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Particle-enhanced turbidimetric immunoassay (PETIA) is a new measurement procedure for detecting fecal calprotectin (FC). We aimed to investigate the accuracy and clinical performance of PETIA for FC. We assessed the accuracy of PETIA for FC measurements through concordance analysis, Passing-Bablok regression and Bland-Altman analysis, using enzyme-linked immunosorbent assay (ELISA) as the reference. To evaluate the clinical performance of PETIA, the FC levels of individuals with significant and non-significant bowel diseases were compared. The receiver operating characteristic (ROC) analysis was performed to determine the appropriate cut-off value of FC detected by PETIA for discriminating subjects with significant and non-significant colorectal lesions. Of the 413 cases analyzed, 340 (82.3%) were concordant between PETIA and ELISA. No significant discordance was observed. There was a good agreement (y = -7.710+0.957x) between PETIA and ELISA for detecting FC. The FC level detected by PETIA in patients with significant bowel diseases (159.1 [31.3, 821.0] µg/g) was significantly higher than that of subjects with non-significant bowel diseases (10.3 [4.2, 38.5] µg/g) ( p  < 0.001). The AUC of FC for identifying significant bowel diseases detected by PETIA was 0.82 ( p  < 0.001). With a cut-off value of 77.6µg/g, the specificity and positive predictive value were 92.2% and 97.1%, respectively. The PETIA for FC measurement showed good clinical performance for detecting bowel diseases.

Background: The incidence and mortality of colorectal cancer (CRC) in China are increasing in recent years. The clarified pathogenesis and detectable precancerous lesions of CRC make it possible to prevent, screen, and diagnose CRC at an early stage. With the development of endoscopic and surgical techniques, the choice of treatment for early CRC is also worth further discussion, and accordingly, a standard follow-up program after treatment needs to be established., Methods: This clinical practice guideline (CPG) was developed following the recommended process of the World Health Organization, adopting Grading of Recommendations Assessment, Development and Evaluation (GRADE) in assessing evidence quality, and using the Evidence to Decision framework to formulate clinical recommendations, thereby minimizing bias and increasing transparency of the CPG development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guides to ensure the guideline's completeness and transparency., Results: This CPG comprises 46 recommendations concerning prevention, screening, diagnosis, treatment, and surveillance of CRC. In these recommendations, we have indicated protective and risk factors for CRC and made recommendations for chemoprevention. We proposed a suitable screening program for CRC based on the Chinese context. We also provided normative statements for the diagnosis, treatment, and surveillance of CRC based on existing clinical evidence and guidelines., Conclusions: The 46 recommendations in this CPG are formed with consideration for stakeholders' values and preferences, feasibility, and acceptability. Recommendations are generalizable to resource-limited settings with similar CRC epidemiology pattern as China., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: With the increasing prevalence of antibiotic resistance, real-world data on the optimal empirical second-line therapy for Helicobacter pylori are still limited., Objectives: To evaluate the real-world efficacy of various second-line therapies for H. pylori., Patients and Methods: This was a retrospective population-based cohort study of all H. pylori-infected patients who had received the second-line treatment after the failure of primary clarithromycin triple therapy in Hong Kong between 2003 and 2018. The retreatment success rates of different second-line therapies were evaluated., Results: A total of 7591 patients who received second-line treatment were included. Notably, the most commonly prescribed regimen was still clarithromycin triple therapy, but the frequency of use had decreased from 59.5% in 2003-06 to 28.7% in 2015-18. Concomitant non-bismuth quadruple therapy had emerged as the commonest regimen (from 3.3% to 43.9%). In a validation analysis, the sensitivity and specificity of retreatment-inferred second-line treatment failure were 88.3% and 97.1%, respectively. The overall success rate of second-line therapies was 73.6%. Bismuth quadruple therapy had the highest success rate of 85.6%, while clarithromycin triple therapy had the lowest success rate of 63.5%. Specifically, bismuth/metronidazole/tetracycline quadruple, metronidazole/tetracycline triple, levofloxacin/metronidazole/tetracycline quadruple, rifabutin/amoxicillin triple and amoxicillin/levofloxacin triple therapies had relatively higher success rates over 80%. Age, treatment duration, baseline conditions and first-line treatment used were associated with success rate., Conclusions: Bismuth quadruple therapy was the most effective second-line regimen for H. pylori in this real-world study. Despite a very low success rate, clarithromycin-containing triple therapies were still commonly used as second-line regimens., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains the most frequent and severe complication following ERCP, elevating both patient suffering and healthcare costs, and posing challenges to the advancement of ERCP techniques. Empirical evidence supports the prophylactic use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of PEP, especially in high-risk populations, as endorsed by both the American Society for Gastrointestinal Endoscopy (ASGE) and the European Society for Gastrointestinal Endoscopy (ESGE). However, the prophylactic efficacy of NSAIDs in average-risk individuals, alongside the ideal drug selection, dosing, and timing of NSAID administration, remains to be elucidated. Furthermore, the synergistic preventive potential of NSAIDs when integrated with other interventions, such as hydration, pancreatic stenting, somatostatin administration, sublingual nitrate application, and epinephrine, warrants further clarification. In this paper, we conduct an exhaustive review of the prophylactic effect and clinical administration of NSAIDs for PEP. We comprehensively synthesize findings from clinical trials investigating NSAIDs, both in monotherapy and combination regimens, for PEP prevention. Additionally, we scrutinize the current landscape of NSAID usage in clinical practice and evaluate their cost-effectiveness. Future research should concentrate on refining NSAID prophylaxis strategies for PEP in patients at different risk levels, while also enhancing adherence to clinical guidelines and alleviating the issue of NSAID cost inflation., (© 2024. The Author(s).)

Background: To examine the cardiovascular disease (CVD) risks associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and different numbers of cardiometabolic risk factors (CMRFs) in patients with inflammatory bowel disease (IBD) based on a long-term prospective cohort., Methods: Prevalent IBD patients at baseline who were free of CVD, cancer, alcoholic liver disease, cancer and hepatitis B/C virus seropositive were included (N = 4204). MASLD, MASLD subtypes [pure MASLD, MASLD with increased alcohol intake (MetALD)], lean/non-lean MASLD and CMRFs at baseline were defined according to the latest criteria proposed by AASLD and EASL. The primary outcome was incident CVD, including ischaemic heart disease (IHD), heart failure (HF) and stroke. Multivariable Cox proportional hazard models were used to estimate the relationship., Results: Overall, 1528 (36.4%) were diagnosed with MASLD at baseline. During a median of 13.1-year follow-up, 503 incident CVDs were identified. Compared with IBD-only, IBD-MASLD patients had an increased risk of CVD (HR = 1.77, 95%CI: 1.26-2.49), especially in those with MetALD (HR = 2.34, 1.34-4.11) and lean MASLD (HR = 2.30, 1.13-4.66). As the number of CMRFs increased, the risks of CVD were significantly increased (p trend  <0.001), with a 116% and 92% excess risk in MASLD with 3 CMRFs (HR = 2.16, 1.48-3.15) and ≥4 CMRFs (HR = 1.92, 1.27-2.91). Similar excess risk of incident IHD and HF was observed in IBD-MASLD, either pure MASLD or MetALD, as well as lean/non-lean MASLD., Conclusions: MASLD is associated with increased CVD risk in IBD patients, with greater risk as number of CMRFs increased and evidently higher risk in MetALD and lean MASLD patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The incidence of multiple primary malignancies (MPMs) after early esophageal cancer is increasing. This study aimed to explore the clinical features of patients with MPMs and identify independent risk factors for the development of MPMs after endoscopic treatment in early esophageal squamous cell carcinoma (ESCC) patients., Methods: Patients diagnosed as early ESCC at Beijing Friendship Hospital were retrospectively analyzed. Independent factors affecting MPMs were selected by univariate and multivariate Cox regression analyses., Results: Among 299 patients with early ESCC, the mean age was 64.22 years; 219 were male (73.24%). Of these, 32 patients (10.70%) developed MPMs during a follow-up period of 120 months; 10 were metachronous and 22 synchronous. Multivariate Cox analysis showed that alcohol drinking ≥5 standard drinks/day [hazard ratio (HR) =4.21, 95% confidence interval (CI): 1.79-9.90, P<0.001], lower location (HR =2.49, 95% CI: 1.18-5.22, P=0.02), submucosal infiltration depth (HR =3.38, 95% CI: 1.31-8.69, P=0.01), and multiple lesions (HR =2.41, 95% CI: 1.15-5.04, P=0.02) were independent risk factors for developing MPMs in patients with early esophageal cancer., Conclusions: Early ESCC is associated with a high risk of developing MPMs. Monitoring the development of MPMs in patients with early ESCC based on identified risk factors is of great importance., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-299/coif). The authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

Nowadays, endoscopic submucosal dissection (ESD) is commonly performed for the removal of large gastrointestinal lesions. Endoscopic mucosal defect closure after ESD is vital to avoid adverse events. In recent years, many innovative instruments have emerged and proved to be beneficial. In this paper, we conducted a thorough literature review and summarized the closure methods for large-size post-ESD mucosal defects over decades. We separated these methods into five categories based on the operational principle: "side closure" method, "ring closure" method, "layered closure" method, "hand suturing closure" method, and "specially designed device closure" method. Side closure with clips assisted by instruments such as threads or loops is applicable for each segment of the gastrointestinal tract to prevent postoperative bleeding. If the defect tension is too large to close with the traditional side closure methods, zigzag closure and ring closure could be applied to gather the bilateral defect edges together and achieve continuous closure. In the stomach and rectum with a high risk of submucosal dead space between the submucosa and muscular layers, side closure methods with muscle layer grasping clip or layered closure methods could enable the involvement of the deep submucosa and muscle layers. The ring closure method and specially designed devices including over-the-scope clip, Overstitch, and X-tack could resolve perforation effectively. Individual closure method requires endoscope reinsertion or sophisticated operation, which may be limited by the deep location and the narrow lumen, respectively. Although specially designed devices are expected to offer promising prospectives, the cost-effectiveness remains to be a problem., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Aim: To examine the bidirectional association between type 2 diabetes (T2D) and irritable bowel syndrome (IBS) in a large prospective population cohort., Methods: Participants free of IBS at baseline in the UK Biobank were included in the analysis of T2D and incident IBS (cohort 1), with 11 140 T2D patients and 413 979 non-T2D patients. Similarly, those free of T2D at baseline were included in the analysis of IBS and incident T2D (cohort 2), with 21 944 IBS patients and 413 979 non-IBS patients. Diagnoses of T2D and IBS were based on International Classification of Disease-10 codes. The Cox proportional hazards model was used to estimate adjusted hazard ratios (HRs)., Results: In cohort 1, 8984 IBS cases were identified during a median 14.5-year follow-up. Compared with non-T2D, T2D patients had a 39.0% increased risk of incident IBS (HR = 1.39, 95% confidence interval [CI]: 1.23-1.56, P < .001), with a higher IBS risk in those with higher fasting blood glucose levels (HR = 1.43, 95% CI: 1.19-1.72, P < .001) or longer T2D duration (HR = 1.47, 95% CI: 1.23-1.74, P < .001). In cohort 2, 29 563 incident T2D cases were identified. IBS patients had an 18.0% higher risk of developing T2D versus non-IBS patients (HR = 1.18, 95% CI: 1.12-1.24, P < .001). A similar excess T2D risk was observed in IBS patients with a duration of either less than 10 years, or of 10 years or longer. Further sensitivity analysis and subgroup analysis indicated consistent findings., Conclusions: T2D and IBS exhibit a bidirectional association, with an increased risk of co-morbidity. Awareness of this association may improve the prevention and management of both diseases., (© 2024 John Wiley & Sons Ltd.)

Aims: The purpose of this study was to investigate the role of DGUOK in the pro-gression of colorectal cancer (CRC) and its impact on the sensitivity of CRC cells to 5-FU treatment., Methods: We conducted bioinformatics analysis and qRT-PCR to evaluate DGUOK expression in CRC tissues/cells. Cell viability of CRC cells treated with 5-FU was assessed using CCK-8 and colony formation assays. Autophagy levels were determined through immunofluorescence assays and Western blot analysis. Additionally, the influence of p-p38 on autophagy was inves-tigated via Western blotting. A rescue assay was performed to confirm whether DGUOK/p38 affects 5-FU sensitivity in CRC cells through autophagy., Results: Our findings indicate that DGUOK is upregulated in CRC tissues compared to normal tissues, correlating with increased cell proliferation and migration. Functionally, inhibition of DGUOK enhances autophagy, thereby decreasing the sensitivity of CRC cells to 5-FU. This ef-fect is partly mediated by DGUOK's impact on the mitogen-activated protein kinase (MAPK) pathway, specifically promoting the phosphorylation of p38 MAPK, a crucial regulator in au-tophagy pathways., Conclusion: These results suggest that DGUOK could serve as a novel marker for predicting the efficacy of 5-FU in CRC treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

It takes more than 20 years for normal colorectal mucosa to develop into metastatic carcinoma. The long time window provides a golden opportunity for early detection to terminate the malignant progression. Here, we aim to enable liquid biopsy of T1a stage colorectal cancer (CRC) and precancerous advanced adenoma (AA) by profiling circulating small extracellular vesicle (sEV)-derived RNAs. We exhibited a full RNA landscape for the circulating sEVs isolated from 60 participants. A total of 58,333 annotated RNAs were detected from plasma sEVs, among which 1,615 and 888 sEV-RNAs were found differentially expressed in plasma from T1a stage CRC and AA compared to normal controls (NC). Then we further categorized these sEV-RNAs into six modules by a weighted gene coexpression network analysis and constructed a 60-gene t-SNE model consisting of the top 10 RNAs of each module that could well distinguish T1a stage CRC/AA from NC samples. Some sEV-RNAs were also identified as indicators of specific endoscopic and morphological features of different colorectal lesions. The top-ranked biomarkers were further verified by RT-qPCR, proving that these candidate sEV-RNAs successfully identified T1a stage CRC/AA from NC in another cohort of 124 participants. Finally, we adopted different algorithms to improve the performance of RT-qPCR-based models and successfully constructed an optimized classifier with 79.3% specificity and 99.0% sensitivity. In conclusion, circulating sEVs of T1a stage CRC and AA patients have distinct RNA profiles, which successfully enable the detection of both T1a stage CRC and AA via liquid biopsy., Competing Interests: LM, FB, JM, QG, XL, SZ, SZ No competing interests declared, XL, LZ, ZL are employed by Echo Biotech Co, Ltd. The authors have no other competing interests to declare, (© 2023, Min et al.)

Background: Non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) have shown similar worsening epidemic patterns globally and shared various overlapping pathophysiological mechanisms. However, evidence on the relationship between NAFLD and IBD risk is lacking. We aimed to investigate the associations between long-term risk of incident IBD and NAFLD in a large prospective cohort., Methods: Participants from the United Kingdom Biobank cohort ( https://biobank.ndph.ox.ac.uk/ ) who were free of IBD and alcoholic liver disease at baseline were enrolled. Baseline non-alcoholic fatty liver degree was measured by the well-established fatty liver index (FLI). The outcomes of interest included incident IBD, ulcerative colitis (UC), and Crohn's disease (CD). Multivariable Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Among 418,721 participants (mean FLI: 48.11 ± 30.11), 160,807 (38.40%) participants were diagnosed as NAFLD at baseline. During a median of 12.4 years' follow-up, 2346 incident IBD cases (1545 UC, 653 CD, and 148 IBD-unclassified) were identified. Due to limited events, those IBD-unclassified were combined in UC or CD when examining the associated risk of UC or CD, separately. Compared with the lowest quartile of FLI, the highest quartile showed a separately 36.00%, 25.00%, and 58.00% higher risk of incident IBD (HR Q4 vs.Q1 = 1.36, 95% CI: 1.19-1.55, Ptrend <0.001), UC (HR Q4 vs.Q1 = 1.25, 95% CI: 1.07-1.46, Ptrend = 0.047), and CD (HR Q4 vs.Q1 = 1.58, 95% CI: 1.26-1.97, Ptrend <0.001) after multivariable adjustment. Compared with non-NAFLD, NAFLD participants had a significantly higher risk of incident IBD (HR = 1.13, 95% CI: 1.04-1.24) and CD (HR = 1.36, 95% CI: 1.17-1.58)., Conclusions: Higher degree of non-alcoholic fatty liver is associated with increased risk of incident IBD. Interventions aimed at improving NAFLD may be a potential targeted strategy for the detection and treatment of IBD., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: Cholelithiasis poses significant health and economic burdens, necessitating novel pharmacological targets to enhance treatment efficacy., Method: Based on genome-wide association analysis (GWAS) studies, we performed two-sample Mendelian randomization (MR) analysis based on plasma proteomics to explore potential drug targets in European (nCase=40,191 and nControl=361,641) and Asian (nCase=9,305 and nControl=168,253) populations. We confirmed the directionality and robust correlation of the drug targets with the results through reverse MR analysis, Steiger filtering, Bayesian colocalization, phenotype scanning and replication in multiple databases. Further exploration of the safety and possible mechanisms of action of phenome-wide MR analysis and protein‒protein interactions (PPIs) as individual drug targets was performed., Results: Our proteomics-based MR analyses suggested that FUT3 (OR=0.87; 95% CI, 0.84-0.89; P=4.70×10-32), NOE1 (OR=0.58; 95% CI, 0.52-0.66; P=4.21×10-23), UGT1A6 (OR=0.68; 95% CI, 0.64-0.73; P=9.58×10-30) and FKBP52 (OR=1.75; 95% CI, 1.37-2.24; P=8.61×10-6) were potential drug targets in Europeans, whereas KLB (OR=1.11; 95% CI, 1.07-1.16; P=7.59×10-7) and FGFR4 (OR=0.94; 95% CI, 0.91-0.96; P=4.07×10-6) were valid targets in East Asians. There was no reverse causality for these drug targets. Evidence from Bayesian colocalization analyses supported that exposure and outcome shared consistent genetic variables. Phenome-wide MR analysis suggested the potential deleterious effects of NOE1 and FGFR4. PPI analysis confirmed the pathways associated with the potential targets involved in bile acid metabolism., Conclusions: Genetically predicted levels of the plasma proteins FUT3, NOE1, UGT1A6 and FKBP52 have potential as prospective targets in Europeans. Moreover, the plasma levels of KLB and FGFR4 may serve as potential targets for the treatment of cholelithiasis in East Asians., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Magnetic compression anastomosis (MCA) is a new method that provides sutureless passage construction for tubular organs. Due to the high recurrence rate of conventional endoscopic treatment and the high morbidity and mortality of surgical procedures, the MCA technique shows promise. The aim of this review is to comprehensively examine the literature related to the use of MCA in different gastrointestinal diseases over the past few years, categorizing them according to the anastomotic site and describing in detail the various methods of magnet delivery and the clinical outcomes of MCA. MCA is an innovative technique, and its use represents an advancement in the field of minimally invasive interventions. Comparison studies have shown that the anastomosis formed by MCA is comparable to or better than surgical sutures in terms of general appearance and histology. Although most of the current research has involved animal studies or studies with small populations, the safety and feasibility of MCA have been preliminarily demonstrated. Large prospective studies involving populations are still needed to guarantee the security of MCA. For technologies that have been initially used in clinical settings, effective measures should also be implemented to identify, even prevent, complications. Furthermore, specific commercial magnets must be created and optimized in this emerging area., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background & Aims: The considerable disease burden of irritable bowel syndrome (IBS) has coincided with the increase of ultraprocessed food (UPF) consumption over the past few decades. However, epidemiologic evidence for an association is lacking. We aimed to examine the long-term risk of IBS associated with UPF consumption in a large-scale prospective cohort., Methods: Participants who completed 24-hour dietary recalls during 2009 to 2012 from the UK Biobank, and free of IBS, celiac disease, inflammatory bowel disease, and any cancer at baseline, were included (N = 178,711; 53.1% female). UPF consumption was defined according to the NOVA food classification system, expressed as a percentage of UPF content in the total diet intake (as grams per day). The primary outcome was incident IBS. A Cox proportional hazard model was performed to estimate associated risk., Results: The mean UPF consumption was 21.0% (SD, 11.0%) of the total diet. During a median of 11.3 years of follow-up, 2690 incident IBS cases were identified. An 8% higher risk of IBS (hazard ratio, 1.08; 95% CI, 1.04-1.12) was associated with every 10% increment of UPF consumption. Compared with the lowest quartile of UPF consumption, the highest quartile was associated with a significantly increased risk of incident IBS (hazard ratio, 1.19; 95% CI, 1.07-1.33; P trend < .001). Subgroup analyses by age, sex, body mass index, smoking, and alcohol drinking status also showed similar results, except for the never/previous drinking subgroup. Further sensitivity analyses confirmed the positive association with a higher UPF consumption., Conclusions: Our findings provide evidence that a higher UPF consumption is associated with an increased risk of incident IBS, with a significant dose-response relationship., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: De novo malignancy is the leading cause of death in liver transplant recipients. Numerous studies consistently show a significantly increased risk of esophageal cancer after liver transplantation. Therefore, this study aims to investigate the incidence and risk factors associated with de novo esophageal cancer post-liver transplantation., Methods: PubMed, Embase, Medline and Cochrane Library were systematically searched. Screening, quality assessment, and data extraction were completed. The search was completed in November 2023. Standardized incidence rates (SIRs) were used to measure the risk of esophageal cancer among liver transplant recipients, along with corresponding 95% confidence intervals (CI). A random effects model was employed for comprehensive analysis, and results were presented using a forest plot. Sensitivity analysis was undertaken by systematically excluding individual studies one by one, while potential publication bias was assessed using funnel plots and Egger's test. Additionally, subgroup analyses were also performed to explore sources of heterogeneity., Results: Out of 1,037 articles collected, only twelve met the inclusion criteria after rigorous screening. Statistical analysis showed a significantly increased risk of esophageal cancer following liver transplantation compared to the general population (SIR =6.75, 95% CI: 4.35-10.46)., Conclusions: The risk of esophageal cancer significantly increases after liver transplantation, so regular gastrointestinal endoscopy is necessary after the procedure., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-66/coif). The authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: The gut microbiota can be influenced by lipid metabolism. We aimed to evaluate the impact of lipid-lowering medications, such as proproteinconvertase subtilisin/kexin type 9 (PCSK9) inhibitors, Niemann-Pick C1-like protein (NPC1L1) inhibitors, and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibitors, on gut microbiota through drug target Mendelian randomization (MR) investigation., Methods: We used genetic variants that were associated with low-density lipoprotein cholesterol (LDL-C) in genome-wide association studies and located within or near drug target genes as proxies for lipid-lowering drug exposure. In addition, expression trait loci in drug target genes were used as complementary genetic tools. We used effect estimates calculated using inverse variance weighted MR (IVW-MR) and summary data-based MR (SMR). Multiple sensitivity analyses were performed., Results: Genetic proxies for lipid-lowering drugs broadly affected the abundance of gut microbiota. High expression of NPC1L1 was significantly associated with an increase in the genus Eggerthella (β = 1.357, SE = 0.337, P = 5.615 × 10 -5 ). An HMGCR-mediated increase in LDL-C was significantly associated with the order Pasteurellales (β = 0.489, SE = 0.123, P = 6.955 × 10 -5 ) and the genus Haemophilus (β = 0.491, SE = 0.125, P = 8.379 × 10 -5 ), whereas a PCSK9-mediated increase in LDL-C was associated with the genus Terrisporobacter (β = 0.666, SE = 0.127, P = 1.649 × 10 -5 ). No pleiotropy was detected., Conclusions: This drug target MR highlighted the potential interventional effects of lipid-lowering drugs on the gut microbiota and separately revealed the possible effects of different types of lipid-lowering drugs on specific gut microbiota., Competing Interests: Declaration of competing interest None of the authors has any conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: Lysophosphatidic acid (LPA) is a small bioactive lipid which acts as a potent regulator in various tumor progressions through six G-protein-coupled receptors (LPA 1 -LPA 6 ). Our previous study demonstrated that the LPA-producing enzyme, autotaxin (ATX), was upregulated in esophageal squamous cell carcinoma (ESCC) and ATX high expression levels indicated a poor prognosis. Esophageal squamous cell carcinoma is a type of malignant tumor which originates from epithelial cells. Its progression can be affected by the interaction between cancer cells and normal cells. However, the impact of LPA on the interaction between esophageal epithelial cells and cancer cells in the development of ESCC remains uncertain., Methods: MTS and Edu assays were performed to determine ESCC cell proliferation in culture medium (CM) derived from LPA-stimulated esophageal epithelial cells (Het-1a). A wound healing assay, transwell migration and an invasion assay were performed to assess the metastatic ability of ESCC cells. Cytokine array analysis was conducted to detect the differentially secreted cytokines in CM. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to uncover the pathways and cytokines that are influenced by LPA in ESCC. Immunohistochemical staining was employed to measure the expression of ATX and CCL2 in early-stage ESCC. Quantitative real-time PCR, western blot, enzyme-linked immunosorbent assay and an antibody neutralization assay were employed to measure the mechanism of LPA-mediated communication between epithelial cells and cancer cells., Results: Functional experiments showed that exposing ESCC cancer cells to CM from LPA-treated Het-1a results in promoting proliferation, migration, invasion and epithelial-mesenchymal transition processes. Using cytokine array analysis, we discovered that LPA triggers the release of multiple cytokines from epithelial cells. After screening of the TCGA and GEO databases, CCL2 was identified and found to be correlated with ATX expression in ESCC. Furthermore, CCL2 levels in both mRNA expression and secretion were observed to be upregulated in epithelial cells upon stimulation with LPA. Blocking CCL2 effectively reduced the pro-migration influence of CM derived from LPA-treated Het-1a. Mechanism studies have demonstrated that LPA activated the NF-κB signaling pathway through LPA 1/3 , ultimately causing an increase in CCL2 expression and secretion in Het-1a., Conclusions: Our findings, taken together, demonstrate that CM from LPA-treated esophageal epithelial cells plays a significant role in promoting the progression of ESCC, with CCL2 acting as the primary regulator., (© 2024 John Wiley & Sons Ltd.)

Background: With increasing antibiotic resistance and regulation, the issue of antibiotic combination has been emphasised. However, antibiotic combination prescribing lacks a rapid identification of feasibility, while its risk of drug interactions is unclear., Methods: We conducted statistical descriptions on 16 101 antibiotic coprescriptions for inpatients with bacterial infections from 2015 to 2023. By integrating the frequency and effectiveness of prescriptions, we formulated recommendations for the feasibility of antibiotic combinations. Initially, a machine learning algorithm was utilised to optimise grading thresholds and habits for antibiotic combinations. A feedforward neural network (FNN) algorithm was employed to develop antibiotic combination recommendation model (ACRM). To enhance interpretability, we combined sequential methods and DrugBank to explore the correlation between antibiotic combinations and drug interactions., Results: A total of 55 antibiotics, covering 657 empirical clinical antibiotic combinations were used for ACRM construction. Model performance on the test dataset showed AUROCs of 0.589-0.895 for various antibiotic recommendation classes. The ACRM showed satisfactory clinical relevance with 61.54-73.33% prediction accuracy in a new independent retrospective cohort. Antibiotic interaction detection showed that the risk of drug interactions was 29.2% for strongly recommended and 43.5% for not recommended. A positive correlation was identified between the level of clinical recommendation and the risk of drug interactions., Conclusions: Machine learning modelling of retrospective antibiotic prescriptions habits has the potential to predict antibiotic combination recommendations. The ACRM plays a supporting role in reducing the incidence of drug interactions. Clinicians are encouraged to adopt such systems to improve the management of antibiotic usage and medication safety., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: The causal relationship between gut microbiota and cerebral cortex development remains unclear. We aimed to scrutinize the plausible causal impact of gut microbiota on cortical thickness via Mendelian randomization (MR) study., Methods: Genome-wide association study (GWAS) data for 196 gut microbiota phenotypes (N = 18,340) were obtained as exposures, and GWAS data for cortical thickness-related traits (N = 51,665) were selected as outcomes. Inverse variance weighted was used as the main estimate method. A series of sensitivity analyses was used to test the robustness of the estimates including Cochran's Q test, MR-Egger intercept analysis, Steiger filtering, scatter plot funnel plot and leave-one-out analysis., Results: Genetic prediction of high Bacillales (β = 0.005, P = 0.032) and Lactobacillales (β = 0.010, P = 0.012) abundance was associated with a potential increase in global cortical thickness. For specific functional brain subdivisions, genetically predicted order Lactobacillales would potentially increase the thickness of the fusiform (β = 0.014, P = 0.016) and supramarginal (β = 0.017, P = 0.003). Meanwhile, order Bacillales would increase the thickness of fusiform (β = 0.007, P = 0.039), insula (β = 0.011, P = 0.003), rostralanteriorcingulate (β = 0.014, P = 0.002) and supramarginal (β = 0.006, P = 0.043). No significant estimates of heterogeneity or pleiotropy were found., Conclusions: Through MR studies, we discovered genetic prediction of the Lactobacillales and Bacillales orders potentially linked to cortical thickness, affirming gut microbiota may enhance brain structure. Genetically predicted supramarginal and fusiform may be potential targets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Early gastric cancer (EGC) is defined as cancer cells confined to the mucosal or submucosal layer, irrespective of size or presence of lymph node metastasis. The recent EGC endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) guidelines (2021 Japan Gastroenterological Endoscopy Society (JGES) guidelines, 2nd edition) revised the concept from "endoscopic curative/non-curative resection" (NCR) to "endoscopic curability (eCura)". Under this, eCuraA and eCuraB signify curative resections (CRs), while eCuraC (including eCuraC-1 and eCura-C2) indicate NCRs. This study retrospectively analyzes clinical and pathological data from EGC patients who underwent endoscopic resection, assessing the long-term clinical outcomes in a substantial cohort after undergoing NCR., Methods: We retrospectively analyzed clinical and pathological data from 443 EGC patients, encompassing 478 lesions, who received endoscopic treatment. The long-term clinical outcomes of patients who underwent NCR were statistically evaluated. Characteristics of the NCR group were compared with those of the surgical group, employing single- and multi-factor logistic regression analyses to identify risk factors that necessitate further surgical intervention. Prognostically, the Kaplan-Meier method and Log-Rank test determined the impact of risk factors on recurrence-free survival post-surgery in NCR patients. Differences were assessed using a method incorporating statistically significant differences in the multi-factor Cox regression analysis, evaluating the hazard ratio (HR) for disease recurrence following NCR., Results: In this study, 443 EGC cases were pathologically diagnosed, comprising a total of 478 lesions. Of these, 127 cases underwent non-curative endoscopic resection, resulting in a NCR rate of 24.4%. Long-term follow-up was achieved for 117 (92.12%) patients. The metastasis/recurrence rate at 6 months stood at 23.1%. Multivariate Cox regression analysis identified lesion size ≥2.0 and <3 cm [P=0.02, HR =0.12, 95% confidence interval (CI): 0.02-0.67], presence of ulceration (P=0.03, HR =5.48, 95% CI: 1.23-24.33), lymphatic invasion (P=0.05, HR =17.51, 95% CI: 1.07-286.23), positive vertical margins (P=0.09, HR =3.77, 95% CI: 0.81-17.53), and flat macroscopic morphology (P=0.048, HR =4.8, 95% CI: 1.01-22.73) as independent risk factors for recurrence-free survival post non-curative endoscopic resection in EGC patients., Conclusions: The recurrence/metastasis rate in patients who underwent NCR is notably higher compared to the control group. Significant prognostic risk factors include tumor size ≥2.0 and <3 cm, positive vertical margins, lymphatic invasion, and flat type (one of pathological gross classification). Patients in the eCuraC-2 category of NCR should consider further surgical intervention. The necessity for additional surgical intervention in these patients warrants further investigation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-168/coif). The authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

Background and Aims: Endoscopic submucosal dissection (ESD) is an effective treatment method for early gastric cancers. The aim of this study was to evaluate the risk factors of recurrence for patients with early gastric cancer after ESD and construct a nomogram for predicting recurrence., Methods: A retrospective observational study was conducted on patients with early gastric cancer who underwent ESD at Beijing Friendship Hospital between 2013 and 2018. The risk factors of gastric cancer recurrence after ESD were analyzed by univariate and multivariate Cox regression., Results: A total of 238 patients with a median follow-up period of 70.5-month were enrolled in the study. Risk factors for recurrence included diabetes (HR = 3.68), alcohol consumption history (HR = 5.73), complications (HR = 5.22), lymphatic invasion (HR = 13.09) and multiple lesions (HR = 4.34). The analysis of the receiver operating characteristic curve, calibration curve, and model consistency index demonstrates that the graphical representation exhibits a good predictive capability., Conclusions: Based on identified risk factors, this study developed the first nomogram with high accuracy to predict the recurrence of early gastric cancer after ESD. This model offers valuable guidance to clinicians for identifying high-risk patient groups and planning more intensive follow-up strategies., Competing Interests: Conflict of interests The authors declare no competing interests in this study., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: To evaluate the effect of Embrella, a novel-designed colonoscopic distal attachment, on adenoma detection rate (ADR) and adenoma per colonoscopy (APC), compared with standard colonoscopy in routine practice., Methods: All consecutive participants who underwent routine colonoscopic examinations at 3 endoscopy centers in China were enrolled. Participants were randomly assigned in a 1:1 ratio to the Embrella-assisted colonoscopy (EAC) or standard colonoscopy (SC) groups. ADR, APC, inspection time, pain scores, and adverse events were recorded., Results: Overall, 1,179 participants were randomized into the EAC (n = 593) and SC groups (n = 586). EAC increased the overall ADR from 24.6% to 34.2% ( P < 0.001) and improved APC from 0.44 to 0.64 ( P = 0.002). Subgroup analyses indicated that EAC significantly improved ADR for adenomas < 10 mm (13.8% vs 8.5%, P = 0.004 for 5-9 mm and 27.0% vs 17.2%, P < 0.001 for < 5 mm), nonpedunculated adenomas (26.6% vs 18.8%, P < 0.001), and adenomas in the transverse (10.8% vs 6.1%, P = 0.004) and left colon (21.6% vs 13.7%, P < 0.001). APC in the subgroup analyses was consistent with ADR. The mean inspection time was shorter with EAC (6.52 vs 6.68 minutes, P = 0.046), with no significant impact on participants' pain scores ( P = 0.377). Moreover, no EAC-related adverse events occurred., Discussion: EAC significantly increased ADR and APC compared with SC, particularly for adenomas <10 mm, nonpedunculated adenomas, and adenomas in the transverse and left colon., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Erosive esophagitis (EE) is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus. Proton pump inhibitors are widely used as maintenance therapy for EE, but many patients still relapse. In this trial, we evaluated the noninferiority of vonoprazan vs. lansoprazole as maintenance therapy in patients with healed EE., Methods: We performed a double-blind, double-dummy, multicenter, phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019. Patients from China, South Korea, and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks. The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10% using a two-sided 95% confidence interval (CI). Treatment-emergent adverse events (TEAEs) were recorded., Results: Among 703 patients, EE recurrence was observed in 24/181 (13.3%) and 21/171 (12.3%) patients receiving vonoprazan 10 mg or 20 mg, respectively, and 47/184 (25.5%) patients receiving lansoprazole (differences: -12.3% [95% CI, -20.3% to -4.3%] and -13.3% [95% CI, -21.3% to -5.3%], respectively), meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks. Evidence of superiority (upper bound of 95% CI <0%) was also observed. At 12 weeks, endoscopically confirmed EE recurrence was observed in 5/18, 2/20, and 7/20 of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. TEAEs were experienced by 66.8% (157/235), 69.0% (156/226), and 65.3% (158/242) of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. The most common TEAE was upper respiratory tract infection in 12.8% (30/235) and 12.8% (29/226) patients in vonoprazan 10 mg and 20 mg groups, respectively and 8.7% (21/242) patients in lansoprazole group., Conclusion: Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE., Trial Registration: https://clinicaltrials.gov; NCT02388737., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background and Aim: Cystic dilatation of the gastric glands within the mucosal layer is the hallmark of the rare condition known as gastritis cystica profunda (GCP). Although it has been proved that GCP is the precursor lesion for early gastric cancer (EGC), the management strategy of GCP-related EGC is not well established.The purpose of this research was to determine if ESD is effective and safe for GCP-related EGC., Methods: Patients with EGC who had ESD at Beijing Friendship Hospital between January 2015 and May 2023 were retrospectively included. All patients were divided into two groups: those with GCP-related EGC, and those with EGC alone. The two groups were matched 1:1 using the propensity score matching (PSM) method. Curative resection rate, postoperative adverse outcome rate (bleeding, perforation, stricture), and recurrence rate were the primary measures used to evaluate the efficacy and safety of ESD., Results: There were a total of 386 participants (44 with GCP and 342 with EGC alone). Following PSM, 44 patients were paired and analyzed separately. Except for the presence of cysts in EUS (multiple/single/none cyst: 12/2/5 versus 1/0/25, P < 0.0001), there was no change in baseline characteristics, EUS appearance, or histology results between groups. Overall, there was no significant difference in curative resection rates between the GCP group (70.5 %) and the control group (81.8 %) (P = 0.211). Postoperative complications were comparative (9/44 vs 5/44, P = 0.244), as were rates of local recurrence (1/44 vs 0/44, P = 1.0), metachronous gastric cancer (1/44 vs 0/44, P = 1.0), and mortality (0/44 vs 0/44, P = 1.0)., Conclusions: Existence of cysts in EUS is a characteristic presentation to distinguish GCP-related EGC from EGC-alone lesions. ESD might be a safe and effective therapy for patients with GCP-related EGC., Competing Interests: The authors have no conflicts of interest to declare. All the authors participated in review of the article and approved the final version of the manuscript., (© 2024 The Authors.)

Gastric cancer (GC) ranks third among cancers in terms of mortality rate worldwide. A clear understanding of the mechanisms underlying the genesis and progression of GC will contribute to clinical decision making. N 6 -methyladenosine (m 6 A) is the most abundant among diverse mRNA modification types and regulates multiple facets of RNA metabolism. In recent years, emerging studies have shown that m 6 A modifications are involved in gastric carcinoma tumorigenesis and progression and can potentially be valuable new prospects for diagnosis and prognosis. This article reviews the recent progress regarding m 6 A in GC., Competing Interests: Conflict of Interest Peng Li is an Editorial Board Member of the journal. The article was subject to the journal’s standard procedures, with peer review handled independently of the editor and his research groups., (© 2024 Jiaxin Wang, Guiping Zhao, Yan Zhao, Zheng Zhao, Shuyue Yang, Anni Zhou, Peng Li, Shutian Zhang, published by De Gruyter on behalf of Scholar Media Publishing.)

Glucose oxidation via the pentose phosphate pathway serves as the primary cellular mechanism for generating nicotinamide adenine dinucleotide phosphate (NADPH). The central regions of solid tumors typically experience glucose deficiency, emphasizing the need for sustained NADPH production crucial to tumor cell survival. This study highlights the crucial role of RIOK3 in maintaining NADPH production and colorectal cancer (CRC) cell survival during glucose deficiency. Our findings revealed upregulated RIOK3 expression upon glucose deprivation, with RIOK3 knockout significantly reducing cancer cell survival. Mechanistically, RIOK3 interacts with heat shock protein 90α (HSP90α), a chaperone integral to various cellular processes, thereby facilitating HSP90α binding to isocitrate dehydrogenase 1 (IDH1). This interaction further upregulates IDH1 expression, enhancing NADPH production and preserving redox balance. Furthermore, RIOK3 inhibition had no discernible effect on intracellular NADPH levels and cell death rates in HSP90α-knockdown cells. Collectively, our findings suggest that RIOK3 sustains colon cancer cell survival in low-glucose environments through an HSP90α-dependent pathway. This highlights the significance of the RIOK3-HSP90α-IDH1 cascade, providing insights into potential targeted therapeutic strategies for CRC in metabolic stress conditions., (© 2024. The Author(s).)

Background: Sympathoexcitation contributes to myocardial remodeling in heart failure (HF). Increased circulating pro-inflammatory mediators directly act on the Subfornical organ (SFO), the cardiovascular autonomic center, to increase sympathetic outflow. Circulating mitochondria (C-Mito) are the novel discovered mediators for inter-organ communication. Cyclic GMP-AMP synthase (cGAS) is the pro-inflammatory sensor of damaged mitochondria., Objectives: This study aimed to assess the sympathoexcitation effect of C-Mito in HF mice via promoting endothelial cGAS-derived neuroinflammation in the SFO., Methods: C-Mito were isolated from HF mice established by isoprenaline (0.0125 mg/kg) infusion via osmotic mini-pumps for 2 weeks. Structural and functional analyses of C-Mito were conducted. Pre-stained C-Mito were intravenously injected every day for 2 weeks. Specific cGAS knockdown (cGAS KD) in the SFO endothelial cells (ECs) was achieved via the administration of AAV9-TIE-shRNA (cGAS) into the SFO. The activation of cGAS in the SFO ECs was assessed. The expression of the mitochondrial redox regulator Dihydroorotate dehydrogenase (DHODH) and its interaction with cGAS were also explored. Neuroinflammation and neuronal activation in the SFO were evaluated. Sympathetic activity, myocardial remodeling, and cardiac systolic dysfunction were measured., Results: C-Mito were successfully isolated, which showed typical structural characteristics of mitochondria with double-membrane and inner crista. Further analysis showed impaired respiratory complexes activities of C-Mito from HF mice (C-Mito HF ) accompanied by oxidative damage. C-Mito entered ECs, instead of glial cells and neurons in the SFO of HF mice. C-Mito HF increased the level of ROS and cytosolic free double-strand DNA (dsDNA), and activated cGAS in cultured brain endothelial cells. Furthermore, C-Mito HF highly expressed DHODH, which interacted with cGAS to facilitate endothelial cGAS activation. C-Mito HF aggravated endothelial inflammation, microglial/astroglial activation, and neuronal sensitization in the SFO of HF mice, which could be ameliorated by cGAS KD in the ECs of the SFO. Further analysis showed C-Mito HF failed to exacerbate sympathoexcitation and myocardial sympathetic hyperinnervation in cGAS KD HF mice. C-Mito HF promoted myocardial fibrosis and hypertrophy, and cardiac systolic dysfunction in HF mice, which could be ameliorated by cGAS KD., Conclusion: Collectively, we demonstrated that damaged C-Mito HF highly expressed DHODH, which promoted endothelial cGAS activation in the SFO, hence aggravating the sympathoexcitation and myocardial injury in HF mice, suggesting that C-Mito might be the novel therapeutic target for sympathoexcitation in HF., (© 2024. The Author(s).)

Helicobacter pylori eradication is crucial in the treatment of peptic ulcers caused by H. pylori infection, a disease highly prevalent in Asia. We present a pooled analysis of two randomized, double-blind, double-dummy, phase 3 studies evaluating the efficacy and safety of vonoprazan-based bismuth-containing quadruple therapy for H. pylori eradication. Patients aged ≥18 years with endoscopically confirmed duodenal or gastric ulcers were randomized 1 : 1 to receive vonoprazan 20 mg or lansoprazole 30 mg once daily for up to 6 (duodenal ulcers) or 8 weeks (gastric ulcers). H. pylori-positive patients received vonoprazan- or lansoprazole-based bismuth-containing quadruple therapy for the first 2 weeks. H. pylori eradication was determined using the carbon-13 urea breath test at a follow-up visit 4 weeks post-treatment. The H. pylori eradication rate was 90.6% with vonoprazan vs. 85.2% with lansoprazole (difference: 5.4%; 95% confidence interval (CI): -0.1, 10.8). H. pylori eradication rates were 7.1% (95% CI: 1.4, 12.8) and 12.6% (95% CI: 3.9, 22.0) higher in patients aged <65 years and current smokers, respectively, with vonoprazan vs. lansoprazole. In the Chinese subpopulation, the H. pylori eradication rate was 92.0% with vonoprazan vs. 86.0% with lansoprazole (difference: 6.1%; 95% CI: 0.5, 11.7). Treatment-emergent adverse events occurred in 72.7 vs. 62.6% of H. pylori-positive patients at baseline in the vonoprazan vs. lansoprazole arm. H. pylori eradication with vonoprazan-based quadruple therapy was noninferior to lansoprazole-based quadruple therapy and exceeded 90%, a clinically relevant threshold for determining the efficacy of H. pylori eradication regimens (ClinicalTrials.gov identifier: NCT03050359; NCT03050307).

Purpose: To investigate the prospective association of frailty status with the long-term risk of elderly-onset IBD in a large prospective cohort., Methods: Participants free of IBD and cancer at enrollment from the UK Biobank cohort were included. Baseline pre-frail and frail status was measured by Fried phenotype including weight loss, exhaustion, low grip strength, low physical activity and slow walking pace, defined as meeting one or two criteria and meeting three or more criteria. Primary outcome was elderly-onset IBD, including elderly-onset ulcerative colitis (UC) and Crohn's disease (CD). Multivariable Cox regression was conducted to examine the related associations., Results: Overall, 417,253 participants (aged 56.18 ± 8.09 years) were included. Of whom, 19,243 (4.6 %) and 188,219 (45.1 %) were considered frail and pre-frail, respectively. During a median of 12.4 years follow-up, 1503 elderly-onset IBD cases (1001 UC, 413 CD, and 89 IBD-Unclassified) were identified. Compared with non-frail, individuals with frail (HR=1.40, 95 %CI: 1.13-1.73) and pre-frail (HR=1.15, 1.03-1.28) showed significantly higher risk of elderly-onset IBD after multivariable adjustment (P trend <0.001). The positive association was more evident regarding risk of elderly-onset CD (HR=2.16, 1.49-3.13 for frail; HR=1.49,1.20-1.85 for pre-frail; P trend <0.001). Sensitivity analyses and subgroup analyses according to age, gender and body mass index (BMI) demonstrated similar results., Conclusions: Frailty and pre-frailty are associated with increased risk of elderly-onset IBD, particularly elderly-onset CD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The influences of TRIM28 on the gastric tumorigenesis together with potential molecular mechanisms remain to be studied. We aimed at exploring the important effects of TRIM28 on gastric cancer (GC) and uncovering underling molecular mechanisms. Through immunohistochemistry analysis of 20 pairs of GC and the peritumoral tissues, the expression level of TRIM28 was determined. A variety of assays were applied to explore the important roles of TRIM28 in GC. Western blotting and qRT-PCR analyses were used to analyze the association between TRIM28 and the Wnt/β-catenin signaling pathway. TRIM28 was highly expressed in GC tissues than peritumoral tissues. And high expression level of TRIM28 in GC was associated with good prognostic effects. In vitro functional assays suggested TRIM28 knockdown enhanced the proliferation and clone formation of GC cell. Moreover, TRIM28 knockdown enhanced the expression level of stemness markers, strengthened sphere-forming and drug-resistance properties of GC cells, suggesting important effect on GC cell stemness. Besides, our analysis showed that the Wnt/β-catenin signaling was involved in the effect of TRIM28 on GC cell stemness property, and blocking Wnt/β-catenin signaling pathway obviously rescued the promotion influence of TRIM28 knockdown. Overall, TRIM28 has an important influence on regulating the stem-like property of GC cell via Wnt/β-catenin signaling, suggesting TRIM28 a promising drug target and a potential predictor of prognosis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Primary Epstein-Barr virus (EBV) infection is observed in 60% of children during the first year after liver transplantation as usage of imm-unosuppressant. Finding predictive indicators of EBV infection is important to reduce the morbidity and mortality of EBV infection-related diseases by suggesting a dose reduction of immunosuppressant., Methods: We compared and analysed the gut microbiome of EBV-infected children with an asymptomatic virus-carrying status and EBV-uninfected children after liver transplantation using high-throughput sequencing., Results: Significant differences in gut microbiome composition in two groups were detected. In detail, Firmicutes and Lactobacillus were increased in EBV-infected group, while Clostridium was increased in EBV-uninfected group. Furthermore, CD4 percentage in T cells of blood showed a significant positive correlation with the content of Clostridium sp. CAG: 127 in EBV-uninfected group., Conclusion: Changes in the gut microbiome could predict and decrease the EBV infection risk of children after liver transplantation., (© 2023 Wiley Periodicals LLC.)

Competing Interests: The authors declare that they have no conflict of interest.

Competing Interests: The authors declare that they have no conflict of interest.

Background and Aim: Neoplastic polyp removal is important for colorectal cancer prevention. Endoscopists have proposed cold snare endoscopic mucosal resection (CS-EMR) as a solution to solve positive cutting edges and postoperative bleeding. However, many controversies regarding its specific performance in practice have been reported. The aim of this pooled analysis was to report the efficacy and safety of CS-EMR., Methods: PubMed/Medline, Embase, Google Scholar, and the Cochrane Library searched up to January 2022 to identify studies in which CS-EMR was performed for the removal of colorectal polyps measuring less than 20 mm. The primary outcome was the complete resection rate (CRR), and the secondary outcome was the rate of adverse events., Results: Eleven studies were included in the final analysis, which included 861 colorectal polyps. The overall CRR with CS-EMR was 96.3% (95% CI, 93.9-98.2%). The early and delayed bleeding rates of CS-EMR were 3.1% (95% CI, 1.2-5.5%) and 1.4% (95% CI, 0.6-2.4%), respectively. There were no statistical significances between CS-EMR and cold snare polypectomy (CSP) in terms of the CRR and adverse events, as well as CS-EMR and hot snare endoscopic mucosal resection (HS-EMR)., Conclusions: For resecting colorectal polyps measuring ≤20 mm, CS-EMR is an effective attempt. However, compared with CSP and HS-EMR, CS-EMR did not improve the efficiency and safety of polypectomy as expected. Multicenter randomized controlled trials are needed to compare CSP with CS-EMR in the resection of <10 mm polyps and HSP with CS-EMR in the resection of ≥10 mm polyps., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Venous thromboembolism (VTE) is the most fatal complication in cancer patients. Unfortunately, the frequent misdiagnosis of VTE owing to the lack of accurate and efficient evaluation approaches may cause belated medical intervention and even sudden death. Herein, we present a rapid, easily operable, highly specific, and highly sensitive procoagulant extracellular vesicle barcode (PEVB) assay composed of TiO 2 nanoflower (TiNFs) for visually evaluating VTE risk in cancer patients. TiNFs demonstrate rapid label-free EV capture capability by the synergetic effect of TiO 2 -phospholipids molecular interactions and topological interactions between TiNFs and EVs. From ordinary plasma samples, the PEVB assay can evaluate potential VTE risk by integrating TiNFs-based EV capture and in situ EV procoagulant ability test with machine-learning-assisted clinical data analysis. We demonstrate the feasibility of this PEVB assay in VTE risk evaluation by screening 167 cancer patients, as well as the high specificity (97.1%) and high sensitivity (96.8%), fully exceeding the nonspecific and posterior traditional VTE test. Together, we proposed a TiNFs platform allowing for highly accurate and timely diagnosis of VTE in cancer patients.

Background: To investigate prospective association of coffee and tea intake with incident irritable bowel syndrome (IBS) in a long-term cohort., Methods: Participants free of IBS, coeliac disease, inflammatory bowel disease and any cancer at baseline from UK Biobank were included. Coffee and tea intake was measured separately via baseline touchscreen questionnaire, with four categories for each intake (0, 0.5-1, 2-3 and ≥4 cups/day). Primary outcome was incident IBS. Cox proportional hazard model was used to estimate associated risk., Results: Among 425 387 participants, 83 955(19.7%) and 186 887(43.9%) consumed ≥4 cups/day of coffee and tea at baseline, respectively. During median 12.4-year follow-up, incident IBS was identified in 7736 participants. Compared with no coffee intake, consumption of 0.5-1, 2-3 and ≥4 cups/day was associated with lower IBS risk [hazard ratio (HR)=0.93, 95% CI: 0.87-0.99; 0.91, 0.85-0.97; 0.81, 0.76-0.88; Ptrend < 0.001]. Specifically, decreased risk was evident in individuals who consumed instant (HR = 0.83, 0.78-0.88) or ground coffee (HR = 0.82, 0.76-0.88) compared with no coffee drink. Regarding tea intake, protective association was only found in individuals who consumed 0.5-1 cup/day (HR = 0.87, 0.80-0.95), whereas no significant association was detected in those who consumed 2-3 (HR = 0.94, 0.88-1.01) or ≥4 cups/day (HR = 0.95, 0.89-1.02) compared with no-tea intake (Ptrend = 0.848)., Conclusions: Higher intake of coffee, particularly instant and ground coffee, is associated with lower risk of incident IBS, with significant dose-response relationship. Moderate-tea intake (0.5-1 cup/day) is associated with lower IBS risk., (© The Author(s) 2023; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Introduction: To evaluate the effect of 3-dimensional (3D) imaging device on polyp and adenoma detection during colonoscopy., Methods: In a single-blind, randomized controlled trial, participants aged 18-70 years who underwent diagnostic or screening colonoscopy were consecutively enrolled between August 2019 and May 2022. Each participant was randomized in a 1:1 ratio to undergo either 2-dimensional (2D-3D) colonoscopy or 3D-2D colonoscopy through computer-generated random numbers. Primary outcome included polyp detection rate (PDR) and adenoma detection rate (ADR), defined as the proportion of individuals with at least 1 polyp or adenoma detected during colonoscopy. The primary analysis was intention-to-treat., Results: Of 1,196 participants recruited, 571 in 2D-3D group and 583 in 3D-2D group were finally included after excluding those who met the exclusion criteria. The PDR between 2D and 3D groups was separately 39.6% and 40.5% during phase 1 (odds ratio [OR] = 0.96, 95% confidence interval [CI]: 0.76-1.22, P = 0.801), whereas PDR was significantly higher in 3D group (27.7%) than that of 2D group (19.9%) during phase 2, with a 1.54-fold increase (1.17-2.02, P = 0.002). Similarly, the ADR during phase 1 between 2D (24.7%) and 3D (23.8%) groups was not significant (OR = 1.05, 0.80-1.37, P = 0.788), while ADR was significantly higher in 3D group (13.8%) than that of 2D group (9.9%) during phase 2, with a 1.45-fold increase (1.01-2.08, P = 0.041). Further subgroup analysis confirmed significantly higher PDR and ADR of 3D group during phase 2, particularly in midlevel and junior endoscopists., Discussion: The 3D imaging device could improve overall PDR and ADR during colonoscopy, particularly in midlevel and junior endoscopists. Trial number: ChiCTR1900025000., (Copyright © 2023 by The American College of Gastroenterology.)

The surface of the small bowel mucosa is covered more than any other section of the digestive canal; however, the overall prevalence of small bowel tumors of the whole gastrointestinal tract is evidently low. Owing to the improvement in endoscopic techniques, the prevalence of small bowel tumors has increased across multiple countries, which is mainly due to an increase in duodenal tumors. Superficial non-ampullary duodenal epithelial tumors (SNADETs) are defined as tumors originating from the non-ampullary region in the duodenum that share similarities and discrepancies with their gastric and colorectal counterparts in the pathogenesis and clinicopathologic characteristics. To date, white light endoscopy (WLE) remains the cornerstone of endoscopic diagnosis for SNADETs. Besides, narrow-band imaging (NBI) techniques and magnifying endoscopy (ME) have been widely used in the clinic and endorsed by multiple guidelines and consensuses for SNADETs' evaluation. Confocal laser endomicroscopy (CLE), endocytoscopy (ECS), and artificial intelligence (AI) are also up-and-coming methods, showing an exceptional value in the diagnosis of SNADETs. Similar to the endoscopic treatment for colorectal polyps, the choices for SNADETs mainly include cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and laparoscopic endoscopic cooperative surgery (LECS). However, owing to the narrow lumen, rich vascularity, weak muscle layer, abundant Brunner's gland, and the hardship of endoscope control, the duodenum ranks as one of the most dangerous operating areas in the digestive tract. Therefore, endoscopists must anticipate the difficulties in endoscopic maneuverability, remain aware of the increased risk of complications, and then select the appropriate treatment according to the advantages and disadvantages of each method., (© 2023 Zheng Zhao, Yue Jiao, Shuyue Yang, Anni Zhou, Guiping Zhao, Shuilong Guo, Peng Li, Shutian Zhang published by De Gruyter on behalf of Scholar Media Publishing.)

Colon cancer is a widespread life-threatening malignancy with complex and multifactorial etiology. Both epidemiological cohort studies and basic research support the substantial role of iron metabolism in colon cancer. Thus, understanding the mechanisms of how essential iron metabolic proteins are dysregulated may provide new treatment strategies for colon cancer. Ferritin is the main iron storage protein that occupies a vital position in iron metabolism. Studies reported that ferritin is differentially highly expressed in tissues from multiple malignancies. However, the source and function of highly expressed ferritin in colon cancer have not been explored. In this study, we found that the protein level but not RNA level of ferritin heavy chain (FTH1) was upregulated in colon cancer using paired clinical samples. Co-culture system was used to mimic the in vivo circumstance and study the cell-cell communication of macrophages and colon cancer cells. Results showed that M2 macrophages could substantially increase the FTH1 levels in colon cancer cells. This effect could be blocked by the exosome biogenesis/ secretion inhibitor GW4869, implying the vital role of exosomes in this biological process. Besides, we found that purified exosomes from M2 macrophages could deliver FTH1 into colon cancer cells and promote cell proliferation. Furtherly, EdU assay and live cell imaging system were performed in FTH1-OE (overexpression) colon cancer cell lines and confirmed the cell proliferation promoting effect of FTH1. Our results unveil the source and function of highly expressed FTH1 in colon cancer and provide a new potential therapeutic target for the treatment of colon cancer., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Adjusting antiplatelet strategies after antiplatelet-associated gastrointestinal bleeding (GIB) is a complex clinical challenge. To assess the risk of outcomes at different times of resumption of antiplatelet therapy in an attempt to find the optimal time to resume therapy. The study analyzed consecutive patients with antiplatelet-associated GIB from Beijing Friendship Hospital Information System between October 2019 and June 2022. The primary outcomes were recurrent bleeding, major adverse cardiovascular and cerebrovascular events (MACE), and all-cause death. Multivariate-adjusted Cox proportional hazards models were used to evaluate the risks of these outcomes. The receiver operating characteristic curve was used to find the optimal time to resume treatment. Of the 617 patients with GIB after antiplatelet therapy successfully followed up, the median follow-up was 246 (interquartile range: 120-466) days, most patients (87.36%) interrupted therapy after GIB and 45.22% resumed within 90 days, of which 35.13% resumed within 7 days and 64.87% resumed after 7 days. Resumption therapy had a low risk of recurrent bleeding (uninterrupted as a reference: HR 0.32, 95% CI 0.15-0.67, p = 0.003), MACE (no resumption as a reference: HR 0.66, 95% CI 0.45-0.98, p = 0.037), and all-cause death (no resumption as a reference: HR 0.18, 95% CI 0.08-0.40, p < 0.001). And resuming therapy within 7 days had a lower risk of MACE (HR 0.18, 95% CI 0.08-0.44, p < 0.001) than after 7 days without a significantly higher risk of re-bleeding. The optimal time point for resuming therapy in this study was 8.5 days. Resuming antiplatelet therapy after GIB provides better clinical benefits compared to discontinued and uninterrupted therapy, especially compared with resuming after 7 days, resuming within 7 days is associated with a lower risk of MACE and a less significant increased risk of recurrent bleeding, leading to a higher net clinical benefit. China Clinical Trial Registration: ChiCTR2200064063., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Background/aims: In patients with acute nonvariceal upper gastrointestinal bleeding (ANVUGIB), the optimal timing of endoscopy is still a matter of dispute. We conducted a systematic review and meta-analysis to determine the clinical benefit of early endoscopy., Methods: A literature search of the MEDLINE, Embase, and Cochrane databases was conducted to identify publications from inception to March 1, 2022. Eligible studies included observational cohort studies and randomized controlled trials that reported clinical outcomes of endoscopy in patients with ANVUGIB. ANVUGIB patients who underwent endoscopy within 24 hours of admission were considered to have had an early endoscopy. The primary outcome was the mortality rate in ANVUGIB patients who had early or nonearly endoscopy., Results: The final analysis included five randomized controlled studies (RCTs) and 20 observational studies from the 1,206 identified articles. The mortality rate was not significantly reduced among patients who received endoscopy performed within 24 hours, whether in cohort studies nor in RCTs. For subgroup analysis, a higher mortality rate was found only among patients who received very early endoscopy within 12 hours (odds ratio, 1.66; p<0.001, I2=0) in cohort studies. No significant difference in mortality rates was found among patients at high risk of bleeding who received early versus nonearly endoscopy., Conclusions: Early endoscopy within 24 hours does not appear to significantly reduce the mortality rates of patients with ANVUGIB. Further well-designed studies are warranted to address if very early endoscopy within 12 hours can provide a clinical benefit for patients at high risk of bleeding.

Objectives: This study aims to compare the efficacy of endoscopic submucosal dissection (ESD) between early gastric cardiac cancer (EGCC) and early gastric non-cardiac cancer (EGNCC), and investigate associated risk factors for non-curative resection., Methods: Early gastric cancer (EGC) patients who underwent ESD from January 2015 to September 2020 in Beijing Friendship Hospital were consecutively enrolled. The clinical, histopathological and endoscopic data were retrospectively analyzed. The study was registered in Chinese Clinical Trial Registry (ChiCTR1800017117)., Results: Among 500 patients with 534 EGC lesions, 117 patients with 118 lesions were allocated to the EGCC group, and 383 patients with 416 lesions to the EGNCC group. The rates of en bloc resection, complete resection and curative resection in the EGCC group were 97.5%, 78.8% and 71.2%, respectively, significantly lower than those in the EGNCC group (99.8%, 94.5% and 90.4%, p  = .010, <.001 and <.001). Among non-curative resected lesions, EGCC had more cases in both endoscopic curability (eCura) C-1 and C-2 groups than EGNCC (10.2% and 18.6% vs. 2.4% and 7.2%, p  < .001). Multivariate analysis showed that tumor size (OR 2.393, 95% CI 1.388-4.126) and submucosal invasion (OR 11.498, 95% CI 3.759-35.175) were risk factors for non-curative resection in the EGCC group. For EGCC larger than 3 cm, none achieved curative resection, 86.7% were classified as eCura C-2 and 46.7% exhibited deep submucosal infiltration., Conclusions: The curative resection rate of ESD for EGCC was lower than that for EGNCC. ESD for EGCC larger than 3 cm should be cautiously considered.

Inflammatory bowel disease (IBD), a chronic and recurrent gastrointestinal inflammatory disorder with a variety of painful clinical manifestations and an increased risk of cancerization or death, has become an emerging challenge to global healthcare due to its rapidly increasing incidence. At present, there is no efficient cure against IBD because of the elusive etiology and pathogenesis of IBD. Therefore, the development of alternative therapeutic strategies with positive clinical efficacy and reduced side effects is urgently needed. In recent years, the great prosperity of nanomedicine promoted by a variety of advanced nanomaterials is redefining more attractive and promising therapeutic strategies for IBD owing to their advantages in the physiological stability, bioavailability, and targeting of inflammatory sites. In this review, firstly the basic characteristics of healthy and inflammatory intestinal microenvironments are presented. Then, different administration routes and targeting strategies of nanotherapeutics for IBD treatment are reviewed. Subsequently, a specific focus is placed on the introduction of nanotherapeutic treatments based on different IBD pathogenesis. Finally, some future challenges and perspectives of the currently developed nanomedicines for IBD treatment are provided. It is believed that the above topics will attract researchers from various fields including medicine, biological sciences, materials, chemistry and pharmaceutics., (© 2023 Wiley-VCH GmbH.)

Objective: Previous studies have indicated that a pro-inflammatory diet is associated with non-alcoholic fatty liver disease (NAFLD), but the role of BMI remains ambiguous. We aim to study the intermediary effect of BMI on the relationship between dietary inflammatory properties and NAFLD., Methods: A total of 19536 adult participants from the National Health and Nutrition Examination Surveys (NHANES) were included. Dietary inflammatory index (DII) was used to evaluate the dietary inflammatory properties and NAFLD was diagnosed by non-invasive biomarkers. Weighted multivariable logistic regression models estimated ORs and 95% CIs between DII and incidence of NAFLD. Interaction effect between DII and BMI on NAFLD was tested and the mediation analysis of BMI was performed., Results: Higher DII scores, representing higher inflammatory potential of diet, were positively associated with a higher risk of NAFLD. Compared with the first quartile of DII, people from the second quartile (OR: 1.23 [95% CI: 1.04, 1.46]) to the fourth quartile (OR: 1.59 [95% CI: 1.31, 1.94]) have a higher risk of NAFLD before adjustment for BMI. The overall association was completely mediated by BMI (89.19%)., Conclusions: Our findings suggested that a higher pro-inflammatory potential diet was associated with a higher prevalence of NAFLD, and this association might be mediated by BMI.

Background: There is evidence supporting the association between Helicobacter pylori infection and colorectal cancer (CRC), but whether H. pylori eradication reduces the risk of CRC is still unknown., Objectives: To compare the incidence of CRC in subjects who had received H. pylori eradication therapy with general population., Design: A population-based retrospective cohort study., Methods: This study included all H. pylori -infected subjects who had received their first course of clarithromycin-containing triple therapy in 2003-2015 in Hong Kong. We compared the observed incidences of CRC in this H. pylori eradicated cohort with the expected incidences in the age- and sex-matched general population. The standardized incidence ratio (SIR) with 95% confidence interval (CI) was computed., Results: Among 96,572 H. pylori -eradicated subjects with a median follow-up of 9.7 years, 1417 (1.5%) developed CRC. Primary analysis showed no significant difference in the observed and expected incidences of CRC (SIR: 1.03, 95% CI: 0.97-1.09). However, when stratified according to the follow-up period, higher incidence of CRC was only observed in the first 5 years after eradication (SIR: 1.47, 95% CI: 1.39-1.55), but it was lower (SIR: 0.85, 95% CI: 0.74-0.99) than general population after 11 years. When stratified by tumor location, the observed incidence was higher for colon (SIR: 1.20, 95% CI: 1.12-1.29) but lower for rectal cancer (SIR: 0.90, 95% CI: 0.81-0.999) among H. pylori -eradicated subjects., Conclusions: H. pylori -infected subjects appeared to have a higher incidence of CRC initially, which declined progressively to a level lower than general population 10 years after H. pylori eradication, particularly for rectal cancer., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)