Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer:A critical review

Gastric cancer(GC)is a common gastrointestinal tumor.Gastric precancerous lesions(GPL)are the last pathological stage before normal gastric mucosa transforms into GC.However,preventing the transformation from GPL to GC remains a challenge.Traditional Chinese medicine(TCM)has been used to treat gastric disease for millennia.A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL.This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC,especially focusing on antiinflammatory,anti-angiogenesis,proliferation,and apoptosis.This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.

Xiaojianzhong decoction prevents gastric precancerous lesions in rats by inhibiting autophagy and glycolysis in gastric mucosal cells

BACKGROUND Gastric precancerous lesions(GPL)precede the development of gastric cancer(GC).They are characterized by gastric mucosal intestinal metaplasia and dysplasia caused by various factors such as inflammation,bacterial infection,and injury.Abnormalities in autophagy and glycolysis affect GPL progression,and their effective regulation can aid in GPL treatment and GC prevention.Xiaojianzhong decoction(XJZ)is a classic compound for the treatment of digestive system diseases in ancient China which can inhibit the progression of GPL.However,its specific mechanism of action is still unclear.AIM To investigate the therapeutic effects of XJZ decoction on a rat GPL model and the mechanisms underlying its effects on autophagy and glycolysis regulation in GPLs.METHODS Wistar rats were randomly divided into six groups of five rats each and all groups except the control group were subjected to GPL model construction for 18 wk.The rats’body weight was monitored every 2 wk starting from the beginning of modeling.Gastric histopathology was examined using hematoxylin-eosin staining and Alcian blue-periodic acid-Schiff staining.Autophagy was observed using transmission electron microscopy.The expressions of autophagy,hypoxia,and glycolysis related proteins in gastric mucosa were detected using immunohistochemistry and immunofluorescence.The expressions of the following proteins in gastric tissues:B cell lymphoma/Leukemia-2 and adenovirus E1B19000 interacting protein 3(Bnip-3),microtubule associated protein 1 light chain 3(LC-3),moesin-like BCL2-interacting protein 1(Beclin-1),phosphatidylinositol 3-kimase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(mTOR),p53,AMP-activated protein kinase(AMPK),and Unc-51 like kinase 1(ULK1)were detected using western blot.The relative expressions of autophagy,hypoxia,and glycolysis related mRNA in gastric tissues was detected using reverse transcription-polymerase chain reaction.RESULTS Treatment with XJZ increased the rats’body weight and improved GPL-related histopathological manifestations.It also decreased autophagosome and autolysosome formation in gastric tissues and reduced Bnip-3,Beclin-1,and LC-3II expressions,resulting in inhibition of autophagy.Moreover,XJZ down-regulated glycolysis-related monocarboxylate transporter(MCT1),MCT4,and CD147 expressions.XJZ prevented the increase of autophagy level by decreasing gastric mucosal hypoxia,activating the PI3K/AKT/mTOR pathway,inhibiting the p53/AMPK pathway activation and ULK1 Ser-317 and Ser-555 phosphorylation.In addition,XJZ improved abnormal gastric mucosal glucose metabolism by ameliorating gastric mucosal hypoxia and inhibiting ULK1 expression.CONCLUSION This study demonstrates that XJZ may inhibit autophagy and glycolysis in GPL gastric mucosal cells by improving gastric mucosal hypoxia and regulating PI3K/AKT/mTOR and p53/AMPK/ULK1 signaling pathways,providing a feasible strategy for the GPL treatment.

Association between interleukin-21 gene rs907715 polymorphism and gastric precancerous lesions in a Chinese population

BACKGROUND The single nucleotide polymorphisms of interleukin-21(IL-21)gene were confirmed to be related to various diseases,but no studies have examined the possible role of IL-21 single nucleotide polymorphisms(SNPs)(rs907715,rs2221903,and rs12508721)in gastric precancerous lesions.AIM To explore the associations between SNPs of IL-21 gene(rs907715,rs2221903,and rs12508721)and gastric precancerous lesions in a Chinese population.METHODS Three SNPs of IL-21 were genotyped using polymerase chain reaction–ligase detection reaction in 588 cases and 290 healthy controls from May 2013 to December 2016 in northwestern China.Gastric precancerous lesions were confirmed by endoscopic examination and categorized as non-atrophic gastritis,atrophic gastritis,and intestinal metaplasia.Descriptive statistic and logistic regression were used for data analyses.RESULTS IL-21 rs907715 genotype CC and C frequencies were higher in in patients with gastric precancerous lesions than in the controls(OR=1.59,95%CI:1.06-2.38,P=0.013;OR=1.28,95%CI:1.01-2.22,P=0.044,respectively)after adjusting for confounding factors.For SNP rs907715 in intestinal metaplasia patients,significant differences between cases and controls were observed in the frequencies of genotype CC and C(OR=1.92,95%CI:1.24-2.98,P=0.004;OR=1.53,95%CI:1.04-2.24,P=0.028,respectively);for non-atrophic gastritis and atrophic gastritis patients,the CC and C genotypes showed no significant association with risk in all models.No association between either rs2221903 or rs12508721 and gastric precancerous lesions was found in the present study.In the haplotype analysis,the TC haplotype(rs907715 and rs12508721)and TT haplotype(rs2221903 and rs907715)were more frequent in the case group than control group(P<0.05).CONCLUSION Our findings indicate that SNP rs907715 of IL-21 gene is associated with gastric precancerous lesions.The TC haplotype(rs907715 and rs12508721)and TT haplotype(rs2221903 and rs907715)increased the risk of gastric precancerous lesions.If confirmed,these findings will shed light on the etiology of precancerous lesions.

Identification of key pathways and genes from gastric precancerous lesions to gastric cancer by integrated bioinformatics analysis

Objective:This work aimed to illuminate the potential key genes and pathways in GC tumorigenesis based on bioinfOrmatics analysis.Methods:The differentially expressed genes(DEGs)between GPL tissue samples and GC tissue samples were investigated using the GSE55696 and GSE87666 microarray data from the Gene Expression Omnibus(GEO)database.DEGs were identified by an empirical Bayes method based on the Limma R package.Then,KEGG and GO enrichment analyses of DEGs were performed followed by protein-protein interaction(PPI)network construction.Finally,the overall survival(OS)analysis of key genes was performed by the Kaplan-Meier plotter online tool.Results:A total of 250 DEGs were obtained,of which 216 were up-regulated and 34 were down-regulated.KEGG pathways analysis showed that the up-regulated DEGs were enriched in cytokine-cytokine receptor interaction,chemokine signaling pathway,metabolic pathways,PI3K-Akt signaling pathway,NF-kappa B signaling pathway,and other signaling pathways about cancer,while no down-regulated pathways were enriched.A PPI network of DEGs was constructed with 117 nodes and 660 edges,and 20 genes were selected as hub genes owing to high degrees in the network.According to the Kaplan-Meier analysis,6 out of 20 hub genes including CCR7,FPR1,C3,CXCR5,GNB4,and PPBP with high mRNA expression were associated with poor OS for GC patients.Conclusion:The results of this study provide possible factors for the occurrence of GC,and the identification of the genes and pathways associated with the progression from GPL to GC provides valuable data for investigating the pathogenesis in future studies.

Review on the progress of treating gastric precancerous lesions with traditional Chinese medicine based on regulatory genes

In recent years,the incidence of Precancerous lesions of gastric cancer(PLGC)has gradually increased,and it is difficult to be cured and easy to recur.Traditional Chinese Medicine(TCM)emphasizes the prevention before the disease.The regulation of PLGC related tumor genes by Chinese medicine has become a research hotspot.This paper summarized PLGC related proto-oncogenes,tumor suppressor genes and apoptosis related genes,and discussed the mechanism of Chinese Medicine Therapy PLGC from the perspective of gene expression,providing new ideas and methods for clinical treatment of PLGC.

Prospects in the application of ultrasensitive chromosomal aneuploidy detection in precancerous lesions of gastric cancer

Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents,the prognosis for GC remains poor.New targeted therapies and immunotherapies are currently under invest-igation,but no significant breakthroughs have been achieved.Studies have indicated that GC is a heterogeneous disease,encompassing multiple subtypes with distinct biological characteristics and roles.Consequently,personalized treatment based on clinical features,pathologic typing,and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer(PLGC).Current research has categorized GC into four subtypes:Epstein-Barr virus-positive,microsatellite instability,genome stability,and chromosome instability(CIN).Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas.Among these,ultrasensitive chromosomal aneuploidy detection(UCAD)can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology,in conjunction with bioinformatics analysis,to achieve qualitative and quantitative detection of chromosomal stability.This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.

Effects of Weipixiao(胃痞消)on Wnt Pathway-Associated Proteins in Gastric Mucosal Epithelial Cells from Rats with Gastric Precancerous Lesions*

Objective： To study the effects of Weipixiao （胃痞消, WPX） on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions （GPL）. Methods： Sprague Dawley rats were randomly divided into control, model, vitacoenzyme （0.2 g·kg-l·day-1）, WPX high-dose （H-WPX, 15 g·kg-l·day-1）, WPX medium-dose （M-WPX, 7.5 g·kg-1·day-1） and WPX low-dose （L-WPX, 3.75 g·kg-l·day-1） groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-protein- coupled receptor 5 （Lgr5）, matrix metalloproteinase-7 （MMP-7）, Wntl, Wnt3a, and 13 -catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software. Results： Gastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wntl, Wnt3a and 13 -catenin than those of the control group （P〈0.01）. Interestingly, we also observed Lgr5＋ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wntl, and 13-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups （P〈0.05）. A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups （P〉0.05）. Conclusion： Our findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wntl, β -catenin and the aberrant activation of Wnt/β -catenin pathway.

Effect of Jinguo Weikang Capsule(金果胃康胶囊) on Proto-oncogene Expression of Gastric Mucosa in Rats with Gastric Precancerous Lesions

Objective： To study the effect of Jinguo Weikang Capsule （金果暖康胶囊, JWC） on the gene expression of H-ras, epidermal growth factor receptor （EGFR）, P53 and C-myc of the gastric mucosa in rats with gastric precancerous lesions, and to investigate the action mechanism of JWC on gastric precancerous lesions. Methods： A rat model with paratypical proliferation of the gastric epithelium mucosa was established by using ^60Co irradiation. Rats were divided into the normal group, model group, high-, medium-, low-dose JWC treatment groups, and the vitacoenzyme control group, and were treated for 30 days. The expression of H-ras, EGFR, P53 and C-myc genes of the gastric mucosa was detected by using immunohistochemical methods. Results： The expression and over-expression rates of H-ras, EGFR, P53 and C-myc gene in the high- and medium-dose JWC treatment groups were significantly lower （P〈0.05） as compared with those of the model group. Conclusion： JWC can inhibit the expression of the H-ras, EGFR, P53 and C-myc genes expression of the gastric mucosa in rats, which may be one of mechanisms involved in suppressing or reversing gastric carcinogenesis.

ANTIGEN MG7 IN GASTRIC CANCER AND GASTRIC PRECANCEROUS LESIONS

Objective: To study the dynamic change and its diagnostic significance of MG7 expression in the process of gastric cancer development. Methods: The expression level of antigen MG7 was determined by immunohistochemistry method in 406 cases of gastric mucosa. The classification of intestinal metaplasia of gastric mucosa was determined by histochemistry method in 82 cases. Results: The positive rate of MG7 expression in normal gastric mucosa, intestinal metaplasia and dysplasia of gastric mucosa and gastric cancer were increased gradually (P<0.01). The positive rate of MG7 expression in superficial gastritis, atrophic gastritis and gastric cancer were increased on sequence (P<0.01). The positive rate of antigen MG7 expression in type III intestinal metaplasia of gastric mucosa had significant difference, compared with that in type I an II intestinal metaplasia (P<0.05). Conclusion: MG7 antigen had close relationship with gastric cancer. Type III intestinal metaplasia, atrophic gastritis and dysplasia should be followed up in order to improve the early detection of gastric cancer. MG7 antigen had great clinical value in the dynamic follow-up of gastric precursors.

Risk Factors of Precancerous Gastric Lesions in A Population at High Risk of Gastric Cancer

Objective： In cancer prevention, the targeting of precancerous lesions has been recognized as the most promising method. However, little attention has been paid to the risk factors of precancerous gastric lesions, especially in rural China where there is high prevalence of precancerous gastric lesions. We therefore conducted a cross-sectional study in Liaoning province, China, to investigate the potential risk and protective factors of these precancerous gastric lesions. Methods： A total of 1,179 subjects with high risk of gastric cancer from Zhuanghe County were included in this study. Standard questionnaires were used in collecting epidemiological factors and the data were then analyzed by the unconditional logistic regression model. Results： Smoking and drinking were the risk factors for the precancerous gastric lesions among rural subjects, and the association of smoking or drinking and the precancerous gastric lesions increased in strength with the daily consumption and duration. As the factors such as age, gender, smoking, alcohol were controlled, a multivariable analysis revealed that there was a significant correlation between the deep-fry food intake and the gastric epithelial dysplasia with the odds ratio （OR） of 1.78 [95% confidence interval （CI）： 1.01-3.12]. Garlic eating was shown to confer protection against the development of gastric ulcer （OR=0.55, 95% CI： 0.33-0.92）. Conclusion： Smoking and drinking were the risk factors for the precancerous gastric lesions among rural subjects. Deep-fry food intake might be one of the risk factors for the precancerous gastric lesions and garlic eating was shown to confer protection against the development of gastric ulcer among rural Chinese population.

Regulative Effect of Traditional Chinese Medicine on Gene-expression Related to Precancerous Lesion of Gastric Cancer

The gene-expression changes related with precancerous lesion of gastric cancer (PLGC) are surveyed. Not only the regulative effect of traditional Chinese medicine (TCM) on oncogene, antioncogene and anti-apoptosis gene that are related with PLGC is analyzed, but also current research state is presented. It's showed that TCM has effects of therapy and inversion on PLGC. These effects are related with the inhibition to related oncogene expression, the regulation and activation to the deletion of antioncogene, the inhibition to the high-expression of mutant gene-protein about antioncogene, and the regulative function to anti-apoptosis gene.

Genetic Polymorphism of PSCA and Risk of Advanced Precancerous Gastric Lesions in a Chinese Population

Objective： To evaluate the relationship between the genetic polymorphism of prostate stem cell antigen （PSCA） and the risk of advanced precancerous gastric lesions including intestinal metaplasia（IM） and dysplasia（Dys）, a population-based study was conducted in Linqu County, a high-risk area of gastric cancer （GC） in China. Methods： The prevalence of gastric lesions including superficial gastritis（SG）, chronic atrophic gastritis（CAG）, IM and Dys was determined by histopathologic examination. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） technique. The effects of PSCA genetic variant on the risks of IM and Dys were calculated by unconditional logistic regression. Results： Multivariate analysis revealed subjects carrying PSCA rs2294008 CT/TT genotype were associated with an increased risk of IM （OR=1.38, 95% CI=1.11-1.71） and Dys （OR=1.75, 95% CI=1.36-2.26）, especially for subjects with H.pylori infection （IM： OR=1.34, 95% CI=1.05-1.71; Dys： OR=1.82, 95% CI=1.37-2.42）. Furthermore, H. pylori infection and PSCA rs2294008 CT/TT genotype were observed to jointly elevate the risk of IM （OR=3.32, 95% CI=2.33-4.71） and Dys （OR=4.58, 95% CI=2.99-7.04）. Conclusion： This study suggested that PSCA rs2294008 might have an impact on the risk of IM or Dys among the high risk population of GC.

AGE AND SITES-SPECIFIC PREVALENCE RATES OF PRECANCEROUS GASTRIC LESIONS AT A HIGH-RISK POPULATION OF STOMACH CANCER

A population-based screening for stomach cancer (SC) and its precancerous lesions was conducted in Linqu County, Shandong, China, one of the highest SC rates found in China and the world. An analysis of precancerous stomach lesions revealed that chronic atrophic gastritis (CAG) was a universal common among people aged 35-64 (96-98%). For 52% and 20% of the residents in this age group had Intestinal metaplasia (IM) or dysplssia (DYS). These more advanced lesions were more pronounced in the antrum for both males and females. Age-specific prevalence rates in different anatomic locations sshowed that CAG, developed in the antrum, particularly along the lesser curvature earter than other sites and spread to fundus. IM and DYS accrued under the background of CAG with a leading time in the antrum than the other part of the stomach. Although CAG, IM and DYS prevalence rates were higher in the antrum than In the fundus, the prevalence rates showed a similar smoothly slope, a result of accumulated somatic geneticdamage, suggesting a similar biological response to the stimulation of initiator of carcinogenesis, promoter leading to progression to SC.

A STUDY OF PRECANCEROUS GASTRIC LESIONS IN A HIGH RISK POPULATION

A study of precancerous gastric lesion was conducted in a randomly selected high risk population in Linqu, Shandong Province of China. 849 subjects aged from 30-64 were examined bioptically. There were 8 cases of gastric cancer, the prevalence rate was 0.9%. 169 subjects were diagnosed to be dysplasia, the prevalence rate of dysplasia was increased significantly with age. The regression equation was Y=0.47X-0.25. The prevalence of CAG was found in 36 per cent of the studied subjects and both dysplasia and CAG were more serious in the antrum than the. fundus. The results showed a natural history of precancerous gastric lesions in a high risk population in a high risk area.

Mn-SOD and CuZn-SOD polymorphisms and interactions with risk factors in gastric cancer

AIM: To investigate the effects of superoxide dismutase (SOD) polymorphisms (rs4998557 , rs4880), Helicobacter pylori (H. pylori ) infection and environmental factors in gastric cancer (GC) and malignant potential of gastric precancerous lesions (GPL). METHODS: Copper-zinc superoxide dismutase (SOD1, CuZn-SOD)-G7958A (rs4998557 ) and manganese superoxide dismutase (SOD2, Mn-SOD)-Val16Ala (rs4880 ) polymorphisms were genotyped by SNaPshot multiplex polymerase chain reaction (PCR) in 145 patients with GPL (87 cases of gastric ulcer, 33 cases of gastric polyps and 25 cases of atrophic gastritis), 140 patients with GC and 147 healthy controls. H. pylori infection was detected by immunoblotting analysis. RESULTS: The SOD1-7958A allele was associated with a higher risk of gastric cancer [odds ratio (OR) = 3.01, 95% confidence intervals (95% CI): 1.83-4.95]. SOD216Ala/Val genotype was a risk factor for malignant potential of GPL (OR = 2.04, 95% CI: 1.19-3.49). SOD216Ala/genotype increased the risk of gastric cancer (OR = 2.85, 95% CI: 1.66-4.89). SOD1-7958A/genotype, SOD2-16Ala/genotype, alcohol drinking, positive family history and type Ⅰ H. pylori infection were associated with risk of gastric cancer, and there were additive interactions between the two genotypes and the other three risk factors. SOD2-16Ala/Val genotype and positive family history were associated with malignant potential of GPL and jointly contributed to a higher risk for malignant potential of GPL (OR = 7.71, 95% CI: 2.10-28.22). SOD1-7958A/genotype and SOD2-16Ala/genotype jointly contributed to a higher risk for gastric cancer (OR = 6.43, 95% CI: 3.20-12.91). CONCLUSION: SOD1-7958A/and SOD2-16Ala/-genotypes increase the risk of gastric cancer in Chinese Han population. SOD2-16Ala/-genotype is associated with malignant potential of GPL.

Preventive and inhibitive effects of Yiwei Xiaoyu granules on the development and progression of spasmolytic polypeptideexpressing metaplasia lesions

BACKGROUND Spasmolytic polypeptide-expressing metaplasia(SPEM)is a potential preneoplastic lesion.AIM To elucidate the microRNA(miR)-7-mediated preventive and inhibitive effects of Yiwei Xiaoyu granules(YWXY)in SPEM lesions.METHODS Gastric mucosa biopsies were collected from chronic atrophic gastritis patients and healthy people with signed informed consent.YWXY was administered to the mice with induced SPEM by tamoxifen,and the gastric mucosa was harvested on the tenth day of the experiment.Then immunohistochemistry and immunofluorescence were performed to validate the SPEM,lesions and the potential mechanism was investigated.RNA transcripts were detected with reverse transcriptionquantitative polymerase chain reaction.RESULTS The expression of miR-7 was downregulated in the SPEM lesions,and expression of trefoil factor 2(TFF2)and clusterin was high in the human gastric mucosa.In vivo experiments showed that YWXY could inhibit the cell proliferation in the tamoxifen-induced SPEM lesions by regulating Ki67.Simultaneously,YWXY could restore the expression of miR-7 by regulating TFF2 by detection with immunofluorescence but not with reverse transcription-quantitative polymerase chain reaction,indicating its potential mechanism of targeting miR-7 by mediating TFF2.The expression of vascular endothelial growth factor-βand gastric intrinsic factor was restored within 3 d of YWXY administration for the SPEM lesions,speculating that the possible mechanism of YWXY is to inhibit the development and progression of SPEM by regulating vascular endothelial growth factor-βand gastric intrinsic factor.CONCLUSION miR-7 downregulation is an early event in SPEM through regulation of TFF2 in human gastric mucosa.YWXY is able to inhibit the cell proliferation and restore the expression of miR-7 by mediating TFF2 in the SPEM mouse model.

A cross-sectional study on traditional Chinese medicine syndromes distribution for chronic atrophic gastritis based on data mining

Background:Chronic atrophic gastritis(CAG)is a common digestive system disease characterized by reduced gastric mucosa inherent glands and often accompanied by intestinal metaplasia and dysplasia.Traditional Chinese medicine believes that syndrome elements dampness and blood stasis are closely related to the occurrence and development of CAG and promote the occurrence of precancerous lesions of gastric cancer.However,there is a lacking of more in-depth and detailed study on the above syndrome elements.This study aimed to made a quantitative description by cross-sectional study on the frequency of key syndrome elements dampness and blood stasis of CAG.Methods:201 CAG patients who met with inclusion criteria were divided into 4 groups including:only dampness group,only blood stasis group,none of dampness and blood stasis group,dampness and blood stasis group according to their four diagnostic information.The severities and levels of patients’clinical symptoms,pathological signs and patient-reported outcome scale used as evaluation indexes were collected.Data mining method of exploratory factor analysis was used for statistics.Results:The results suggested that the frequencies of dampness and blood stasis were reflected in the severity and levels of gastric symptoms,helicobacter pylori infection and the distribution and severity of dysplasia.And blood stasis played a more prominent role in promoting the progression of the CAG to cancer.Conclusion:Our results might provide a quantitative syndrome description for the traditional Chinese medicine differentiation in treating precancerous lesions of gastric cancer and preventing gastric cancer.

A comprehensive update:gastrointestinal microflora,gastric cancer and gastric premalignant condition,and intervention by traditional Chinese medicine

With the recent upsurge of studies in the field of microbiology,we have learned more about the complexity of the gastrointestinal microecosystem.More than 30 genera and 1000 species of gastrointestinal microflora have been found.The structure of the normal microflora is relatively stable,and is in an interdependent and restricted dynamic equilibrium with the body.In recent years,studies have shown that there is a potential relationship between gastrointestinal microflora imbalance and gastric cancer(GC)and precancerous lesions.So,restoring the balance of gastrointestinal microflora is of great significance.Moreover,intervention in gastric premalignant condition(GPC),also known as precancerous lesion of gastric cancer(PLGC),has been the focus of current clinical studies.The holistic view of traditional Chinese medicine(TCM)is consistent with the microecology concept,and oral TCM can play a two-way regulatory role directly with the microflora in the digestive tract,restoring the homeostasis of gastrointestinal microflora to prevent canceration.However,large gaps in knowledge remain to be addressed.This review aims to provide new ideas and a reference for clinical practice.