Meta-analysis And Network Pharmacology Study Of Chaihu Plus Longgumuli Decoction In The Treatment Of Tumor-related Depression

Objective:1.Understand the clinical efficacy and safety of Chaihu plus Longgumuli Decoction and provide evidence-based evidence for its clinical application.2.To explore the mechanism of Chaihu plus Longgumuli Decoction in the treatment of tumor-related depression.Method:1.Meta-analysis: using China Knowledge Network,Wanfang,Chongqing Weipu,Cochrane Library,Pubmed and other databases and various academic and conference reports,search for the period from January 1,2010 to December 31,2020,using Bupleurum A clinical randomized controlled trial of Jialonggumuli Decoction in the treatment of tumor-related depression.The literature outcome indicators include HAMD score,adverse reactions,total effective rate and quality of life score.Finally,the Revman5.3 software was used to conduct a meta-analysis of the outcome indicators.2.Network pharmacology research: extract the active ingredients and related targets of Bupleurum by searching the Chinese Medicine System Pharmacology Database(TCSP);search Gene Cards and OMIM databases to extract tumor-related depression disease targets;use STRING database to construct proteins Interaction network,Cytoscape constructs drug-compound-target-disease network,DAVID database performs GO enrichment analysis and KEGG pathway enrichment analysis on the target,and finally uses software such as Py MOL(pymol)for molecular docking.Result:Meta analysis:1.Finally,18 literatures were included,with 1764 cases,including879 cases in the experimental group(or observation group,treatment group)and 885 cases in the control group.2.11 literatures reported the Hamilton Depression Rating Scale(HAMD).Among them,"Zhao Jinwei 2019" was not included in the Hamilton Depression Rating Scale Meta-analysis due to missing data.Meta analysis results of the remaining 10 articles: test for heterogeneity X2=182.20,P<0.00001,I2=95%.Combined effect size MD overall=-5.26,MD overall 95%CI=[-7.63,-2.90].The test for overall effect Z value=4.37,P<0.00001.3.11 articles reported adverse reactions.Meta-analysis results: test for heterogeneity results: X2=19.75,P<0.03,I2=49%.The combined effect size RR overall=0.31,and the overall RR 95%CI=[0.24,0.41].The test for overall effect Z value=4.74,P<0.00001.Among them:(1)5reports reported drowsiness and fatigue.Meta-analysis results: test for heterogeneity X2=2.34,P=0.67,I2=0%.Combined effect size RR drowsiness and fatigue=0.14,RR drowsiness,fatigue 95%CI=[0.05,0.41].The test for overall effect Z value=3.53,P=0.0004.(2)Eight papers reported dry mouth.Meta analysis results: test for heterogeneity X2=9.35,P=0.23,I2=25%.The combined effect size RR dry mouth = 0.37,RR dry mouth 95% CI = [0.23,0.60].Test for overall effect(test for overall effect)Z value = 4.11,P <0.0001.(3)Nine articles reported dizziness and headache.Meta analysis results: test for heterogeneity X2=4.96,P=0.76,I2=0%.Combined effect size RR dizziness,headache=0.26,RR dizziness,headache 95%CI=[0.12,0.56].Combined test for overall effect(test for overall effect)Z value = 3.46,P = 0.0005.(4)Seven reports reported nausea,and the results of the Meta analysis: test for heterogeneity X2=3.86,P=0.70,I2=0%.Combined effect size RR nausea=0.52,RR nausea 95%CI=[0.26,1.03].The test for overall effect(test for overall effect)Z value = 1.87,P = 0.06.(5)Four reports reported on constipation,and the results of Meta analysis: test for heterogeneity X2=1.19,P=0.76,I2=0%.Combined effect size RR constipation=0.47,RR constipation95%CI=[0.24,0.90].Test for overall effect(test for overall effect)Z value= 2.27,P = 0.02.(6)Four reports reported blurred vision and the results of Meta analysis: test for heterogeneity X2=0.29,P=0.96,I2=0%.Combined effect size RR blurred vision=0.43,RR blurred vision95%CI=[0.19,1.00].The test for overall effect(test for overall effect)Z value = 1.96,P = 0.05.4.In terms of quality of life score:(1)4 articles reported physiological function,and the results of Meta analysis: test for heterogeneity X2=0.67,P=0.88,I2=0%.Combined effect size MD physiological function=11.66,MD physiological function95%CI=[8.46,14.82].The test for overall effect Z value=7.17,P<0.00001.(2)Four articles reported on physiological functions.Meta analysis results: test for heterogeneity results: X2=0.22,P=0.97,I2=0%.Combined effect size MD physiological function=22.46,MD physiological function 95%CI=[18.91,26.01].The combined effect size test(test for overall effect)Z value = 12.40,P <0.00001.(3)Four articles reported physical pain,and the results of the Meta analysis: test for heterogeneity X2=1.01,P=0.80,I2=0%.Combined effect size MD somatic pain=8.47,MD somatic pain 95%CI=[4.64,12.31].The test for overall effect Z value=4.33,P<0.00001.(4)Five reports reported on general health.Meta-analysis results: test for heterogeneity X2=3.32,P=0.51,I2=0%.Combined effect size MD overall health=10.65,MD overall health 95%CI=[8.54,12.76].The test for overall effect Z value=9.87,P<0.00001.(5)Four reports reported on vitality.Meta analysis results: test for heterogeneity X2=0.04,P=1,I2=0%.The combined effect size MD activity = 14.44,MD activity 95% CI = [10.42,18.46].The test for overall effect Z value=7.04,P<0.00001.(6)Four articles reported on social function.Meta analysis results: test for heterogeneity X2=1.45,P=0.69,I2=0%.Combined effect size MD social function=25.54,MD social function 95%CI=[20.22,30.86].The test for overall effect Z value=9.41,P<0.00001.(7)Four articles reported on affective functions.Meta analysis results: test for heterogeneity X2=2.07,P=0.56,I2=0%.Combined effect size MD affective function=9.24,MD affective function 95%CI=[5.88,12.60].The test for overall effect Z value=5.39,P<0.00001.(8)Four articles reported on mental health.Meta-analysis results: test for heterogeneity X2=2.12,P=0.55,I2=0%.The combined effect size MD mental health=1.23,MD mental health95%CI=[1.12,1.34].The combined effect size test(test for overall effect)Z value = 21.60,P <0.00001.5.15 papers reported the total effective rate and the results of the Meta analysis: test for heterogeneity X2=31.39,P=0.005,I2=55%.The combined effect size RR overall = 1.17,and the overall RR 95% CI =[1.09,1.25].The test for overall effect Z value=4.63,P<0.00001.Network pharmacology research: searching for TCMSP and screening through OB value and DL value to obtain 17 active ingredients,9 of which act on tumor-related depression-related protein targets.Search Gene Cards database and OMIM database to get 18367 disease targets,and map compound targets to disease targets to get 157 intersection targets.Import the results into Cytoscape software to construct a "drug-compound-target-disease" network.Import the key targets into the STRING database to obtain the protein interaction network diagram.The specific results of GO enrichment and KEGG enrichment analysis of 157 key targets are shown in the text.Molecular docking shows that quercetin,isorhamnetin,Longikaurin A,Cubebin and other compounds dock well with the top 5 proteins.Conclusions:1.Mate analysis: Compared with the control group,Chaihu plus Longgumuli Decoction in the treatment of tumor-related depression,in the Hamilton Depression Scale score,total effective rate,quality of life changes: physiological function,physiological function,physical pain,overall Health,social function,vitality,emotional function,mental health,adverse reactions: Drowsiness,fatigue,dry mouth,dizziness,headache,constipation,etc.are more advantageous.There is no significant difference from the control group in terms of nausea and blurred vision.In terms of many outcome indicators,the difference between the experimental group and the control group is statistically significant.In clinical practice,in addition to conventional western medicine for antidepressant,the use of Chaihu plus Longgumuli Decoction to treat tumor-related depression can become a new option and worthy of promotion.The conclusion has guiding significance for clinical work.However,due to the relatively small number of documents and sample size included in this study,and the low quality scores,the final results of the Meta analysis may be biased and the reliability of the conclusions will be reduced.Therefore,to obtain more true,objective,and reliable clinical research data,a larger sample size,multi-center clinical randomized double-blind controlled trial is still needed,so that the treatment of Chinese medicine can move from individual cases to groups,and at the same time pay attention to the meta-analysis.Relevant methodological research can further promote the development of evidence-based medicine and modern research in Chinese medicine.2.Network pharmacology research: The clinical efficacy of Bupleurum in the treatment of tumor-related depression is definite,and its therapeutic effect is based on the overall pharmacodynamic effects of multiple components,multiple pathways and multiple targets.This article excavated Bupleurum in the treatment of tumor-related depression.The underlying mechanism of disease provides a theoretical basis for further experimental research.