• Helicobacter pylori
• Ligilactobacillus salivarius NCUH062003
• antibacterial activity
• gut microbiota
• inflammatory effect

• Project No. 20232BCD44005 the National Key Laboratory Project
• Project No. 2022-PYXM-04 Jiangxi Institute of Nutrition and Health Management 2022 Cultivation Project
• Project No. JXNK202303-05 Jiangxi Provincial Agricultural Key Core Technology Tackling Project

• angiogenesis
• chemoresistance
• cytokines
• epigenetic regulation
• gastric cancer (GC)
• metastasis

• Humans
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Epigenesis, Genetic
• Cytokines/metabolism
• Drug Resistance, Neoplasm/genetics
• Angiogenesis

• 5mC
• CIMP
• DNA methylation
• epigenetic regulation
• mCRPC

• Helicobacter pylori
• IL-1 polymorphism
• IL-1β
• IL1RN VNTR
• rs1143627
• rs16944

• # IAO 134212 Canadian Institutes of Health Research

• Atrophic gastritis
• Gastric cancer
• Methylation
• Risk factor

• gastrointestinal cancer
• tumour biomarkers
• cancer therapy

• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• ErbB Receptors/metabolism
• Humans
• Phosphatidylinositol 3-Kinases/genetics
• Phosphatidylinositol 3-Kinases/metabolism
• Signal Transduction
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/genetics
• Stomach Neoplasms/therapy
• Tumor Suppressor Protein p53

• Guangdong Basic and Applied Basic Research Foundation #2021A1515010117
• The National Key Research and Development Program of China #2018YFA0902801 The 100 Top Talents Program of Sun Yat-Sen University (ZSQYBRJH0001)
• National Natural Science Foundation of China (National Science Foundation of China)
• Guangdong Provincial Key Laboratory of Digestive Cancer Research #2021B1212040006

• Helicobacter pylori
• DNA methylation
• metachronous neoplasm

• Adult gastroenterology
• Gastrointestinal infections
• Thromboembolism

• Anti-Bacterial Agents/therapeutic use
• Cohort Studies
• Female
• Helicobacter Infections/complications
• Helicobacter Infections/drug therapy
• Helicobacter Infections/epidemiology
• Helicobacter pylori
• Humans
• Male
• Middle Aged
• Peptic Ulcer/epidemiology
• Venous Thromboembolism/chemically induced

• National Natural Science Foundation of China

Chronic atrophic gastritis (CAG) is a precancerous disease that often leads to the development of gastric cancer (GC) and is positively correlated with GC morbidity. However, the sensitivity of the endoscopic diagnosis of CAG is only 42%. Therefore, we developed a real-time video monitoring model for endoscopic diagnosis of CAG based on U-Net deep learning (DL) and conducted a prospective nested case–control study to evaluate the diagnostic evaluation indices of the model and its consistency with pathological diagnosis.

Our cohort consisted of 1539 patients undergoing gastroscopy from December 1, 2020, to July 1, 2021. Based on pathological diagnosis, patients in the cohort were divided into the CAG group or the chronic nonatrophic gastritis (CNAG) group, and we assessed the diagnostic evaluation indices of this model and its consistency with pathological diagnosis after propensity score matching (PSM) to minimize selection bias in the study.

After matching, the diagnostic evaluation indices and consistency evaluation of the model were better than those of endoscopists [sensitivity (84.02% vs. 62.72%), specificity (97.04% vs. 81.95%), positive predictive value (96.60% vs. 77.66%), negative predictive value (85.86% vs. 68.73%), accuracy rate (90.53% vs. 72.34%), Youden index (81.06% vs. 44.67%), odd product (172.5 vs. 7.64), positive likelihood ratio (28.39 vs. 3.47), negative likelihood ratio (0.16 vs. 0.45), AUC (95% CI) [0.909 (0.884–0.934) vs. 0.740 (0.702–0.778)] and Kappa (0.852 vs. 0.558)].

Our prospective nested case–control study proved that the diagnostic evaluation indices and consistency evaluation of the real-time video monitoring model for endoscopic diagnosis of CAG based on U-Net DL were superior to those of endoscopists.

Trial registrationChiCTR2100044458, 18/03/2020.

• Artificial intelligence
• Chronic atrophic gastritis
• Deep learning
• Gastroscopy
• U-Net

• Helicobacter pylori
• IL-1β
• gastric cancer
• inflammation

The microenvironment in the stomach is different from other digestive tracts, mainly because of the secretion of gastric acid and digestive enzymes, bile reflux, special mucus barrier, gastric peristalsis, and so on, which all contribute to the formation of antibacterial environment. Microecological disorders can lead to gastric immune disorders or lead to the decrease of dominant bacteria and the increase of the abundance and virulence of pathogenic microorganisms and then promote the occurrence of diseases. The body performs its immune function through innate and adaptive immunity and maintains microbial balance through the mechanism of immune homeostasis. Microecological imbalance can lead to the invasion of pathogenic microorganisms and damage mucosal barrier and immune system. The coexistence of gastric microorganisms (including viruses and fungi) may play a synergistic or antagonistic role in the pathogenesis of gastric diseases. Probiotics have the ability to compete with intestinal pathogens, increase the secretion of immunoglobulin A (IgA), stimulate the production of mucin, bacteriocin, and lactic acid, regulate the expression and secretion of cytokines, and regulate the growth of microbiota, which all have beneficial effects on the host microbial environment. At present, most studies focused on Helicobacter pylori, ignoring other stomach microbes and the overall stomach microecology. So, in this article, we reviewed advances in human gastric microecology, the relationship between gastric microecology and immunity or gastric diseases, and the treatment of probiotics in gastric diseases, in order to explore new area for further study of gastric microorganisms and treatment of gastric diseases.

A predictive marker for the development of synchronous/metachronous gastric cancer (GC) would be highly desirable in order to establish an effective strategy for endoscopic surveillance. Herein, we examine the significance of gastric xanthelasma (GX) and molecular abnormalities for the prediction of synchronous/metachronous GC. Patients (n = 115) were followed up (range, 12–122; median, 55 months) in whom the presence of GX and molecular alterations, including microsatellite instability (MSI) and methylation of human mutL homolog 1 (hMLH1), cyclin-dependent kinase inhibitor 2A (CDKN2A) and adenomatous polyposis coli (APC) genes, had been confirmed in non-neoplastic gastric mucosa when undergoing endoscopic submucosal dissection (ESD) for early GC. At the start of surveillance, the numbers of positive subjects were as follows: GX, 59 (51.3%); MSI, 48 (41.7%); hMLH1, 37 (32.2%); CDKN2A, 7 (6.1%); APC, 18 (15.7%). After ESD treatment, synchronous/metachronous GCs occurred in patients with the following positive factors: GX, 16 (27.1%); MSI, 7 (14.6%); hMLH1, 6 (16.2%); CDKN2A, 3 (42.9%); APC, 3 (16.7%). The presence of GX had no significant relationship to positivity for MSI or methylation of hMLH1, CDKN2A or APC. GX was significantly (p = 0.0059) and independently (hazard ratio, 3.275; 95% confidence interval, 1.134–9.346) predictive for the development of synchronous/metachronous GC, whereas those genetic alterations were not predictive. GX is a simple and powerful marker for predicting the development of synchronous or metachronous GC.

Whether Helicobacter pylori eradication actually reduces the risk of metachronous gastric cancer (MGC) development remains a controversial question. In this review, we addressed this topic by reviewing the results of clinical investigations and molecular pathological analyses of the roles of H. pylori eradication and aspirin administration in the prevention of MGC. In regard to the clinical studies, the results of meta-analyses and randomized control trials differ from those of retrospective studies: the former trials show that H. pylori eradication has a preventive effect on MGC, while the latter studies do not. This discrepancy may be at least partly attributable to differences in the follow-up periods: H. pylori eradication is more likely to prevent MGC over a long-term follow-up period (≥5 years) than over a short-term follow-up period. In addition, many studies have shown that aspirin may have an additive effect on MGC-risk reduction after H. pylori eradication has been achieved. Both H. pylori eradication and aspirin use induce molecular alterations in the atrophic gastritis mucosa but not in the intestinal metaplasia. Unfortunately, the molecular pathological analyses of these interventions have been limited by short follow-up periods. Therefore, a long-term prospective cohort is needed to clarify the changes in molecular events caused by these interventions.

• Aspirin
• Eradication
• Helicobacter pylori
• Pathology
• Stomach neoplasms
• molecular

• DNA methylation
• MRSA
• Staphylococcus aureus
• epigenetics
• persistence

• Anti-Bacterial Agents/administration & dosage
• Bacteremia/drug therapy
• Bacteremia/metabolism
• CCAAT-Enhancer-Binding Protein-beta/metabolism
• DNA Methylation
• Female
• Humans
• Male
• Methicillin-Resistant Staphylococcus aureus/metabolism
• Middle Aged
• Response Elements
• STAT1 Transcription Factor/metabolism
• Staphylococcal Infections/drug therapy
• Staphylococcal Infections/metabolism
• p300-CBP Transcription Factors/metabolism

• R33 AI111661 NIAID NIH HHS
• R01 AI139244 NIAID NIH HHS
• R01 AI068804 NIAID NIH HHS
• KL2 TR001882 NCATS NIH HHS
• U01 AI124319 NIAID NIH HHS

• DNA methylation
• Family history
• Gastric cancer
• Helicobacter pylori

Helicobacter pylori is a class one carcinogen which causes chronic atrophic gastritis, gastric intestinal metaplasia, dysplasia and adenocarcinoma. The mechanisms by which H. pylori interacts with other risk and protective factors, particularly vitamin C in gastric carcinogenesis are complex. Gastric carcinogenesis includes metabolic, environmental, epigenetic, genomic, infective, inflammatory and oncogenic pathways. The molecular classification of gastric cancer subtypes has revolutionized the understanding of gastric carcinogenesis. This includes the tumour microenvironment, germline mutations, and the role of Helicobacter pylori bacteria, Epstein Barr virus and epigenetics in somatic mutations. There is evidence that ascorbic acid, phytochemicals and endogenous antioxidant systems can modify the risk of gastric cancer. Gastric juice ascorbate levels depend on dietary intake of ascorbic acid but can also be decreased by H. pylori infection, H. pylori CagA secretion, tobacco smoking, achlorhydria and chronic atrophic gastritis. Ascorbic acid may be protective against gastric cancer by its antioxidant effect in gastric cytoprotection, regenerating active vitamin E and glutathione, inhibiting endogenous N-nitrosation, reducing toxic effects of ingested nitrosodimethylamines and heterocyclic amines, and preventing H. pylori infection. The effectiveness of such cytoprotection is related to H. pylori strain virulence, particularly CagA expression. The role of vitamin C in epigenetic reprogramming in gastric cancer is still evolving. Other factors in conjunction with vitamin C also play a role in gastric carcinogenesis. Eradication of H. pylori may lead to recovery of vitamin C secretion by gastric epithelium and enable regression of premalignant gastric lesions, thereby interrupting the Correa cascade of gastric carcinogenesis.

• CagA
• Correa pathway
• Helicobacter pylori
• ascorbic acid
• chronic atrophic gastritis
• dietary salt
• gastric cancer
• glutathione
• nitrosamines
• oxidative stress
• phytochemicals
• vitamin C

• H. pylorieradication
• atrophy
• gastric inflammation
• gastric microbes
• intestinal metaplasia

• Carcinogenesis
• DNA repair
• Helicobacter pylori
• Mismatch repair
• Nucleotide excision repair
• cagA

• Adult
• DNA Mismatch Repair
• DNA Repair
• DNA-Binding Proteins/genetics
• Endonucleases/genetics
• Female
• Gastritis/enzymology
• Gastritis/etiology
• Gastritis/genetics
• Gastritis/microbiology
• Gene Expression Regulation
• Gene Expression Regulation, Neoplastic
• Helicobacter Infections/complications
• Helicobacter pylori
• Humans
• Male
• Middle Aged
• Mismatch Repair Endonuclease PMS2/genetics
• Stomach Neoplasms/enzymology
• Stomach Neoplasms/etiology
• Stomach Neoplasms/genetics
• Stomach Neoplasms/microbiology

• Helicobacter pylori
• epigenetic
• gastric cancer
• methylation
• miRNAs

• Carcinogenesis/genetics
• Cell Transformation, Neoplastic/genetics
• Epigenesis, Genetic/genetics
• Helicobacter Infections/complications
• Helicobacter pylori/genetics
• Humans
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism

Non-ampullary duodenal adenocarcinoma (NADC) is extremely rare. Little is known about its clinicopathological and molecular features or its management. Herein we retrospectively analyzed the cases of 32 NADC patients, focusing on microsatellite instability (MSI), genetic mutations, CpG island methylator phenotype (CIMP), and immunostaining including mucin phenotype and PD-L1 expression. The incidence of MSI, KRAS/BRAF/GNAS mutations and CIMP was 51.6%, 34.4%/3.1%/6.5% and 28.1%, respectively. PD-L1 expression was seen in 34.4% of patients. No significant associations between clinicopathological features and KRAS/BRAF/GNAS genetic mutations or CIMP were found. Histologically non-well-differentiated-type NADCs and those in the 1st portion of the duodenum were significantly associated with later stages (stages III–IV) (P = 0.006 and P = 0.003, respectively). Gastric-phenotype NADCs were frequently observed in the 1st portion and in late-stage patients; their cancer cells more frequently expressed PD-L1. Histologically, the non-well-differentiated type was an independent predictor of PD-L1 expression in cancer cells (OR 25.05, P = 0.04) and immune cells (OR 44.14, P = 0.02). Only late-stage disease (HR 12.23, P = 0.01) was a prognostic factor for worse overall survival in a Cox proportional hazards regression model. Our observation of high proportions of MSI and PD-L1 expression may prompt the consideration of immune checkpoint inhibitors as a new treatment option for NADCs.

Long noncoding RNAs (lncRNAs) have emerged as important regulators of human cancers. LncRNA GAS5 (GAS5) is identified as a tumor suppressor involved in several cancers. However, the roles of GAS5 and the mechanisms responsible for its functions in gastric cancer (GC) have not been well documented. Herein, the decreased GAS5 and increased miRNA-106a-5p levels were observed in GC and cell lines. GAS5 level was significantly inversely correlated with miRNA-106a-5p level in GC tissues. Moreover, dual-luciferase reporter and qRT-PCR assays showed that GAS5 bound to miRNA-106a-5p and negatively regulated its expression in GC cells. Functional experiments showed that GAS5 overexpression suppressed GC cell proliferation, migration and invasion capabilities, and promoted apoptosis, while miRNA-106a-5p overexpression inverted the functional effects induced by GAS5 overexpression. In vivo, GAS5 overexpression inhibited tumor growth by negatively regulating miRNA-106a-5p expression. Mechanistic investigations revealed that GAS5 overexpression inactivated the Akt/mTOR pathway by suppressing miRNA-106a-5p expression in vitro and in vivo. Taken together, our findings conclude the GAS5 overexpression suppresses tumorigenesis and development of gastric cancer by sponging miR-106a-5p through the Akt/mTOR pathway.

Summary: GAS5, a tumor suppressor, was confirmed to suppress tumorigenesis and development of gastric cancer by sponging miR-106a-5p through the Akt/mTOR pathway, which provides a novel regulatory axis of GC progression.

• Akt/mTOR pathway
• GAS5
• Gastric cancer
• miR-106a-5p

• cancer
• chromosome instability
• intratumoral heterogeneity
• quantitative imaging microscopy
• single cell approaches