Acute pancreatitis (AP) is a common gastrointestinal disorder, and acute kidney injury (AKI) is a frequent and severe complication, significantly increasing mortality risk. Mean arterial pressure (MAP) is crucial for maintaining organ perfusion in critically ill patients. However, the optimal MAP target for minimizing mortality in AP patients complicated by AKI (AP-AKI) remains unclear. This retrospective cohort study analyzed data from the MIMIC-IV database, including 934 critically ill adult patients diagnosed with AP-AKI between 2008 and 2019. We investigated the relationship between MAP and in-hospital mortality using logistic regression models, adjusting for demographics, comorbidities, disease severity scores and intensive care interventions. Smooth curve fitting was used to explore potential non-linear associations. Subgroup analyses were performed to assess the impact of MAP across different clinical and demographic groups. Our analysis revealed a non-linear, L-shaped relationship between MAP and in-hospital mortality, with an inflection point at 71.32 mmHg. Below this threshold, increasing MAP was associated with significantly decreased odds of mortality (OR: 0.93, 95% CI: 0.87-0.99, p = 0.026). However, above this threshold, the association was no longer significant (OR: 1.015, 95% CI: 0.98-1.03, p = 0.699). Subgroup analyses showed consistent trends across most subgroups, with the benefit of maintaining MAP above the threshold being most pronounced in AKI stage 1 and 2 patients. This study suggests a potential association between maintaining specific MAP levels, particularly above 71.32 mmHg, and reduced in-hospital mortality in critically ill AP-AKI patients.

To evaluate temporal trends in gender, etiology, severity, outcomes, cost and median length of stay (MLS) in patients with acute pancreatitis (AP) in a third-tier Chinese city.

Patients with AP admitted to a university hospital between January 2013 and December 2021. Relationships between etiology, prevalence of severe acute pancreatitis (SAP) and survey years were investigated by joinpoint regression analysis.

A total of 5459 (male 62.3%) patients with AP were included. Between January 2013 and December 2021, we observed: (a) the prevalence of biliary diseases-related AP was stable, while the prevalence of hypertriglyceridemia (HTG)-associated AP (Ptrend = 0.04) and alcohol-associated AP (Ptrend < 0.0001) both increased; (b) there was an increase in crude prevalence of SAP from 4.97% to 12.2% between 2013 and 2021 (Ptrend < 0.0001); (c) compared to female populations, male gender had a higher prevalence of AP; (d) there was a decrease in MLS from 11 days to 8 days (Ptrend < 0.0001) and in median cost of hospitalization (MCH) for all patients (from 20,166 to 12,845 YUAN) (Ptrend < 0.0001); (e) the overall in-hospital mortality rate was 1.28% (70/5459) for patients with AP. There was no statistically significant in the time trend of mortality during the study period (Ptrend = 0.5873). At multivariate analysis, survey year was associated with prevalence of SAP after adjustment by age and biliary diseases (OR: 1.07; 95% CI: 1.03-1.12). Based on the stratification by severity of disease, the decrease of MLS and MCH was more significant in non-SAP vs. SAP patients.

Over the observational period, the proportion of male patients with AP, prevalence of age-adjusted rate of HTG and alcohol-associated AP and SAP increased, while MLS and MCH for all patients decreased, and the time trend of mortality of AP was stable.

Severe acute pancreatitis (SAP)-induced intestinal bacterial translocation and enterogenic infection are among the leading causes of mortality in patients. However, the mechanisms by which SAP disrupted the intestinal barrier and led to bacterial translocation remained unclear. Therefore, we employed multi-omics analysis including microbiome, metabolome, epigenome, transcriptome, and mass cytometry (CyTOF) to identify potential targets, followed by functional validation using transgenic mice. The integrated multi-omics analysis primarily indicated overgrowth of intestinal flagellated bacteria, upregulation of intestinal Toll-like receptor 5 (TLR5) and acute inflammatory response, and increased infiltration of intestinal high-expressing TLR5 lamina propria dendritic cells (TLR5hi LPDC) after SAP. Subsequently, intestinal flagellin-TLR5 signaling was activated after SAP. Intestinal barrier disruption, bacterial translocation, and helper T cells (Th) differentiation imbalance caused by SAP were alleviated in TLR5 knocked out (Tlr5-/-) or conditionally knocked out on LPDC (Tlr5ΔDC) mice. However, TLR5 conditional knockout on intestinal epithelial cells (Tlr5ΔIEC) failed to improve SAP-induced bacterial translocation. Moreover, depletion of LPDC and regulatory T cells (Treg) ameliorated bacterial translocation after SAP. Our findings identify TLR5 on LPDC as a potential novel target for preventing or treating intestinal bacterial translocation caused by SAP.

Acute pancreatitis (AP) is a common gastrointestinal disease characterized by pancreatic cell damage and inflammation. Given the early clinical diagnosis and management challenges, exploring novel analytical frameworks from new orientations for interrogating AP is urgent. The release of damage-associated molecular patterns (DAMPs) and their receptor recognition initiate sterile inflammation, serving as key drivers in the development and progression of AP. Thus, this study aimed to delineate the underlying correlations between alterations in the DAMP profile and the AP state. We have developed a new framework combining potential DAMPs profiles obtained from pseudotargeted metabolomics method with machine learning (ML) models for AP prediction. 2-(1-Piperazinyl) pyrimidine chemical labeling was utilized to provide characteristic fragment ions and improve the quantitative sensitivity of targeted metabolites. A total of 49 potential DAMPs were identified and semi-quantified from collected serum samples (n = 84), positive or negative for APs. For modeling obtained datasets with five different ML algorithms, the support vector machine model was chosen as the optimal model to differentiate with high accuracy, achieving an area under the receiver-operating characteristic curve (AUROC) of 0.944. It also showed a strong performance in an external independent validation set (AUROC: 0.907). Moreover, the model was interpreted using the Shapley Additive exPlanations analysis to specify the important features and identify specific free fatty acids as key contributors. Overall, the novel framework enables high accuracy in predicting the presence of AP status. Meanwhile, it underlines the utility of DAMPs in inflammatory diseases and provides reference values for diagnosing in first-line clinics.

Cytochrome P450 2E1 (CYP2E1) is a key enzyme in the cytochrome P450 family, playing a crucial role in metabolizing a wide range of endogenous and exogenous compounds. It is also pivotal in the onset and progression of inflammation. Despite the demonstrated anti-inflammatory effects of existing CYP2E1 inhibitors in various animal models, their clinical application remains limited due to poor selectivity, high toxicity, degradation susceptibility, and limited in vivo solubility. Through virtual screening, synthesis, and optimization, we identified compound 10 as a favorable selective and potent CYP2E1 inhibitor, with a Kd of 7.02 μM, an IC50 of 1.64 μM, and a Ki of 0.897 μM. Notably, treatment with 10 significantly reduced mortality, inflammation, and oxidative stress in mouse models of severe acute pancreatitis (SAP) induced by Caerulein combined with lipopolysaccharide (LPS) or l-Arginine. 10 significantly promoted the expression of Nrf2 in pancreatic tissues of the two SAP models; in vitro studies revealed that inactivation of Nrf2 signaling and increase of reactive oxygen species (ROS) were reversed by 10 in Caerulein-treated AR42J cells. Overall, our study identified a selective and potent small molecule CYP2E1 inhibitor 10, which may not only serve as a candidate compound for the treatment of SAP but also lay the groundwork for future drug development of anti-inflammatory agents.

This study aimed to elucidate the protective effects of Da Cheng Qi Decoction (DCQD) on severe acute pancreatitis (SAP) by targeting ferroptosis in pancreatic acinar cells and to establish a predictive signature and nomogram for acute pancreatitis (AP) risk assessment.

We utilized microarray analysis to delineate gene expression patterns among 32 healthy controls and 87 AP patients stratified by severity. Employing SAP models and NOX2-deficient cells, we investigated the molecular underpinnings of ferroptosis. The impact of DCQD and the ferroptosis inhibitor Fer-1 on gene expression, oxidative stress, and inflammation was assessed. Machine learning algorithms identified differentially expressed genes (DEGs) sensitive to DCQD, SAP, and ferroptosis (DSNFGs), which were validated across multiple datasets. A predictive nomogram integrating DSNFGs was developed, and single-cell analysis provided a comprehensive view of the cellular dynamics.

The microarray analysis revealed upregulation of NOX2 and downregulation of GPX4 in AP, with expression patterns correlating with disease severity. DCQD ameliorated SAP-induced pancreatic acinar cell damage and ferroptosis by reducing inflammatory markers and enhancing GPX4 expression. NOX2 knockout mitigated ferroptosis in SAP models, suggesting a key role in the disease process. DCQD and Fer-1 differentially regulated the expression of ferroptosis-related genes, reduced reactive oxygen species (ROS) and high-mobility group box 1 (HMGB1) levels, and suppressed the inflammatory response in a SAP mouse model. The HPLC analysis of DCQD constituents indicated eight components (aloe-emodin, rhein, emodin, chrysophanol, naringin, hesperidin, magnolol, and honokiol) with the capacity to modulate ferroptosis. Venn analysis identified 48 DSNFGs, with a subset of five genes demonstrating significant predictive value. The developed nomogram, based on LASSO regression, showed high accuracy in validation cohorts. Single-cell RNA sequencing (scRNA-seq) and CellChat analysis uncovered heterogeneity and cell-cell communication networks in the pancreas during recovery from pancreatitis, implicating several signaling pathways.

DCQD and its eight ingredients exert its protective effect in SAP by inhibiting ferroptosis through the NOX2/GPX4 pathway. The DCQD-SAP-ferroptosis-related signature and nomogram offer a novel tool for AP risk assessment, prognosis prediction, and personalized therapeutic strategies in SAP management.

Acute pancreatitis (AP) is an acute inflammation of the pancreas, which is considered a prevalent gastrointestinal emergency characterized by rapid progression and significant mortality. Currently available medications primarily serve as adjunctive therapies, yielding suboptimal therapeutic outcomes. Consequently, there remains a dearth of specific and efficient treatment modalities for AP. In recent years, nanomedicine-based treatment strategies have exhibited significant potential as drug therapy approaches for pancreatitis. The distinctive features of the AP microenvironment encompass aberrant activation of pancreatic enzymes, oxidative stress induced by elevated reactive oxygen species levels, and excessive production of pro-inflammatory cytokines; these factors offer promising targeted sites for early diagnosis and treatment using nanomedicine. This article comprehensively delineates the pathological microenvironmental characteristics associated with AP while highlighting the application of microenvironment-responsive strategies in nanodrug delivery systems for its treatment, thereby providing insights into future prospects.

Acute pancreatitis (AP) is a heterogeneous inflammatory condition. Although emerging therapeutic strategies targeting pathways such as calcium signaling, TNF-α, the NLRP3 inflammasome, and HMGB1 have shown promise, their efficacy may be limited by the underlying biological heterogeneity of the disease. In this multinational retrospective cohort study across three large ICU databases (ICU-HAI, MIMIC-IV, and eICU-CRD), we used group-based trajectory modeling of early vital signs to identify four distinct AP subphenotypes: hyperinflammatory, hypertensive, hypotensive, and hypoinflammatory. These subtypes differed markedly in 30-day mortality, inflammatory burden, and hemodynamic stability. Compared to the hypertensive phenotype, hyperinflammatory and hypotensive patients had significantly higher 30-day mortality risks (HR = 3.38 and HR = 1.87, respectively), while the hypoinflammatory phenotype carried no excess risk. Fluid resuscitation responses were phenotype-specific: hyperinflammatory patients benefited from higher fluid volumes, whereas hypoinflammatory patients were at risk of fluid overload. Notably, distinct subphenotypes displayed unique responses to fluid intake over the first two ICU days. For hyperinflammatory phenotype, the algorithm-estimated lowest-risk fluid range was 4100-4300 mL on day 1 and 3400-3600 mL on day 2; for phenotype hypoinflammatory phenotype, the optimal ranges were 2800-3800 mL and 1400-2600 mL, respectively. Early use of lactated Ringer's solution, which inhibited NLRP3, was associated with reduced mortality in hypotensive phenotype. These findings underscore the clinical relevance of early physiological trajectories and support precision fluid resuscitation based on subtype. This study establishes the largest early-trajectory-based classification of AP to date, offering new insights into immune and vascular mechanisms that drive heterogeneity and therapeutic responsiveness.

Microchip-based exosome analysis has emerged as a promising approach for liquid biopsy in cancer diagnosis, treatment monitoring, and prognostic evaluation. However, current microchips for exosome analysis typically rely on planar, 2D channel structures with affinity properties, which require complex fabrication but deliver suboptimal separation and detection performance. This study presents a novel vessel-like microtunnel chip, integrated with biomimetic octopus tentacles, achieving an exosome isolation efficiency of 90.4%. The innovative design incorporates interwoven, 3D micropathways, enhancing fluid dynamics and promoting efficient mixing between exosomes and microchannels. Nanofiber-coated silicon microspheres, functionalized with synthetic peptides, mimic octopus tentacles to anchor the microtunnels, dynamically extending under fluid shear forces to specifically recognize lipid bilayer structures for exosome capture. This platform incorporates enzyme-catalyzed signal amplification using Au nanoprobes for colorimetric detection to sensitively analyze four protein markers on plasma-derived exosomes from 60 clinical samples. Machine learning is used to develop a diagnostic model, achieving an area under the curve (AUC) of 0.9888 in distinguishing pancreatic cancer from pancreatitis and healthy controls. This approach provides a rapid, sensitive, accurate, and user-friendly method for pancreatic cancer diagnosis, addressing the clinical challenges of early detection and the frequent misdiagnosis of pancreatic cancer as pancreatitis.

Infected necrotizing pancreatitis (INP) is a serious complication that can increase the length of hospital stay and the cost of treatment, and is the leading cause of death in patients with acute pancreatitis (AP). This article aimed to predict the possibility of pancreatic and peripancreatic infections by early clinical indicators of AP and construct a clinical prediction model. We retrospectively studied consecutive patients admitted to the Nankai Hospital for moderate severe AP and severe AP, which developed within 2 weeks. Logistic regression was used to evaluate potential factors that could lead to INP and to develop clinical prediction model. Persistent organ failure, pancreatic necrosis area, and procalcitonin account were risk factors for INP. A prediction model was constructed based on the risk factors. The results showed that the model had good predictive performance. We developed a clinical prediction model with good predictive results that can be helpful for clinicians to identify and prevent the development of INP at an early stage.

The in-hospital mortality of acute pancreatitis (AP) is determined by severity of AP, but also significantly impacted by patients' comorbidities. Therefore, we aimed to examine the association between comorbid risk-profiles and survival in hospitalized patients admitted with AP.

We utilized the German nationwide inpatient statistics to identify all AP patient-cases (ICD code K85) admitted to hospitals in Germany between 2005 and 2019. Hospitalization cases for AP were stratified by survival, and risk factors for in-hospital mortality were examined.

In total, 797,364 hospitalization-cases of patients admitted due to AP (median age 56.0 [IQR 44.0-71.0] years, 39.2 % females) were treated in Germany 2005-2019. Of these, 22,022 (2.8 %) patients died during hospitalization. AP survivors were younger (56.0 [44.0-71.0] vs. 76.0 [64.0-84.0], P < 0.001), more often males (61.0 % vs. 54.1 %, P < 0.001), and were less often afflicted by cardiovascular risk factors and diseases than non-survivors. Cardiovascular diseases (OR 2.08 (95 %CI 2.02-2.15), P < 0.001) and raising number of cardiovascular diseases (OR 1.48 (95 %CI 1.45-1.50), P < 0.001) were independently associated with increasing mortality. In particular, heart failure (OR 2.16 [95 %CI 2.09-2.24], P < 0.001), peripheral artery disease (OR 1.25 [1.15-1.35], P < 0.001), atrial fibrillation/flutter (OR 1.61 [95 %CI 1.55-1.66], P < 0.001), myocardial infarction (OR 4.71 [95 %CI 4.28-5.18], P < 0.001), pulmonary embolism (OR 12.19 [95 %CI 10.91-13.62], P < 0.001), and stroke (OR 7.21 [95 %CI 6.42-8.11], P < 0.001) were independently associated with in-hospital mortality.

Between 2005 and 2019, the in-hospital mortality among hospitalized AP patients was 2.8 % in Germany. Presence of cardiovascular diseases was associated with significantly reduced survival in AP patients.

We report the design of liquid crystal-infused "slippery" liquid-infused porous surfaces (LC-SLIPS) that permit naked-eye detection and reporting on the structural differences and activities of peptides and protease enzymes in aqueous media. We demonstrate that small (e.g., 20 μL) droplets of aqueous solutions placed in contact with LC-SLIPS exhibit sliding behaviors that vary substantially with the concentrations, structures, and physicochemical properties (e.g., hydrophobicity) of model amphiphilic β- and α/β-peptides dissolved within them. These large differences in sliding times permit naked-eye detection and discrimination of changes in peptide structure, including side-chain substitution, end group structure, backbone structure, and charge that correlate with differences in peptide amphiphilicity. We demonstrate further that LC-SLIPS can be used to monitor other biochemical processes, including digestion by proteases, that affect changes in the structures of amphiphilic peptides and can, thus, be used to develop novel, naked-eye assays that can report sensitively on enzymatic activity. As proof of concept, we show that large and visually observable changes in droplet sliding resulting from the degradation of a model peptide can be used to detect the presence of trypsin in aqueous solutions at levels as low as 12.5 ng/mL. That result, in turn, served as the basis of an LC-SLIPS-based assay that can be used to detect clinically relevant concentrations (from 25 to 25,000 ng/mL) of trypsinogen, a well-established biomarker for acute pancreatitis, in samples of synthetic urine. This "sliding" assay is conceptually straightforward and requires only visual monitoring and/or a hand-held stopwatch for readout, highlighting the potential for low-cost, point-of-care diagnostics applications. Overall, our results demonstrate the ability of LC-SLIPS to capture and report structural information relevant to other therapeutic properties and applications of amphiphilic peptides that could also be useful in the context of drug design and screening.

Background/Objectives: Acute pancreatitis (AP) remains a pressing clinical challenge, largely due to its potential to lead to life-threatening complications and increased mortality. Over the years, numerous tools have been proposed to evaluate the intensity of AP and estimate likely health outcomes. Despite their usefulness, many of these assessment models are complex and rely on a wide array of clinical inputs, making them less practical in everyday healthcare settings. In contrast, the Aggregate Systemic Inflammation Index (AISI), which is calculated using routine blood count parameters, provides a simpler and more inclusive approach to measuring systemic inflammation. This research focuses on examining how effectively AISI can be used to gauge disease severity and project clinical trajectories in individuals affected by pancreatitis. Methods: This retrospective study reviewed the medical records of 412 individuals diagnosed with acute pancreatitis, all of whom received care at the Internal Medicine Clinic of Ankara Bilkent City Hospital between 1 April 2019 and 1 September 2024. The investigation encompassed a thorough analysis of patients' demographic characteristics, lab parameters, and clinical findings, with special attention given to inflammatory markers, including the Aggregate Systemic Inflammation Index (AISI), its revised version, the Platelet-to-Lymphocyte Ratio (PLR), the Neutrophil-to-Lymphocyte Ratio (NLR), and the Systemic Inflammatory Response Index (SIRI). Comparative analyses between groups were performed using independent sample t-tests and one-way ANOVA, complemented by Tukey's post hoc tests where appropriate. Correlations among continuous variables were determined through Pearson's analysis, and the prognostic accuracy of both AISI and its modified form was assessed using Receiver Operating Characteristic (ROC) curve methodology. Results: The mean age among participants was 63.47 ± 17.92 years, while the average AISI value was calculated as 1183.89 ± 1067.42. Both the original and modified versions of the AISI index showed strong positive correlations with several key clinical measures, including prolonged hospitalization, a Glasgow score of 2 or above, BISAP, Ranson scoring, the revised Atlanta classification, and APACHE II. AISI was also significantly linked to the presence of complications and overall mortality (p < 0.01). Analysis through ROC curves demonstrated that an AISI level above 236.626 effectively predicted hospital stays exceeding 10 days, with a sensitivity of 94.40% and a specificity of 91.00%. Moreover, both AISI and its modified form reliably distinguished patients who had a Ranson score of zero, with high diagnostic accuracy. Conclusions: AISI and its modified version demonstrate a strong association with both the intensity and clinical course of acute pancreatitis. Thanks to their simplicity, low cost, and broad usability in healthcare settings, these indices hold considerable promise as practical and dependable tools for assessing the severity and likely outcomes of this increasingly prevalent disease.

Chemotherapy drug-related acute pancreatitis (CDRAP) is a rare adverse event that poses significant challenges to clinicians. This study aimed to describe plain computed tomography (CT)- and contrast-enhanced computed tomography (CECT)-based conventional imaging features and texture analysis characteristics of CDRAP.

A total of 62 patients with initial clinical and/or biochemical evidence of pancreatitis and 34 patients with normal pancreatic manifestations who underwent CT during chemotherapy were retrospectively included. The diagnosis of CDRAP was established based on clinical, imaging, and biochemical findings. Conventional imaging features, texture analysis characteristics, clinical and biochemical parameters, other complications, chemotherapy drugs, and patient outcomes related to CDRAP were recorded.

A total of 20 (32.26%) patients who were clinically diagnosed with CDRAP had normal pancreatic morphology on CT, while 42 (67.74%) patients presented with changes indicative of acute pancreatitis. The CT findings of 62 CDRAP cases were as follows: diffuse (n = 19) or focal (n = 21) pancreatic enlargement, diffuse (n = 12) or focal (n = 4) heterogeneous enhancement, peripancreatic stranding (n = 20), acute peripancreatic fluid collection (n = 10), and pseudocyst (n = 2). A total of 17 texture features were identified to differentiate CDRAP from normal pancreatic manifestations.

CDRAP mainly manifested as interstitial edematous pancreatitis with/without normal pancreatic morphology on CT. Imaging texture analysis may serve as a potential biomarker for its detection. By combining conventional imaging features with texture analysis characteristics, there is potential to assist radiologists and clinicians in the identification of CDRAP, thereby improving the quality of life for cancer patients.

This study aims to analyze the risk factors requiring early intervention in severe acute pancreatitis (SAP) patients with persistent organ failure and evaluate the clinical outcomes following treatment. This was a retrospective observational study. Inverse probability treatment weighting using propensity score methods was employed to balance baseline characteristics. Univariate and multivariate logistic regression analyses were performed to identify risk factors associated with early intervention. Smooth curve fitting was applied to explore potential relationships between variables and intervention timing. Threshold effect analysis was conducted to identify the optimal inflection point in nonlinear relationship. A total of 310 patients were included in this study. Compared to the standard treatment group (n = 162), the early intervention group (n = 148) had a higher proportion of multiple organ failure (77.1% vs. 63.6%, P = 0.021) and higher mortality (27.7% vs. 16.0%, P = 0.013), but early intervention was not significantly associated with adverse outcome (OR 1.52, 95% CI 0.71-3.26, P = 0.283). Risk factors associated with early intervention included computed tomography severity index, SOFA score, intra-abdominal pressure (IAP), and remifentanil equivalents. Among these, the SOFA score showed a negative linear relationship with intervention timing, while distinct threshold effects were observed between IAP, remifentanil equivalents, and intervention timing. One week after intervention, most patients showed improved organ function, along with reduced requirements for sedation and analgesia, as well as decreased C-reactive protein level levels and IAP (all P < 0.05). SAP patients requiring early intervention tended to have higher disease severity. Although early intervention can improve short-term organ function, reduce IAP, and lower analgesic requirements, its impact on reducing mortality remains uncertain.

The symptoms of pancreatic cancer (PC) are usually nonspecific or absent, and the early diagnosis remains challenging. 7-14% of PC patients present initially with acute pancreatitis (AP). This study aims to distinguish the PC patients initially presenting with AP from simple AP patients, further evaluating the role of endoscopic ultrasound (EUS) in the early diagnosis.

We retrospectively evaluated 1376 consecutive patients with AP between 2010 and 2023.To overcome selection bias, we used propensity score matching between PC patients initially presenting with AP and non-cancer-related AP patients. Clinical information, especially EUS were collected for comparison.

After matching, 72 patients (PC group) and 216 patients (AP group) were included. The unknown etiology in the PC group was significantly higher than that in the AP group (54.2% vs. 27.8%). Regarding initial symptoms, non-cancer-related AP patients exhibited significantly more abdominal distension, vomiting and fever compared to the PC group (p < 0.05). In terms of lab results, PC group patients had lower serum amylase (p < 0.001), but higher CA19-9, CA72-4, and CA242 levels when compared to AP group patients (p < 0.001). Additionally, AP group patients had more systematic and local complications, and the severity of AP was much higher than that of PC group patients. Moreover, PC patients exhibited more frequent imaging findings, such as pancreatic duct dilation or atrophy, and enlarged lymph nodes (p < 0.05). Notably, the EUS examination in PC patients missing diagnosis initially and PC patients presenting with relapsed AP showed more sensitive results and more detective rates.

Pancreatic cancer patients presenting initially with acute pancreatitis tend to exhibit mild, recurrent pancreatitis than common AP patients. EUS holds potential diagnostic value in detecting pancreatic cancer in patients with initially negative cross-sectional imaging and recurrent pancreatitis.

Severe acute pancreatitis (SAP) is a highly morbid acute digestive disorder linked to pyroptosis. N-acetyltransferase 10 (NAT10) facilitates the production of N4-acetylcytidine (ac4C) modifications in mRNA, thereby contributing to the progression of various diseases. However, the specific role of NAT10 in SAP remains to be elucidated. This study aimed to elucidate the mechanism through which NAT10 mediates pyroptosis in SAP. Sprague-Dawley rats and AR42J rat pancreatic exocrine cells were used to establish in vivo and in vitro models of SAP. The levels of ac4C and NAT10 expression were quantified using dot blot analysis and quantitative real-time PCR. Assessment of cell viability, apoptosis, amylase content, and concentrations of lactate dehydrogenase, IL-1β, and IL-18 was conducted to evaluate the severity of SAP both in vivo and in vitro . Pyroptosis was assessed by measuring caspase-1 and gasdermin D (GSDMD)-N-terminal (GSDMD-N) expression. Further mechanistic insights were gained using methylated RNA immunoprecipitation, RNA immunoprecipitation, and dual-luciferase reporter assays. Our findings indicate that the levels of ac4C modification and NAT10 were elevated in both in vivo and in vitro SAP models. Knockdown of NAT10 inhibited cell death and reduced the levels of amylase, lactate dehydrogenase, IL-1β, and IL-18 as well as the protein expression of caspase-1 and GSDMD-N, suggesting that NAT10 knockdown suppresses pyroptosis in SAP cell models. Mechanistically, NAT10 knockdown decreased the expression and stability of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) mRNA by inhibiting ac4C modification of NLRP3. Moreover, NAT10 knockdown alleviated pancreatic tissue pathology, mitigated SAP severity, and suppressed pyroptosis in an SAP rat model. Collectively, these results demonstrate that NAT10 exacerbates pancreatic injury in SAP by promoting pyroptosis through ac4C modification of NLRP3, thereby enhancing its expression. These findings suggest a potential novel therapeutic target for SAP.

Although acute pancreatitis is common and much is known about its management, further research could lead to targets identified for improvements in care. This study aimed to analyze factors, both medical and socioeconomic, associated with morbidity and mortality at a safety net hospital.

This was a retrospective review of patients with acute pancreatitis admitted between 2015 and 2022. Variables were collected from the electronic medical record and primary outcomes of interest were morbidity and mortality. Standard statistics were used for analysis.

Of the 404 patients that met inclusion criteria, the average age was 48 y, 46% were female, the majority were English speaking, most were Black, and the majority had public insurance. Four percent of patients died and 19.6% had a complication within 30 d. Most patients were admitted to medicine. Public insurance or self-pay status was associated with complications, as was presence of comorbidities and interventional radiology consultation. Surgery and interventional radiology consultation, among other factors, were associated with mortality. Thirty-nine percent of patients with gallstone pancreatitis underwent cholecystectomy. Many patients were started on antibiotics, and of those, 44.1% had no clear indication.

This study reveals novel factors associated with morbidity and mortality in patients with acute pancreatitis, as well as demonstrating that best practices are not uniformly practiced. The study provides further areas of study, including investigations into best pathways for consultations of services and admission service, interventions for at risk patients to improve morbidity and mortality, and how to reduce inappropriate antibiotic use.

Acute pancreatitis (AP) is the most common disease in emergency and intensive care units; early mortality predictions and intervention are crucial for improving patient prognosis. We investigated the association of serum phosphate with mortality among AP patients using a large public database.

This was a retrospective study. All AP patients in the MIMIC-IV database were included. Based on the tertiles of serum phosphate, all AP patients were divided into 3 groups. Two generalized additive models were performed to explore the association of serum phosphate with in-hospital and 30-day mortality. Kaplan-Meier analysis was introduced for survival probability.

A total of 1088 AP patients admitted to the ICU were included. The mortalities of in-hospital (n=137) and 30-day (n=118) were 12.59% and 10.85%, respectively. The median levels of serum phosphate in the survivor and the non-survivor groups were 3.20 and 3.90 mg/dL, respectively (P<0.001). After adjusting for all potential confounders, with 1 mg/dL increment in serum phosphate, the risk of in-hospital and 30-day mortality increased by 20% (HR=1.20, 95% CI: 1.00-1.44, P=0.0443) and 25% (HR=1.25, 95% CI: 1.03-1.52, P=0.0214), respectively. The areas under the ROC curve (AUC) of serum phosphate for predicting in-hospital and 30-day mortality were 0.650 (95% CI: 0.599-0.701) and 0.659 (95% CI: 0.605-0.714), respectively. The cutoff values of serum phosphate were 3.65 and 4.35 mg/dL, respectively.

A linear positive relationship was found between serum phosphate and in-hospital and 30-day mortality in AP. Serum phosphate was associated with in-hospital and 30-day mortality in AP. Our results could be used for screening out those AP patients with a higher risk of worse outcomes.

Severe acute pancreatitis (SAP) is a life-threatening condition associated with high mortality and limited therapeutic options. Current management strategies focus on infection prevention, immune regulation, and anticoagulation. Xuebijing Injection (XBJ), a widely used traditional Chinese medicine-derived intravenous preparation, has shown promising therapeutic effects in SAP. Herein, we sought to evaluate clinical and preclinical evidence on XBJ to reveal its potential mechanisms of action, and provide insights to guide future research and clinical applications.

We conducted a comprehensive survey of studies on XBJ in the treatment of SAP across PubMed, Embase, Cochrane Library, CBM, CNKI, Wanfang and VIP databases from their inception to March 21st, 2024.

A total of 239 studies were included, comprising 12 animal experiments, 7 systematic reviews, 220 clinical trials. Mechanistic studies suggest that XBJ downregulates the expression of inflammatory mediators, improves immune function, and alleviates oxidative stress via multiple signaling pathways, including the TLR4/NF-κB, p38-MAPK, HMGB1/TLR, TLR4/NF-κB, FPR1/NLRP3, and JAK/STAT pathways. These effects contribute to reducing organ damage. Compared to standard treatment, XBJ has more effective at reducing mortality and complications, improving overall clinical outcomes, shortening ventilator use time, and hospital stay in SAP patients.

Preclinical evidence and clinical trial data indicated that XBJ can simultaneously regulate inflammatory responses, immune function, microcirculatory disorders, oxidative stress, and apoptosis. However, further research is required to elucidate the specific mechanisms of action, clinical characteristics and safety of XBJ.

AMP-activated protein kinase (AMPK) is the master regulator of cellular energy which gets activated during energy stress and restores tissue homeostasis. AMPK is widely expressed in the pancreas and is involved in protein synthesis. In cerulein-induced acute pancreatitis (AP), diminished AMPK activity in the pancreatic tissue may be associated with pancreatic inflammation and oxidative stress. Our results demonstrated that berberine (BR) treatment produced significant decrease in plasma amylase and lipase levels and improved histopathological features in AP mice model. Myeloperoxidase (MPO) activity indicated that BR suppressed the infiltration of neutrophils in pancreas. BR treatment markedly decreased the levels of proinflammatory cytokines including interleukins (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) via inhibition of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression. In addition, BR activates the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and inhibits cerulein-induced oxidative-nitrosative stress. Mechanistically, we found inhibition of AMPK activity in cerulein-induced AP, while BR-treated animals showed marked increase in the AMPK expression. Together, our study indicated that BR-mediated AMPK activation in pancreatic tissues demonstrated attenuation of cerulein-induced oxidative stress and inflammation. Based on our observations, further exploration of this promising natural product against AP and associated complications may lead to promising therapeutic options.

There is no effective drug treatment for the organ failure (OF) caused by severe acute pancreatitis (SAP).

We aimed to evaluate the efficacy of cyclooxygenase-2 inhibitors (COX-2-Is) on the treatment of SAP and its safety.

In this multicentre, double-blind, randomised, placebo-controlled, investigator-initiated trial, 348 patients with acute pancreatitis aged 18-75 years, <1 week from onset of illness to admission, and Acute Physiology and Chronic Health Evaluation II Score ≥7 or modified Marshall Score ≥2, were randomly assigned (1:1) to the COX-2-Is group (parecoxib sequential with imrecoxib) or the placebo group. SAP occurrence, duration of OF, local complications, clinical outcomes and serum inflammatory mediators were measured.

Compared with the placebo group, SAP occurrence was reduced by 20.7% (77.6% vs 61.5%, p=0.001) and the persistent OF duration in SAP was shortened by 2 days (p<0.001) after COX-2-Is treatment. For patients enrolled within or after 48 hours from symptom onset, SAP occurrence was reduced by 23.8% (p=0.001) and 8.5% (p=0.202), and the persistent OF duration in SAP was shortened by 3 days (p=0.001) and 2 days (p=0.010) after COX-2-Is treatment, respectively. The occurrence of local complications in the COX-2-Is group was significantly lower than those in the placebo group, 33.7% vs 49.1%, p=0.004. The serum levels of inflammatory mediators and 30-day mortality (from 8.6% to 3.4%) were significantly reduced after COX-2-Is treatment, p<0.05. The incidence of adverse events was similar between the two treatment groups.

Parecoxib sequential with imrecoxib was effective and well tolerated in reducing the occurrence and duration of SAP and local complications through suppression of systemic inflammatory response, leading to decreased morbidity.

Low- and middle-income countries are facing an increase in the incidence of acute pancreatitis (AP)-characterized by rapid onset, fast progression, high rate of severity, and high mortality. Progression of AP into severe AP (SAP) results in a series of complications such as organ dysfunction, local abscesses, pseudocysts, and necrosis. Although the treatment of AP is primarily supportive, including fluid resuscitation and organ support, there is still a lack of consensus on the optimal management regimen for fluid therapy, and strategies to promote gastrointestinal recovery remain limited. As no effective intervention measure has yet been developed, supportive therapy remains the primary approach for the early treatment of AP. DaXianXiong decoction is a widely used traditional Chinese medicine formulation; however, limited research has been conducted on its clinical efficacy.

This study aims to evaluate the efficacy and safety of DaXianXiong decoction in preventing AP from progressing to SAP, assessing its impact on SAP incidence, clinical severity scores, inflammation markers, and gastrointestinal function, and providing evidence for AP management.

This study is a randomized, double-blind, placebo-controlled, single-center clinical trial. The primary outcomes will include the incidence of SAP, modified computed tomography severity index score, APACHE II (Acute Physiology and Chronic Health Evaluation II) score, modified Marshall score, and levels of the inflammation factor. The secondary outcomes will include the effect of the gastrointestinal dysfunction treatment. Evaluations will be conducted at baseline; 24 hours after the intervention; and on days 3, 7, and 28 after the intervention in both groups. A total of 60 eligible patients will be randomly allocated in a 1:1 ratio to the intervention group and the control group. Both groups will receive standard Western medical treatment for pancreatitis. The intervention group will additionally receive DaXianXiong decoction, while the control group will receive a placebo similar to the decoction.

This study has been funded by the Performance Incentive Project of Scientific Research Institutions in Chongqing. The trial was registered in April 2024, and data analysis is expected to be completed by April 2025. The study results will be presented at both national and international conferences and published in peer-reviewed journals.

This trial will help us assess the effectiveness and safety of DaXianXiong decoction in patients with AP and provide clinical evidence on the efficacy and safety of DaXianXiong decoction in preventing the progression of AP to SAP. By evaluating its impact, the findings will contribute to the understanding of DaXianXiong decoction as an adjunct therapy in AP management and may offer a novel complementary treatment strategy for AP, potentially improving patient outcomes and reducing complications.

Chinese Clinical Trial Registry ChiCTR2300076885; https://www.chictr.org.cn/showproj.html?proj=207084.

DERR1-10.2196/67392.

Background: Radiological imaging has improved our insight into how obesity and sarcopenia impacts acute pancreatitis via several measured variables. However, we lack understanding of the association between social determinants of health and these variables within the acute pancreatitis population. Methods: This study included patients at a single tertiary care center between 1 January 2008 and 31 December 2021. Measurements of visceral adiposity (VA), subcutaneous adiposity (SA), the ratio of visceral to total adiposity (VA/TA), and degree of sarcopenia via psoas muscle Hounsfield unit average calculation (HUAC) were obtained on CT scans performed at presentation. Using geocoded patient data, we calculated the social vulnerability index (SVI) from CDC metrics. Descriptive and regression analyses were performed utilizing clinical and radiological data. Results: In 484 patients with 592 acute pancreatitis-related hospitalization, median (IQR) VA was 176 (100-251), SA was 209.5 (138.5-307), VA/TA ratio was 43.5 (32.3-55.3), and HUAC was 51.3 (44.4-58.9). For our primary outcome, geospatial analyses showed a reverse association between VA and SVI with a coefficient of -9.0 (p = 0.04) after adjustment for age, health care behaviors (i.e., active smoking and drinking), and CCI, suggesting residence in areas with higher SVI is linked to lower VA. However, VA/TA, SA, and HUAC showed no significant association with SVI. The SVI subdomain of socioeconomic status had significant association with VA (-39.78 (95% CI: -75.88--3.70), p = 0.03) after adjustments. For our secondary outcome, acute pancreatitis severity had significant association with higher VA (p ≤ 0.001), VA/TA (p ≤ 0.001), and lower HUAC (p ≤ 0.001). When comparing single vs. recurrent hospitalization patients, there was significantly higher median VA with recurrences (VA-single acute pancreatitis: 149 (77.4-233) vs. VA-recurrent acute pancreatitis: 177 (108-256); p = 0.04). Conclusions: In this study we found that patients residing in more socially vulnerable areas had lower visceral adiposity. This paradoxical result potentially conferred a protective effect against severe and recurrent acute pancreatitis; however, this was not found to be statistically significant.

Acute pancreatitis (AP) is a severe inflammatory condition of the digestive system which, in severe cases, can lead to persistent organ failure (POF). Developing novel therapeutic interventions and diagnostic biomarkers is critical to improve the management and prognosis of this disease. Exosomes, small extracellular vesicles, can reflect the inflammatory state of the pancreas, providing valuable insights into disease progression. Moreover, these vesicles are essential mediators of intercellular communication, modulating inflammatory responses by affecting patterns of cell death and macrophage polarization-key factors in determining AP clinical outcomes. Their stability, bioavailability, and capacity to transport various bioactive molecules render exosomes promising tools for early diagnosis and precision therapy, potentially enhancing patient outcomes. This review highlights the innovative potential of exosomes in transforming the management of AP, providing a foundation for more accurate diagnostics and targeted treatments with clinical applicability.

Acute pancreatitis is a common gastrointestinal condition, primarily caused by gallstones and alcohol abuse, with other causes including hypertriglyceridemia, trauma, infections, etc. While most cases are mild and self-limiting, up to 20% of patients develop severe pancreatitis with pancreatic necrosis, increasing the risk of multi-organ failure and mortality. Conservative management involves fluid resuscitation, nutritional support, and antibiotics for infected peripancreatic fluid collections (PFCs). When PFCs are infected or symptoms persist, invasive interventions such as endoscopic ultrasound (EUS)-guided drainage or percutaneous drainage are recommended. Dual modalities (endoscopic and percutaneous drainage) offer better outcomes with fewer complications. Direct endoscopic necrosectomy is considered for patients who do not improve with drainage. A multidisciplinary team, including endoscopists, interventional radiologists, surgeons, and specialists, is essential for optimal management of severe necrotizing pancreatitis.

Acute pancreatitis (AP) is an emergency gastrointestinal disease that requires immediate diagnosis and urgent clinical treatment. An accurate assessment and precise staging of severity are essential in initial intensive therapy.

To explore the prognostic value of inflammatory markers and several scoring systems [Acute Physiology and Chronic Health Evaluation II, the bedside index of severity in AP (BISAP), Ranson's score, the computed tomography severity index (CTSI) and sequential organ failure assessment] in severity stratification of early-phase AP.

A total of 463 patients with AP admitted to our hospital between 1 January 2021 and 30 June 2024 were retrospectively enrolled in this study. Inflammation marker and scoring system levels were calculated and compared between different severity groups. Relationships between severity and several predictors were evaluated using univariate and multivariate logistic regression models. Predictive ability was estimated using receiver operating characteristic curves.

Of the 463 patients, 50 (10.80%) were classified as having severe AP (SAP). The results revealed that the white cell count significantly increased, whereas the prognostic nutritional index measured within 48 hours (PNI48) and calcium (Ca2+) were decreased as the severity of AP increased (P < 0.001). According to multivariate logistic regression, C-reactive protein measured within 48 hours (CRP48), Ca2+ levels, and PNI48 were independent risk factors for predicting SAP. The area under the curve (AUC) values for the CRP48, Ca2+, PNI48, Acute Physiology and Chronic Health Evaluation II, sequential organ failure assessment, BISAP, CTSI, and Ranson scores for the prediction of SAP were 0.802, 0.736, 0.871, 0.799, 0.783, 0.895, 0.931 and 0.914, respectively. The AUC for the combined CRP48 + Ca2+ + PNI48 model was 0.892. The combination of PNI48 and Ranson achieved an AUC of 0.936.

Independent risk factors for developing SAP include CRP48, Ca2+, and PNI48. CTSI, BISAP, and the combination of PNI48 and the Ranson score can act as reliable predictors of SAP.

Blood urea nitrogen (BUN) and serum albumin (ALB) are strongly associated with the prognosis in acute pancreatitis (AP). The BUN/ALB ratio (BAR) reflects renal, nutritional, inflammatory, and endothelial functions. In this study, we investigated the association between the BAR and all-cause mortality in critically ill patients with AP. Using data from the Medical Information Market for Intensive Care (MIMIC-IV) database, we conducted a retrospective cohort analysis. The relationship between BAR and mortality was assessed through Kaplan-Meier survival curves, restricted cubic spline models, and multivariable Cox proportional hazards regression. The predictive capacity of BAR for 30-day and 1-year mortality was evaluated using receiver operating characteristic analysis. Our study included 780 participants, with 30-day and 1-year mortality rates of 12.6% and 23.6%, respectively. Higher BAR values were associated with poorer survival outcomes. BAR demonstrated superior predictive performance achieving an area under the curve of 0.74, surpassing BUN, ALB, and SOFA scores. The Cox model indicated a significant independent association between elevated BAR and increased mortality risk, with hazard ratios of 1.43 (95% CI 1.20-1.70) for 30-day mortality and 1.37 (95% CI 1.17-1.60) for 1-year mortality. Stratified and sensitivity analyses confirmed the robustness of these findings. Our results suggest that elevated BAR is associated with poor prognosis in critically ill patients with AP and may serve as a valuable tool for early risk stratification and for assessing both short- and long-term prognosis.

Systemic inflammatory response syndrome (SIRS) is a frequent and serious complication of acute pancreatitis (AP), often associated with increased mortality. This study aims to leverage automated machine learning (AutoML) algorithms to create a model for the early and precise prediction of SIRS in AP.

This study retrospectively analyzed patients diagnosed with AP across multiple centers from January 2017 to December 2021. Data from the First Affiliated Hospital of Soochow University and Changshu Hospital were used for training and internal validation, while testing was conducted with data from the Second Affiliated Hospital. Predictive models were constructed and validated using the least absolute shrinkage and selection operator (LASSO) and AutoML. A nomogram was developed based on multivariable logistic regression (LR) analysis, and the performance of the models was assessed through receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Additionally, the AutoML model's effectiveness and interpretability were assessed through DCA, feature importance, SHapley Additive exPlanation (SHAP) plots, and locally interpretable model-agnostic explanations (LIME).

A total of 1,224 patients were included, with 812 in the training cohort, 200 in validation, and 212 in testing. SIRS occurred in 33.7% of the training cohort, 34.0% in validation, and 22.2% in testing. AutoML models outperformed traditional LR, with the deep learning (DL) model achieving an area under the ROC curve of 0.843 in the training set, and 0.848 and 0.867 in validation and testing, respectively.

The AutoML model using the DL algorithm is clinically significant for the early prediction of SIRS in AP.

Xuebijing injection (XBJI), as a Chinese patent medicine injection, consists of five botanical drugs for anti-inflammatory treatment. Acute pancreatitis (AP) is induced by localized inflammation, potentially resulting in multiple organ dysfunction syndromes, specifically including acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Recent studies suggest that XBJI effective in alleviating potentially easing ALI and ARDS.

We illustrated the efficacy and safety of XBJI for pulmonary function of AP by conducting a systematic literature review and meta-analysis.

We conducted searches across eight databases, including PubMed, Embase, and the Cochrane Library, up to September 2024. Two independent investigators screened and selected the literature based on predefined inclusion and exclusion criteria, followed by data extraction. The quality of the selected studies was assessed using the Cochrane Collaboration's Risk of Bias 2.0 tool. The data were then qualitatively analyzed and synthesized by using Review Manager software, in accordance with the PRISMA guidelines and the Cochrane Handbook.

This study showed that using conventional therapy combined with XBJI might increase the oxygenation index, lower the respiratory rate, and improve APACHE II scores and inflammatory biomarkers. However, there is a high risk of bias and the quality of the included studies is low. More well-designed, large-sample, and high-quality trials are needed to be conducted in multiple centers.

Severe acute pancreatitis is a life-threatening condition characterized by systemic inflammatory response syndrome and an increased risk of complications such as venous thrombosis, all of which contributes to a high mortality rate. Heparin resistance, although rare, can lead to ineffective anticoagulation and thrombus formation during unfractionated heparin therapy, complicating management.

We report a case of heparin resistance in which, despite increasing the unfractionated heparin dosage, the patient's activated partial thromboplastin time remained subtherapeutic.

Laboratory findings indicated normal antithrombin levels but undetectable anti-Xa activity, confirming non-antithrombin-mediated heparin resistance. A multidisciplinary approach led to the successful management of thrombosis with rivaroxaban, resulting in substantial clinical improvement.

This case highlights the importance of early recognition and management of heparin resistance in patients with severe acute pancreatitis. Combined monitoring of activated partial thromboplastin time and anti-Xa activity is crucial for optimizing anticoagulation therapy and preventing complications such as deep vein thrombosis.

Effective early diagnosis and timely intervention in acute pancreatitis (AP) are essential for improving patient outcomes. This study aims to evaluate the clinical utility of the neutrophil CD64 index (nCD64) in stratifying patients with SAP and assessing mortality risk.

A total of 302 AP patients were enrolled and divided into a training cohort (n = 226) and a validation cohort (n = 76). Venous blood samples were collected within 24 hours of admission, and the nCD64 index was measured via flow cytometry. Other clinical parameters, including C-reactive protein (CRP) and procalcitonin (PCT), were also recorded. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic value of the nCD64 index and its capacity to predict mortality risk.

ROC curve analysis identified a cutoff value of 1.45 for the nCD64 index. Patients with nCD64 > 1.45 had significantly higher risks of complications, including systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS), multiple organ failure (MOF), and death. Over 65% of patients with acute pancreatitis (AP) can be effectively risk-stratified at a low cost, and it has been demonstrated that AP patients with an nCD64 value ≤ 1.45 have an extremely low mortality rate (no mortality in present training and validation cohort). Kaplan-Meier survival analysis revealed a significant survival difference between high-risk (nCD64 > 1.45) and low-risk groups (p < 0.001).

The nCD64 index is an effective tool for early identification of SAP patients, allowing for the classification of over 65% of cases as low-risk for mortality.

Early acute pancreatitis is an acute inflammatory disease that involves multiple modes of cell death, including apoptosis, necrotic apoptosis, and pyroptosis in its disease process. PANoptosis, a type of cell death that includes pyroptosis, apoptosis, and necroptosis, has had an important role in a variety of infectious and inflammatory diseases in recent years. To judge the relationship between PANoptosis and AP, we first analyzed the data from pancreatic transcriptome data by bioinformatics techniques, and we found the enrichment of PANoptosis pathway in AP. Next, we screened the genes and identified differentially expressed genes (DEGs) associated with AP and PANoptosis. Finally, we found that Zbp1 may have a major role in the process of PANoptosis. For this purpose, we constructed AP models in mice and in vitro cell line 266-6 and intervened by inhibiting Zbp1. The final results showed that the PANoptosis in mice was significantly suppressed after inhibition of Zbp1. In conclusion, inflammatory injury in AP can be significantly improved by inhibiting Zbp1- PANoptosome-mediated PANoptosis.

Acute pancreatitis (AP) is a heterogeneous inflammation of the pancreas, most frequently attributable to gallstones or alcohol. AP accounts for an estimated 300 000 patients admitted each year in the USA, and an estimated US$2.6 billion/year in hospitalization costs. Disease severity is classified as mild, moderate, or severe, dependent on the presence or degree of concomitant organ failure. Locally, pancreatitis may be complicated by fluid collections, necrosis, infection, and hemorrhage. Infection of necrotizing pancreatitis (NP) is associated with a doubling of mortality risk. The modern management of AP is evolving. Recent data suggest a shift from normal saline to lactated Ringer's solution, and from aggressive to more judicious volume resuscitation. Similarly, while historical wisdom advocated keeping patients nothing by mouth to 'rest the pancreas', recent data convincingly show fewer complications and reduced mortality with early enteral nutrition, when tolerated by the patient. The use of antibiotics in NP is controversial. Current recommendations suggest reserving antibiotics for cases with highly suspected or confirmed infected necrosis, as well as in patients with biliary pancreatitis complicated by acute cholecystitis or cholangitis. Regarding the management of local complications, control of acute hemorrhage can be attained either endovascularly or via laparotomy. Abdominal compartment syndrome is associated with a mortality risk of 50%-75%. Routine monitoring of intra-abdominal pressure is recommended in patients at high risk. Pancreatic pseudocysts require intervention in symptomatic patients or those with infection or other complications. Endoscopic transmural drainage may be considered as the first step when technically feasible. Necrotizing pancreatitis without suspicion of infection is often managed medically, while the delay, drain, debride approach remains the standard of care for the vast majority of infected pancreatic necrosis. Robotic surgery, in appropriately selected patients, allows for a one-step approach, and merits further study to explore its initially promising results.

Acute pancreatitis (AP) is an inflammatory disease that can progress to systemic immune responses and multi-organ damage in its severe forms. Anoectochilus roxburghii (Wall.) Lindl. (AR), a traditional Chinese medicinal plant, has been reported to exhibit anti-inflammatory, hypoglycemic, hepatoprotective, and analgesic properties. Kinsenoside (KD), the primary bioactive glycoside in AR, is responsible for many of its therapeutic effects. Given its anti-inflammatory and immunomodulatory properties, KD may have the potential to mitigate pancreatic inflammation in AP. However, its protective role in AP has not yet been investigated.

This study aimed to investigate the protective effects of the natural active compound KD against acute pancreatitis (AP) and its associated molecular mechanisms.