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Background This study aimed to investigate whether probiotics can ameliorate the H. pylori -induced Wnt/β-catenin-related COX-2 carcinogenesis signaling pathway by regulating the expression of microRNAs (miRNAs). Methods An H. pylori isolate and GES-1 cells were used to establish a COX-2-associated carcinogenesis axis. Western blot analysis was conducted to investigate Wnt/β-catenin and COX-2 signaling. Next-generation sequencing and DIANA Tools identified significant differences in miRNA expressions. The probiotics Lactobacillus acidophilus and Bifidobacterium lactis were used to study anti-carcinogenesis effects in GES-1 and miRNA-transfected GES-1 cells. The H. pylori -infected patients with intestinal metaplasia (IM) were randomly allocated into probiotic treatment or not after successful eradication, the IM regression was assessed by the 2nd esophagogastroduodenoscopy one year after treatment. Results Pretreatment with probiotics significantly reduced H. pylori -induced nuclear β-catenin phosphorylation and COX-2 levels in GES-1 cells. Among 9 significantly altered miRNAs, miR-185 was the only miRNA targeting the Wnt/β-catenin signaling pathway. H. pylori increased miR-185 expression and upregulated COX-2 carcinogenesis through the Wnt/β-catenin pathway, but not the JAK2/STAT3 pathway. B. lactis ameliorated H. pylori -induced miR-185 expression and nuclear β-catenin/COX-2 signaling in a dose-dependent manner. In the 6-month probiotic-treated patients had a significantly higher IM regression rate than controls (intention-to-treat: 37.5 vs 11.5%, OR: 4.60, 95% CI: 1.134–18.65, p  = 0.025; per-protocol: 46.2 vs 17.6%, OR: 4.00, 95% CI: 0.923–17.33, p  = 0.055). Patients without IM regression had significantly higher miR-185 levels in follow-up biopsies ( p  < 0.01). Conclusions Pretreatment with B. lactis ameliorated the H. pylori -induced COX-2 carcinogenesis pathway by reducing miR-185 expression, which targets Wnt/β-catenin signaling. (ClinicalTrials.gov, NCT05544396).

Background: Reduction of Faecalibacterium prausnitzii abundance is related to inflammatory bowel diseases (IBDs), and supplement of it exists protective effects. Aim: This study aimed to establish a F. prausnitzii ‐colonized mouse model and investigate that the presence of F. prausnitzii in the gut can ameliorate the severity of dextran sulfate sodium (DSS)‐induced colitis. Methods: A F. prausnitzii (ATCC 27768) strain was maintained on the PS‐BHI agar plates and manipulated in a strictly anaerobic chamber. A F. prausnitzii ‐colonized C57BL/6 mice model was tested by a rectal enema with 1 × 10 9 bacteria/day for 3 days. The 5% DSS was added to drinking water for 3 days to induce colitis and diarrhea in experimental mice. The clinical, cytological, and histological severities were compared between groups. Results: The F. prausnitzii ‐colonized mice model was successfully established via rectal enema with the property of transfer to offspring. DSS treatment altered gut microbiota and significantly attenuated the abundance of F. prausnitzii in colonized mice. Mice with F. prausnitzii colonization had significantly improved weight loss, anal bleeding, stool consistency, cecum weight, colon length, and serum amyloid A (SAA) level than those without after DSS treatment. Furthermore, the F. prausnitzii ‐colonized mice significantly reduced the transcription levels of TNF‐α, INF‐γ and IL‐18, and epithelial damage and PMN infiltration in the lamina propria and had better preservation of goblet cells than the control group. Conclusion: We have successfully established a mouse model colonized with F. prausnitzii via rectal enema administration and showed colonization of F. prausnitzii in the gut has a protective effect against DSS‐induced colitis.

Background Indwelling urethral catheters are widely used in clinical settings. Catheter-associated urinary tract infection has been recognized as a common adverse event in older patients. However, noninfectious complications are almost 5 times as common as infectious complications, and insufficient attention has been given to noninfectious complications. Given this importance, a novel intervention related to removing unnecessary catheters in a timely manner to promote, after removal, the recovery of self-voiding function is herein developed to reduce infectious and noninfectious complications associated with indwelling urethral catheters in hospitalized older patients. Methods A quasi-experimental study design was adopted. Patients aged 65 and older who had a urinary catheter placed within 24 h of hospital admission were included. All patients were allocated into either an intervention group, in which the novel intervention developed in the study was implemented, or a control group, who received care as usual. The outcomes of this study were to evaluate whether the novel intervention reduced the incidence of the following: catheter-associated urinary tract infections, catheter-associated noninfectious complications, decline in activities of daily living, and new nursing home admissions. Results Of 106 hospitalized older patients who consented to participate, 92 completed follow-up until discharge, including 49 in the control group and 43 in the intervention group. The patients in the intervention group were significantly older than those in the control group [83.72 ± 9.18 vs. 80.26 ± 7.66, p  = 0.038], and no differences were found between the groups in other demographics or present health conditions. Multivariable logistic regression analysis showed that the control group was more likely to develop noninfectious complications [adjusted odds ratio: 3.01, 95% confidence interval: 1.32–6.81] and a decline in ADLs [adjusted odds ratio: 11.20, 95% confidence interval: 3.68–34.00]. Conclusions A novel intervention can be effective as a means of reducing noninfectious complications associated with indwelling urethral catheters in hospitalized older patients. This approach will help to standardize urethral catheter care, and it highlights the fact that health care professionals can play a crucial role in preventing harm from urethral catheters.

BackgroundThe Forrest classification is widely applied to guide endoscopic hemostasis for peptic ulcer bleeding. Accordingly, practice guidelines suggest medical treatment only for ulcer with a Forrest IIc lesion because it has low rebleeding risk even without endoscopic therapy, ranging from 0 to 13%. However, the risk ranges widely and it is unclear who is at risk of rebleeding with such a lesion. This study assessed whether the Rockall score, which evaluates patients holistically, could indicate the risk of recurrent bleeding among patients with a Forrest IIc lesion at the second-look endoscopy.MethodsPatients who had peptic ulcer bleeding with Ia-IIb lesions received endoscopic hemostasis at the primary endoscopy, and they were enrolled if their Ia-IIb lesions had been fading to IIc at the second-look endoscopy after 48- to 72-h intravenous proton pump inhibitor (PPI) infusion. Primary outcomes were rebleeding during the 4th–14th day and 4th–28th day after the first bleeding episode.ResultsThe prospective cohort study enrolled 140 patients, who were divided into a Rockall scores ≥ 6 group or a Rockall scores < 6 group. The rebleeding rates in the Rockall scores ≥ 6 group and the Rockall scores < 6 group during the 4th–14th day and the 4th–28th day were 13/70 (18.6%) versus 2/70 (2.9%), p = 0.003 and 17/70 (24.3%) versus 3/70 (4.3%), p = 0.001, respectively, based on an intention-to-treat analysis and 5/62 (8.1%) versus 0/68 (0%), p = 0.023 and 6/59 (10.2%) versus 0/67 (0%), p = 0.009, respectively, based on a per-protocol analysis. The Kaplan–Meier curves showed that the Rockall scores ≥ 6 group had a significantly lower cumulative rebleeding-free proportion than the Rockall scores < 6 group (p = 0.01).ConclusionsCombined Rockall scores ≥ 6 on arrival with a Forrest IIc lesion at the second-look endoscopy can identify patients at risk of recurrent peptic ulcer bleeding following initial endoscopic and intravenous PPI treatment.Trial registration Trial registration identifier: NCT01591083

Background H. pylori CagL-Y58/E59 increase gastric cancer risk by stronger binding with integrin to faciliate type IV secretory system (T4SS). H. pylori can secrete high temperature requirement A (HtrA) to mediate E-Cadherin cleavage for gastric epithelial junction disruption, so H. pylori CagL can adhere to integrin located on basolateral side of epithelium. The study test whether H. pylori HtrA amino acid polymorphisms can increase gastric cancer risk synergistically with CagL-Y58/E59. Methods One-hundred and sixty-four H. pylori -positive patients, including 71 with non-ulcer dyspepsia (NUD), 63 with peptic ulcers (PU), and 30 with gastric cancers (GC), were enrolled to receive upper gastrointestinal endoscopy to obtain gastric biopsies for H. pylori culture and histology by the updated Sydney system. Each isolate was screened for htrA & cagL genotype by polymerase chain reaction and HtrA & CagL-Y58/E59 amino acid sequence polymorphisms by sequencing. Results The prevalence rates of htrA & cagL gene were both 100%. The HtrA amino acid sequence polymorphisms were not different between NUD and PU. The H. pylori isolates of GC had higher rates of HtrA residue 171 as leucine than those of NUD (73.3% vs. 50.7%, P  = 0.036, OR[95%CI] = 2.7[1.1–6.8]). The risk of the H. pylori -infected subjects to get gastric cancer was increased up to 15.4-fold, if the infected isolates had presence of both HtrA-L171 and CagL-Y58/E59 ( P  < 0.001). Conclusions The H. pylori isolates of gastric cancer subjects had a higher rate of HtrA-L171. H. pylori isolates with presence of both HtrA-171 & CagL-Y58/E59 can synergistically increase the risk of gastric cancer.

ObjectiveA global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC).Methods28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed.ResultsConsensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of ‘the point of no return’. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori.ConclusionEvidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

Background Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients. Methods We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n  = 60) or once-daily (Group S, n  = 60). Thereafter, they were divided into the PPI-on-demand ( n  = 32) and PPI-discontinued ( n  = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n  = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively. Results For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C ( P  = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C ( P  = 0.07, log-rank test); however, only the Rockall score was the independent factor. Conclusions An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015).

INTRODUCTION:Delayed postpolypectomy bleeding occurs in approximately 1%-2% of all patients undergoing colonoscopic polypectomy, and this rate increases to 6% in patients with large (>2 cm) colon polyps. Sucralfate can protect the mucosa and promote its healing. This study was conducted to investigate whether colonoscopic spraying of sucralfate powder on polypectomy wounds can prevent delayed postoperative bleeding.METHODS:This randomized controlled trial included patients with polyps (size ≥0.5 cm) who had undergone colonoscopic polypectomy at our hospital between May 2023 and January 2024. After polypectomy, the patients received standard treatment for immediate bleeding. Then, they were randomly allocated to either a sucralfate group (prophylactic spraying of sucralfate powder [3 g] on polypectomy wounds) or a control group. All patients were monitored for delayed bleeding within 28 days after colonoscopy.RESULTS:A total of 160 patients were divided into the sucralfate and control groups (80 per group). The baseline characteristics were balanced between the groups. The rate of delayed postpolypectomy bleeding (0% vs 6.3%, respectively; P = 0.029) and postpolypectomy overt bloody stool (2.4% vs 18.8%, respectively; P = 0.001) were lower in the sucralfate group than in the control group. The duration of freedom from delayed bleeding was longer in the sucralfate group than in the control group (P = 0.024). Multivariate Cox regression analysis confirmed the additional sucralfate spray as an independent factor against postpolypectomy overt bloody stool (relative risk, 0.03; 95% confidence interval, 0.003-0.43; P = 0.009).DISCUSSION:Colonoscopic spraying of sucralfate powder is a safe approach with potential to reduce the risk of delayed postpolypectomy bleeding. Trial registration: NCT05817656.

H. pylori CagL amino acid polymorphisms such as Y58/E59 can increase integrin α5β1 expression and gastric cancer risk. Hypochlorhydria during chronic H. pylori infection promotes gastric carcinogenesis. The study test whether CagL-Y58/E59 isolates may regulate integrin α5β1 to translocate CagA via the type IV secretory system even under adverse pH conditions, and whether the integrin α5β1 expression primed by H. pylori is a pH-dependent process involving hypochlorhydria in a vicious cycle to promote gastric carcinogenesis. The expressions of integrin α5 and β1, CagA phosphorylation, IL-8, FAK, EGFR, and AKT activation of AGS cells exposed to CagL-Y58/E59 H. pylori, isogenic mutants, and different H. pylori CagL amino acid replacement mutants under different pH values were determined. Differences in the pepsinogen I/II ratio (indirectly indicating gastric acidity) and gastric integrin α5β1 expression were compared among the 172 H. pylori-infected patients with different cancer risks. Even under adversely low pH condition, H. pylori CagL-Y58/E59 still keep active integrin β1 with stronger binding affinity, CagA translocation, IL-8, FAK, EGFR, and AKT activation than the other mutants (p<0.05). The in vitro assay revealed higher priming of integrin α5β1 by H. pylori under elevated pH as hypochlorhydria (p<0.05). In the H. pylori-infected patients, the gastric integrin α5β1 expressions were higher in those with pepsinogen I/II ratio <6 than in those without (p<0.05). H. pylori CagL-Y58/E59 prime higher integrin under adverse pH and may involve to enhance hypochlorhydria vicious cycle for gastric carcinogenesis, and thus require an early eradication.

ObjectiveTo convene a global consensus on Helicobacter pylori (H pylori) screening and eradication strategies for gastric cancer prevention, identify key knowledge gaps and outline future research directions.Methods32 experts from 12 countries developed and refined consensus statements on H pylori management, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess evidence and the Delphi method to achieve ≥80% agreement.ResultsConsensus was achieved on 28 statements. Eradication of H pylori, the primary cause of gastric cancer, reduces the risk of gastric cancer across all age groups, with the greatest risk reduction before the onset of premalignant conditions. H pylori eradication also promotes ulcer healing, prevents ulcer recurrence and reduces the risk of NSAID/aspirin related ulcers. H pylori transmission primarily occurs within families, making family based approaches promising for reducing spread and improving treatment outcomes. H pylori screening should prioritise high risk populations. 13C-urea breath test or monoclonal stool antigen tests are preferred. Validated serological testing is a feasible alternative in low prevalence settings when followed by confirmatory non-serological testing. Integrating H pylori screening into existing health programmes may optimise patient adherence and resource utilisation. Empiric eradication treatment, especially bismuth quadruple therapy, is recommended in regions with high H pylori antibiotic resistance for conventional antibiotics. Potassium competitive acid blocker based regimens are alternatives. Confirmatory testing is strongly recommended to ensure H pylori eradication. Endoscopy is suggested for H pylori infected individuals with a high risk of gastric cancer and/or alarm features. H pylori eradication does not increase the risk of reflux oesophageal adenocarcinoma. Long term disruptions to the microbiota and resistome, as well as the environmental impact of increased antibiotic use, warrant further investigation. The development of an H pylori vaccine remains an unmet need, as does the establishment of a risk stratified approach informed by advanced genetic research.Conclusion H pylori eradication is an effective prevention strategy for gastric cancer that should be offered to all infected adult individuals. Future research should prioritise determining the optimal timing for screening, evaluating long term individual and population outcomes, as well as identifying more precise risk stratification parameters.