Spatial Variation of the Gastrointestinal Microbiota in Response to Long-Term Administration of Vonoprazan in Mice With High Risk of Gastric Cancer.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, is superior to traditional proton pump inhibitor (PPI) in acid suppression and has been approved in the treatment of acid-related disorders. Accumulating evidence suggest associations between PPI use and gut microbiota, yet the effect of vonoprazan on GI microbiota is obscure. METHODS: Transgenic FVB/N insulin-gastrin (INS-GAS) mice as a model of gastric cancer (GC) were administered vonoprazan by gavage every other day for 12 weeks. Stomachs were evaluated by histopathology, Ki-67 proliferation index, and inflammatory cytokines. The mucosal and lumen microbiota from stomach, jejunum, ileum, cecum, and feces were detected using 16S rRNA gene sequencing. RESULTS: Higher incidence of intestinal metaplasia and epithelial proliferation were observed in the vonoprazan group than that in the control mice. Vonoprazan also elevated the gastric expression of proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6. Each mice comprised a unique microbiota composition that was consistent across different niches. The structure of GI microbiota changed dramatically after vonoprazan treatment with the stomach being the most disturbed segment. Vonoprazan administration shifted the gut microbiota toward the enrichment of pathogenic Streptococcus, Staphylococcus, Bilophila, and the loss of commensal Prevotella, Bifidobacterium, and Faecalibacterium. Interestingly, compared to the controls, microbial interactions were weaker in the stomach while stronger in the jejunum of the vonoprazan group. CONCLUSIONS: Long-term vonoprazan treatment promoted gastric lesions in male INS-GAS mice, with the disequilibrium of GI microbiome. The clinical application of vonoprazan needs to be judicious particularly among those with high risk of GC.

Assessing Accuracy of ChatGPT on Addressing Helicobacter pylori Infection-Related Questions: A National Survey and Comparative Study.

BACKGROUND: ChatGPT is a novel and online large-scale language model used as a source providing up-to-date and useful health-related knowledges to patients and clinicians. However, its performance on Helicobacter pylori infection-related questions remain unknown. This study aimed to evaluate the accuracy of ChatGPT's responses on H. pylori-related questions compared with that of gastroenterologists during the same period. METHODS: Twenty-five H. pylori-related questions from five domains: Indication, Diagnostics, Treatment, Gastric cancer and prevention, and Gut Microbiota were selected based on the Maastricht VI Consensus report. Each question was tested three times with ChatGPT3.5 and ChatGPT4. Two independent H. pylori experts assessed the responses from ChatGPT, with discrepancies resolved by a third reviewer. Simultaneously, a nationwide survey with the same questions was conducted among 1279 gastroenterologists and 154 medical students. The accuracy of responses from ChatGPT3.5 and ChatGPT4 was compared with that of gastroenterologists. RESULTS: Overall, both ChatGPT3.5 and ChatGPT4 demonstrated high accuracy, with median accuracy rates of 92% for each of the three responses, surpassing the accuracy of nationwide gastroenterologists (median: 80%) and equivalent to that of senior gastroenterologists. Compared with ChatGPT3.5, ChatGPT4 provided more concise responses with the same accuracy. ChatGPT3.5 performed well in the Indication, Treatment, and Gut Microbiota domains, whereas ChatGPT4 excelled in Diagnostics, Gastric cancer and prevention, and Gut Microbiota domains. CONCLUSION: ChatGPT exhibited high accuracy and reproducibility in addressing H. pylori-related questions except the decision for H. pylori treatment, performing at the level of senior gastroenterologists and could serve as an auxiliary information tool for assisting patients and clinicians.

Investigation of the prevalence and risk factors of Helicobacter pylori infection and the value of different gastric cancer screening methods in a low-risk region of gastric cancer in China.

BACKGROUND: The aim of this current study was to identify the prevalence and risk factors of H. pylori infection in the low-risk area of gastric cancer in China, and evaluate the value of different gastric cancer screening methods. METHODS: An epidemiological study was conducted in Yudu County, Jiangxi, China, and participants were followed up for 6 years. All participants completed a questionnaire, laboratory tests and endoscopy. Patients were divided into H. pylori positive and negative groups, and risk factors for H. pylori infection were identified using multivariate logistic regression analysis. RESULTS: A total of 1962 residents were included, the prevalence of H. pylori infection was 33.8%. Multivariate analysis showed that annual income ≤20,000 yuan (OR: 1.44, 95% CI: 1.18-1.77, p < 0.001), loss of appetite (OR: 1.71, 95% CI: 1.29-2.26, p < 0.001), PG II >37.23 ng/mL (OR: 2.11, 95% CI: 1.50-2.97, p < 0.001), G-17 > 1.5 and ≤5.7 pmol/L (OR: 2.52, 95% CI: 1.93-3.30, p < 0.001), and G-17 > 5.7 pmol/L (OR: 1.96, 95% CI: 1.48-2.60, p < 0.001) were risk factors of H. pylori infection, while alcohol consumption (OR: 0.70, 95% CI: 0.54-0.91, p = 0.006) was a protective factor. According to the new gastric cancer screening method, the prevalence of low-grade intraepithelial neoplasia in the low-risk group, medium-risk group and high-risk group was 4.4%, 7.7% and 12.5% respectively (p < 0.001). CONCLUSIONS: In a low-risk area of gastric cancer in China, the infection rate of H. pylori is relatively low. Low income, loss of appetite, high PG II, and high G-17 were risk factors for H. pylori infection, while alcohol consumption was a protective factor. Moreover, the new gastric cancer screening method better predicted low-grade intraepithelial neoplasia than the ABC method and the new ABC method.

Alcohol Consumption within 48 hours before Onset Is Associated with Adverse Clinical Outcomes in Hypertriglyceridemic Pancreatitis.

(1) Background: Some patients with hypertriglyceridemic pancreatitis (HTGP) drink occasionally or moderately, but do not meet the diagnostic criteria for alcoholic pancreatitis. This study aims to investigate whether occasional or moderate alcohol consumption affects the clinical outcomes of patients with HTGP. (2) Methods: This retrospective study included 373 patients with HTGP from January 2007 to December 2021. HTGP patients with occasional or moderate alcohol (OMA) consumption before onset were divided into the OMA group, and HTGP patients without alcohol (WA) consumption were divided into the WA group. The OMA group was further divided into two groups: the drinking within 48 h before onset (DW) group, and the without drinking within 48 h before onset (WDW) group. The clinical data of the two groups were compared and multivariable logistic regression was used to analyze independent risk factors for the primary outcomes. (3) Results: The proportion of men (95.7% vs. 67.6%, p < 0.001) and smoking history (61.7% vs. 15.1%, p < 0.001) in the OMA group were higher than those in the WA group. Occasional or moderate alcohol consumption was independently associated with a high incidence of SAP (adjusted odds ratio (AdjOR), 1.57; 95% CI, 1.02-2.41; p = 0.041), and necrotizing pancreatitis (AdjOR, 1.60; 95% CI, 1.04-2.48; p = 0.034). After dividing the OMA group into two subgroups, we found that drinking within 48 h before onset was independently associated with a high incidence of SAP (AdjOR, 3.09; 95% CI, 1.66-5.77; p < 0.001), and necrotizing pancreatitis (AdjOR, 2.71; 95% CI, 1.46-5.05; p = 0.002). (4) Conclusion: Occasional or moderate alcohol consumption is associated with poor clinical outcomes in patients with HTGP, particularly if they drank alcohol within 48 h before the onset of the disease.

YAP and ß-catenin cooperate to drive H. pylori-induced gastric tumorigenesis.

H. pylori infection is the strongest known risk factor for gastric carcinoma. The activation of the yes-associated protein 1 (YAP) and ß-catenin pathways has been associated with multiple tumor types. In this study, we investigated the crosstalk between the YAP and ß-catenin pathways in H. pylori-associated gastric tumorigenesis. Immunohistochemical analysis of YAP and ß-catenin expression was performed in human gastric cancer tissues. The small molecules Super-TDU and KYA1797K, pharmacological inhibitors of YAP and ß-catenin, respectively, were used to investigate the role of these signaling pathways in H. pylori-induced gastric carcinogenesis in murine models of infection. The common downstream targets of YAP and ß-catenin signaling were evaluated by RNA sequencing (RNA-seq). Western blot, immunofluorescence, luciferase, RT-PCR, immunoprecipitation, cell counting kit-8 (CCK8), EdU and spheroid assays were used. H. pylori infection promoted YAP and ß-catenin nuclear accumulation and transcriptional activity in gastric epithelial cells and transgenic insulin-gastrin (INS-GAS) mice, whereas silencing of both YAP and ß-catenin synergistically inhibited H. pylori-induced cell proliferation and expansion. In addition, YAP was found to directly interact with ß-catenin and knockdown of YAP suppressed H. pylori-induced nuclear translocation of ß-catenin. Moreover, downstream genes caudal-type homeobox 2 (CDX2), leucine-rich repeat containing G protein-coupled receptor 5 (LGR5) and RuvB like AAA ATPase 1 (RUVBL1) were shared by both YAP and ß-catenin signaling. Furthermore, treatment with the YAP inhibitor Super-TDU or ß-catenin inhibitor KYA1797A significantly alleviated gastric inflammation and epithelial DNA damage in H. pylori-infected mice. Finally, the elevation of gastric YAP was positively correlated with ß-catenin expression in human gastric cancer tissues. These findings indicate that YAP and ß-catenin synergistically promote H. pylori-induced gastric carcinogenesis via their physical interaction and reveal that CDX2, LGR5 and RUVBL1 are the downstream genes shared by both the YAP and ß-catenin signaling pathways, and potentially contribute to H. pylori pathogenesis.

The management of Helicobacter pylori infection and prevention and control of gastric cancer in China.

Helicobacter pylori (H. pylori) infection, a type-1 carcinogen, was closely associated with gastric cancer (GC). Successfully eradicating H. pylori infection could reduce the incidence of GC. China was a country with high incidence of GC and high prevalence of H. pylori infection. Nearly half of worldwide GC new cases and deaths attributed to H. pylori infection occurred in China. H. pylori prevalence varied over time with the improvement of socioeconomic status and sanitary conditions. The knowledge of antibiotic resistance rate in time was important to guide the clinical choice of antibiotics use in the regimens. With the publication of five Chinese consensus reports on the management of H. pylori infection and the effort of public preach of H. pylori-related knowledge, the standardization of H. pylori diagnosis and treatment by clinicians was improved. Bismuth-containing quadruple therapy was widely applied in clinical practice of H. pylori eradication because of high efficacy and safety. High-dose Proton Pump Inhibitor-amoxicillin dual therapy or vonoprazan-amoxicillin dual therapy showed comparable efficacy and lower side effects than bismuth-containing quadruple therapy, which were the alternative choice. The diagnosis rate of early GC was low and distinguishing Chinese GC risk population for the further endoscopy screening was important. Efforts have been done to establish prediction models to stratify GC risk in the Chinese GC risk population. We reviewed the current situation of the management of H. pylori infection and prevention and control of GC in China here.

Convergent dysbiosis of gastric mucosa and fluid microbiome during stomach carcinogenesis.

BACKGROUND: A complex microbiota in the gastric mucosa (GM) has been unveiled recently and its dysbiosis is identified to be associated with gastric cancer (GC). However, the microbial composition in gastric fluid (GF) and its correlation with GM during gastric carcinogenesis are unclear. METHODS: We obtained GM and GF samples from 180 patients, including 61 superficial gastritis (SG), 55 intestinal metaplasia (IM) and 64 GC and performed 16S rRNA gene sequencing analysis. The concentration of gastric acid and metabolite nitrite has been measured. RESULTS: Overall, the composition of microbiome in GM was distinct from GF with less diversity, and both were influenced by H. pylori infection. The structure of microbiota changed differentially in GM and GF across histological stages of GC, accompanied with decreased gastric acid and increased carcinogenic nitrite. The classifiers of GC based on microbial markers were identified in both GM and GF, including Lactobacillus, Veillonella, Gemella, and were further validated in an independent cohort with good performance. Interestingly, paired comparison between GM and GF showed that their compositional distinction remarkably dwindled from SG to GC, with some GF-enriched bacteria significantly increased in GM. Moreover, stronger interaction network between microbes of GM and GF was observed in GC compared to SG. CONCLUSION: Our results, for the first time, revealed a comprehensive profile of both GM and GF microbiomes during the development of GC. The convergent microbial characteristics between GM and GF in GC suggest that the colonization of carcinogenic microbes in GM might derive from GF.

Probiotics mitigate Helicobacter pylori-induced gastric inflammation and premalignant lesions in INS-GAS mice with the modulation of gastrointestinal microbiota.

BACKGROUND: Dysbiosis of gastric microbiota including Helicobacter pylori (H. pylori) infection is associated with the development of stomach cancer. Probiotics have been shown to attenuate H. pylori-induced gastritis, although their role in cancer prevention remains unclear. Thus, we aimed to explore the effects of probiotics on H. pylori-induced carcinogenesis and the alterations of gastrointestinal microbiota. METHODS: Male INS-GAS mice were randomly allocated to H. pylori-infected and non-infected groups. After 4 weeks, probiotic combination (containing Lactobacillus salivarius and Lactobacillus rhamnosus) was administered in drinking water for 12 weeks. Stomachs were collected for RNA-Sequencing and the differentially expressed genes were validated using RT profiler PCR array. 16S rRNA gene sequencing was performed to assess the alterations of gastrointestinal microbiota. RESULTS: Probiotics significantly alleviate H. pylori-induced gastric pathology, including reduced infiltration of inflammation and lower incidence of precancerous lesions. RNA-Sequencing results showed that probiotics treatment decreased expressions of genes involved in pro-inflammatory pathways, such as NF-κB, IL-17, and TNF signaling pathway. Of note, probiotics did not suppress the growth of H. pylori, but dramatically reshaped the structure of both gastric and gut microbiota. The microbial diversity was increased in H. pylori-infected group after probiotics treatment. While gastric cancer-associated genera Lactobacillus and Staphylococcus were enriched in the stomach of H. pylori-infected group, the beneficial short-chain fatty acids-producing bacteria, including Bacteroides, Alloprevotella, and Oscellibacter, were more abundant in mice treated with probiotics. Additionally, probiotics restored the H. pylori-induced reduction of anti-inflammatory bacterium Faecalibaculum in the gut. CONCLUSIONS: Probiotics therapy can protect against H. pylori-associated carcinogenesis probably through remodeling gastrointestinal microbiota, which in turn prevent host cells from malignant transformation.

Research trends on the relationship between gut microbiota and colorectal cancer: A bibliometric analysis.

Background: Colorectal cancer (CRC)is the third most common cancer in the world and the second leading cause of cancer-related deaths, and over the past two decades, many of these researchers have provided a substantial amount of important information on the role of gut microbes in the development and progression of CRC. A causal relationship between the presence of specific microorganisms and CRC development has also been validated. Although a large number of papers related to this area have been published, no bibliometric study has been conducted to review the current state of research in this area and to highlight the research trends and hotspots in this area. This study aims to analyze the current status and future research trends of gut microbiota and CRC through bibliometric analysis. Methods: Publications from 2001 to 2022 were retrieved from the Web of Science Core Collection database and screened according to inclusion criteria. VOSviewer and CiteSpace software were used to visualize the research trends in this field, including the analysis of title, country, institution, author, number of publications, year of publication, number of citations, journal, and H-index. Results: A total of 863 studies were eventually identified, and the articles retrieved were cited an average of 44.85 times each. The number of publications on this topic has been increased steadily since 2011. China and the USA have made the largest contribution in the field. FRONTIERS IN MICROBIOLOGY is the top productive journal with 26 papers, and Gut journal has the highest average citation (167.23). Shanghai Jiao Tong University is the most contributive institution. Professor Yu J, Sung, Joseph J. Y and Fang JY are the most productive authors in this field. Keyword co-occurrence analysis showed that the terms of "Gut Microbiota", "Colorectal Cancer", "Inflammation", "Probiotic" and "Fusobacterium Nucleatum" were the most frequent, which revealed the research hotpots and trends in this field. Conclusions: There has been a growing number of publications over the past two decades according to the global trends. China and the USA still maintained the leading position in this field. However, collaboration between institutions needs to be strengthened. It's commended to pay attention to the latest hotspots, such as "F. nucleatum" and "probiotics". This bibliometric analysis evaluates the scope and trends of gut microbiota and CRC, providing a useful perspective on current research and future directions for studying the link between the gut microbiota and CRC.

A positive feedback loop of the TAZ/ß-catenin axis promotes Helicobacter pylori-associated gastric carcinogenesis.

Background: Helicobacter pylori infection is the strongest known risk factor for gastric cancer. The Hippo signaling pathway controls organ size and maintains tissue homeostasis by coordinately regulating cell growth and proliferation. Here, we demonstrate the interactive role of TAZ, the transcriptional coactivator of the Hippo pathway, and beta-catenin in promoting the pathogenesis of H. pylori infection. Methods: TAZ expression was evaluated in human gastric tissues and H. pylori-infected insulin-gastrin (INS-GAS) mice. Western blot, immunofluorescence, immunohistochemistry, and RT-PCR assays were performed. Coimmunoprecipitation was performed to examine the interaction between TAZ and ß-catenin. TAZ and ß-catenin were silenced using small interfering RNAs. HA-ß-catenin and Flag-TAZ were constructed. Results: Increased TAZ was noted in human gastric cancer tissues compared to chronic gastritis tissues and in H. pylori-positive gastritis tissues compared to H. pylori-negative gastritis tissues. In addition, H. pylori infection induced TAZ expression and nuclear accumulation in the gastric tissue of INS-GAS mice and cultured gastric epithelial cells, which was dependent on the virulence factor CagA. Moreover, TAZ or ß-catenin knockdown significantly suppressed H. pylori infection-induced cell growth, survival, and invasion. Furthermore, the interactive regulation of TAZ and ß-catenin activation was revealed. Finally, ß-catenin was required for H. pylori-induced TAZ activation. Conclusion: These findings suggest the existence of a positive feedback loop of activation between TAZ and ß-catenin that could play an important role in CagA+ H. pylori infection-induced gastric carcinogenesis. TAZ inhibition represents a potential target for the prevention of H. pylori infection-associated gastric cancer.

MiR155 Disrupts the Intestinal Barrier by Inducing Intestinal Inflammation and Altering the Intestinal Microecology in Severe Acute Pancreatitis.

BACKGROUND: Intestinal dysfunction is a common complication of acute pancreatitis. MiR155 may be involved in the occurrence and development of intestinal dysfunction mediated by acute pancreatitis, but the specific mechanism is not clear. AIMS: To investigate the effect of miR155 on severe acute pancreatitis (SAP)-associated intestinal dysfunction and its possible mechanism in a mice model. METHODS: In this study, SAP mice model was induced by intraperitoneal injection of caerulein and LPS in combination. Adeno-associated virus (AAV) was given by tail vein injection before the SAP model. The pancreatic and intestinal histopathology changes were analyzed. Cecal tissue was collected for 16S rRNA Gene Sequencing. Intestinal barrier proteins ZO-1 and E-cad were measured by Immunohistochemistry Staining and Western Blot, respectively. Intestinal tissue miR155 and inflammatory factors TNF-α, IL-1ß, and IL-6 were detected by Q-PCR. The expression levels of protein associated with TNF-α and TLR4/MYD88 pathway in the intestinal were detected. RESULTS: In miR155 overexpression SAP group, the levels of tissue inflammatory factor were significantly increased, intestinal barrier proteins were significantly decreased, and the injury of intestinal was aggravated. Bacterial 16S rRNA sequencing was performed, showing miR155 promotes gut microbiota dysbiosis. The levels of TNF-α, TLR4, and MYD88 in the intestinal were detected, suggesting that miR155 may regulate gut microbiota and activate the TLR4/MYD88 pathway, thereby affecting the release of inflammatory mediators and regulating SAP-related intestinal injury. After application of miR155-sponge, imbalance of intestinal flora and destruction of intestinal barrier-related proteins have been alleviated. The release of inflammatory mediators decreased, and the histopathology injury of intestinal was improved obviously. CONCLUSION: MiR155 may play an important role in SAP-associated intestinal dysfunction. MiR155 can significantly alter the intestinal microecology, aggravated intestinal inflammation through TLR4/MYD88 pathway, and disrupts the intestinal barrier in SAP mice.

Discovery and Validation of Novel Methylation Markers in Helicobacter pylori-Associated Gastric Cancer.

Previous studies have shown that abnormal methylation is an early key event in the pathogenesis of most human cancers, contributing to the development of tumors. However, little attention has been given to the potential of DNA methylation patterns as markers for Helicobacter pylori- (H. pylori-) associated gastric cancer (GC). In this study, an integrated analysis of DNA methylation and gene expression was conducted to identify some potential key epigenetic markers in H. pylori-associated GC. DNA methylation data of 28 H. pylori-positive and 168 H. pylori-negative GC samples were compared and analyzed. We also analyzed the gene expression data of 18 H. pylori-positive and 145 H. pylori-negative GC cases. Finally, the results were verified by in vitro and in vivo experiments. A total of 5609 differentially methylated regions associated with 2454 differentially methylated genes were identified. A total of 228 differentially expressed genes were identified from the gene expression data of H. pylori-positive and H. pylori-negative GC cases. The screened genes were analyzed for functional enrichment. Subsequently, we obtained 28 genes regulated by methylation through a Venn diagram, and we identified five genes (GSTO2, HUS1, INTS1, TMEM184A, and TMEM190) downregulated by hypermethylation. HUS1, GSTO2, and TMEM190 were expressed at lower levels in GC than in adjacent samples (P < 0.05). Moreover, H. pylori infection decreased HUS1, GSTO2, and TMEM190 expression in vitro and in vivo. Our study identified HUS1, GSTO2, and TMEM190 as novel methylation markers for H. pylori-associated GC.

Expression and prognostic significance of the DNA damage response pathway and autophagy markers in gastric cancer.

Gastric cancer (GC) is a leading cause of mortality and morbidity worldwide. We assessed the expression patterns of DNA damage response (DDR)-related markers, including ATM, CHK2, p-p53 (S15), Rad51, and BRCA2 and autophagy-related proteins including p62 and Beclin-1 in 153 GC specimens using immunohistochemistry staining. GC tissues showed lower levels of ATM, CHK2, p-p53, BRCA2, and higher levels of Rad51 compared to adjacent normal tissues. The autophagy-related protein p62 was upregulated, whereas Beclin-1 was downregulated in human GC groups. Additionally, different statuses of DDR pathways and autophagy characterized by protein expression were associated with overall survival. Our results indicated that the impairment of DNA damage and autophagy may be implicated in gastric cancer progression and its clinical prognosis.

Upregulation of oncogene Activin A receptor type I by Helicobacter pylori infection promotes gastric intestinal metaplasia via regulating CDX2.

BACKGROUND: Activin A receptor type I (ACVR1) is involved in tumorigenesis. However, the underlying molecular mechanisms of ACVR1 in gastric cancer (GC) and its association with Helicobacter pylori remained unclear. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) database were utilized to explore the ACVR1 expression in GC and normal control and its association with survival. The ACVR1 was knocked out using CRISPR/Cas-9; RNA sequencing analysis was performed in AGS cells with ACVR1 knockout and normal control. Functional experiments (CCK-8, colony-forming, and transwell assays) were conducted to demonstrate the role of ACVR1 in cell proliferation, invasion, and metastasis. H. pylori-infected C57/BL6 models were established. ACVR1, p-Smad1/5, and CDX2 were detected in AGS cells cocultured with H. pylori strains. The CDX2 and key elements of BMP signaling pathway were detected in AGS cells with ACVR1 knockout and normal control. In addition, Immunohistochemistry was performed to detect the ACVR1 and CDX2 expression in gastric samples. RESULTS: ACVR1 expression was higher in GC than normal control from TCGA, GEPIA, and samples collected from our hospital (p < 0.05). ACVR1 promoted cell proliferation, migration, and invasion in vitro. Both cagA+ and cagA- H. pylori could upregulate the expression ACVR1 (p < 0.05). Downregulation of ACVR1 inhibited the H. pylori-induced cell proliferation, migration, and invasion (p < 0.05). H. pylori increased the expression of p-Smad 1/5 and CDX2. The CDX2 and key elements of BMP signaling pathway were downregulated in AGS cells with ACVR1 knockout. ACVR1 and CDX2 were upregulated in the stage of intestinal metaplasia (IM). Moreover, ACVR1 and CDX2 expressions were higher in H. pylori-positive group than H. pylori-negative group (p < 0.05). CONCLUSION: Our data indicate that H. pylori infection increases ACVR1 expression, promoting gastric IM via regulating CDX2, which is an essential step in H. pylori carcinogenesis.

Effect of Helicobacter pylori eradication on hyperplastic gastric polyps: A systematic review and meta-analysis.

BACKGROUND: There is increasing evidence that the eradication of Helicobacter pylori leads to the regression of gastric hyperplastic polyps (GHPs). We performed a systematic review with a meta-analysis of randomized controlled trials and observational studies that assessed the effects of eradication. MATERIALS AND METHODS: We searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies with a combination of the terms "Helicobacter pylori" and "polyps." The risk ratio was used to compare the effect of H. pylori eradication/treatment on GHP. We also calculated the pooled disappearance rate of GHP in the H. pylori eradication/treatment group and persistent infection group. RESULTS: We analyzed data from 6 studies, including 3 RCTs. A total of 58/394 patients were included in the H. pylori treatment/successful eradication group, and 57/302 patients were included in the H. pylori untreated/persistent infection group. The pooled rate of GHP elimination after H. pylori treatment/successful eradication was 59% (95% CI, 43%-75%)/79% (95% CI, 72%-86%). H. pylori treatment/successful eradication significantly increased the GHP elimination rate [ITT: (pooled rate: 58% vs. 0%, RR =22.24, 95% CI, 4.51- 109.78, p = 0.0001), PP: (pooled rate: 65% vs. 0%, RR =22.25, 95% CI, 4.52- 109.37, p = 0.0001)/(pooled rate: 79% vs. 9%, RR =26.87, 95% CI, 1.34-540.5, p = 0.03)]. CONCLUSIONS: Our meta-analysis showed that after the eradication of H. pylori, most GHPs are eliminated. Moreover, the treatment/successful eradication of H. pylori increased the GHP elimination rate by more than 20 times that in the control group.

Research Trends on Clinical Helicobacter pylori Eradication: A Bibliometric Analysis from 1983 to 2020.

BACKGROUND: Numerous studies related to Helicobacter pylori (H. pylori) eradication have been published since the discovery of H. pylori. This study aimed to use a quantitative method to assess the development of this field. MATERIALS AND METHODS: We performed a search of related articles from Web of Science published in 1983-2020 using a combination of the search terms "H. pylori" and "eradication". Eligible studies were included after a two-stage screening process, and the following data were extracted: title, author, institution, country, study type, sample size, eradication regimen, publication year, number of citations, journal, and H-index. RESULTS: A total of 1402 studies were finally identified. The results showed that the period from 1994-2003 was the most influential period in this field. Italy and the USA were dominant countries in this field, while China's publication number increased sharply in the last ten years. Baylor College of Medicine was the most influential institution. Alimentary Pharmacology Therapeutics was the most productive journal. The effects of H. pylori eradication on peptic ulcers and gastric cancer and H. pylori eradication therapy were the most cited topics in this field. After the publish of Maastricht/Florence Ⅳ guideline, the research of quadruple therapy was more than triple therapy. Bismuth-containing quadruple therapy became the most focused regimen after Maastricht/Florence Ⅴ guideline. CONCLUSIONS: In this study, we summarized the characteristics of the publications; identified the most influential countries, institutions, journals; identified the popular research topics and eradication regimen of clinical H. pylori eradication.

Diagnosis of malignant versus tuberculous ascites using tumor markers and globulin ratios in serum and ascites: A Fisher discriminant model.

BACKGROUND AND STUDY AIMS: This study was conducted to investigate the significance of tumor and biochemical markers in serum and ascitic fluid in the differential diagnosis of tuberculous and malignant ascites. PATIENTS AND METHODS: Based on findings from natural orifice transluminal endoscopic surgery and postoperative pathology or cytology of 63 patients, they were divided into the malignant group (31 patients) and the tuberculous group (32 patients). Levels of tumor markers, albumin, globulin, and lactate dehydrogenase were measured simultaneously. Data were statistically analyzed, and a Fisher discriminant model was established. The receiver operating characteristic curve was constructed to confirm the discriminant value. RESULTS: The levels of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 19-9 (CA 19-9), and globulin in serum and ascitic fluid were different between the tuberculous and malignant ascites groups (P < .05). The ratios of ascites-to-serum levels of CEA, CA125, and CA 19-9, as well as the ratio of serum-to-ascites of globulin levels, were different between the two groups (P < .05). The Fisher discriminant model was established based on the ascites-to-serum ratios of CEA, CA125, and CA 19-9 levels and the serum-to-ascites ratio of globulin levels. The area under the curve was 0.908, the sensitivity was 0.838 (26/31), and the specificity was 0.875 (28/32). CONCLUSION: A Fisher discriminant model can be established using serum and ascites tumor markers and globulin ratios, which is valuable in the differential diagnosis of tuberculous versus malignant ascites.

Helicobacter pylori induces epithelial-mesenchymal transition in gastric carcinogenesis via the AKT/GSK3ß signaling pathway.

Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3ß signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3ß and p-GSK3ß (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3ß (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3ß did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3ß were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3ß, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development.