| Background and AimEpidemiology shows that the global burden of cancer incidence and mortality is still increasing,and the disease burden of gastric cancer(GC)is particularly serious in China,so moving forward the "gateway" of gastric cancer intervention can effectively reduce its incidence and mortality.Chronic atrophic gastritis(CAG)is important precancerous disease of gastric cancer,both as an important window for pre-cancerous intervention and as a key risk factor for recurrence of early gastric cancer after surgery.At present,the clinical treatment of this disease in China is mainly based on traditional Chinese medicine(TCM),and there are no specific treatment options in Western medicine.Reviewing CAG-related TCM studies,the following characteristics:①Current research on CAG disease risk factors is mainly based on disease risk studies,and less research has been conducted according to GC risk stratification and combined with TCM symptom factor.②Traditional Chinese medicine(TCM)has achieved good clinical efficacy,but there is a lack of high-quality evidence-based medical evidence.③The mechanism of TCM treating CAG based on strict evaluation has not yet been elucidated.To further clarify the risk factors for CAG disease,critically evaluate the clinical efficacy of TCM interventions for CAG and elucidate its pharmacological mechanisms,we propose to conduct a study on risk factors for high-risk CAG covering TCM symptom factor,evaluate the clinical efficacy of Xinkai Kujiang Tiaoshu prescription based on the blind method of central pathology,and elucidate its pharmacological mechanisms using network pharmacology and molecular docking techniques to guide on chronic disease management for CAG patients,and provide references for clinical practice and pharmacological efficacy studies of TCM interventions for CAG.1 Research of risk factors for high-risk CAGMethodsBy cross-sectional study,a questionnaire survey was conducted on CAG patients in Wangjing Hospital of China Academy of Chinese Medical Sciences,the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine and Shanxi Provincial Hospital of Traditional Chinese Medicine,with OLGIM risk stratification(stage 0-Ⅱ as low risk,stage Ⅲ-Ⅳ as high risk)as the dependent variable,general information,lifestyle,symptoms,TCM symptom factors,and disease history as independent variable,and binary logistic regression was used to analyze the correlation between them.ResultsA total of 119 valid questionnaires were collected,including 56 cases of low-risk OLGIM and 63 cases of high-risk OLGIM,and the CAG pathological diagnoses were all assessed by central pathology blinded method;Four risk factors associated with high-risk OLGIM were screened(P<0.05),among which coarse food intake maybe a protective factor for high-risk OLGIM,and dietary taste heavy salt,tea consumption and TCM symptom factor of blood deficiency maybe high risk factors for high-risk OLGIM.2 Clinical research on the intervention of CAG by Xinkai Kujiang Tiaoshu prescription based on the blind method of central pathologyMethodsBy multicenter,randomized,double-blind,controlled clinical study,patients with CAG were recruited at Wangjing Hospital of China Academy of Chinese Medical Sciences,the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine and Shanxi Provincial Hospital of Traditional Chinese Medicine,and the diagnosis of CAG was clarified by central pathology blinded method,they were included in the experiment and control groups according to the case random assignment table,and the ratio of experiment and control groups was 2:1.The experiment group was given the Xinkai Kujiang Tiaoshu prescription,and the control group was given placebo.The treatment was for 24 weeks and followed up for 24 weeks.The changes of gastric mucosal pathology(chronic inflammation,atrophy,intestinal metaplasia,and dysplasia),gastric cancer risk(OLGA and OLGIM assessment),clinical symptoms and safety were evaluated after treatment and during the follow-up period.ResultsA total of 176 patients with a proposed diagnosis of C AG by gastroscopy were screened,and after blinded assessment by central pathology,135 patients were diagnosed with CAG and included in the study;Ninety cases entered the experiment group and 45 cases entered the control group.Eight cases were automatically withdrawn during the treatment period;three cases were lost during the follow-up period,three cases obtained clinical symptoms during the follow-up but did not review the gastroscopy;five case was excluded due to mis-including or protocol violation.Finally,a total of 122 cases completed post-treatment gastroscopy,of which 116 cases continued to complete follow-up gastroscopy and 119 cases completed follow-up of clinical symptoms.No diagnosis of dysplasia was seen in all cases included in this study.Statistical analysis using the full analysis set(FAS)showed that:①With regard to the pathological findings,the difference in the distribution of the difference between the two groups in the degree of chronic inflammation,atrophy and intestinal metaplasia at each site of the gastric mucosa minus baseline after 24 weeks of treatment was not statistically significant(P>0.05);after 24 weeks of follow-up,the difference in the distribution of the difference between the two groups in the degree of atrophy and intestinal metaplasia of corpus mucosa minus baseline was statistically significant(P<0.05),with the experiment group being lower than the control group,while the differences in the remaining sites and lesions were not statistically significant(P>0.05).②In terms of overall gastric mucosal carcinoma risk,the differences in the distribution of the difference between the two groups obtained from OLGA and OLGIM stages minus baseline were not statistically significant after 24 weeks of treatment and after 24 weeks of follow-up(P>0.05).③In terms of symptoms,compared with the control group,the total symptom score of the experiment group decreased significantly after 24 weeks of treatment(P<0.05),and the rest of the time also showed a downward trend,but there was no statistical significance(P>0.05);the stomach pain score of the experiment group decreased significantly after 8 weeks and 24 weeks of treatment(P<0.05),and the rest of the time also showed a downward trend,but there was no statistical significance(P>0.05);the bloating score of the experiment group showed a decreasing trend after 8 weeks,12 weeks,20 weeks,24 weeks and 24 weeks of follow-up,but there was no statistical significance(P>0.05).④Regarding safety,there was no significant difference in the distribution of adverse events between the two groups,and no significant abnormalities were observed in the remaining safety indicators during the study period.3 Mechanism research for Xinkai Kujiang Tiaoshu prescription treating CAG based on network pharmacology research and molecular docking technologyMethodsThe chemical components of Xinkai Kujiang Tiaoshu prescription were searched and screened using the Chinese medicine network database,and their targets of action were predicted;the CAG disease targets were searched using the disease network database,and the Xinkai Kujiang Tiaoshu prescription targets and CAG disease targets were intersected to obtain the Xinkai Kujiang Tiaoshu prescription targets of treating CAG.The network computation method was used to screen the important nodes in the Xinkai Kujiang Tiaoshu prescription treating CAG target network,discover the core components and core targets,and evaluate the binding mode and affinity of the core components and core targets by molecular docking technique.ResultsBased on the results of the "component-disease-target" network,target PPI network,MCODE functional module,and related gene functional enrichment of the decoction,we concluded that quercetin,kaempferol,luteolin,beta-sitosterol,and schottenol may be the core components of the prescription,and AKT1,SRC,EGFR,XDH,AR,and CYP17A1 may be the core targets.Molecular docking of the above core components and targets revealed that they all bind well to each other,among which AR-Betasitosterol,AR-Schottenol,CYP17A1-Beta-sitosterol can bind below-10.0 kcal/mol,indicating that they have high strength binding affinity to each other.Conclusions(1)Coarse grain intake may be a protective factor for high-risk CAG,and a diet heavy in salt,tea consumption,and blood deficiency evidence may be risk factors for highrisk CAG.(2)The efficacy of Xinkai Kujiang Tiaoshu prescription to intervene in the atrophy and intestinal metaplasia of the gastric corpus mucosa is better than that of placebo,and prescription can significantly relieve symptoms of patients,and has a good safety.(3)The mechanism of Xinkai Kujiang Tiaoshu prescription treating CAG has the characteristics of multi-component,multi-pathway and multi-target,quercetin,kaempferol,lignan,β-sitosterol and shottol may be the core components,AKT1,SRC,EGFR,XDH,AR and CYP17A1 may be the core targets,all the above components and targets have good binding affinity. |
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