Study On The Clinical Efficacy And Mechanism Of "treating Carbuncle" In Treating Chronic Atrophic Gastriti

Objectives: To investigate the clinically effective TCM treatment of chronic atrophic gastritis;to elaborate Professor Jiang Shumin’s academic thinking and clinical experience in treating chronic atrophic gastritis through theoretical discussion and to evaluate the efficacy and safety of Qing Zhong Xiao Yong Tang in the treatment of CAG in conjunction with clinical trials;To elucidate the basic formula used by Professor Jiang Shumin in clinical practice,The study also aims to elucidate the active ingredients and disease targets of chronic atrophic gastritis in the formula "Huang Qi-Ku Shen-Bai Ji-Zhe Bei Mu-Chai Hu",and to predict the main targets and pathways.Materials and Methods:1.Using "Chinese medicine,Chinese medical treatment,Chinese and Western combination,chronic atrophic gastritis,atrophic gastritis" as the search term,we searched for documents that met the nadir criteria in CNKI,CBM,Wanfang and VIP databases since the establishment of the database until August 2022.The literature was extracted.After evaluating the quality of the included literature using the Cochrane Risk Bias Assessment Tool,a network Meta-analysis was performed using Stat 16 to compare the differences in the efficacy of various Chinese medical treatments for chronic atrophic gastritis.2.Through theoretical discussion,the academic lineage of Professor Jiang Shumin’s academic thought of "treating CAG with carbuncles" was reviewed,his understanding of the etiology and pathogenesis of CAG in traditional Chinese medicine was summarized,and his treatment characteristics and experience of the disease were explored,and the formulation characteristics,principles of the formula and efficacy of Qing Zhong Xiao Yong Tang were analyzed.Secondly,126 patients with CAG who met the inclusion criteria were randomly divided into a control group and a treatment group.The control group was treated with Rebapet and the treatment group was treated with Qing Zhong Xiao Yong Tang granules on top of this treatment.3.The active ingredients of Huang Qi-Ku Shen-Bai Ji-Zhe Bei Mu-Chai Hu were searched and screened by the TCMSP and Uniprot databases,and the key targets were screened by Cytoscape software.Genecards,OMIM and Drugbank databases were used to screen the targets related to chronic atrophic gastritis.The intersecting targets were imported into the String database for PPI analysis to construct a protein interaction network.The network topology analysis function was used to screen the core genes of Huang Qi-Ku Shen-Bai Ji-Zhe Bei Mu-Chai Hu for the treatment of CAG.GO enrichment analysis and KEGG pathway analysis were performed on the intersecting targets in the Metascape database,and molecular docking verification was performed by Auto Dock software to obtain the key active molecules and potential molecular mechanisms of "Huang Qi-Ku Shen-Bai Ji-Zhe Bei Mu-Chai Hu" in the treatment of chronic atrophic gastritis.Results:1.A total of 44 RCT studies with a sample size of 3934 cases were included in the reticulated meta-analysis study,involving 6 TCM treatment methods,namely the method of strengthening the spleen and stomach,the method of clearing the liver and stomach,the method of draining the liver and stomach,the method of nourishing yin and benefiting the stomach,the method of resolving dampness and awakening the spleen,and the method of regulating qi and invigorating blood.Reticulated Meta-analysis showed that in terms of improvement in clinical efficiency and Hp clearance rate,the efficacy of the six Chinese medical methods combined with conventional Western medicine was superior compared with conventional Western medicine,and was statistically significant(P< 0.05).In turn,SUCRA cumulative probability ranking of the efficacy of the six Chinese medical methods combined with conventional Western medicine showed that in terms of clinical efficiency and Hp clearance rate treatment effect In terms of the improvement of gastroscopic efficiency,the efficacy of the method of strengthening the spleen and the stomach,the method of resolving dampness and awakening the spleen,and the method of invigorating blood and regulating qi + conventional western medicine was superior compared with that of conventional western medicine,and was statistically significant(P< 0.05),while the SUCRA cumulative probability ranking of the efficacy of the four Chinese medical methods combined with conventional western medicine showed that the efficacy of the method of invigorating blood and regulating qi + conventional western medicine was superior to that of the method of invigorating blood and regulating qi.The combination of the four Chinese medical methods combined with conventional Western medicine was the best treatment option in terms of improving the efficacy of gastroscopy.The study proved that the combination of Chinese and Western medicine has good clinical effects in the treatment of CAG,and is important in improving patients’ clinical symptoms and delaying disease progression.2.Prof.Jiang believes that the cause of chronic atrophic gastritis is related to external aggressions and emotional disorders,and that the patient’s old age and physical weakness,as well as the weakness of the spleen and stomach,are the main causes.Prof.Jiang Shumin pointed out that the microscopic tortuousness of the ligaments in CAG patients is a sign of the pathological products of the loss of glory of the stomach ligaments,such as poison,heat,dampness and blood stasis blocking the stomach ligaments.At the same time,the pathological products are also pathogenic factors,which further lead to the internal growth of turbid toxins and damage to the stomach,resulting in intestinal transformation and heterogeneous hyperplasia.In the treatment,our master was mindful of the pathogenesis of the disease,and based on the deficiency of the disease and the combination of deficiency and reality,combined with the root cause of the weakness of the spleen and stomach and the congestion of qi,he proposed the CAG method of "treating with carbuncles",which is to "regulate qi and strengthen the spleen,detoxify and eliminate carbuncles,remove decay and create new ones".The method of "regulating qi and strengthening the spleen,detoxifying and eliminating carbuncles,removing decay and creating new ones" is based on the use of clearing,moistening and lowering products that are sweet,warm and beneficial to the stomach,eliminating poisonous heat in the stomach,tonifying the essence of the latter,and moving qi to remove stagnation.The clinical study showed that(1)before treatment,there was no significant difference between the two groups of patients in terms of TCM symptom scores,including stomach pain,gastric distension,stuffiness,little food and dullness,body fatigue,bitterness and bad breath,etc.,P was > 0.05;after treatment,the TCM symptoms of both groups were significantly lower than before treatment,and the observation group had lower scores than the control group,P was < 0.05;(2)Before treatment,there was no significant difference between the two groups in terms of the lesions of chronic inflammation,glandular atrophy,intestinal epithelial metaplasia and heterotypic hyperplasia,etc.;after treatment,the points of lesions of chronic inflammation,glandular atrophy,intestinal epithelial metaplasia and heterotypic hyperplasia under gastroscopy in both groups were significantly lower than before treatment,and the score of the observation group was lower than that of the control group,P < 0.05;(3)After the course of treatment,the total effective rate of the observation group was significantly(4)Safety evaluation,no adverse reactions occurred during the treatment period in both groups.3.The results of the network pharmacological analysis showed that the top 10 active ingredients screened by the network topology analysis were: quercetin,kaempferol,formononetin,isorhamnetin,luteolin,7-O-methylisomucronulatol,beta-sitosterol,Stigmasterol,8-Isopentenyl-kaempferol,Phaseolin,and the top 10 active ingredients of the Astragalus-Bezoic Ginseng-Bezoic Ginseng-Chaihu combination.isorhamnetin,luteolin,7-O-methylisomucronulatol,beta-sitosterol,Stigmasterol,8-Isopentenyl-kaempferol,Phaseolin,which are probably the core components of this formula for the treatment of CAG.By constructing a PPI network of Huang Qi-Ku Shen-Bai Ji-Zhe Bei Mu-Chai Hu for the treatment of CAG,the top 10 core key targets were analyzed,namely: TPT53,AKT1,TNF,IL6,MAPK1,MAPK14,FOS,IL10,STAT1,EGFR.GO enrichment analysis showed that the main biological processes of Huang Qi-Ku Shen-Bai Ji-Zhe Bei Mu-Chai Hu Tang for the treatment of KEGG enrichment analysis showed that Huang Qi-Ku Shen-Bai Ji-Zhe Bei Mu-Chai Hu Tang mainly exerted anti-inflammatory,anti-cancer and immunosuppressive effects through MAPK signaling pathway,NF-κB signaling pathway and HIF-1 signaling pathway in the treatment of CAG.Molecular docking of the active ingredients of the drug in Astragalus-Braised Ginseng-Baihe-Zhebei Mu-Chaihu with key receptor proteins showed that MAPK1 and TNF could bind more stably and spontaneously with prickly mangosteen,and AKT1 could bind more stably and spontaneously with lignocaine,prickly mangosteen and kaempferol,indicating that the active ingredients of Astragalus-Braised Ginseng-Baihe-Zhebei Mu-Chaihu bind freely to the receptors and may influence the disease progression of CAG through the above modes of actionConclusion:1.Chronic atrophic gastritis,as a common and recurrent clinical disease,is a major difficulty in clinical treatment,causing great suffering to patients and families,and adding a heavy burden to public health.Many studies have proven that the first-line treatment of modern medicine is effective for this disease,and there are many methods of TCM treatment for this disease.In this study,we compared the differences in the efficacy of different TCM treatments for chronic atrophic gastritis through reticulated Meta-analysis,and ranked the results,suggesting that strengthening the spleen and stomach + conventional treatment method has the best improvement in clinical efficiency and Hp clearance rate,and invigorating blood and Qi + conventional method has the best improvement in gastroscopic efficacy.2.Professor Jiang Shumin’s CAG theory of "treating canker sores" has clear theoretical origins and distinctive academic features,and he has created "Qing Zhong Xiao Yong Tang",which provides a new treatment idea for the clinical treatment of this disease.In the clinical study,the combination of Qing Zhong Xiao Yong Tang with western medicine showed that the patients’ TCM symptom scores,gastroscopic histological scores and overall clinical efficiency improved better than those of western medicine alone.During the study,Qing Zhong Xiao Yong Tang effectively improved the patients’ clinical symptoms without adverse effects.The study confirms that Qing Zhong Xiao Yong Tang is effective in treating CAG without toxic side effects and can be promoted in clinical practice.3.The results of the study showed that the Huang Qi-Ku Shen-Bai Ji-Zhe Bei Mu-Chai Hu combination could modulate different targets through its same compound,while the modulation of the same target could affect different biological processes and signaling pathways,reflecting the comprehensive effects of the multi-component,multi-target and multi-pathway Huang Qi-Ku Shen-Bai Ji-Zhe Bei Mu-Chai Hu combination.It also showed that the regulation of the whole network could be achieved by modulating single or multiple core targets in the network,which provides theoretical support for the remarkable efficacy of Huang Qi-Ku Shen-Bai Ji-Zhe Bei Mu-Chai Hu in the treatment of CAG,suggests a target for the subsequent validation of the clinical efficacy evaluation index of Huang Qi-Ku Shen-Bai Ji-Zhe Bei Mu-Chai Hu,and suggests a target for exploring the potential action of Huang Qi-Ku Shen-Bai Ji-Zhe Bei Mu-Chai Hu mechanism.