| Objective1.To clarify the overall efficacy and safety of Pingwei Jianzhong Jiedu prescription in the treatment of patients with gastric precancerous lesions;To explore the dominant population characteristics of Pingwei Jianzhong Jiedu prescription from individual level.2.Proteomics and metabolomics techniques were used to explore the target and signal pathway of Pingwei Jianzhong Jiedu prescription in the treatment of gastric precancerous lesions,and to reveal its mechanism from the molecular perspective.Methods1.Prospective cohort study of Pingwei Jianzhong Jiedu prescription in the treatment of patients with gastric precancerous lesions:a prospective cohort study was used to register the demographic sociology,living habits and disease-related information,TCM syndrome factors and gastroscope pathology of patients.The patients were divided into the exposed group and the non-exposed group according to whether they were treated with Pingwei Jianzhong Jiedu prescription.The changes and differences of pathological(chronic inflammation,inflammatory activity,gland atrophy,intestinal metaplasia,dysplasia)and TCM symptoms(epigastric pain,gastric distention,belching,anorexia,anti-acid heartburn)scores before and after treatment in the two groups were evaluated.All patients were regrouped according to disease progression,and the differences in distribution of gender,age,marital status,educational level,emotional state,dietary rhythm and hobbies,smoking history,drinking history,Hp infection,family history and disease course were compared between the effective group and the ineffective group.The exposed group was regrouped according to the curative effect,and the two groups were compared in terms of gender,age,marital status,educational level,emotional state,dietary rhythm and hobbies,smoking history,drinking history,Hp infection and other factors.2.Plasma proteomics study of Pingwei Jianzhong Jiedu prescription in the treatment of precancerous lesions of gastric cancer:Plasma of exposed patients and healthy volunteers were collected to compare the protein expression levels in different groups.Significant differential proteins were screened with P<0.05,FC>1.2 or<0.83.GO functional and KEGG pathway enrichment analysis of differential proteins were performed by Blast2GO and DAVID.Non-targeted metabolomics study of Pingwei Jianzhong Jiedu prescription in the treatment of gastric precancerous Lesions:Plasma of exposed patients and healthy subjects were collected to detect metabolite levels.Principal component analysis and orthogonal partial least-squares discrimination analysis were performed on the detected data.P<0.05,FC>1.2 or<0.83,and VIP>1 were used as screening criteria to identify the differential metabolites between groups.KEGG pathway enrichment analysis was performed for the selected differential metabolites.Proteomics and metabolomics combined analysis:The quantitative information of all the differentially expressed proteins and metabolites was standardized,the Pearson correlation coefficient between the differentially expressed proteins and metabolites was calculated between groups,and KEGG pathway annotation was performed for the differentially expressed proteins and metabolites.Results1.A total of 94 patients were included in the analysis,including 46 in the exposed group and 48 in the non-exposed group.Pathological comparison between the two groups after treatment showed that the degree of inflammation in the two groups was significantly improved after treatment(P<0.05),but the difference between the two groups was not statistically significant(P>0.05).In terms of inflammatory activity,atrophy and intestinal metaplasia,the exposure group was significantly improved after treatment(P<0.05).Compared with non-exposed group,inflammatory activity and intestinal metaplasia were significantly improved(P<0.05),while there were no significant differences in atrophy and dysplasia between the two groups(P>0.05).In terms of overall efficacy,39 patients in the exposed group improved after treatment,with a total effective rate of 84.80%,and 28 patients in the non-exposed group improved,with a total effective rate of 58.30%,and the difference between the two groups was statistically significant(P<0.05).There was no statistically significant difference in the scores of TCM symptoms between the two groups before treatment(P>0.05),and the levels of epigastric pain,bloating,belching,poor appetite,acid reflux heartburn and total scores in the exposed group after treatment were lower than those before treatment,and the differences were statistically significant(P<0.05).After treatment,there were no significant differences in epigastric pain,stomach distension,belching,difference in appetite and total score in non-exposed group compared with before treatment(P>0.05),and there were statistically significant differences in acid reflux heartburn compared with before treatment(P<0.05).After treatment,there were statistically significant differences in epigastric pain and total score between the two groups(P<0.05),and the epigastric pain and total symptom scores in the exposed group were significantly improved compared with the non-exposed group.No obvious adverse reactions occurred in the exposed group during observation.There were no significant differences in age,sex,marital status,educational level,diet rhythm and hobbies,smoking history,family history and disease course between effective group and invalid group(P>0.05).There were statistically significant differences in emotional state,drinking history and Hp infection between the two groups(P<0.05).There were statistically significant differences in the qi deficiency and dampness elements between the two groups(P<0.05),while there were no statistically significant differences in the distribution of qi stagnation,blood stasis,yin deficiency and heat toxicity(P>0.05).The differences in the distribution of factors between the effective group and the ineffective group were compared.The results showed that there were no significant differences in age,sex,marital status,educational level,dietary rhythm and addiction,smoking history,drinking history,family history and disease course between the two groups(P>0.05),while there were significant differences in emotional status and Hp infection between the two groups(P<0.05).There was no significant difference in the distribution of TCM syndrome elements between the two groups in the distribution of qi deficiency,qi stagnation,blood stasis,dampness resistance,yin deficiency and heat toxicity(P>0.05).2.Proteomic study results showed that there were 49 proteins with significant differences between patients with precancerous gastric cancer and healthy subjects,which could be used as potential biomarkers.Enriched in salmonella infection,amyotrophic lateral sclerosis,glutathione metabolism,regulation of actin cytoskeleton,phagosome,thyroid hormone synthesis,arrhythmogenic right ventricular cardiomyopathy,apoptosis,glycolysis and other signaling pathways.Forty-eight proteins were screened out after Pingwei Jianzhong Jiedu prescription treatment compared with those without treatment.Intersection analysis showed that Pingwei Jianzhong Jiedu prescription had significant regulation on 9 potential biomarkers of PLGC,including TRAP1,LDHB,GPLD1 and MAN1A1,involving 10 KEGG pathways,including N-polysaccharide biosynthesis,central carbon metabolism in cancer,glycolysis/gluconiogenesis,HIF-1 signaling pathway and propanoate metabolism.The results of metabonomics showed that there were differences among the three groups.Twenty-eight potential markers of gastric precancerous lesions were identified,involving sphingolipid signaling metabolism,biosynthesis of unsaturated fatty acids,tyrosine metabolism,PPAR signaling pathway,arachidonic acid metabolism and other pathways.After treatment of Pingwei Jianzhong Jiedu prescription,25 metabolites appeared callback,close to the level of healthy people.Among them,9 were statistically significant(P<0.05),including arachidonic acid,N-laurylsarosine,P-coumaryl alcohol,fructose,suberic acid,L-serine,etc.Twenty-five regulated potential markers involved arachidonic acid metabolism,biosynthesis of unsaturated fatty acids,and tyrosine metabolism pathways.The results of proteomics and metabolomics combined analysis showed that there was a certain degree of correlation between metabolomics and proteomics.There are three common pathways involved in differential proteins and metabolites in PLGC patients and healthy people,including cysteine and methionine metabolism,inflammatory mediator regulation of TRP channels and central carbon metabolism in cancer pathway.Differential expression of proteins and metabolites before and after treatment of Pingwei Jianzhong Jiedu prescription involved 13 signaling pathways,including protein digestion and absorption,central carbon metabolism in cancer,tryptophan metabolism,cysteine and methionine metabolism,glyoxylic acid and dicarboxylic acid metabolism,African trypanosomiasis,pyruvate metabolism and so on.The central carbon metabolism in cancer is an important pathway in which two groups of differential proteins and metabolites participate together.ConclusionPingwei Jianzhong Jiedu prescription can improve the pathological conditions of PLGC patients,relieve clinical symptoms such as epigastric pain,stomach distension and belching,without adverse reactions,and has a good short-term efficacy.Abnormal mood,Hp infection,alcohol consumption,qi deficiency and dampness may be related to the outcome of precancerous lesions of gastric cancer.At the same time,mood disorders and Hp infection can affect the efficacy of Pingwei Jianzhong Jiedu prescription in the treatment of patients with gastric precancerous lesions.The mechanisms may be by adjusting central carbon metabolism in cancer,glycolysis/gluconeogenesis,pyruvate metabolism,arachidonic acid metabolism,biosynthesis of unsaturated fatty acids,tyrosine metabolism and other multiple pathways related proteins and metabolites,regulate inflammation,sugar metabolism and the immune response.Play a multi-target,multi-channel therapeutic effect.It is consistent with the TCM treatment of PLGC from the perspective of "dampness,deficiency and toxin". |
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