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Clinical ResearchUnsupervised data mining based research on syndromes distribution characteristics of chronic atrophic gastritisObjectiveChronic atrophic gastritis is defined as precancerous lesions of gastric cancer.As a common multiple incurable disease in China,aggressive treatment of chronic atrophic gastritis to block its malignant transformation plays a key role in early gastric cancer prevention,the clinical and social significance of which is of great importance.Clarifying syndrome elements,syndromes combination,correlation between the four diagnostic information,core of the four diagnostic information and their distribution is very important for resolving key pathogenesis and the core target of clinical treatment.This will provide syndrome-based evidence for establishing the therapeutic principle.MethodIn this clinical study,four diagnostic information was collect based on cross-sectional survey of patients with chronic atrophic gastritis.A four diagnostic information database was established.Factor analysis,cluster analysis,simple correspondence analysis,multiple correspondence analysis,apriori algorithm of association rule analysis and association rules based complex system entropy clustering were applied in systematic analysis of chronic atrophic gastritis syndrome information.Specific study include factor analysis based syndrome factor extraction and distribution,simple and multiple correspondence analysis based study on associate degree of syndrome factors,apriori algorithm of association rule based analysis on core four diagnostic information,association rules based complex system entropy clustering based extraction on syndrome elements.Result1.Factor analysis based syndrome factor extraction and distribution revealed that chronic atrophic gastritis syndrome factors include qi deficiency,qi stagnation,blood stasis,phlegm,heat and Yang deficiency.In terms of trends on the distribution of syndrome factors,qi deficiency,qi stagnation,blood stasis,phlegm and heat are relatively common,while yang dificiency is relatively rare.2.Simple and multiple correspondence analysis based study on associate degree of syndrome factors revealed that the core group of syndrome elements is constituted by qi stagnation,qi deficiency,heat,phlegm and blood stasis.3.Apriori algorithm of association rule based analysis on four diagnostic information revealed that under ordinary conditions established screening,core group of four diagnostic information covers characteristics of all six syndrome elements.Under harsh conditions established strict screening,core group of four diagnostic information covers characteristics of five syndrome elements including qi stagnation,qi deficiency,heat,phlegm and blood stasis.4.Association rules based complex system entropy clustering revealed that extracted syndrome elements include qi deficiency,qi stagnation,blood stasis,phlegm,heat,Yang deficiency and Yin deficiency.ConclusionKey pathogenesis of chronic atrophic gastritis is constituded by qi deficiency,qi stagnation,blood stasis,phlegm,heat,Yang deficiency and Yin deficiency.Deficiency,stagnation,stasis and heat toxic may act as the most important common basic pathogenesis throughout the entire course of this disease.The core target of clinical treatment include qi deficiency,qi stagnation,blood stasis,phlegm and heat.Regulating qi(promoting qi,tonifying qi),activating blood and detoxicating should be the most important principles of treatment.Comprehensive coverage of key pathogenesis and core syndrome factor targets of chronic atrophic gastritis is syndrome-based evidence of the excellent efficacy of regulating qi,activating blood and detoxicating therapeutic principle in clinical application.Section II Experimental ResearchCell dynamic phenotype based research on mechanisms for the treatment of chronic atrophic gastritis by regulating qi,activating blood and detoxicatingObjectiveProgression of chronic atrophic gastritis is a typical long-phased,multi-staged sequence course of malignant transformation.Gastric epithelial cell dynamics disorder is an important cellular mechanism of chronic atrophic gastritis and gastric malignant transformation.Ezrin is a connection protein between the cytoskeleton and cell membrane.Conformation change mediated by phosphorylation at threonine 567 protein induces activation of ezrin,which assume a series of key dynamics functions in cell migration,proliferation,invasion,apoptosis,intracellular transport and cell polarization.Ezrin is an important participant in chronic atrophic malignant transformation process,the expression level of which closely related to pathological progression and prognosis.Ezrin also regulates the steady-state of gastric microenvironment for that it is also a critical functional protein in regulating acid secretion of gastric parietal cells.As an important principles of treatment,syndrome-based evidence of the excellent efficacy of regulating qi,activating blood and detoxicating therapeutic principle in clinical application is clarifyed in the clinical research mentioned above.Xiao-pi-ling prescription is a classic representative prescription based on regulating qi,activating blood and detoxicating therapeutic principle and applied in treatment of chronic atrophic gastritis.It palys definite role in blocking chronic atrophic gastritis malignant transformation.Cell dynamic phenotype based research on mechanisms for the treatment of chronic atrophic gastritis by regulating qi,activating blood and detoxicating in Xiao-pi-ling carrier will elucidate possible intervention of this therapeutic principle in gastric epithelial cell kinetics disorder,which is of great importance.MethodCrude drug extracts,drug serum and control serum were prepared.Primary cultured rabbit parietal cells,immortalized human gastric epithelial cell line GES-1,MNNG-induced malignant transformed human gastric epithelial cell line MC,human gastric adenocarcinoma cell line AGS were applied as varied gastric epithelial cell model system in this research.The study includes:1.Immunofluorescence assay based assessment of primary cultured rabbit parietal cells acid secretion function and regulation of subcellular localization of key acid secretion related proteins Ezrin,Thr567 phosphorylated Ezrin and H,K-ATPase under Xiao-pi-ling intervention.2.Living cell migration assay and wound-healing assay based assessment of GES-1,MC and AGS cell migration under Xiao-pi-ling intervention.3.MTS assay and three-dimensional culture assay based assessment of GES-1,MC,AGS cell viability under Xiao-pi-ling intervention.4.Transwell assay based assessment of AGS cell invasion under Xiao-pi-ling intervention.5.Western-blotting assay based assessment of Ezrin expression and phosphorylation of Ezrin 567 threonine.Result1.Both crude drug extracts and drug serum may not regulate acid secretion function of primary cultured rabbit parietal cells and subcellular localization of key acid secretion related proteins Ezrin,Thr567 phosphorylated Ezrin and H,K-ATPase.2.Crude drug extracts reduce accumulated distance and velocity of GES-1 cell migration,journey,increased euclidean distance and speed of GES-1 migration.Crude drug extracts inhibit MC cell migration.Both crude drug extracts and drug serum inhibit AGS cell migration.3.Crude drug extracts may enhance GES-1 cell viability,but drug serum may not regulate GES-1 cell viability.Both crude drug extracts and drug serum inhibit MC and AGS cell viability.4.Both crude drug extracts and drug serum inhibit AGS cell invasion.5.Both crude drug extracts and drug serum can reduce protein levels of ezrin and Thr567 phosphorylated Ezrin.ConclusionIn vitro experiments,regulating qi,activating blood and detoxicating can regulate kinetics phenotypic characteristics of gastric epithelial cell including adjusting proliferation and apoptosis dynamics disorder of normal gastric epithelial cell,malignant and malignant potential gastric epithelial cell.It can also inhibit kinetics phenotype of high proliferation and low apoptosis in malignant and malignant potential gastric epithelial cell.Regulating qi,activating blood and detoxicating also inhibits high mobility phenotype of malignant and malignant potential gastric epithelial cell while high invasion phenotype of malignant gastric epithelial cell can also be inhibited by this therapeutic principle.These dynamics changes in malignant and malignant potential gastric epithelial cells are induced by down regulation of both Ezrin expression and Ezrin Thr567 phosphorylation.Acid secretion function of primary cultured rabbit parietal cells may not be regulated by regulating qi,activating blood and detoxicating directly in vitro.However,regarding the the complexity of gastric acid secretion mechanism and the fact that stomach microenvironment changes closely related to progression of chronic atrophic gastritis,further animal and clinical studies are still needed to confirm whether it can play a regulatory role in vivo or not.In conclusion,the mechanism of regulating qi,activating blood and detoxicating in Xiao-pi-ling carrier in treatment of chronic atrophic gastritis is closely related to adjusting gastric epithelial cell kinetics disorders.These interventions are induced by down regulation of both Ezrin expression and Ezrin Thr567 phosphorylation. |
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