Curcumol alleviates acute pancreatitis by inhibiting RIPK1/RIPK3/MLKL pathway-mediated necroptosis: integrated bioinformatics, network pharmacology, molecular docking and dynamics simulations, and experimental validation.

Da-Cheng-Qi decoction attenuates inflammatory edema and endoplasmic reticulum stress in acute pancreatitis via suppressing NF-κB pathway.

Revealing the temporal metabolic trajectory and potential pharmacodynamic substances of Da-Cheng-Qi Decoction in treating patients with acute pancreatitis: A serum metabolomics-based study.

Acute pancreatitis (AP) necessitates accurate severity and prognosis assessment. While the Computed Tomography Severity Index (CTSI) is widely used, its time-dependent predictive value remains unclarified. This meta-analysis compares the predictive efficacy of CTSI across assessment times for AP outcomes. Systematic searches were performed in PubMed, Cochrane, Embase, and Web of Science. Literature was collated by using EndNote 20. Methodological quality was assessed using QUADAS-2. Bivariate meta-analyses were conducted with Stata 16 and Meta-Disc 1.4. Analysis of 28 studies (n = 5,419) revealed significant time-dependent variations: CTSI achieved optimal sensitivity for severity prediction at ≤ 48h (0.84, 95%CI 0.78-0.89) with specificity 0.79 (0.76-0.82), and peak sensitivity for organ failure at ≤ 48h (0.90, 0.82-0.95) though with moderate specificity (0.52, 0.48-0.57). Mortality prediction showed the highest sensitivity at ≤ 72h (0.89, 0.74-0.97), despite suboptimal specificity (0.65, 0.61-0.68). Pancreatic necrosis detection demonstrated superior accuracy at > 72h (sensitivity 0.91, 0.84-0.95; specificity 0.82, 0.79-0.85). The pooled area under the receiver operating characteristic curve values with 95% CI for overall predictive performance were: severity, 0.85 (0.82-0.88); organ failure, 0.86 (0.82-0.88); mortality, 0.85 (0.81-0.88); and pancreatic necrosis, 0.94 (0.99 - 0.96). CTSI exhibits distinct temporal predictive patterns: ≤48h assessments optimise early evaluation of severity/organ failure, ≤ 72h scans best predict mortality, while delayed imaging (> 72h) maximises pancreatic necrosis accuracy at the expense of clinical timeliness. Future research must standardise imaging timepoints, integrate CTSI with physiological biomarkers, and develop dynamic assessment models to resolve discrepancies in anatomical-pathophysiological prognostic factors in AP management.

The relationship between thyroid function and pancreatic disease has been observed clinically, yet causality remains unestablished. We applied bidirectional Mendelian randomization using genetic instruments from genome-wide association studies encompassing over 500,000 individuals to determine causal relationships. We demonstrate that genetic liability to hypothyroidism substantially protects against acute pancreatitis (odds ratio 0.37, 95 % CI 0.17-0.80). Genetically elevated basal metabolic rate increases acute pancreatitis risk (OR 1.16) while decreasing chronic pancreatitis risk (OR 0.77), revealing divergent pathophysiological mechanisms. No causal relationship exists between thyroid function and pancreatic cancer. To elucidate underlying mechanisms, we performed multi-omics analysis including bulk RNA sequencing from 172 pancreatic adenocarcinomas, single-cell RNA sequencing from acute pancreatitis (32,830 cells), chronic pancreatitis (30,426 cells), and pancreatic cancer (95,751 cells), and GeoMx spatial transcriptomics (253 regions). High metabolic gene expression predicts favorable cancer survival (hazard ratio 0.52, P = 0.0015). Single-cell analysis reveals myeloid-specific metabolic gene downregulation in chronic pancreatitis and 31-fold upregulation of the thyroid hormone-inactivating enzyme DIO3 in tumor epithelial cells. Spatial transcriptomics demonstrates that PPARGC1A downregulation occurs in preneoplastic lesions before malignant transformation. These findings establish thyroid function as a causal determinant of pancreatitis susceptibility, identify cell type-specific mechanisms including local thyroid hormone inactivation and metabolic reprogramming, and demonstrate that patient-derived organoids better preserve prognostically favorable metabolic phenotypes than cell lines. Thyroid function represents a potentially modifiable risk factor for inflammatory pancreatic disease.

Hypertriglyceridemia is a common lipid disorder linked to residual cardiovascular risk and acute pancreatitis despite standard therapy. Olezarsen, an antisense oligonucleotide targeting apolipoprotein C-III (ApoC-III), offers a novel triglyceride-lowering strategy. We performed an updated meta-analysis to evaluate its efficacy and safety. We performed a meta-analysis of randomised controlled trials (RCTs) identified through PubMed, Cochrane, Scopus and Web of Science up to December 2025. Random-effects models were used to pool mean percentage changes (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs). CRD420261279110. Six RCTs with 2676 participants were analysed. Olezarsen significantly reduced triglycerides at 50 mg (MD -46.61%, 95% CI -49.59 to -43.64) and 80 mg (MD -54.37%, 95% CI -61.26 to -47.48), both p < 0.0001. ApoC-III was markedly reduced (50 mg: MD -63.51%, 95% CI -74.18 to -52.84; 80 mg: MD -66.88%, 95% CI -77.91 to -55.85; both p < 0.0001). Non-HDL-C also decreased significantly (50 mg: MD -21.41%, 95% CI -25.12 to -17.70; p < 0.0001; 80 mg: MD -25.28%, 95% CI -33.99 to -16.58; p = 0.001). LDL-C increased modestly at 50 mg (MD 17.58%, 95% CI 0.24 to 34.93; p = 0.047). Olezarsen reduced acute pancreatitis risk (50 mg: RR 0.16, 95% CI 0.05-0.48; p = 0.001; 80 mg: RR 0.33, 95% CI 0.14-0.76; p = 0.009). Overall adverse events were comparable to placebo, while ALT/AST ≥ 3 × ULN increased with 80 mg (RR 2.56, 95% CI 1.20-5.44; p = 0.01). Olezarsen provides substantial triglyceride reduction with favourable effects on atherogenic lipoproteins and a tolerable short-term safety profile. Longer-term trials are needed to confirm cardiovascular outcomes and safety.

Evaluation of Duration of Mechanical Ventilation Associated with Short-Course Midazolam Infusion in the Emergency Department.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes and obesity, conditions frequently encountered in gastroenterological practice. Their pleiotropic effects along the gut-pancreas-liver axis have raised both therapeutic interest and safety concerns, particularly regarding hepatic outcomes, gastrointestinal cancers, peri-endoscopic management, and gastrointestinal adverse events. This position paper, endorsed by the Italian Society of Gastroenterology (SIGE), was developed according to the GRADE framework and provides evidence-based recommendations for the safe and effective management of GLP-1RAs in gastroenterology, highlighting their favorable benefit-risk profile while identifying key knowledge gaps requiring future prospective studies. GLP-1RAs may be safely used in patients with diabetes or obesity and metabolic dysfunction-associated steatotic liver disease. In cirrhotic patients with diabetes or obesity, GLP-1RAs appear safe and are associated with reduced hepatic decompensation. Available evidence does not support an increased risk of esophageal, gastric, colorectal, or pancreatic cancer, while a potential reduction in hepatocellular carcinoma incidence is suggested. Routine discontinuation of GLP-1RAs before upper gastrointestinal endoscopy is not recommended. GLP-1RAs increase the risk of mild, transient gastrointestinal adverse events and cholelithiasis but are not associated with severe gastrointestinal complications or acute pancreatitis.

Multi-modal deep learning model for predicting recurrence of moderately severe and severe acute pancreatitis.

Analysis of pathological histochemical characteristics of yak pancreas induced by Fasciola hepatica.

Percutaneous endoscopic necrosectomy using a novel slim gastroscope with a large working channel for pancreatic walled-off necrosis.

Hypertriglyceridemia is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). We aimed to evaluate the efficacy and safety of apolipoprotein C-III (ApoC-III) inhibitors in patients with hypertriglyceridemia. Electronic databases were systematically searched for randomised controlled trials (RCTs) comparing ApoC-III inhibitors (Volanesorsen, Olezarsen and Plozasiran) with placebo. A frequentist network meta-analysis was performed. Continuous outcomes were presented as mean differences (MDs), and dichotomous outcomes as risk ratios (RRs), both with 95% confidence intervals (CIs). A total of 15 RCTs involving 3934 patients were included. All ApoC-III inhibitors demonstrated significant reductions in TG, except for Volanesorsen 100 mg Q1W and Olezarsen 10 mg Q4W. Olezarsen 80 mg administered every 4 weeks had the highest SUCRA ranking for TG reduction (MD: -63.26; 95% CI: -70.04 to -56.47; p < 0.01). Moreover, ApoC-III inhibitors were associated with a significant reduction in the incidence of pancreatitis (HR: 0.16, 95% CI: 0.07-0.33, p < 0.01). None of the agents significantly increased the risk of serious adverse events. ApoC-III inhibitors significantly improved triglyceride levels and other lipid parameters and, most importantly, substantially reduced the risk of acute pancreatitis. Future trials are needed to evaluate their effects on cardiovascular outcomes.

Acute recumbency associated with necrotizing pancreatitis in a donkey.

Paeonolisan herbal medicine. The work explored the alleviation of paeonol on acute pancreatitis andaction mechanism. Thirty mice were divided into control, model and treatment groups. The acute pancreatitis model was established in model and treatment groups.The treatment group was treated with paeonol for seven days. After treatment, compared with model group, in treatment group the pancreas index was significantly decreased, with significantly decreased pancreas and ileum injury scores, the serum lipase, amylase, interleukin 1β, interleukin 6, tumor necrosis factor α and malondialdehyde levels were significantly decreased, the SOD level was significantly increased, and the pancreas tissue nuclear factor E2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1)expression levels were significantly increased(p&lt;0.05). In conclusion, paeonol can alleviate the acute pancreatitis in mice. The action mechanism may be related to its inhibition of inflammatory response and oxidative stress and activation of Nrf2/HO-1 signaling pathway.

Acute pancreatitis during pregnancy is a rare but potentially severe condition that may adversely affect both maternal and fetal outcomes. Although advances in intensive care have improved prognosis, the impact of the disease on pregnancy outcomes remains an important clinical concern. This study aimed to investigate maternal and fetal outcomes in pregnancies complicated by acute pancreatitis and to evaluate the effect of disease severity on these outcomes. This retrospective study was conducted at a tertiary care center and included 25 pregnant women diagnosed with acute pancreatitis and 100 healthy controls between February 2020 and February 2025. Maternal and fetal outcomes were first compared between the acute pancreatitis and control groups. Subsequently, patients with acute pancreatitis were classified into mild and severe subgroups according to disease severity, and subgroup analyses were performed. Clinical, laboratory, and obstetric outcomes were analyzed using appropriate statistical methods. Patients with acute pancreatitis had significantly longer hospital stays and higher rates of maternal intensive care unit admission compared with controls (p < 0.001 for both). Gestational age at delivery was lower and neonatal birth weights were reduced in the acute pancreatitis group (p < 0.001 and p = 0.004, respectively). Neonatal mortality was also higher in this group (p < 0.001). In subgroup analyses, patients with severe acute pancreatitis had higher maternal ICU admission rates (p = 0.001), longer ICU stays (p = 0.005), and increased neonatal ICU admissions (p = 0.022). Acute pancreatitis during pregnancy is associated with adverse maternal, fetal, and neonatal outcomes, particularly in severe cases. Early recognition and close multidisciplinary management in tertiary centers may help reduce complications and improve pregnancy outcomes.

Acute pancreatitis (AP) is an inflammatory disease that can lead to systemic complications in severe cases. The endocannabinoid system has emerged as a potential modulator of inflammation in AP. We investigated the role of the endocannabinoid 2-arachidonoylglycerol (2-AG) and the cannabinoid receptors CB1 and CB2 during AP. A severity-dependent decrease in circulating 2-AG was found both in patients and a murine AP model. Restoring 2-AG - by avoiding its degradation via monoacylglycerol lipase inhibitor or direct 2-AG administration - reduced local and systemic inflammation, modulated peritoneal macrophage polarization, and mitigated lung injury. Notably, endocannabinoid system effects were consistent across sexes. Both cannabinoid receptors were involved in disease pathophysiology. Genetic Cnr1 knockout and pharmacological CB2 blockade showed distinct and complementary roles of both receptors in regulating inflammation, immune infiltration, and pulmonary damage. These findings highlight a protective role for 2-AG and highlight the endocannabinoid system - and cannabinoid receptors in particular - as a promising therapeutic target to modulate inflammation and reduce systemic complications in acute pancreatitis. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Vagus nerve stimulation (VNS) holds promise for modulating inflammation and gastrointestinal function, but its efficacy as an adjunctive therapy for acute pancreatitis (AP) remains unclear. This study aimed to investigate the protective effects of transcutaneous VNS (taVNS) in patients with AP. Patients with mild acute pancreatitis (MAP) and a PAN-PROMISE score ≥15 were recruited from five tertiary hospitals in China. Patients were randomly assigned to receive taVNS or sham-taVNS plus standard care. Stimulation parameters were set as follows: pulse width 0.5 ms, frequency of 25 Hz, and amplitude ranging from 0.5 to 1.5 mA. Patients, care providers and outcome assessors remained blinded to treatment allocation throughout the study. The primary endpoint was the median time to achieve a PAN-PROMISE score ≤ 6. A total of 60 patients were randomized. The taVNS group had a shorter median time to reach a PAN-PROMISE score ≤ 6 than the sham-taVNS group (3.00 vs. 4.00 days; HR = 1.956, P = 0.002). The proportion of patients achieving a PAN-PROMISE score ≤ 6 within the first 3 days was significantly higher in the taVNS group than in the sham-taVNS group (50.00% vs. 13.33%, P = 0.002). taVNS was associated with a more significant improvement in the subscales of the PAN-PROMISE, including abdominal pain, abdominal distension, and dysphagia (all P < 0.05). By day 3, the taVNS group showed a greater reduction in CRP levels compared with the sham-taVNS group (-32.40 mg/L vs. 12.75 mg/L, P = 0.005). Adverse events were mild and did not differ between the groups. In patients with MAP, taVNS was associated with earlier symptom resolution and potential anti-inflammatory effects with a favorable safety profile ( ClinicalTrial.gov: NCT06998784).

Acute necrotizing pancreatitis (ANP) is associated with pancreatic parenchymal necrosis and may lead to exocrine and endocrine dysfunction. However, the natural course and determinants of pancreatic functional impairment remain incompletely defined. We prospectively evaluated the pancreatic exocrine and endocrine function in patients with ANP and attempted to identify associated risk factors. Patients aged 18-80years with ANP defined by theRevised Atlanta Classificationwere enrolled and prospectively followed for 6months. Exocrine function was assessed using fecal elastase-1 (FE-1), and endocrine function was evaluated using fasting glucose, postprandial glucose, HbA1c, and homeostatic model assessment of insulin resistance (HOMA-IR). Clinical severity, etiology, anatomic distribution of necrosis, infected necrosis, and interventions were analyzed as predictors of dysfunction. Thirty patients completed 6-month follow-up. At 6months, exocrine insufficiency occurred in 40% of patients (mild 16.7%, severe 23.3%). Endocrine dysfunction was observed in 30% of patients, including diabetes mellitus (6.7%) and prediabetes (23.3%). Necrosis involving the pancreatic head was significantly associated with exocrine insufficiency (p = 0.003). Moderately severe acute pancreatitis independently predicted exocrine dysfunction (p = 0.01). No clinical or radiologic factor predicted endocrine insufficiency. Exocrine insufficiency appears to be relatively common following ANP, with a possible association observed in patients with moderately severe disease and head-dominant necrosis; however, these findings require further validation. Endocrine dysfunction was observed in approximately one-third of patients, but no consistent predictors were identified in this cohort.

Myeloperoxidase (MPO)-mediated oxidative stress drives inflammatory tissue injury, yet converting this enzyme activity into a selective and sustained imaging readout remains chemically challenging. To address this limitation, we report Mn-TyrCDTA, a manganese chelate designed to couple kinetic inertness with MPO-triggered activation and retention mechanism. Replacement of a flexible EDTA backbone with a rigidified CDTA scaffold improved the kinetic inertness 3-fold under a Zn2+ challenge (dissociation t1/2 = 61.7 min). Incorporation of a tyramine-derived phenolic moiety enabled MPO/H2O2-mediated, one-electron oxidation and covalent protein anchoring, resulting in a 3.6-fold relaxivity enhancement and prolonged inflamed tissue retention. In rat models of acute pancreatitis, contrast enhancement correlated with tissue MPO activity (R2 = 0.83), enabling quantitative disease severity stratification. Complementary 68Ga-TyrCDTA PET studies demonstrated enzyme-dependent tracer accumulation, and MPO inhibition reduced the imaging signal by 85% (R2 = 0.98). These findings establish a rational design framework for the quantitative imaging of neutrophil-driven oxidative tissue injury.

We aimed to evaluate the efficacy and safety of early analgesic interventions, particularly NSAIDs versus opioids, in reducing pain and improving clinical outcomes among adults with AP. A systematic literature search was conducted across PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, and ClinicalTrials.gov from database/registry inception to December 2025 to obtain relevant data. Randomized controlled trials involving adults aged ≥18 years diagnosed with AP, irrespective of the etiology and severity, who were administered analgesics (opioids, non-steroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, epidural anesthesia, local anesthesia, and paracetamol) and compared with placebo, conventional treatment, or another analgesic modality were included in this review. The primary outcome assessed was pain reduction. The secondary outcomes assessed were the need for rescue analgesia, length of hospital stay, complications (local and/or systemic), mortality, and adverse drug effects. Risk of bias was assessed using the Cochrane Risk of Bias tool 2.0. Effect estimates were pooled using a random-effects meta-analysis (DerSimonian-Laird approach), while non-pooled outcomes were summarized narratively. A total of 13 studies were included in the analysis. NSAIDs provided pain relief comparable to opioids, with a lower incidence of local complications (RR: 0.59, 95% CI: 0.37-0.94). No significant differences in the need for rescue analgesia (OR: 0.88, 95% CI: 0.33-2.35), length of hospital stay (MD: -2.68 days, 95% CI: -6.27-0.91), mortality (RR: 0.76, 95% CI: 0.19-3.05), and adverse drug effects (RR: 0.55, 95% CI: 0.17-1.76) were observed. However, the findings are limited by study bias and heterogeneity. Early analgesia with NSAIDs has efficacy and safety comparable to opioids in adults with AP, with the advantage of reducing local complications.