Purpose This study evaluated the diagnostic accuracy of bowel ultrasound combined with inflammatory biomarkers for assessing ulcerative colitis disease activity. Materials and Methods The single-center derivation cohort retrospectively enrolled 60 ulcerative colitis patients from our institution who underwent colonoscopy and bowel ultrasound. Patients were stratified into active disease and remission groups. Bowel ultrasound parameters and clinical features were analyzed. Diagnostic performance was assessed using receiver operating characteristic curve analysis. The resulting model was externally validated from 35 patients at an independent tertiary hospital retrospectively. A nomogram was plotted for clinical application. Results In the derivation cohort (31 remission: age 42.6±18.3, male 48%; 29 active: age 44.4±14.5, male 48%), univariate analysis identified bowel wall thickness (cutoff value 3.95 mm), submucosal index (cutoff value 46.1%), bowel wall flow (cutoff value Grade 2), fecal calprotectin (cutoff value ≥200 μg/g), and erythrocyte sedimentation rate (cutoff value 26.5 mm/h) as significant predictors of disease activity. Bowel wall thickness and flow were independent risk factors. The combined model demonstrated an area under curve of 0.908 (0.829-0.986). External validation (19 remission, 16 active) provided preliminary evidence supporting the model's discriminative ability, showing an area under curve of 0.862 (0.743-0.981). The nomogram provided individualized risk prediction with acceptable calibration in both cohorts. Conclusion An integrated model combining bowel ultrasound and inflammatory biomarkers was developed and externally validated for the assessment of ulcerative colitis activity. The model, presented as a clinically practical nomogram, exhibits acceptable calibration, supporting its potential as a valuable non-invasive tool for patient management.

Background:Patients with small-bowel stricturing Crohn's disease (sbsCD) usually have a higher risk of intestinal surgical resection. We aimed to develop a machine-learning model for predicting the 1-year surgery risk in these patients. Methods:This study included 520 retrospectively enrolled patients with sbsCD (training cohort, n = 416; testing cohort, n = 104) from January 2018 to May 2021 and 126 prospectively enrolled patients in the validation cohort from July 2021 to December 2023 across four centers for inflammatory bowel disease in China. Clinical and radiological features were assessed by using logistic regression analyses to identify independent surgery risk factors. Six predictive machine-learning models for 1-year surgical risk were developed and the model performance was comprehensively evaluated by constructing receiver-operating characteristic (ROC) curves and comparing area under the curve (AUC) values. Four simplified Bayesian network (BN)-based risk matrices were constructed for clinical practice. Results:There were 158 (24.4%) Crohn's disease (CD)-related surgeries during the 1-year follow-up. Eight selected predictors of surgery included penetrating lesions, nonuse of biologics, nonuse of corticosteroids, a CD obstructive score of ≥3, endoscopic strictures, anemia, radiologic luminal narrowing, and prestenotic dilation. Among the six models evaluated, the Tree-Augmented Naïve Bayes (TAN) model demonstrated optimal performance, with a mean AUC of 0.878. A further prospective validation cohort verified the efficacy of the model, with 87.5% specificity, 76.7% sensitivity, and 84.9% accuracy for predicting 1-year surgery. Four simplified BN-based risk matrices were constructed for practical use. An online prediction tool is available at http://prebn.site/. Conclusion:We developed and validated a TAN-based BN model incorporating clinical and radiological features to accurately predict the 1-year surgical risk for clinical application in patients with sbsCD, thereby providing a promising tool for decision-making.

The symptoms of pancreatic cancer (PC) are usually nonspecific or absent, and the early diagnosis remains challenging. 7–14

Intestinal fibrosis is often observed in inflammatory bowel disease (IBD) and seriously affects intestinal health. Our previous study identified that triphenyl phosphate (TPhP), one kind of frequently used organophosphate flame retardants (OPFRs), induced IBD-like features in colon. Herein, we firstly observed extracellular matrix deposition in colon tissues, indicative of appearance of colonic fibrosis. Further studies showed that TPhP downregulated epithelial marker E-cadherin levels but upregulated alpha smooth muscle actin (α-SMA) in mouse colon tissues, and similar results were observed in cultured colon cells, indicating that fibrogenesis might be attributed to epithelial-mesenchymal transition (EMT). Further transcriptome and experimental data demonstrated that TPhP-induced EMT was closely associated with activated Wnt/β-catenin pathway. Moreover, FOXM1 facilitated the entrance of β-catenin into nucleus to regulate expression of Wnt target genes, promoting EMT initiation. Collectively, these findings demonstrated that TPhP induced colonic fibrosis in mice by activating EMT, and this work may provide new perspectives in exploring etiology of intestinal fibrosis and developing relevant treatment strategies.

Colonoscopic withdrawal time is crucial for achieving a high adenoma detection rate (ADR) and reducing post-colonoscopy colorectal cancer risk. Enhanced qualified mucosal observation improves ADR, but manual quantification of qualified mucosal observation time (QMOT) in routine is challenging. We developed an artificial intelligence (AI) system, QAMaster, for automatic QMOT calculation during colonoscopy withdrawal. QAMaster comprises two models: Model I for image quality analysis (trained with 57,235 images from 64 patients) and Model II for anatomical landmark identification (trained with 7712 images from 3013 patients). Patients were stratified by QMOT, and ADR was compared. The areas under the curve (AUC) of Model I were 0.980–0.991, and Model II were 0.977–0.997. Among 482 patients, ADR was 36.54

Non-alcoholic fatty liver disease (NAFLD) has a higher prevalence in inflammatory bowel disease (IBD) patients compared to the general population. Herein, the prevalence and predictors of NAFLD in a large IBD cohort were evaluated by non-invasive method. A multicenter retrospective study was conducted among 592 inpatients diagnosed with IBD who underwent abdominal ultrasound. Characteristics of IBD and metabolic status were collected, presence of hepatic steatosis was assessed, and predictors for NAFLD were analyzed. A total of 509 IBD patients were included in the final analysis including 245 NAFLD (48.1%) subjects. IBD patients with NAFLD were older than those without NAFLD. NAFLD patients had more diabetes, higher body mass index (BMI) and more obesity. The patients with NAFLD showed increased levels of gamma-glutamyl transferase, uric acid, glycemia, triglycerides and low density lipoprotein. The localization of ulcerative colitis showed a more extensive trend in NAFLD patients compared with non-NAFLD subjects. Multivariate analysis showed that NAFLD was independently associated with BMI levels, biologic agents using, and prior surgery in IBD patients. NAFLD is common in Chinese patients with IBD. Obesity and biologics using are risk factors, and prior intestinal surgery is a protective factor of NAFLD development. These findings should be interpreted in the context of an inpatient-based study population.

Purpose:Ustekinumab (UST) is effective for Crohn's disease (CD), yet reliable biomarkers for predicting long-term response remain scarce. This study aimed to identify novel plasma proteomic biomarkers and develop predictive models for long-term endoscopic response to UST therapy in patients. Methods:Baseline plasma inflammatory proteins were profiled using the Olink platform in 40 CD patients treated with UST (20 responders, 20 non-responders). Differentially expressed proteins (DEPs) were identified after adjusting for age, age at diagnosis, and SES-CD scores. Stable DEPs were selected via bootstrap resampling and further validated in an independent patient group from the same center (n=20) using ELISA. Predictive models were constructed using logistic regression, random forest, and support vector machine (SVM) algorithms. Results:Non-responders had elevated baseline interleukin-8 (IL8) and CD6 levels and reduced thymic stromal lymphopoietin (TSLP) compared to responders. ELISA confirmed differential expression of IL8, CD6, and TSLP, with CD6 showing the best diagnostic accuracy (AUC=0.800). The logistic regression model combining these markers achieved an AUC of 0.828 (95% CI: 0.701-0.954), outperforming random forest (AUC=0.745) and SVM (AUC=0.775). Conclusion:Baseline plasma IL8, CD6, and TSLP are potential predictive biomarkers of long-term endoscopic response to UST in CD, providing a basis for personalized treatment strategies.

Inflammatory bowel disease (IBD) is an inflammatory disease that occurs to the intestinal tract. Many patients with IBD often develop anemia and often receive oral iron supplementation. Many of them develop non-compliance with oral iron therapy, but the mechanisms are not well understood. We interrogated whether colonic epithelial iron overload impacts cell viability and disease severity. We observed increased expression of iron importers and iron accumulation in mature colonocytes in dextran sulfate sodium (DSS)-induced acute colitis and in humans with active colitis. Administration of hepcidin increased epithelial iron overload and aggravated colonic inflammation in DSS-treated mice and IL10-/- mice. Hepcidin-induced iron accumulation increased colonic epithelial death, which was prevented by treatment with Trolox, a vitamin E analog and a scavenger of lipid peroxides. By using cultured Caco-2 cells, we showed that iron and inflammatory cytokines (TNF-α and IL-1β) induced a synergistic increase in the number of necrotic cells. We then showed that the combined treatment by hepcidin and cytokines increased labile iron content and lipid peroxidation in Caco-2 cells. Moreover, liproxstatin-1, a ferroptosis inhibitor, and deferoxamine, an iron chelator, both abolished the hepcidin/cytokines induced death of Caco-2 cells, suggesting ferroptosis. We further elucidated that inflammatory cytokines promote lipid peroxidation and ferroptosis by inducing NOX1-dependent exhaustion of reduced glutathione (GSH). Collectively, our findings demonstrate that the inflammatory context predisposes colonic epithelial cells to iron overload mediated ferroptosis, exacerbating colonic inflammation.

The gut has been a focal point in the research of digestive system disorders. The internal microbiota generates metabolites that function as signaling molecules and substrates, interacting with the intestinal wall and influencing host physiology and pathology. Besides, the gut microbiota and metabolites owe highly diverse types and quantities, posing challenges for quantitative analysis, and monitoring frequent interactions between digestive tract metabolites and the intestinal wall remains a challenge. However, research targeting gut microbiota metabolites has elucidated their relevance to digestive diseases. By modulating metabolites such as short-chain fatty acids, bile acids, and lipopolysaccharides, it is possible to intervene in the progression of diseases such as inflammatory bowel disease and non-alcoholic fatty liver disease. Currently, research on gut microbiota is advancing, and more work is required to explore the interactions between host, microbes and underlying mechanisms. In this review, we have revisited the generation of gut microbiota-related metabolites, their impact on diseases, and modes of interaction, emphasizing the significant role of metabolites in digestive system disorders. It is believed that the linkage between gut microbiota and diseases in current research can be established through metabolites, providing a framework and foundation for research in the field of metabolomics and fundamental mechanisms.

Crohn’s disease (CD) is a chronic inflammatory disease of the digestive tract with unknown etiology. It follows a relapse-remission pattern, making disease activity assessment crucial for treatment. Our study aims to evaluate the diagnostic accuracy of various imaging modalities and to validate and compare the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS), the multidetector computed tomography enterography score (MDCTEs), and the simplified endoscopic activity score for Crohn’s disease (SES-CD). We assessed diagnostic performance using the CD Activity Index (CDAI). We first categorized patients into remission and active groups. For those in the active stage, we further categorized them into mild/moderate and severe activity groups. We used Spearman rank correlation to evaluate the relationships among IBUS-SAS, bowel wall thickness (BWT), Color Doppler imaging signal (CDS), inflammatory fat (i-fat), bowel wall stratification (BWS), and clinical inflammatory indicators. A total of 103 CD patients were evaluated. The IBUS-SAS cut-off for remission and activity was 23.8, with an AUC of 0.923, sensitivity of 91.4

Background and Aims Inflammatory bowel disease (IBD) is a global disease that is evolving with increasing incidence. However, there are few works on computationally assisted diagnosis of IBD based on pathological images. Therefore, based on the UK and Chinese IBD diagnostic guidelines, our study established an artificial intelligence-assisted diagnostic system for histologic grading of inflammatory activity in ulcerative colitis (UC). Methods We proposed an efficient deep-learning (DL) method for grading inflammatory activity in whole-slide images (WSIs) of UC pathology. Our model was constructed using 603 UC WSIs from Nanjing Drum Tower Hospital for model train set and internal test set. We collected 212 UC WSIs from Zhujiang Hospital as an external test set. Initially, the pre-trained ResNet50 model on the ImageNet dataset was employed to extract image patch features from UC patients. Subsequently, a multi-instance learning (MIL) approach with embedded self-attention was utilized to aggregate tissue image patch features, representing the entire WSI. Finally, the model was trained based on the aggregated features and WSI annotations provided by senior gastrointestinal pathologists to predict the level of inflammatory activity in UC WSIs. Results In the task of distinguishing the presence or absence of inflammatory activity, the Area Under Curve (AUC) value in the internal test set is 0.863 (95% confidence interval [CI] 0.829, 0.898), with a sensitivity of 0.913 (95% [CI] 0.866, 0.961), and specificity of 0.816 (95% [CI] 0.771, 0.861). The AUC in the external test set is 0.947 (95% confidence interval [CI] 0.939, 0.955), with a sensitivity of 0.889 (905% [CI] 0.837, 0.940), and specificity of 0.858 (95% [CI] 0.777, 0.939). For distinguishing different levels of inflammatory activity in UC, the average Macro-AUC in the internal test set and the external test set are 0.827 (95% [CI] 0.803, 0.850) and 0.908 (95% [CI] 0.882, 0.935). the average Micro-AUC in the internal test set and the external test set are 0.816 (95% [CI] 0.792, 0.840) and 0.898 (95% [CI] 0.869, 0.926). Conclusions Comparative analysis with diagnoses made by pathologists at different expertise levels revealed that the algorithm reached a proficiency comparable to the pathologist with 5 years of experience. Furthermore, our algorithm performed superior to other MIL algorithms.

Abstract Background: Cavernous transformation of the portal vein (CTPV) is often associated with portal hypertension and varicose bleeding. Endoscopic treatments (ETs) and transjugular intrahepatic portosystemic shunts (TIPS) can be able to prevent rebleeding in patients with CTPV. This study aimed to compare the clinical outcomes of TIPS and ET in patients with CTPV presenting with variceal bleeding. Methods: We reviewed the data of patients with portal cavernous transformation presenting with variceal bleeding in Nanjing Drum Tower Hospital from February 2014 to January 2021, which included 38 patients who underwent endoscopic treatment and 25 patients who underwent TIPS therapy. Results: During the follow-up period, the upper gastrointestinal rebleeding rate and survival rate have no significant difference between the ET group and TIPS group (P ＞0.05). The median hospitalization cost in the TIPS group ( 93258.00 Chinese Yuan) was significantly higher than that in the ET group (47109.00 Chinese Yuan) (P = 0.001), and the length of hospital stay in the TIPS group ( 14.52 ± 12.00 days) was much shorter than that in the ET group ( 23.05 ± 12.87 days) (P = 0.003). The incidence of OHE in the TIPS group was higher than that in the ET group (P = 0.013). Conclusions: For patients with CTPV presenting with variceal bleeding, TIPS was not superior to ET regarding preventing rebleeding and long-term survival. ET, rather than TIPS, may be a better choice for patients with CTPV presenting with variceal bleeding regarding medical expenses and postoperative complications.

Nanoplastics (NPs), regarded as the emerging contaminants, can enter and be mostly accumulated in the digest tract, which pose the potential threat to intestinal health. In this study, mice were orally exposed to polystyrene (PS), PS-COOH and PS-NH2 NPs with the size of ∼100 nm at a human equivalent dose for 28 consecutive days. All three kinds of PS-NPs triggered Crohn's ileitis-like features, such as ileum structure impairment, increased proinflammatory cytokines and intestinal epithelial cell (IEC) necroptosis, and PS-COOH/PS-NH2 NPs exhibited higher adverse effects on ileum tissues. Furthermore, we found PS-NPs induced necroptosis rather than apoptosis via activating RIPK3/MLKL pathway in IECs. Mechanistically, we found that PS-NPs accumulated in the mitochondria and subsequently caused mitochondrial stress, which initiated PINK1/Parkin-mediated mitophagy. However, mitophagic flux was blocked due to lysosomal deacidification caused by PS-NPs, and thus led to IEC necroptosis. We further found that mitophagic flux recovery by rapamycin can alleviate NP-induced IEC necroptosis. Our findings revealed the underlying mechanisms concerning NP-triggered Crohn's ileitis-like features and might provide new insights for the further safety assessment of NPs.

[This corrects the article on p. 546 in vol. 9, PMID: 30949409.].

Inflammatory bowel disease (IBD) is a systemic disorder affecting intestinal tract and other organs outside the gut, known as extraintestinal manifestations (EIMs). These EIMs are complex and diverse, and early treatment may reduce teratogenic rates and improve quality of life. However, our understanding of EIMs in IBD is currently limited by a lack of mechanistic insight. Fortunately, advances in our understanding of intestinal microecology are allowing us to uncover the underlying mechanisms of EIMs. The gut microbiota can drive aberrant immune activation and intestinal inflammation. Intriguingly, chronic inflammation can also shape the microbiome in reverse and aggravate dysbiosis. Recent research has revealed that microbiome-derived signal molecules play a crucial role in catalyzing enterocolitis and altering mucosal barrier function. Furthermore, gut microbiota-associated antigens can translocate from the intestine to extraintestinal sites, leading to systemic inflammatory responses. The microbiome is showing its potential in treating IBD and EIMs, and microbial engineering approaches, such as probiotic engineering and engineered fecal microbiota transplantation, are exhibiting great promise for IBD therapeutics.

目的 分析英夫利西单抗(infliximab,IFX)治疗的克罗恩病(CD)患者诱导治疗后和维持期的两次治疗药物监测(TDM),与随访中原发无应答(PNR)、继发失应答(SLR)、内镜黏膜愈合(MH)、急性输液反应以及停药的关系.方法 回顾性纳入2018年6月至2022年9月在南京鼓楼医院治疗的中重度CD患者47例,均为生物制剂初治.诱导治疗后第14周时行首次TDM,检测IFX谷浓度和抗肿瘤坏死因子药物抗体(ATI)的滴度,IFX谷浓度≥3 μg/mL判断为达标,根据检测结果允许药物调整优化,维持期第二次行TDM.分析14周IFX谷浓度达标(n=25)和不达标组(n=22)组间及维持期IFX谷浓度不同亚组间的PNR、SLR、MH、急性输液反应和停药的差别,并分析不同IFX谷浓度与ATI阳性率的关系.结果 14周达标组和不达标组在(32±4)周时的MH率分别是80.0％和31.8％,差异有统计学意义(x2=11.113,P＜0.01).14周达标组中,二次达标和不达标组亚组间的ATI率、输液反应率、停药率差异均有统计学意义(P＜0.01).14周不达标组中,二次谷浓度达标和不达标组亚组间的ATI率差异有统计学意义(P＜0.05).极低IFX谷浓度亚组(＜1.0 μg/mL)的ATI阳性率高达53.9％,显著高于其他浓度亚组(P＜0.05).结论 14周IFX谷浓度与CD患者治疗后首次内镜复查MH有密切关系,维持期IFX谷浓度与ATI产生、输液反应、停药均有关,期待经济、便捷的主动TDM以保持药物疗效.

A 31-year-old man was admitted to our hospital due to recurrent abdominal pain and intermittent melena for 9 years. He also suffered from skin thickening and digital clubbing since adolescence (Fig. 1A and B). He denied intake of non-steroidal, anti-inflammatory drugs. Blood tests revealed normocytic normochromic anemia (hemoglobin, 110 g/dL). Other examinations such as T-SPOT.TB, autoantibody biomarkers, cytomegalovirus, Epstein-Barr virus, and growth hormone level were normal. X-ray showed irregular cortical thickening of the tibiofibular and hand (Fig. 1C).