Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication following ERCP, and its prevention remains a major concern for biliopancreatic endoscopists. This umbrella review aims to assess existing meta-analytic evidence on the effectiveness of pharmacological interventions (PIs) and procedural technical modifications (PTMs) in reducing the incidence and severity of PEP. We searched multiple databases to identify meta-analyses of randomized controlled trials (RCTs) that assessed the impacts of PIs or PTMs on the incidence and severity of PEP, from database inception to September 24, 2024. Evidence credibility was classified based on pre-specified criteria as: convincing (Class I), highly suggestive (Class II), suggestive (Class III), weak (Class IV), or non-significant evidence. Furthermore, the GRADE approach was employed to assess the quality of the evidence, categorizing it into four levels: high, moderate, low, and very low. A review of 47 meta-analyses (137,391 participants; 25 on PIs, 22 on PTMs) identified five PIs with suggestive evidence for PEP prevention: indomethacin (odds ratio [OR] 0.52, 95

Aims: ERCP training should adapt to the rapid development of ERCP technology and indications. China has a large population and vast land area, but ERCP training resources are insufficient. To make effective use of scarce ERCP training resources, the Standardized Training for ERCP Procedure (STEP) program was launched as a pilot trial. We aimed to report the graduation and competence situations and analyze the predictive factors. Methods: This was a prospective multicenter study from January 2015 to May 2021 containing 2 stages: the training program stage and the graduate questionnaire survey stage. The graduation and competence rates were investigated and analyzed. Results: In the training stage, 146 trainees completed the training, 113 (77.4%) graduated. The gender ratio (men vs. women) was 6.7:1. The mean age was 40.14±4.13 years. In total, 11 trainees failed the institutional mentored training phase (IMTP), 18 failed the practice strengthen training phase (PSTP), and 4 failed the comprehensive theoretical test. In the questionnaire survey stage, the response rate was 92%, of which 76.9% (80/104) achieved competence. ERCP cases performed independently in IMTP (OR=1.129, P=0.025) and ERCP volume in training years (OR=1.018, P=0.026) were predictive factors for graduation. Job title (senior physician) (OR=78.811, P=0.018) and main practice form of PSTP (independently) (OR=17.062, P=0.031) were predictive factors for competence in available graduates. Conclusions: The STEP achieved an acceptable graduation and competence rate. We gained valuable experience in framework organization and multiple assessment checkpoints. Therefore, this standardized training model is suitable for developing countries with rapid progress in ERCP.

Autoimmune pancreatitis (AIP) is a rare immune-mediated form of chronic pancreatitis. It may affect multiple organs, and its heterogeneous clinical manifestations complicate diagnosis and management. Based on the Chinese Guidelines for the Diagnosis and Management of Autoimmune Pancreatitis (Shanghai 2012 Draft), together with the latest domestic and international guidelines and research advances, the present guideline provides 20 recommendations covering four aspects: diagnosis, treatment, follow-up, and prognosis. The aim is to improve the diagnosis and management of AIP in China and ultimately improve patient outcomes.

Pancreatic cancer has an early diagnosis rate below 5% and is largely resistant to conventional chemotherapy. Aerobic glycolysis, a metabolic hallmark, drives Epithelial-Mesenchymal Transition (EMT) to promote tumor progression and drug resistance. Hexokinase 2 (HK2) is the rate-limiting enzyme that initiates glycolysis. It is specifically overexpressed in pancreatic cancer cells and is a potential therapeutic target. To identify HK2 inhibitors, we performed structure-based virtual screening of over 70,000 compounds. The top candidate, Lomitapide Mesylate (LM), was validated through molecular docking, molecular dynamics simulations, Drug Affinity Responsive Target Stability (DARTS), and Cellular Thermal Shift Assay (CETSA), confirming direct HK2 binding. In vitro, LM inhibited HK2 activity, exerting anti-proliferative and pro-apoptotic effects. In a mouse organoid-derived xenograft model, LM monotherapy suppressed tumor growth. Importantly, LM combined with gemcitabine significantly enhanced anti-tumor efficacy, indicating potential to reverse gemcitabine resistance. Mechanistically, this synergy was linked to LM-mediated reversal of HK2-driven EMT. Thus, LM inhibits HK2 to block EMT and synergize with gemcitabine, offering a novel therapeutic strategy.

Pancreatic cancer (PC) is deadly and distinguishing it from inflammatory conditions in chronic pancreatitis (CP) patients is challenging. We aimed to develop machine learning models to predict PC in CP patients with focal pancreatic lesions. For this bicentric retrospective study, CP patients with indeterminate focal pancreatic lesions discovered through contrast-enhanced computed tomography scans were enrolled. Final diagnosis of focal pancreatic lesions was established by surgical pathology or follow-up outcomes. We used Boruta algorithm for feature screening, and conducted six machine learning models (Logistic Regression, Random Forest, eXtreme Gradient Boosting, Light Gradient Boosting Machine, K-Nearest Neighbors and Naive Bayes). The input data this study used were clinical information and laboratory data. Finally, SHAP was employed for interpretation. Receiver operating characteristic curve, area under curve (AUC), accuracy, sensitivity and specificity were used to evaluate model performance. A total of 187 participants were enrolled, and 44 patients (23.5

Microbial signatures in tumors of HCC patients with early-relapse versus non-relapse

Background and Objectives:Various lumen-apposing metal stents (LAMSs) were used for pancreatic fluid collection (PFC) drainage for many years. The structural design of LAMS needs to be improved to reduce the occurrence of adverse events. This trial assessed the efficacy and safety of a novel modified LAMS for the drainage of PFCs. Methods:This open-label, multicenter, prospective trial was done at 11 tertiary care hospitals. This study enrolled patients (18-75 years old) with confirmed diagnosis of PFC with cyst diameter no less than 6 cm. Novel LAMS (Micro-Tech Co, Ltd, Nanjing, China) was used. The primary end point was the 1-month postoperative drainage success rate. The secondary end points were technical success rate and adverse events. This study is registered with Chictr.org.cn, ChiCTR2000039955. Results:Between December 9, 2020, and December 27, 2021, 100 patients with PFC were assessed for eligibility, and 94 patients met the criteria and agreed to participate in the trial. The median size of PFC cyst was 11.23 ± 3.84 cm. The drainage success rate was 90.48% (95% CI, 83.6%-97.3%) and achieved the prespecified target value of 75% (P < 0.0001). In subgroup analysis, the clinical success rates of pancreatic pseudocyst (PPC) and walled-off necrosis (WON) were 95.45% and 85%, respectively (P = 0.143). The overall technical success rate was 98.94%. Postoperative early adverse events occurred in 57 (60.64%) of 94 patients, and late adverse events were encountered in 16 (17.02%) of 94 patients. The overall rate of serious adverse event (bleeding-related death) was 2.13% (2/94). Patients with WON had a significantly higher rate of early adverse events compared to those with PPC (77.78% vs. 44.90%, P = 0.001). Conclusions:The novel LAMS used in this trial was technically feasible, efficient, and safe for the treatment of PFCs. Comparable with WON, the usage of LAMS in PPC achieved a high drainage success rate and acceptable adverse events.

Pancreatic cancer faces the challenges of tumor progression and postoperative pancreatic fistula during the perioperative period, which severely affect patient prognosis. In this study, an injectable self-healing multifunctional hydrogel (CMCGel) was developed based on dynamic cross‑linking between manganese ions (Mn2+) and carboxymethyl chitosan loaded with chlorella extract (CE). This platform implements an integrated “Remove–Remodel–Repair” (3R) strategy for comprehensive perioperative management. CMCGel exhibits distinctive pH/laser dual-responsive behavior: In the acidic tumor microenvironment, the accelerated release of CE and Mn2+ enhances photodynamic therapy and chemodynamic therapy (CDT). This combination, activated by laser and gated by endogenous pH, achieves remarkable tumor suppression rates of 85.81

Capsule endoscopy has transformed small bowel evaluation but remains limited for gastric examination because of passive, peristalsis-dependent movement. Magnetically controlled capsule endoscopy (MCE) addresses this limitation by enabling real-time external steering of the capsule, allowing systematic visualization of the spacious gastric cavity without sedation or intubation. Since the first human application in 2010, multiple MCE platforms have been developed and validated, including handheld, magnetic resonance-based, and robotic arm systems, with the latter now representing the dominant clinical platform. Clinical trials have demonstrated that robotic arm MCE achieves diagnostic accuracy comparable with conventional esophagogastroduodenoscopy for the detection of gastric lesions while offering superior patient tolerance. In parallel, standardized examination protocols have been established, ensuring reproducible gastric preparation, complete mucosal coverage, and structured reporting. Recent technological advances, including higher resolution imaging, detachable string technology for combined esophageal and gastric examination, improved magnetic steering, and artificial intelligence-assisted image analysis, have further expanded the diagnostic capability and efficiency of MCE. Importantly, the noninvasive and well-tolerated nature of MCE supports its use in populations at increased risk from conventional endoscopy, including children, elderly patients, individuals with liver cirrhosis, and those receiving antiplatelet therapy. This review summarizes current MCE technologies, standardized clinical practice, and diagnostic performance and discusses emerging clinical roles and future challenges. MCE is evolving from a novel diagnostic tool into a practical and well-tolerated noninvasive modality for upper gastrointestinal evaluation.

BACKGROUND Previous studies have not clarified a universally acknowledged treatment approach that can eradicate small bowel hemangiomas while minimizing harm to patients. Although studies have indicated that endoscopic interventions have promising treatment effects with minimal invasiveness, no comparison of different types of endoscopic therapies has been conducted. AIM To compare the clinical efficacy, safety, and procedural outcomes of lauromacrogol injection, argon plasma coagulation (APC), and endoscopic ligation via double-balloon enteroscopy for the treatment of small bowel hemangiomas, and to identify lesion-specific optimal endoscopic strategies. METHODS Seventy-five participants were enrolled in this study. Thirteen patients received conservative treatment, 20 received lauromacrogol injection, 22 underwent APC, 18 underwent endoscopic ligation therapy, and two received hemostatic clip therapy. Key indicators and prognostic information for different treatment methods were compared between conservative-interventional and within interventional therapies. Categorical variables were compared using the chi 2 or Fisher's exact test, and continuous variables were compared using the Student's t-test or Wilcoxon rank sum test. RESULTS Compared with conservative therapy, interventional therapy was associated with a lower rebleeding rate. Compared with ligation therapy, lauromacrogol therapy was associated with less intraprocedural bleeding and showed a higher technical success rate and shorter operative duration. Compared with lauromacrogol and ligation therapies, APC was associated with a shorter procedure duration, a higher technical success rate, and less intraprocedural bleeding. CONCLUSION Our observational data suggest that lauromacrogol injection may be a more suitable option for raised small bowel hemangiomas, while APC may be preferable for flat lesions.

Univariate and Multivariate Cox Regression Analysis of Disease-free Survival in Cohort 2

Intestinal inflammation and malignancy represent two critical pathological states in the gut that severely impair patients’ quality of life. Understanding their molecular mechanisms holds significant therapeutic implications. Lactate plays a key role in cellular signaling and immune regulation. Lactylation, a modification mediated by lactate, plays a key role in epigenetic regulation. Targeting lactate metabolism and lactylation has emerged as a promising intervention strategy for intestinal diseases. This review summarizes the basic framework of the lactate metabolic system and the biological functions of lactate and lactylation, with a focus on the core mechanisms of lactylation in intestinal inflammation and malignancy. Lactylation exerts a context-dependent “paradoxical modulation” role. In intestinal inflammation, as exemplified by inflammatory bowel disease, lactylation drives macrophage phenotypic conversion, mediates gut microbiota-host interactions, regulates fibrosis progression, and modulates intestinal inflammation and tissue repair. Colorectal cancer, a major form of intestinal malignancy, is promoted by lactylation through mechanisms including immunosuppression, malignant proliferation, drug resistance, and tumor metastasis. Finally, we discuss the basis of the paradoxical modulation role of lactylation and explore the therapeutic potential of targeting lactate metabolism and lactylation as novel treatment strategies. In summary, this review highlights lactylation as a central player in intestinal diseases, providing insights into the pathomechanisms of intestinal inflammation and colorectal cancer. Lactate metabolism and lactylation hold significant potential as therapeutic targets for intestinal inflammation and malignancy, providing a promising path for precise intervention strategies in intestinal diseases.

L.johnsonii promotes the enrichment of cytotoxic-exhausted CD8+ T cells

Background:Acute pancreatitis (AP) is characterized by dysregulated pancreatic enzyme activation and pancreatic tissue injury. Orosomucoid (ORM), an acute-phase protein with immunomodulatory functions, exhibits organ-specific expression patterns, but its role in AP remains unclear. This study investigated the isoform-specific effects of ORM2 in AP pathogenesis and repair. Methods:We established cerulein-induced mouse model of AP using both wild-type and pancreas-specific ORM2 knockout mice to investigate ORM2's protective role. Primary acinar cells were used for in vitro validation. Proteomics and functional assays elucidated mechanisms. Results:In AP models, we observed opposing expression patterns of ORM, with increased levels in the liver but decreased levels in the pancreas. Genetic deletion of pancreatic ORM2 significantly worsened AP severity, while exogenous ORM2 administration provided protection against pancreatic injury. Specifically, ORM2 upregulated SPINK1 while downregulating PRSS2, leading to reduced trypsin activation. Conclusions:ORM2 protects against AP by modulating the SPINK1-PRSS2 axis to prevent premature trypsin activation and alleviate acinar cell injury. Its tissue-specific regulation suggests therapeutic potential for AP.

Flow cytometry process of human CD45+ (hCD45) cells in peripheral blood of humanized mice