OBJECTIVES:To evaluate whether combining thumb-tack needle treatment with routine nursing can safely reduce pain after gastric endoscopic submucosal dissection (ESD). METHODS:Seventy-eight patients after gastric ESD were randomized into an intervention group (n=39) and a control group (n=39), with 2 cases drop-off in the intervention group. Patients in the control group received postoperative conventional treatment. Patients in the intervention group received thumb-tack needle therapy at bilateral Zusanli (ST36) and Hegu (LI4) acupoints within 1 h after surgery in addition to conventional treatment, which lasted for 72 h. The primary outcome was the incidence of moderate-to-severe pain (visual analog scale [VAS] score ≥4) within 72 h after surgery. The secondary outcomes included pain intensity, analgesic usage rate, anxiety/depression score, numbers of gastrointestinal symptoms, surgery-related complications, and treatment-related adverse events. RESULTS:The incidence of moderate-to-severe pain was 21.6% (8/37) in the intervention group, significantly lower (absolute difference:-24.6%;OR:0.322;95% CI:0.118-0.879;P<0.05) than that in the control group (46.2% [18/39]). Compared with the control group, the intervention group showed reduced scores in the Short-Form McGill Pain Questionnaire at the 6th, 12th, and 24th hour after surgery (P<0.01), and the median VAS score decreased by 2-3 points compared to the control group(P<0.01, P<0.001). No statistical differences were observed between the two groups in analgesic usage rate, anxiety/depression score, numbers of gastrointestinal symptoms or surgery-related complications. Two patients (5.4%) removed the needles prematurely due to psychological reasons, which did not affect clinical outcomes. CONCLUSIONS:Thumb-tack needling therapy can effectively reduce the incidence of moderate-to-severe pain after gastric ESD and improve early postoperative pain symptoms, with a favorable safety profile.

BACKGROUND:Keverprazan offers a new perspective for Helicobacter pylori eradication. This study compared 14-day keverprazan-amoxicillin therapy with esomeprazole-amoxicillin therapy to explore a superior treatment strategy. METHODS:This was a prospective, open-label, multicenter, randomized controlled trial in adult patients with treatment-naive H. pylori infection. Participants were randomly assigned to receive either 14-day of KA therapy (Keverprazan 20 mg b.i.d plus amoxicillin 1 g t.i.d) or 14-day of EA therapy (Esomeprazole 40 mg b.i.d plus amoxicillin 1 g t.i.d). The primary outcome was the H. pylori eradication rate. Secondary outcomes were the incidence of adverse events and patient adherence. RESULTS:A total of 264 patients were enrolled in the study. In the intention-to-treat (ITT) analysis, the eradication rates for the 14-day KA group and the 14-day EA group were 87.9% and 80.3%, respectively (p = 0.092); in the modified intention-to-treat (mITT) analysis, the eradication rates were 92.1% and 86.2%, respectively (p = 0.135); and in the per-protocol (PP) analysis, the eradication rates were 93.5% and 88.3%, respectively (p = 0.155). Non-inferiority was confirmed between the two groups (all p < 0.001). Adverse events and patient adherence were similar between the two groups. CONCLUSION:For treatment-naive H. pylori infection, the 14-day KA therapy is non-inferior to EA therapy. Given its good tolerability, pharmacogenomic independence, and potent acid suppression, KA is a rational first-line alternative to EA in the Chinese population.

Insulin-like growth factor-1 (IGF-1) regulates gastrointestinal mucosal repair, hepatocyte function, and metabolic homeostasis, but its association with a broad spectrum of digestive diseases remains unsystematic. We analyzed 461,401 UK Biobank participants (aged 40-69 years) with baseline IGF-1 measurements (stratified into quartiles: Q1 ≤ 17.525, Q2 17.526-21.253, Q3 21.254-24.825, Q4 ≥ 24.826 nmol/L) and followed up to August 2024 (median: 66-184 months). Cox proportional hazards regression and restricted cubic spline (RCS) analyses assessed associations between IGF-1 and 27 ICD-10-classified digestive diseases. Cox proportional hazards regression models confirmed inverse associations between IGF-1 levels and 17 diseases. RCS analysis uncovered key non-linear relationships between IGF-1 levels and disease risk: excessively high IGF-1 levels were associated with an elevated risk of ventral hernia, paralytic ileus and intestinal obstruction without hernia, diverticular disease of the intestine, and haemorrhoids; inguinal hernia exhibited a non-linear positive correlation with IGF-1 levels; and IGF-1 deficiency contributed to an increased risk of 19 diseases.

BackgroundAberrant lipid profiles have been associated with several chronic diseases; however, their relationship with atrophic gastritis remains unclear. This study aimed to examine the association between serum lipid levels and the prevalence of chronic atrophic gastritis among participants from the Wuwei cohort.MethodsWe conducted a cross-sectional analysis of 5,194 participants from the Wuwei cohort, including individuals with pathologically confirmed chronic atrophic gastritis and individuals with normal gastric mucosa. Serum lipid parameters, including total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, were assessed. Odds ratios and 95% confidence intervals for prevalent chronic atrophic gastritis were estimated using binary logistic regression models.ResultsIn Model 1, elevated total cholesterol was identified as a risk factor for the development of chronic atrophic gastritis (CAG) with an odds ratio (OR) of 1.07 (95% CI = 1.01–1.14). Similarly, elevated LDL was associated with an increased risk of atrophic gastritis, with an OR of 1.20 (95% CI = 1.10–1.32) compared to the group without CAG. These associations remained significant in Model 2, with odds ratios of 1.10 (95% CI = 1.03–1.17) for total cholesterol and 1.21 (95% CI = 1.10–1.34) for LDL.ConclusionIn this cross-sectional study, higher total cholesterol and LDL cholesterol levels were associated with greater odds of prevalent chronic atrophic gastritis.

Gastric cancer is one of the most common primary malignant tumors of the digestive system. Chemoresistance remains a major obstacle in the clinical management of gastric cancer, and targeting the metabolic reprogramming of tumor cells has emerged as a promising therapeutic strategy. N4-acetylcytidine (ac4C), an important post-transcriptional RNA modification, is catalyzed by the key acetyltransferase N-acetyltransferase 10 (NAT10). Through drug screening, we identified the phosphoinositide 3-kinase (PI3K) inhibitor GNE-493 as a potent suppressor of gastric cancer cell proliferation. GNE-493 markedly reduced glucose uptake and lactate production, indicating inhibition of aerobic glycolysis. Mechanistically, GNE-493 binds directly to NAT10, resulting in decreased ac4C acetylation within the coding sequence of hexokinase 2 (HK2), a critical glycolytic enzyme. This reduction impairs the stability and translation of HK2 transcripts, diminishes glycolytic flux, and consequently restrains gastric cancer progression. Furthermore, GNE-493 demonstrated strong efficacy in cisplatin-resistant gastric cancer cell lines, underscoring its potential to overcome conventional chemoresistance. By targeting the epitranscriptomic control of metabolic reprogramming, GNE-493 offers a novel therapeutic avenue for gastric cancer patients with highly active glucose metabolism.

Cholelithiasis affects 10-20% of adults globally, and while cheese consumption may influence risk, underlying biological pathways remain unclear. In this prospective cohort study of 399,467 UK Biobank participants without prior cholelithiasis, we examined cheese intake frequency (never to ≥1/day) via baseline food-frequency questionnaires and identified incident cholelithiasis through hospital records, primary care data, and self-reports. Multivariable COX regression and causal mediation analyses assessed risk associations and mediation by cholesterol subtypes. Over follow-up, 15,897 participants developed cholelithiasis. Higher cheese intake showed a dose-dependent inverse association, with daily consumers having 26.3% lower odds (adjusted OR = 0.737, 95% CI: 0.653-0.832) versus non-consumers. HDL-C significantly mediated this association (proportion mediated: 4.03-6.98%). Frequent cheese consumption was associated with significantly lower cholelithiasis risk, partially mediated by HDL-C, suggesting a potential dietary strategy for prevention, though residual confounding and mechanisms require further investigation.

PURPOSE:This study aimed to quantify the extent to which IGF-1 mediates the association between BMI and liver cancer risk, clarifying its role in adiposity-related liver carcinogenesis. METHODS:A prospective analysis was conducted using data from 432,203 UK Biobank participants, using four liver cancer definitions: ICD-10 C22 and C220, each excluding diagnoses within 24 or 60 months post-baseline. Linear regression assessed the BMI-IGF-1 relationship. Cox proportional hazards models and restricted cubic spline analyses examined associations between BMI, IGF-1, and liver cancer risk, with adjustments for covariates. Mediation analysis with 5000 bootstrap iterations evaluated IGF-1's mediating effect. RESULTS:Elevated BMI was positively correlated with liver cancer risk (multivariable HR = 1.071; p < 0.0001). This association attenuated after adjusting for IGF-1 (HR = 1.037; p < 0.0001). BMI negatively correlated with IGF-1 (multivariable β = -0.150; p < 0.0001). IGF-1 showed a non-linear relationship with liver cancer risk, with lower levels (approximately less than 18 nmol/L) linked to higher risk. IGF-1 mediated 37.76%-53.64% of the BMI-liver cancer association. CONCLUSION:IGF-1 substantially mediates the association between BMI and liver cancer risk, suggesting BMI-related IGF-1 reduction is a potential mechanistic pathway.

BACKGROUND & AIMS:Sessile serrated lesions (SSLs) are precursors to post-colonoscopy colorectal cancer but are frequently missed because of their subtle morphology. Previous studies have reported the effectiveness of narrow-band imaging (NBI) for detecting colorectal adenomas, but its value for detecting SSLs remains unclear. This study aimed to determine whether NBI reduces the SSL miss rate (SSLMR). METHODS:This multicenter, randomized tandem trial was conducted in a colorectal cancer screening population across 15 endoscopy centers. The participants were randomly assigned to NBI-first or white light imaging-first (WLI-first) colonoscopy, followed by a second examination using the alternate modality. The primary outcome was the SSLMR, and secondary outcomes included the proximal serrated polyp miss rate, adenoma miss rate, and changes in surveillance intervals. RESULTS:NBI significantly reduced the SSLMR compared with WLI (17.5% vs 43.6%; P = .003), with consistent decreasing trends in subgroups stratified by location, sex, age, and other variables. The NBI-first group also had lower miss rates for proximal serrated lesions (19.3% vs 40.7%; P < .001) and adenomas (20.1% vs 29.5%; P = .002). However, the detection rates of adenomas and SSLs did not significantly differ between the 2 groups. NBI was the only independent factor associated with a reduced SSLMR in a multivariate regression model (odds ratio, 0.24) and increased the proportion of individuals recommended for intensive surveillance (11.8% vs 6.0%; P = .003). CONCLUSIONS:NBI significantly reduces the miss rates of SSLs, proximal serrated lesions, and adenomas without reducing that of advanced SSLs. CLINICALTRIALS:gov, Number: NCT05684328).

BACKGROUND:Pump-based chromoendoscopy is recommended for the surveillance of dysplasia associated with inflammatory bowel disease. This study was designed to compare the efficacy of pump-based pan chromoendoscopy (PCE) with white-light endoscopy (WLE) for the detection of colorectal neoplasia in patients at high risk of colorectal cancer (CRC). METHOD:This randomized controlled trial prospectively recruited 366 participants who were randomly allocated in a 1:1 ratio to the WLE group and the PCE group. PRIMARY OUTCOME:adenoma detection rate (ADR); secondary outcome: mean number of adenomas per procedure (MAP), sessile serrated lesion detection rate (SDR), flat adenoma detection rate (FDR), and advanced adenoma detection rate (AADR). RESULT:The ADR was significantly higher with PCE (86/167, 51.5%) versus WLE (57/165, 34.5%; RR 1.49 [95% 1.15 to 1.93]: p = 0.002). The FDR and SDR were significantly higher in PCE than in WLE (50.3% vs. 32.1% RR 1.57 [95% 1.20 to 2.05] p = 0.001; 10.8% vs. 2.4% RR 4.45 [95% CI 1.54 to 12.86] p = 0.002). CONCLUSIONS:This study demonstrated that using a novel spraying technique with low-concentration indigo carmine during colonoscopy achieved a significantly higher detection rate for colorectal lesions. Moreover, PCE significantly increased ADR, particularly for flat adenomas and the detection rate of sessile serrated lesions. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT06596317.

AIMS:Evaluating the feasibility of cold snare polypectomy (CSP) for small-bowel polyps in patients with Peutz-Jeghers syndrome (PJS). METHODS:PJS patients aged 8-60 years were prospectively enrolled. Small-bowel polyps measuring 5-9mm of the stubby/wide pedicle or sessile type were resected using CSP. RESULTS:Forty patients with 187 target polyps were included. Median size 6 mm and mean polypectomy time 66.4±46.6s. Immediate bleeding rate was 5.9%, with bleeding polyps significantly larger (8mm vs 6mm, P < 0.001). No perforation or delayed bleeding occurred. CONCLUSION:CSP is feasible and safe for 5-9 mm small-bowel polyps in PJS patients.

BACKGROUND While numerous studies have examined the associations between dietary polyphenol subclasses (i.e. , flavonoids, phenolic acids, lignans, and stilbenes) and the risk of gastric cancer (GC), evidence regarding their relationships with gastric precancerous lesions (GPL) and their subtypes [i.e. , chronic atrophic gastritis, intestinal metaplasia (IM), and low-grade dysplasia (LGD)] remains extremely limited. AIM To investigate the associations between dietary polyphenol subclasses and both GPL subtypes and GC in a high-risk population. METHODS This cross-sectional study utilized baseline data from the Wuwei Cohort. The intakes of dietary polyphenol subclasses were estimated using a food frequency questionnaire and the Phenol-Explorer database. Gastric diseases were diagnosed via endoscopic screening followed by pathological confirmation and further classified into three distinct groups: Normal control group, GPL group, and GC group. Logistic regression model and restricted cubic spline (RCS) analyses were employed to assess the associations between dietary polyphenol subclasses and the risks of GPL and GC. RESULTS Higher stilbenes intake was associated with lower GPL risk [odds ratio (OR) T3 vs T1 = 0.78, 95% confidence interval (CI): 0.67-0.89]. For specific lesions, strong inverse associations were observed in IM and phenolic acids (ORT3 vs T1 = 0.75, 95%CI: 0.62-0.91), lignans (ORT3 vs T1 = 0.80, 95%CI: 0.66-0.96), and stilbenes (ORT3 vs T1 = 0.58, 95%CI: 0.48-0.69). Flavonoids intake was associated with an increased risk of IM (ORperLog2 = 1.13, 95%CI: 1.02-1.25). RCS analyses revealed a reverse U -shaped relationship between flavonoids and LGD risk (P = 0.022). Regarding GC risk, an inverse association for stilbenes (ORT3 vs T1 = 0.59, 95%CI: 0.42-0.84; ORperLog2 = 0.92, 95%CI: 0.86-0.97) was observed, and a positive association for flavonoids (ORperLog2 = 1.25, 95%CI: 1.02-1.55). However, these associations were attenuated and became non-significant after comprehensive covariate adjustment. CONCLUSION Specific dietary polyphenol subclasses, including stilbenes, lignans, and phenolic acids, are associated with reduced risks of GPL, particularly IM. Flavonoids intake may be associated with increased risks of GPL and GC.

The colorectal cancer (CRC) tumor microenvironment contains diverse myeloid populations that critically regulate antitumor immunity and therapeutic response. Tumor-associated macrophages are key regulators of macrophage–T-cell crosstalk within the CRC microenvironment. This study aimed to investigate the antitumor effects of Ethyl caffeate (EC) and determine whether EC modulates macrophage-associated immune remodeling in CRC. Public single-cell RNA sequencing data from CRC tissues were analyzed to characterize myeloid infiltration, macrophage heterogeneity, Cell-cell communication, pseudotime trajectories, and macrophage-associated prognostic signatures. RAW264.7 cells and bone marrow-derived macrophages (BMDMs) were used to evaluate the effects of EC on macrophage viability and polarization in vitro. An immunogenic syngeneic MC38 CRC model was established in C57BL/6 mice to assess the antitumor activity of EC. Flow cytometry was used to quantify tumor infiltrating macrophages, CD86⁺ M1-like macrophages, CD8⁺ T cells, Granzyme B expression, and PD-1 expression. Clodronate liposome-mediated macrophage depletion was performed to determine whether the antitumor effect of EC was macrophage dependent. Single-cell analysis revealed extensive myeloid infiltration and marked TAM heterogeneity in CRC. State-specific analyses identified CXCL9/CXCL10 IFN-responsive TAMs as a transitional immune activating population closely associated with CXCL10-CD8+ T-cell immune signatures. Macrophage-derived gene signatures were associated with overall survival in the TCGA-COAD/READ cohort. EC showed limited cytotoxicity at 30 and 60 µM and promoted macrophage polarization toward an M1-like antitumor phenotype in RAW264.7 cells and BMDMs. In the immunogenic MC38 syngeneic CRC model, EC treatment significantly suppressed tumor growth, reducing tumor volume by 31.3

BACKGROUND:Endoscopic submucosal dissection (ESD) is limited by unstable visualization, insufficient traction, and the ergonomic burden of manual endoscope manipulation, particularly in the colorectum. METHODS:We developed EndoDreams, a flexible robotic ESD assistant integrating master-slave control for both dual-arm instrumentation and endoscope guidance (insertion, withdrawal, and rotation). Master-slave responsiveness was quantified in benchtop latency and repeatability tests. In vivo feasibility was evaluated in a porcine, lesion-level randomized study (n = 24; 12 gastric, 12 colorectal), with each lesion resected under robotic assistance using standardized ESD protocols. RESULTS:Bench testing showed minimal master-slave latency (within 300 ms). In vivo, with comparable lesion sizes (approximately 2.3 cm2), EndoDreams significantly increased dissection efficiency, with shorter dissection time and higher standardized dissection speed, which improved submucosal exposure in both gastric lesions and colorectal lesions. EndoDreams. Safety outcomes suggested a potential benefit for EndoDreams platform, particularly in the colorectal lesions (lower muscular injury and perforation), and in which operator workload (NASA-TLX) was reduced as well. CONCLUSIONS:The EndoDreams system addresses major limitations in conventional ESD by enabling endoscope delivery and precise, dual-arm tissue handling under a master-slave control framework. The combined benchtop and in vivo validations confirm its feasibility and clinical safety.

Circadian Syndrome (CircS), a cluster encompassing metabolic dysregulation, short sleep duration, and depression, has been implicated in various chronic diseases. Gastroesophageal reflux disease (GERD) is a highly prevalent digestive disorder; however, its prospective association with CircS remains unclear. This prospective cohort study utilized data from the UK Biobank, including 330,925 participants free of GERD at baseline. CircS was defined as meeting at least four of seven components. The primary outcome was incident GERD, identified through the first recorded diagnosis code from linked hospital, primary care, death registry, and self-report data. Cox proportional hazards models were used to estimate hazard ratios with sequential adjustments for demographics, socioeconomic status, lifestyle factors, and medication use. Over a median follow-up of 13.05 years, 28,554 incident GERD cases were documented. In the fully adjusted model, CircS was associated with a significantly increased risk of GERD (HR = 1.20; 95

Environmental factors play an important role in the natural history of Inflammatory bowel disease (IBD). As a key modifiable environmental factor, diet profoundly influences gut microbiota, mucosal barrier integrity, and host immunity, making dietary strategies an attractive target for IBD prevention and management. Nevertheless, the potential of microbiota-supportive dietary strategies for reducing disease incidence remains unclear. Furthermore, the proteomic signatures linking such a dietary pattern to IBD risk require further exploration. We examined the association between adherence to a microbiota-supportive dietary pattern, quantified using the Dietary Index for Gut Microbiota (DI-GM), and incident IBD in a prospective cohort (n = 208,143). High-throughput plasma proteomic data from a subset (n = 21,919) were further integrated to identify diet-associated circulating proteins, followed by exploratory mediation analysis to investigate candidate proteomic signatures underlying the observed association. Over a mean follow-up of 10.77 years, higher adherence to the microbiota-supportive dietary pattern was associated with a 16

Gastric cancer (GC) is a lethal gastrointestinal malignancy regulated by genetic alterations and tumour microenvironment (TME) remodelling. Gut microbiota metabolites can regulate tumour progression through the microbiota–metabolite–immune axis. However, the relationship among GC-associated gut microbiota dysbiosis, succinate accumulation, and macrophage-related immune features remains unclear. This study aimed to investigate whether GC-associated gut microbiota dysbiosis is linked to succinate accumulation and to elucidate the role of succinate in tumour progression and immune microenvironment remodelling. We screened for GC-related and succinate-related microbes using the Peryton and GutMGene databases. Faecal 16S rRNA sequencing and untargeted metabolomics were performed on tumour-bearing and control mice. Network-based target analysis was used to identify potential succinate-related signalling pathways in GC. The effects of succinate on GC cell proliferation, colony formation, migration/invasion, apoptosis, and tumour growth were evaluated using in vitro experiments and a subcutaneous tumour-bearing model. Public single-cell RNA sequencing (scRNA-seq) data were analysed to characterise the GC immune microenvironment, macrophage subset distribution, and CXC chemokine receptor 4 (CXCR4) expression. Bone marrow-derived macrophages (BMDMs) were used to verify the regulatory effects of succinate on CXCR4 expression. GC was associated with significant gut microbiota remodelling and increased faecal succinate levels. Succinate promotes GC cell proliferation, colony formation, migration/invasion, cell survival, and in vivo tumour growth. Multiplex cytokine and chemokine assays revealed upregulated CXCL12 and downregulated CXCL10 levels in succinate-treated tumour tissues. Network analysis revealed that succinate-related targets were enriched in metabolic reprogramming, hypoxic responses, inflammatory immune regulation, and hypoxia-inducible factor-1 and peroxisome proliferator-activated receptor signalling pathways. scRNA-seq analysis indicated enhanced immune-stromal infiltration, intensified intercellular communication, expansion of SPP1⁺ macrophages, and CXCR4-high features in macrophages within GC tissues. In vitro experiments confirmed that succinate upregulated CXCR4 mRNA expression in BMDMs. These findings suggest that GC-bearing status is associated with gut microbiota dysbiosis and faecal succinate accumulation, and that succinate may contribute to malignant phenotypes and CXCL12/CXCR4-related macrophage features in vitro and in a subcutaneous tumour model. However, the current data do not directly demonstrate that microbiota-derived succinate reaches the native gastric tumour microenvironment or that CXCL12/CXCR4-dependent macrophage remodelling is required for tumour growth. Further blocking, rescue, and orthotopic or spontaneous gastric cancer model studies are needed to validate this candidate mechanism in the native gastric tumour microenvironment.