Bile acids (BAs) have evolved from their classical role in lipid digestion to become central signaling molecules that integrate host metabolism, gut microbiota, and immune function. This review examines how diverse BAs regulate both innate and adaptive immunity through specific receptors—including farnesoid X receptor, Takeda G-protein-coupled receptor 5, vitamin D receptor, and retinoid orphan receptors—modulating the activity of macrophages, dendritic cells, T cells, natural killer cells, and natural killer T cells. Tissue−specific BA signaling influences immune homeostasis in the intestine, liver, central nervous system, and tumor microenvironment. Furthermore, we discuss the pathogenic role of dysregulated BA signaling in inflammatory, autoimmune, metabolic, and malignant diseases, and evaluate emerging therapeutic strategies that target BA pathways via synthetic ligands, engineered microbes, and dietary modulation. Leveraging BA-immune crosstalk to advance research on precision immunotherapy and microbiome-based interventions is a promising area of research.

Postoperative esophageal stricture remains a significant challenge following endoscopic submucosal dissection (ESD), with limited effective prophylactic options in clinic. Here, we report the development of an injectable and tissue-adhesive hydrogel drug delivery system composed of quaternary ammonium chitosan and polyethylene glycol (QCS-PEG), which was loaded with triamcinolone acetonide (QCS-PEG@TA), designed to mitigate post-ESD strictures. In vitro assays demonstrated that the hydrogel formulation modulated macrophage polarization and inhibited fibroblast migration. In an ESD-induced porcine esophageal stricture model, treatment with drug-encapsulated hydrogel efficiently suppressed esophageal stricture and promoted tissue repair, which were superior over drug or hydrogel alone. Histological and immunohistochemical analyses revealed that the administration of hydrogel formulation reduced fibrosis and inflammatory cell infiltration in esophageal tissues. These findings suggest that QCS-PEG@TA hydrogel provides mechanical support, inflammation-modulatory and pro-healing effects that collectively prevent stricture formation, offering a clinically translatable approach to improve therapeutic outcomes after ESD.

ERPD serves as the first-line endoscopic interventional therapy for pediatric chronic pancreatitis (CP). However, pediatric-specific risk factors for post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) and the optimal stent exchange intervals remain poorly defined. In this single-center retrospective study, pediatric CP patients (≤ 14 years) undergoing ERPD procedures (2015–2024) were enrolled. PEP was diagnosed per ESGE 2020 criteria (new/worsened abdominal pain + amylase/lipase > 3×ULN). Univariate and multivariate logistic regression identified PEP risk factors. Stent exchange intervals (standard interval vs. long interval) were compared for symptoms and acute pancreatitis occurrence. A cohort of 51 pediatric CP patients underwent 131 successful ERPD procedures. PEP occurred in 23 procedures (17.6

OBJECTIVES:Diagnosis of undifferentiated-type-predominant mixed-type early gastric cancer (UM-EGC) remains challenging due to its complex histological features and overlapping characteristics with other gastric cancer types. We aimed to develop a novel nomogram based on clinicopathological and endoscopic features and validate its performance in predicting UM-EGC prior to endoscopic treatment. METHODS:In this retrospective single-center study, 808 patients with early gastric cancer (EGC) who underwent curative endoscopic submucosal dissection were included. Among them, 493 were assigned to the training cohort and 84 to the external validation cohort. Clinicopathological characteristics and endoscopic features were compared between differentiated EGC and UM-EGC using logistic regression analysis. A predictive nomogram was constructed and evaluated. RESULTS:Multivariable regression analysis identified open-type atrophic gastritis (O1-O3) (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.08-0.82), IIb (OR 9.72, 95% CI 3.01-31.35), IIc (OR 7.75, 95% CI 2.81-21.39), discolored lesion (OR 4.12, 95% CI 1.57-10.80), horizontal location at the greater curvature (OR 2.98, 95% CI 1.15-7.75) or anterior wall (OR 2.91, 95% CI 1.26-6.74), and previous H. pylori eradication (OR 0.23, 95% CI 0.09-0.55) as independently associated with UM-EGC. UM-EGC was also more susceptible to metachronous cancer (OR 5.50, 95% CI 1.30-23.21). The nomogram demonstrated good discriminative ability with an area under the receiver operating characteristic curve of 0.83 (95% CI 0.77-0.87) in the training cohort and 0.82 (95% CI 0.69-0.98) in the external validation cohort. CONCLUSION:This nomogram comprising clinicopathological and endoscopic features may assist in the preoperative prediction of UM-EGC risk. TRIAL REGISTRATION:The clinical trial registration number for patient source in this study is ChiCTR1800017117.

ABSTRACT Aims Esophagogastric variceal bleeding (EGVB) is a life‐threatening complication associated with cirrhosis and portal hypertension. Although endoscopic treatment is central to EGVB management, evidence of its effectiveness in acute‐on‐chronic liver failure (ACLF) remains limited because of severe coagulation and multi‐organ dysfunction. This study aims to evaluate the efficacy of endoscopic treatment in ACLF patients with EGVB and identify prognostic factors associated with 6‐week rebleeding and mortality. Methods In this single‐center retrospective cohort study, we analyzed 106 patients with ACLF experiencing an EGVB episode between January 1, 2021, and June 30, 2024. Patients were categorized into endoscopic and non‐endoscopic treatment groups. Endoscopic treatment was performed within 12 to 24 h after admission once hemodynamic stability was achieved. The primary outcomes were 6‐week rebleeding rate and 6‐week all‐cause mortality, and the secondary outcome was bleeding‐related mortality. Multivariable logistic regression was used to identify risk factors for early rebleeding (72 h to 6 weeks), 6‐week mortality, and hemorrhage‐related death. Results Early rebleeding occurred in 36.8% (39/106) of patients. Moderate‐to‐severe ascites independently predicted early rebleeding (odds ratio [OR] = 3.379, 95% confidence interval [CI], 1.376–8.300, p = 0.008). By contrast, endoscopic treatment was a protective factor (OR = 0.266, 95% CI, 0.108–0.657, p = 0.004). The early rebleeding rate was significantly lower in the endoscopic group (26.8%, 19/71) compared to the non‐endoscopic group (57.1%, 20/35; p = 0.002). The 6‐week mortality was 46.2% (49/106) and was associated with moderate‐to‐severe ascites (OR = 2.587, 95% CI, 1.043–6.418, p = 0.040) and elevated total bilirubin level (OR = 1.004, 95% CI, 1.001–1.008, p = 0.012). First bleeding was a protective factor (OR = 0.304, 95% CI, 0.120–0.772, p = 0.012). Endoscopic treatment did not significantly affect overall survival (p = 0.734) but reduced hemorrhage‐related mortality (OR = 0.186, 95% CI, 0.040–0.857, p = 0.031). Among the 49 deaths, 20 were attributed to gastrointestinal hemorrhage and 29 to other causes, primarily severe infections (n = 12), hepatic encephalopathy (n = 7), and renal failure (n = 7). Portal vein thrombosis (PVT) was independently associated with bleeding‐related death regardless of whether endoscopic treatment was performed (OR = 8.262, 95% CI, 1.514–45.092, p = 0.015). Conclusion In ACLF patients with EGVB, moderate‐to‐severe ascites was the key predictor of early rebleeding and 6‐week mortality. Endoscopic therapy reduced early rebleeding and hemorrhage‐related death but did not improve overall survival; higher total bilirubin levels, prior bleeding, and PVT may further identify high‐risk patients.

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.

With over 968,000 new cases and approximately 660,000 deaths reported in 2022, gastric cancer represents a global health burden. Despite rising evidence from animal and organoid models identifying spasmolytic polypeptide-expressing metaplasia as a critical precancerous lesion, the mechanisms governing its initiation and progression remain incompletely understood. This review situates spasmolytic polypeptide-expressing metaplasia within the classical Correa cascade and synthesizes current literature by categorizing the underlying mechanisms into six distinct domains: paligenosis, intracellular redox homeostasis, oncogenic pathways, inflammatory responses, parietal cell lineage, and cancer-associated fibroblasts. Furthermore, this article comprehensively summarizes in vivo/vitro and human models of spasmolytic polypeptide-expressing metaplasia, aiming to provide a practical framework for future investigations and, ultimately, to offer novel perspectives on the prevention, diagnosis, and treatment of gastric cancer.

Objective: Autoimmune metaplastic atrophic gastritis (AMAG) is a chronic inflammatory disease characterized by autoimmune destruction of parietal cells, causing profound gastric body and fundus atrophy. AMAG is frequently overlooked or misdiagnosed in clinical practice. This study aimed to identify optimal cut-off values for serum pepsinogens (PGs) as a non-invasive diagnostic tool for AMAG in a retrospective cohort. Methods: We retrospectively analyzed the clinical and laboratory data of 520 AMAG patients from our center and compared them with those of 223 control patients who underwent serum PG testing and esophagogastroduodenoscopy (EGD) for various indications during the same period. Results: The AMAG cohort demonstrated a marked female predominance compared with controls (74.6% vs. 45.2%, p G 0.001), and 23.1% of patients were asymptomatic at diagnosis. Serological profiling showed that anti-parietal cell antibody was positive in 65.9% (309/469) of tested individuals, while anti-intrinsic factor antibody was detected in 39.1% (61/156). Gastric neuroendocrine tumors (NETs) were the most frequent neoplastic finding in AMAG (105 patients, 20.2%). Fasting gastrin-17 levels were significantly elevated in AMAG patients alongside markedly decreased pepsinogen I (PG I) and PG I/II ratio compared with controls (all p G 0.001). Receiver operating characteristic analysis identified PG I G 22.45 ng/mL (AUC: 0.964, 95% CI: 0.950-0.978; sensitivity: 88.9%, specificity: 96.0%) and PG I/II ratio G2.25 (AUC: 0.957, 95% CI: 0.941-0.974; sensitivity: 89.6%, specificity: 95.1%) as optimal cut-offs for distinguishing AMAG from controls. The combined use of PG I G 22.45 ng/mL and PG I/II ratio G2.25 achieved a specificity of 97.3% (95% CI: 94.2%-99.0%). Conclusions: Serum PG I and the PG I/II ratio demonstrate good diagnostic performance for AMAG, with high specificity in particular. These biomarkers may serve as a useful non-invasive screening tool for AMAG.

In Helicobacter pylori (H. pylori) associated gastritis, fibroblasts are recruited to inflammatory sites and secrete multiple pro-inflammatory cytokines, but the underlying mechanism remains unclear. Here, immunohistochemical staining revealed that ASPN expression was significantly upregulated in fibroblasts from H. pylori positive gastritis tissues, whereas its level remained unchanged in fibroblasts directly infected with H. pylori. Co-culture assays demonstrated that exosomes released from H. pylori infected epithelial cells induced the upregulation of ASPN and its downstream cytokines (IL-4, IL-6, and TGF-β) in fibroblasts. MicroRNA sequencing and correlation analyses identified miR-143-5p as an exosomal miRNA enriched after H. pylori infection that potentially regulates ASPN. Immunofluorescence confirmed that exosomes derived from epithelial cells carrying miR-143-5p were internalized by fibroblasts. Further immunofluorescence and immunohistochemical analyses showed nuclear accumulation of miR-143-5p in fibroblasts in both the H. pylori infected epithelial cell co-culture system and H. pylori positive gastritis tissues. Mechanistic studies demonstrated that miR-143-5p functions as a nuclear activating microRNA (NamiRNA-143-5p), binding to the super-enhancer region of ASPN, increasing H3K27ac enrichment, and promoting its transcription. In vivo, antagomir-143-5p reduced H. pylori induced ASPN and cytokine overexpression, thereby alleviating gastric inflammation. Thus, we conclude that exosomal NamiRNA-143-5p from H. pylori infected epithelial cells upregulate pro-inflammatory cytokines in fibroblasts by activating ASPN expression through a super-enhancer-dependent pathway, thereby positioning this axis as a potential therapeutic target for H. pylori associated gastric disease.

Objective:Autoimmune metaplastic atrophic gastritis (AMAG) is a chronic inflammatory disease characterized by autoimmune destruction of parietal cells, causing profound gastric body and fundus atrophy. AMAG is frequently overlooked or misdiagnosed in clinical practice. This study aimed to identify optimal cut-off values for serum pepsinogens (PGs) as a non-invasive diagnostic tool for AMAG in a retrospective cohort. Methods:We retrospectively analyzed the clinical and laboratory data of 520 AMAG patients from our center and compared them with those of 223 control patients who underwent serum PG testing and esophagogastroduodenoscopy (EGD) for various indications during the same period. Results:The AMAG cohort demonstrated a marked female predominance compared with controls (74.6% vs. 45.2%, p < 0.001), and 23.1% of patients were asymptomatic at diagnosis. Serological profiling showed that anti-parietal cell antibody was positive in 65.9% (309/469) of tested individuals, while anti-intrinsic factor antibody was detected in 39.1% (61/156). Gastric neuroendocrine tumors (NETs) were the most frequent neoplastic finding in AMAG (105 patients, 20.2%). Fasting gastrin-17 levels were significantly elevated in AMAG patients alongside markedly decreased pepsinogen I (PG I) and PG I/II ratio compared with controls (all p < 0.001). Receiver operating characteristic analysis identified PG I < 22.45 ng/mL (AUC: 0.964, 95% CI: 0.950-0.978; sensitivity: 88.9%, specificity: 96.0%) and PG I/II ratio <2.25 (AUC: 0.957, 95% CI: 0.941-0.974; sensitivity: 89.6%, specificity: 95.1%) as optimal cut-offs for distinguishing AMAG from controls. The combined use of PG I < 22.45 ng/mL and PG I/II ratio <2.25 achieved a specificity of 97.3% (95% CI: 94.2%-99.0%). Conclusions:Serum PG I and the PG I/II ratio demonstrate good diagnostic performance for AMAG, with high specificity in particular. These biomarkers may serve as a useful non-invasive screening tool for AMAG.

BACKGROUND:This is a multicenter, randomized, double-blind, placebo-controlled interventional clinical study to evaluate the efficacy and safety of pronase in improving visibility in colonoscopy and to evaluate whether pronase can increase the detection rate of intestinal lesions and the colonoscopist's satisfaction. METHODS:From June 2023 to December 2023, a total of 1942 patients undergoing air insufflation colonoscopy in 10 hospitals (The First Medical Center, Chinese PLA General Hospital, et al ) were selected as the study subjects. They were randomly divided into two groups: (1) the experimental group ( n = 969) was given pronase for flushing in colonoscopy; and (2) the control group ( n = 973) was given physiological saline for flushing in colonoscopy. The improvement of the visibility at the target site (region of interest) in colonoscopy was evaluated in two groups to verify the efficacy of pronase in improving visibility in colonoscopy. The safety of pronase for flushing in colonoscopy was evaluated by comparing the incidence of adverse events between the two groups. RESULTS:After the use of pronase in colonoscopy, the patient's vital signs remained stable, without serious adverse reactions. The improvement rate of visibility in the pronase group was significantly higher than that in the physiological saline group (97.21% [942/969] vs. 86.74% [844/973], P <0.0001), and the subgroup analysis (Boston Bowel Preparation Scale ≥6 points) showed similar results to the overall ones. The physician's satisfaction score in the pronase group was significantly increased. There was no statistically significant difference in the detection rates of adenoma, colorectal cancer, minimal lesions, non-polypoid colorectal lesions, polyps, and precancerous lesions between the two groups. CONCLUSIONS:Pronase can improve the visibility in colonoscopy and help physicians observe the lesions better. Pronase demonstrates good safety in colonoscopy, with no significant difference compared to physiological saline. REGISTRATION:Chinese Clinical Trial Registry (ChiCTR2300071702).

Ulcerative colitis (UC) is an inflammatory disease characterized by colonic epithelial damage. With prolonged disease duration, the risk of malignant transformation increases significantly. However, the mechanisms driving the progression from chronic inflammation to tumorigenesis remain incompletely understood. This study aimed to identify a set of genes that may contribute to the transition from healthy controls (HC) to UC and ultimately to colitis-associated colorectal cancer (CAC). We conducted bioinformatic analysis of four Gene Expression Omnibus (GEO) datasets to identify genes involved in the transitions from HC to UC and from UC to CAC. Functional enrichment and immune infiltration analyses were performed. Immunohistochemistry (IHC) validated the expression of key genes in UC patients. In vitro experiments assessed the effect of IFN-γ and TNF-α stimulation on PDL1 expression in neutrophils. Seven key genes—S100A8, IL33, MGP, MMP3, CFI, CLU, and CLEC4E—were upregulated during HC to UC and UC to CAC transitions. These genes were linked to neutrophils and pathways like Interferon (IFN)-γ, Tumor Necrosis Factor (TNF)-α and oxidative phosphorylation. Immunohistochemistry in mice confirmed expression levels, with five genes showing statistical significance. Additionally, IFN-γ and TNF-α stimulation significantly increased Programmed Death-Ligand 1 (PD-L1) expression in neutrophils. We identified seven genes that are persistently upregulated during the progression from HC to UC and CAC. These genes influence neutrophils and inflammatory/tumorigenic pathways. The upregulation of PD-L1 in neutrophils suggests that neutrophil-mediated immune suppression may contribute to CAC progression, supporting their potential as molecular markers and therapeutic targets for early intervention in UC-related cancer.

Cholangiocarcinoma (CCA) has shown increasing incidence in recent years. In this case, a 69-year-old male patient with a history of cholecystectomy due to gallbladder carcinoma underwent Magnetic Resonance Cholangiopancreatography (MRCP), which revealed thickening and narrowing of the hilar bile duct wall. The patient underwent endoscopic retrograde cholangiopancreatography (ERCP). Three biopsy samples were obtained via standard White Light Imaging cholangioscopy. Histopathological analysis indicated no evidence of malignancy. Two weeks later, a follow-up ERCP guided by Selective Spectral Imaging (SSI) cholangioscopy was performed. The lesion in the common bile duct was re-evaluated, and one biopsy sample was collected guided by SSI cholangioscopy. Histopathology revealed adenocarcinoma. This case demonstrates the limitations of conventional ERCP with cholangioscopy in accurately targeting lesions during biopsy. In contrast, SSI cholangioscopy facilitated identification of potentially abnormal areas for higher yield sampling. Additional prospective studies are needed to further evaluate the performance of SSI technology in the diagnosis of cholangiocarcinoma.

ABSTRACT Background Systemic inflammation is associated with cancer prognosis, but commonly used inflammatory indices show limited discrimination across heterogeneous malignancies. We developed and validated a novel inflammatory burden index, ALNCR, and tested whether integrating ALNCR with TNM stage improves overall survival (OS) prediction. Methods We analysed 6374 adults with cancer from the multicentre INSCOC cohort (2013–2021), randomly split into a training cohort (n = 4464) and internal validation cohort (n = 1910), and an external validation cohort from Fujian Cancer Hospital (n = 759). Female proportions were 39.0%, 41.2% and 32.0%, and median ages were 60, 60 and 58 years, respectively; Stage IV disease accounted for 45.4%, 45.8% and 64.8%. ALNCR was defined as (albumin × lymphocyte) / (neutrophil × C‐reactive protein). Discrimination was assessed using C‐index and time‐dependent AUC, with comparisons to NLR, PLR, CAR, SII and PNI. A combined model (ALNCR.TNM) used ALNCR (cutoff 3.21) and TNM stage (I/II vs. III/IV); incremental value was quantified by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results ALNCR showed the highest discrimination for OS among evaluated indices (C‐index 0.645 [95% CI 0.631–0.658] in training; 0.666 [0.645–0.686] in internal validation; and 0.657 [0.624–0.690] in external validation). High ALNCR (≥ 3.21) was associated with longer OS than low ALNCR (median OS not reached vs. 22.3 months; log‐rank p < 0.001). After multivariable adjustment, high ALNCR remained associated with lower mortality (HR 0.56 [0.51–0.61], 0.50 [0.43–0.58] and 0.53 [0.42–0.67] across the three cohorts; all p < 0.001). Adding ALNCR to TNM improved prediction over TNM alone (ΔC‐index +0.021; NRI 0.067, p = 0.010; IDI 0.004, p < 0.001) and stratified patients into four risk groups (p < 0.0001), with consistent associations across major cancer types and clinical strata. Conclusions ALNCR is a simple inflammation‐based prognostic index that outperforms conventional inflammatory markers for OS prediction. Integrating ALNCR with TNM stage improves risk stratification and prognostic accuracy, supporting clinical implementation via a nomogram and web‐based calculator.

When polyps are detected during colonoscopy, endoscopists describe and record their characteristics based on endoscopic images, a process that is time-consuming and prone to error. Automated report generation has emerged as a promising approach to address this challenge. In this study, we propose SAM-ColonPolypGen, an automated model for colon polyp report generation that combines the Segment Anything Model (SAM) with a generative language model. Specifically, SAM-ColonPolypGen first extracts segmentation masks from endoscopic images using the SAM image encoder. These segmentation masks provide semantic information relevant to colon polyp description. Then the extracted masks are concatenated with textual prompts and provided as input to the generative language model to generate the corresponding colon polyp report. To further enhance the accuracy of our proposed model in describing colon polyp size and morphology, and to improve the professionalism of the generated reports, we integrate Reinforcement Learning (RL) and Prompt Chaining (PC) techniques. The entire framework was trained in an end-to-end manner. Comprehensive ablation studies and comparative experiments were conducted to evaluate the performance of the proposed SAM-ColonPolypGen model. Model assessment was performed using standard metrics, including METEOR, ROUGE, and BLEU, along with polyp size accuracy and polyp morphology accuracy. SAM-ColonPolypGen achieved the following results: METEOR 0.3961, ROUGE 0.6645, BLEU-1 0.5578, BLEU-2 0.4763, BLEU-3 0.4038, BLEU-4 0.3532, and polyp size accuracy of 62.00%, polyp morphology accuracy of 39.33%. These results indicate that SAM-ColonPolypGen outperforms baseline models, particularly in accurately describing polyp size, while also producing colon polyp reports that are more consistent and descriptive.