Background: Hepatic ischemia-reperfusion injury (HIRI) is a major complication in liver transplantation with limited treatment options. Peptidomics offers a promising approach to discover therapeutic peptides.
Aim: To identify novel peptides from human liver transplants that could mitigate HIRI and preliminarily explore their mechanisms.
Methods: Liver samples from six transplant patients were analyzed using nano-liquid chromatography-tandem mass spectrometry. A candidate peptide, human liver transplantation peptide 1 (HLTP1), was screened in a murine HIRI model and validated in vitro using AML12 cells. Mechanisms were probed via Jun N-terminal kinase (JNK) phosphorylation analysis and rescue experiments with a JNK activator.
Results: HLTP1 was identified as a protective peptide. It reduced liver damage and apoptosis in mice, enhanced cell viability and proliferation, and decreased apoptosis in AML12 cells. Mechanistically, HLTP1 inhibited JNK phosphorylation, and its effects were reversed by JNK activation.
Conclusion: HLTP1 alleviates HIRI by inhibiting JNK-mediated apoptosis, representing a potential therapeutic strategy for liver transplantation.
Viral infections, particularly those triggered by emerging pathogens like severe acute respiratory syndrome coronavirus 2, are increasingly recognized for their profound impact on the gut microbiota, causing dysbiosis, a condition characterized by an imbalance in microbial communities. Recent studies suggest that alterations in gut microbiota can influence disease progression, immune responses, and clinical outcomes. The bidirectional relationship between the gut microbiota and the host immune system is crucial in shaping responses to infection. Furthermore, dysbiosis has been linked to exacerbated inflammation, impaired mucosal barrier function, and altered drug metabolism, thereby complicating both disease pathogenesis and treatment efficacy. This review examines the interplay between viral infections and gut microbiota dysbiosis, with a focus on the underlying mechanisms and potential therapeutic strategies to modulate host immunity. We also evaluate the potential of microbiome-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, as therapeutic strategies for restoring microbial balance and mitigating the severity of infections. The paper underscores the need for further research to optimize microbiota-targeted therapies and integrate them into clinical practice, offering a comprehensive approach to managing dysbiosis in viral infectious diseases.
Background: Ulcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease. The gut microbiome undergoes significant changes in UC. Fatigue is a highly prevalent and debilitating extraintestinal symptom of UC, which negatively affects quality of life. However, its relationship with gut microbes and metabolites remains unclear.
Aim: To assess the gut microbiota and metabolomic characteristics of patients with UC with fatigue (HUCF).
Methods: A total of 120 participants were recruited and divided into four groups (n = 30 per group) based on the diagnosis of UC and Fatigue Scale-14 scores: HUCF, UC without fatigue (HUCN), healthy with fatigue (HHF), and healthy without fatigue (HHN). Fresh stool samples were collected for 16S rRNA sequencing and untargeted metabolomic analysis.
Results: Metabolomic analysis revealed significant differences among the four groups (principal component analysis/partial least squares discriminant analysis, P = 0.001), with differential expression of metabolites such as linoleoyl ethanolamide, arachidonoyl ethanolamide, glycocholic acid, and thromboxane (TX). Notably, TX was detected only in the HUCF group. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed alterations in eicosanoid, tryptophan, and tyrosine metabolism in the HUCF group. Microbial richness and diversity were significantly lower in the HUCF group than in the other three groups. The HUCF group showed enrichment of Hyphomicrobiales, Brucella, Eisenbergiella, Pediococcus, and Sellimonas. The HUCN group showed enrichment of Campylobacter-related taxa. The HHF group showed enrichment of Fusobacterium, Desulfovibrionaceae, and Bilophila. The HHN group showed enrichment of beneficial genera such as Adlercreutzia. Notably, Anaerococcus, a beneficial genus, was enriched in the HUCF group. Correlation analysis indicated that specific microbes (e.g., Faecalibacterium and Escherichia-Shigella) were associated with the severity of UC and fatigue.
Conclusion: Patients with HUCF exhibit a distinct gut microbial structure and metabolomic profile. The pro-inflammatory metabolite TX and the genus Anaerococcus are uniquely enriched in patients with HUCF, suggesting their potential roles in the development of HUCF. These findings provide novel insights and a theoretical basis for improving the clinical management of HUCF.
Background: Clinically, patients with nonvariceal gastrointestinal bleeding (NVGB) are prone to thromboembolic events, but the specific risk remains unclear.
Aim: To identify risk factors and evaluate the performance of five machine learning (ML) models in predicting the risk of thromboembolic events in patients with NVGB.
Methods: This retrospective cohort study enrolled 866 patients from a tertiary hospital for model training and internal validation, and 282 patients from three other tertiary hospitals for external validation. These data were used to develop five ML models to predict the risk of thromboembolic events in patients with NVGB. After initial feature selection by training ML models, ten variables were selected to construct simplified ML models. Model performance was evaluated using accuracy, precision, sensitivity, specificity, F1-score and area under the receiver operating characteristic curve. Calibration curve and decision curve analysis were used to further evaluate the predicted probabilities and net benefits of the models.
Results: During hospitalization, the incidence of thromboembolic events was 25.61% in patients with NVGB. The categorical boosting (CatBoost) algorithm which combined variable importance and SHapley Additive exPlanations values identified 10 independent predictors of thromboembolic events: (1) History of anticoagulant drug use; (2) D-dimer level; (3) Age; (4) History of thromboembolism; (5) Length of hospital stays; (6) Intensive care unit (ICU) admission; (7) Hemoglobin level; (8) Use of hemostatic drugs; (9) Heart rate; and (10) Serum albumin level. We developed five simplified ML prediction models (L1 regularized logistic regression, random forest, support vector machines, extreme gradient boosting, and CatBoost) based on the above 10 predictors, which achieved area under the receiver operating characteristic curves of 0.805, 0.804, 0.806, 0.746, and 0.815 in external validation, respectively. The performance of all five ML models significantly exceeded that of D-dimer alone in both internal and external validation. The CatBoost model demonstrated good calibration and accuracy, achieving the lowest Brier score of 0.131 and 0.110 in the internal and external validation set, respectively. Of the five models, the CatBoost model was considered the preferred choice in clinical settings.
Conclusion: The findings in this study enable effective and timely preventive interventions for high-risk patients, and help avoid unnecessary monitoring in low-risk patients.
Enhanced recovery after surgery (ERAS) programs have transformed perioperative care, yet delayed gastrointestinal function and excessive neuroendocrine stress remain major obstacles to optimal recovery. Hong et al's randomized controlled trial embedded acupoint-based neuromodulation - meridian-timed acupoint application combined with transcutaneous electrical acupoint stimulation - within an ERAS framework and demonstrated accelerated gastrointestinal recovery accompanied by endocrine attenuation. This article offers a structured critical appraisal of the trial, emphasizing methodological rigor, mechanistic plausibility, and alignment with ERAS core principles of stress mitigation, functional restoration, and patient experience. The observed reductions in norepinephrine, cortisol, and aldosterone suggest modulation of the hypothalamic-pituitary-adrenal axis as a key mediator of benefit. Future research priorities include multicenter, sham-controlled validation; integration of autonomic and inflammatory biomarkers (heart rate variability, interleukin-6, tumor necrosis factor-α, C-reactive protein); and pragmatic evaluation of cost-effectiveness and acceptability. Positioning acupoint stimulation within precision-integrative perioperative care could advance ERAS from a recovery protocol to a system of host-response modulation. Integrative acupoint neuromodulation thus represents a biologically coherent, low-risk, and scalable strategy for enhancing resilience, accelerating gastrointestinal recovery, and improving surgical outcomes worldwide.
Background: Endoscopy is the gold standard for examining inflammatory bowel disease (IBD), and fecal calprotectin (FC) is a widely used surrogate marker for IBD. However, both methods are considered unpleasant by patients because of their invasiveness and inconvenience. Leucine-rich α-2-glycoprotein (LRG) is a novel serum biomarker that has been previously studied only in Japanese populations.
Aim: To evaluate the predictive utility of LRG in a Taiwanese cohort.
Methods: Patients with IBD were prospectively enrolled between 2022 and 2024. Serum and stool samples were collected within 1 month of endoscopy, and patient albumin, hemoglobin (Hb), and C-reactive protein (CRP) levels were measured. Active endoscopic disease was defined as a Mayo endoscopic subscore ≥ 2 for ulcerative colitis (UC) or a Simple Endoscopic Score for Crohn's Disease ≥ 6 for Crohn's disease (CD). Correlations and diagnostic performance of biomarkers were analyzed.
Results: A total of 203 patients (100 with UC and 103 with CD) were enrolled. LRG was positively correlated with FC and CRP but negatively correlated with Hb and albumin (P < 0.05). In UC, the area under the curves (AUCs) for CRP, LRG, and FC in predicting endoscopic activity were 0.54, 0.56, and 0.77, respectively (P < 0.001). In CD, the corresponding AUCs were 0.69, 0.60, and 0.72 (P > 0.05). The addition of LRG modestly improved predictive ability for endoscopic activity in patients with UC. In patients with UC with low CRP levels, combining CRP, Hb, and LRG significantly improved diagnostic accuracy (AUC increased from 0.60 to 0.76, P < 0.05), achieving a performance comparable to, though slightly lower than, that of FC (AUC: 0.78).
Conclusion: LRG may serve as a supportive biomarker, particularly in combination with other markers, for assessing disease activity in Taiwanese patients with IBD. In patients with UC with normal CRP levels, adding LRG and Hb could enhance the predictive accuracy for endoscopic activity to nearly that of FC.
Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy remains a challenging field in therapeutic endoscopy due to the complex anatomical reconstructions that limit access to the biliary tree. Over the past two decades, device-assisted enteroscopy (DAE), including single-balloon, double-balloon, and motorized spiral enteroscopy, has expanded the feasibility of ERCP in this population, with overall technical success rates generally reported between 70% and 90%. Nevertheless, these techniques are technically demanding, time-consuming, and frequently affected by limited reach and unstable positioning. More recently, interventional endoscopic ultrasound (EUS)-guided procedures have emerged as highly effective alternatives, significantly improving clinical outcomes in selected patients, particularly in those with long-limb Roux-en-Y reconstructions where conventional methods are less effective. Percutaneous transhepatic biliary drainage continues to represent a valuable salvage option when endoscopic approaches fail, though it is associated with a greater burden of reinterventions and adverse events. This minireview provides a comprehensive overview of the main endoscopic strategies for biliary drainage in altered anatomy, focusing on technical considerations, efficacy, and safety profiles of DAE-assisted ERCP, EUS-guided interventions, and motorized systems. The evolving landscape of biliary drainage in this setting highlights the need for tailored treatment strategies, multidisciplinary collaboration, referral to high-volume centers, and further prospective studies to refine patient selection and optimize clinical outcomes.
Colorectal cancer (CRC) with lung oligometastases, particularly in the presence of extrapulmonary disease, poses considerable therapeutic challenges in clinical practice. We have carefully studied the multicenter study by Hu et al, which evaluated the survival outcomes of patients with metastatic CRC who received image-guided thermal ablation (IGTA). These findings provide valuable clinical evidence supporting IGTA as a feasible, minimally invasive approach and underscore the prognostic significance of metastatic distribution. However, the study by Hu et al has several limitations, including that not all pulmonary lesions were pathologically confirmed, postoperative follow-up mainly relied on dynamic contrast-enhanced computed tomography, no comparative analysis was performed with other local treatments, and the impact of other imaging features on efficacy and prognosis was not evaluated. Future studies should include complete pathological confirmation, integrate functional imaging and radiomics, and use prospective multicenter collaboration to optimize patient selection standards for IGTA treatment, strengthen its clinical evidence base, and ultimately promote individualized decision-making for patients with metastatic CRC.
Background: Data comparing the outcomes of hepatocellular carcinoma (HCC) ablation by multibipolar radiofrequency ablation (mbp-RFA) and microwave ablation (MWA) are lacking. This study compares safety and efficacy of the two techniques in treatment-naive HCC.
Aim: To compare the risk of local tumor progression (LTP) according to the technique; secondary endpoints included technique efficacy rate at one-month, overall survival and major complication rate.
Methods: A bi-institutional retrospective analysis of patients undergoing treatment-naive HCC ablation by either technique was performed. Inverse probability of treatment weighting was used to compare the two groups. Mixed effects multivariate Cox regression was applied to identify risk factors for LTP.
Results: A total of 362 patients (mean age, 66.1 ± 6.2 years, 308 men) were included, of which 242 (323 tumors) treated by mbp-RFA and 120 (168 tumors) by MWA. After a median follow-up of 27 months, cumulative LTP was 11.4% after mbp-RFA and 25.2% after MWA. Independent risk factors for LTP at multivariate analysis were MWA (hazard ratio = 2.85, P < 0.001) and tumor size (hazard ratio = 1.08, P < 0.001). Two-year LTP-free survival was higher after mbp-RFA than MWA regardless of size (< 3 cm: 96% vs 87.1%, P < 0.01; ≥ 3 cm: 87.5% vs 74%, P = 0.04). Technique efficacy rate was higher after mbp-RFA (94.1% vs 87.5%, P = 0.01). No difference was observed in major complication rate (9.5% vs 7.5%, P = 0.59), nor 5-year overall survival (63.6% vs 58.3%, P = 0.33).
Conclusion: Mbp-RFA leads to better local tumor control of treatment-naïve HCC than MWA regardless of tumor size and has better primary efficacy, while maintaining a comparable safety profile.
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