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Helicobacter pylori, a pathogenic bacterium residing in the human gut microbiome, is a forefront pillar of biological factors known to cause gastric cancer (GC) in human. At genetic levels, the emerging field of RNAomics has shed light on the need to investigate a significant biological macromolecule known as Noncoding RNA that plays pivotal role in diverse biological and functional facets of bacterial pathogenesis and survival. Notably, H. pylori harbour an array of coding and non-coding RNAs (ncRNAs). These ncRNAs exert pleiotropic effects, targeting numerous cellular pathways and thereby orchestrating transcriptomic-level regulation to adapt to various environmental conditions. Regrettably, the existing literature on H. pylori lacks a comprehensive and concise overview about these RNAs. Acknowledging this significant gap, our study systematically explores the regulation of biomarker ncRNA classes, associated molecules, and their therapeutic targets within the different cellular realm of bacterium. This elucidation of functional domains by computational and in vitro approach will provide essential insights for developing modern, synthetic, and personalized strategies to target these ncRNAs, ultimately eradicating the pathogenesis. Therefore, this research holds significant promise for advancing our potential understanding of H. pylori pathogenesis and paving the way for innovative therapeutic interventions., Competing Interests: Declaration of competing interest There are no competing interests to declare from authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The presence of Helicobacter pylori ( H. pylori ) infection has been indicated to have a protective influence on esophageal cancer (EC) in some studies, but its specific impact on the risk of esophageal squamous cell carcinoma and esophageal adenocarcinoma remains inconclusive. This manuscript comment addresses the recent study by López-Gómez et al . Despite it was a retrospective observational study without a control group, this study revealed a notably low prevalence of H. pylori infection among EC patients, indicating a potential association between H. pylori and EC in Spain. It is important to note that the relationship between H. pylori and the risk of EC varies geographically. We also conducted a meta-analysis focusing on this association in Asian populations to offer precise clinical insights. However, no significant correlation between H. pylori infection and EC was identified, suggesting that the perceived protective effect of H. pylori against EC may have been overestimated in the Asian population., Competing Interests: Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Helicobacter pylori was described in 1979. This bacterium, which thrives in the harsh conditions of the stomach, is typically acquired during childhood and can remain colonized for life. Approximately, 90% of the global population is affected, and H. pylori is linked to various conditions, including gastritis, peptic ulcers, lymphoproliferative gastric lymphoma, and even gastric cancer. Currently, antibiotics are the primary treatment method, but the associated challenges of antibiotic use have led to the consideration of oral vaccination as a viable preventive measure against this infection. However, the stomach's harsh environment characterized by its acidic conditions and numerous proteolytic enzymes poses significant obstacles to the development and effectiveness of oral vaccines. To address these challenges, researchers have proposed and evaluated several delivery systems. One of the most promising options is the use of probiotics. Among the various probiotics, Lactococcus lactis stands out as a suitable candidate for oral vaccine delivery against H. pylori due to the advancements in genetic engineering that have been applied to it. This review article discusses the limitations of current treatment strategies and rationalizes the shift toward vaccination, particularly oral vaccination for this infection. It also explores the advantages and challenges of using probiotic bacteria, with a focus on L. lactis as a delivery system. Ultimately, despite the existing challenges, L. lactis continues to be recognized as a promising delivery system. Nonetheless, further research is essential to fully assess its effectiveness and address the challenges associated with this approach., Competing Interests: Declarations. Conflict of interest: The authors report no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: Helicobacter pylori ( H. pylori ) infects approximately half of the population worldwide and causes chronic gastritis, peptic ulcers, and gastric cancer. Test-and-treat strategies have been recommended for the prevention of H. pylori -associated diseases. Advancements in high-throughput sequencing technologies have broadened our understanding of the complex gastrointestinal (GI) microbiota and its role in maintaining host homeostasis. Recently, an increasing number of studies have indicated that the colonization of H. pylori induces dramatic alterations in the gastric microbiota, with a predominance of H. pylori and a reduction in microbial diversity. Dysbiosis of the gut microbiome has also been observed after H. pylori infection, which may play a role in the development of colorectal cancer. However, there is concern regarding the impact of antibiotics on the gut microbiota during H. pylori eradication. In this review, we summarize the current literature concerning how H. pylori infection reshapes the GI microbiota and the underlying mechanisms, including changes in the gastric environment, immune responses, and persistent inflammation. Additionally, the impacts of H. pylori eradication on GI microbial homeostasis and the use of probiotics as adjuvant therapy are also discussed. The shifts in the GI microbiota and their crosstalk with H. pylori  may provide potential targets for H. pylori -related gastric diseases and extragastric manifestations., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Importance: In the US, peptic ulcer disease affects 1% of the population and approximately 54 000 patients are admitted to the hospital annually for bleeding peptic ulcers., Observations: Approximately 10% of patients presenting with upper abdominal pain in a primary care setting have a peptic ulcer as the cause of their symptoms. The principal causes of peptic ulcer disease are Helicobacter pylori infection, which affects approximately 42% of patients with peptic ulcer disease, and aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, which are etiologic factors in approximately 36% of people with peptic ulcer disease. Complications of peptic ulcer include bleeding (73% of patients), perforation (9% of patients), and pyloric obstruction (3% of patients). Annually, 10 000 people die of peptic ulcer disease in the US. Endoscopy definitively diagnoses peptic ulcer disease. Acid blockers, such as omeprazole, can heal peptic ulcers in approximately 80% to 100% of patients within 4 weeks, but gastric ulcers larger than 2 cm may require 8 weeks of treatment. Eradication of H pylori decreases peptic ulcer recurrence rates from approximately 50% to 60% to 0% to 2%. Discontinuing NSAIDs heals 95% of ulcers identified on endoscopy and reduces recurrence from 40% to 9%. When discontinuing an NSAID is not desirable, changing the NSAID (eg, from ketorolac to ibuprofen), adding a proton pump inhibitor such as omeprazole or lansoprazole, and eradicating H pylori with treatment such as bismuth, metronidazole, and tetracycline combined with omeprazole can reduce recurrence rates., Conclusions and Relevance: Peptic ulcer disease is associated with increased hospitalization rates and mortality. Acid blocking with proton pump inhibitors, such as omeprazole or lansoprazole, is the primary treatment. Recurrence of ulcers can be prevented by eradicating H pylori if present and discontinuing aspirin or NSAIDs if applicable.

Objective: The purpose of this study was to investigate the relationship between Helicobacter pylori ( H. pylori ) infection-induced changes in gastric mucosal immune cells and glandular epithelial cell damage and the histopathological characteristics of these changes., Methods: We performed a detailed histomorphometry and immunohistochemical analysis of a total of 1635 H. pylori -infected gastric mucosal specimens., Results: Stage-wise features were as follows: Early stage of infection: H. pylori was colonized in the mucous layer, and very few neutrophils were visible in the layer. Gastric surface epithelial cell infection stage: H. pylori specifically and selectively adhered to the cytoplasm of the surface mucous cells, with the presence of a small number of neutrophils, eosinophils, and lymphocytes infiltration, which is termed early immune response. Compensatory mucous neck cell hyperplasia stage: proliferation of stem cells in the deep gastric pit and infiltration of a large number of lymphocytes in the superficial layer of lamina propria were observed, which is termed immune cell mobilization counterinsurgency. Lamina propria lesion stage: excessive upward migration of the proliferative area. Infiltration of a large number of lymphocytes, plasma cells, monocytes, macrophages, and other immune cells was observed in the whole layer of the gastric mucosa, which is termed automatic replication of immune cells. Abnormal proliferative transformation stage: presence of intranuclear milky globular body cells or signet-ring cell-like heterotypic cells at the junction of the gastric pit and the gastric gland, with proliferation of large numbers of immune cells and vacuolar degeneration of immune cells, which is termed the proliferation and degeneration of immune cells. Intraepithelial neoplasia stage: clonal hyperplasia of epithelial cells and immunosuppression., Conclusion: For controlling the occurrence and development of gastric cancer and effective immune intervention, it is essential to grasp the relationship between H. pylori infection-induced changes in gastric mucosal immune cells and glandular epithelial cell damage and its histopathological characteristics.

Helicobacter pylori ( H. pylori ) is a gram-negative, spiral-shaped bacterium that colonizes the human stomach, leading to various gastric diseases. The efficacy of traditional treatments, such as bismuth-based triple and quadruple therapies, has been reduced due to increasing antibiotic resistance and drug toxicity. As a result, the development of effective vaccines was proposed to control H. pylori -induced infections; however, one of the primary challenges is the lack of potent adjuvants. Although various adjuvants, both toxic (e.g. cholera toxin and Escherichia coli heat-labile toxin) and non-toxic (e.g. aluminum and propolis), have been tested for vaccine development, no clinically favorable adjuvants have been identified due to high toxicity, weak immunostimulatory effects, inability to elicit specific immune responses, or latent side effects. Outer membrane vesicles (OMVs), mainly secreted by gram-negative bacteria, have emerged as promising candidates for H. pylori vaccine adjuvants due to their potential applications. OMVs enhance mucosal immunity and Th1 and Th17 cell responses, which have been recognized to have protective effects and guarantee safety and efficacy. The development of an effective vaccine against H. pylori infection is ongoing, with clinical trials expected in the future.

Helicobacter pylori (H. pylori) antibiotic resistance has been widespread and increasing worldwide, which presented a significant challenge to the successful eradication of H. pylori infection. Identification of antibiotic resistance and exploration of potential resistance mechanisms are thus necessary for effective treatment. For this purpose, we herein develop a whole genome sequencing (WGS) assay based on next-generation sequencing (NGS) to detect the entire genome of 73 H. pylori strains isolated from gastric mucosa of patients in Tianjin, China, and analyzed the association between single-nucleotide polymorphism (SNP) in resistance-related genes and phenotypic sensitivity. We discovered the consistent relationship between genotypic and phenotypic resistance by A2143 C/G in 23S rRNA for clarithromycin (Kappa: 0.882), N87 K/I in gyrA for levofloxacin (Kappa: 0.883), and wild-type of pbp1 for amoxicillin. In addition, we obtained 4 super-resistant clinical strains of H. pylori, which formed thick, sticky biofilms, were extremely resistant to all antibiotics regardless of the present of mutations in antibiotic targets sites. Therefore, biofilm formation is also a mechanism of drug resistance, and biofilm-related proteins or genes are also expected to be used as screening markers for H. pylori resistance., Competing Interests: Declaration of competing interest There is no conflict of interest in this study. Each author reveals any financial interests or connections, direct or indirect, or other situations that might raise the question of bias in the work reported or the conclusions, implications, or opinions stated— including pertinent commercial or other sources of funding for the individual author(s) or for the associated department(s) or organization(s), personal relationships, or direct academic competition., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Helicobacter pylori (H. pylori) has infected approximately 4.4 billion individuals worldwide. The known virulence genes and the existing H. pylori typing methods have not been shown to have a recognized correlation with its infectivity. The aim of this study was to elucidate the relationships among known important virulence genes, coccoid transformation, and cytotoxicity of H. pylori isolated from individuals with different clinical diseases to provide guidance for the development of new virulence typing methods for H. pylori ., Methods: The known important virulence genes of 35  H. pylori strains were identified by whole-gene next-generation sequencing (WGS) and polymerase chain reaction (PCR). The chronological changes in the proportion of coccoid forms of H. pylori and their ultramicroscopic structures were observed chronologically using transmission electron microscopy. Human gastric mucosal epithelial cells (GES-1) were infected with H. pylori strains in vitro to evaluate cytotoxicity of H. pylori ., Results: There were no significant correlations among the known important virulence genes, coccoid transformation and cytotoxicity of H. pylori isolated from patients with different clinical diseases. We developed a new virulence classification based on the defensive and offensive abilities of H. pylori ., Conclusions: Coccoid transformation and virulence are two independent characteristics of H. pylori that reflect its defensive and offensive abilities, respectively. These two abilities work synergistically, warranting the construction of a new virulence typing method for H. pylori . However, the correlation between the new virulence classification and pathogenic ability still needs to be further verified.

Most gastric cancers (95%) are related to an initial Helicobacter pylori infection worldwide. Treatments against this pathogen include a mix of antibiotics, antimicrobials, and proton-pump inhibitors. Over time, H. pylori mutated, generating resistance to treatments and making it hard to combat its infection. The purpose of this review is Hibiscus sabdariffa , commonly known as hibiscus, as a potential agent for anti- H. pylori activity. Scientific interest has increased toward plant-derived bioactive compounds, which have the ability to enhance the antibiotic effect and can lead to the development of new drugs, such is the case for H. sabdariffa. In general, studies show that natural products, such as plant-derived bioactive compounds, can be used as alternative treatments from natural origin against the pathogen. The specific action mechanism of these bioactive compounds is still controversial, but it is suggested that they have an anti-inflammatory effect, and they also act as antibiotic coadjutants. Research has been conducted regarding different bioactive compounds such as polyphenols, epicatechins, alkaloids, and caryophyllenes. H. sabdariffa contains several of these compounds; therefore, more studies are needed to establish its effect against H. pylori .

CagA is a significant oncogenic factor injected into host cells by Helicobacter pylori , which is divided into two subtypes: East Asian type (CagA E ), characterized by the EPIYA-D motif, and western type (CagA W ), harboring the EPIYA-C motif. CagA E has been reported to have higher carcinogenicity than CagA W , although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagA E . Co-Immunoprecipitation and Pull-down assays showed that CagA E bind more SHIP2 than CagA W . Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagA E to the plasma membrane catalyzes the conversion of PI(3,4,5)P 3 into PI(3,4)P 2 . This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagA E and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagA E and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagA E into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagA E hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of H. pylori CagA E .

Background: Helicobacter pylori (H. pylori), the only bacterium classified as a type I (definite) carcinogen, is strongly associated with the development of gastric inflammation and adenocarcinoma. It infects the stomach of approximately half of the global population, equivalent to nearly 4.4 billion people. However, due to physiological barriers in the stomach, microbial barriers and increased antibiotic resistance, the therapeutic efficiency of standard antibiotic therapy is limited and cannot meet the clinical needs in some areas. Combining stimulus-responsive biomaterials with certain stimuli is an emerging antibacterial strategy. Stimulus-responsive biomaterials can respond to chemical, biological or physical cues in the environment with corresponding changes in their own properties and functions, highlighting a more intelligent, targeting and efficient aspect for H. pylori therapy., Aim of Review: This review describes the critical obstacles in the current treatment of H. pylori, summarizes the recent advances in stimulus-responsive biomaterials against H. pylori by elucidating their working mechanisms and antibacterial performances under different types of stimuli (pH, enzymes, light, magnetic and ultrasound irradiations), and attempts to analyze the future prospects of such smart biomaterial for H. pylori eradication. Key Scientific Concepts of Review: Any characteristic property or change in the biomilieu at the H. pylori infected site (endogenous stimuli) or specific iatrogenic conditions in vitro (exogenous stimuli) can act as cues to activate or potentiate the antibacterial activity of responsive biomaterials. The responsiveness of these materials to endogenous stimuli enhances antimicrobial targeting, and makes physiological barriers that would otherwise hinder conventional H. pylori therapies a key factor in facilitating antibacterial effects. The responsiveness to exogenous stimuli greatly prolongs the action time of antimicrobial materials and pinpoints the site of infection, thereby reducing toxic side effects. These findings pave the way for the development of more precise and effective anti-H. pylori treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Helicobacter pylori causes globally prevalent infections that are highly related to chronic gastritis and even development of gastric carcinomas. With the increase of antibiotic resistance, scientists have begun to search for better vaccine design strategies to eradicate H. pylori colonization. However, while current strategies prefer to formulate vaccines with a single H. pylori antigen, their potential has not yet been fully realized. Outer membrane vesicles (OMVs) are a potential platform since they could deliver multiple antigens. In this study, we engineered three crucial H. pylori antigen proteins (UreB, CagA, and VacA) onto the surface of OMVs derived from Salmonella enterica serovar Typhimurium ( S . Typhimurium) mutant strains using the hemoglobin protease (Hbp) autotransporter system. In various knockout strategies, we found that OMVs isolated from the Δ rfbP Δ fliC Δ fljB Δ ompA mutants could cause distinct increases in immunoglobulin G (IgG) and A (IgA) levels and effectively trigger T helper 1- and 17-biased cellular immune responses, which perform a vital role in protecting against H. pylori . Next, OMVs derived from Δ rfbP Δ fliC Δ fljB Δ ompA mutants were used as a vector to deliver different combinations of H. pylori antigens. The antibody and cytokine levels and challenge experiments in mice model indicated that co-delivering UreB and CagA could protect against H. pylori and antigen-specific T cell responses. In summary, OMVs derived from the S . Typhimurium Δ rfbP Δ fliC Δ fljB Δ ompA mutant strain as the vector while importing H. pylori UreB and CagA as antigenic proteins using the Hbp autotransporter system would greatly benefit controlling H. pylori infection.

Gastric cancer constitutes a malignant neoplasm characterized by heightened invasiveness, posing significant global health threat. Inspired by the analysis that gastric cancer patients with Helicobacter pylori (H. pylori) infection have higher overall survival, whether H. pylori can be used as therapeutics agent and oral drug delivery system for gastric cancer. Hence, we constructed engineered H. pylori for gastric cancer treatment. A type Ⅱ H. pylori with low pathogenicity, were conjugated with photosensitizer to develop the engineered living bacteria NIR-triggered system (Hp-Ce6). Hp-Ce6 could maintain activity in stomach acid, quickly infiltrate through mucus layer and finally migrate to tumor region owing to the cell morphology and urease of H. pylori. H. pylori, accumulated in the tumor site, severed as vaccine to activate cGAS-STING pathway, and synergistically remodel the macrophages phenotype. Upon irradiation within stomach, Hp-Ce6 directly destroyed tumor cells via photodynamic effect inherited by Ce6, companied by inducing immunogenic tumor cell death. Additionally, Hp-Ce6 exhibited excellent biosafety with fecal elimination and minimal blood absorption. This work explores the feasibility and availability of H. pylori-based oral delivery platforms for gastric tumor and further provides enlightening strategy to utilize H. pylori invariably presented in the stomach as in-situ immunomodulator to enhance antitumor efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Helicobacter pylori (H. pylori) , a globally prevalent pathogen Group I carcinogen, presents a formidable challenge in gastric cancer prevention due to its increasing antimicrobial resistance and strain diversity. This comprehensive review critically analyzes the limitations of conventional antibiotic-based therapies and explores cutting-edge approaches to combat H. pylori infections and associated gastric carcinogenesis. We emphasize the pressing need for innovative therapeutic strategies, with a particular focus on precision medicine and tailored vaccine development. Despite promising advancements in enhancing host immunity, current Helicobacter pylori vaccine clinical trials have yet to achieve long-term efficacy or gain approval regulatory approval. We propose a paradigm-shifting approach leveraging artificial intelligence (AI) to design precision-targeted, multiepitope vaccines tailored to multiple H. pylori subtypes. This AI-driven strategy has the potential to revolutionize antigen selection and optimize vaccine efficacy, addressing the critical need for personalized interventions in H. pylori eradication efforts. By leveraging AI in vaccine design, we propose a revolutionary approach to precision therapy that could significantly reduce H. pylori -associated gastric cancer burden., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor JK declared a shared parent affiliation with the authors at the time of review., (Copyright © 2024 Tu, Wang, Liang and Liu.)

Background: Helicobacter pylori (H. pylori) stands as the predominant infectious agent linked to the onset of gastritis, peptic ulcer diseases, and gastric cancer (GC). Identified as the exclusive bacterial factor associated with the onset of GC, it is classified as a group 1 carcinogen by the World Health Organization. The elimination of H. pylori plays a crucial role in the primary prevention of GC. While the prevalence has declined in recent decades, H. pylori infection is still highly prevalent in China, accounting for a significant part of the disease burden of GC. Therefore, updated prevalence information for H. pylori infection, especially regional and demographic variations in China, is an important basis for the design of targeted strategies that will be effective for the prevention of GC and application of policies for H. pylori control., Aim: To methodically evaluate the occurrence of H. pylori infection throughout China and establish a reference point for subsequent investigations., Methods: A systematic review and meta-analysis was conducted following established guidelines, as detailed in our methodology section., Results: Our review synthesized data from 152 studies, covering a sample of 763827 individuals, 314423 of whom were infected with H. pylori . We evaluated infection rates in mainland China and the combined prevalence of H. pylori was 42.8% (95%CI: 40.7-44.9). Subgroup analysis indicated the highest prevalence in Northwest China at 51.3% (95%CI: 45.6-56.9), and in Qinghai Province, the prevalence reached 60.2% (95%CI: 46.5-73.9). The urea breath test, which recorded the highest infection rate, showed a prevalence of 43.7% (95%CI: 41.4-46.0). No notable differences in infection rates were observed between genders. Notably, the prevalence among the elderly was significantly higher at 44.5% (95%CI: 41.9-47.1), compared to children, who showed a prevalence of 27.5% (95%CI: 19.58-34.7)., Conclusion: Between 2014 and 2023, the prevalence of H. pylori infection in China decreased to 42.8%, down from the previous decade. However, the infection rates vary considerably across different geographical areas, among various populations, and by detection methods employed., Competing Interests: Conflict-of-interest statement: The authors disclose that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Helicobacter pylori infection is a major risk factor for gastric adenocarcinomas. In the case of the intestinal subtype, chronic gastritis and intestinal metaplasia are well-known sequential steps in carcinogenesis. H. pylori has high genetic diversity that can modulate virulence and pathogenicity in the human host as a cag Pathogenicity Island (cagPAI). However, bacterial gene combinations do not always explain the clinical presentation of the disease, indicating that other factors associated with H. pylori may play a role in the development of gastric disease. In this context, we characterized the microbial composition of patients with chronic gastritis (inactive and active), intestinal metaplasia, and gastric cancer as well as their potential association with H. pylori. To this end, 16 S rRNA metagenomic analysis was performed on gastric mucosa samples from patients with different types of lesions and normal gastric tissues. Our main finding was that H. pylori virulence status can contribute to significant differences in the constitution of the gastric microbiota between the sequential steps of the carcinogenesis cascade. Differential microbiota was observed in inactive and active gastritis dependent of the H. pylori presence and status (p = 0.000575). Pseudomonades, the most abundant order in the gastritis, was associated the presence of non-virulent H. pylori in the active gastritis. Notably, there are indicator genera according to H. pylori status that are poorly associated with diseases and provide additional evidence that the microbiota, in addition to H. pylori, is relevant to gastric carcinogenesis., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: The study was approved by Ethics Committee (COMEP) of the Federal University of Ceará (protocol 071002/10) and conducted in accordance with the Declaration of Helsinki. All participants of the study signed individual informed consent forms., (© 2024. The Author(s).)

This study aimed to investigate the combination of the four regions of Helicobacter pylori vacA with cagA, cagE, dupA genes and cagA-EPIYA motifs to identify the most likely combination that could be used as a disease determinant marker in the Moroccan population. A total of 838 H. pylori-positive samples were obtained from consenting patients, that were previously analyzed by PCR to characterize vacA-s, -m, and -i regions; cagE status; and cagA 3' region polymorphism, were used to characterize vacA-d region and to determine dupA gene status. The analysis showed the predominance of the less virulent combination {vacA(s2m2i2d2)dupA(-)cagE(-)cagA(-)}, and showed that the risk of gastric cancer is 13.33 fold higher (95% confidence interval [CI] = 1.06-166.37) in patients infected with strains harboring vacA(s1m1i1d1)dupA(-)cagE(+)cagA(2EPIYA-C) compared to patients with gastritis without lesions and infected by H. pylori strains harboring vacA(s2m2i2d2)dupA(-) cagE(-)cagA(-). Infection with strains harboring the vacA(s1m1i1d1)dupA(+)cagE(+)cagA(1EPIYA-C) genotype combination represented a risk factor for both gastric ulcer and duodenal ulcer than gastritis without lesions; odds ratio (OR) =16 (95% CI = 1.09-234.24) and OR = 12.39 (95% CI = 1.09-140.81), respectively. These results suggest that the combination of the active form of vacA genotypes, dupA gene status, and the number of EPIYA-C motifs may be helpful markers for discriminating between several gastric diseases.

The immune cellular landscape from the gastric mucosa remains largely unknown despite its relevance in several inflammatory conditions. Human gastric biopsies were obtained from the antrum, body and incisura from 10 individuals to obtain lamina propria mononuclear cells that were further characterized by spectral cytometry. Phenotypic hierarchical analyses identified a total of 52 different immune cell subsets within the human gastric mucosa revealing that T-cells (> 60%) and NK cells (> 20%) were the main populations. Within T-cells, CD4 + and CD8 + were equally represented with both subsets displaying mainly a memory and effector phenotype. NK cells, on the contrary, were largely of the early phenotype. No regional differences were observed for any subsets among the 3 locations. Following unsupervised analysis, a total of 82 clusters were found. Again, no differences were observed amongst locations although a great degree of inter-individual variability was found, largely influenced by the presence of H. pylori infection and dyspepsia. We have unraveled the human gastric immune cellular subset composition and a unique interindividual immune fingerprint with no inter-regional variations., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Importance: Effects of screening for Helicobacter pylori on gastric cancer incidence and mortality are unknown., Objective: To evaluate the effects of an invitation to screen for H pylori on gastric cancer incidence and mortality., Design, Setting, and Participants: A pragmatic randomized clinical trial of residents aged 50 to 69 years in Changhua County, Taiwan, eligible for biennial fecal immunochemical tests (FIT) for colon cancer screening. Participants were randomized to either an invitation for H pylori stool antigen (HPSA) + FIT assessment or FIT alone. The study was conducted between January 1, 2014, and September 27, 2018. Final follow-up occurred December 31, 2020., Intervention: Invitation for testing for H pylori stool antigen., Main Outcomes and Measures: The primary outcomes were gastric cancer incidence and gastric cancer mortality. All invited individuals were analyzed according to the groups to which they were randomized., Results: Of 240 000 randomized adults (mean age, 58.1 years [SD, 5.6]; 46.8% female), 63 508 were invited for HPSA + FIT, and 88 995 were invited for FIT alone. Of the 240 000 randomized, 38 792 who were unreachable and 48 705 who did not receive an invitation were excluded. Of those invited, screening participation rates were 49.6% (31 497/63 508) for HPSA + FIT and 35.7% (31 777/88 995) for FIT alone. Among 12 142 participants (38.5%) with positive HPSA results, 8664 (71.4%) received antibiotic treatment, and eradication occurred in 91.9%. Gastric cancer incidence rates were 0.032% in the HPSA + FIT group and 0.037% in the FIT-alone group (mean difference, -0.005% [95% CI, -0.013% to 0.003%]; P = .23). Gastric cancer mortality rates were 0.015% in the HPSA + FIT group and 0.013% in the FIT-alone group (mean difference, 0.002% [95% CI, -0.004% to 0.007%]; P = .57). After adjusting for differences in screening participation, length of follow-up, and patient characteristics in post hoc analyses, an invitation for HPSA + FIT was associated with lower rates of gastric cancer (0.79 [95% CI, 0.63-0.98]) but not with gastric cancer mortality (1.02 [95% CI, 0.73-1.40]), compared with FIT alone. Among participants who received antibiotics, the most common adverse effects were abdominal pain or diarrhea (2.1%) and dyspepsia or poor appetite (0.8%)., Conclusions and Relevance: Among residents of Taiwan, an invitation to test for HPSA combined with FIT did not reduce rates of gastric cancer or gastric cancer mortality, compared with an invitation for FIT alone. However, when differences in screening participation and length of follow-up were accounted for, gastric cancer incidence, but not gastric cancer mortality, was lower in the HSPA + FIT group, compared with FIT alone., Trial Registration: ClinicalTrials.gov Identifier: NCT01741363.

Helicobacter pylori (H. pylori) infection is widely acknowledged as the primary risk factor for gastric cancer, facilitating its progression via the Correa cascade. Concurrently, Hexokinase Domain Containing 1 (HKDC1) has been implicated in the mediation of aerobic glycolysis, contributing to tumorigenesis across various cancers. However, the precise role of HKDC1 in the inflammatory transformation associated with H. pylori-induced gastric cancer remains elusive. In this study, transcriptome sequencing revealed a significant correlation between HKDC1 and H. pylori-induced gastric cancer. Subsequent validation using qRT-PCR, immunohistochemistry, and Western blot analysis confirmed elevated HKDC1 expression in both human and murine gastritis and gastric tumors. Moreover, in vitro and in vivo experiments demonstrated that H. pylori infection up-regulates TGF-β1 and p-Smad2, thereby activating the epithelial-mesenchymal transition (EMT) pathway, with HKDC1 playing a pivotal role. Suppression of HKDC1 expression or pharmacological inhibition of TGF-β1 reversed EMT activation, consequently reducing gastric cancer cell proliferation and metastasis. These results underscore HKDC1's essential contribution to H. pylori-induced gastric cancer progression via EMT activation., Competing Interests: Declarations Competing interests The authors have no relevant financial or non-financial interests to disclose. Ethics approval This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. Ethical approval was obtained from the Ethics Committee of Anhui Medical University. Consent to participate Written informed consent was obtained from each patient. The study complies with all ethical regulations regarding human participants. Consent to publish The authors confirm that all human research participants provided informed consent for the publication of the images included in Tables 1 and 2., (© 2024. The Author(s).)

Helicobacter pylori is a major pathogen associated with various gastric diseases. Despite decades of research, the treatment of H. pylori remains challenging. One of the primary mechanisms contributing to failures of therapies targeting this bacterium is genetic mutations in drug target sites, although the growing body of scientific data highlights that efflux pumps may also take part in this process. Efflux pumps are proteinaceous transporters actively expelling antimicrobial agents from the interior of the targeted cells and reducing the intracellular concentration of these compounds. Considering that efflux pumps contribute to both antimicrobial resistance and biofilm formation, an in-depth understanding of their properties may constitute a cornerstone in the development of novel therapeutics against H. pylori . In line with this, the aim of the current review is to describe the multitude of efflux pumps produced by H. pylori and present the data describing the involvement of these proteins in tolerance and/or resistance to various classes of antimicrobial substances.

Helicobacter pylori ( H. pylori , HP), recognized globally as one of the most widespread bacteria, serves as primary etiological agent for numerous gastroduodenal diseases, highlighting the urgent need to develop rapid and sensitive diagnostic method for H. pylori infection. Here, we devised a new diagnostic test that merged multiple cross displacement amplification (MCDA) with nanoparticle-based lateral flow biosensor (LFB), termed HP-MCDA-LFB, to facilitate the rapid and sensitive detection of H. pylori . The whole detection workflow, which includes stages such as DNA template extraction (~15 min), MCDA pre-amplification (~40 min), and result readout (~2 min), was efficiently completed within 1 h. After optimization, the HP-MCDA-LFB assay demonstrated remarkable sensitivity in detecting H. pylori , with a detection threshold as low as 60 fg of genomic DNA (~56 copies) per microliter. Furthermore, the HP-MCDA-LFB assay also achieved a perfect specificity rate of 100%, exhibiting no cross-reactivity with non- Helicobacter isolates. Particularly, the clinical feasibility of HP-MCDA-LFB assay was validated using 40 antral mucosa samples, among which 17 tested positive for H. pylori , which was in complete agreement with the results obtained from the rapid urease test. In conclusion, the HP-MCDA-LFB method developed in this study is a rapid, sensitive, and specific method for diagnosing H. pylori infection, indicating great potential for H. pylori eradication therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Zhou, Wang, He, Huang, Xiao, Jia, Wang and Zhong.)

This article reviews the cohort study published in the World Journal of Gastroenterology , which reported low rates of Helicobacter pylori ( H. pylori ) infection among esophageal cancer (EC) patients, coupled with proton pump inhibitor (PPI) overuse. These findings suggest a potential protective role of H. pylori against EC and indicate a possible association between PPI use and increased cancer risk. In light of these findings, our article examines the complex relationship between H. pylori and esophageal precancerous lesions, exploring the potential underlying mechanisms. We also address growing concerns regarding PPI overuse, including its potential effects on cancer therapy efficacy and the risk of drug interactions. Ultimately, this article highlights the urgent need for further research to evaluate the safety and efficacy of PPIs in cancer patients and to better understand their broader implications., Competing Interests: Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Chronic infection by Helicobacter pylori strains expressing cytotoxin-associated gene A (CagA) are the strongest risk factor for gastric cancer. CagA can be classified into East Asian-type and Western-type (CagA E and CagA W ), with CagA E being more closely associated with gastric cancer. This study aimed to investigate the impact of CagA E on intracellular signaling pathways to explain its high oncogenicity., Results: Mutant H. pylori strains expressing either CagA E or CagA W were generated by transforming CagA E/W -expression plasmid into CagA-deleted G27 strain (G27 ΔCagA ). In human gastric epithelial cells (GES-1) infection, CagA E induced more severe cytopathic changes, including higher interleukin-8 (IL-8) secretion, reduced cell viability, more pronounced "hummingbird phenotype" alterations, and increased cell migration and invasion compared to CagA W . Transcriptome analysis revealed that CagA E had a stronger effect on the up-regulation of key intracellular processes, including tumor necrosis factor-ɑ (TNF-ɑ) signal pathway via nuclear factor kappa-B (NF-κB), inflammatory response, interferon-γ (IFN-γ) response, hypoxia, ultraviolet (UV) response, and Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) signaling. A significant upregulation of hypoxia-related genes was a notable feature of CagA E . GES-1 cells infected with CagA E exhibited more severe intracellular hypoxia and higher levels of reactive oxygen species (ROS) than those infected with CagA W . Inhibition of hypoxia-inducible factor-1α (HIF-1α), which blocks hypoxia signaling, mitigated CagA E -induced cell migration, emphasizing the role of hypoxia in mediating CagA E effects., Conclusions: The study provides transcriptome evidence of CagA-associated intracellular regulation during H. pylori infection, demonstrating that CagA E exerts stronger effects on intracellular signaling than CagA W . These findings offer insights into the heightened carcinogenic potential of CagA E in H. pylori-induced gastric cancer., Competing Interests: Declarations Ethical approval The animal experiments were approved by the Animal Ethics Committee of Binzhou Medical University (Approval number: 2021-010). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Helicobacter pylori (H. pylori) infection has been found associated with Alzheimer's disease (AD) with unclear mechanisms. Outer Membrane Vesicles (OMVs) are spherical particles secreted by Gram-negative bacteria. Here we explore the effect of H. pylori OMVs on Aβ aggregation and toxicity. We show intraperitoneally-injected H. pylori OMVs enter the brain and co-localize with Aβ plaques in APP/PS1 mice, accompanied by aggravated Aβ pathology, exacerbated cognitive deficits and synaptic impairment, indicating that H. pylori OMVs promote β-amyloidosis and AD development. The in vitro results further identify that H. pylori OMVs significantly accelerate Aβ aggregation and increase Aβ-induced neurotoxicity. Through lipidomic analysis, we reveal that lipid components, particularly LPC 18:0 in H. pylori OMVs accelerate Aβ aggregation and enhance Aβ neurotoxicity. Moreover, H. pylori OMVs-enhanced Aβ neurotoxicity is mediated by Ca 2+ . These findings reveal a mechanism of H. pylori OMVs in accelerating AD development in which the bacterial OMVs-originated lipid components play a key role in promoting Aβ aggregation and neurotoxicity., (© 2024. The Author(s).)

Background: Helicobacter pylori ( H. pylori ) persistently colonizes the human gastric mucosa in more than 50% of the global population, leading to various gastroduodenal diseases ranging from chronic gastritis to gastric carcinoma. Cytotoxin-associated gene A (CagA) protein, an important oncoprotein, has highly polymorphic Glu-Pro-Ile-Tyr-Ala segments at the carboxyl terminus, which play crucial roles in pathogenesis. Our previous study revealed a significant association between amino acid deletions at positions 893 and 894 and gastric cancer., Aim: To investigate the impact of amino acid deletions at positions 893 and 894 on CagA function., Methods: We selected a representative HZT strain from a gastric cancer patient with amino acid deletions at positions 893 and 894. The cagA gene was amplified and mutated into cagA -NT and cagA -NE (sequence characteristics of strains from nongastric cancer patients), cloned and inserted into pAdtrack-CMV, and then transfected into AGS cells. The expression of cagA and its mutants was examined using real-time polymerase chain reaction and Western blotting, cell elongation via cell counting, F-actin cytoskeleton visualization using fluorescence staining, and interleukin-8 (IL-8) secretion via enzyme-linked immunosorbent assay., Results: The results revealed that pAdtrack/ cagA induced a more pronounced hummingbird phenotype than pAdtrack/ cagA -NT and pAdtrack/ cagA -NE (40.88 ± 3.10 vs 32.50 ± 3.17, P < 0.001 and 40.88 ± 3.10 vs 32.17 ± 3.00, P < 0.001) at 12 hours after transfection. At 24 hours, pAdtrack/ cagA- NE induced significantly fewer hummingbird phenotypes than pAdtrack/ cagA and pAdtrack/ cagA- NT (46.02 ± 2.12 vs 53.90 ± 2.10, P < 0.001 and 46.02 ± 2.12 vs 51.15 ± 3.74, P < 0.001). The total amount of F-actin caused by pAdtrack/ cagA was significantly lower than that caused by pAdtrack/ cagA- NT and pAdtrack/ cagA- NE (27.54 ± 17.37 vs 41.51 ± 11.90, P < 0.001 and 27.54 ± 17.37 vs 41.39 ± 14.22, P < 0.001) at 12 hours after transfection. Additionally, pAdtrack/ cagA induced higher IL-8 secretion than pAdtrack/ cagA- NT and pAdtrack/ cagA- NE at different times after transfection., Conclusion: Amino acid deletions at positions 893 and 894 enhance CagA pathogenicity, which is crucial for revealing the pathogenic mechanism of CagA and identifying biomarkers of highly pathogenic H. pylori ., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest and financial disclosures., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Eupatilin, a flavone isolated from Artemisia species, exerts anti-inflammatory, anti-oxidative, and anti-neoplastic activities. However, the effects of eupatilin on H. pylori-associated gastritis remain unclear. Thus, this study aimed to investigate the anti-inflammatory effects of eupatilin on gastric epithelial cells infected with cytotoxin-associated gene A (CagA)-positive Helicobacter pylori., Materials and Methods: AGS human gastric carcinoma cells were infected with a CagA-positive H. pylori strain and then treated with 10, 50, or 100 ng of eupatilin. After 24 h, the expression levels of CagA, phosphoinositide 3-kinase 1 (PI3K), nuclear factor (NF)-κB, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α in the cell lysates were measured using western blotting, and the mRNA levels of IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1 were measured using real-time polymerase chain reaction., Results: CagA translocation into AGS cells resulted in an elongated cell morphology, which was significantly suppressed by eupatilin treatment in a dose-dependent manner. Immunofluorescence staining for anti-CagA showed that eupatilin treatment dose-dependently inhibited CagA expression in the H. pylori-infected AGS cells. H. pylori infection increased the levels of pro-inflammatory cytokines including IL-1β, TNF-α, IL-6, IL-8, and MCP-1, and eupatilin treatment significantly reduced the levels of these cytokines in a dose-dependent manner. Additionally, eupatilin treatment dose-dependently suppressed the expression of PI3K and NF-κB., Conclusions: Eupatilin treatment demonstrated anti-inflammatory effects on CagA-positive H. pylori-infected gastric epithelial cells by inhibiting CagA translocation, thereby suppressing the NF-κB signaling pathway. These results suggest that eupatilin plays a protective role against CagA-positive H. pylori-induced gastritis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The objective of the study was to ascertain an optimal Helicobacter pylori diagnostic strategy using population-level laboratory data comparing the performance of serology against urea breath test (UBT). H. pylori diagnostic test results for serology and UBT from two laboratories over a 12-year period (2006-20017) were extracted, linked, and analyzed. A subset of this population underwent both methods of testing within days of each other, enabling a direct comparison of the two methods. The average prevalence of H. pylor i positivity was 21.3% by serology and 17.5% by UBT. There were 2,612 individuals who had serology performed first, followed by UBT within 14 days. For this subset, the sensitivity of serology compared with UBT was 96.5% with a specificity of 79.2%. The negative predictive value for serology was 98.4%. Contrary to various recent clinical guidelines, the data show that serology still has utility as a sensitive enough test to be used as an initial H. pylori screening test in a lower prevalence population. Negative serology can be used with confidence to rule out active infection, whereas a positive serology could be followed up with a UBT or a similar performing test such as stool antigen to differentiate active from past infection. For population-based diagnostic recommendations, such a strategy may be ideal since serology generally costs less than UBT and may be combined with a blood draw being done for other diagnostic tests. Continuing to offer serology increases options for patients and may provide economic benefits for single-payer health care systems or health maintenance organizations., Importance: This study compares the performance of serology with urea breath test in the diagnosis of Helicobacter pylori in a population-level data set and mimics a head-to-head direct comparison as the study population had both tests performed within 2 weeks of each other. This provides new information supporting the use of serology in a diagnostic algorithm. There are several instances where serology could be preferable to patients to rule out disease, despite some guidelines suggesting serology should not be used., Competing Interests: The authors declare no conflict of interest.

Background/aims: Determining antibiotic use history accurately is challenging due to its reliance on patient recall. By determining macrolide exposure using the Korean drug utilization review (DUR) system, we analyzed the impact of previous macrolide use on antibiotic resistance profiles and compared the eradication rate between tailored therapy based on macrolide exposure history and empirical therapy., Methods: Patients with confirmed Helicobacter pylori (H. pylori) infection who agreed to access prescription information using the Health Insurance Review and Assessment Service DUR system were enrolled between 2021 and 2023. Patients received tailored therapy, which was clarithromycin (CLR)-based triple therapy in cases without macrolide exposure and bismuth quadruple (BQ) therapy in cases with macrolide exposure. The empirical therapy group was prospectively recruited at the same time to compare the eradication rate., Results: A total of 418 patients (tailored therapy group, n = 57; empirical therapy group, n = 361) were analyzed. Among the tailored therapy group, 24.6% took macrolide antibiotics for the past 5 years. CLR resistance rates were higher in patients with previous macrolide use than in those without (66.7% vs. 7.5%, p < 0.001). The tailored therapy group showed a higher eradication rate than the empirical therapy group for intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses (ITT, 86.0% vs. 75.6%; MITT, 94.2% vs. 80.3%; PP, 94.2% vs. 85.1%)., Conclusions: Previous macrolide exposure identified using the DUR system was associated with a higher rate of CLR resistance. Tailored therapy based on macrolide exposure history led to higher eradication rates compared to empirical therapy., (© 2024 John Wiley & Sons Ltd.)

Helicobacter pylori infection is usually acquired during childhood and represents one of the most common infections in humans. It is well known that H. pylori has belonged to humankind for hundreds of thousands of years and it accompanied the human migration from Africa. The adult international guidelines recommend treating all infected patients as H. pylori was classified among the first-class human carcinogens by the WHO in 1994 and it is one of the main factors involved in the development of gastric cancer. Conversely, the pediatric international guidelines are more restrictive in recommending the eradication of the infection in children. Although many studies have shown evidence regarding the pathological role of H. pylori regardless of the age of the infected patients, many others have highlighted its protective/positive role in several extra-gastric diseases in children. In this review, both points of view regarding the eradication in children are critically analyzed., (© 2024 John Wiley & Sons Ltd.)

Around half of the world's population is infected with Helicobacter pylori (H. pylori), which is closely related to several ocular diseases. The study aims to evaluate the retinal and choroidal thickness changes in subjects with H. pylori infection by swept-source optical coherence tomography (SS-OCT). The ophthalmic examination and 13 C-urea breath test ( 13 C-UBT) were performed on all subjects participating in the cross-sectional study. The participants were divided into H. pylori (+) and H. pylori (-) groups depending on the 13 C-UBT results. This study covered 2574 right eyes from 2574 subjects with H. pylori infection and 2574 right eyes from 2574 age- and sex-matched individuals without H. pylori infection. Out of the nine sectors of the early treatment diabetic retinopathy study (ETDRS) grid, the maximum retinal thickness was in the inner superior sector, while the minimum was in the center sector. The maximum choroidal thickness was in the inner superior sector, while the minimum was in the outer nasal sector. The choroid of each area of the ETDRS subfield in the H. pylori (+) group was significantly thicker than that in the H. pylori (-) group, but retinal thickness did not show any difference between the two groups. Increased choroidal thickness may be an early indicator of H. pylori-associated retinal or choroidal diseases.

Helicobacter pylori is a bacterium that infects approximately half of the world's population, being more prevalent in low- and middle-income countries. H. pylori can cause gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric cancer, which is among the five most frequent cancers worldwide. Other factors such as a diet low in vegetables and high in processed red meat have been associated with gastric cancer. Here, we studied the effects of high altitude and diet on gastric disease severity in H. pylori infection in a multicenter cross-sectional study in Peru (N = 343). We recruited people from villages with distinct eating habits (high meat consumption, mixed, and limited meat consumption diet) in the Andes (Puno), and compared them to people living at sea level with a mixed diet (Lima). H. pylori infection prevalence was higher at high altitude than at sea level. High altitude, diet, and age showed a significant correlation with the severity of gastric disease, whereas H. pylori infection and sex did not. However, high altitude was not found to be a risk factor for intestinal metaplasia, while diet and age were. At high altitude, a meat-rich diet was associated with a higher incidence of metaplasia compared to a plant-based diet. This study provides a comparison of communities living at high altitude with spontaneously different diets, showing that high processed red meat consumption is a risk factor for gastric disease. Further studies are needed to explain this phenomenon and its impact on the development and progression of gastric pathologies., (© 2024 John Wiley & Sons Ltd.)

Background: Given the increasing antibiotic resistance and the inadequate acid-suppressing effects of proton pump inhibitors (PPIs), it is crucial to continuously optimize existing Helicobacter pylori (H. pylori) treatment regimens. This study aimed to evaluate the clinical efficacy and safety of novel potassium-competitive acid blocker (P-CAB)-based eradication regimens compared with traditional PPI-based regimens for the initial treatment of H. pylori., Materials and Methods: We conducted a systematic review and network meta-analysis, searching seven electronic databases for randomized controlled trials (RCTs) evaluating initial P-CAB-based H. pylori eradication therapy. The primary outcome was the H. pylori eradication rate. Secondary outcomes included adverse events and patient compliance. We synthesized the effect sizes of the trials using odds ratios (OR) and 95% confidence intervals (95% CI)., Results: A total of 54 RCTs involving 15,320 patients (74.9% male, mean age 30.2 years) were included in this study. In the intention-to-treat (ITT) analysis, VPZ-HD-dual, VPZ-triple, and VPZ-quadruple regimens demonstrated significantly higher eradication rates than PPI-triple, PPI-quadruple, and VPZ-dual regimens. Similar trends were observed in the per-protocol (PP) analysis. Subgroup analysis indicated that poor patient compliance significantly reduced eradication rates. Resistance to clarithromycin and metronidazole significantly weakened the eradication effects of PPI-triple, TPZ-triple, and VPZ-triple regimens. Additionally, the eradication rates for 7-day regimens were significantly lower than those for 14-day or 10-day regimens, but there was no significant difference between the eradication rates of 10-day and 14-day regimens. Notably, the risk of adverse events with VPZ-HD-dual was significantly lower than with VPZ-quadruple., Conclusion: Vonoprazan combined with high-dose amoxicillin dual therapy not only provides satisfactory eradication rates but also exhibits lower adverse event rates and good patient compliance, indicating its potential as a promising regimen for further promotion., (© 2024 John Wiley & Sons Ltd.)

Background: The continuous increase in drug-resistant strains, the lack of novel antibiotics, and the fewer options available to combat antibiotic-resistant infections in pediatrics pose significant challenges to the eradication of Helicobacter pylori (H. pylori) in children. This study evaluated the efficacy of first-line therapy with bismuth quadruple therapy in H. pylori-positive pediatric patients with peptic ulcers., Materials and Methods: 136 patients (aged between 8 and 17 years) diagnosed with active peptic ulcers with H. pylori infection were enrolled in this study. Patients with H. pylori strain sensitive to tetracycline and metronidazole were assigned to bismuth quadruple therapy, including a proton pump inhibitor (PPI), bismuth, tetracycline, and metronidazole. Antibiotic resistance of H. pylori was analyzed by the Epsilometer test. Treatment efficacy was evaluated at 12 weeks based on H. pylori eradication and peptic ulcer healing rates. H. pylori infection status was evaluated by a 13 C-urea breath test., Results: Most isolates showed extremely high rates of resistance to commonly prescribed antibiotics used for children, including clarithromycin (97.0%) and amoxicillin (84.6%), while the low rate of resistance to levofloxacin (16.2%). The overall success rate of eradication therapy in the intention-to-treat and the per-protocol group were 86.0% and 89.3%, respectively. Peptic ulcer healing rates for total patients at 6 weeks and 12 weeks were 75.0% and 97.7%, respectively. There were no entail unpleasant adverse events, and peptic ulcer symptoms decreased steadily over time in all cases., Conclusions: The bismuth quadruple therapy with a 2-week PPI pretreatment and followed by prolonged PPI was highly successful in eradicating H. pylori infection and healing ulcers in pediatric patients with active peptic ulcer. This might be preferable as a first-line empiric treatment regimen for H. pylori-positive pediatric patients with peptic ulcers, especially in populations with high rates of resistance to amoxicillin and clarithromycin., (© 2024 John Wiley & Sons Ltd.)

Aim: DNA methylation is associated with gastric cancer and Helicobacter pylori ( H. pylori ) infection, while increasing evidence indicated involvement of other microbes reside in gastric mucosa during gastric tumorigenesis. We investigated bacterial communities in the gastric mucosa accompanied with H. pylori related methylation anomaly. Materials & methods: Gastric mucosa samples from antrum were obtained from 182 cancer-free patients. Bacterial communities were evaluated using 16S rRNA sequencing. The result was correlated with H. pylori related promoter CpG island (CGI) methylation of five genes ( IGF2, SLC16A12, SOX11, P2RX7 and MYOD1 ), LINE1 hypomethylation and telomere length. Results & conclusion: We showed correlation between lower bacterial alpha diversity and higher CGI methylation. Multivariate analysis demonstrated older age (t = 3.46, p  = 0.0007), H. pylori infection (t = 9.99, p  < 0.0001) and lower bacterial alfa diversity (Shannon index: t = -2.34, p  = 0.02) were significantly associated with CGI hypermethylation. In genus or family levels, increased abundance of Helicobacter was associated with hyper CGI methylation with strongest correlation, while decreased abundance of four bacteria ( Intrasporangiaceae family, Macellibacteroides , Peptostreptococcus and Dietziaceae family ) was also associated with hyper CGI methylation. Our findings suggest the potential correlation between CGI methylation induction and lower bacterial alpha diversity in the gastric mucosa accompanied by H. pylori infection.

Gastric cancer remains one of the top cancers in China compared with Western countries, mainly attributed to the high rates of Helicobacter pylori infection. However, recent discoveries on the non-H. pylori gastric microbiome have led to a paradigm shift in our understanding of microbial risk factors driving gastric cancer, which will impact future screening and prevention strategies., (©2024 American Association for Cancer Research.)

In this investigation, we explored the molecular dynamics guiding the progression of castration-resistant prostate cancer (CRPC) influenced by Helicobacter pylori (H. pylori)-mediated M2 polarization of macrophages through the IL-17RA/CTSK/EMT axis. An 830-patient clinical trial categorized subjects into hormone-sensitive prostate cancer (HSPC) and CRPC groups. H. pylori infection, evaluated by ELISA, exhibited a higher incidence in CRPC patients, impacting overall survival (OS) and progression-free survival. In-depth in vitro and in vivo experiments, including 16S rDNA sequencing, immunohistochemical tests, and transcriptome analysis, unveiled that H. pylori promotes CRPC growth and metastasis by upregulating IL-17RA and CTSK, leading to enhanced EMT. Notably, M2 macrophages emerged as pivotal immune cells influencing CRPC progression. This study uncovers a novel pathway wherein H. pylori enrichment exacerbates CRPC by inducing macrophage M2 polarization, IL-17RA/CTSK expression, and EMT activation, shedding light on a previously unrecognized mechanism contributing to the growth and metastasis of CRPC., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The Ethics Committee of Fudan University Shanghai Cancer Center approved all research protocols, and the study’s content and objectives were clearly explained to the patients and their families, acquiring their informed consent. We strictly adhered to the Helsinki Declaration guidelines and ensured the anonymization of patient data. The animal experimental processes were approved by the Ethnic Committee of Fudan University Shanghai Cancer Center and in strict accordance with the recommendations of the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (050432-4-1911D). Adequate measures were taken to minimize suffering of the included animals., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

It was aimed to determine the prevalence of Helicobacter in some reptilian and amphibian species in Türkiye and to describe the bacteria. For this purpose, 73 cloacal swab samples were used as material. The description of the isolates was performed by detailed phenotypic tests, whole genome analyses, and MALDI-TOF MS. As a result of the phenotypic analysis, two helical, curved Gram-negative, motile isolates were recovered. It was determined through the analysis of 16S rRNA gene sequences that two isolates belonged to the genus Helicobacter. These isolates were found to be in a distinct group from other Helicobacter species. However, the 16S rRNA sequence did not match any identified species, with the closest match being Helicobacter mustelae strain R85-13-6 T , which had an identity level of 96.2 %. Additionally, it was found that strains faydin-H75 T and faydin-H76 had a 99.3 % identity level for their 16S rRNA genes. After conducting dDDH and ANI analyses, it was found that strains faydin-H75 T and their close neighbors H.anseris ATCC BAA-1299 T shared 13.5 % and 68.8 % similarity, respectively. The genome size of the strains was 1.7 Mb while G + C contents were 33.5 %. Metagenomic analyses using IMNGS and Protologger tools revealed the presence of faydin-H75 T in various lizard species with high similarity, confirming its broad distribution and host specificity. The results indicated that these two strains represent a novel species, for which we propose the name Helicobacter cappadocius with faydin-H75 T (=NCTC014972 = LMG 33382 = DSM117062) as the respective type strain. The current novel species is the first Helicobacter species to exhibit a psychrotrophic feature., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Helicobacter pylori disturbs the stomach lining during long-term colonization of its human host, with sequelae including ulcers and gastric cancer 1,2 . Numerous H. pylori virulence factors have been identified, showing extensive geographic variation 1 . Here we identify a 'Hardy' ecospecies of H. pylori that shares the ancestry of 'Ubiquitous' H. pylori from the same region in most of the genome but has nearly fixed single-nucleotide polymorphism differences in 100 genes, many of which encode outer membrane proteins and host interaction factors. Most Hardy strains have a second urease, which uses iron as a cofactor rather than nickel 3 , and two additional copies of the vacuolating cytotoxin VacA. Hardy strains currently have a limited distribution, including in Indigenous populations in Siberia and the Americas and in lineages that have jumped from humans to other mammals. Analysis of polymorphism data implies that Hardy and Ubiquitous coexisted in the stomachs of modern humans since before we left Africa and that both were dispersed around the world by our migrations. Our results also show that highly distinct adaptive strategies can arise and be maintained stably within bacterial populations, even in the presence of continuous genetic exchange between strains., (© 2024. The Author(s).)

Introduction: Helicobacter pylori (H. pylori) causes several gastrointestinal diseases. Its virulence factors contributing to disease development include biofilm formation, cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) proteins that induce host tissue damage. In addition, urease activity enables H. pylori growth in the gastric acidic environment. This work aimed to characterize bacterial factors associated with biofilm production among 89 clinical H. pylori isolates, collected from patient gastric biopsies., Methods: Biofilm production was detected using the crystal violet method. PCR was performed to determine vacA genotype (s1m1, s1m2, s2m1 and s2m2) and cagA gene presence. Urease activity was measured via the phenol red method. Susceptibility to six antibiotics was assessed by the Etest method., Results: Most H. pylori isolates produced biofilm. No association was found between biofilm-formation capacity and cagA presence or vacA genotype. Urease activity levels varied across isolates; no association was found between biofilm-formation and urease activity. Clarithromycin resistance was measured in 49 % of the isolates. Isolates susceptible to tetracycline were more commonly strong biofilm producers. In contrast, a significantly higher rate of strong biofilm producers was observed among resistant isolates to amoxicillin, levofloxacin and rifampicin, compared to susceptible isolates. Non-biofilm producers were more common among isolates sensitive to rifampicin and metronidazole, compared to resistant isolates., Conclusions: Further studies are needed to understand the factors that regulate biofilm production in order to search for treatments for H. pylori biofilm destruction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Description: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to summarize the available evidence and offer expert Best Practice Advice on the integration of potassium-competitive acid blockers (P-CABs) in the clinical management of foregut disorders, specifically including gastroesophageal reflux disease, Helicobacter pylori infection, and peptic ulcer disease., Methods: This expert review was commissioned and approved by the AGA Institute Governing Board and CPU Committee to provide timely guidance on a topic of high clinical importance to the AGA membership. This CPU expert review underwent internal peer review by the CPU Committee and external peer review through the standard procedures of Gastroenterology. These Best Practice Advice statements were developed based on review of the published literature and expert consensus opinion. Because formal systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Based on nonclinical factors (including cost, greater obstacles to obtaining medication, and fewer long-term safety data), clinicians should generally not use P-CABs as initial therapy for acid-related conditions in which clinical superiority has not been shown. BEST PRACTICE ADVICE 2: Based on current costs in the United States, even modest clinical superiority of P-CABs over double-dose proton pump inhibitors (PPIs) may not make P-CABs cost-effective as first-line therapy. BEST PRACTICE ADVICE 3: Clinicians should generally not use P-CABs as first-line therapy for patients with uninvestigated heartburn symptoms or nonerosive reflux disease. Clinicians may use P-CABs in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs. BEST PRACTICE ADVICE 4: Although there is currently insufficient evidence for clinicians to use P-CABs as first-line on-demand therapy for patients with heartburn symptoms who have previously responded to antisecretory therapy, their rapid onset of acid inhibition raises the possibility of their utility in this population. BEST PRACTICE ADVICE 5: Clinicians should generally not use P-CABs as first-line therapy in patients with milder erosive esophagitis (EE) (Los Angeles classification of erosive esophagitis grade A/B EE). Clinicians may use P-CABs in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs. BEST PRACTICE ADVICE 6: Clinicians may use P-CABs as a therapeutic option for the healing and maintenance of healing in patients with more severe EE (Los Angeles classification of erosive esophagitis grade C/D EE). However, given the markedly higher costs of the P-CAB presently available in the United States and the lack of randomized comparisons with double-dose PPIs, it is not clear that the benefits in endoscopic outcomes over standard-dose PPIs justify the routine use of P-CABs as first-line therapy. BEST PRACTICE ADVICE 7: Clinicians should use P-CABs in place of PPIs in eradication regimens for most patients with H pylori infection. BEST PRACTICE ADVICE 8: Clinicians should generally not use P-CABs as first-line therapy in the treatment or prophylaxis of peptic ulcer disease. BEST PRACTICE ADVICE 9: Although there is currently insufficient evidence for clinicians to use P-CABs as first-line therapy in patients with bleeding gastroduodenal ulcers and high-risk stigmata, their rapid and potent acid inhibition raises the possibility of their utility in this population., (Published by Elsevier Inc.)

Background: Empirical treatment needs to be supported by regional data, but knowledge of interregional differences is currently lacking in China. This study aimed to summarize and map the primary and secondary antibiotic resistance of Helicobacter pylori in different regions of mainland China., Methods: PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure and Wanfang databases were systematically reviewed for studies published between 1 January 2000 and 15 July 2023. Data related to primary and secondary H. pylori antibiotic resistance rates were included. Random-effects models were used to synthesize the pooled resistance rates., Results: Ultimately, 74 studies were included in the final analysis. A total of 16 provinces reported resistance data. The overall resistance rates of H. pylori in mainland China were 30.72% (95% CI 27.53%-33.99%) to clarithromycin, 70.14% (95% CI 29.53%-37.46%) to metronidazole and 32.98% (95% CI 28.73%-37.37%) to levofloxacin; for amoxicillin, tetracycline, and furazolidone, the rates were 2.41% (95% CI 1.43%-3.60%), 2.53% (95% CI 1.19%-4.28%) and 1.54% (95% CI 0.28%-3.62%), respectively. Spatial and temporal differences were observed. The resistance rates increased after treatment failure; however, secondary resistance to amoxicillin, tetracycline and furazolidone were still low across the vast majority of study regions., Conclusion: Surveillance of the updated prevalence of antibiotic resistance of H. pylori for different regions is warranted, which should factor into clinical decision making and guideline recommendations., Competing Interests: Declarations Funding: This study was supported by the National Natural Science Foundation of China (82270580 and 82070552), Key Research and Development Program of Shandong Province (2021CXGC010506). Competing interests: The all authors in this study report no conflicts of interest. Ethical approval: This study was exempt from ethical review since it not involve patients. The study had been registered on PROSPERO with the ID: CRD42023447179. Sequence information: Not applicable. Author contributions: Qingzhou Kong conceived of the study. Shuyan Zeng and Qingzhou Kong performed the systematic review and were responsible for editing the manuscript. Yueyue Li supervised the entire study and performed a critical revision of this article. Shuyan Zeng, Qingzhou Kong and Xiaoqi Wu were responsible for data collection, selecting, interpretation. Miao Duan and Xueping Nan assisted with data processing and analysis. Xiaoyun Yang, Xiuli Zuo and Yanqing Li critically reviewed and revised the article. All authors commented on or edited drafts and approved the final version of the manuscript., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Introduction and Objectives: Recent studies have suggested an association between H. pylori and metabolic dysfunction associated steatotic liver disease (MASLD). We aim to evaluate the association of H. pylori virulence genes with non-invasive markers of liver injury and fibrosis in MASLD subjects., Patients and Methods: A total of 362 dyspeptic patients who underwent gastroscopy were selected. Biochemical, clinical parameters, ultrasound, FIB-4 score, liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE), gastric biopsies, and H. pylori virulence genes (cagA, vacA) were evaluated., Results: A cohort comprised of 61 % women and 39 % men with a median age of 52 (40-60) years. MASLD was observed in 42 %, and H. pylori-positive in 45 %. No differences were observed regarding H. pylori status at co-morbid metabolic conditions. In MASLD cohort, H. pylori-positive was associated with higher AST, ALT, FIB-4 and LSM. Indeed, carriers of cagA/vacA-s1/m1-positive allelic combination were associated with higher AST, ALT, FIB-4 and LSM but not cagA/vacA-s1/m1-negative. The OR for high-risk of significant/advanced- fibrosis by VCTE (≥8 kPa) with H. pylori-positive was 2.56 (95 % CI, 1.2-5.75) and for cagA/vacA-s1/-m1-positive allelic carriers was 4.01 (95 % CI, 1.38-11.56), but non-significant association in cagA/vacA-s1/-m1-negative. After adjusting for age, gender, diabetes, BMI and hypertension the OR for VCTE ≥8 kPa with H. pylori-positive was 2.43 (95 % CI, 1.88-12.44), and cagA/vacA-s1/m1-positive allelic carriers was 4.06 (95 % CI, 1.22-14.49)., Conclusions: In our cohort of functional dyspepsia (FD) patients with MASLD, H. pylori was associated with non-invasive markers of liver injury and fibrosis. Carriers of cagA/vacA-s1/m1-positive allelic combination showed an independent risk of significant/advanced fibrosis by VCTE., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest. All authors have approved the final version of the manuscript., (Copyright © 2024 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13 C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 ., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background and Aim: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori., Methods: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion., Results: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001)., Conclusion: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Obesity and diabetes mellitus (DM) have become public health concerns worldwide. Both conditions have severe consequences and are associated with significant medical costs and productivity loss. Additionally, Helicobacter pylori infection may be a risk factor for the development of these conditions. However, whether eradicating H. pylori infection directly causes weight loss or improves insulin sensitivity is unknown., Methods: In this study, we confirmed the effect of sleeve gastrectomy according to the state of the gastric microbiota in 40 patients with obesity, DM, and H. pylori infection. Patients with obesity were divided into four groups: non-DM without H. pylori infection (ND), non-DM with H. pylori infection (ND-HP), DM, and DM with H. pylori infection (DM-HP) using 16S V3-V4 sequencing., Results: In the DM group, ALT, hemoglobin, HbA1c, blood glucose, and HSI significantly decreased, whereas high-density lipoprotein significantly increased. However, in the H. pylori-positive group, no significant difference was observed. The diversity of gastric microbiota decreased in the order of the ND > DM > ND-HP > DM-HP groups. We also conducted a correlation analysis between the preoperative microbes and clinical data. In the ND-HP group, most of the top 20 gastric microbiota were negatively correlated with glucose metabolism. However, H. pylori infection was positively correlated with pre-insulin levels., Conclusion: Therefore, these findings indicate that patients with obesity and diabetes clearly benefit from surgery, but H. pylori infection may also affect clinical improvement., (© 2024. The Author(s).)

Background: In familial adenomatous polyposis (FAP) patients, fundic gland polyps (FGPs) have been considered a risk factor for gastric neoplasms. We speculated that FGPs in FAP patients spread directionally from the greater to the lesser curvature of the gastric body and investigated the relationship between the distribution of FGPs and gastric neoplasm development., Methods: We extracted 195 FAP patients from two institutions and reviewed their medical records. Gastric polyposis was classified based on the FGP distribution (P0, no FGPs; P1, localized in the fundus or greater curvature of the gastric body; P2, spreading to the anterior or posterior wall; P3, involving the proximal half of the lesser curvature; and P4, spreading from P3 to the anal side of the lesser curvature)., Results: The 195 eligible patients were divided into the neoplasm group (n = 54, 28%) and the non-neoplasm group (n = 141, 72%). Overall, 24% of the patients were Helicobacter pylori (H. pylori)-positive. In the FGP distribution, the rate of patients with gastric neoplasm tended to increase significantly with each step towards an increasingly wide distribution from P0 to P4 in H. pylori-negative patients, but not in H. pylori-positive ones. In addition, in H. pylori-negative patients, the likelihood of neoplasm increased consistently from P0 to P4, with the highest odds ratio (95% confidence interval) at P4 of 14.1 (2.5-154.4). Furthermore, multivariate analysis showed P4 and Spigelman stage ≥III were significantly associated with gastric neoplasm development., Conclusion: FGP distribution was correlated with gastric neoplasm development in FAP patients., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Introduction: We assessed the expression levels of interleukin-8 (IL-8) and Wnt2 in Helicobacter pylori-infected gastric cancer (GC) patients, and investigated the association of these proteins with prognosis., Methodology: Seventy-two GC patients, including 40 cases with H. pylori infection and 32 cases without H. pylori infection, were enrolled. Tumor and para-tumor normal tissues were collected. H. pylori infection was determined using the rapid urease test and Warthin-Starry silver staining. The expressions of IL-8 and Wnt2 were assessed using immunohistochemistry. The association between H. pylori infection, IL-8, Wnt2, and pathological and clinical data was analyzed. The relationship between H. pylori, IL-8, Wnt2, and prognosis was assessed using survival curves and regression analyses., Results: The expression levels of IL-8 and Wnt2 in GC tissue significantly exceeded that in normal mucosa. The expression levels of IL-8 and Wnt2 were significantly higher in patients with H. pylori infection, than in those without H. pylori infection; and a positive correlation was observed between IL-8 and Wnt2 expressions. The positivity rate of IL-8 and Wnt2 in early-stage GC without lymph node metastasis markedly differed from that in advanced-stage GC with lymph node metastasis. Additionally, the survival rate of GC patients with positive IL-8 and Wnt2 expressions was significantly lower than in patients without such expression patterns. Clinical stage and Wnt2 were identified as independent prognostic factors of GC., Conclusions: IL-8 and Wnt2 were prognostic indicators for GC. H. pylori and IL-8 were not independent prognostic factors, whereas Wnt2 could independently serve as a prognostic factor for GC., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Li Lin, Ruiyu Tao, Yonggang Cai, Qiang Zhao, Ke Yang, Wenjuan Yang, Fengxia Guo.)