World Journal of Gastroenterology最新文献

This editorial critically analyses the recent article by Jung et al, which investigates the utility of 4-hour serum amylase and lipase as early blood markers for post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis prediction. Although these enzymes are valuable for the early diagnosis of post-ERCP pancreatitis, they lack specificity for disease etiology and provide limited insight into the molecular mechanisms underlying disease progression. Several cytokines, notably interleukin (IL)-6, tumor necrosis factor-alpha, and IL-8, are increased in post-ERCP pancreatitis and may serve as potential predictors for disease severity. The incorporation of these biomarkers in early enzymatic biomarkers and established prognostic scoring systems could further enhance their accuracy and allow for earlier, more effective management of patients with post-ERCP pancreatitis.

Background: Lifestyle factors are closely associated with the onset and progression of inflammatory bowel disease (IBD). Studies have demonstrated the positive effects of exercise on clinical outcomes and quality of life in individuals with IBD. Despite the well-documented role of exercise in improving IBD outcomes, the underlying mechanisms remain unclear.

Aim: To compare the efficacy of different exercise modalities and explore their potential physiological mechanisms in rodent models of colitis.

Methods: We conducted a comprehensive search of five databases from inception to September 24, 2024, which yielded 19 animal studies in rodent colitis models. We compared the efficacy of various forms of exercise and explored the possible physiological mechanisms. The effects of different exercise modalities, namely forced treadmill running (FTR), voluntary wheel running (VWR), swimming, climbing, and jumping, on both macroscopic symptoms (e.g., body weight, disease activity, and colon length) and microscopic parameters (e.g., histopathology, immune markers, oxidative/antioxidant balance, and gut microbiota) in colitis models were compared.

Results: VWR (simulated recreational physical activity), swimming (aerobic exercise), and strength training (climbing and jumping) consistently promoted overall health in animal colitis models. However, evidence for FTR remains inconsistent, with a notable number of studies suggesting potential exacerbation of colitis symptoms, possibly due to stress or fatigue resulting from its coercive nature. Overall, various exercise (e.g., VWR, swimming, strength training) ameliorates colitis symptoms possibly by suppressing immune hyperactivation, enhancing antioxidant defenses, and modulating gut microbiota composition. In contrast, FTR was inconsistent, with several studies indicating a potential exacerbation of colitis symptoms, possibly due to stress or fatigue induced by its coercive nature.

Conclusion: Exercise modality is critical in influencing colitis outcomes, with voluntary and low-stress forms generally being beneficial, while forced exercise may yield adverse effects. These findings highlight the importance of exercise type and individual tolerance in designing therapeutic exercise interventions for IBD. Further research is warranted to establish a robust therapeutic framework for exercise-based interventions in IBD management.

Background: Due to their significantly lower incidence than colorectal polyps and macroscopic features resembling those of hyperplastic polyps, rectal neuroendocrine tumors (rNETs) are frequently misdiagnosed and resected as polyps. To date, no reports have been written on the application of artificial intelligence for assisting in the white-light endoscopy of rNETs.

Aim: To establish a neuroendocrine tumor lesion detection algorithm based on the YOLOv7 model and evaluate the performance of the algorithm in identifying neuroendocrine tumors.

Methods: In total, 137748 white-light endoscopic images were collected in this study, including 2232 images of rNET, 4429 images of submucosal lesions other than rNET, 42563 images of polyps, and 88593 images of normal mucosa. All the images were randomly divided into a training set, a validation set, and a test set. To evaluate the ability of the algorithm to diagnose rNETs, we selected 1578 images to form the test set. The performance of the algorithm was compared with that of endoscopists at different levels.

Results: The accuracy of the algorithm in identifying rNET from all the images was 97.8%, the sensitivity was 72.6%, the specificity was 99.7%, the positive predictive value was 93.9%, and the negative predictive value was 98.1%.

Conclusion: Our model, which was based on YOLOv7, could effectively detect rNET lesions, which was better than that of most endoscopists.

Background: The association between the serum uric acid-to-high-density lipoprotein cholesterol ratio (UHR) and cardiovascular disease (CVD) risk in Asian populations with metabolic dysfunction-associated steatotic liver disease (MASLD) remains insufficiently elucidated.

Aim: To investigate the relevance and dose-responsive relationship between UHR and 10-year CVD risk among Asian MASLD patients.

Methods: In this retrospective analysis, 3901 MASLD patients were enrolled based on established screening criteria. As measured by the Framingham risk score, participants were stratified according to their 10-year CVD risk. The association between UHR and CVD risk was evaluated using binary logistic regression, while dose-response patterns were explored through restricted cubic spline (RCS) modeling. The discriminatory capability of UHR, in comparison with conventional biomarkers, was further examined by receiver operating characteristic curve analysis.

Results: Multivariable-adjusted analyses revealed that elevated UHR levels were significantly associated with an increased likelihood of intermediate-to-high CVD risk. RCS modeling demonstrated a linear dose-response relationship between UHR and the Framingham risk score (P for nonlinearity = 0.114). Sex-stratified RCS analyses further indicated that this linear association persisted among males (P for nonlinearity = 0.167) but was not statistically significant in females (P for nonlinearity = 0.476). Further stratified analyses revealed that the association was particularly pronounced among younger individuals (< 50 years), males, and those with central obesity, whereas it was attenuated in older adults (≥ 50 years) and females. Receiver operating characteristic analysis demonstrated that UHR outperformed individual biomarkers in predicting 10-year CVD risk, showing an area under the curve of 0.655 (95% confidence interval: 0.635-0.674).

Conclusion: UHR functioned as an independent predictor of 10-year CVD risk in Asian patients with MASLD, demonstrating a linear dose-response association and superior discriminative performance relative to conventional biomarkers, especially among younger individuals, males, and those with central obesity.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), has been increasingly associated with the progression of neurodegenerative disorders, particularly Alzheimer's disease (AD). Emerging data from population-based meta-analyses and in vivo experimental models demonstrate that systemic inflammation associated with IBD exacerbates disruption of the gut-brain axis (GBA). This disruption promotes the deposition of amyloid-β (Aβ) plaques, and cognitive decline. Together, these effects contribute to the progression of AD. Chronic colitis, a hallmark of IBD, accelerates Aβ pathology and induces cognitive impairment in transgenic mouse models, providing direct evidence of the detrimental effects of gut inflammation on neurodegeneration. Although numerous clinical and meta-analytical studies have examined the prevalence of AD in IBD patients, the molecular mechanisms underlying this association remain inadequately understood. In particular, the roles of immune regulation and GBA interactions require further investigation. This review aims to critically compile current evidence that elucidates the shared pathophysiological mechanisms underlying this association, such as chronic systemic inflammation, gut dysbiosis, and dysregulated immune responses. Although anti-inflammatory therapies, probiotics, and modulation of the gut microbiota have the potential to reduce the risk of AD and slow its progression, age-related gut inflammation and dysbiosis can aggravate AD pathology. This underscores the necessity for treatments that specifically target IBD-associated inflammation to limit AD progression. In addition, this review also meticulously examines how immune signaling and regulatory pathways in IBD, such as triggering receptor expression via myeloid cell receptor activation; NLRP3 inflammasome-driven inflammation; disrupted interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) signaling; and elevated C-reactive protein levels, contribute to increased amyloidogenesis. This paper proposes a comprehensive framework for therapeutic strategies targeting IBD-related inflammation and elucidates their potential to attenuate the progression of AD.

Background: Sepsis-induced intestinal injury disrupts barrier function and exacerbates systemic inflammation, contributing to high mortality.

Aim: To investigate the mechanism by which sphinganine protects against sepsis-induced intestinal injury, focusing on macrophage polarization and toll like receptor 2 (TLR2)/nuclear factor kappa-B (NF-κB) signaling.

Methods: A cecal ligation and puncture sepsis model was established in mice (n = 20/group). Treatments included sphinganine (15 mg/kg) and a TLR2 agonist [fibroblast-stimulating lipopeptide-1 (FSL-1), 10 μg/kg]. Serum markers [diamine oxidase (DAO), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6] were measured by enzyme-linked immunosorbent assay. Intestinal injury and macrophage polarization [cluster of differentiation (CD) 86⁺ M1, CD206⁺ M2] were assessed via hematoxylin and eosin and immunofluorescence staining. Proteomic analysis, molecular docking, and Western blot were used to evaluate TLR2/NF-κB signaling. Data were analyzed by analysis of variance and t-test.

Results: Sphinganine significantly reduced serum levels of DAO (P < 0.05), IL-1β, TNF-α, and IL-6 (P < 0.05), preserved intestinal crypt structure, and enhanced tight junction protein zonula occludens-1 expression. It promoted a shift from M1 (CD86⁺) to M2 (CD206⁺) macrophages. Proteomics identified TLR2 as the most differentially expressed protein, and molecular docking confirmed strong binding between sphinganine and TLR2 (-4.3 kcal/mol). Sphinganine downregulated TLR2 and phosphorylated-NF-κB p65 expression (P < 0.05), effects reversed by FSL-1. Total NF-κB p65 levels remained unchanged.

Conclusion: Sphinganine protects against sepsis-induced intestinal injury by inhibiting TLR2/NF-κB signaling, modulating macrophage polarization toward the M2 phenotype, and preserving intestinal barrier integrity.

Background: Biologic therapies have transformed the management of inflammatory bowel disease (IBD), yet their high cost poses substantial challenges for healthcare systems. Biosimilars offer a cost-effective alternative, with extensive evidence supporting the safety and efficacy of non-medical switching for infliximab and adalimumab. However, real-world data on ustekinumab biosimilars in IBD remain limited. Given increasing mandates for non-medical switches in Canada, evaluating clinical outcomes is critical to ensure patient safety and treatment sustainability. We hypothesized that switching from originator ustekinumab to a biosimilar would preserve clinical efficacy, safety, and drug persistence in patients with IBD.

Aim: To evaluate clinical efficacy, treatment persistence, biomarker activity, and adverse events in IBD patients who underwent non-medical biosimilar switching from the ustekinumab originator to a biosimilar.

Methods: This was an observational study of consecutive IBD patients who underwent a biosimilar switch. Disease activity, biomarkers, drug sustainability, and adverse events were captured 8 weeks before the switch, at the time of switch (baseline), 12 weeks, and 24 weeks after the switch.

Results: Of 81 patients were included [85.2% had Crohn's disease, the median age at inclusion: 42 years (interquartile ranges: 29-61)]. Previous biological exposure was 82.7% and a dose optimization of the originator ustekinumab was performed in 63% before the switch. Drug sustainability at 12 weeks and 24 weeks of switch was 96.3% and 95%, regardless of disease type or phenotype. The discontinuation rate was 4.9%. There was no significant difference in the rates of clinical remission at week 8 before switch, baseline, week 12, and 24 after switch: 87%, 85.9%, 84.3%, and 92.7%, P = not statistically significant. The biomarker activity was not significantly different for C-reactive protein, hemoglobin, albumin, and fecal calprotectin (P = not statistically significant). All patients who stopped therapy after the non-medical switch needed a dose optimisation of the originator ustekinumab and had previous biological therapy prior to starting the ustekinumab originator.

Conclusion: Despite prior biologic exposure and frequent dose escalation, switching to ustekinumab biosimilar showed stable efficacy, unchanged biomarkers, and high treatment persistence.

Acute pancreatitis (AP) is a life-threatening inflammatory condition triggered by the premature activation of trypsin. The limited understanding of its underlying pathophysiology remains a key obstacle to the development of targeted therapies. Mounting evidence now underscores mitochondrial dysfunction as a critical pathogenic driver in AP. Cellular mitochondrial dysfunction often precedes both cytokine release and trypsin activation, potentially serving as a primary initiator in the development and advancement of AP. Mitochondrial dysfunction is associated with calcium overload, inflammatory reactions, mitochondrial permeability transition pore opening, mitophagy damage, and other potential pathogenesis of pancreatic cell injury. Elucidating the impact of mitochondrial injury in AP may facilitate the development of innovative treatment approaches. This review provides a comprehensive and systematic analysis of the pivotal role of mitochondria in regulating pancreatic homeostasis, while evaluating emerging therapeutic strategies aimed at mitigating mitochondrial dysfunction. By integrating cutting-edge research findings, this work highlights the translational potential of these advancements in redefining diagnostic frameworks and optimizing therapeutic approaches for the management of AP.

The transverse incision with longitudinal ligation (TILL) procedure is a new method for treating circumferential prolapsed hemorrhoids. A study by Song et al found TILL to be better than the traditional Milligan-Morgan hemorrhoidectomy for short-term results, showing less pain, quicker healing, and lower risk of anal stenosis. TILL reduces tissue tension and controls blood supply, allowing effective removal of diseased tissue while maintaining anal function and structure. However, the study's limitations, including its retrospective, single-center design, small sample size, and short follow-up, restrict the findings' generalizability and ability to assess long-term outcomes like recurrence. Larger, multicenter trials are needed for a thorough evaluation and wider clinical adoption of TILL.

Epstein-Barr virus (EBV), a linear double-stranded DNA herpesvirus, is universally prevalent in humans. Infection is mostly invisible in early childhood, subsequently leading to a latent infection in the B-lymphatic system that persists throughout life. However, in immunocompromised hosts, it may infect more cell types, especially epithelial cells. Furthermore, EBV can reactivate and employ multiple mechanisms to evade the immune system, and it can also induce host immune dysfunction, leading to exacerbation or triggering of the inflammatory process. Inflammatory bowel disease (IBD), an immune-mediated gastrointestinal inflammatory, is increasingly recognized as having multiple stages of development, similar to other inflammatory diseases (systemic lupus erythematosus and rheumatoid arthritis). EBV, a commonly encountered opportunistic infection in IBD, can cause rapid disease progression loss of response to drug treatment, and induction of lymphoid tissue proliferative diseases or EBV-associated lymphomas, and may even lead to death in affected patients. To comprehend the complex interactions between EBV and the different stages of IBD disease progression, we comprehensively review the current evidence of the relevance of EBV to the clinical stages of IBD, including the risk, initiation, and development stages, with the aim of developing a more comprehensive predictive and therapeutic strategy for IBD.