Meta-analysis And Network Pharmacology Study On The Treatment Of Infertility With The Method Of Tonifying Kidney And Soothing Liver

Objective:Meta-analysis system was used to evaluate the clinical efficacy and safety of the method of tonifying the Kidney and soothing the Liver in the treatment of female infertility,the network pharmacological method was used to predict the main active components,targets and pathways of the treatment of female infertility with the method of tonifying the Kidney and soothing the Liver,to provide the theoretical basis for the follow-up experimental verification,drug development,clinical application and so on.Methods:We searched six databases at home and abroad for literature published up to February 2022,and completed the literature search and screening according to the inclusion and exclusion criteria,the general data,intervention measures,outcome measures and other related data were extracted and sorted by Excel software,and the literature quality was evaluated by referring to Cochrane bias risk assessment method.Revman software was used to conduct a Meta-analysis of the primary and secondary outcome measures,and a single-study sensitivity analysis was used for each study with large heterogeneity.To standardize the names of Traditional Chinese Medicine（TCM）,to organize the included TCM prescriptions,to analyze the association rules of TCM based on Apriori function and using SPSS Modeler software,according to the degree of support,confidence and promotion,the core drug combination of kidney-tonifying and liver-soothing method was obtained.All active components of core drugs were retrieved from the TCMSP database,and candidate compounds for core drugs were screened according to OB≥30%and DL≥0.18,the gene numbers and the standardized nomenclature of the corresponding targets were obtained by Uniprot database.Cytoscape software was used to construct the“Drug-active ingredient-target”network map,and to obtain the main components of drugs.Using Gene Cards,OMIM,Drugbank,TTD and other databases to obtain the disease targets of female infertility,the drug targets and the disease targets were deleted duplicate values,and the intersection targets of core drugs and diseases were obtained by using Venny software,at the same time,the target information was input into the String platform,and a visualized PPI network of protein interaction was constructed.The core targets were selected from the PPI network graph,and the core targets were imported into the Metascape platform to complete the GO and KEGG analysis,the result of enrichment pathway is visualized by Bioinformatics platform.Cytoscape was used to construct the relationship of drug-component-pathway-core target to construct a visual interaction network map to obtain the core components,targets and pathways that may play a role.Results:1 Meta-analysis:1.1 A total of 898 articles were retrieved from the database.After de-weighting,some articles were excluded according to the exclusion criteria,and 12 studies were finally included.Of the included studies,more than half did not mention the diagnostic criteria,and some had subjective biases,such as the lack of mention of efficacy criteria and the imprecise setting of interventions.1.2 The sample size of each index group is small,the quality of the whole article is general,and the data is unstable.1.3 In the analysis of the main outcome measures,except that the ovulation rate was not meta-analyzed because of the differences in the calculation methods of the included studies,the remaining total response rate,pregnancy rate and endometrial thickness showed little heterogeneity between studies（I²<50%）,the effect of Bushenshugan Group on improving endometrial thickness,increasing total effective rate and pregnancy rate was significantly better than that of the control group（p<0.05）.1.4 The analysis of 4secondary outcome measures showed that the heterogeneity of LH,E₂,P,T and PRL was large（I²>70%）,and the source of heterogeneity of T was not found,so meta analysis was abandoned The levels of E₂,P and PRL were significantly decreased after exclusion of some literatures.The results showed that the levels of E₂,P and PRL were significantly improved after treatment in the TCM Group compared with those in the western medicine group（P<0.05）,but there was no significant difference in LH level（P>0.05）.There was no heterogeneity in the study of FSH level and the incidence of adverse reactions.The results showed that the level of FSH in the Chinese medicine group was significantly improved compared with that in the Western medicine group after treatment（P<0.05）,however,there was no significant difference in the incidence of adverse reactions between the two groups（P>0.05）.1.5According to the Association rules of TCM,the support,confidence,promotion and frequency of Cuscutae semen,Angelica sinensis,Bupleurum chinense and Rehmannia glutinosa in the association rules were higher,it is the core drug combination of kidney-tonifying and liver-soothing therapy for female infertility.2 Network pharmacology research:The network interaction map was constructed to screen out that Isorhamnetin,Kaempferol and Quercetin were the main components of the therapy of tonifying Kidney and soothing Liver,and the core targets were AKT1,TP53,ERBB2,VEGFA and IL6,the key Pathways were In cancer,Human cytomegalovirus infection,PI3K-Akt,Micro RNA and MAPK.Conclusions:1 Meta-analysis1.1 The curative effect of TCM Group was better than that of Western medicine group.1.2 There was no obvious advantage in the treatment of sterility between the TCM group and the Western medicine group.1.3 The core medicine combination of the method of tonifying the Kidney and soothing the Liver in treating Infertility is Cuscutae semen,Angelica sinensis,Bupleurum chinense and Rehmannia glutinosa.2 Network pharmacological researchPathways in cancer,Human cytomegalovirus infection,PI3K-Akt,Micro RNA,MAPK and other key Pathways mediated by AKT1,TP53,Erbb2,VEGFA and IL6 may play anti-infection,anti-tumor,anti-oxidation and regulation of metabolism in the treatment of female infertility.