Infectious diseases can cause lasting immune disturbances, but whether they contribute to later inflammatory bowel disease (IBD) is unclear. Hospital-treated infections may be especially informative because they reflect substantial immune challenge, yet their relation to IBD risk and the role of host genetics remain poorly defined. It examines hospital-treated infections and incident IBD in a prospective cohort and integrates gene-environment interaction analyses to identify susceptibility pathways and develop a post-infection risk score. Hospital-treated infections of multiple pathogen types and sites were associated with higher subsequent IBD risk. This association is stronger in carriers of immune-related risk variants, with Crohn's disease linked mainly to innate immune and autophagy pathways and ulcerative colitis to JAK-STAT, T-cell differentiation, and chemokine signaling. An Infection IBD Score based on 44 immune-related genes stratified post-infection risk. These findings support infections as triggers of IBD in genetically susceptible individuals and highlight a potential tool for risk stratification.

Despite treatment advances, intestinal surgery remains common in Crohn’s disease (CD), with over half of patients experiencing postoperative recurrence. Intestinal fibrosis represents a key pathological feature underlying this clinical course. This study aimed to investigate the relationship between fibrosis severity and the risk of postoperative recurrence. A multi-center retrospective cohort study included CD patients undergoing intestinal resection. Histopathological slides from lesion sites and resection margins were analyzed using Masson’s trichrome staining to quantify the proportion of collagen fiber area, representing fibrosis extent. Postoperative endoscopic and clinical recurrence data were collected via electronic medical records and patient follow-up interviews. Multivariable Cox regression models estimated hazard ratios (HRs) with 95

Dietary fibre-based interventions are of growing interest for the prevention and treatment of digestive diseases. In this study, we investigated the effect of resistant starch (RS) on intestinal fibrosis, a stricturing condition driven by excessive extracellular matrix (ECM) accumulation. RS was found to alleviate intestinal fibrosis in a dextran sulfate sodium (DSS)-induced chronic colitis mouse model, as evidenced by restored colon length, reduced ECM deposition (fibronectin and collagen I), and decreased levels of α-smooth muscle actin. Given that RS is fermented by the gut microbiota in the colon, metagenomic sequencing revealed that RS reshaped the composition of the gut microbiota and increased the abundance of beneficial gut bacteria, including Bacteroides acidifaciens, Faecalibaculum rodentium, and Bifidobacterium pseudolongum, which are known to enhance the production of short-chain fatty acids. Targeted metabolomic analysis further showed a marked increase in acetate levels, which was associated with reduced intestinal fibrosis. However, direct in vivo evidence that acetate is required for the anti-fibrotic effect of RS remains lacking. Using human (CCD-18Co) and primary mouse intestinal fibroblasts, the major ECM-producing cells that drive fibrosis progression, we demonstrated that acetate inhibited TGF-β-induced fibroblast activation by inhibiting histone deacetylase 2, thereby enhancing the acetylation level of histone H3 at lysine 27. Collectively, these results suggest a potential microbial-metabolic-epigenetic axis linking RS and acetate to fibrosis attenuation, which awaits causal validation in vivo. This axis holds promise as a therapeutic target for fibrotic diseases.

BACKGROUND:Fibrostenosis is a common and disabling complication of Crohn's disease (CD) with no reliable early biomarkers, limited treatment options and high postoperative recurrence. OBJECTIVE:To investigate the contribution of glioma-associated oncogene homolog 1 (GLI1+) mesenchymal cells to fibrostenotic progression and their potential as a therapeutic target. DESIGN:Fibrotic and non-fibrotic tissue samples were collected from patients with CD undergoing surgery for fibrostenotic obstruction. Chronic colitis was induced in mice using dextran sodium sulfate (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Single-cell RNA sequencing was performed on human and murine intestinal tissues. Gli1-CreERT2; R26-tdTomato and Gli1-CreERT2; R26-iDTR mice were used for lineage tracing and targeted cell ablation. GLI1+ mesenchymal cells were isolated to identify pathogenic determinants. A surgical CD fibrostenosis cohort was analysed. RESULTS:Single-cell transcriptomics and immunofluorescence revealed enrichment of GLI1+ mesenchymal cells at fibrotic sites. Lineage tracing showed that these cells expanded and adopted a myofibroblast phenotype in chronic colitis, whereas their ablation alleviated fibrosis. GLI1+ mesenchymal cells exhibited a distinct transcriptional expression profile with prominent expression of SPARC-related modular calcium-binding protein 2 (SMOC2). SMOC2 was upregulated in human and murine fibrosis, and its knockdown in vivo and in vitro attenuated fibrosis. Mechanistically, GLI1+ mesenchymal cells secreted SMOC2, promoting extracellular matrix deposition and fibroblast activation. In surgical CD cohorts, high SMOC2 expression in intestinal tissue correlated with postoperative recurrence, confirmed in the validation cohort. CONCLUSION:GLI1+ mesenchymal cells drive intestinal fibrostenosis through SMOC2-mediated niche formation. SMOC2 may serve as a predictive biomarker for postoperative recurrence and a potential therapeutic target for CD.

Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disorder marked by a compromised intestinal epithelial barrier and deficient autophagic activity. Suramin, a known antiparasitic medication, exhibits diverse anti-inflammatory properties, though its specific molecular targets and therapeutic efficacy in UC are not well-defined. This study evaluated suramin's protective effects in a DSS-induced acute murine colitis model and identified the underlying molecular pathways. Suramin treatment attenuated clinical symptoms, colon shortening, and mucosal inflammation in a dose-related manner. These positive outcomes included the restoration of intestinal epithelial barrier integrity, demonstrated by increased expression of tight junction proteins (ZO-1, Occludin, and Claudin-1), and enhanced autophagic flux in colonic tissues. Phosphoinositide 3-kinase (PI3K) was identified as a potential direct target of suramin through protein-protein interaction network analysis and molecular docking simulation. A biotin-suramin pull-down assay demonstrated that suramin directly interacts with the p85α regulatory subunit of PI3K, resulting in the inhibition of the overactivated PI3K/AKT/mTOR signaling pathway. Importantly, pharmacological reactivation of PI3K with its specific agonist 740 Y-P abolished the protective effects of suramin, causing intensified intestinal inflammation and barrier failure. Taken together, our results indicate that suramin protects against experimental colitis mainly by directly engaging PI3K p85α, thereby restraining the PI3K/AKT/mTOR axis to stimulate autophagy and reinforce intestinal epithelial barrier integrity. This research identifies suramin as a potential drug repurposing candidate for treating UC.

Tissue-resident memory T cells (TRM cells) have been shown to play an instrumental role in driving the onset and relapse of inflammatory bowel diseases (IBD). However, the underlying mechanism of TRM cells differentiation and its regulation in intestines remain to be unveiled. Mothers against decapentaplegic homolog 3 (SMAD3) is translocated from nucleus to membrane and activated in response to transforming growth factor beta (TGF-β), which is a key cytokine in the process of TRM cells polarization. Cysteine palmitoylation (S-palmitoylation) is a post-translational modification catalyzed by the DHHC family, regulating protein membrane associations. Genes associated with the classic SMAD3 signaling pathway, along with most genes in the DHHC family, were upregulated in TRM cells. Our study demonstrated that SMAD3 underwent reversible S-palmitoylation on Cys31 by DHHC6, leading to SMAD3 endomembrane recruitment and its subsequent colocalization with TGF-β receptor I (TGF-βRI) under TRM polarization conditions. The membrane recruitment of SMAD3 activated SMAD3 and subsequently upregulated the expression of its target genes, inducing the differentiation of TRM cells. In contrast, perturbation in DHHC6-induced palmitoylation with MYD-4 inhibited TRM cells differentiation and alleviated colitis in IBD model mice. Our work provides an example how the immune responses are regulated through the S-palmitoylation-dependent SMAD3 signaling in TRM cells differentiation and reveals protein S-palmitoylation as a potential target in IBD treatment, which could be of greater application considering the wide involvement of protein S-palmitoylation in the signal transduction in mammalian cells. The differentiation of TRM cells is promoted through TGF-β/SMAD3 pathway. The palmitoylation of SMAD3 on Cys31 by DHHC6 drives the membrane localization, the phosphorylation and the activation of SMAD3 under TRM polarization conditions. Inhibiting the differentiation of TRM cells by blocking palmitoylation of SMAD3 ameliorates colitis.

Objective: Idiopathic pulmonary fibrosis (IPF) is a highly heterogeneous interstitial lung disease with poor prognosis. Currently, there is little research using multimodel data and artificial intelligence (AI) for IPF prognostic evaluation. Therefore, constructing a prognostic model with AI system integrating multimodal data is essential to improve clinical management of this disease. Method: The data of IPF patients diagnosed between January, 2018 and November, 2022 were collected from 22 teaching hospitals of 6 provinces in China, including clinical information, blood test indicators, lung function, longitudinal high-resolution computed tomography (HRCT) and survival (latest follow-up result by September, 2024) in Chinese multi-center and multi-modal cohort study of IPF (CMM-IPF). A novel survival analysis framework was developed for survival prediction. Predictive clinical variables were screened using Cox model and Lasso regression. Radiomics features and attention-driven 3D convolutional deep learning features were extracted through pyradiomics and 3D-ResNet respectively. Multimodal data were fused for 1 to 3 years survival rate. Result: There were 285 IPF patients with mean age of 71.1 years and median survival time of 36 months (95% CI, 30-46 months) in the CMM-IPF study. The study identified four important variables: D-dimer, forced vital capacity (FVC), total lung capacitiy (TLC), and direct bilirubin, with hazard ratios of 1.35, 0.98, 0.99, and 1.13. After incorporating the image data with AI system, the performance of the prognostic model is improved, and the AUC of 1 to 3 years survival rate increased from 0.657, 0.735, and 0.762 to 0.719, 0.752, and 0.805. Conclusion: The CMM-IPF study provided up-to-date and real-world information about Chinese IPF patients survival in multi-center, and offered an accurate prognostic evaluation model based on AI system and multi-modal data.

Background:Ulcerative colitis (UC), a chronic inflammatory bowel disease, is characterized by a multifactorial etiology and limited therapeutic options. Recent advancements in plant-derived exosome-like nanoparticles (PDENs) have demonstrated promising potential for UC treatment. This study explored the therapeutic efficacy of Andrographis paniculata-derived exosome-like nanoparticles (APELNs) in alleviating dextran sodium sulfate (DSS)-induced colitis.Methods:APELNs were isolated and purified using sucrose gradient centrifugation and subsequently characterized through visualization techniques. Their stability was assessed under simulated stomach-like and intestine-like conditions. The therapeutic potential of APELNs was evaluated through both in vivo and in vitro experiments. In addition, the biosafety of APELNs was comprehensively analyzed in these settings.Results:APELNs exhibited excellent stability and biosafety, with a targeted accumulation in inflamed colonic tissues under gastrointestinal conditions. The nanoparticles displayed a desirable size (about 180 nm) and a negative zeta potential (-40 mV). Treatment with APELNs significantly ameliorated colonic pathologies in vivo and suppressed the expression of pro-inflammatory cytokines in vitro. Mechanistically, APELNs enhanced gut microbiota richness and diversity, fostering the growth of the probiotic Lactobacillus murinus. Moreover, APELNs reduced intestinal permeability and preserved intestinal barrier integrity by upregulating tight junction proteins, including Claudin-1, zonula occludens-1, Mucin2, and anti-occludin. Importantly, oral administration of APELNs shifted macrophage polarization in the colon, inhibiting the pro-inflammatory M1 subset while promoting the anti-inflammatory M2 subset. This polarization was mediated through the activation of the phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) and Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathways and the upregulation of interleukin-4 receptor expression.Conclusion:These findings highlighted the potential of APELNs as a novel therapeutic strategy for UC, offering a promising alternative for effective disease management.

Previous research has conducted meta-analyses on the diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). However, studies on adverse events (AEs) have been limited and sporadic and have included a highly diverse group of patients (with upper and lower gastrointestinal tract issues) and needles of varying sizes (19-22-25G). The purpose of this systematic review and meta-analysis was to determine the incidence of AEs related to the utilization of 20–22G second-generation EUS-FNB needles subsequent to puncture of the upper gastrointestinal tract and adjacent organs. We searched the PubMed, Embase, and SCIE databases from January 1, 2010, to December 31, 2023. The primary outcome was percentage of summary AEs. Subgroup analyses were based on needle type, needle size, and lesion site. A total of 99 studies were included in the analysis, with 9303 patients. The overall AE rate for 20–22G second generation EUS-FNB needles in upper gastrointestinal EUS-FNB was 1.8% (166/9303), with bleeding being the most common AE at 44.0%. The percentages of pancreatitis, abdominal pain, and other AEs were 24.1%, 21.1%, and 10.8%, respectively. Patients undergoing hepatic EUS-FNB had the highest incidence of AEs at 14.0%, followed by submucosal lesions at 3.2% and pancreatic lesions at 2.6%. EUS-FNB is a safe procedure with a relatively low risk of upper gastrointestinal AEs (1.8%) and no associated deaths. Postoperative bleeding and pancreatitis are the most common complications of EUS-FNB. Most AEs are mild and self-limiting in severity, and serious complications are very rare.

OBJECTIVE:Cinitapride, a gastrointestinal prokinetic, is commonly used for treating functional dyspepsia. However, large-scale, real-world data on its efficacy, especially in patients with overlapping symptoms, are limited. The aim of this study was to evaluate the clinical effectiveness and safety of cinitapride in Chinese patients with functional dyspepsia, including those with overlapping symptoms, in a real-world setting. METHODS:In this single-arm, prospective, multicentric study, 1,012 Chinese outpatients with functional dyspepsia and functional dyspepsia overlapping with gastroesophageal reflux disease, irritable bowel syndrome, and/or functional constipation were treated with cinitapride (1 mg t.i.d.) from May 2019 to March 2021. Symptom improvement was assessed at weeks 2 and 4, with adverse events recorded. RESULTS:At weeks 2 and 4, the overall symptom improvement rate was 62.4 and 90.9%, respectively. Subgroup improvement rates were as follows: functional dyspepsia-gastroesophageal reflux disease, 86.8%; functional dyspepsia-irritable bowel syndrome, 96.2%; functional dyspepsia-functional constipation, 91.7%; and functional dyspepsia-gastroesophageal reflux disease-irritable bowel syndrome, 67.6%. functional dyspepsia patients showed statistically significantly higher improvement than those with overlapping symptoms at weeks 2 (p=0.018) and 4 (p=0.009). The dyspepsia symptom score decreased by 51.0% at week 2 and 74.4% at week 4 (p<0.001). The most common adverse event was asymptomatic electrocardiogram abnormalities (n=8). CONCLUSION:Cinitapride is effective and well-tolerated in treating functional dyspepsia and functional dyspepsia-overlapping gastroesophageal reflux disease, irritable bowel syndrome, and functional constipation in Chinese patients.

Background and objectives:We recently developed a balloon-assisted device for EUS-guided gastroenterostomy (EUS-GE) to enhance the safety and convenience of the procedure. This pilot study was conducted to evaluate the safety and feasibility of this device. Methods:A retrospective analysis of data of patients who underwent EUS-GE using this balloon-assisted device at our institution from March 2024 to July 2024 was conducted. The primary end point was the procedure time, and the secondary end points were the volume of water injection, technical success rate, clinical success rate, and adverse events (AEs). Results:A total of 20 patients (male: 55%; female: 45%) were enrolled, with a mean age of 67.7 ± 9.9 years. The mean procedure time was 29.3 ± 9.4 minutes, and the mean intraoperative water infusion in the jejunum was 92.5 (80-117.5) mL. The technical success rate was 100% (20/20). The clinical success rate was 95% (19/20). One patient (5%) experienced mild abdominal pain after the procedure. No other AEs, such as bleeding, perforation, stent occlusion, or migration, were observed during follow-up. The median follow-up duration was 132 (74-170) days. Conclusion:The balloon-assisted device facilitates the application of EUS-GE, with short procedure time, less intraoperative water injection, high technical success rate, and low incidence of AEs.

BACKGROUND:Infliximab (IFX) is the first biologic to be approved to treat inflammatory bowel disease (IBD). Serum IFX concentrations can be correlated with the clinical prognosis of IBD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an alternative to clinical immunoassays owing to its higher selectivity and sensitivity. An efficient antibody-free LC-MS/MS method was developed in this study to determine serum IFX levels. Methods Protein G-coated magnetic beads were used to capture IFX and the internal standard (cadonilimab [CADO]) in human serum. After enrichment, IFX and CADO were digested using trypsin, and signature peptides were selected for subsequent LC-MS/MS analysis. The results were compared with those from the corresponding immunoassay. Results The selected peptides had good specificity, and the total precision was within 10.5 %. The accuracy was between 92.8 % and 97.6 % in the linear range of 0.5-100 mg/L. The results from the sample assay were in agreement with those from the immunoassay. Conclusion Determination of IFX using LC-MS/MS is more sensitive and robust than other analytical methods. Therefore, the method reported in this study shows potential for use in therapeutical drug monitoring and developing individualized treatment modalities.

evidence from animal experiments indicates that anthocyanin supplements can contribute to intestinal health. Nevertheless, no evidence has linked dietary anthocyanins to the prevention potential against inflammatory bowel disease (IBD) in humans. We leveraged data from 188,044 IBD-free individuals (mean age 59 years; 55.2% females) from the prospective cohort UK Biobank. The anthocyanin intake was estimated using dietary information from validated 24 h dietary recalls. Incident IBD was ascertained via national health-related records. Genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) was estimated by polygenic risk scores and further categorized into low- and high-risk groups by median value. The Cox proportional regression model was applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). During the mean follow-up of 9.7 years, we documented 255 CD and 606 UC. We found that compared with participants with the lowest quartiles of anthocyanin intake, those in the highest quartiles were associated with 24% (95% CI 6%-38%, p = 0.012; p-trend = 0.003) and 35% (95% CI 16%-49%, p = 0.001; p-trend < 0.001) reduced risk of IBD and UC, respectively. The inverse associations were stronger (p-interaction = 0.022) among individuals with a high genetic risk of UC. We did not observe a significant association between anthocyanin intake and CD (p-trend = 0.536). Higher dietary anthocyanin intake was associated with reduced risk of IBD and UC, but not CD. Genetic factors may modify the influence of dietary anthocyanin on UC susceptibility, and possible mechanisms need to be further elucidated in the future.

To the Editor: Irritable bowel syndrome (IBS) is one of the most common adult functional gastrointestinal disorders (FGIDs), with an estimated global prevalence of 1.5–11.2%. The prevalence rates for anxiety and depressive symptoms and disorders underscore the psychological impact on IBS patients, emphasizing the need for comprehensive diagnostic tools tailored to specific populations.[1] The main diagnostic reference for IBS is the Rome criteria which is now the standard practice for IBS diagnosis worldwide. The most recent iteration is Rome IV [Supplementary Table 1, https://links.lww.com/CM9/C102]. Despite its broad acceptance, validation studies demonstrated that the Rome criteria only performed modestly in diagnosing IBS and, in clinical practice, Rome criteria are not commonly used. The overlap between the symptoms of IBS and FGIDs must be considered in the diagnosis of IBS and should be taken into consideration in the development of symptom-based diagnostic tools. Presently, there is no specific gold standard for IBS diagnostic method in Asia and only Japanese Society of Gastroenterology (JSGE) published the second edition of evidence-based clinical practice guidelines for IBS in 2020.[2] Hence, we developed the simplified diagnosis tool for IBS with predominant constipation (IBS-C) diagnosis in Chinese patients. The tool was derived based on the relevant parts of the Rome IV and Asian FGID scales. Similar to Rome IV, the simplified diagnosis tool for IBS-C is a patient self-reported questionnaire [Supplementary Table 2, https://links.lww.com/CM9/C102]. It comprises eight questions: one question on the duration of the disease, two questions on the main symptoms, three questions on the change of symptoms, and two questions on stool appearance [Supplementary Table 2, https://links.lww.com/CM9/C102]. The presence of mid–upper abdominal symptoms is assessed in questions 2 and 6. The objective of this study was to assess the diagnostic accuracy of the simplified diagnosis tool for IBS-C in the Chinese population, using Rome IV as the standard reference. This was a multicenter, prospective, observational study (ClinicalTrials.gov Identifier: NCT04968652) that included a face-to-face visit, during which patients underwent the IBS-C diagnostic assessment by an experienced gastrointestinal (GI) clinician. Patients were identified by investigators during routine clinical visits at 10 participating study centers between November 1, 2021, and October 28, 2022. The key eligibility criteria are mentioned in supplementary files, https://links.lww.com/CM9/C102. Diagnostic assessments for patients were first performed using Rome IV criteria [Supplementary Table 1, https://links.lww.com/CM9/C102], followed by the simplified diagnosis tool during the same visit [Supplementary Table 2, https://links.lww.com/CM9/C102]. Patients were assigned to the IBS-C group if their Rome IV results were marked as "IBS-C," or to the non-IBS-C group if their Rome IV results were marked as "non-IBS-C." The study protocol and the informed consent form were approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University. Written informed consent was provided upon enrollment and patients were permitted to discontinue the study at any time. The primary outcome was the sensitivity and specificity of the simplified diagnosis tool related to IBS-C diagnosis in Chinese patients diagnosed with IBS-C using Rome IV criteria as the standard reference. Secondary outcomes were the accuracy of the simplified diagnosis tool for IBS-C, negative and positive predictive values, and kappa coefficient. The definitions for each endpoint are shown in Supplementary Tables 3 and 4, https://links.lww.com/CM9/C102. A total of 301 patients were screened and 300 patients were enrolled and completed the study. FAS included 133 patients assigned to the IBS-C group and 167 patients to the non-IBS-C group based on Rome IV criteria [Supplementary Figure 1, https://links.lww.com/CM9/C102]. Based on the simplified diagnosis tool for IBS-C, 205 (68.3%) patients were diagnosed with IBS-C, and 95 (31.7%) patients without IBS-C [Supplementary Table 5, https://links.lww.com/CM9/C102]. A total of 285 patients were included in the sensitivity analysis. The mean (±SD) age of the total population was 43.9 (±16.4) years; 77.7% of the patients were female and all patients were Asian [Supplementary Table 6, https://links.lww.com/CM9/C102]. Of 285 patients, 133 and 152 patients were assigned to the IBS-C and non-IBS-C groups, respectively, using Rome IV criteria, while 204 patients were diagnosed with IBS-C and 81 without IBS-C, respectively, using the simplified diagnosis tool for IBS-C diagnosis [Supplementary Table 7, https://links.lww.com/CM9/C102]. Using Rome IV as the standard reference, the sensitivity and specificity of the simplified diagnosis tool for IBS-C were 86.5% (95% confidence interval [CI], 79.5–91.8%) and 46.1% (95% CI, 38.4–54.0%), respectively [Table 1]. In the sensitivity analysis, the sensitivity and specificity were 86.5% (95% CI, 79.5–91.8%) and 41.4% (95% CI, 33.5–49.7%), respectively [Supplementary Table 8, https://links.lww.com/CM9/C102]. The accuracy of the simplified diagnosis tool for IBS-C was 64.0% (95% CI, 58.3–69.4%), the positive predictive value was 56.1% (95% CI, 49.0–63.0%), the negative predictive value was 81.1% (95% CI, 71.7–88.4%), and the kappa coefficient was 0.31 (95% CI, 0.22–0.40) [Table 1]. In the sensitivity analysis, the accuracy was 62.5% (95% CI, 56.6–68.1%), the positive predictive value was 56.4% (95% CI, 49.3–63.3%), the negative predictive value was 77.8% (95% CI, 67.2–86.3%), and the kappa coefficient was 0.27 (95% CI, 0.17–0.37) [Supplementary Table 8, https://links.lww.com/CM9/C102]. Table 1 - Diagnostic accuracy of the simplified diagnosis tool for IBS-C (FAS) (N = 300). Variables Values Rome IV, n (%) IBS-C 133 (44.3) Non-IBS-C 167 (55.7) Simplified diagnosis tool, n (%) IBS-C 205 (68.3) Non-IBS-C 95 (31.7) Sensitivity (%) (95% CI)* 86.5 (79.5–91.8) Specificity (%) (95% CI)* 46.1 (38.4–54.0) Accuracy (%) (95% CI)* 64.0 (58.3–69.4) Positive predictive value (%) (95% CI)* 56.1 (49.0–63.0) Negative predictive value (%) (95% CI)* 81.1 (71.7–88.4) Kappa coefficient (95% CI)† 0.31 (0.22–0.40) CI: Confidence interval; FAS: Full analysis set; IBS-C: Irritable bowel syndrome with predominant constipation. *95% CI was determined using the Clopper–Pearson exact method. †95% CI was determined using the Cohen (1960) method. Overall, the simplified diagnosis tool displayed high sensitivity for diagnosing IBS-C. A high proportion of patients diagnosed with IBS-C using Rome IV were also diagnosed with IBS-C using the simplified diagnosis tool for IBS-C (i.e., a low false negative rate). The use of this tool in routine clinical practice may minimize unnecessary investigations during the diagnostic workup for patients with IBS-C, thus reducing the economic and psychological burden on these patients.[3,4] The modest specificity of this tool for IBS-C highlights several important points. First, it may incorrectly diagnose with IBS-C in patients who do not have the disease (i.e., false positives). The potential false positives must be considered when interpreting the results of the simplified diagnosis tool for IBS-C in clinical practice. Further research is also required to confirm the sensitivity and specificity of this tool for the diagnosis of IBS-C in Asian populations. Second, there is a lack of a gold standard diagnostic tool or standardized biomarker to diagnose IBS with acceptable precision in studies that assessed the accuracy of diagnostic tests for IBS. A major limitation of using Rome IV in Asian populations is that it was validated in Western populations, who have a lower prevalence of dyspeptic upper abdominal symptoms than patients from Asian countries. In the present study, 34.6% of patients who were diagnosed with IBS-C using Rome IV had upper abdominal symptoms when assessed using the simplified diagnosis tool for IBS-C, and half of these patients reported that the upper abdominal symptoms were related to meal intake. By incorporating questions about upper abdominal symptoms, the simplified diagnosis tool for IBS-C may better distinguish between patients with IBS-C and functional disease and therefore be a more accurate diagnostic tool for use in Asian patients than Rome IV. Abdominal discomfort or bloating is often the most important feature of IBS among Asian patients, which may lead to underdiagnosis of IBS using Rome IV. These differences in symptoms between patients in Western and Asian countries may contribute to the modest sensitivity of the Rome criteria in diagnosing IBS in Asian patients, as well as the modest specificity of the simplified diagnosis tool for IBS-C using Rome IV as a reference. Consistent with these observations, the kappa coefficient in this study indicated poor agreement between Rome IV and the simplified diagnosis tool for IBS-C. Overall, 13.5% of patients diagnosed with IBS-C using Rome IV criteria were judged as not having IBS-C by the simplified diagnosis tool, while 53.9% of patients diagnosed with non-IBS-C using Rome IV were judged as having IBS-C using the simplified diagnosis tool. In addition to the factors described earlier, this disagreement could be due to the stricter diagnostic criteria used by Rome IV, which exclude patients with mild-to-moderate symptoms. As patients were required to recall their symptoms from 6 months before completing the questionnaire, this could have resulted in a recall bias. Although any recall bias is unavoidable in questionnaire-based study, shorter timeframe of the simplified diagnosis tool has minimized the recall bias, but it is susceptible to the occurrence of infrequent events. To minimize selection bias, eligible patients included in the study were diagnosed during routine clinic visits by experienced GI clinicians who were trained with both Rome IV and the simplified diagnosis tool for IBS-C. There was no loss to follow-up as all assessments were completed within the initial visit. In conclusion, the simplified diagnosis tool demonstrated good sensitivity and may help identify more Chinese patients with IBS-C; thus, it might be an alternative to Rome IV in China and even Asia, although further validation is required by conducting more studies consisting of various sample sizes and other Asian or international cohorts to further validate the results of this study. This would help in greater regional or global applicability of the simplified diagnosis tool questionnaire. Moreover, the simplified diagnosis tool for IBS-C is easy to administer and accounts for the differences in symptoms between Asian and Western populations. The simplified diagnosis tool for IBS-C may provide a valuable input for developing Rome V. Acknowledgments Medical writing assistance was provided by Zhi Yang Loh, BSc; Liting Hang, PhD; and Alice Carruthers, PhD, of Nucleus Global Asia-Pacific. We would like to thank all researchers and patients who participated in the study, and AstraZeneca for sponsoring this study. Conflicts of interest The study was funded by AstraZeneca, China. Availability of data and materials The data that support the findings of this study are available from the corresponding author upon reasonable request.

BACKGROUND:Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM:To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China.METHODS:We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment.RESULTS:Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising.CONCLUSION:CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.

Background: The role of diet on the risk of chronic pancreatitis (CP) is understudied. The health benefits of the Mediterranean diet (MedDiet) pattern have long been recognized, but its association with CP risk is unclear. We aimed to investigate the association between adherence to MedDiet and the incidence of CP in a large-scale cohort. Methods: 190 790 participants from the UK Biobank were involved, all free of CP and with typical diet recall data at recruitment. The diagnosis of CP was ascertained by the combination of hospital inpatient data, primary care data, and death registry data. Multivariable Cox regression models were used to evaluate the associations between MedDiet adherence, measured by the Mediterranean Diet Adherence Screener (MEDAS) continuous score, and the incidence of CP. The mediating role of inflammation (assessed by C-reactive protein) and metabolic status between MedDiet adherence and CP risk was also investigated. Results: During a mean of 10.8 years of follow-up, 214 participants developed CP. Individuals with the highest adherence to MedDiet, defined by continuous MEDAS scores, exhibited significantly lower risk of developing CP (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.40-0.82; p = 0.002) compared to those in the lowest tertiles. Metabolic status mediated 4.74% of the association between MedDiet adherence and CP risk, while the mediating role of C-reactive protein was not significant. Conclusion: Greater Mediterranean diet adherence is associated with reduced chronic pancreatitis risk. The role of diet on the risk of chronic pancreatitis (CP) is understudied.

Importance:With the widespread use of anti-SARS-CoV-2 drugs, accumulating data have revealed potential viral load rebound after treatment. Objective:To compare COVID-19 rebound after a standard 5-day course of antiviral treatment with VV116 vs nirmatrelvir-ritonavir. Design, Setting, and Participants:This is a single-center, investigator-blinded, randomized clinical trial conducted in Shanghai, China. Adult patients with mild-to-moderate COVID-19 and within 5 days of SARS-CoV-2 infection were enrolled between December 20, 2022, and January 19, 2023, and randomly allocated to receive either VV116 or nirmatrelvir-ritonavir. Interventions:Participants in the VV116 treatment group received oral 600-mg VV116 tablets every 12 hours on day 1 and 300 mg every 12 hours on days 2 through 5. Participants in the nirmatrelvir-ritonavir treatment group received oral nirmatrelvir-ritonavir tablets with 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 hours for 5 days. Participants were followed up every other day until day 28 and every week until day 60. Main Outcomes and Measures:The primary outcome was viral load rebound (VLR), defined as a half-log increase in viral RNA copies per milliliter compared with treatment completion. Secondary outcomes included a reduction in the cycle threshold value of 1.5 or more, time until VLR, and symptom rebound, defined as an increase of more than 2 points in symptom score compared with treatment completion. The primary outcome and secondary outcomes were analyzed using the full analysis set. Sensitivity analyses were conducted using the per protocol set. Adverse events were analyzed using the safety analysis set. Results:The full analysis set included 345 participants (mean [SD] age, 53.2 [16.8] years; 175 [50.7%] were men) who received VV116 (n = 165) or nirmatrelvir-ritonavir (n = 180). Viral load rebound occurred in 33 patients (20.0%) in the VV116 group and 39 patients (21.7%) in the nirmatrelvir-ritonavir group (P = .70). Symptom rebound occurred in 41 of 160 patients (25.6%) in the VV116 group and 40 of 163 patients (24.5%) in the nirmatrelvir-ritonavir group (P = .82). Viral whole-genome sequencing of 24 rebound cases revealed the same lineage at baseline and at viral load rebound in each case. Conclusions and Relevance:In this randomized clinical trial of patients with mild-to-moderate COVID-19, viral load rebound and symptom rebound were both common after a standard 5-day course of treatment with either VV116 or nirmatrelvir-ritonavir. Prolongation of treatment duration might be investigated to reduce COVID-19 rebound. Trial Registration:Chinese Clinical Trial Registry Identifier: ChiCTR2200066811.

BackgroundUp to 45.9% of polyps are missed during colonoscopy, which is the major cause of post-colonoscopy colorectal cancer (CRC). Computer-aided detection (CADe) techniques based on deep learning might improve endoscopists’ performance in detecting polyps. We aimed to evaluate the effectiveness of the CADe system in assisting endoscopists in a real-world clinical setting.MethodsThe CADe system was trained to detect colorectal polyps, recognize the ileocecal region, and monitor the speed of withdrawal during colonoscopy in real-time. Between 17 January 2021 and 16 July 2021. We recruited consecutive patients aged 18–75 years from three centers in China. We randomized patients in 1:1 groups to either colonoscopy with the CADe system or unassisted (control). The primary outcomes were the sensitivity and specificity of the endoscopists. We used subgroup analysis to examine the polyp detection rate (PDR) and the miss detection rate of endoscopists.ResultsA total of 1293 patients were included. The sensitivity of the endoscopists in the experimental group was significantly higher than that of the control group (84.97 vs. 72.07%, p < 0.001), and the specificity of the endoscopists in these two groups was comparable (100.00 vs. 100.00%). In a subgroup analysis, the CADe system improved the PDR of the 6–9 mm polyps (18.04 vs. 13.85%, p < 0.05) and reduced the miss detection rate, especially at 10:00–12:00 am (12.5 vs. 39.81%, p < 0.001).ConclusionThe CADe system can potentially improve the sensitivity of endoscopists in detecting polyps, reduce the missed detection of polyps in colonoscopy, and reduce the risk of CRC.RegistrationThis clinical trial was registered with the Chinese Clinical Trial Registry (Trial Registration Number: ChiCTR2100041988).Clinical trial registrationwebsite www.chictr.org.cn, identifier ChiCTR2100041988.

Cronkhite-Canada综合征(CCS)是一组以胃肠道弥漫性息肉和外胚层变化为特征的综合征,其临床表现主要为慢性腹泻和吸收不良,由于发病率罕见,早期发现和诊断对医生来说是一个挑战.本文报告1例CCS病例,58岁男性,临床表现为慢性水样腹泻、便血、体重减轻和皮肤变化,包括指甲营养不良和色素沉着;实验室检查结果提示贫血和低蛋白血症;CT小肠造影检查发现全消化道黏膜息肉样增生,高度怀疑CCS,随后行内镜检查证实了该诊断.患者经治疗后,症状明显好转,在近1年的随访中,CT小肠造影和内镜检查均提示明显缓解.本文对该疾病进行文献综述,旨在总结其CT小肠造影表现,以提高临床医生对本病的认识,为CCS的早期诊断提供一定的思路.