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Mechanism of action of the bile acid receptor TGR5 in obesity

Acta Pharmaceutica Sinica B 2024年第2期14卷 468-491页

作者： Weijun Lun Qihao Yan Xinghua Guo Minchuan Zhou Yan Bai Jincan He Hua Cao Qishi Che Jiao Guo Zhengquan Su guangdong Engineering research center of Natural Products and New Drugs Guangdong Provincial University Engineering Technology Research Center of Natural Products and DrugsGuangdong Pharmaceutical UniversityGuangzhou 510006China guangdong metabolic disease research center of integrated chinese and western medicine Key Laboratory of Glucolipid Metabolic DisorderMinistry of Education of ChinaGuangdong TCM Key Laboratory for Metabolic DiseasesGuangdong Pharmaceutical UniversityGuangzhou 510006China School of Public Health Guangdong Pharmaceutical UniversityGuangzhou 510310China School of Chemistry and Chemical Engineering Guangdong Pharmaceutical UniversityZhongshan 528458China Guangzhou Rainhome Pharm&Tech Co. Ltd.Science CityGuangzhou 510663China

G protein-coupled receptors(GPCRs)are a large family of membrane protein receptors,and Takeda G protein-coupled receptor 5(TGR5)is a member of this family.As a membrane receptor,TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism,including the processes of energy consumption,weight loss and blood glucose homeostasis.Recent studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver,obesity and diabetes.With the global obesity situation becoming more and more serious,a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently needed.In this review,we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target,and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands,which can effectively provide new ideas for ligand research and promote drug research.

关键词： Obesity TGR5 Bile acids Ligand Appetite Metabolism GLP-1 Inflammation

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Fu-Zheng-Yi-Liu Formula inhibits the stem cells and metastasis of prostate cancer via tumor-associated macrophages/C-C motif chemokine ligand 5 pathway in tumor microenvironment

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chinese Journal of Natural medicines 2024年第6期22卷 501-514页

作者： CHEN Chiwei HUANG Renlun WANG Neng ZHENG Yifeng ZHOU Jianfu YANG Bowen WANG Xuan ZHANG Juping PAN Bo CHEN Zhiqiang WANG Shengqi WANG Zhiyu XIANG Songtao The research center of Integrative Cancer medicine Discipline of Integrated Chinese and Western Medicinethe Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou 510000China The First Clinical College of Guangzhou University of chinese medicine Guangzhou 510000China guangdong Provincial Key Laboratory of Clinical research on Traditional chinese medicine Syndrome Guangdong Provincial Academy of Chinese Medical SciencesGuangdong Provincial Hospital of Chinese MedicineGuangzhou 510000China guangdong-Hong Kong-Macao Joint Lab on chinese medicine and Immune disease research Guangzhou University of Chinese MedicineGuangzhou 510000China The research center for Integrative medicine School of Basic Medical SciencesGuangzhou University of Chinese MedicineGuangzhou 510000China State Key Laboratory of Dampness Syndrome of chinese medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510000China

Prostate cancer(PCa)is the second most common malignancy among men globally.The Fu-Zheng-Yi-Liu(FZYL)Formula has been widely utilized in the treatment of PCa.This study investigates whether the FZYL Formula can inhibit PCa by tar-geting the TAMs/CCL5 pathway.We conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their in-teraction.Results showed that the FZYL Formula significantly reduced the proliferation,colony formation,subpopulations of PCSCs,and sphere-formation efficacy of PCa cells,even in the presence of TAM co-culture.Additionally,the Formula markedly decreased the migration,invasion,and epithelial-mesenchymal transition(EMT)of PCa cells induced by TAMs.The FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion,with minimal cytotoxicity observed.Mechanistic studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula,as the addition of exogen-ous CCL5 partially reversed the formula’s inhibitory effects on PCSCs self-renewal in the co-culture system.Importantly,the Formula also significantly inhibited the growth of PCa xenografts,bone metastasis,and PCSCs activity in vivo by targeting the TAMs/CCL5 pathway.Overall,this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target.

关键词： Traditional chinese medicine Tumor-associated macrophages Prostate cancer stem cells CCL5 Tumor microenvironment

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Bioactive components, pharmacological properties and underlying mechanism of Ganoderma lucidum spore oil: A review

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chinese Herbal medicines 2024年第3期16卷 375-391页

作者： Jianying Liu Binzhi Zhang Leqi Wang Shasha Li Qinqiang Long Xue Xiao guangdong metabolic diseases research center of integrated chinese and western medicine (Institute of chinese medicine) Guangdong Pharmaceutical University The Second Clinical College of Guangzhou University of chinese medicine Guangzhou Higher Education Mega Center NMPA Key Laboratory for Rapid Testing Technology of Drugs Guangdong Institute for Drug Control

Ganoderma lucidum is a chinese medicinal fungus with a long history of use in healthcare and disease treatment.G.lucidum spores（GLS） are tiny germ cells released from the mushroom cap during the mature stage of growth.They contain all the genetic active substances of G.lucidum.G.lucidum spore oil（GLSO） is a lipid component extracted from broken-walled Ganoderma spores using supercritical CO2extraction technology.GLSO contains fatty acids,Ganoderma triterpenes,sterols and other bioactive compounds.Previous studies have demonstrated that GLSO has a wide range of pharmacological properties,including anti-tumor,anti-aging,neuroprotection,immunomodulation,hepatoprotection and modulation of metabolic diseases.This review summarizes the research progress of GLSO over the past two decades in terms of its bioactive components,extraction and processing techniques,pharmacological effects and safety evaluation.This provides a solid foundation for further research and application of GLSO.

关键词： anti-aging anti-tumor bioactive components Ganoderma lucidum spore oil hepatoprotection immune regulation pharmacological properties

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Distribution of Traditional chinese medicine syndromes in diabetic kidney disease chronic kidney disease 1-5: a correlation study

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Journal of Traditional chinese medicine 2024年第3期44卷 572-580页

作者： LI Shuang DUAN Shuwei DONG Zheyi QU Yilun LUO Yayong KE Jianghua WANG Conghui PENG Yangzhi ZHOU Xuefeng CHEN Xiangmei Department of Nephrology First Medical Center of Chinese PLA General HospitalNephrology Institute of the Chinese People's Liberation ArmyNational Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease Research School of Clinical medicine Guangdong Pharmaceutical University Basic Medical College Chengdu University of Traditional Chinese Medicine

OBJECTIVE: To analyze the distribution of Traditional chinese medicine(TCM) syndromes in patients with diabetic kidney disease(DKD) and its related factors.METHODS: We enrolled 435 patients with DKD, who were not undergoing dialysis, admitted to the Department of Nephrology, First Medical center, chinese PLA General Hospital from April 2020 to August 2021.Analysis of their TCM syndromes and related factors was carried out.RESULTS: The 435 patients included 109, 117, 86, and 123 chronic kidney disease(CKD) 1-2, CKD3, CKD4, and CKD5 cases, respectively. With the progression of CKD1-5, the proportion of Yin deficiency and dry heat syndrome,and that of Qi and Yin deficiency syndrome showed a downward trend, whereas the proportion of spleen-kidney Yang deficiency, blood deficiency, blood stasis, water stagnation, and phlegm turbidity syndromes showed an upward trend; the differences were statistically significant(P < 0.05). Multivariate logistic regression analysis showed that Yin deficiency and dry heat syndrome was positively correlated with hemoglobin [odds ratio(OR) =1.022, P = 0.005], albumin(OR = 1.058, P = 0.006), and estimated glomerular filtration rate(eGFR)(OR = 1.020,P < 0.001) but negatively correlated with male sex(OR =0.277, P = 0.004). Qi and Yin deficiency syndrome was positively correlated with albumin(OR = 1.056, P < 0.001)and eGFR(OR = 1.008, P = 0.022) but negatively correlated with age(OR = 0.977, P = 0.023). Liver-kidney Yin deficiency syndrome was positively correlated with age(OR = 1.028, P = 0.021) and glycosylated hemoglobin(OR = 1.223, P = 0.007) but negatively correlated with total cholesterol(OR = 0.792, P = 0.006).Spleen-kidney Yang deficiency syndrome was negatively correlated with hemoglobin(OR = 0.977, P < 0.001),albumin(OR = 0.891, P < 0.001), and eGFR(OR = 0.978,P < 0.001) but positively correlated with high density lipoprotein(OR = 3.376, P = 0.001). CONCLUSION: With CKD1-5 progression, TCM syndromes changed from Yin deficiency and dry heat syndrome to syndrome of deficiency of both

关键词： albumins correlation of data diabetic nephropathies glomerular filtration rate hemoglobins syndrome and complex

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Tissue-resident macrophages exacerbate lung injury after remote sterile damage

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Cellular & Molecular Immunology 2024年第4期21卷 332-348页

作者： Hanhui Zhong Jingjing Ji Jinling Zhuang Ziying Xiong Pengyun Xie Xiaolei Liu Jundi Zheng Wangli Tian Xiaoyang Hong Jing Tang The Department of Anesthesiology Affiliated Hospital of Guangdong Medical UniversityZhanjiangGuangdongChina The Department of Critical Care medicine General Hospital of Southern Theater Command of PLAGuangzhouChina The Department of Respiratory medicine Guangdong Provincial Hospital of Integrated Chinese and Western MedicineFoshanChina Pediatric Intensive Care Unit Senior Department of Pediatricsthe Seventh Medical Center of PLA General HospitalBeijingChina

Remote organ injury,which is a common secondary complication of sterile tissue damage,is a major cause of poor prognosis and is difficult to manage.Here,we report the critical role of tissue-resident macrophages in lung injury after trauma or stroke through the inflammatory response.We found that depleting tissue-resident macrophages rather than disrupting the recruitment of monocyte-derived macrophages attenuated lung injury after trauma or stroke.Our findings revealed that the release of circulating alarmins from sites of distant sterile tissue damage triggered an inflammatory response in lung-resident macrophages by binding to receptor for advanced glycation end products(RAGE)on the membrane,which activated epidermal growth factor receptor(EGFR).Mechanistically,ligand-activated RAGE triggered EGFR activation through an interaction,leading to Rab5-mediated RAGE internalization and EGFR phosphorylation,which subsequently recruited and activated P38;this,in turn,promoted RAGE translation and trafficking to the plasma membrane to increase the cellular response to RAGE ligands,consequently exacerbating inflammation.Our study also showed that the loss of RAGE or EGFR expression by adoptive transfer of macrophages,blocking the function of RAGE with a neutralizing antibody,or pharmacological inhibition of EGFR activation in macrophages could protect against trauma-or stroke-induced remote lung injury.Therefore,our study revealed that targeting the RAGE-EGFR signaling pathway in tissue-resident macrophages is a potential therapeutic approach for treating secondary complications of sterile damage.

关键词： tissue-resident macrophage RAGE remote sterile damage

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Caveolin‑1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease

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Military Medical research 2024年第2期11卷 206-227页

作者： Guang-Hui Deng Chao-Feng Wu Yun-Jia Li Hao Shi Wei-Chao Zhong Mu-Keng Hong Jun-Jie Li Jia-Min Zhao Chang Liu Meng-Chen Qin Zhi-Yun Zeng Wei-Min Zhang Ken Kin Lam Yung Zhi-Ping Lv Lei Gao Department of Gastroenterology Integrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510315China School of Traditional chinese medicine Southern Medical UniversityGuangzhou 510515China Department of Hepatology Cancer CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510315China Shenzhen Traditional chinese medicine Hospital Shenzhen 518033GuangdongChina Department of Biology Hong Kong Baptist UniversityKowloon TongKowloonHong Kong SAR 999077China

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the liver.This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.Methods:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study.Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro.Moreover,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload model.Besides,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,western blotting,immunofluorescence staining,immunohistochemical staining and ELISA.The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.Results:Significant disorder of lipid and iron metabolism occurred in NAFLD.The expression of Cav-1 was decreased in NAFLD hepatocytes(Pmetabolic homeostasis.It i

关键词： Caveolin-1 Nonalcoholic fatty liver disease Iron metabolism Ferritin Oxidative stress

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Effects of plants-associated microbiota on cultivation and quality of chinese herbal medicines

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chinese Herbal medicines 2024年第2期16卷 190-203页

作者： Yue Ouyang Qiqing Cheng Chunsong Cheng Ziyu Tang Yufeng Huang Eyu Tan Shaofeng Ma Xinheng Lin Ying Xie Hua Zhou guangdong Provincial Hospital of chinese medicine Guangdong Provincial Academy of Chinese Medical SciencesState Key Laboratory of Dampness Syndrome of Chinese MedicineSecond Affiliated Hospital of Guangzhou University of Chinese MedicineGuangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease ResearchGuangzhou 510006China Faculty of chinese medicine Macao University of Science and TechnologyMacao 999078China School of Pharmacy Hubei University of Science and TechnologyXianning 437100China Key Laboratory of Plant Ex-situ Conservation and research center of Resource Plant Lushan Botanical GardenChinese Academy of SciencesJiujiang 332900China Jiangmen Wuyi Hospital of Traditional chinese medicine Jiangmen 529020China Joint Laboratory for Translational Cancer research of chinese medicine Ministry of EducationGuangzhou University of Chinese MedicineGuangzhou 510006China

Microbial resource influences the life activities of medicinal plants from several perspectives.Endophytes,rhizosphere microorganisms,and other environmental microorganisms play essential roles in medicinal plant growth and development,plant yield,and clinical efficacy.The microbiota can influence the biosynthesis of active compounds in medicinal plants by stimulating specific metabolic pathways.They induce host plants to improve their resistance to environmental stresses by accumulating secondary metabolites.Microorganisms can interact with their host plants to produce long-term,targeted selection results and improve their ability to adapt to the environment.Due to the interdependence and interaction between microorganisms and medicinal plants,chinese herbal medicines(CHMs)quality is closely related to the associated microorganisms.This review summarizes the relationship between medicinal plants and their associated microorganisms,including their species,distribution,life activities,and metabolites.Microorganisms can aid in quality control,improve the efficacy of medicinal plants,and provide markers for identifying the origin and storage time of CHMs.Therefore,a comprehensive understanding of the relationship between microorganisms and medicinal plants will help to control the quality of CHMs from different perspectives.

关键词： chinese herbal medicines endophytes environmental microorganisms microbiota rhizosphere microorganisms

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Hepatic Zbtb18 (Zinc Finger and BTB Domain Containing 18) alleviates hepatic steatohepatitis via FXR (Farnesoid X Receptor)

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Signal Transduction and Targeted Therapy 2024年第2期9卷 766-781页

作者： Lei Zhang Jiabing Chen Xiaoying Yang Chuangpeng Shen Jiawen Huang Dong Zhang Naihua Liu Chaonan Liu Yadi Zhong Yingjian Chen Kaijia Tang Jingyi Guo Tianqi Cui Siwei Duan Jiayu Li Shangyi Huang Huafeng Pan Huabing Zhang Xiaoqiang Tang Yongsheng Chang Yong Gao State Key Laboratory of Traditional chinese medicine Syndrome Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouChina Key Laboratory of Immune Microenvironment and disease(Ministry of Education) Tianjin Key Laboratory of Cellular Homeostasis and DiseaseDepartment of Physiology and PathophysiologyTianjin Medical UniversityTianjinChina Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogen Biology and ImmunologyJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhouChina Department of Endocrinology The First Clinical CollegeGuangzhou University of Chinese MedicineGuangdongChina The Fourth Clinical Medical College of Guangzhou University of chinese medicine ShenzhenChina Jiangsu Collaborative Innovation center of Traditional chinese medicine in Prevention and Treatment of Tumor Nanjing University of Chinese MedicineNanjingChina Department of Biochemistry and Molecular Biology Metabolic Disease Research CenterSchool of Basic MedicineAnhui Medical UniversityHefeiChina Key Laboratory of Birth Defects and Related diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan UniversityChengduChina

A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease(NAFLD),coupled with hepatitis and insulin resistance.Yet the details of the underlying mechanisms are not fully understood.Here,we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of NAFLD.Hepatic Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation(FAO),and induced insulin resistance.Conversely,hepatic Zbtb18 overexpression alleviated hepato-steatosis,insulin resistance,and hyperglycemia in mice fed on a high-fat diet(HFD)or in diabetic mice.Notably,in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor(FXR)mediated FAO and Clathrin Heavy Chain(CLTC)protein hinders NLRP3 inflammasome activity.This key mechanism by which hepatocyte’s Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXR’s deletion and forced expression in mice and cultured mouse primary hepatocytes(MPHs).Moreover,CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLRP3 inflammasome activity in macrophages.Altogether,Zbtb18 transcriptionally activates the FXR-mediated FAO and CLTC expression,which inhibits NLRP3 inflammasome’s activity alleviating inflammatory stress and insulin resistance,representing an attractive remedy for hepatic steatosis and fibrosis.

关键词： hepatic Hepatic impaired

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Multi-omics analyses of G6PD deficiency variants in chinese population

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Journal of Genetics and Genomics 2024年第1期51卷 100-104页

作者： He Ji Jiahuan Chen Peide Huang Zhimin Feng Weining Hu Mengyao Dai Xiaohui Sun Xiao Jin Guangquan Chen Guang Ning Lin Li Weiqing Wang Yanan Cao Department of Endocrine and metabolic diseases Shanghai Institute of Endocrine and Metabolic DiseasesNational Clinical Research Centre for Metabolic DiseasesState Key Laboratory of Medical GenomicsResearch Unit of Clinical and Basic Research on Metabolic Diseases of Chinese Academy of Medical SciencesRuijin Yangtze River Delta Health InstituteWuxi Branch of Ruijin HospitalRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China National research center for Translational medicine National Key Scientific Infrastructure for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China SJTU-BGI Innovation research center Shanghai 200240China BGI-ShenZhen ShenzhenGuangdong 518083China

Glucose-6-phosphate dehydrogenase(G6PD)deficiency is one of the most prevalent hereditary and X-linked enzyme disorders caused by the pathogenetic G6PD(NM_001042351.2)variants(Yang et al.,2016).The clinical manifestations of G6PD deficiency offer a wide spectrum of diverse disease phenotypes(Hecker et al.,2013).Investigations of prevalence and molecular epidemiology demonstrate that G6PD deficiency affects over 400 milion individuals worldwide and leads to thousands of deaths annually(Mortality and Causes of Death,2015).

关键词： al. G6PD epidemiology

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Trial characteristics and treatment effect estimates in randomized controlled trials of chinese herbal medicine: A meta-epidemiological study

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Journal of Integrative medicine 2024年第3期22卷 223-234页

作者： Betty H.Wang Ya-li Lin Yin-yan Gao Jin-lu Song Lang Qin Ling-qi Li Wen-qi Liu Claire C.W.Zhong Mary Y.Jiang Chen Mao Xiao-bo Yang Vincent C.H.Chung Irene X.Y.Wu Jockey Club School of Public Health and Primary Care the Chinese University of Hong KongHong Kong 999077China Xiangya School of Public Health Central South UniversityChangsha 410006Hunan ProvinceChina School of chinese medicine the Chinese University of Hong KongHong Kong 999077China School of Public Health Southern Medical UniversityGuangzhou 510080Guangdong ProvinceChina State Key Laboratory of Dampness Syndrome of chinese medicine the Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120Guangdong ProvinceChina chinese medicine Syndrome research Team the Second Affiliated HospitalGuangzhou University of Chinese MedicineGuangzhou 510120Guangdong ProvinceChina guangdong Provincial Key Laboratory of Clinical research on Traditional chinese medicine Syndrome Guangzhou 510120Guangdong ProvinceChina Hunan Provincial Key Laboratory of Clinical Epidemiology Central South UniversityChangsha 410006Hunan ProvinceChina

Background:Previously published meta-epidemiological studies focused on western medicine have identified some trial characteristics that impact the treatment effect of randomized controlled trials(RCTs).Nevertheless,it remains unclear if similar associations exist in RCTs on chinese herbal medicine(CHM).Further,chinese medicine-related characteristics have not been explored yet.Objective:To investigate trial characteristics related to treatment effect estimates on CHM RCTs.Search strategy:This meta-epidemiological study searched 5 databases for systematic reviews on CHM treatment published between January 2011 and July 2021.Inclusion criteria:An eligible systematic review should only include RCTs of CHM and conduct at least one meta-analysis.Data extraction and analysis:Two reviewers independently conducted data extraction on general characteristics of systematic reviews,meta-analyses and included RCTs.They also assessed the risk of bias of RCTs using the Cochrane risk of bias tool.A two-step approach was used for data analyses.The ratio of odds ratios(ROR) and difference in standardized mean differences (dSMD) with 95%confidence interval (CI) were applied to present the difference in effect estimates for binary and continuous outcomes,respectively.Results:Ninety-one systematic reviews,comprising 1338 RCTs were identified.For binary outcomes,RCTs incorporated with syndrome differentiation (ROR:1.23;95%CI:[1.07,1.39]),adopting chinese medicine formula (ROR:1.19;95%CI:[1.03,1.34]),with low risk of bias on incomplete outcome data (ROR:1.29;95%CI:[1.06,1.52]) and selective outcome reporting (ROR:1.12;95%CI:[1.01,1.24]),as well as a trial size≥100 (ROR:1.23;95%CI:[1.04,1.42]) preferred to show larger effect estimates.As for continuous outcomes,RCTs with chinese medicine diagnostic criteria (dSMD:0.23;95%CI:[0.06,0.41]),judged as high/unclear risk of bias on allocation concealment (dSMD:-0.70;95%CI:[-0.99,-0.42]),with low risk of bias on incomplete outcome data (dSMD:0.30;95%CI:[0.18,0.43]),conducted at a single center

关键词： chinese herbal medicine Randomized controlled trial Risk of bias Meta-epidemiological study Effect estimates

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