Gastric microbiota and metabolites may interact and play collaborative roles in the carcinogenesis process. This study aims to investigate differential metabolites and microbes, as well as the possible roles of microbe-metabolite interactions in gastric cancer (GC) development. Targeted metabolomics assays and 16S rRNA sequencing were performed to compare metabolic and microbial profiles in gastric tissues from subjects with superficial gastritis/chronic atrophic gastritis (SG/CAG), intestinal metaplasia/low-grade intraepithelial neoplasia (IM/LGIN) and GC. Significant differences were found in metabolic and microbial profiles between the GC and SG/CAG or IM/LGIN groups, respectively (all p < .05). By comparing GC with the other lesions, 69 differential metabolites mainly comprised triglycerides and phosphatidylcholines, and 21 differential microbes included Peptostreptococcus, Lactobacillus, Dialister, Helicobacter pylori, and Streptococcus anginosus (all p < .05). The altered metabolites and microbes in GC were both significantly enriched in the glycerophospholipid metabolism pathway, in which the predicted down-regulation of phospholipase C (plc) and up-regulation of 1-acyl-sn-glycerol-3-phosphate acyltransferase (plsC) by microbiota may affect phosphatidylcholine hydrolysis and triglyceride biosynthesis modules. More and stronger microbe-metabolite correlations in GC compared to the other lesion group further supported the potential microbial regulations to the important metabolites in gastric carcinogenesis, such as Lactobacillus and phosphatidylcholines (.32 ≤ r ≤ .57, all p < .05), Peptostreptococcus (.36 ≤ r ≤ .60, all p < .05) or Dialister (.36 ≤ r ≤ .62, all p < .05) and triglycerides. We simultaneously identified differential metabolites and microbes and their altered correlations between GC and gastric lesions. The main GC-associated phosphatidylcholines and triglycerides may be affected by gastric microbes, which provides new perspectives on the microbiota-metabolite interactions during the development of GC.

Due to the common developmental origination and influences by similar unhealthy lifestyle, upper and lower gastrointestinal (GI) diseases may be closely associated. However, the evidence remains elusive. This study aims to determine the prevalence of GI endoscopic lesions and the correlations between endoscopic lesions in individuals undergoing gastroscopy and colonoscopy simultaneously.

A retrospective study was conducted on 18,556 individuals who underwent simultaneous gastroscopy and colonoscopy at the Endoscopy Center of Xijing Hospital of Digestive Diseases from January 2020 to March 2023. Data on sex, age, pathological and endoscopic results were collected. The Pearson chi-square test was used to analyze the occurrence of various GI lesions among age groups and correlations between GI lesions, and logistic regression was used to determine risk factors for common upper and lower GI lesions.

The mean age was 50.35 ± 12.31 years, and 55.5% of participants were male. At least one endoscopic abnormality was observed in 16,530 cases (89.1%), with 8253 cases (44.5%) showing abnormalities in both the upper and lower GI tract. The most common upper GI endoscopic lesions were chronic atrophic gastritis (CAG, 47.7%), reflux esophagitis (RE, 24.7%), and other gastritis (18.1%). Colorectal polyps (CPs) were the most prevalent lower GI endoscopic condition, observed in 37.5% of cases. The detection of CAG, RE, CPs increased with age, and was higher in man. Moreover, the presence of CAG was associated with the occurrence of CPs (kappa value = 0.135, p < 0.001), which was independent of age and gender.

Most GI diseases are more prevalent in men and the elderly. Additionally, CAG is independently correlated with the occurrence of endoscopic CPs.

To develop a risk prediction model for the transformation of chronic atrophic gastritis (CAG) to high-grade intraepithelial neoplasia (HGIN) based on Traditional Chinese Medicine (TCM) syndrome patterns.

Clinical data of 201 chronic atrophic gastritis patients who visited the Department of Gastroenterology at the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine and Dong'erhuan Branch between January 2022 and March 2023 were retrospectively analyzed, including 32 patients with HGIN (HGIN group) and 169 patients with moderate and severe chronic atrophic gastritis (non-HGIN group). The information of demographic characteristics, dietary habits, lifestyle factors, psychosocial factors, family history of tumors, medical history and comorbidities, long-term medication, endoscopic findings, histopathological examination results, as well as TCM syndrome types were collected. Potential HGIN risk factors of were screened using LASSO regression, and then significant risk factors for establishing an HGIN risk prediction model were identified using logistic regression analysis. The final model was visually presented using a nomogram, and its diagnostic performance was evaluated through receiver operating characteristic curve analysis.

Spleen-stomach Qi deficiency was the most common TCM syndrome in both HGIN and non-HGIN groups. LASSO-logistic regression model analysis showed that heavy alcohol consumption (X1), syndrome of static blood in stomach collaterals (X2), low-grade intraepithelial neoplasia (X3), high-salt diet (X4), and age (X5) were independent risk factors related to the occurrence of HGIN, and the predictive model was I n P 1- P=2.159X1+2.23X2+1.664X3+2.07X4+0.122X5- 11.096. The model demonstrated good discriminative ability, calibration, and goodness-of-fit.

The TCM syndrome of static blood in stomach collaterals shows a certain correlation with the transformation from chronic atrophic gastritis to HGIN. The HGIN prediction model based on TCM syndrome patterns developed in the study demonstrates potential clinical application value.

Gastric cancer (GC) is diagnosed more than one million times each year and represents a major cause of cancer-related death worldwide. Although GC presents as a group of different types of disease, chronic inflammation has been strongly associated with tumorigenesis. Monocyte/macrophage play important roles in the development of inflammation and are vital components of the tumor microenvironment (TME). Monocyte/macrophage exert protumor and/or antitumor effects through the release of angiogenic and lymphangiogenic factors. Furthermore, tumor associated macrophages (TAMs) are emerging as key players in GC development. It is necessary to review and elucidate the roles of TAM subsets in GC and their molecular features. In this study, we focused on GC-related subsets of monocytes/macrophages and analyzed signaling related to TAMs in GC as well as the potential roles of these cells as therapeutic targets.

This study investigated the potential association between gastric intestinal metaplasia, Helicobacter pylori (H pylori) positivity and ABO/Rh blood types. Additionally, the study examined the association between intestinal metaplasia and H pylori positivity. The study population consisted of 297 patients aged 19 years and older who underwent endoscopic biopsies for the assessment of intestinal metaplasia and H pylori infection. Patients' ABO/Rh blood type information was retrieved from the hospitals electronic archive system. Comparative analyses were performed to assess the distribution of ABO/Rh blood types among patients with and without intestinal metaplasia and H pylori infection. No statistically significant correlation was observed between H pylori positivity on endoscopic biopsy and ABO/Rh blood types. Similarly, there was no statistically significant correlation between intestinal metaplasia and ABO/Rh blood types. However, a significant association was identified between H pylori infection and intestinal metaplasia. The observed association between H pylori infection and intestinal metaplasia underscores the importance of H pylori testing in patients diagnosed with intestinal metaplasia. While our findings suggest that ABO/Rh blood type may not be a risk factor for intestinal metaplasia or H pylori infection, further research with a larger sample size is warranted to confirm these results, particularly in light of existing conflicting data in the literature.

Zuojin pill is a well-known traditional Chinese medicine (TCM) for treating gastric disorders. The modified Zuojin pill (SQQT) has been used in the treatment of gastric metaplasia (GM) in China for decades. However, the mechanisms of SQQT treat GM remain unclear.

Our goals are to evaluate the effect of SQQT on GM and to investigate its potential mechanisms.

An animal model of metaplasia was established to study the mechanism of SQQT. RNA-seq was employed to analyze the pathogenesis of GM. Network pharmacological approaches and molecular docking were used to elucidate the mechanisms of SQQT. Common targets of the SQQT and GM mechanism pathways are defined as the key mechanisms of SQQT's treatment in GM. The key mechanisms were validated through in vivo and in vitro experiments.

RNA-seq analysis of GM animals and network pharmacology of SQQT indicated that SQQT might treat GM via 20 pathways, including the PPAR pathway. Among the 3 core targets of the PPAR pathway, only PPARG is related to GM progression. Besides, the core components of SQQT have a lower affinity for binding to PPARG. The main mechanism of SQQT ameliorated GM is related to PPARG. In animal experiments, SQQT ameliorated GM through ROS decreasing, mitochondrial damage repairing, and protein marker rectification. In cell experiments, SQQT notably decreased the levels of ferroptosis and metaplasia markers including GPX4, PPARG, MUC6, and ACSL4.

SQQT ameliorated gastric metaplasia by inhibiting the PPARG/ferroptosis pathway.

Helicobacter infection, which is the leading cause of gastritis and stomach cancer, has become common worldwide. Almost all Helicobacter-infected patients have chronic active gastritis, also known as Helicobacter-associated gastritis (HAG). However, the eradication rate of Helicobacter is decreasing due to the poor efficacy of current medications, which causes infection to recur, inflammation to persist, and stomach cancer to develop. Natural components have robust antibacterial activity and anti-inflammatory capacity, as confirmed by many studies of alternative natural medicines.

This article aimed to conduct a comprehensive search and meta-analysis to evaluate the efficacy of anti-Helicobacter and anti-inflammatory activities of plant-derived extracts or compounds that can treat HAG in animal experiments. We intended to provide detailed preclinical-research foundation including plant and compound information, as well as the mechanisms by which these plant-derived substances inhibit the progression of Helicobacter infection, gastritis and neoplasms for future study.

The systematic review is aligned with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and the protocol was registered in PROSPERO (CRD42024527889). An extensive search was performed across multiple databases, including PubMed, Scopus, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal database (VIP), the Wanfang database, and the China biomedical literature service system (SinoMed), up until November 2023. Meta-analysis on Review Manager software (RevMan 5.4) estimating anti-Helicobacter and anti-inflammatory activity was performed. We used the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk of bias tool to evaluate the risk of bias of each study included.

Our study encompassed 61 researches, comprised 36 extracts and 37 compounds improving HAG by inhibiting Helicobacter infection, the inflammatory response, oxidative stress, and regulating apoptosis and proliferation. Sixteen families especially Asteraceae, Fabaceae and Rosaceae and nine classes including Terpenoids, Alkaloids, Phenols, and Flavonoids may be promising directions for valuable new drugs. The Meta-analyse demonstrated the plant-base substance treatments possess significant anti-Helicobacter and anti-inflammation activity comparing to control groups. The included plants and compounds confirmed that signaling pathways NF-κB, JAK2/STAT3, MAPK, TLR4/MyD88, PI3K/AKT, NLRP3/Caspase-1 and NRF2/HO-1 play a key role in the progression of HAG.

Plant-derived extracts or compounds actively improve HAG by modulating relevant mechanisms and signaling pathways, particularly through the anti-Helicobacter and inflammatory regulation ways. Further researches to apply these treatments in humans are needed, which will provide direction for the future development of therapeutic drugs to increase eradication rate and alleviate gastritis.

Detecting gastric precancerous lesions (GPLs) is critical for the early diagnosis and treatment of gastric cancer. Endoscopy combined with tissue examination is an important method for detecting GPLs. However, negative biopsy results often increase patients' risks, economic burdens, and lead to additional healthcare costs. Improving the detection rate of GPLs and reducing the rate of negative biopsies is currently a key focus in endoscopic quality control.

To explore the relationships between the endoscopist biopsy rate (EBR), qualifications of endoscopists and endoscopic assistants, and detection rate of GPLs.

EBR, endoscopists, and endoscopic assistants were divided into four groups: Low, moderate, high, and very high levels. Multivariable logistic regression analysis was used to analyze the relationships between EBR and the qualifications of endoscopists with respect to the detection rate of positive lesions. Pearson and Spearman correlation analyses were used to evaluate the correlation between EBR, endoscopist or endoscopic assistant qualifications, and the detection rate of positive lesions.

Compared with those in the low EBR group, the odds ratio (OR) values for detecting positive lesions in the moderate, high, and very high EBR groups were 1.12 [95% confidence interval (CI): 1.06-1.19, P < 0.001], 1.22 (95%CI: 1.14-1.31, P < 0.001), and 1.38 (95%CI: 1.29-1.47, P < 0.001), respectively. EBR was positively correlated with the detection rate of gastric precancerous conditions (atrophic gastritis/intestinal metaplasia) (ρ = 0.465, P = 0.004). In contrast, the qualifications of the endoscopists were positively correlated with GPLs detection (ρ = 0.448, P = 0.005). Compared to endoscopists with low qualification levels, those with moderate, high, and very high qualification levels endoscopists demonstrated increased detection rates of GPLs by 13% (OR = 1.13, 95%CI: 0.98-1.31), 20% (OR = 1.20, 95%CI: 1.03-1.39), and 32% (OR = 1.32, 95%CI: 1.15-1.52), respectively. Further analysis revealed that the qualifications of endoscopists were positively correlated with the detection rates of GPLs in the cardia (ρ = 0.350, P = 0.034), angularis (ρ = 0.396, P = 0.015) and gastric body (ρ = 0.453, P = 0.005) but not in the antrum (ρ = 0.292, P = 0.079). Moreover, the experience of endoscopic assistants was positively correlated with the detection rate of precancerous lesions by endoscopists with low or moderate qualifications (ρ = 0.427, P = 0.015).

Endoscopists and endoscopic assistants with high/very high qualifications, but not EBR, can improve the detection rate of GPLs. These results provide reliable evidence for the development of gastroscopic quality control indicators.

Chronic atrophic gastritis (CAG) is an important stage of precancerous lesions of gastric cancer. Effective treatment and regulation of CAG are essential to prevent its progression to malignancy. Traditional Chinese medicine (TCM) has shown multi-targeted efficacy in CAG treatment, with advantages in enhancing gastric mucosal barrier defense, improving microcirculation, modulating inflammatory and immune responses, and promoting lesion healing, etc. Clinical studies and meta-analyses indicate that TCM provides significant benefits, with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation, anti-oxidation, and regulation of cellular proliferation and apoptosis, etc. Finally, it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards, and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.

This study aimed to characterize salivary microbiota in patients with oral cancer using 16S rRNA amplicon sequencing. DNA was extracted from saliva samples of 23 patients with oral cancer and 95 age-matched controls. A metagenomic analysis was performed using 16S rRNA amplicon sequencing. Patients with oral cancer exhibited lower α-diversity, as indicated by the Chao-1 index, compared to the control group, and significant differences in β-diversity were observed between the two groups. At the genus level, 25 bacterial species such as Lautropia, Megasphaera, Lactobacillus, Kingella, Gemella, Staphylococcus, and Propionibacterium were identified in patients with oral cancer, with more than half being Gram-positive facultative anaerobes or anaerobes. The reduced bacterial diversity in saliva of patients with oral cancer suggests dysbiosis during oral carcinogenesis may contribute to changes in bacterial distribution within the oral cavity.

Stomach cancer is one of the leading causes of cancer death, and its epidemiologic characteristics are regionally heterogeneous worldwide. The BRICS nations (Brazil, Russian Federation, India, China, and South Africa) have markedly increasing influences on the international stage. We aim to investigate time trends in stomach cancer mortality among the BRICS countries from 1982 to 2021.

Data for this study were obtained from the Global Burden of Disease (GBD) 2021 public dataset to investigate the deaths, all-age mortality rate, and age-standardized mortality rate (ASMR) of stomach cancer. The age-period-cohort (APC) model was employed to estimate net drift, local drift, age-specific curves, and period (cohort) relative risks, and the Bayesian generalized linear model was employed to evaluate the relationship between food intake and mortality rate.

In 2021, there were approximately 572,000 stomach cancer deaths across the BRICS, accounting for 59.9% of global death. Russian Federation exhibited the most significant reduction in ASMR of stomach cancer among the BRICS. In contrast, China continued to report the highest number of stomach cancer deaths. The risk of mortality associated with stomach cancer exhibited a marked increase with advancing age, both within these countries and at the global level. PUFA, sodium, calcium and trans fat may have an impact on the mortality rate of stomach cancer. Favorable trends in period and birth cohort effects were observed in these five nations over the past decades.

BRICS countries have made varying progress in reducing stomach cancer mortality. Given the diverse environments, it is recommended to progressively develop customized stomach cancer prevention strategies, utilizing available resources. Healthcare services should be extended to all age groups, with a particular emphasis on vulnerable populations.

Gastric adenocarcinoma is a highly lethal neoplasm with a short survival especially when metastatic. Few effective treatments are available for the control of the disease and palliation of patients with metastatic gastric cancer. Although progress has been made in the elucidation of molecular pathways invoked in gastric carcinogenesis, this knowledge has not yet led to major breakthroughs, in contrast to several other types of cancer. The role of stem cell transcription factors SOX2 and CDX2 is of particular interest in the pathogenesis of gastric cancer.

The cohort of gastric adenocarcinomas from The Cancer Genome Atlas (TCGA) was interrogated and two groups of gastric cancers, with CDX2 induction and SOX2 suppression on the one hand and with CDX2 induction and SOX2 maintained expression on the other hand were retained. The induction of expression of the two transcription factors was defined as a mRNA expression z score compared with normal samples above zero. The two groups were compared for clinical-pathologic and genomic differences.

Among gastric cancers with up-regulated CDX2 mRNA, cancers with suppressed SOX2 mRNA were slightly more numerous (55.9%) than those with a maintained SOX2 expression. The SOX2 suppressed group had a higher prevalence of MSI high cancers (30.9% versus 10%) and of cases with high tumor mutation burden (35% versus 12.4%) than cancers with a SOX2 maintained expression, which presented more frequently high Chromosomal Instability (CIN). The group with SOX2 suppression had higher rates of mutations in many gastric cancer-associated genes such as epigenetic modifiers ARID1A, KMT2D, KMT2C, and KMT2B, as well as higher rates of mutations in genes encoding for receptor tyrosine kinases ERBB4 and FGFR1. On the other hand, TP53 mutations and amplifications in MYC, ERBB2, and CCNE1 were more common in the group with a maintained expression of SOX2, approaching significance for MYC.

Notable differences are present in the genomic landscape of CDX2-induced gastric cancer depending on the level of expression of SOX2 mRNA. Despite this, SOX2 mRNA expression levels were not prognostic.

Chronic atrophic gastritis (CAG) is considered to be closely related to Helicobacter pylori (H. pylori) infection and characterized by the atrophy and/or intestinal metaplasia (IM) of the gastric mucosa in pathology. CAG is often regarded as the precancerous lesion of gastric cancer and H. pylori infection stimulates the development of atrophy and IM and the progression of gastric cancer through the persistent effect acting on the gastric mucosa, including releasing inflammatory factors such as Interleukin-8(IL-8). From the molecular biology perspective, growing evidence shows that H. pylori probably induce the expression of NF-κB, miR-204, miR-27a, hnRNPA2B1, and JARID1B, which play crucial roles in the progression of CAG into gastric cancer. In addition, H. pylori can increase Epstein-Barr virus (EBV) infection, and the co-infection will jointly increase gastric cancer risk. Furthermore, H. pylori induces cellular senescence and promotes atrophy progression and finally increases the gastric cancer risk. This review aims to explore the carcinogenic mechanisms of H. pylori related CAG in order to provide theoretical foundations for the pathogenesis mechanism and early detection and prevention of gastric cancer.

Detecting gastric intestinal metaplasia (GIM) with white light endoscopy (WLE) remains a challenge and virtual chromoendoscopy methods have been shown to increase accuracy. We aimed to externally validate the Endoscopic Grading of Gastric Intestinal Metaplasia (EGGIM) using blue light imaging (BLI).

First, the reliability of BLI and the EGGIM score was evaluated through assessment of 90 images divided into three sets of 30. A multicenter cross-sectional study was conducted at two Italian centers involving 102 patients (510 biopsies). Both per-biopsy and per-patient analyses were performed to ascertain accuracy of BLI in detecting and staging GIM (vs. histology).

BLI significantly enhanced interobserver agreement of endoscopic diagnosis of GIM, with a Fleiss Kappa of 0.4 (95% confidence interval [CI] 0.3-0.5), compared to 0.2 (95% CI 0.2-0.3) with WLE. Concordance was particularly strong in applying the EGGIM score (weighted Kappa 0.7; 95% CI 0.5-0.9). BLI showed significant improvements in sensitivity over WLE, with an increase observed in both per-biopsy analysis (82%; 95%CI 73.7-89.0 vs. 50%;95% CI 40.6-60.3) and per-patient analysis (96%; 95% CI 84.5-99.4 vs. 68%;95% CI 52.4-81.4). The area under the curve of EGGIM in diagnosing OLGIM III/IV was 0.9 (95% CI 0.8-1.0), confirming EGGIM > 4 being the optimal threshold (sensitivity of 80%, specificity of 88%).

Our study validates BLI integrated with the EGGIM system as an effective strategy, highlighting its precision in identifying advanced GIM stages. BLI's notable sensitivity enhances its use as a complementary tool to WLE, significantly improving gastric cancer risk assessment.

Gastric cancer (GC) is the fifth leading cause of cancer-related death worldwide. The oral microbiota was investigated for distinguishable characteristics between GC, premalignant gastric conditions (Pre-GC), and control participants.

Mouthwash samples from GC, Pre-GC, and control participants at a tertiary care center were prospectively collected. Following DNA extraction and sequencing, analyses of oral microbiome biodiversity and composition were performed, and receiver operating characteristic curves were created to evaluate the discriminative power of oral microbiome signatures.

Oral samples from 98 participants included 30 (30.6%) GC, 30 (30.6%) Pre-GC and 38 (38.8%) controls. Of these, 61 (62.2%) were female, 31 (31.6%) were Hispanic, and 18 (18.3%) were smokers. GC compared to controls demonstrated notable differences in beta diversity (Jensen-Shannon Divergence and Bray-Curtis Dissimilarity, p<0.02). 32 bacterial genera were found to be differentially abundant when comparing GC and controls, and 23 bacterial genera demonstrated differential abundance when comparing Pre-GC and controls (W-statistic >2). Minimal compositional differences between GC and Pre-GC were found, with only three differentially abundant bacterial genera (W-statistic >2). Models were constructed from the most significant bacterial signatures (W-statistic >5). These models discriminated between GC and control oral samples with an AUC of 0.880 (95% CI 0.808, 0.952) and between Pre-GC and control oral samples with an AUC of 0.943 (95% CI 0.887, 0.999).

Oral rinses of GC and Pre-GC participants exhibited distinct but similar microbiome profiles, distinguishing them from controls. This compositional difference raises the possibility of utilizing these microbial signatures to predict GC risk.

The implementation of computer-aided detection (CAD) devices in esophagogastroduodenoscopy (EGD) could autonomously identify gastric precancerous lesions and neoplasms and reduce the miss rate of gastric neoplasms in prospective trials. However, there is still insufficient evidence of their use in real-life clinical practice.

A real-world, two-center study was conducted at Wenzhou Central Hospital (WCH) and Renmin Hospital of Wuhan University (RHWU). High biopsy rate and low biopsy rate strategies were adopted, and CAD devices were applied in 2019 and 2021 at WCH and RHWU, respectively. We compared differences in gastric precancerous and neoplasm detection of EGD before and after the use of CAD devices in the first half of the year.

A total of 33 885 patients were included and 32 886 patients were ultimately analyzed. In WCH of which biopsy rate >95%, with the implementation of CAD, more the number of early gastric cancer divided by all gastric neoplasm (EGC/GN) (0.35% vs 0.59%, P = 0.028, OR [95% CI] = 1.65 [1.0-2.60]) was found, while gastric neoplasm detection rate (1.39% vs 1.36%, P = 0.897, OR [95% CI] = 0.98 [0.76-1.26]) remained stable. In RHWU of which biopsy rate <20%, the gastric neoplasm detection rate (1.78% vs 3.23%, P < 0.001, OR [95% CI] = 1.84 [1.33-2.54]) nearly doubled after the implementation of CAD, while there was no significant change in the EGC/GN.

The application of CAD devices devoted to distinct increases in gastric neoplasm detection according to different biopsy strategies, which implied that CAD devices demonstrated assistance on gastric neoplasm detection while varied effectiveness according to different implementation scenarios.

Helicobacter pylori (Hp) is the main trigger of chronic gastric atrophy and the main leading cause of gastric cancer. Hp infects the normal gastric mucosa and can lead to chronic inflammation, glandular atrophy, intestinal metaplasia, dysplasia and finally adenocarcinoma. Chronic inflammation and gastric atrophy associated with Hp infection appear initially in the distal part of the stomach (the antrum) before progressing to the proximal part (the corpus-fundus). In recent years, endoscopic developments have allowed for the characterization of various gastric conditions including the normal mucosa (pyloric/fundic gland pattern and regular arrangement of collecting venules), Hp-related gastritis (Kyoto classification), glandular atrophy (Kimura-Takemoto classification), intestinal metaplasia (Endoscopic Grading of Gastric Intestinal Metaplasia), and dysplasia/adenocarcinoma (Vessel plus Surface classification). Despite being independent classifications, all these scales can be integrated into a single model: the endoscopic model for gastric carcinogenesis. This model would assist endoscopists in comprehending the process of gastric carcinogenesis and conducting a systematic examination during gastroscopy. Having this model in mind would enable endoscopists to promptly recognize the implications of Hp infection and the potential patient's risk of developing gastric cancer.

The human microbiome is the complex ecosystem consisting of trillions of microorganisms that play a key role in developing the immune system and nutrient metabolism. Alterations in the gut microbiome have been linked to cancer initiation, progression, metastasis, and response to treatment. Accumulating evidence suggests that levels of vitamins and minerals influence the gut environment and may have implications for cancer risk and progression. Bifidobacterium has been reported to reduce the colorectal cancer risk by binding to free iron. Additionally, zinc ions have been shown to activate the immune cells and enhance the effectiveness of immunotherapy. Higher selenium levels have been associated with a reduced risk of several cancers, including colorectal cancer. In contrast, enhanced copper uptake has been implicated in promoting cancer progression, including colon cancer. The interaction between cancer and gut bacteria, as well as dysbiosis impact has been studied in animal models. The interplay between prebiotics, probiotics, synbiotics, postbiotics and gut bacteria in cancer offers the diverse physiological benefits. We also explored the particular probiotic formulations like VSL#3, Prohep, Lactobacillus rhamnosus GG (LGG), etc., for their ability to modulate immune responses and reduce tumor burden in preclinical models. Targeting the gut microbiome through antibiotics, bacteriophage, microbiome transplantation-based therapies will offer a new perspective in cancer research. Hence, to understand this interplay, we outline the importance of micronutrients with an emphasis on the immunomodulatory function of the microbiome and highlight the microbiome's potential as a target for precision medicine in cancer treatment.

Atrophic gastritis and intestinal metaplasia may progress to gastric malignancy. Non-invasive serum biomarkers have been extensively studied and proven to be useful as a screening tool to stratify risk and identify patients for endoscopy to detect early gastric cancer. These non-invasive biomarkers have been endorsed and recommended by many international consensus guidelines. In this letter, we reviewed the literature and evidence supporting the use of serum biomarkers as a dynamic test to monitor the status of atrophic gastritis.

As a biologically essential transition metal, copper is widely involved in various enzymatic reactions and crucial biological processes in the body. It plays an increasingly important role in maintaining normal cellular metabolism and supporting the growth and development of the human body. As a trace element, copper maintains the dynamic balance of its concentration in body fluids through active homeostatic mechanisms. Both excess and deficiency of copper ions can impair cell function, ultimately leading to cell damage and death. Cuproptosis is a novel form of cell death where copper ions cause cell death by directly binding to the lipoylated components of the citric acid cycle (CAC) in mitochondrial respiration and interfering with the levels of iron-sulfur cluster (Fe-S cluster) proteins, ultimately causing protein toxic stress. Its primary characteristics are Cu2+ concentration dependence and high expression in mitochondrial respiratory cells. Recent research has revealed that, compared to other forms of programmed cell death such as apoptosis, necrosis, and autophagy, cuproptosis has unique morphological and biochemical features. Cuproptosis is associated with the occurrence and development of various diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases. This article focuses on a review of the relevance of cuproptosis in gastric cancer (GC).

Emerging evidence highlights the crucial role of gastrointestinal microbiota in the pathogenesis of gastric cancer. Helicobacter pylori (H. pylori) infection stands out as a primary pathogenic factor. However, interventions such as anti-H. pylori therapy, gastric surgeries, immunotherapy, and chronic inflammation significantly remodel the gastric microbiome, implicating a broader spectrum of microorganisms in cancer development. These microbial populations can modulate gastric carcinogenesis through various mechanisms, including sustained chronic inflammation, bacterial genotoxins, alterations in short-chain fatty acids, elevated gastrointestinal bile acids, impaired mucus barrier function, and increased concentrations of N-nitrosamines and lactic acid. The dynamic changes in gut microbiota also critically influence the outcomes of anti-cancer therapies by modifying drug bioavailability and metabolism, thus affecting therapeutic efficacy and side effect profiles. Additionally, the effectiveness of radiotherapy can be significantly impacted by gut microbiota alterations. Novel therapeutic strategies targeting the microbiome, such as dietary interventions, probiotic and synbiotic supplementation, and fecal microbiota transplantation, are showing promise in cancer treatment. Understanding the intricate relationship between the gut microbiota and gastric cancer is essential for developing new, evidence-based approaches to the prevention and treatment of this malignancy.

Gastric cancer is a major cause of cancer-related death worldwide, despite the reduction in its incidence. The disease is still burdened with a poor prognosis, particularly in Western countries. The main risk factor is the infection by Helicobacter pylori, classified as a class I carcinogen by the IARC, and It is well-known that primary prevention of gastric cancer can be achieved with the eradication of the infection. Moreover, non-invasive measurement of pepsinogens (PGI and PGI/PGII ratio) allows the identification of patients that should undergo upper gastrointestinal (GI) endoscopy. Gastric non-cardia adenocarcinoma is indeed preceded by a well-defined precancerous process that involves consecutive stages, described for the first time by Correa et al. more than 40 years ago, and patients with advance stages of gastric atrophy/intestinal metaplasia and with dysplastic changes should be followed-up periodically with upper GI endoscopies. Despite these effective screening and surveillance methods, national-level screening campaigns have been adopted only in few countries in eastern Asia (Japan and South Korea). In this review, we describe primary and secondary preventive measures for gastric cancer, discussing the need to introduce screening also in Western countries. Moreover, we propose a simple algorithm for screening that could be easily applied in clinical practice.

Chronic atrophic gastritis (CAG) is a prevalent preneoplastic condition of the stomach. Palmatine (PAL), an isoquinoline alkaloid isolated from Rhizoma Coptidis (RC), has significant anti-inflammatory properties and is often used to treat gastrointestinal disorders. However, the mechanism of PAL on CAG remains unclear. In this study, N-methyl-N'-nitrosoguanidine (MNNG) was used to induce CAG inflammatory disease models in vivo and in vitro. The efficacy of five alkaloids in RC and the dose-dependent effects of the most effective PAL in CAG mice were evaluated in two animal experiments. RNA-seq and western blot revealed that PAL significantly improved IL-17, TNF, and NF-kappa B inflammation-related signaling pathways. Further hub gene prediction and experimental validation revealed that PAL modulated the STAT1/CXCL10 axis, thereby exerting attenuation of CAG through the regulation of IL-17, TNF-α, and p-p65 expression. In conclusion, PAL was proposed to mitigate MNNG-induced CAG, potentially through the inhibition of oxidative stress and inflammatory responses via the STAT1/CXCL10 axis. This approach is an effective complement to the use of PAL in the treatment of CAG.

Early screening is crucial for the prevention of intestinal-type gastric cancer. The objective of the current study was to ascertain molecular evolution of intestinal-type gastric cancer according to the Correa cascade for the precise gastric cancer screening. We collected sequential lesions of the Correa cascade in the formalin-fixed and paraffin-embedded endoscopic submucosal dissection-resected specimens from 14 Chinese patients by microdissection, and subsequently determined the profiles of somatic aberrations during gastric carcinogenesis using the whole exome sequencing, identifying multiple variants at different Correa stages. The results showed that TP53, PCLO, and PRKDC were the most frequently mutated genes in the early gastric cancer (EGC). A high frequency of TP53 alterations was found in low-grade intraepithelial neoplasia (LGIN), which further increased in high-grade intraepithelial neoplasia (HGIN) and EGC. Intestinal metaplasia (IM) had no significant correlation with EGC in terms of mutational spectra, whereas both LGIN and HGIN showed higher genomic similarities to EGC, compared with IM. Based on Jaccard similarity coefficients, three evolutionary models were further constructed, and most patients showed linear progression from LGIN to HGIN, ultimately resulting in EGC. The ECM-receptor interaction pathway was revealed to be involved in the linear evolution. Additionally, the retrospective validation study of 39 patients diagnosed with LGIN indicated that PRKDC mutations, in addition to TP53 mutations, may drive LGIN progression to HGIN or EGC. In conclusion, the current study unveils the genomic evolution across the Correa cascade of intestinal-type gastric cancer, elucidates the underlying molecular mechanisms of gastric carcinogenesis, and provides some evidence for potential personalized gastric cancer surveillance.

A systematic review and meta-analysis was performed to evaluate the preventive effectiveness of Helicobacter pylori eradication against metachronous gastric cancer (MGC) or dysplasia following endoscopic resection (ER) for early gastric cancer (EGC) or dysplasia.

PubMed, Cochrane Library, MEDLINE, and EMBASE were searched until 31 October 2023, and randomized controlled trials or cohort studies were peer-reviewed. The incidence of metachronous gastric lesions (MGLs) including MGC or dysplasia was compared between Helicobacter pylori persistent and negative groups, eradicated and negative groups, and eradicated and persistent groups.

Totally, 21 eligible studies including 82,256 observations were analyzed. Compared to those never infected, Helicobacter pylori persistent group (RR = 1.58, 95% CI = 0.98-2.53) trended to have a higher risk of MGLs and significantly in partial subgroups, while the post-ER eradicated group (RR = 0.79, 95% CI = 0.43-1.45) did not increase the risk of MGLs. Moreover, successful post-ER eradication could significantly decrease the risk of MGLs (RR = 0.54, 95% CI = 0.44-0.65) compared to those persistently infected. Sensitivity analysis obtained generally consistent results, and no significant publication bias was found.

The persistent Helicobacter pylori infection trends to increase the post-ER incidence of MGC or dysplasia, but post-ER eradication can decrease the risk correspondingly. Post-ER screening and eradication of Helicobacter pylori have preventive effectiveness on MGC, and the protocol should be recommended to all the post-ER patients.Systematic review registration: The PROSPERO registration identification was CRD42024512101.

Patients with stage III or IV of operative link for gastric intestinal metaplasia assessment (OLGIM) are at a higher risk of gastric cancer (GC). We aimed to construct a deep learning (DL) model based on magnifying endoscopy with narrow-band imaging (ME-NBI) to evaluate OLGIM staging.

This study included 4473 ME-NBI images obtained from 803 patients at three endoscopy centres. The endoscopic expert marked intestinal metaplasia (IM) regions on endoscopic images of the target biopsy sites. Faster Region-Convolutional Neural Network model was used to grade IM lesions and predict OLGIM staging.

The diagnostic performance of the model for IM grading in internal and external validation sets, as measured by the area under the curve (AUC), was 0.872 and 0.803, respectively. The accuracy of this model in predicting the high-risk stage of OLGIM was 84.0%, which was not statistically different from that of three junior (71.3%, p = 0.148) and three senior endoscopists (75.3%, p = 0.317) specially trained in endoscopic images corresponding to pathological IM grade, but higher than that of three untrained junior endoscopists (64.0%, p = 0.023).

This DL model can assist endoscopists in predicting OLGIM staging using ME-NBI without biopsy, thereby facilitating screening high-risk patients for GC.

The diagnosis and stratification of gastric atrophy (GA) predict patients' gastric cancer progression risk and determine endoscopy surveillance interval. We aimed to construct an artificial intelligence (AI) system for GA endoscopic identification and risk stratification based on the Kimura-Takemoto classification.

We constructed the system using two trained models and verified its performance. First, we retrospectively collected 869 images and 119 videos to compare its performance with that of endoscopists in identifying GA. Then, we included original image cases of 102 patients to validate the system for stratifying GA and comparing it with endoscopists with different experiences.

The sensitivity of model 1 was higher than that of endoscopists (92.72% vs. 76.85 %) at image level and also higher than that of experts (94.87% vs. 85.90 %) at video level. The system outperformed experts in stratifying GA (overall accuracy: 81.37 %, 73.04 %, p = 0.045). The accuracy of this system in classifying non-GA, mild GA, moderate GA, and severe GA was 80.00 %, 77.42 %, 83.33 %, and 85.71 %, comparable to that of experts and better than that of seniors and novices.

We established an expert-level system for GA endoscopic identification and risk stratification. It has great potential for endoscopic assessment and surveillance determinations.

Chronic infection of Helicobacter pylori is considered the principal cause of gastric cancers, but evidence has accumulated regarding the impact of tobacco smoking and alcohol consumption on the development of gastric cancers. Several possible mechanisms, including the activation of nicotinic acetylcholine receptors, have been proposed for smoking-induced gastric carcinogenesis. On the other hand, local acetaldehyde exposure and ethanol-induced mucosal inflammation have been proposed as the mechanisms involved in the development of gastric cancers in heavy alcohol drinkers. In addition, genetic polymorphisms are also considered to play a pivotal role in smoking-related and alcohol-related gastric carcinogenesis. In this review, we will discuss the molecular mechanisms involved in the development of gastric cancers in relation to tobacco smoking and alcohol consumption.

Chronic atrophic gastritis (CAG) is a global digestive system disease and one of the important causes of gastric cancer. The incidence of CAG has been increasing yearly worldwide.

This article reviews the latest research on the common causes and future therapeutic targets of CAG as well as the pharmacological effects of corresponding clinical drugs. We provide a detailed theoretical basis for further research on possible methods for the treatment of CAG and reversal of the CAG process.

CAG often develops from chronic gastritis, and its main pathological manifestation is atrophy of the gastric mucosa, which can develop into gastric cancer. The drug treatment of CAG can be divided into agents that regulate gastric acid secretion, eradicate Helicobacter. pylori (H. pylori), protect gastric mucous membrane, or inhibit inflammatory factors according to their mechanism of action. Although there are limited specific drugs for the treatment of CAG, progress is being made in defining the pathogenesis and therapeutic targets of the disease. Growing evidence shows that NF-κB, PI3K/AKT, Wnt/ β-catenin, MAPK, Toll-like receptors (TLRs), Hedgehog, and VEGF signaling pathways play an important role in the development of CAG.

Helicobacter pylori is a highly prevalent human gastric pathogen that causes gastritis, ulcer disease, and gastric cancer. It is not yet fully understood how H. pylori injures the gastric epithelium. The Na,K-ATPase, an essential transporter found in virtually all mammalian cells, has been shown to be important for maintaining the barrier function of lung and kidney epithelia. H. pylori decreases levels of Na,K-ATPase in the plasma membrane of gastric epithelial cells, and the aim of this study was to demonstrate that this reduction led to gastric injury by impairing the epithelial barrier. Similar to H. pylori infection, the inhibition of Na,K-ATPase with ouabain decreased transepithelial electrical resistance and increased paracellular permeability in cell monolayers of human gastric cultured cells, 2D human gastric organoids, and gastric epithelium isolated from gerbils. Similar effects were caused by a partial shRNA silencing of Na,K-ATPase in human gastric organoids. Both H. pylori infection and ouabain exposure disrupted organization of adherens junctions in human gastric epithelia as demonstrated by E-cadherin immunofluorescence. Functional and structural impairment of epithelial integrity with a decrease in Na,K-ATPase amount or activity provides evidence that the H. pylori-induced downregulation of Na,K-ATPase plays a role in the complex mechanism of gastric disease induced by the bacteria.

Helicobacter pylori is a type of Gram-negative bacteria belonging to the Proteobacteria phylum which is known to cause gastrointestinal disorders such as gastritis and gastric ulcers. Its treatment is based on current eradication regimens, which are composed of combinations of antibiotics such as clarithromycin, metronidazole, levofloxacin and amoxicillin, often combined with a proton pump inhibitor (PPI). With the development of sequencing technologies, it has been demonstrated that not only does the colonization of the gastric and gut environment by H. pylori cause microbial changes, but also the treatment regimens used for its eradication have a significant altering effect on both the gastric and gut microbiota. Here, we review current knowledge on microbiota modulations of current therapies in both environments. We also summarize future perspectives regarding H. pylori infection, the integration of probiotics into therapy and what challenges are being faced on a global basis when we talk about eradication.

MicroRNAs (miRNAs) regulate gene expression and play a critical role in cancer physiology. However, there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer (GC).

To investigate the role and molecular mechanism of miRNA-145-5p (miR145-5p) in the progression of GC.

Real-time polymerase chain reaction (RT-PCR) was used to detect miRNA expression in human GC tissues and cells. The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays, respectively. Cell proliferation was measured using cell counting kit-8 and colony formation assays, and apoptosis was evaluated using flow cytometry. Expression of the epithelial-mesenchymal transition (EMT)-associated protein was determined by Western blot. Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system. Serpin family E member 1 (SERPINE1) expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining. The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis. The association between SERPINE1 and GC progression was also tested. A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p. The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.

GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA. Overexpression of miR-145-5p was associated with decreased GC cell proliferation, invasion, migration, and EMT, and these effects were reversed by forcing SERPINE1 expression. Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression. Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2 (ERK1/2).

This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC. MiR-145-5p was found to affect GC cell proliferation, migration, and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.

Using endoscopic images, we have previously developed computer-aided diagnosis models to predict the histopathology of gastric neoplasms. However, no model that categorizes every stage of gastric carcinogenesis has been published. In this study, a deep-learning-based diagnosis model was developed and validated to automatically classify all stages of gastric carcinogenesis, including atrophy and intestinal metaplasia, in endoscopy images.

A total of 18,701 endoscopic images were collected retrospectively and randomly divided into train, validation, and internal-test datasets in an 8:1:1 ratio. The primary outcome was lesion-classification accuracy in six categories: normal/atrophy/intestinal metaplasia/dysplasia/early /advanced gastric cancer. External-validation of performance in the established model used 1427 novel images from other institutions that were not used in training, validation, or internal-tests.

The internal-test lesion-classification accuracy was 91.2% (95% confidence interval: 89.9%-92.5%). For performance validation, the established model achieved an accuracy of 82.3% (80.3%-84.3%). The external-test per-class receiver operating characteristic in the diagnosis of atrophy and intestinal metaplasia was 93.4 ± 0% and 91.3 ± 0%, respectively.

The established model demonstrated high performance in the diagnosis of preneoplastic lesions (atrophy and intestinal metaplasia) as well as gastric neoplasms.

The progression from gastric mucosal inflammation to cancer signifies a pivotal event in the trajectory of gastric cancer (GC) development. Chinese medicine (CM) exhibits unique advantages and holds significant promise in inhibiting carcinogenesis of the gastric mucosa. This review intricately examines the critical pathological events during the transition from gastric mucosal inflammation-cancer transformation (GMICT), with a particular focus on pathological evolution mechanisms of spasmolytic polypeptide-expressing metaplasia (SPEM). Moreover, it investigates the pioneering applications and advancements of CM in intervening within the medical research domain of precancerous transformations leading to GC. Furthermore, the analysis extends to major shortcomings and challenges confronted by current research in gastric precancerous lesions, and innovative studies related to CM are presented. We offer a highly succinct yet optimistic outlook on future developmental trends. This paper endeavors to foster a profound understanding of forefront dynamics in GMICT research and scientific implications of modernizing CM. It also introduces a novel perspective for establishing a collaborative secondary prevention system for GC that integrates both Western and Chinese medicines.

Currently, the diagnostic strategy for chronic gastritis (CG) is aimed not just at fixing the presence of gastric mucosal inflammation, but also at gastric cancer (GC) risk stratification in a particular patient. Modern classification approach with the definition of the stage of gastritis determines the need, activities and frequency of dynamic monitoring of a patient. However, this attitude to the patient suffering from CG was far from always. The present publication is a literature review describing the key milestones in the history of CG research, from the description of the first observations of inflammation of the gastric mucosa, assessment of gastritis as a predominantly functional disease, to the advent of endoscopy of the upper digestive tract and diagnostic gastric biopsy, assessment of the role of Helicobacter pylori infection in progression of inflammatory changes to atrophy, intestinal metaplasia, dysplasia and GC.

Helicobacter pylori (H pylori) infection is the primary cause of gastric cancer (GC). The role of Disabled-2 (DAB2) in GC remains largely unclear. This study aimed to investigate the role of DAB2 in H pylori-mediated gastric tumorigenesis.

We screened various datasets of GC to analyze DAB2 expression and cell signaling pathways. DAB2 expression was assessed in human GC tissue microarrays. H pylori infection in vivo and in vitro models were further explored. Immunostaining, immunofluorescence, chromatin immunoprecipitation, co-immunoprecipitation, Western blot, quantitative polymerase chain reaction, and luciferase reporter assays were performed in the current study.

The bioinformatic analysis verified that DAB2 was 1 of the 8 genes contributed to tumorigenesis and associated with poor prognosis in GC. The median overall survival and disease-free survival rates in DAB2high group were significantly less than those in DAB2low group. These findings demonstrated that H pylori transcriptionally activated DAB2 expression via signal transducer and activator of transcription 3 (STAT3)-dependent pathway. By bioinformatics analysis and knockdown or overexpression of DAB2, we found that DAB2 upregulated Yes-associated protein 1 (YAP1) transcriptional activity. Mechanistically, DAB2 served as a scaffold protein for integrin beta 3 (ITGB3) and SRC proto-oncogene non-receptor tyrosine kinase (SRC), facilitated the phosphorylation of SRC, promoted the small GTPase ras homolog family member A (RHOA) activation and phosphorylation of YAP1, and ultimately enhanced the YAP1 transcriptional activity.

Altogether, these findings indicated that DAB2 is a key mediator in STAT3-regulated translation of YAP1 and plays crucial roles in H pylori-mediated GC development. DAB2 might serve as a novel therapeutic target for GC.

Gastric precancerous lesions (GPL) significantly elevate the risk of gastric cancer, and precise diagnosis and timely intervention are critical for patient survival. Due to the elusive pathological features of precancerous lesions, the early detection rate is less than 10%, which hinders lesion localization and diagnosis. In this paper, we provide a GPL pathological dataset and propose a novel method for improving the segmentation accuracy on a limited-scale dataset, namely RGB and Hyperspectral dual-modal pathological image Cross-attention U-Net (CrossU-Net). Specifically, we present a self-supervised pre-training model for hyperspectral images to serve downstream segmentation tasks. Secondly, we design a dual-stream U-Net-based network to extract features from different modal images. To promote information exchange between spatial information in RGB images and spectral information in hyperspectral images, we customize the cross-attention mechanism between the two networks. Furthermore, we use an intermediate agent in this mechanism to improve computational efficiency. Finally, we add a distillation loss to align predicted results for both branches, improving network generalization. Experimental results show that our CrossU-Net achieves accuracy and Dice of 96.53% and 91.62%, respectively, for GPL lesion segmentation, providing a promising spectral research approach for the localization and subsequent quantitative analysis of pathological features in early diagnosis.