Clinical Efficacy Evaluation And Transcriptomic-based Mechanism Study Of Xinkai Kujiang Method In The Treatment Of Chronic Atrophic Gastritis

Objective:1.To explore the clinical curative effect of Banxia Xiexin Decoction(BXD),a representative prescription of xinkai kujiang method,on serological indicators of gastric function,symptoms of traditional Chinese medicine,anxiety and depression,sleep quality and inflammatory factors of patients with chronic atrophic gastritis(CAG).To observe the safety of BXD in CAG patients.2.Through high-throughput transcriptomics sequencing technology,the differentially expressed genes in the treatment of CAG with BXD were screened,the potential targets and signal pathways were explored,and the molecular mechanism of its action was revealed.Method:1.Clinical Study on the Treatment of CAG with BXDA prospective,randomized,placebo-controlled clinical trial design was adopted,and the inclusion and exclusion criteria were established.116 patients with CAG were randomly divided into two groups,and all patients were given CAG health education.The experimental group and the control group were treated with BXD and placebo for 8 weeks respectively.With serological indicators of gastric function,(PGI?PGII?PGR?G-17),symptoms of traditional Chinese medicine(epigastric pain,epigastric fullness,noisy stomach,listlessness,anorexia),anxiety state(SAS),depression state(SDS),sleep quality(PSQI)inflammatory factorsand(IL-6?IL-17?TNF-?)and safety indicators as evaluation indexes.The clinical efficacy and safety of xinkai kujiang method in treating CAG were evaluated.The study can provide new evidence-based medical evidence for its clinical application.2.Transcriptomic-based Mechanism Study of BXD in the Treatment of Chronic Atrophic GastritisThe fasting blood of 15 patients in Banxia Xiexin Decoction group and 12 patients in placebo group were collected,Use TRIzo to extract total RNA.of blood Illumina novaseq 6000 platform was used for high-throughput non-chain-specific RNA sequencing.The sequencing data were preprocessed and assembled,Bioinformatics analysis of differential gene expression,differential expression genes between samples were analyzed using DEGse software.Genetic interaction analysis using Cytoscape software was performed on the genes of Banxia Xiexin decoction group,The related gene distance was enriched and visualized.Using Metacore software for pathway enrichment analysis and GO biological process clustering analysis of differential gene expression,Mapping the functions GO biological processes and pathways of differentially expressed genes,construct protein interaction networks.Results:1.Clinical Study on the Treatment of CAG with BXDAll patients completed eight weeks of treatment,Three cases,In 13 cases,The final sample size included in the statistical analysis was 113 cases.A little more women than men,Average age in the trial group(54.93±7.85)years,Average duration(49.00±48.16)months;The average age(56.15±8.78)of the control group was 46.29±55.04)months.There was no difference in the two groups of sex,age,course of disease,traditional Chinese medicine(TCM)syndrome types,family history of gastric cancer,atrophy,intestinal metaplasia,BMI index,etc.The characteristics of basic disease were comparable.Comparison of improvement of serological index status of gastric function after treatment,By rank sum test,BXD group was superior to the control group in improving the status of pepsinogen I(PGI)and gastrin-17(G-17),difference was statistically significant(P<0.05).Comparison of quality of life SF-12 improvement score groups,By rank sum test,BXD group is superior to the control group in improving physical health score,difference was statistically significant(P<0.05),and there was no significant difference in mental health score between the two groups(P>0.05).Comparison among TCM symptom scores,By rank sum test,BXD group is superior to the control group in improving the symptoms of epigastric pain,epigastric fullness,fatigue and food intake,difference was statistically significant(P<0.05).To improve the effectiveness of TCM syndrome comparison,The total efficiency of BXD group was 84.48%,The total effective rate in the control group was 29.09%,By ran.k sum test,and the difference was statistically significant(P<0.05).Anxiety,depression,After an independent sample t test,BXD group was superior to the control group in improving SAS score and SDS score,difference was statistically significant(P<0.05).Sleep quality comparison,after independent sample t test,BXD group in improving the PSQI score were better than the control group,the difference was statistically significant(P<0.01).Through rank sum test,BXD was better than the control group in improving inflammatory factor(IL-6?IL-17?TNF-?),the difference was statistically significant(P<0.05).During the treatment in February,the control group had 3 adverse events(headache,diarrhea,abnormal liver function).Other patients had no other symptoms and no serious adverse events occurred during the study.2.Transcriptomic-based Mechanism Study of BXD in the Treatment of Chronic Atrophic GastritisCompared with the healthy control group,228 genes were overexpressed in the CAG model group(experimental group before treatment),and 66 genes were reversed by BXD.At the same time,compared with the healthy control group,554 genes were lower expressed in the CAG model group,and BXD could reverse the abnormal expression of 34 genes.The results of differential expression gene GO enrichment analysis showed that Banxia Xiexin decoction mainly deals with immune regulation(G protein-coupled receptor signaling pathway),inflammatory response(activation of MAPK activity,negative regulation of interleukin-1? production),neural regulation(positive regulation of synaaptic transmission,positive regulation of neurotransmitter transport,excitatory postsynaptic potential)and so on.Based on the differential expression gene pathway enrichment analysis,For the treatment of CAG differential expression genes,the main focus is on 5 signaling pathways,They are JAK/STAT signaling pathway,MEK/ERK signaling pathway,PI3K/AKT signaling pathway,NF-?B signaling pathway,and WNT/Beta-catenin signaling pathway.Conclusion:1.Clinical Study on the Treatment of CAG with BXDOn the basis of health education,after 8 weeks of treatment,compared with placebo,Banxia Xiexin Decoction significantly improved the serological gastric function(PGI,G-17)status of CAG patients,relieved the clinical symptoms such as stomach pain or distending pain,stomach fullness,fatigue and anorexia,improved the quality of life of CAG patients,relieved anxiety and depression,improved sleep quality,and had no adverse reactions.Therefore,Banxia Xiexin Decoction is a treatment for CAG patients.This study provides new evidence-based medicine evidence for treating CAG with Banxia Xiexin Decoction.2.Transcriptomic-based Mechanism Study of BXD in the Treatment of Chronic Atrophic GastritisThrough the study of transcriptomics,using the techniques of differential gene expression comparison,GO function enrichment,pathway enrichment,PPI network,it is found that the mechanism of the treatment of CAG with bitter taste may involve biological processes such as immune regulation,inflammatory reaction,anti-tumor and neural regulation,regulating JAK/STAT signaling pathway,MEK/ERK signaling pathway,PI3K/AKT signaling pathway,NF-?B signaling pathway,and WNT/Beta-catenin signaling pathway.