| Objective:(1)To systematically evaluate the efficacy and safety of Huazhuojiedu method in the treatment of precancerous lesions of chronic atrophic gastritis,in order to provide evidence-based medical evidence for the clinical treatment of precancerous lesions of chronic atrophic gastritis(2)The studies included in the meta-analysis were analyzed on the medication rules,and the drug ideas of Huazhuojiedu method for the treatment of precancerous lesions of chronic atrophic gastritis were discussed,in order to provide a reference for prescription medication(3)A network pharmacological study was conducted to clarify the mechanism of action of the basic formula,baihuasheshecao-guanghuoxiangsharen,obtained from the analysis of the medication rule.Methods:(1)Meta-analysis: In the computer search for clinical studies using Huazhuojiedu in the databases of CNKI,Wanfang,VIP,CBM,Pub Med,Embase and Cochrane Library in the treatment of precancerous lesions of chronic atrophic gastritis,the search time was established until January 3,2023,according to inclusion exclusion criteria,obtaining eligible literature,data extraction,quality evaluation using the Cochrane Risk of Bias Assessment tool,and Rev Man 5.4 were used to analyze the collected outcome data.(2)Medication rule: Entry of prescription data used in meta-analysis into the literature into Excel tables,database creation,drug frequency statistics,SPSS Modeler 18 for association rules and SPSS Statistics 28 for high-frequency drug cluster analysis to obtain core drug combination.(3)Network pharmacology research: The TCMSP database was used to obtain the active ingredients and potential targets of the core drug combination baihuasheshecao-guanghuoxiang-sharen,the names of potential targets of drugs were standardized with the help of the Uniprot database,and the core drug-active ingredient-target network diagram was drawn by Cytoscape 3.9.0 software.The disease targets of precancerous lesions of chronic atrophic gastritis were obtained through Gene Cards and OMIM databases,the common targets of core drugs and diseases were obtained by intersection based on Venny2.1 software,and imported into STRING11.5database to obtain protein interaction information and PPI network diagram was constructed with Cytoscape3.9.0 software to obtain potential core targets and Hub genes.At the same time,DAVID was used to perform GO function enrichment analysis and KEGG pathway enrichment analysis for common targets.Results:(1)Meta-analysis: 23 studies totaling 2574 patients were included,including 1413 patients in the experimental group and 1354 patients in the control group.The results of meta-analysis showed that the treatment of precancerous lesions of chronic atrophic gastritis in the experimental group improved clinical efficacy(total effective rate),(RR=1.29,95%CI=[1.22,1.37],Z=8.99,P<0.00001),TCM symptom efficacy(RR=1.41,95%CI= [1.28,1.55],Z=6.85,P<0.00001),gastroscopy efficacy(RR=1.33,95%CI= [ 1.21,1.46],Z=6.02,P<0.00001),pathological efficacy(RR=1.53,95%CI= [1.33,1.76],Z=6.00,P<0.00001),pathological efficacy of gastroscopy(RR=1.15,95%CI= [1.02,1.29],Z=6.02,P=0.02),The main clinical symptoms include gastric pain(MD=-0.99,95%CI= [-1.30,-0.68],Z=6.30,P<0.00001),ruffian integral(MD=-0.94,95%CI= [-1.40,-0.49],Z=4.03,P<0.00001),belching integral(MD=-0.51,95%CI= [-0.81,-0.21],Z=3.35,P=0.0008),Na difference integral(MD=-0.71,95%CI= [-1.04,-0.37],Z=4.13,P<0.0001),gastroscopic integration(RR=-0.50,95%CI= [-0.83,-0.17],Z=2.93,P=0.003),Hp negative rate(RR=1.44,95%CI= [1.29,1.60],Z=6.44,P<0.00001),serum markers included serum PGI levels(SMD=0.56,95%CI= [0.32,0.80],Z= 4.55,P<0.00001),serum PGR level(SMD=0.38,95%CI= [0.07,0.69],Z=2.37,P=0.02),serum G-17 level(SMD=0.48,95%CI= [0.18,0.78],Z=3.12,P=0.002),serum TFF3 level(SMD=-2.85,95%CI= [-4.44,-1.26],Z=3.52,P= 0.0004),etc.,better than the control group,and the incidence of adverse reactions was low.(2)Medication rule: a total of 23 Chinese medicine prescriptions were included,including 62 flavors of traditional Chinese medicines,and the frequency statistical analysis of these 62 flavors of traditional Chinese medicines showed that the total frequency of medication was 290 times,and the frequency of use was greater than the average frequency of drugs with a total of 25 flavors,namely: huanglian,baihuasheshecao,sharen,quanxie,guanghuoxiang,fuling,banzhilian,peilan,yinchen,baishu,huangqin,pugongying,banbianlian,banxia,baishao,danggui,kushen,tengligen,chuanxiong,donglingcao,ezhu,gualou,sanqi,zexie,zidoukou.The medicinal properties are mostly cold,warm and flat,cold and warm,the medicinal taste is mostly bitter,bitter and sweet,and the spleen meridian,stomach meridian and liver meridian are the mainstay.According to the association rules and high-frequency drug statistics,the basic square baihuasheshecao-guanghuoxiang-sharen was obtained,and 5 new drug groups were obtained by cluster analysis.(3)Network pharmacology research: a total of 28 active compounds involved in the regulation of the network were screened out,including 7baihuasheshecao,11 guanghuoxiang and 10 sharen(some of which contain the same ingredients),and 169 target proteins of traditional Chinese medicine,of which quercetin,stigmasterol and beta-sitosterol were the main active ingredients.2141 disease target proteins were obtained,108 drug anddisease intersection targets were obtained,PPI protein interaction network topology analysis was done,and 52 core proteins were obtained,and the top 10 core target proteins ranked by Degree value were AKT1,VEGFA,JUN,MYC,CASP3,IL6,EGFR,ESR1,HIF1 A,PTGS2;Pass The Cyto Hubba plug-in uses MCC algorithms to obtain Hub genes,which are AKT1,VEGFA,MMP9,PTGS2,IL6,EGF,IL1 B,JUN,FOS,CASP3.GO enrichment analysis yielded 512 entries,including 372 BPs,42 CCs and98 MFs,mainly involving inflammatory response,cell proliferation and apoptosis,angiogenesis,metastasis progression,tissue repair,etc.KEGG obtained 144 signaling pathways,among which the significantly enriched pathways related to precancerous lesions of chronic atrophic gastritis included Pathways in cancer,AGE-RAGE signaling pathway in diabetic complications,Chemical carcinogenesis-receptor activation,IL-17 signaling pathway,HIF-1 signaling pathway,etc.Conclusion:(1)The results of meta-analysis showed that the treatment of precancerous lesions of chronic atrophic gastritis by the huazhuojiedu method was better than the control group in terms of clinical efficacy(total effective rate),TCM symptom efficacy,gastroscopy efficacy,pathological efficacy,gastroscopic pathological efficacy,gastric pain score,ruffian score,belching score,differential score,gastroscopy score,Hp conversion rate,improvement of PGI,PGR,G-17 and TFF3 serum level indexes,and had few adverse reactions and high safety.(2)The results of the analysis of the medication rule showed that the core drugs of the huazhuojiedu method for the treatment of precancerous lesions of chronic atrophic gastritis were 25 flavors of traditional Chinese medicines,such as huanglian,baihuasheshecao,sharen,quanxie,guanghuoxiang,and the basic formula were baihuasheshecaoguanghuoxiang-sharen.(3)The results of network pharmacology showed that baihuasheshecaoguanghuoxiang-sharen,the basic formula of the huazhuojiedu method for the treatment of precancerous lesions of chronic atrophic gastritis,which had the characteristics of multi-component,multi-target and multi-pathway,mainly through key active ingredients such as quercetin,Stigmasterol,betasitosterol,etc.,acting on core targets such as AKT1,VEGFA,JUN,MYC,CASP3,IL6,EGFR,ESR1,HIF1 A,PTGS2,and regulate Pathways in cancer,AGE-RAGE signaling pathway in diabetic complications,Chemical carcinogenesis-receptor activation,IL-17 signaling pathway HIF-1 signaling pathway,etc.and other signaling pathways play a role in inhibiting gastric mucosal inflammatory response,regulating tumor cell proliferation and apoptosis,inhibiting neoangiogenesis,and restoring gastric mucosal cell proliferation and apoptosis equilibrium,so as to achieve the purpose of treating precancerous lesions of chronic atrophic gastritis. |
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