Integrated Approaches Revealed the Therapeutic Mechanisms of Zuojin Pill Against Gastric Mucosa Injury in a Rat Model with Chronic Atrophic Gastritis.

Background: The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated. Purpose: This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism. Methods: The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins. Results: The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin. Conclusion: Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice.

Chronic active and atrophic gastritis as significant contributing factor to the development of gastric cystica profunda.

Gastric cystica profunda (GCP) is an uncommon but underestimated gastric lesion. Its precancerous potential determines its significance. In addition to previous mucosa injury due to operations, biopsy or polypectomy, chronic active and atrophic gastritis may also lead to the development of GCPs. By carefully examining the stomach and taking biopsy samples from the susceptible regions, the stage of atrophy can be determined. Chronic atrophic gastritis is a risk factor for cancer evolvement and it can also contribute to GCPs formation. GCPs frequently occur close to early gastric cancers (EGCs) or EGC can arise from the cystic glands. Endoscopic resection is an effective and minimally invasive treatment in GCP.

Clinical manifestation, lifestyle, and treatment patterns of chronic erosive gastritis: A multicenter real-world study in China.

BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.

Clinicopathologic and endoscopic characteristics of ten patients with gastric hamartomatous inverted polyp: a single center case series.

BACKGROUND: Gastric hamartomatous inverted polyps (GHIPs) are not well characterized and remain diagnostically challenging due to rarity. Therefore, this study aims to investigate the clinicopathologic and endoscopic characteristics of patients with GHIP. METHODS: We retrospectively reviewed clinicopathologic and endoscopic features of ten patients with GHIP who were admitted to Beijing Friendship Hospital from March 2013 to July 2022. All patients were treated successfully by endoscopic resection. RESULTS: GHIPs were usually asymptomatic and found incidentally during gastroscopic examination. They may be sessile or pedunculated, with diffuse or local surface redness or erosion. On endoscopic ultrasonography, the sessile submucosal tumor-type GHIP demonstrated a heterogeneous lesion with cystic areas in the third layer of the gastric wall. Histologically, GHIPs were characterized by a submucosal inverted proliferation of cystically dilated hyperplastic gastric glands accompanied by a branching proliferation of smooth muscle bundles. Inflammatory cells infiltration was observed in the stroma, whereas only one patient was complicated with glandular low-grade dysplasia. Assessment of the surrounding mucosa demonstrated that six patients (60%) had atrophic gastritis or Helicobacter pylori-associated gastritis, and four patients (40%) had non-specific gastritis. Endoscopic resection was safe and effective. CONCLUSIONS: GHIPs often arise from the background of abnormal mucosa, such as atrophic or H.pylori-associated gastritis. We make the hypothesis that acquired inflammation might lead to the development of GHIPs. We recommend to make a full assessment of the background mucosa and H. pylori infection status for evaluation of underlying gastric mucosal abnormalities, which may be the preneoplastic condition of the stomach.

Chronological Trend of Opportunistic Endoscopic Screening for Gastric Cancer and Atrophic Gastritis.

BACKGROUND: Opportunistic endoscopic screening for gastric cancer was initiated in 2004 at our institute. We investigated chronological trends in gastric cancer detection rates based on individual characteristics and atrophic gastritis prevalence. METHODS: Overall, 15,081 asymptomatic individuals aged ≥40 years without a medical history of gastric cancer underwent first-time esophagogastroduodenoscopy in our institute between February 2004 and December 2017. We retrospectively investigated individual characteristics and endoscopic diagnoses by period (early period: 2004-2007, middle period: 2008-2012, and late period: 2013-2017), clarified the long-term detection rate and the characteristics of endoscopic screening-detected gastric cancer, and evaluated the relationship between gastric cancer and atrophic gastritis. RESULTS: Gastric cancer detection rates in the early, middle, and late periods were 1.01% (76/7,503, men/women: 4,360/3,143, average age: 59.4 years, prevalence of atrophic gastritis: 72%), 0.69% (40/5,820, men/women: 3,668/2,152, average age: 56.8 years, prevalence of atrophic gastritis: 48%), and 0.46% (8/1,758, men/women: 1,083/675, average age: 58.7 years, prevalence of atrophic gastritis: 37%), respectively. Multivariate analysis revealed that male sex (odds ratio 1.92, 95% confidence interval 1.28-2.95), age ≥75 years (2.73, 95% CI 1.32-5.05), and atrophic gastritis (C1-C3: 2.21, 1.36-3.73, O1-O3: 5.36, 3.17-9.30) were significantly associated with the incidence of gastric cancer. CONCLUSIONS: The gastric cancer detection rate and atrophic gastritis prevalence have decreased over time. However, continuing endoscopic screening is important, especially for those at a high risk of developing gastric cancer complicated by severe atrophic gastritis.

Helicobacter Pylori and Gastric Cancer: An Update in the Literature.

Of the chronic bacterial infections that affect humans, Helicobacter pylori (H. pylori) infection is one of the most common. It inhabits the stomachs of half of the adult human population. In Puerto Rico, a US territory, it has an overall prevalence of 33%, similar to the prevalence reported in the population of the US as a whole. Helicobacter pylori infection is responsible for mucosal inflammation that may lead to chronic gastritis, most peptic ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. The International Agency for Research on Cancer identified H. pylori as a definite carcinogen in 1994, the only bacterium to be given such a classification. Its oncogenic effect has been postulated to be caused by different mechanisms, including bacterial characteristics and host factors. Epidemiologic studies have shown that gastric cancer risk differs among regions. One of the top 10 causes of cancer death in Puerto Rico is gastric cancer. Although the eradication of H. pylori has well-known benefits, there are some concerns when considering mass screening and treatment of infected patients. These include the fact that such eradication could provoke an increase in antibiotic resistance rates, the disturbance of the gut microbiota, an increase in body weight, and the aggravation of existing gastroesophageal reflux symptoms. Gastric cancer is a major health concern, and we should understand the role of H. pylori eradication in its prevention. This article is geared to summarize current knowledge and controversies.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

Gastric juice analysis in clinical practice: why, how, and when. The experience with EndoFaster.

Gastric juice analysis may be useful for clinical purposes, including the detection of H. pylori infection and diffuse atrophic gastritis on gastric mucosa. EndoFaster is a novel device which performs real-time analysis of gastric juice revealing the infection and hypochlorhydria by measuring ammonium concentrations and pH levels. This review aimed to evaluate the clinical applications of such a tool. By considering data from overall 11 studies, the values of sensitivity, specificity, positive predictive value, negative predictive value, accuracy, positive likelihood ratio, and negative likelihood ratio were 90%, 86%, 67%, 96%, 87%, 8.5, and 0.13, respectively, for H. pylori diagnosis, and 83%, 92%, 58%, 97%, 91%, 9.9 and 0.2, respectively, for suspecting diffuse atrophic gastritis. The very high value of negative predictive values for both H. pylori and mucosal atrophy would allow avoiding to perform useless negative gastric biopsies when the results of the test are negative. Some promising data suggest that gastric juice analysis may be useful also to diagnose H. pylori infection in patients with chronic active gastritis without evidence of bacteria at histology, as well as in predicting persistent acid reflux in patients on proton pump inhibitor therapy for reflux disease.

Diagnosing and grading gastric atrophy and intestinal metaplasia using semi-supervised deep learning on pathological images: development and validation study.

OBJECTIVE: Patients with gastric atrophy and intestinal metaplasia (IM) were at risk for gastric cancer, necessitating an accurate risk assessment. We aimed to establish and validate a diagnostic approach for gastric biopsy specimens using deep learning and OLGA/OLGIM for individual gastric cancer risk classification. METHODS: In this study, we prospectively enrolled 545 patients suspected of atrophic gastritis during endoscopy from 13 tertiary hospitals between December 22, 2017, to September 25, 2020, with a total of 2725 whole-slide images (WSIs). Patients were randomly divided into a training set (n = 349), an internal validation set (n = 87), and an external validation set (n = 109). Sixty patients from the external validation set were randomly selected and divided into two groups for an observer study, one with the assistance of algorithm results and the other without. We proposed a semi-supervised deep learning algorithm to diagnose and grade IM and atrophy, and we compared it with the assessments of 10 pathologists. The model's performance was evaluated based on the area under the curve (AUC), sensitivity, specificity, and weighted kappa value. RESULTS: The algorithm, named GasMIL, was established and demonstrated encouraging performance in diagnosing IM (AUC 0.884, 95% CI 0.862-0.902) and atrophy (AUC 0.877, 95% CI 0.855-0.897) in the external test set. In the observer study, GasMIL achieved an 80% sensitivity, 85% specificity, a weighted kappa value of 0.61, and an AUC of 0.953, surpassing the performance of all ten pathologists in diagnosing atrophy. Among the 10 pathologists, GasMIL's AUC ranked second in OLGA (0.729, 95% CI 0.625-0.833) and fifth in OLGIM (0.792, 95% CI 0.688-0.896). With the assistance of GasMIL, pathologists demonstrated improved AUC (p = 0.013), sensitivity (p = 0.014), and weighted kappa (p = 0.016) in diagnosing IM, and improved specificity (p = 0.007) in diagnosing atrophy compared to pathologists working alone. CONCLUSION: GasMIL shows the best overall performance in diagnosing IM and atrophy when compared to pathologists, significantly enhancing their diagnostic capabilities.

Impact of autoimmune gastritis on chronic urticaria in paediatric patients - pathophysiological point of views.

We would like to provide an updated comprehensive perspective and identify the components linked to chronic spontaneous urticaria (CSU) without specific triggers in autoimmune atrophic gastritis (AAG). AAG is an organ-specific autoimmune disease that affects the corpus-fundus gastric mucosa. Although we lack a unified explanation of the underlying pathways, when considering all paediatric patients reported in the literature, alterations result in gastric neuroendocrine enterochromaffin-like (ECL) cell proliferation and paracrine release of histamine. Several mechanisms have been proposed for the pathogenesis of CSU, with much evidence pointing towards AAG and ECL cell responses, which may be implicated as potential factors contributing to CSU. The excessive production/release of histamine into the bloodstream could cause or trigger exacerbations of CSU in AAG, independent of Helicobacter pylori; thus, the release of histamine from ECL cells may be the primary modulator. CONCLUSION: Considering the understanding of these interactions, recognising the respective roles of AAG in the pathogenesis of CSU may strongly impact the diagnostic workup and management of unexplained/refractory CSU and may inform future research and interventions in the paediatric population. WHAT IS KNOWN: • Autoimmune atrophic gastritis is a chronic immune-mediated inflammatory disease characterised by the destruction of the oxyntic mucosa in the gastric body and fundus, mucosal atrophy, and metaplastic changes. • Autoimmune atrophic gastritis in paediatric patients is important because of the poor outcome and risk of malignancy and possibly underestimated entities primarily reported in single-case reports. WHAT IS NEW: • Upper gastrointestinal inflammatory disorders, independent of H. pylori, have been implicated as potential inducing factors in the development of chronic spontaneous urticaria. • If a paediatric patient presents with symptoms such as anaemia, reduced vitamin B12 levels, recurrent urticaria with no other detectable aetiology, positive anti-parietal cell antibodies, and elevated gastrin levels, autoimmune atrophic gastritis should be considered a possible cause of chronic urticaria.

A case of nodular gastritis progression to autoimmune gastritis after 10 years of Helicobacter pylori eradication.

A 61-year-old female patient underwent upper gastrointestinal endoscopy, which confirmed the presence of Helicobacter pylori (H. pylori)-positive nodular gastritis (NG). Routine upper gastrointestinal endoscopy after H. pylori eradication revealed atrophic changes of the corpus, having gradually progressed over the 10 years after successful eradication. Serological and biopsy specimen examination showed hypergastrinemia (1200 pg/mL), positive anti-parietal cell antibody (with a titer of more 160), and endocrine cell micronests after 11 years of H. pylori eradication. The patient was diagnosed with autoimmune gastritis (AIG) based on endoscopic, serological, and histological findings. This is the first report of AIG diagnosed in a patient with NG over a long period of time after H. pylori eradication.

Prevalence and temporal trend of gastric preneoplastic lesions in Asia: A systematic review with meta-analysis.

BACKGROUND: Gastric cancer is the fifth most common cancer globally, with about 75% of cases occurring in Asia. While chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) are well-recognized preneoplastic gastric lesions, we determined the prevalence and temporal trend of CAG and IM in Asia over the past 50 years. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, MEDLINE, Scopus, and Web of Science for studies reporting the prevalence of CAG and IM in Asia (according to the United Nations geoscheme) published between 1970 and 2022. Heterogeneity was assessed by the I2 index and Cochran Q test. We adopted the random effects model to estimate the pooled prevalence and 95% confidence interval (CI). The slope of prevalence was estimated as a function of time in simple linear regression and weighted meta-regression models to demonstrate the temporal trend. Studies that reported the odds ratio (OR) of Helicobacter pylori infection and CAG/IM were analyzed separately to compile a pooled OR with a 95% CI. This study was registered in INPLASY2022120028. RESULTS: Of the 81 studies from 19 Asian countries identified, the pooled prevalence for CAG and IM in Asia was 26.1% (95%CI: 22.7-30.0) and 22.9% (95%CI: 19.7-26.6), respectively. Over the past 5 decades, there was a significant decline in the prevalence of IM (slope in adjusted meta-regression models: -0.79 [95%CI: -1.28 to -0.26], P = 0.003), but there was no significant change in the pooled prevalence of CAG. Within Asia, the prevalence varied significantly among different regions. Southern Asia reported the highest pooled prevalence of CAG (42.9%, 95%CI: 27.5%-67.1%), while Western Asia reported the lowest level (12.7%, 95%CI: 5.0%-32.3%). For IM, Eastern Asia reported the highest prevalence (27.1%, 95%CI: 21.1-34.9), with the lowest prevalence reported in Western Asia (3.1%; 95% CI 1.2%-8.0%). H. pylori infection was linked to CAG and IM with OR of 2.16 (95%CI: 2.09-2.22) and 1.64 (95%CI: 1.57-1.72), respectively. CONCLUSION: This updated meta-analysis showed that up to 26% of study individuals in Asia harbored preneoplastic gastric lesions. There was a declining temporal trend in the prevalence of IM, but not for CAG, in Asia.

Do atrophic gastritis and intestinal metaplasia reverse after Helicobacter pylori eradication?

BACKGROUND: It's still controversial whether Helicobacter pylori (H. pylori) eradication can reverse atrophic gastritis (AG) and intestinal metaplasia (IM). Therefore, we performed a meta-analysis to estimate the effect of H. pylori eradication on AG and IM. METHODS: We searched the PubMed, Web of Science and EMBASE datasets through April 2023 for epidemiological studies, which provided mean glandular atrophy (GA) or IM score before and after H. pylori eradication, or provided ORs, RRs or HRs and 95% CIs for the association of AG or IM with H. pylori eradication. Weighted mean difference (WMD) and pooled ORs and 95%CIs were used to estimate the effect of H. pylori eradication on AG and IM. RESULTS: Twenty articles with a total of 5242 participants were included in this meta-analysis. H. pylori eradication significantly decreased GA score in the antrum (WMD -0.36; 95% CI: -0.52, -0.19, p < 0.01), GA score in the corpus (WMD -0.35; 95% CI: -0.52, -0.19, p < 0.01), IM score in the antrum (WMD -0.16; 95% CI: -0.26, -0.07, p < 0.01) and IM score in the corpus (WMD -0.20; 95% CI: -0.37, -0.04, p = 0.01). H. pylori eradication significantly improved AG (pooled OR 2.96; 95% CI: 1.70, 5.14, p < 0.01) and IM (pooled OR 2.41; 95% CI: 1.24, 4.70, p < 0.01). The association remained significant in the subgroup analyses by study design, sites of lesions, regions and follow-up time. Although Publication bias was observed for AG, the association remained significant after trim-and-fill adjustment. CONCLUSIONS: H. pylori eradication could significantly improve AG and IM at early stage.

A novel telomere biology disease-associated gastritis identified through a whole exome sequencing-driven approach.

A whole exome sequencing (WES)-driven approach to uncover the etiology of unexplained inflammatory gastritides has been underutilized by surgical pathologists. Here, we discovered the pathobiology of an unusual chronic atrophic gastritis in two unrelated patients using this approach. The gastric biopsies were notable for an unusual pattern of gastritis with persistent dense inflammation, loss of both parietal and neuroendocrine cells in the oxyntic mucosa, and sparing of the antral mucosa. The patients were found to harbor pathogenic variants in telomeropathic genes (POT1 and DCLRE1B). Clonality testing for one of the patients showed evidence of evolving clonality of TCR-gene rearrangement. Both patients showed significantly decreased numbers of stem/progenitor cells by immunohistochemistry, which appears to be responsible for the development of mucosal atrophy. No such cases of unusual chronic atrophic gastritis in the setting of telomeropathy have been previously reported. The loss of stem/progenitor cells suggests that stem/progenitor cell exhaustion in the setting of telomere dysfunction is the likely mechanism for development of this unusual chronic atrophic gastritis. The results underscore the need for close monitoring of these gastric lesions, with special regard to their neoplastic potential. This combined WES-driven approach has promise to identify the cause and mechanism of other uncharacterized gastrointestinal inflammatory disorders.

Socio-economic factors and medical conditions affecting regular stomach cancer screening in Korea: a retrospective longitudinal study using national public health data for 11 years.

OBJECTIVE: This study aimed to explore socio-economic factors and medical conditions that affect regular stomach cancer (SC) screening among Korean adults. STUDY DESIGN: This was a retrospective observational study. METHODS: Study subjects were 5545 adults aged ≥40 years who participated in the 2007-2012 Korean National Health and Nutrition Examination Survey and were followed up to year 2017 based on data linking to the Korean National Health Insurance Service and Korean Health Insurance Review and Assessment. Socio-economic factors included sex, age, residential area, education, occupation, marital status, disability, public and private health insurance, service through local public health organizations, history of cancer except for SC, and family history of SC. Medical factors included six gastric lesions with the possibility of facilitating SC screening, including benign gastric neoplasm, chronic atrophic gastritis, gastric polyp, Helicobacter pylori infection, intestinal metaplasia, and peptic ulcers. The outcome was adherence to SC screening, which was divided into non-adherence, irregular adherence, and regular adherence. RESULTS: After adjusting for the effects of socio-economic factors, multivariate ordinal logistic regression revealed that participants with a history of four types of gastric lesions were more likely to regularly participate in SC screening: chronic atrophic gastritis (odds ratio [OR] 1.567; 95% confidence interval [CI] = 1.276-1.923), gastric polyps (OR 1.565; 95% CI = 1.223-2.003), H. pylori infection (OR 1.637; 95% CI = 1.338-2.003), and peptic ulcer (OR 2.226; 95% CI 1.750-2.831). CONCLUSIONS: To improve participation in SC screening, it is necessary to implement personalized strategies for individuals at risk for gastric cancer in addition to population-based strategies for vulnerable groups.

Chronic gastritis may predict risk of cerebral small vessel disease.

BACKGROUND AND PURPOSE: Chronic gastritis, especially that caused by helicobacter pylori (HP) infection, has been associated with increased risk of ischemic stroke. But the relationship between chronic gastritis and cerebral small vessel disease (CSVD) remains largely undetermined. This study aimed to determine the potential predictors for CSVD, with chronic gastritis and its proxies as alternatives. METHOD: Patients aged 18 years or older with indications for electronic gastroscopy were enrolled. Presence of CSVD was evaluated with brain magnetic resonance imaging (MRI) results. Degree of CSVD was scored according to established criteria. Logistic regression analysis was used for identifying possible risk factors for CSVD. RESULTS: Of the 1191 enrolled patients, 757 (63.6%) were identified as with, and 434 (36.4%) as without CSVD. Multivariate analysis indicated that patients with chronic atrophic gastritis had an increased risk for CSVD than those without (adjusted odds ratio = 1.58; 95% CI, 1.08-2.32; P < 0.05). CONCLUSIONS: Chronic atrophic gastritis is associated with the presence of CSVD. We should routinely screen the presence of CSVD for patients with chronic atrophic gastritis.

Methylation Status of CDH1 Gene in Gastric Biopsy Specimens and Its Association with H. Pylori Infection.

BACKGROUND: Helicobacter pylori (H. pylori) have been accepted as having an etiologic role in gastro-duodenal diseases as chronic gastritis, peptic ulcer, and gastric carcinoma. Methylation of CGI has been correlated with the tumorigenic process since it can inactivate tumor suppressor genes. CDH1 is a tumor suppressor gene that encodes the E-cadherin protein, which is preserving cell-cell connections. Early stages of gastric carcinogenesis may be affected by the promoter methylation-mediated inactivation of this gene. OBJECTIVE: This study aimed to investigate the methylation status of CDH1 using Methylation-Specific PCR (MSP) technique in clinical suspected patients with H. pylori infection who undergoing upper gastrointestinal endoscopy and correlated it with H. pylori detection by glmM PCR test. METHODS: Fifty gastric mucosal biopsies were selected from one hundred and five samples included in this study. The detection of H. pylori was performed with the PCR primers specific to glmM gene. Bisulfite modification was done and the methylation status of the CDH1 gene was detected using MSP reaction. RESULTS: H. pylori was detected in 36% (18/50) of study population using glmM gene PCR test, 89% (16/18) of H. pylori positive cases were CDH1 methylated  positive (chi-square, p-value=0.002). CDH1 methylation can be present in cancerous and noncancerous gastric mucosa, where 60% (18/30) of CDH1 methylation positive gastric mucosa showed gastritis as an endoscopy finding and gastric cancer in 6% (2/30). There was a significant correlation between and CDH1 methylation positive results and age group (P-value = 0.02). There was no significant correlation between CDH1 methylation positive results and participants gender (p-value=0.431) and clinical symptoms (all P-value > 0.05). CONCLUSION: This work suggested strong significance association between H. pylori infection and CDH1 methylation.

Therapeutic effects and potential mechanisms of endoscopic submucosal injection of mesenchymal stem cells on chronic atrophic gastritis.

Previous studies have demonstrated the rejuvenating and restorative actions of mesenchymal stem cells (MSCs) in multiple diseases, but their role in reversing chronic atrophic gastritis (CAG) is not well understood owing to their low efficiency in homing to the stomach. In this work, we investigated the therapeutic effect of umbilical cord-derived MSCs (UC-MSCs) on CAG by endoscopic submucosal injection and preliminarily explored possible mechanisms in vitro. MSCs and normal saline (NS) were injected into the submucosa of the stomach in randomly grouped CAG rabbits. Therapeutic effects on serum indices and histopathology of the gastric mucosa were analyzed in vivo at 30 and 60 days after MSCs injection. GES-1 cells were co-cultured with MSCs in vitro using a Transwell system and cell viability, proliferation, and migration ability were detected. Additionally, in view of the potential mechanisms, the relative protein expression levels of apoptosis, autophagy and inflammation in vitro were explored by Western Blotting. We found that submucosal injection of MSCs up-regulated serum indices (G-17, PGI and PGI/PGII) and alleviated histopathological damage to the gastric mucosa in CAG rabbits. Co-culture of GES-1 cells with MSCs improved cell viability, proliferation, and migration ability, while suppressing apoptosis. We also observed a reduction in the expression of apoptosis indicators, including Bax and cleaved caspase-3, in GES-1 cells after co-culture with MSCs in vitro. Our findings suggest that submucosal injection of MSCs is a promising approach for reversing CAG, and attenuating apoptosis plays a potential role in this process.

Effects of oxidative stress regulation in inflammation-associated gastric cancer progression treated using traditional Chinese medicines: A review.

Gastric cancer (GC) is a global public health concern that poses a serious threat to human health owing to its high morbidity and mortality rates. Due to the lack of specificity of symptoms, patients with GC tend to be diagnosed at an advanced stage with poor prognosis. Therefore, the development of new treatment methods is particularly urgent. Chronic atrophic gastritis (CAG), a precancerous GC lesion, plays a key role in its occurrence and development. Oxidative stress has been identified as an important factor driving the development and progression of the pathological processes of CAG and GC. Therefore, regulating oxidative stress pathways can not only intervene in CAG development but also prevent the occurrence and metastasis of GC and improve the prognosis of GC patients. In this study, PubMed, CNKI, and Web of Science were used to search for a large number of relevant studies. The review results suggested that the active ingredients of traditional Chinese medicine (TCM) and TCM prescriptions could target and improve inflammation, pathological status, metastasis, and invasion of tumor cells, providing a potential new supplement for the treatment of CAG and GC.

Radiation-induced gastric injury during radiotherapy: molecular mechanisms and clinical treatment.

Radiotherapy (RT) has been the standard of care for treating a multitude of cancer types. Radiation-induced gastric injury (RIGI) is a common complication of RT for thoracic and abdominal tumors. It manifests acutely as radiation gastritis or gastric ulcers, and chronically as chronic atrophic gastritis or intestinal metaplasia. In recent years, studies have shown that intracellular signals such as oxidative stress response, p38/MAPK pathway and transforming growth factor-ß signaling pathway are involved in the progression of RIGI. This review also summarized the risk factors, diagnosis and treatment of this disease. However, the root of therapeutic challenges lies in the incomplete understanding of the mechanisms. Here, we also highlight the potential mechanistic, diagnostic and therapeutic directions of RIGI.