Journal of Gastroenterology and Hepatology最新文献

Background: High antibiotic resistance and limited tetracycline accessibility severely restrict the clinical application of classic bismuth quadruple therapy (BQT), creating an urgent demand for alternative regimens.

Methods: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science up to June 3, 2025, for trials comparing Helicobacter pylori eradication rates and adverse events between semisynthetic tetracycline-containing quadruple therapies and non-semisynthetic tetracycline controls. Statistical analysis was performed using RevMan 5.4.

Results: This meta-analysis included 11 randomized controlled trials (RCTs) and two retrospective studies (3667 participants). Semisynthetic tetracycline-containing regimens yielded significantly higher Hp eradication rates (per-protocol [PP] analysis: 91.8% vs. 85.6%; OR = 1.47, 95% CI: 1.08-2.00; p = 0.01) and fewer adverse events (32% vs. 39.2%; OR = 0.73, 95% CI: 0.56-0.94; p = 0.02). Minocycline-containing regimens were associated with a higher incidence of dizziness/headache (18.9% vs. 10.5%; OR = 2.22, 95% CI: 1.74-2.84; p < 0.00001). Subgroup PP analysis showed doxycycline-containing regimens outperformed controls (82.6% vs. 71.8%; OR = 1.56, 95% CI: 1.03-2.35; p = 0.04), and a 14-day course improved eradication rates (92.3% vs. 88.5%).

Conclusions: Semisynthetic tetracycline-containing regimens exhibit favorable efficacy and safety for H. pylori eradication, representing promising alternatives to traditional tetracyclines in clinical practice.

Gastrointestinal (GI) cancers remain a leading cause of cancer-related death worldwide, and many patients with advanced disease still respond poorly to standard treatments such as surgery, chemotherapy, and radiotherapy. Immune checkpoint inhibitors have changed the management of several solid tumors, but their benefit in most GI malignancies is limited by low tumor mutational burden, microsatellite stability, and "cold" tumor immune microenvironments. This has created interest in safe adjuvant agents that can boost antitumor immunity and improve responses to immunotherapy. Ginseng, a traditional medicinal herb, contains ginsenosides and polysaccharides with documented antitumor and immunomodulatory activities. Experimental studies in liver, colorectal, gastric, and esophageal cancer models show that selected ginsenosides can promote apoptosis, modulate DNA damage responses, inhibit angiogenesis, reshape inflammatory signaling, and downregulate PD-L1 or other resistance pathways. Ginseng-derived nanoparticles and liposomal formulations further suggest a role in drug delivery and microenvironment remodeling. At the same time, clinical experience from traditional Chinese medicine indicates that ginseng-based preparations may alleviate cancer-related fatigue, support host immunity, and enhance tolerance to chemoradiotherapy. However, the pharmacological targets, optimal combinations, and predictive biomarkers for ginsenoside-based adjuvant therapy remain poorly defined. Integration of systems pharmacology, single-cell technologies, and modern clinical trial design will be essential to clarify the role of ginsenosides as partners in immunotherapy for GI cancers.

Background and aim: Intestinal injury is a common complication following burn injury, increasing patient adverse outcomes. Hk2, a key glycolysis gene, promotes lactylation by raising intracellular lactate levels. While pyroptosis is crucial for intestinal homeostasis, its mediation by Hk2-induced lactylation remains unclear. This study elucidates how Hk2 regulates postburn intestinal injury via pyroptosis modulation.

Methods: BALB/c mice were exposed to a boiling water bath to induce a mouse burn model. Mouse intestinal epithelial cells were treated with lipopolysaccharide (LPS) to simulate intestinal injury in vitro. The role of Hk2 on LPS-induced mouse intestinal epithelial cells was evaluated by detecting cell viability, lactate dehydrogenase release, levels of inflammation, and pyroptosis factors and pyroptosis rate. The underlying mechanism was determined by quantitative real-time PCR, coimmunoprecipitation, and IP. Intestinal injury was evaluated by hematoxylin and eosin staining and measurements of inflammation factors.

Results: LPS promoted glycolysis and upregulated Hk2 in both models. Increased inflammation, pyroptosis, glycolysis, and histone lactylation caused by LPS were inhibited by Hk2 knockdown but enhanced by Hk2 overexpression. Exogenous addition of lactate reversed the inhibition of Hk2 knockdown on pyroptosis and inflammation in LPS-induced mouse intestinal epithelial cells. Mechanistically, Hk2 knockdown reduced the stability of the Gsdmc2 protein by decreasing its lactylation. Moreover, Hk2 knockdown improved survival rate, pathological changes, and inflammation of the intestine and downregulated Gsdmc2 in the mouse burn model.

Conclusion: Hk2 knockdown mitigated postburn intestinal injury by inhibiting pyroptosis through decreased Gsdmc2 lactylation, providing a theoretical basis for developing clinical treatment strategies for this condition.

Background and aim: Transcolonic endoscopic appendectomy is an emerging minimally invasive alternative to traditional appendectomy, offering potential benefits such as reduced postoperative pain, faster recovery, and avoidance of external incisions. The variable anatomical location of the appendix, however, influences both the surgical approach and technical difficulty. The appendiceal stump-defined as the residual portion of the appendix after prior appendectomy-poses a unique challenge, as the main body of the appendix has already been removed. This study aimed to evaluate the feasibility, safety, and efficacy of transcolonic endoscopic appendectomy for the removal of appendiceal stump lesions.

Methods: This retrospective study included patients who underwent the procedure between December 2020 and December 2024 after prior appendectomy for appendiceal remnant lesions. The primary outcome was technical success; secondary outcomes included postoperative complications, hospital stay, and recurrence.

Results: Nine patients (mean age 60.7 years; 4 males, 5 females) were included. Lesion size averaged 1.34 cm. Complete en bloc resection was achieved in all cases. Mean operative time was 70 min, with fasting and hospitalization durations of 3.4 and 5.8 days, respectively. No postoperative complications occurred, and 3-month colonoscopy showed no residual lesions or recurrence.

Conclusions: Transcolonic endoscopic appendectomy for appendiceal stump lesions is a safe and effective minimally invasive treatment option within experienced endoscopic centers. Due to their anatomical simplicity, these lesions represent a straightforward indication, making the procedure suitable as an entry-level application for endoscopists. Further investigation and structured training programs are warranted to assess long-term outcomes and broaden the generalizability of this technique.

Background and aims: Accurate assessment of advanced fibrosis and steatosis is essential for prognostication in chronic liver disease. This study aimed to evaluate the diagnostic performance of MRI in assessing liver fibrosis and steatosis in patients undergoing liver transplantation (LT).

Methods: Patients who underwent LT between January 2019 and December 2023 with pretransplant MR elastography (MRE) and MRI-based proton density fat fraction (MRI-PDFF) examinations were included. Explanted livers were assessed for fibrosis and steatosis, with cirrhosis subclassified using the Laennec system. Diagnostic performance was evaluated using area under the receiver operating characteristic curve (AUC) analysis.

Results: Among 187 patients (median age, 57 years), 72.2% were male. Hepatitis B virus (55%) and alcoholic liver disease (21.4%) were the most common etiologies. The median Model for End-Stage Liver Disease (MELD) score was 11. MRE detected cirrhosis (F4) with an AUC of 0.92 (95% confidence interval [CI], 0.87-0.97) and severe cirrhosis (F4c) with an AUC of 0.85 (95% CI, 0.79-0.91), at threshold values of 4.76 and 6.43 kPa, respectively. MRI-PDFF identified steatosis with an AUC of 0.83 (95% CI, 0.76-0.89) at a threshold of 2.80%. Comparisons of patients stratified by the threshold values for cirrhosis and severe cirrhosis revealed significant differences in MELD scores, history of portal hypertension-related complications, liver function parameters, and intraoperative transfusion requirements (all p < 0.05).

Conclusions: MRI demonstrated high diagnostic accuracy for detecting cirrhosis and steatosis in patients with advanced fibrosis undergoing LT. MRE further stratified cirrhosis severity, suggesting clinical applicability in cirrhosis staging and risk assessment.

Background: Effective adjuvant treatments in resected or ablated hepatocellular carcinoma (HCC) were elusive over the preceding decades. Recently, immune checkpoint inhibitors (ICIs) have been investigated in the adjuvant setting, with conflicting results.

Methods: A systematic literature search was conducted in multiple databases. Studies investigating adjuvant ICIs as monotherapy or combined with tyrosine kinase inhibitors (TKIs) or anti-angiogenics compared with surveillance in resected or ablated HCC were eligible. The primary and secondary outcomes were recurrence-free survival (RFS) and overall survival (OS). The generic inverse-variance method and random-effects model were utilized.

Results: Eighteen studies with a total of 3478 patients were included. The adjuvant treatment modalities were "ICI monotherapy" and "ICI plus TKI/anti-angiogenic" in eight and 10 of the studies, respectively. RFS was significantly improved by "all ICI-based" (HR: 0.51, 95% CI: 0.44-0.60, p < 0.001), "ICI monotherapy" (HR: 0.46, 95% CI: 0.35-0.60, p < 0.001), and "ICI-TKI/anti-angiogenic" combinatory (HR: 0.55, 95% CI: 0.45-0.68, p < 0.001) adjuvant treatments, with no difference between the two (p = 0.29). Subgroup analyses showed consistent benefits regardless of curative treatment modalities of resection or ablation, presence of transarterial chemoembolization, and study design. OS was improved by ICI-based adjuvant therapies compared with surveillance (HR: 0.51, 95% CI: 0.40-0.65, p < 0.001).

Conclusion: Adjuvant ICIs with or without TKI/anti-angiogenics may provide survival benefits in resected or ablated HCC. Yet the results are limited by the observational nature and territoriality of the included studies. The results of global, randomized, controlled, phase III clinical trials with longer follow-up data will inform clinical practice.

Prospero id: CRD42025640036.

Background and aim: The development of novel agents with curative intent for chronic hepatitis B (CHB) has accelerated, but few candidates transition to phase III trials. We evaluated trial design features associated with registry-defined trial completion and phase transition, and synthesized end-of-treatment hepatitis B surface antigen (HBsAg) decline as an on-treatment antiviral signal.

Methods: We systematically reviewed clinical trial registries and bibliographic databases for CHB cure trials. Associations between trial design characteristics and trial performance were analyzed using Cox regression (time to registry-defined completion), logistic regression (phase I to phase II transition), and random-effects meta-analysis of end-of-treatment HBsAg decline.

Results: Larger sample size (HR = 0.819, 95% CI = 0.710-0.945) and longer treatment duration (HR = 0.897, 95% CI = 0.816-0.987) were associated with a lower likelihood of registry-defined completion in phase I trials. In phase II trials, larger sample size was associated with a lower likelihood of registry-defined completion (HR = 0.936, 95% CI = 0.879-0.997). Novel trial designs were not associated with faster completion. Among phase I trials with a definitive status, trials enrolling healthy volunteers were more often followed by phase II registration (adjusted OR = 2.82, 95% CI = 1.16-7.08). Meta-analysis showed that direct-acting antivirals were associated with marked end-of-treatment HBsAg decline (SMD = 1.28, 95% CI = 0.47-2.08).

Conclusions: Smaller and shorter early-phase trials were more likely to complete, whereas novel trial designs were not associated with faster completion. Direct-acting antivirals showed marked end-of-treatment HBsAg decline, an on-treatment signal rather than durable functional cure.

Background: Colorectal cancer (CRC) represents a major cause of cancer-related mortality worldwide. Exosomes derived from cancer-associated fibroblasts (CAFs-Exo) transfer oncogenic signals to cancer cells, promoting tumor growth, metastasis, and glutamine metabolism. However, the specific contribution of CAFs-Exo to the pathogenesis of CRC is still largely unexplored.

Methods: The conditioned medium of CAFs (CAF-CM) and CAFs-Exo were used to treat CRC cells. The effects on cell behaviors were evaluated by measuring cell viability, proliferation, migration, invasion, and sphere formation. The influence on glutamine metabolism was assessed by detecting glutamine consumption and glutamine and α-ketoglutarate production. MeRIP, RIP, RNA pull-down, and mRNA stability assays were used to assess the METTL1/SLC1A5 mRNA interaction. Animal experiments were used to evaluate the function of CAFs-Exo in vivo.

Results: CAF-CM promoted CRC cell proliferation, migration, invasion, sphere formation, and glutamine metabolism in vitro. CAF-CM increased METTL1 expression and m7G modification levels in CRC cells. Si-METTL1-CAF-CM exerted inhibitory effects on CRC cell malignant behaviors and glutamine metabolism. Mechanistically, METTL1 stabilized SLC1A5 mRNA by mediating its m7G modification. SLC1A5 overexpression reversed the inhibitory effects of si-METTL1-CAF-CM on CRC cell malignant behaviors and glutamine metabolism. Furthermore, CAFs-Exo increased METTL1 protein levels in CRC cells. Sh-METTL1-CAFs-Exo suppressed tumor growth and lung metastasis in vivo.

Conclusion: Our findings identify a novel CAFs-Exo/METTL1/SLC1A5 axis that drives CRC progression partially by reprogramming glutamine metabolism, revealing new potential therapeutic targets for CRC treatment.