Background and aims Long-term outcomes for Crohn's disease (CD) patients treated with infliximab (IFX) remain suboptimal. We developed and validated a clinical decision support tool (CDST) to predict sustained remission in CD patients treated with infliximab (IFX). Methods This multicenter observational study analyzed 746 CD patients across three cohorts. Sustained clinical remission (CREM) was defined as steroid-free Crohn's Disease Activity Index (CDAI) <150 at week 104. Using logistic regression, predictors were weighted by inverse variance. The CDST was internally validated (Cohort I, n = 113) and externally validated (Cohort II, n = 367). Results Key predictors of CREM included: prior biologic exposure (-18 points), penetrating disease (B3 phenotype, -7 points), albumin (+0.5/gL), younger age (-0.3/year), and absence of antibody to infliximab formation (ATI, +17 points). The model demonstrated strong discrimination (AUC 0.791 [95% CI 0.708-0.875]) and calibration (Brier score: 0.191). External validation AUC was 0.611 (95% CI 0.546-0.675), indicating modest generalizability. Risk stratification via CDST categorized patients into low- (<6 points), intermediate- (6-25), and high-risk (>25) groups. A cutoff of 25 points predicted 2-year CREM with 60% (95%CI 53.2%-66.5%) sensitivity and 52% (95% CI 41.2%-1.8%) specificity. Conclusions We developed and validated a CDST to identify CD patients likely to achieve sustained remission on IFX therapy. By stratifying patients into distinct risk profiles, it guides personalized therapy initiation and monitoring.

Gastrointestinal diseases impose a growing global health burden, and endoscopy is a primary tool for early diagnosis. However, routine endoscopic image interpretation still suffers from missed lesions and limited efficiency. Although AI-assisted diagnosis has shown promise, existing models often lack generalizability, adaptability, robustness, and scalability because of limited medical data, domain shift, and heterogeneous annotations. To address these challenges, we develop RATNet, a foundation model for gastrointestinal endoscopy imaging based on analogical reasoning. RATNet acquires and transfers knowledge from heterogeneous expert annotations across five gastrointestinal endoscopy datasets through a cyclic pre-training strategy. Its architecture consists of an encoder, a relevance-knowledge acquisition and transfer (RAT) module, a projector, and a multi-task head, and supports fine-tuning, linear probing, and zero-shot transfer. Evaluations show that RATNet outperforms existing foundation models, including GastroNet and GastroVision, across six scenarios: diagnosis of common gastrointestinal diseases, few-shot learning for rare diseases, zero-shot transfer to new medical sites, robustness under long-tailed disease distributions, adaptation to novel diseases, and privacy-preserving deployment via federated learning. Its advantage comes from an analogical reasoning mechanism that matches image-derived posterior knowledge to a learned prior knowledge base and transfers relative knowledge to guide diagnosis, improving generalization and resistance to bias. RATNet is open and cost-effective, supports automatic integration of heterogeneous annotations without manual label unification, and reduces data acquisition costs, making it a practical foundation for intelligent gastrointestinal diagnosis, especially in resource-limited settings.

Background: Blue rubber bleb nevus syndrome (BRBNS) is a hereditary disease characterized by venous malformation on the skin and throughout the gastrointestinal tract, which is usually considered a benign disease without elevated risk of carcinogenesis. Nevertheless, lumen narrowing caused by hemangiomas may result in repeated mucosal damage from mechanical stimuli such as solid food. Therefore, it is important to recognize the potential of malignancy as a result of such chronic inflammation due to partial obstruction. Case presentation: A 50-year-old patient presented with progressive dysphagia and fatigue. Physical examination showed bluish-violet and non-blanching blisters measuring 0.5 to 2 cm distributed over the skin. The patient has recurrent positive fecal occult blood tests 8 years ago and a low hemoglobin level 14 years ago. Chest computed tomography revealed obvious lumen wall thickening of the mid- and lower thoracic esophagus, accompanied by multiple nodular calcifications. Esophagogastroduodenoscopy and colonoscopy were performed to find multiple hemangiomas scattered throughout the GI tract, which is consistent with blue rubber bleb nevus syndrome (BRBNS). Additionally, biopsy of an ulcerated lesion in the esophageal lumen confirmed esophageal carcinoma. Subsequent positron emission tomography-computed tomography (PET-CT) and endoscopic ultrasound confirmed no metastasis. An esophagectomy was performed. At the 3-month follow-up, there was no evidence of recurrence. Conclusion: Currently, there are about 200 BRBNS cases reported, and none of these cases developed concurrent esophageal carcinoma. To our knowledge, this is the first case of BRBNS with concurrent esophageal carcinoma. Even though BRBNS is considered a benign disease, lumen narrowing caused by hemangiomas may result in repeated mucosal damage from mechanical irritation such as solid food, and physicians should be aware of the potential of malignancy due to chronic inflammation caused by partial obstruction.

BackgroundNumerous studies indicated inflammatory bowel disease (IBD) patients suffered from sleep disturbances. Although melatonin (MT) exerts positive effects on maintaining circadian rhythms and anti-inflammation, its impact on the gut microbiome and its function in mediating gut health remain largely unexplored. To evaluate the efficacy and investigate the mechanisms of MT in repairing the intestinal mucosal barrier in IBD.MethodsFecal MT and its metabolites in IBD patients were detected. A DSS-induced colitis mice model and a LPS-stimulated NCM460 cell inflammation model were used to explore the mechanism of melatonin in IBD.ResultsIBD patients had lower levels of serum MT and fecal 2-oxomelatonin. Furthermore, MT enhances intestinal antimicrobial peptides and effectively alleviates colitis. Mechanistically, MT restored the abundance of the probiotic Akkermansia and decreased the conditional pathogen Desulfovibrio. MT upregulates the SIRT1 (Sirtuin 1) and pAMPK (phosphorylated AMP-Activated Protein Kinase) in mouse colonic tissues. Whereas Ex-527 (the SIRT1 inhibitor) and Compound C (the pAMPK inhibitor) abolished the protective effects of MT in DSS mice. In LPS-stimulated cells, the inhibitor blocked the regulation of MT on proinflammatory factors, antimicrobial peptides and tight junctions. Mechanistically, MT was associated with activation of the SIRT1-LKB1-pAMPK pathway, suggesting its potential involvement in regulating the above changes.ConclusionOur findings suggest that MT may ameliorate colitis by regulating gut microbiota, modulating antimicrobial peptide secretion, and reinforcing intestinal epithelial barrier integrity potentially via activation of the SIRT1-LKB1-pAMPK axis.

Background: Chronic enteropathy associated with SLCO2A1 (CEAS) is a rare genetic disorder that is prone to misdiagnosis and characterized by significant challenges in achieving an early diagnosis. Current diagnosis relies on clinical manifestation combined with genetic sequencing. This study aimed to evaluate immunohistochemical (IHC) staining for SLCO2A1 protein deficiency as a diagnostic alternative, in addition to clinical pathological features. Method: Ten patients diagnosed with CEAS between January 2018 and August 2024 were enrolled. Clinicodemographic data, endoscopic findings, and treatment history were collected. Whole-exome sequencing identified SLCO2A1 variants. IHC staining for SLCO2A1 protein was performed from small intestine lesions and accessible GI sites. Results: Complete absence of SLCO2A1 protein expression was demonstrated by IHC in 9/10 patients, with significantly reduced expression in 1/10. This protein deficiency was consistently observed not only in the small intestine but also in the gastric antrum, duodenum, and terminal ileum. Genetic analysis revealed 7 novel SLCO2A1 variants among a total of 11 variants. A median diagnostic delay of 15 years (IQR 6-24) was observed. Ileal involvement and hypoalbuminemia (median albumin 28.02 g/L, IQR 22.1-33.0) were present in all patients. Common symptoms included abdominal pain (70%), melena (60%), and ileus (50%). Conclusions: The diagnosis of CEAS has been time-consuming and challenging. Detection of SLCO2A1 protein deficiency via IHC in either the disease-predominant small bowel or accessible non-lesional upper/lower GI mucosa demonstrates high diagnostic sensitivity for CEAS. This method could provide a practical, cost-effective alternative to genetic sequencing, particularly in resource-limited settings, and has the potential to significantly reduce diagnostic delays for this condition.

Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of immune dysregulation. Here, we presented the case of a young male diagnosed with psoriasis and Crohn's disease (CD), after multiple therapy failures, he started upadacitinib (UPA) in 2023. After induction and maintenance therapy, colonoscopy revealed suboptimal disease control. In November 2024, he was admitted to our hospital with fever and elevated liver enzymes, the final diagnosis was HSV-1-associated secondary HLH. After antiviral and hormonal treatment, the patient was discharged in stable condition. This case illustrates that HLH in such patients is rarely attributable to a single drug, rather, it results from the convergence of underlying CD, cumulative multi-agent immunosuppression, and an acute infectious trigger (HSV-1). Clinicians should maintain high vigilance for virus-associated HLH in heavily immunosuppressed IBD patients.

Alcohol-associated hepatocellular carcinoma (A-HCC) shows more aggressive progression and has a poorer prognosis than nonalcohol-associated HCC (NA-HCC), but the underlying tumor microenvironment (TME) heterogeneity remains poorly characterized. Here, we performed single-cell RNA sequencing (scRNA-seq) on tumor and adjacent normal tissues from two A-HCC patients, constructing the first single-cell transcriptomic profile of human A-HCC. This dataset was integrated with public NA-HCC scRNA-seq data to compare cellular composition, functional states, and intercellular communication. Both HCC subtypes displayed immunosuppressive TME features, which were significantly more pronounced in A-HCC. Specifically, A-HCC tumors showed greater enrichment of regulatory T cells (Tregs) with enhanced suppressive function, anti-inflammatory macrophage polarization, and more severe CD8+ T and NK cell depletion and dysfunction with reduced metabolic activity. Malignant hepatocytes in A-HCC exhibited increased copy-number variation, epithelial-mesenchymal transition (EMT), stemness, proliferation, and drug resistance associated gene signature scores. Cell-cell communication analysis further suggested A-HCC-specific upregulation of immunosuppressive signaling pathways (LTA/LTB, TGF-β, LGALS9-HAVCR2) that reinforce this pro-tumorigenic ecosystem. A Treg-derived gene signature from A-HCC was associated with worse overall survival in independent TCGA cohorts. This first comprehensive single-cell comparison uncovers a coordinated immunosuppressive and malignant ecosystem in A-HCC that may be distinct from NA-HCC, providing a mechanistic framework to understand its aggressive clinical behavior and to identify potential etiology-targeted therapeutic strategies. Despite the limited sample size, this study provides the first single-cell resource for A-HCC and lays the foundation for future large-scale validation.

BACKGROUND:Biosimilar infliximab (B-IFX) offers a lower-cost alternative to originator infliximab (O-IFX) for treating Crohn's disease (CD), but real-world data on comparative effectiveness and economic impact in China remain limited. This study assessed clinical outcomes and economic consequences of B-IFX versus O-IFX from a healthcare payer perspective. METHODS:This retrospective cohort study evaluated 473 adult CD patients initiating O-IFX (n = 345) or B-IFX (n = 128) at a tertiary care center for Chron's disease in China between October 2021 and February 2024. The clinical endpoints over 12 months included treatment failure, clinical remission, endoscopic response, and adverse events. A budget impact analysis evaluated direct healthcare costs (Chinese Yuan, CNY) and projected medical insurance fund expenditures under a reference scenario (continued O-IFX use) and a base-case scenario with increased B-IFX uptake for 2025-2027. One-way sensitivity analyses assessed model robustness. RESULTS:Rates of treatment failure, clinical remission, endoscopic response, and adverse events were comparable between O-IFX and B-IFX. Relative to the reference scenario, increased B-IFX adoption was associated with lower annual direct medical costs and reduced insurance fund expenditures, yielding estimated savings of 0.60, 1.09, and 1.75 million CNY in 2025-2027, respectively (cumulative savings: 3.44 million CNY). Sensitivity analyses identified the unit price of O-IFX as the main cost driver; B-IFX remained cost saving across all parameter ranges, with cumulative 3-year savings ranging from 2.49 to 4.39 million CNY. CONCLUSIONS:B-IFX demonstrated comparable real-world effectiveness and safety to O-IFX while generating substantial cost savings for China's medical insurance system. These findings support broader biosimilar adoption as a value-based strategy to enhance the affordability and sustainability of biologic therapy for CD.

BACKGROUND:This study aimed to develop predictive models for acute severe ulcerative colitis (ASUC) using data from East Asian (EA) patients and to validate their performance in an Australia/New Zealand (ANZ) cohort. METHODS:A retrospective international study was conducted across 23 referral hospitals in EA and ANZ, enrolling consecutive ASUC patients between January 2015 and December 2022. Logistic regression analyses were used to construct predictive models for 1-year colectomy and non-response to corticosteroid therapy (NRS). RESULTS:Overall, 826 patients with ASUC were included (411 EA and 415 ANZ). Among EA patients, independent predictors of 1-year colectomy included female sex, prior exposure to tumor necrosis factor inhibitors, and admission albumin ≤3 g/dL. Independent predictors of NRS in the EA cohort were age at diagnosis  ≤37 years, baseline steroid use, admission albumin ≤2.5 g/dL, and the presence of extraintestinal manifestations. The EA-derived scoring systems demonstrated strong predictive performance within the EA cohort (1-year colectomy: P < .0001; NRS: P = .001) but showed limited utility in the ANZ cohort (P = .106 and P = .012). In contrast, European-developed models-including the French 1-year colectomy score and the ADMIT-ASC index for NRS-accurately predicted outcomes in the ANZ cohort (P = .007 and P < .0001) but had reduced predictive capacity in the EA cohort (P = .106 and P = .026). These findings were consistent in both cohorts following propensity score matching. CONCLUSIONS:Predictive factors for ASUC differ substantially between EA and ANZ patients, highlighting the need for population-specific predictive tools.

Infliximab (IFX) for inflammatory bowel disease (IBD) treatment may increase the risk of hepatitis B virus (HBV) reactivation, particularly in areas with high HBV prevalence such as China. This study aimed to evaluate HBV reactivation/infection, liver dysfunction, vaccination efficacy and strategies in IBD patients undergoing IFX therapy. This retrospective, multicenter study included 4183 IBD patients from 15 hospitals across China, who were divided into six groups according to the HBV status. Demographic features, HBV vaccination status, reactivation/infection rates, and liver dysfunction outcomes were collected, with data collection performed from 2009 to 2022. We found that HBV reactivation rate was notably higher in HBsAg positive group than other groups (P < 0.05) despite antiviral treatment. Although only 29% of patients were immunized at IFX initiation and almost no patients got vaccinated against HBV during IFX treatment, no patients experienced HBV infection in the susceptible population group. The study underscores a critical need for rigorous HBV screening before IFX initiation. Despite antiviral prophylaxis, the importance of continuous monitoring of HBV DNA is necessary for HBsAg positive patients. HBsAg negative patients, including the susceptible population, had a very low risk of new HBV infection, thus reassuring patients and physicians of the safety of IFX in this cohort.

Perianal fistulizing Crohn’s disease (PFCD) represents a distinct, inflammation driven subtype of perianal fistula that differs fundamentally from idiopathic perianal fistula (IPF), which typically arises from cryptoglandular infection and follows a predominantly infectious and mechanical pathogenesis. PFCD is characterized by chronic inflammation, complex fistula tracts, and poor healing despite combined surgical and medical therapy. In contrast, IPF often responds well to drainage and local interventions. The biological basis underlying these divergent clinical behaviors remains poorly defined. We aim to elucidate the unique pathological features of PFCD and identify potential therapeutic targets. We enrolled 26 patients with PFCD, 26 patients with IPF, and 3 hemorrhoid patients as non-fistulous controls. Surgical specimens were collected for bulk RNA sequencing, single-cell RNA sequencing, and untargeted metabolomic analysis. Fibroblast phenotype was assessed in the CCD-18co cell line in vitro by using cell counting kit-8 (CCK-8) assays, apoptosis detection assays, and wound healing scratch assays. Single-cell RNA analyses revealed that PFCD exhibited distinct cellular composition and molecular features (Figure.1A, B). Compared to non-fistulous controls and IPF, PFCD showed a more pronounced inflammatory response and impaired tissue-reparative capacity (Figure.1C). While both PFCD and IPF displayed activation of NF-κB and TNF signaling pathways, CD-associated fistulas demonstrated stronger activation of IFN-γ and JAK/STAT signaling (Figure.1D, E). PFCD also showed decreased proportions of reparative fibroblasts and myofibroblasts (Figure.2A, B), accompanied by upregulation of pro-inflammatory genes and disruption of polyamine metabolism in these cells (Figure.2C, D). Untargeted metabolomic profiling confirmed elevated spermidine levels in PFCD (Figure.2E). In vitro, spermine and spermidine inhibited fibroblast proliferation (P < 0.05), while spermidine and putrescine suppressed the migration of CCD-18co cells (P < 0.05, Figure.2F-H), suggesting that local accumulation of polyamines may impair fibroblast-mediated tissue repair. Our study provides a comprehensive molecular and cellular landscape of PFCD, highlighting its distinct immune and stromal microenvironment compared to idiopathic perianal fistulas and non-fistulous controls. Local polyamine accumulation may contribute to defective fibroblast function and impaired tissue repair, highlighting a potential metabolic target to promote fistula healing in PFCD. Conflict of interest: Tian, Chuwen: No conflict of interest Wu, Lexi: No conflict of interest Liu, Wei: No conflict of interest Huang, Lingjie: No conflict of interest Cao, Qian: No conflict of interest Figure 1. Single-cell RNA profiling and inflammatory expression patterns.

BackgroundCrohn’s disease (CD) frequently exhibits malnutrition and systemic inflammation, both of which are closely linked to elevated surgical risks and postoperative complications. Exclusive enteral nutrition (EEN) is a standard nutritional therapy for CD, yet whether its core mechanism functions via nutritional support to improve body mass index (BMI) or via nutritional treatment to modulate inflammation, altering the C-reactive protein-to-albumin ratio (CAR) remains inadequately understood. Besides its related alterations in computed tomography enterography (CTE) parameters and laparoscopic surgery outcomes also remain important points.MethodsA cohort study was conducted at our Inflammatory Bowel Disease Center, enrolling 89 CD patients undergoing bowel resection. Those patients received EEN for 6 weeks preoperatively. All data were collected from a database. Moreover, cross-sectional imaging metrics were assessed by CTE parameters to further demonstrate the impact brought by EEN. Postoperative complications within 30 days were also recorded.ResultsPreoperative EEN treatment significantly increased albumin levels (from 34.4 ± 4.1 g/L at baseline to 38.9 ± 4.5 g/L before surgery, p < 0.001), as well as improving inflammatory status via reduced CRP levels [from 23.0 (10.1, 36.5) mg/L at baseline to 2.8 (1.2, 5.0) mg/L before surgery, p < 0.001] and consequently decreased CAR (from 0.83 ± 0.79 g/L at baseline to 0.28 ± 0.75 g/L before surgery, p < 0.001). Patients receiving EEN also experienced fewer postoperative complications and a shorter postoperative length of stay. However, it was worth noting that BMI remained relative unchanged after EEN therapy (from 19.2 ± 3.4 kg/m2 at baseline to 19.3 ± 3.1 kg/m2 before surgery, p = 0.821).ConclusionPreoperative EEN in CD patients effectively ameliorates the CAR without prominently affecting BMI. As a targeted anti-inflammatory strategy in the immediate preoperative period, EEN exerts its benefits primarily through rapid modulation of inflammation rather than weight gain.