compared with those in the OGD/R group, no significant changes in the above protein expressions in group of OGD/R+AS-derived inhibitory sequence exosomes were noted ( P>0.05). Compared with the OGD/R group (18.22%), group of OGD/R+AS-derived exosomes and group of OGD/R+AS-derived negative sequence exosomes had significantly decreased apoptosis rate (14.09% and 13.79%, P<0.05), while group of OGD/R+AS-derived inhibitory sequence exosomes had no significant change (18.41%, P>0.05). Compared with the OGD/R group (13.55%), group of OGD/R+AS-derived exosomes and group of OGD/R+AS-derived negative sequence exosomes had significantly increased migration ability (43.01% and 40.59%, P<0.05), while group of OGD/R+AS-derived inhibitory sequence exosomes had no significant change (16.26%, P>0.05). Conclusion:AS-derived exosomes can suppress TRPM2 protein expression in brain microvascular endothelial cells distantly by miR-193b-3p to improve the brain microvascular endothelial cell injury caused by OGD/R, and then improve OGD/R injury.
6.Analysis of the application effect of orthopedic medical equipment maintenance model based on analytic hierarchy process
Jingning WEN ; Xiaoying LI ; Yunfei ZHANG ; Lining WEN ; Xueting YANG ; Tian TIAN ; Wen WEI ; Shuangqian YU
China Medical Equipment 2024;21(8):121-126
Objective:To establish a medical equipment maintenance model based on the analytic hierarchy process(AHP),and to study its application effect in the management of orthopedic medical equipment in hospitals.Methods:Based on the analytic hierarchy process(AHP),the equipment maintenance model was constructed from the classification of the service life,failure mode,failure consequences and other indicators of orthopedic medical equipment.25 sets of medical equipment in clinical use in the Department of Orthopedics of The Second Affiliated Hospital of the Air Force Medical University from 2019 to 2022 were randomly selected,taking the time as the dividing point,the traditional orthopedic medical equipment management model(referred to as traditional management)was implemented during the equipment use period from 2019 to 2020,and the equipment maintenance model based on AHP was used to manage orthopedic medical equipment(referred to as model management)during the equipment use period from 2021 to 2022.A total of 1,000 equipment usage records were collected,500 for each mode,and the effect of equipment repair and maintenance,the satisfaction score of equipment usage management and the incidence of adverse events were compared under different management modes.Results:The cost-effectiveness of equipment using the model management mode was an average of CNY(34,500.00±4,700.00)per unit per year,which was higher than that of the traditional management mode,the difference was statistically significant(t=8.417,P<0.05),the maintenance costs and operating costs were CNY(15,381.95±13.67)per year and CNY(31,600.00±10,500.00)per year,respectively,which lower than those of the traditional management model,the difference was statistically significant(t=858.675,5.371,P<0.05).The scores of equipment management personnel on equipment performance,timeliness and cleanliness of the equipment using the model management mode,and the patients'satisfaction with convenience,effect and comfort of the equipment(9.65±1.14),(9.74±1.38),(9.53±1.09),(9.58±1.07),(9.62±1.14)and(9.81±1.28),respectively,which were all higher than those of the traditional management mode,the difference was statistically significant(t=5.629,5.687,4.736,8.085,5.330,7.680,P<0.05).The total incidence of adverse events in equipment using model management mode was 4.8%(24/500),which was lower than that of the traditional management mode,the difference was statistically significant(x2=12.515,P<0.05).Conclusion:The application of medical equipment maintenance model based on analytic hierarchy process to the management of orthopedic medical equipment can effectively reduce the equipment maintenance cost,improve the cost-effectiveness of the equipment,and improve the satisfaction of the equipment use management personnel.
7.Expert consensus on the construction, evaluation and application of bone organoids (version 2024)
Jian WANG ; Long BAI ; Xiao CHEN ; Yuanyuan LIU ; Guohui LIU ; Zhongmin SHI ; Kaili LIN ; Chuanglong HE ; Jing WANG ; Zhen GENG ; Weiyang SHI ; Wencai ZHANG ; Fengjin ZHOU ; Qiang YANG ; Lili YANG ; Zhiwei WANG ; Haodong LIN ; Yunfei ZHANG ; Fuxin WEI ; Wei CHEN ; Wenguo CUI ; Fei LUO ; Jun FEI ; Hui XIE ; Jian LUO ; Chengtie WU ; Xuanyong LIU ; Yufeng ZHENG ; Changsheng LIU ; Jiacan SU
Chinese Journal of Trauma 2024;40(11):974-986
Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.
8.Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine (version 2024)
Xiao CHEN ; Hao ZHANG ; Man WANG ; Guangchao WANG ; Jin CUI ; Wencai ZHANG ; Fengjin ZHOU ; Qiang YANG ; Guohui LIU ; Zhongmin SHI ; Lili YANG ; Zhiwei WANG ; Guixin SUN ; Biao CHENG ; Ming CAI ; Haodong LIN ; Hongxing SHEN ; Hao SHEN ; Yunfei ZHANG ; Fuxin WEI ; Feng NIU ; Chao FANG ; Huiwen CHEN ; Shaojun SONG ; Yong WANG ; Jun LIN ; Yuhai MA ; Wei CHEN ; Nan CHEN ; Zhiyong HOU ; Xin WANG ; Aiyuan WANG ; Zhen GENG ; Kainan LI ; Dongliang WANG ; Fanfu FANG ; Jiacan SU
Chinese Journal of Trauma 2024;40(3):193-205
Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.
9.Mental health status and its influencing factors among residents in Zhuhai
Ning WEI ; Jingju QUAN ; Yixuan WU ; Yongyong TENG ; Chun MAO ; Jiaju HUANG ; Yunfei KE ; Yajun SUN
Sichuan Mental Health 2024;37(5):457-463
Background Currently,there has been a gradual increase in the incidence of mental diseases,becoming a problem that has attracted great concern of the general public.Zhuhai is a core city of the Guangdong-Hong Kong-Macao Greater Bay Area,and the local government have attached great importance to the mental health of residents.The systematic study on the mental health has focused largely on pregnant women and medical workers,yet few are on the adult residents.Objective To investigate the prevalence and its influencing factors of anxiety and depression among adult residents in Zhuhai,so as to provide references for formulating targeted psychological intervention strategies.Methods From September 1 to December 1,2021,a cohort of 5 600 permanent residents aged 18 years and above in Zhuhai were selected through multistage sampling.All participants were subjected to complete Patients' Health Questionnaire Depression Scale-9 item(PHQ-9),Generalized Anxiety Disorder Scale-7 item(GAD-7)and National Mental Health Literacy Questionnaire based on Wenjuanxing software.Then Logistic regression was employed to identify the factors associated with anxiety and depression among the residents.Results Among the 5 600 residents,depressive symptoms were detected in 842(15.04%)residents and anxiety symptoms in 579(10.34%)residents.Logistic regression analysis yielded that female gender(OR=1.488),living in Doumen district(OR=1.942),junior college/undergraduate level(OR=3.602),postgraduate and above(OR=5.904),irregular meal pattern(OR=3.320),comorbid chronic diseases(OR=3.244),disqualification of self-assessment(OR=3.414)and disqualification of mental health skill(OR=2.131)were risk factors for depression symptoms,whereas age≥25 years old(of all age groups OR<1),monthly per capita income>20 000 yuan(OR=0.438)and exercising≥3 times a week(OR=0.431)were protective factors for depression symptoms.Age of 25~34 years old(OR=2.051),living in Jinwan district(OR=1.729)or Doumen district(OR=1.901),junior college/undergraduate level(OR=2.955),postgraduate and above(OR=6.662),irregular meal pattern(OR=2.741),comorbid chronic diseases(OR=3.535),disqualification of self-assessment(OR=3.325)and disqualification of mental health skill(OR=1.838)were risk factors for anxiety symptoms,while monthly per capita income of 6 001~9 000 yuan(OR=0.665)and exercising≥3 times a week(OR=0.572)were protective factors for anxiety symptoms.Conclusion The mental health status of adult residents in Zhuhai is affected by various factors,including gender,age,region of residence,education level,meal pattern,exercise frequency and chronic diseases.
10.Challenges and suggestions for human genetic resource management in international cooperation of medical institutions caused by the Implementation Rules of the Regulations on the Management of Human Genetic Resources: A case study of Peking University Cancer Hospital
Shuanglei KONG ; Yunfei GENG ; Luopei WEI ; Lingling BAI ; Shuqin JIA
Chinese Journal of Medical Science Research Management 2024;37(1):18-21
Objective:According to the international cooperation project of Peking University Cancer Hospital on human genetic resource management practices, combined with the development direction of human genetic resource management laws and regulations, and propose reference suggestions for medical institutions to strengthen human genetic resource management.Methods:Sort out the projects that Peking University Cancer Hospital obtained international cooperation approval on the government platform of the Ministry of Science and Technology from July 2019 to June 2023, analyze the current situation of human genetic resource management in the hospital, summarize the challenges brought by the implementation of new regulations on human genetic resource management in medical institutions, and propose corresponding suggestions.Results:A total of 1276 international cooperation projects on human genetic resources have been approved, including 345 initial declarations and 931 change declarations. Involving 453 studies, including 286 clinical trials of drugs or devices on the market, accounting for 63.13%, and 100 clinical trials of Phase I drugs, accounting for 34.97% of the market studies. On average, there are 3.14 changes per project for listed research, and 1.56 changes per project for non listed research.Conclusions:Regulations on the Management of Human Genetic Resources ( short for Rules) limit the management scope of international cooperation projects involving human genetic resources and delegate management authority to medical institutions. Adjusting the scope of application for international cooperative clinical trial filing may result in some administrative approval projects being transferred to filing. The approval process for international cooperative scientific research projects on human genetic resources has been adjusted. Suggest medical institutions to strengthen the management of samples and intellectual property outside the scope of application of Rules.Strengthen the entire process management of international cooperation in scientific research. Pay attention to and timely communicate the dynamics of human genetic resource management.

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