Background:Optimal length of proximal resection margin (PRM) for locally advanced Siewert type II adenocarcinoma of esophagogastric junction (AEG) remained undetermined. Especially, the relationship between PRM length after neoadjuvant chemotherapy (NAC) and survival were seldom reported. Methods:A total of 108 consecutive locally advanced Siewert type II AEG patients were enrolled. The clinicopathological characteristics, PRM length and survival outcomes were collected. Cox proportional hazard model was used to compare the hazard rates of survival and recurrence between patients with length above and below the cut-off value. Univariable and multivariable analyses were performed to analysis association between PRM length and prognosis. Results:The mean PRM length was 13mm (range: 1-45 mm). PRM status was independent factor for recurrence-free survival (RFS) (HR 3.177, 95%CI 1.098-9.193, p = 0.033). 4 patients (3.7%) had positive PRM on histological pathology, and they suffered shorter RFS than patients with negative PRM (16.0 ± 4.3 months vs 60.1 ± 3.9 months, p = 0.002). In 104 patients with negative PRM, NAC was administered to 53 patients (51.0%). The length of PRM was not associated with survival outcomes in NAC group and surgery alone (SA) group, respectively. The hazard rates of survival and recurrence did not differ between the patients with length of PRM above and below the cut-off value (p>0.05). No statistically significant differences in survival outcomes were observed between patients with different PRM lengths in either the NAC group or the SA group. Similarly, no statistically significant differences in survival outcomes were found across different PRM lengths, no matter which treatment strategy was chosen. Conclusions:A positive status of PRM appears to be associated with adverse survival outcomes of patients with locally advanced Siewert type II AEG after surgery. However, for patients with negative status, the length of the PRM does not influence survival, regardless of whether they undergo surgical resection alone or NAC followed by surgery.

Background: Although endoscopic remission is a primary therapeutic target in ulcerative colitis (UC), a meaningful proportion of patients with endoscopic healing still experience clinical relapse (CR). Histologic activity and epithelial barrier dysfunction may help explain this residual risk. Objectives: To develop and internally assess an exploratory tissue-based risk prediction model combining histologic activity with epithelial barrier and immunoregulatory markers for relapse risk stratification in UC patients with endoscopic healing. Design: Multicenter prospective observational cohort study with internal model assessment. Methods: Consecutive UC patients with confirmed endoscopic remission (Mayo Endoscopic Subscore 0 or 1) were followed for 12 months. Baseline colonic biopsies were assessed using the Nancy Histological Index (NHI) and immunohistochemical quantification of vitamin D receptor (VDR), Claudin-2, and mucin-2 (MUC-2). A prespecified four-marker logistic regression model was developed using these tissue-based predictors. Model performance was described by receiver operating characteristic analysis, calibration assessment, 1000-sample bootstrap internal validation, and exploratory therapeutic subgroup analyses. Results: Among 145 patients, 36 (24.8%) experienced CR within 12 months. In the final four-marker model, higher Claudin-2 and NHI were associated with increased relapse risk, whereas higher VDR and MUC-2 expression were protective. The model showed high apparent discrimination in the development cohort (area under the curve (AUC) = 0.968, 95% confidence interval: 0.943–0.992). Bootstrap internal validation yielded an optimism-corrected AUC of 0.957, Brier score of 0.075, calibration intercept of −0.067, and calibration slope of 0.827. A data-derived Youden cut-off of 0.379 classified 39 patients as higher risk, of whom 32 relapsed, and 106 patients as lower risk, of whom 4 relapsed. These estimates reflect internal model performance and should be interpreted cautiously because of the limited number of events and absence of external validation. Conclusion: A tissue-based model integrating Claudin-2, VDR, MUC-2, and NHI may help identify UC patients with different relapse risks despite endoscopic healing. These findings are exploratory and hypothesis-generating, and external validation with standardized biomarker quantification is required before clinical implementation.

Adverse drug events (ADEs) are a major source of preventable harm. Inflammatory bowel disease (IBD) requires long-term multidrug management, making ADEs frequent and clinically significant. Extracting ADEs from electronic health records (EHRs) is central to pharmacovigilance but challenging due to overlapping disease activity and drug toxicity, complex polypharmacy, and heterogeneous Chinese clinical narratives. Conventional named entity recognition (NER)–relation extraction (RE) pipelines and fixed vocabularies often miss evolving expressions. Large language models (LLMs) show promise for ADE detection[1], yet most current approaches are not end-to-end and rely on constrained annotation schemas, limiting scalability and real-world generalizability in IBD. We developed an end-to-end LLM pipeline for open-vocabulary detection of ADEs following treatment with corticosteroids, immunomodulators, biologics, and small-molecule inhibitors in IBD. A total of 8406 IBD notes (Peking Union Medical College Hospital = 7936; Zunyi Medical University = 216; Guizhou Provincial People’s Hospital = 254) were annotated. The system directly reads clinical text, expands candidate events through knowledge-augmented retrieval, and normalizes outputs to MedDRA to ensure reliable and scalable pharmacovigilance. It integrates (i) a high-recall pre-screening module to retain plausible ADE signals while minimizing unnecessary LLM calls, (ii) graph-based retrieval over a drug–event bipartite network to broaden candidate scope, (iii) ensemble LLM inference guided by a self-learned instruction set, and (iv) ontology-aware normalization aligning terms with MedDRA and ensuring cross-center consistency. In the binary classification task of detecting the presence of any AE within a patient’s record, we ultimately select HYBRID + LR model for subsequent analyses which achieved Area Under the Curve (AUC) of 0.809 in CD test set(Figure1A), and 0.828 in UC test set(Figure1B). Our model then achieved the good performance on identifying drug-AE pairs: CD test set an F1-score of 0.577, a recall of 0.706, and a precision of 0.488 for the CD cohort; For the UC cohort, the model achieved an overall F1-score of 0.545, recall of 0.624, and precision of 0.484. We identified the top five ADEs in the IBD cohort: bone marrow suppression (n = 137), liver function abnormality (n = 134), C.difficile infection (n = 73), rash (n = 71), and paresthesia (n = 70). The pipeline enables near real-time ADE detection and supports risk prediction in IBD. Embedding LLM-based pharmacovigilance in EHRs may deliver continuous safety surveillance and bridge clinical practice with regulatory science for data-driven, real-time monitoring. Reference: 1. Syrowatka A, Song W, Amato MG, et al. Key use cases for artificial intelligence to reduce the frequency of adverse drug events: a scoping review. Lancet Digit Health. Feb 2022;4(2):e137-e148. doi:10.1016/s2589-7500(21)00229-6 Conflict of interest: Ms. Wei, Yuge: None Ronghao, Li: None Gechong, Ruan: None Bai, Xiaoyin: None Yinghao, Sun: None Dejun, Cui: None Fang, Yan: None Huijun, Shu: None Xuemin, Yan: None Honglei, Liu: None Yang, Hong: None

Background Colorectal cancer (CRC) is a leading cause of cancer death worldwide, however, the risk of newly-diagnosed CRC and its related mortality after polypectomy have not been conclusively determined. Methods Prospective cases with polypectomy were identified in the UK Biobank. The age- and sexstandardized incidence ratio (SIR) and standardized mortality ratio (SMR) were calculated to assess the risk of CRC between the removal group and both the non-index-colonoscopy group (no record of diagnostic colonoscopy) from the UK Biobank and the general population in England. We also estimated the effect of removal compared with the polyp-free group using a competing risk model. Results During a median follow up of 10 (1-44) years (51,136 person-years), 78 incident CRCs (153/100,000 person-years), and 16 CRC-specific deaths (31/100,000 person-years) were identified in the removal group. Compared with the general population in England, the removal group had a similar risk of incident CRC (SIR 0.81, 95% confidence interval [CI] 0.64-1.01; P=0.060), whereas the CRC-specific mortality was 52% lower (SMR 0.48, 95%CI 0.28-0.78; P=0.004). Compared with the non-index-colonoscopy group, CRC-specific deaths after polyp removal were not significantly different (SMR 1.64, 95%CI 0.94-2.66; P=0.050). Compared with the polyp-free group, the risks of incidence and mortality in the removal group were both greater (incidence: adjusted hazard ratio [HR] 6.17, 95%CI 4.36-8.74; P<0.001; mortality: adjusted HR 3.25, 95%CI 1.65-6.41; P<0.001). Conclusion Polypectomy reduced but not eliminated the risk of CRC for polyp-positive participants to the level of the general population, reinforcing the importance of procedural quality and tailored surveillance strategies.

Melanoma is an aggressive malignant tumor with an increasing incidence worldwide. Ganglioside GD3 is recognized as a human melanoma-specific antigen and is highly expressed in melanoma tissues and cell lines. GD3 synthase (GD3s) is the rate-limiting enzyme for the synthesis of GD3. However, the function and mechanism of GD3s in melanoma remains poorly understood. The expression of GD3s was evaluated by an in silico analysis and detected by melanoma tissue microarray. Cell loss-of-function and gain-of-function, proliferation, colony formation, wound healing assay, transwell assay, tumor xenograft mouse model and a tail vein-injection mouse model were conducted to determine the functional role of GD3s in melanoma progression. Proteomic analysis and metabolomic analysis were used to identify downstream targets of GD3s. Quantification of triglyceride and cholesterol, nile red staining, Western blot, Real-time quantitative PCR (RT-qPCR) and Co-immunoprecipitation (Co-IP) assays were employed to validate the underlying mechanisms of GD3s which aggravate progression of melanoma. High-throughput screening method was used to identify the inhibitor of GD3s. Dysregulated high levels of GD3s were correlated with advanced clinical stages and poor prognoses of melanoma. GD3s promoted the proliferation and metastasis of melanoma by reprograming lipid metabolism. GD3s induced extensive lipid accumulation and elevated expression levels of lipogenic enzymes in melanoma cells by regulating AMPK/SREBP1 signaling pathway. ENMD-2076 L-(+)-Tartaric acid was considered to be a novel GD3s inhibitor and exhibited good anti-tumor activity both in vivo and in vitro. Mechanistically, consistent with shRNA-mediated silencing of GD3s, ENMD-2076 L-(+)-Tartaric acid inhibited de novo fatty acid synthesis through AMPK/SREBP1 pathway. The current findings uncovered a novel mechanism by which GD3s modulated aberrant lipid metabolism and promoted the progression of melanoma. ENMD-2076 L-(+)-Tartaric acid was firstly discovered as a new inhibitor of GD3s and had good anti-tumor effect both in vitro and in vivo.

Abstract Objectives To evaluate the efficacy and safety of upadacitinib in patients with anti-TNF -refractory intestinal Behçet’s disease (BD). Methods We conducted a single-center retrospective study using data from a maintained BD registry at Peking Union Medical College Hospital between July 2024 and April 2026. Seventeen consecutive patients were included. Upadacitinib was initiated at a daily dose of 15 mg for all patients, with dose escalation to 30 mg in nine cases due to an inadequate response. The primary endpoint was a complete remission (CR) at Month 6, defined by a composite disease activity index incorporating global gastrointestinal (GI) symptom score and endoscopic evaluation. Secondary endpoints included changes in Disease Activity Index for Intestinal Behçet’s Disease (DAIBD), inflammatory markers, glucocorticoid dosage, and safety. Results At Month 6, 50.0% (8/16) of patients who underwent endoscopy evaluation achieved CR based on the composite disease activity index. CR of global GI symptom score was observed in 76.5% (13/17) of patients and mucosal healing in 50% (8/16). Median DAIBD score decreased markedly from 55.0 (IQR 45.0-80.0) at baseline to 0.0 (IQR 0.0-10.0), accompanied by significant reductions in C-reactive protein and erythrocyte sedimentation rate. Upadacitinib demonstrated a glucocorticoid-sparing effect and was generally well tolerated. Conclusions Upadacitinib represents a potential therapeutic option for patients with anti-TNF-refractory intestinal BD.

BACKGROUND:Cancer-associated fibroblasts (CAFs) within the tumour microenvironment play a pivotal role in colorectal cancer (CRC) progression and therapeutic resistance. Serine/threonine protein kinase 25 (STK25) exerts multiple roles in tumourigenesis; however, its role in mediating tumour-stroma crosstalk remains largely unexplored. METHODS:Primary CAFs were isolated from CRC patient tissues and characterised to confirm their identity. The effects of STK25 expression on CAF activity and CAF-mediated tumour progression were evaluated both in vitro and in vivo. Western blot, qRT-PCR, ChIP and dual-luciferase reporter assays were performed to elucidate the mechanism by which STK25 regulated CAF activation. Moreover, the effect of STK25 expression on CAF-induced cetuximab resistance was assessed in vitro and in vivo. The clinical significance of STK25 expression was determined in CRC patient tissues, tissue microarrays and patient-derived organoids. RESULTS:Knockdown of STK25 in CRC cells enhanced CAF proliferation, migration and activation, whereas its overexpression exhibited the opposite effect. STK25-knockdown-mediated CAF activation subsequently promoted CRC cell proliferation and metastasis. Moreover, STK25 depletion combined with CAFs significantly enhanced CRC tumour growth in vivo. Mechanistically, STK25 deficiency activated the NF-κB pathway, leading to p50 phosphorylation which directly bound to the AREG promoter, thereby transcriptionally up-regulating AREG expression. In addition, STK25-regulated AREG/EGFR axis mediated the crosstalk between CRC cells and CAFs. More importantly, CAFs conferred resistance to the anti-EGFR antibody cetuximab, which could be reversed either by STK25 overexpression or by AREG-neutralising antibody treatment. Clinically, low STK25 expression correlated with elevated CAFs marker levels and poor cetuximab response in CRC patients. CONCLUSIONS:Our findings identified STK25 as a critical regulator of the NF-κB/AREG/EGFR axis in tumour-CAF communication and highlight its potential as a therapeutic target for overcoming CAF-induced cetuximab resistance in CRC. KEY POINTS:STK25 deficiency enhanced CAF-mediated CRC growth via the NF-κB/AREG/EGFR axis. STK25 overexpression or AREG antibody overcame CAF-mediated cetuximab resistance. CRC patients with high STK25 and low CAFs marker levels might benefit from cetuximab treatment.

Background: Crohn’s disease (CD) has an evolving course and may progress to stricturing or penetrating complications, intestinal surgery, and treatment escalation. Existing models often rely on baseline or time-agnostic data, limiting risk assessment during routine follow-up. We developed and externally validated a time-updated model CD-ProFormer for prediction of CD progression using longitudinal electronic health records (EHRs). Methods: We assembled multicenter EHR cohorts: a development cohort from Peking Union Medical College Hospital (PUMCH) (761 patients; 11,984 visits) and external validation cohorts from Guizhou (74 patients; 510 visits) and Nanjing (271 patients; 3934 visits). Using each visit as index, CD-ProFormer, a time-aware Transformer that used EHR trajectories to predict 1-, 3-, and 5-year risks of behavior progression, CD-related intestinal surgery, and major medication initiation. Global SHAP, temporal SHAP, decision curve analysis, and representative cases assessed interpretability and clinical utility. Findings: CD-ProFormer showed strong internal discrimination for behavior progression, with AUROCs of 0.979, 0.951, and 0.910 at 1, 3, and 5 years; macro-area under the curve for first-progression time-window classification was 0.811. External validation remained acceptable, with AUROCs of 0.725–0.879 in Guizhou and 0.856–0.913 in Nanjing, consistently exceeding recurrent baselines. Performance for surgery and medication initiation was comparable to recurrent models and better than conventional models. Interpretation: In this prognostic study, CD-ProFormer enabled time-updated, horizon-specific prediction of CD behavior progression, with surgery and medication initiation assessed in parallel. These findings suggest that prognosis in CD can be updated at follow-up visits using routinely collected longitudinal data and may support risk stratification, monitoring intensity, and timely treatment planning.

BACKGROUND Despite 5-aminosalicylic acid (5-ASA) being the first-line therapy for ulcerative colitis (UC), there is limited real-world evidence concerning sex-specific differences in the efficacy of 5-ASA therapy and patient prognosis. AIM To investigate sex-disparities in 5-ASA treatment responses and long-term outcomes in a Chinese large-scale UC cohort. METHODS A retrospective study was conducted on 554 consecutive UC patients treated with 5-ASA at Peking Union Medical College Hospital between January 2003 and June 2023. The rates of endoscopic mucosal healing (EMH) and colectomy were compared between the female and male cohorts, and 1:1 propensity score matching (PSM) was performed for demographics, comorbid conditions and drugs, disease conditions, laboratory parameters, and UC medication use. Cox regression analysis and Kaplan-Meier curves were constructed for survival analyses. RESULTS There were 243 patients in the female cohort (mean age, 34.8 +/- 11.3 years; 21.4% with ulcerative proctitis) and 311 patients in the male cohort (mean age, 36.2 +/- 13.5 years; 22.8% with ulcerative proctitis). After PSM, there was a higher risk of UC flare-up in the male vs female cohort [adjusted odds ratio = 2.78, 95% confidence interval (CI): 1.69-4.55, P < 0.001]. Male sex was an independent protective factor against EMH [adjusted hazard ratio (aHR) = 0.89, 95%CI: 0.87-0.91, P = 0.03] and a risk factor for colectomy (aHR = 1.93, 95%CI: 1.13-3.29, P = 0.02). Male patients had longer EMH-free survival (aHR = 0.63, 95%CI: 0.39-1.00, P = 0.048) and shorter colectomy-free survival (aHR = 1.80, 95%CI: 1.06-3.05, P = 0.027). CONCLUSION Pronounced sex-specific differences exist in 5-ASA therapy efficacy and patient prognosis. Male sex is associated with more frequent relapses, a lower likelihood of EMH, and a higher risk of colectomy.

In recent years, immunotherapy has shown obvious advantages in treating cancers. The close interaction between cancer cells and immune cells in the tumor microenvironment (TME) underlies the progression of glioblastoma multiforme (GBM). However, there are no effective immune-related targets against GBM. Here, in silico analyses and experimental data showed that Interferon Gamma Inducible Protein 30 (IFI30), modulated by histone modifications both H3K4me3 and H3K27ac, was up-regulated in GBM and had a potential role in the antitumor immune responses. In vitro and in vivo experiments further revealed that IFI30 modulated the infiltration of tumor-associated macrophages (TAMs) and reduced the proportion of CD8+ T cells. Mechanistically, IFI30 induced PGE2 expression in GBM cells via the MAFF/PTGS2 pathway, and PGE2 bound to macrophage EP2/EP4, activating the downstream ERK1/2 and KLF4/STAT6 pathways, stimulating the infiltration of TAMs. Taken together, we characterized the role and mechanisms of IFI30 in the malignant progression of GBM by regulating TAMs, highlighting that IFI30 may benefit GBM patients as a therapeutic target.

OBJECTIVES:Emerging evidence highlights the role of diet in modulating the disease course of ulcerative colitis (UC). This prospective study investigated the association between diet quality, dietary inflammatory index (DII), and short-term clinical outcomes in UC patients. METHODS:A total of 108 UC patients in remission or with mild disease activity were recruited. Dietary intake over 6 wk was prospectively recorded using a digital health management platform to assess nutrient composition and calculate DII scores. Subsequently, a cluster-controlled intervention was implemented using a modified antiinflammatory diet tailored to UC-specific needs. Clinical outcomes and fecal microbiota were evaluated. RESULTS:Findings revealed that the majority of patients had inadequate intake of staple foods (78.7%) and vegetables (69.4%). Higher DII scores were significantly associated with an increased risk of relapse or persistent disease activity (OR = 5.82, 95% CI: 1.75-19.39, P = 0.004) and reduced abundance of butyrate-producing gut bacteria. After 6 wk, the intervention group achieved a greater reduction in DII scores (median change -1.31, P = 0.019) and demonstrated improved nutritional intake. Compared with general dietary advice, the structured intervention significantly reduced the risk of short-term adverse outcomes (OR = 0.022, 95% CI: 0.001-0.629, P = 0.026). CONCLUSIONS:This study underscores the significant role of diet quality and DII in predicting UC prognosis. A targeted, digitally delivered antiinflammatory diet improved nutrient intake, modulated gut microbiota, and reduced short-term relapse risk. These findings support the integration of structured dietary strategies into UC management and suggest the feasibility of digital platforms in guiding personalized nutrition therapy.

Crohn’s disease (CD) has a non-negligible prevalence globally especially in the developed countries. Due to its large influenced population over world and great medical burden after disease progression, numerous researches focus on the risk factors and prediction models of CD. However, CD is a chronic and dynamically progressive disease, previous models were mostly convention models utilized only baseline data and ignored medical events during disease course, causing a low prediction efficiency and lack of real time prediction capacity. Here we developed a Transformer-based prediction framework: Time-Aware CD Progression Prediction Model (TACDPPM) that utilized patients’ all longitudinal electronic health records (EHRs) to predict future CD related events including disease behavior progression, surgery and medical usage and compare the prediction efficiency with Long Short Term Memory (LSTM) model, Gated Recurrent Unit (GRU) model, Logistic regression model and Time-varying Cox regression model. Based on transformer structure we developed TACDPPM with an input-aware module, an expert knowledge module and a multi-scale time-aware module. As for datasets we collected 66 static and dynamic variables from 761 CD patients from Peking Union Medical College Hospital as internal training/validation cohort, 74 CD patients from Guizhou Provincial People’s Hospital and Zunyi Medical University Affiliated Hospital as external validation 1 and 170 CD patients from Nanjing Jing Hospital as external validation 2. TACDPPM forecasts the risk of three types of events mentioned above in 1 year, 3 years, and 5 years after supposed starting time points. Also, SHAP of each variable was calculated to show the association with outcome. TACDPPM showed excellent results in internal validation with 0.910-0.979 AUROC (0.835-0.955 for LSTM; 0.821-0.955 for GRU) in predicting 1-, 3- and 5-years disease behavior progression; 0.811 Macro-AUROC in predicting disease behavior progression; 0.729-0.823 AUROC (0.698-0.715 for LSTM; 0.704-0.724 for GRU) in predicting 1-, 3- and 5-years surgery; 0.811 Macro-AUROC in predicting disease behavior progression; 0.813-0.930 AUROC (0.738-0.884 for LSTM; 0.748-0.876 for GRU) in predicting 1-, 3- and 5-years glucocorticoid usage; 0.796-0.901 AUROC (0.735-0.855 for LSTM; 0.738-0.854 for GRU) in predicting 1-, 3- and 5-years immunosuppressant usage; 0.939-0.943 AUROC (0.844-0.873 for LSTM; 0.831-0.874 for GRU) in predicting 1-, 3- and 5-years biologics usage. Our TACDPPM showed much better predicting results in CD related medical events than LSTM, GRU and conventional results. But heterogeneity of CD patients, lack of EHR data and different therapy habits may decrease the efficiency of TACDPPM. Conflict of interest: Dr. Wang, Beiming: No conflict of interest Yang, Yingliang: No conflict of interest Liu, Honglei: No conflict of interest Yang, Hong: No conflict of interest Bai, Xiaoyin: No conflict of interest Xu, Hui: No conflict of interest Ruan, Gechong: No conflict of interest Xu, Zhiwei: No conflict of interest Cui, Dejun: No conflict of interest Yan, Fang: No conflict of interest

Colorectal cancer (CRC) incidence and mortality rates are steadily on the rise, which brings significant public health concern worldwide, especially in China. Methyltransferase-like 7 A (METTL7A), a member of the methyltransferase-like family, is associated with various cancers including CRC. Notably, CRC progression is closely linked to metabolic reprogramming. However, its precise role in CRC, particularly metabolic reprogramming of CRC, remains unclear. METTL7A was identified as a pivotal gene closely associated with CRC by bioinformatics analyses. Through a series of cellular functional assays and several animal experiments, such as in situ tumor and spontaneous tumor in C57BL/6 mice, the role of METTL7A in the development of colorectal cancer was evaluated. Transcriptomics and proteomics were used to analyze the effects of METTL7A on the expression of numerous genes, especially those involved in metabolic processes including cholesterol synthesis pathway within CRC cells. Western-blotting, co-immunoprecipitation and immunofluorescence were used to elucidate the relationship of METTL7A and the cholesterol metabolic pathway. METTL7A exhibited low expression in CRC cell lines and CRC tissues and it was demonstrated to function as a tumor suppressor in CRC. Transcriptomic and proteomic analyses indicated that METTL7A affects genes related to the cholesterol metabolism pathway. METTL7A was further proven to directly bind to Sterol Regulatory Element-Binding Protein1 (SREBP1) and SREBP Cleavage-Activating Protein (SCAP), hindering the nuclear translocation of SREBP1 and thereby reducing intracellular cholesterol content. This study provides valuable insights into the role of METTL7A in CRC and its impact on metabolic reprogramming, particularly cholesterol synthesis, and identifies METTL7A as a potential therapeutic target of CRC.

Inflammatory bowel disease (IBD) is a chronic, relapsing, inflammatory condition of the gastrointestinal tract that primarily includes Crohn's disease and ulcerative colitis. Beyond the typical gastrointestinal symptoms, IBD is frequently associated with various extraintestinal manifestations (EIMs) affecting organs such as joints, skin, eyes, and the hepatobiliary system. As the prevalence of IBD rises in China, the identification and management of EIMs have become increasingly important. However, there is currently variation among Chinese physicians in their attention to, comprehensive assessment of, and management of EIMs in IBD. Therefore, this consensus aims to provide guidance for the systematic evaluation and multidisciplinary management of IBD-associated EIMs.

BackgroundChina’s healthcare system is confronting a rising burden of antimicrobial resistance, chronic complex diseases, and an aging population requiring long-term, post-acute care. As a value-based care model in the USA for over 50 years, home infusion therapy (HIT), combined with home health services (HHS), presents a sustainable alternative to prolonged hospitalization for intravenous medication administration. In this two-part narrative review, Part 1 provides a needs assessment describing the demographic, clinical, and public health factors driving the demand for HIT and HHS in China.MethodsWe conducted a literature search up to January 2026 using MEDLINE, EMBASE, PubMed, Web of Science, and China National Knowledge Infrastructure.ResultsIn Part 1, we present the impact of the aging population and chronic conditions requiring prolonged infusion therapy (including cancer, malnutrition and infections like osteomyelitis, endocarditis, and bacteremia) on the rising antimicrobial resistance, hospital burden and healthcare expenditures. Through the patient-centric solution of HIT and HHS, patients can receive intravenous medications and nutrition in the comfort of their homes, enabling the continuity of care beyond the hospital. Services include outpatient parenteral antibiotic therapy, hospice and palliative care in patients with cancer, and management of nutritional needs through total parenteral nutrition. Under this care model, reimbursement is tied to success in improved patient outcomes and reduced hospital readmissions. A detailed reimbursement and cost-effectiveness considerations are addressed in Part 2 of this review.ConclusionWith proper infrastructure development and reimbursement mechanisms that align payment with value, HIT and HHS could mitigate antimicrobial resistance, and transform and sustain affordable care delivery in China, especially for older adults and those with chronic conditions.Part 2 is available at https://doi.org/10.3389/fpubh.2026.1761870.

Hui Xu1 Junmei Zhang2 Lin Liu3 Li Wang6 Wei Han6 Xinjuan Liu7 Yanjun Chen8 Yue Yang9 Zuoyan Wu10 Xuren Sun4* Linting Xun5* Hong Yang1* 1. Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College 2. Beijing Rectum Hospital 3. The second Affiliated Hospital of Baotou Medical Colledge 4. The first Hospital of China Medical University 5. The First People’s Hospital of Yunnan Province 6. Chinese Academy of Medical Sciences & Peking Union Medical College 7. Beijing Chaoyang Hospital Capital Medical University 8. The First Affiliated Hospital of Soochow University 9. Heilongjiang Provincial Hospital 10. Beijing Sixth Hospital The incidence rate of ulcerative colitis (UC) in China is increasing during the past few decades. All UC patients need to undergo colonoscopy repeatedly for diagnosis, which all depend on adequate bowel preparation for a clear vision. While bowel preparation would be a burden for patients with UC, especially for those with severe activity. The aim of this study was to evaluate the efficacy, tolerability, and safety of the ultra-low dosage bowel preparation strategy for patients with UC. We conducted a prospective multicenter randomized investigator-blinded non-inferiority trial. Patients diagnosed with UC aged from 18-70 years old were recruited. Patients were randomly assigned to receive 3L polyethylene glycol (PEG), or ultra-low dosage (1L) PEG with wholly enteral nutrition diet 1 day before plus glycerin enema before colonoscopy for bowel preparation. Efficacy were assessed by Boston Bowel Preparation Score (BBPS), with tolerability and safety assessed by questionnaires. Nine territory hospitals from different regions of China participated in this study from September 2022 to December 2024. A total of 155 patients in the 1L PEG group and 156 patients in the 3L PEG group were included in the analysis of BBPS. Disease extent, disease type, hematochezia, stool frequency, physician’s global assessment score, medication and laboratory test results didn’t differ significantly between two groups. The mean of BBPS in the 1L PEG group and 3L PEG group were 6.80 ± 1.57 and 7.24 ± 1.43, respectively (non-inferiority test, p = 0.0007). The tolerance score in 1L PEG group was significantly higher than 3L PEG group (8.28 ± 1.67 vs 7.63 ± 2.31, p = 0.001), and patients in 1L PEG group expressed a better willingness to accept the same bowel preparation method than 3L PEG group (“very willing” vs “acceptable”, p = 0.014). Nausea was the most common adverse reaction, followed by abdominal distension and thirsty. Patients in 3L PEG group had a significant higher proportion of nausea (28.0% vs 14.5%, p = 0.007), while had no significant in vomiting, abdominal distension, thirsty, abdominal pain and other reactions. Abdominal pain, diarrhea and hematochezia were not worsened either within 24 hours or 1 week in both groups. No patients were hospitalized due to bowel preparation or complications related to colonoscopy. This multicenter RCT showed a non-inferior effect with a better tolerability and willingness to repeat of 1L PEG bowel preparation protocol than the traditional 3L PEG protocol in patients with UC. Very low-dosage (1L) PEG with 1 day total enteral nutrition diet plus glycerin enema before colonoscopy may be an adequate and more acceptable choice of bowel preparation. References: 1. Yang H, Zhou R, Bai X, et al. Trend and Geographic Variation in Incidence and Prevalence of Inflammatory Bowel Disease in Regions Across China: A Nationwide Employee Study Between 2013 and 2016. Frontiers in Medicine 2022;9. 2. Murthy SK, Feuerstein JD, Nguyen GC, et al. AGA Clinical Practice Update on Endoscopic Surveillance and Management of Colorectal Dysplasia in Inflammatory Bowel Diseases: Expert Review. Gastroenterology 2021;161:1043–1051.e4. 3. Chatterjee A, Kaur S, Jena A, et al. Strategies to Improve Colonoscopy Preparation in Inflammatory Bowel Disease. A Systematic Review and Network Meta-analysis of Randomized Trials. J Of Gastrointest And Liver Diseases 2024;33:245–253. 4. Megna B, Weiss J, Ley D, et al. Clear liquid diet before bowel preparation predicts successful chromoendoscopy in patients with inflammatory bowel disease. Gastrointest Endoscopy 2019;89:373–379.e2. Conflict of interest: Dr. Xu, Hui: No conflict of interest Yang, Hong: No conflict of interest

Mounting evidence suggests that psychosocial stressors, such as social isolation and loneliness, contribute to gastrointestinal disorders by disrupting gut-brain interactions. We aim to investigate the associations of social isolation, loneliness, and their related alterations in metabolism and circulating proteins with the risk of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). 275,157 adults from the UK Biobank were analyzed, including metabolomic data from 68,362 participants and proteomic profiling from 29,339 participants. The exposures included social isolation, loneliness, and their related metabolites and circulating proteins, with incident IBD as the outcome. Cox regression and two-sample Mendelian randomization (TSMR) analysis were utilized to examine the associations. Over a mean follow-up of 13.49 years, this cohort study identified 1565 incident IBD cases, comprising 1063 UC cases and 492 CD cases. Social isolation and loneliness showed significant associations with an elevated risk of IBD (social isolation: hazard ratio [HR]most isolated: 1.31, 95%CI: 1.01-1.70; loneliness: 1.29, 95%CI: 1.04-1.60). Social isolation and loneliness jointly increased the risk of IBD by 85%, with an HR of 1.85 (95% CI: 1.02-3.36). TSMR analyses further indicated that more sports or gym activity reduced IBD and CD risk, more religious activity lowered UC risk, while fewer leisure/social activities increased UC risk. For the metabolomic analysis, eight and five metabolites were identified to be associated with social isolation and loneliness, respectively. Additionally, 22 circulating proteins consistently associated with both loneliness and social isolation were identified, predominantly enriched in cytokine-related pathways. The derived protein scores were positively associated with an increased risk of IBD. This study demonstrates social isolation and loneliness significantly raise IBD risk, with related metabolite and circulating proteins shedding light on underlying biological mechanisms.

Crohn's disease (CD) is frequently complicated by intestinal strictures, which substantially affect patients quality of life and long-term outcomes. Accurate classification of strictures-as inflammatory, fibrotic, or mixed-is critical for selecting optimal therapeutic strategies. In clinical practice, multidisciplinary team (MDT) consultation is often employed to assess stricture characteristics. However, the accuracy and inter-specialty consistency of stricture evaluation within MDTs remain inadequately characterized. This study aimed to assess the intra-disciplinary consistency and accuracy of decision-making for CD-related strictures, evaluate the accuracy of post MDT decisions, and propose recommendations for stricture nature assessment and MDT workflow optimization. A mixed-methods study was conducted at Peking Union Medical College Hospital involving 42 patients with CD and intestinal strictures. MDT participants-including specialists from gastroenterology, surgery, ultrasound, and MDT meeting chairs-were involved in evaluating intra-disciplinary decision consistency and accuracy. Semi-structured qualitative interviews were also conducted to explore factors influencing clinical decision-making. Gastroenterologists demonstrated the highest intra-team consistency (PABAK = 0.75) and diagnostic accuracy (89.3%). Ultrasound specialists showed improved consistency following targeted training (from 0.46 to 0.93). The overall accuracy of historical MDT decisions was 92.9%. Key factors influencing stricture nature judgment included clinical presentation, laboratory findings, imaging features, and endoscopic evaluation. Seven core components were identified to improve MDT workflow: expert selection, team building, training, pre-meeting preparation, in-meeting procedures, post-meeting actions, and continuous quality improvement. This study reveals variability in decision-making for CD-related strictures across different specialties. To improve diagnostic accuracy and treatment planning, we propose clear stricture classification criteria and a structured MDT workflow to standardize and enhance multidisciplinary management of CD.

BackgroundChina's healthcare system may benefit from the integration of home infusion therapy (HIT) combined with home health services (HHS) to address the urgent need for a sustainable long-term, post-acute care model for the aging population and those with chronic complex diseases. In this Part 2, we presented the current landscape of home- and community-based care models in China and formulated recommendations for successful implementation of HIT and HHS.MethodsWe conducted a literature search up to October 2025 using MEDLINE, EMBASE, PubMed, Web of Science, and China National Knowledge Infrastructure.ResultsTo address the urgent need to support aging at home, China has initiated home- and community-based services nationwide. Despite these services, including a pilot of hospital-at-home, utilization remains low due to limited facilities, suboptimal service quality, and inadequate promotion. Notably, HIT and HHS that provide outpatient parenteral antibiotic therapy and total parenteral nutrition at home, and chemotherapy at infusion centers have not been adopted in China; yet this value-based modality has existed in western countries (including the United States, the United Kingdom, Australia, Canada, France, among others) for decades to provide patient-centric care that is safe and cost-effective. Implementing HIT requires a robust accreditation system, sterile compounding standards, technological integration, and professional training to ensure patient safety and quality of care.ConclusionThe shift of care from hospitals to homes through HIT supported by HHS holds great potential to alleviate healthcare costs, reduce hospital burden, and enhance patient comfort and dignity in China.Part 1 is available at https://doi.org/10.3389/fpubh.2026.1761871.