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Background: Severe acute pancreatitis (SAP) is characterized by inflammation, with inflammatory immune cells playing a pivotal role in disease progression. This study aims to understand variations in specific immune cell subtypes in SAP, uncover their mechanisms of action, and identify potential biological markers for predicting Acute Pancreatitis (AP) severity. Methods: We collected peripheral blood from 7 untreated SAP patients and employed single-cell RNA sequencing for the first time to construct a transcriptome atlas of peripheral blood mononuclear cells (PBMCs) in SAP. Integrating SAP transcriptomic data with 6 healthy controls from the GEO database facilitated the analysis of immune cell roles in SAP. We obtained comprehensive transcriptomic datasets from AP samples in the GEO database and identified potential biomarkers associated with AP severity using the “Scissor” tool in single-cell transcriptomic data. Results: This study presents the inaugural construction of a peripheral blood single-cell atlas for SAP patients, identifying 20 cell subtypes. Notably, there was a significant decrease in effector T cell subsets and a noteworthy increase in monocytes compared to healthy controls. Moreover, we identified a novel monocyte subpopulation expressing high levels of PPBP and PF4 which was significantly elevated in SAP. The proportion of monocyte subpopulations with high CCL3 expression was also markedly increased compared to healthy controls, as verified by flow cytometry. Additionally, cell communication analysis revealed insights into immune and inflammation-related signaling pathways in SAP patient monocytes. Finally, our findings suggest that the subpopulation with high CCL3 expression, along with upregulated proinflammatory genes such as S100A12, IL1B, and CCL3, holds promise as biomarkers for predicting AP severity. Conclusion: This study reveals monocytes’ crucial role in SAP initiation and progression, characterized by distinct pro-inflammatory features intricately linked to AP severity. A monocyte subpopulation with elevated PPBP and CCL3 levels emerges as a potential biomarker and therapeutic target [ABSTRACT FROM AUTHOR]

Objective To explore the regulation of Chaihuang Qingyi Huoxue Granule on intestinal microecological changes in rats with severe acute pancreatitis (SAP) and the potential mechanism for its treatment of SAP. Methods Forty-eight rats were randomly divided into sham operation group (SHAM), SAP model group (SAP), and Chaihuang Qingyi Huoxue Granule (CH) group, with 16 rats in each group. Each group was further divided into 12 h and 24 h subgroups. The SAP model was induced by retrograde injection of 5% sodium taurocholate into the pancreaticobiliary duct through duodenal wall. The SHAM and SAP groups received normal saline by gavage, while the CH group received 1.2 g·kg-1 Chaihuang Qingyi Huoxue Granule solution by gavage every six hours. At 12 h and 24 h after operation, eight rats from each group were sacrificed to collect abdominal aortic blood, pancreatic and ileal tissues for analysis. Ascites, pancreatic and ileal tissues were observed. Serum amylase (AMY) and lipase (LPS) levels were measured biochemically. Pathological changes in pancreatic and ileal tissues were investigated by HE staining. Claudin-1 protein expression in ileal tissue was detected by Western Blot. Changes in the intestinal flora of ileocecal contents were analyzed by 16S rDNA high-throughput sequencing. Results Compared to the SHAM group at the same time points, the SAP group exhibited extensive pancreatic edema and necrosis. Serum AMY and LPS levels, pancreatic and ileal histopathological scores increased, and Claudin-1 protein expression in ileal tissue markedly decreased (all P＜0.05). The differences in abundance of microbial community increased, while the evenness of community composition reduced. The microbial richness showed no significant change (P＞0.05), but the microbial diversity decreased (P＜0.05). Proteobacteria were dominant intestinal bacteria. Relative abundances of Oscillospira, Ruminococcus, Bifidobacterium, and Bacteroides S24-7 decreased, whereas relative abundances of Shigella and Allobaculum increased. The differences in abundance of microbial community reduced, and the evenness of community composition increased. The microbial richness showed no significant change (P＞0.05), but the microbial diversity increased (P＜0.05). Firmicutes and Bacteroidetes were the dominant intestinal bacteria. Relative abundances of Oscillospira, Ruminococcus, Bifidobacterium, and Bacteroides S24-7 increased, whereas relative abundances of Shigella and Allobaculum decreased. After the intervention of CH, pathological damage in ileal tissue was improved. The expression of Claudin-1 protein in the intestinal mucosal barrier increased compared to the model group (P＜0.05). The differences in abundance of microbial community reduced, and the evenness of community composition increased. CH group showed an increase in some beneficial bacteria and decrease in pathogenic bacteria compared to model group. Conclusion Chaihuang Qingyi Huoxue Granule may reduce pancreas injury in rats with SAP, which may be involved in modulating the intestinal microecology and improving intestinal mucosal barrier function. [ABSTRACT FROM AUTHOR]

Objective To observe the effect of BOC-Phe-Leu-Phe-Leu-Phe (BOC2) on the expression of six types of mitochondrial N-formyl peptides (NFPs) in blood and two formyl peptide receptors (FPRs) in pancreatic tissue of rats with severe acute pancreatitis (SAP), and to explore its mechanism of alleviating inflammatory damage of SAP. Methods Forty male SD rats were randomly divided into four groups: the sham group, the SAP model group, the BOC2 low-dose and the BOC2 high-dose group (0.1 and 0.2 mg/kg), with 10 animals in each group. The SAP model was prepared by retrograde injection of 5% sodium taurocholate (50 mg/kg) into biliary and pancreatic ducts in the last 3 groups. BOC2 was intraperitoneally injected at 0.5 hours after SAP modeling, and samples were taken 4 hours after modeling. HE staining was used to observe pathological changes in pancreas. Western blot assay was used to detect the expression of NFPs in plasma. IHC staining was used to detect the expression of FPRs in pancreatic tissue. ELISA was used to detect interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α levels in plasma. qPCR was used to detect expression levels of inflammatory factors in local pancreatic tissue. Results Compared with the model group, the BOC2 high-dose group and the BOC2 low- dose group showed improvement in pathological phenomena, such as pancreatic bleeding, acinar cell necrosis, inflammatory cell infiltration and edema. The pancreatic injury score, pancreatic FPRs expression, plasma MT-ND1, MT-ND2, MT-ND3, MT- ND5, MT-ND6 expression, as well as expression levels of three inflammatory factors in plasma and local pancreatic tissue, were significantly reduced (P＜0.05). Conclusion BOC2 can reduce the production of inflammatory factors and alleviate SAP inflammatory damage by antagonizing mitochondrial NFPs/FPRs signaling pathway. [ABSTRACT FROM AUTHOR]

Background and Aim: The development of acute pancreatitis (AP) is strongly linked to blood clotting and fibrinolysis issues. Modern clinical practices now utilize advanced blood markers like thrombin–antithrombin III complex (TAT), plasmin‐α2‐plasmin inhibitor complex, thrombomodulin (TM), and tissue plasminogen activator–inhibitor complex (t‐PAIC) to assess thrombosis risk. Our study used a highly sensitive chemiluminescence technique to measure these markers in AP patients, aiming to determine their early predictive value for AP severity. Methods: There were 173 patients with AP, all of whom developed symptoms within 72 h; 102 individuals had onset symptoms within 48 h. The biomarkers were measured upon admission before determining the severity of AP. Results: The levels of TAT, plasmin‐α2‐plasmin inhibitor complex, TM, and t‐PAIC were significantly higher in the severe acute pancreatitis (SAP) group compared with the mild acute pancreatitis and moderate severe acute pancreatitis groups. For the patients within 72 h of onset, TAT, TM, and t‐PAIC predicted the occurrence of SAP. For the patients within 48 h of onset, TAT and t‐PAIC predicted the occurrence of SAP. The area under the curve (AUC) of prediction models is similar to Bedside Index for Severity in Acute Pancreatitis (BISAP) but significantly higher than C‐reactive protein (P < 0.05). Notably, t‐PAIC had a larger AUC than TAT, BISAP, and C‐reactive protein. Conclusion: In the initial 48 h, plasma TAT and t‐PAIC levels may predict the development of SAP. Within 72 h, plasma levels of TAT, TM, and t‐PAIC may predict the development of SAP, and the TAT + TM + t‐PAIC prediction model achieved a maximum AUC of 0.915, comparable to BISAP. [ABSTRACT FROM AUTHOR]

Severe acute pancreatitis (SAP) is an inflammatory disease with varying severity, ranging from mild local inflammation to severe systemic disease, with a high incidence rate and mortality. Current drug treatments are not ideal. Therefore, safer and more effective therapeutic drugs are urgently needed. 7α,14β-dihydroxy-ent-kaur-17-dimethylamino-3,15-dione DGA, a diterpenoid compound derivatized from glaucocalyxin A, exhibits anti-inflammatory activity. In this study, we demonstrated the therapeutic potential of DGA against SAP and elucidated the underlying mechanisms. Treatment with DGA markedly (1) inhibited death of RAW264.7 and J774a.1 cells induced by Nigericin and lipopolysaccharide, (2) alleviated edema, acinar cell vacuolation, necrosis, and inflammatory cell infiltration of pancreatic tissue in mice, and (3) inhibited the activity of serum lipase and the secretion of inflammatory factor IL-1β. DGA significantly reduced the protein expression of IL-1β and NLRP3 and inhibited the phosphorylation of NF-κB. However, DGA exhibited no inhibitory effect on the expression of caspase-1, gasdermin D (GSDMD), NF-κB, TNF-α, or apoptosis-associated speck-like protein (ASC) and on the cleavage of caspase-1 or GSDMD. Molecular docking simulation confirmed that DGA can bind to TLR4 and IL-1 receptor. In conclusion, DGA may effectively alleviate the symptoms of SAP in mice and macrophages by inhibiting the binding of TLR4 and IL-1 receptor to their ligands; therefore, DGA is a promising drug candidate for the treatment of patients with SAP. [ABSTRACT FROM AUTHOR]

Background: Myricetin, a flavonoid, has anti-inflammation effects and can improve pancreatic β cells dysfunction. However, the role of myricetin in severe acute pancreatitis (SAP) and the precise mechanism remain unclear. Objectives: This study aimed to investigate how myricetin affects pancreatic damage induced by SAP. Results: Myricetin substantially reduced the expression of lipase and amylase, and ameliorated pancreatic damage induced by SAP. Moreover, myricetin inhibited the release of several inflammatory relevant cytokines including tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-10, alleviated apoptosis of pancreatic alveolar cells, and ameliorated microcirculatory dysfunction in SAP rats. Furthermore, myricetin inhibited the acetylation of forkhead box protein O1(FOXO1) and the phosphorylation of NF-kB. Conclusion: Myricetin improves SAP-induced pancreatic injury through suppressing microcirculation dysfunction, overactive inflammatory response, and cell apoptosis. In addition, myricetin deregulates acetylated FOXO1 and phosphorylated nuclear factor kappa B (NF-kB), which may be the potential mechanism for SAP alleviation. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect and mechanism of tauroursodeoxycholic acid (TUDCA) on severe acute pancreatitis (SAP)-induced liver injury in rat model. Methods Thirty SD rats were randomly divided into three groups(10 in each ):shame operation group(SO group),severe acute pancreatitis group(SAP group) and tauroursodeoxycholic acid group(TUDCA group).The SAP model was established by retrogradely injecting 5% sodium taurocholate (STC) solution (1 mL/kg) into pancreaticobiliary duct. The TUDCA group rats were intraperi- toneally injected with TUDCA(400 mg/kg·d-1) for three days continuously fore establishing models and the SAP and SO group rats were intraperitoneally injected with the same volume of saline. Rats were sacrificed 12 hrs after modeling, and then peripheral blood and part of pancreatic and liver tissues were collected. The level of amylase(AMY), aspartate aminotransferase(AST) and alanine aminotransferase(ALT) was detected by automatic biochemical analyzer. The expression of interleukin-6(IL-6) was detected by enzyme-linked immunosorbent assay (ELISA).The histo-pathological profile of pancreas and liver was examined by hematoxylin-eosin (HE) staining microscopy and liver apoptosis was observed by in situ terminal deoxynucleotide transferase labeling (TUNEL). The expression level of glucose-regulating protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP), nuclear factor-κB p65(NF-κB p65) and caspase-3 protein was determined by Western blot. Results Compared with SO group, the expression level of AMY,AST, ALT and IL-6 was increased in SAP group(P＜0.05); pancreas and liver necrosis and hepatocyte apoptosis were found to be more significant and the level of GRP78, PERK, CHOP, NF-κB p65 and caspase-3 protein increased (P＜0.05). Compared with SAP group, the expression of AMY, AST, ALT and IL-6 was reduced in TUDCA group and pancreas and liver necrosis and hepatocyte apoptosis were less severe. The level of GRP78, PERK, CHOP, NF-κB p65 and caspase-3 protein significantly decreased(P＜0.05). Conclusions TUDCA may have a protective mechanism to alleviate pancreatitis-induced severe and acute liver injury in rats by reducing the occurrence of endoplasmic reticulum stree(ERS), alleviating the inflammation and apoptosis as well as inhibiting PERK signaling pathway. [ABSTRACT FROM AUTHOR]

Purpose: To assess the prognosis of liver cirrhosis complicated with severe acute pancreatitis (SAP) after treatment with octreotide in combination with sodium tanshinone IIA sulfonate. Methods: A total of 164 patients with cirrhosis complicated with SAP were randomly assigned to two groups, each with 82 patients. Serum levels of inflammatory factors, as well as vascular endothelial function and liver function indices were determined. Treatment outcomes in the patients were recorded in terms of abdominal pain relief time, gastrointestinal function recovery time, hospital stay duration, and incidence of complications. Results: Relative to the control group, there were decreases in concentrations of inflammatory indices in the study cohort. Endothelial function index levels increased in the two groups, but the levels of endothelin (ET) and von Willebrand Factor (vWF) decreased more in the study group of patients, when compared to the control group, while nitric oxide (NO) level was raised (p < 0.05). Liver function improved in both groups. There were marked reductions in serum ALT, AST and total bilirubin (TBIL) in study cohort, relative to the control cohort (p < 0.05). However, albumin (ALB) levels were comparable in the two groups. Abdominal pain relief time, duration of hospitalization and time taken for normal digestive system function were shorter in the study cohort (p < 005). Receiver operating characteristic (ROC) curve analysis revealed that after treatment with octreotide and sodium tanshinone IIA sulfonate, values of area under the curve (AUC) for abdominal pain relief time, gastrointestinal function recovery time and hospital stay were 0.886, 0.918 and 0.794, respectively. Conclusion: The combined use of octreotide and sodium tanshinone IIA sulfonate inhibits the release of inflammatory factors in cirrhotic patients with SAP, and improves vascular endothelial and liver functions, thereby improving disease prognosis. These data constitute a good scientific basis for the use of octreotide and sodium tanshinone IIA sulfonate in the treatment of liver cirrhosis complicated with SAP. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical effect of probiotics combined with Ulinastatin and Somatostatin in the treatment of severe acute pancreatitis. Methods: A retrospective study was conducted on 160 patients with severe acute pancreatitis treated in the First Affiliated Hospital of Bengbu Medical College from July 2021 to June 2023. There were 78 patients received Ulinastatin and Somatostatin treatment (Control group), and 82 patients received probiotics in addition to Ulinastatin and Somatostatin treatment (Observation group). The treatment effect and the time required to alleviate clinical symptoms were compared between the two groups. Serum levels of inflammatory factors, intestinal mucosal indexes and the incidence of adverse reactions before and after treatment were analyzed. Results: The total efficacy of the Observation group (95.12%) was higher than that of the Control group (85.90%) (P<0.05). Combined probiotic/Ulinastatin + Somatostatin treatment was associated with shorter time to remission of the clinical symptoms (P<0.05). After the treatment, serum levels of inflammatory factors in the two groups were decreased, and was significantly lower in the Observation group compared to the Control group (P<0.05). Similarly, post-treatment serum levels of intestinal mucosal indexes in the two groups were lower than before the treatment, and significantly lower in the Observation group (P<0.05). There was no significant difference in the incidence of adverse reactions between the groups (P>0.05). Conclusions: A combined regimen of probiotics, Ulinastatin and Somatostatin is safe and can more effectively relieve clinical symptoms in patients with severe acute pancreatitis, reduce levels of inflammatory factors, lower intestinal mucosal damage and improve the overall treatment effect compared to Ulinastatin and Somatostatin regimen alone. [ABSTRACT FROM AUTHOR]

We aim to assess the early use of contrast-enhanced computed tomography (CECT) of patients with severe acute pancreatitis (SAP) using the computed tomography severity index (CTSI) in prognosis prediction. The CTSI combines quantification of pancreatic and extrapancreatic inflammation with the extent of pancreatic necrosis. Post-hoc retrospective analysis of a large, multicentric database (44 institutions) of SAP patients in Japan. The area under the curve (AUC) of the CTSI for predicting mortality and the odds ratio (OR) of the extent of pancreatic inflammation and necrosis were calculated using multivariable analysis. In total, 1097 patients were included. The AUC of the CTSI for mortality was 0.65 (95 % confidence interval [CI:] [0.59–0.70]; p < 0.001). In multivariable analysis, necrosis 30–50 % and >50 % in low-enhanced pancreatic parenchyma (LEPP) was independently associated with a significant increase in mortality, with OR 2.04 and 95 % CI 1.01–4.12 (P < 0.05) and OR 3.88 and 95 % CI 2.04–7.40 (P < 0.001), respectively. However, the extent of pancreatic inflammation was not associated with mortality, regardless of severity. The degree of necrosis in LEPP assessed using early CECT of SAP was a better predictor of mortality than the extent of pancreatic inflammation. [ABSTRACT FROM AUTHOR]

Abstract NLRP3 inflammasomes- pyroptosis axis is activated by microcirculation dysfunction and touched off severe acute pancreatitis (SAP). Activation of PGC-1α can improve microcirculation dysfunction by promoting mitochondrial biogenesis. Resveratrol (RSV), one typical SIRT1 agonist, possesses the ability of alleviating SAP and activing PGC-1α. Therefore, the study was designated to explore whether the protective effect of RSV in SAP was though suppressing NLRP3 inflammasomes- pyroptosis axis via advancing SIRT1/PGC-1α-dependent mitochondrial biogenesis. The models of SAP were induced by treating with sodium taurodeoxycholate in rats and AR42J cells. The pathological injury, water content (dry/wet ratio) and microcirculation function of pancreas, activity of lipase and amylase were used to evaluate pancreatic damage. The expression of inflammatory cytokine was measured by ELISA and RT-PCR. The damage of mitochondrial was evaluated by measuring the changes in Mitochondrial Membrane Potential (ΔΨm), mitochondrial ROS, ATP content and MDA as well as relocation of mtDNA and the activity of SOD and GSH. The expressions of NLRP3 inflammasomes- pyroptosis axis proteins were detected by Western blotting as well as SIRT1/PGC-1α/NRF1/TFAM pathway protein. Moreover, the modification of PGC-1α was measured by co-immunoprecipitation. The results displayed that RSV can significantly improve the damage of pancreas and mitochondrial, decrease the expression of pro-inflammatory factor and the activation of NLRP3 inflammasomes- pyroptosis axis, promote the expression of an-inflammatory factor and the deacetylation of PGC-1α together with facilitating SIRT1/PGC-1α-mediating mitochondrial biogenesis. Therefore, the protective effect of RSV in SAP is though inactivation of NLRP3 inflammasomes- pyroptosis axis via promoting mitochondrial biogenesis in a SIRT1/PGC-1α-dependent manner.

Objective To investigate the effect and mechanism of tauroursodeoxycholic acid (TUDCA) on severe acute pancreatitis (SAP)-induced liver injury in rat model. Methods Thirty SD rats were randomly divided into three groups(10 in each ):shame operation group(SO group),severe acute pancreatitis group(SAP group) and tauroursodeoxycholic acid group(TUDCA group).The SAP model was established by retrogradely injecting 5% sodium taurocholate (STC) solution (1 mL/kg) into pancreaticobiliary duct. The TUDCA group rats were intraperi- toneally injected with TUDCA(400 mg/kg·d-1) for three days continuously fore establishing models and the SAP and SO group rats were intraperitoneally injected with the same volume of saline. Rats were sacrificed 12 hrs after modeling, and then peripheral blood and part of pancreatic and liver tissues were collected. The level of amylase(AMY), aspartate aminotransferase(AST) and alanine aminotransferase(ALT) was detected by automatic biochemical analyzer. The expression of interleukin-6(IL-6) was detected by enzyme-linked immunosorbent assay (ELISA).The histo-pathological profile of pancreas and liver was examined by hematoxylin-eosin (HE) staining microscopy and liver apoptosis was observed by in situ terminal deoxynucleotide transferase labeling (TUNEL). The expression level of glucose-regulating protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP), nuclear factor-κB p65(NF-κB p65) and caspase-3 protein was determined by Western blot. Results Compared with SO group, the expression level of AMY,AST, ALT and IL-6 was increased in SAP group(P＜0.05); pancreas and liver necrosis and hepatocyte apoptosis were found to be more significant and the level of GRP78, PERK, CHOP, NF-κB p65 and caspase-3 protein increased (P＜0.05). Compared with SAP group, the expression of AMY, AST, ALT and IL-6 was reduced in TUDCA group and pancreas and liver necrosis and hepatocyte apoptosis were less severe. The level of GRP78, PERK, CHOP, NF-κB p65 and caspase-3 protein significantly decreased(P＜0.05). Conclusions TUDCA may have a protective mechanism to alleviate pancreatitis-induced severe and acute liver injury in rats by reducing the occurrence of endoplasmic reticulum stree(ERS), alleviating the inflammation and apoptosis as well as inhibiting PERK signaling pathway.

Hongwei Huang,1 Jiacheng Mo,2 Gui Jiang,2 Zheng Lu1 1Intensive Care Unit, Guangxi Hospital Division of the First Affiliated Hospital, Sun Yat-Sen University, Nanning, Guangxi, 530022, People’s Republic of China; 2Intensive care unit, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Zheng Lu, Intensive Care Unit, Guangxi Hospital Division of the First Affiliated Hospital, Sun Yat-sen University, Nanning, Guangxi, 530022, People’s Republic of China, Email iculuzheng@163.comPurpose: To evaluate the long-term efficacy and cost-efficiency of blood purification (BP) in severe acute pancreatitis (SAP) through single-center data.Patients and Methods: A total of 155 SAP patients were collected and followed up for 6 months. The participants were divided into control (49 cases) and BP group (106 cases) according to whether they received BP treatment or not. The primary outcomes were 6-month mortality, length of hospital stay, and hospitalization costs. Propensity score matching (PSM) analysis was performed based on various factors such as gender, age, etiology, SOFA score, JSS score, and creatinine value on day 1.Results: There were significant differences in all baseline data between BP and control groups (p< 0.05). However, there was a significant difference in the mortality, length of hospital stay, hospital costs and infection aggravation rate the in outcome data for 6-months (all p< 0.05). BP was not considered a death factor in any adjusted models, with p-values ranging from 0.81 to 0.93. The results of subgroup analysis after PSM showed that BP mode had no significant impact on prognostic indicators, but the length of ICU stay and total costs were significantly increased (all p< 0.001). There was no significant difference in mortality among the cases that did not require early intervention after 6 months (p=0.487). However, the patients in BP group had longer ICU stays (p=0.001) and higher hospitalization costs (p< 0.001) compared to the control group.Conclusion: The utilization of BP therapy did not decrease the 6-month mortality in SAP patients. Additionally, BP therapy has a significant impact on the duration of ICU stay or hospitalization expenses. However, the effectiveness and cost-efficiency of this therapy are unsatisfactory, and early intervention does not enhance survival benefits. Furthermore, there was no substantial variation in survival benefits between continuous veno-venous hemofiltration (CVVH) alone and compound BP.Keywords: severe acute pancreatitis, blood purification, long-term efficacy, cost-efficiency

Abstract Background Guidelines must be interpreted comprehensively and correctly to standardize the clinical process. However, this process is challenging and requires interpreters to have a medical background and qualifications. In this study, the accuracy of ChatGPT3.5 in answering clinical questions related to the 2019 guidelines for severe acute pancreatitis was evaluated. Methods and results An observational study was conducted using the 2019 guidelines for severe acute pancreatitis. The study compared the accuracy of ChatGPT3.5 in English versus Chinese and found that it was more accurate in English (71%) than in Chinese (59%) (P value: 0.203). Additionally, the study assessed the accuracy of ChatGPT3.5 in answering short-answer questions versus true/false questions and found that it was more accurate in answering short-answer questions (76%) than in answering true/false questions (60%) (P value: 0.405). Conclusions For clinicians managing severe acute pancreatitis, ChatGPT3.5 may have potential value. However, it should not be relied upon excessively for clinical decision making.

Abstract Background Ferroptosis is a newly recognized form of regulatory cell death characterized by severe lipid peroxidation triggered by iron overload and the production of reactive oxygen species (ROS). However, the role of ferroptosis in severe acute pancreatitis(SAP) has not been fully elucidated. Methods We established four severe acute pancreatitis models of rats including the sham control group, the SAP group, the Fer -1-treated SAP (SAP + Fer-1) group, the 3-MA-treated SAP (SAP + 3-MA) group. The SAP group was induced by retrograde injection of sodium taurocholate into the pancreatic duct. The other two groups were intraperitoneally injected with ferroptosis inhibitor (Fer-1) and autophagy inhibitor (3-MA), respectively. The model of severe acute pancreatitis with amylase crest-related inflammatory factors was successfully established. Then we detected ferroptosis (GPX4, SLC7A1 etc.) and autophagy-related factors (LC3II, p62 ect.) to further clarify the relationship between ferroptosis and autophagy. Results Our study found that ferroptosis occurs during the development of SAP, such as iron and lipid peroxidation in pancreatic tissues, decreased levels of reduced glutathione peroxidase 4 (GPX 4) and glutathione (GSH), and increased malondialdehyde(MDA) and significant mitochondrial damage. In addition, ferroptosis related proteins such as GPX4, solute carrier family 7 member 11(SLC7A11) and ferritin heavy chain 1(FTH1) were significantly decreased. Next, the pathogenesis of ferroptosis in SAP was studied. First, treatment with the ferroptosis inhibitor ferrostatin-1(Fer-1) significantly alleviated ferroptosis in SAP. Interestingly, autophagy occurs during the pathogenesis of SAP, and autophagy promotes the occurrence of ferroptosis in SAP. Moreover, 3-methyladenine (3-MA) inhibition of autophagy can significantly reduce iron overload and ferroptosis in SAP. Conclusions Our results suggest that ferroptosis is a novel pathogenesis of SAP and is dependent on autophagy. This study provides a new theoretical basis for the study of SAP.

Abstract Purpose There is a lack of adequate models specifically designed for elderly patients with severe acute pancreatitis (SAP) to predict the risk of death. This study aimed to develop a nomogram for predicting the overall survival of SAP in elderly patients. Methods Elderly patients diagnosed with SAP between January 1, 2017 and December 31, 2022 were included in the study. Risk factors were identified through least absolute shrinkage and selection operator regression analysis. Subsequently, a novel nomogram model was developed using multivariable logistic regression analysis. The predictive performance of the nomogram was evaluated using metrics such as the receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). Results A total of 326 patients were included in the analysis, with 260 in the survival group and 66 in the deceased group. Multivariate logistic regression indicated that age, respiratory rate, arterial pH, total bilirubin, and calcium were independent prognostic factors for the survival of SAP patients. The nomogram demonstrated a performance comparable to sequential organ failure assessment (P = 0.065). Additionally, the calibration curve showed satisfactory predictive accuracy, and the DCA highlighted the clinical application value of the nomogram. Conclusion We have identified key demographic and laboratory parameters that are associated with the survival of elderly patients with SAP. These parameters have been utilized to create a precise and user-friendly nomogram, which could be an effective and valuable clinical tool for clinicians.

Refeeding syndrome is a serious complication of malnutrition that occurs when someone who has been starved begins feeding again. Due to the lack of specificity, it is difficult to distinguish and the incidence is relatively high. Patients with severe acute pancreatitis are vulnerable to refeeding syndrome as high level of metabolism caused by serious condition or infection. Current researches mainly focus on pathogenesis, risk factors, prevention and nursing care of the refeeding syndrome. Because of the complexity and variation of clinical manifestations and weak specificity, the clinical practice of patients with refeeding syndrome is still controversial. This paper reviews studies on concept, current research status, pathogenesis, risk factors and other issues of refeeding syndrome in patients with severe acute pancreatitis, and puts forward suggestions for clinical practice, in order to provide reference for clinical diagnosis, prevention and treatment of refeeding syndrome. (再喂养综合征(RFS)是长期营养不良患者重新摄入营养初期机体代谢异常所导致的一系列代谢紊乱症候群, 由于缺乏特异性, 不易辨别, 发生率较高。重症急性胰腺炎患者因病情危重、感染等原因, 机体处于高分解、高代谢状态, 发生RFS风险较高。目前国内外关于RFS的研究, 涉及发病机制、危险因素、预防及护理等多方面, 但由于RFS的临床症状复杂多样且缺乏特异性, 易被临床医护人员忽视, 且具体护理措施仍然存在争议。本文通过对再喂养综合征定义、国内外现状、发生机制、危险因素等进行综述, 并提出护理建议, 以期为医护人员观察、识别和预防RFS提供参考依据。)

Hui Liu,1,2 Xuan Xu,3 Ji Li,3 Zheyu Liu,1 Yuwen Xiong,1 Mengli Yue,4 Pi Liu1 1Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2Gastroenterology Institute of Jiangxi Province, Nanchang, People’s Republic of China; 3Department of Gastroenterology, The People’s Hospital of Longhua, Shenzhen, People’s Republic of China; 4Affiliated Longhua People’s Hospital, The Third School of Clinical Medicine, Southern Medical University, Shenzhen, People’s Republic of ChinaCorrespondence: Pi Liu, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China, Tel +86-13507913736, Email liupi126@sina.comPurpose: Capillary leak syndrome (CLS) is an intermediary phase between severe acute pancreatitis (SAP) and multiple organ failure. As a result, CLS is of clinical importance for enhancing the prognosis of SAP. Plakophilin2 (PKP2), an essential constituent of desmosomes, plays a critical role in promoting connections between epithelial cells. However, the function and mechanism of PKP2 in CLS in SAP are not clear at present.Methods: We detected the expression of PKP2 in mice pancreatic tissue by transcriptome sequencing and bioinformatics analysis. PKP2 was overexpressed and knocked down to assess its influence on cell permeability, the cytoskeleton, tight junction molecules, cell adhesion junction molecules, and associated pathways.Results: PKP2 expression was increased in the pancreatic tissues of SAP mice and human umbilical vein endothelial cells (HUVECs) after lipopolysaccharide (LPS) stimulation. PKP2 overexpression not only reduced endothelial cell permeability but also improved cytoskeleton relaxation in response to acute inflammatory stimulation. PKP2 overexpression increased levels of ZO-1, occludin, claudin1, β-catenin, and connexin43. The overexpression of PKP2 in LPS-induced HUVECs counteracted the inhibitory effect of SB203580 (a p38/MAPK signaling pathway inhibitor) on the p38/MAPK signaling pathway, thereby restoring the levels of ZO-1, β-catenin, and claudin1. Additionally, PKP2 suppression eliminated the enhanced levels of ZO-1, β-catenin, occludin, and claudin1 induced by dehydrocorydaline. We predicted that the upstream transcription factor PPARγregulates PKP2 expression, and our findings demonstrate that the PPARγactivator rosiglitazone significantly upregulates PKP2, whereas its antagonist GW9662 down-regulates PKP2. Administration of rosiglitazone significantly reduced the increase in HUVECs permeability stimulated by LPS. Conversely, PKP2 overexpression counteracted the GW9662-induced reduction in ZO-1, phosphorylated p38/p38, and claudin1.Conclusion: The activation of the p38/MAPK signaling pathway by PKP2 mitigates CLS in SAP. PPARγactivator rosiglitazone can up-regulate PKP2. Overall, directing efforts toward PKP2 could prove to be a feasible treatment approach for effectively managing CLS in SAP. Keywords: severe acute pancreatitis, plakophilin2, capillary leak syndrome, tight junction, p38/MAPK signaling pathway

Severe acute pancreatitis (SAP) is a common disease that seriously threatens human life and health, characterized by rapid progression, complexity and variability, and multiple complications. SAP can lead to intestinal microbiota imbalance and intestinal mucosal barrier dysfunction in the early stages. Traditional Chinese medicine has shown unique advantages in regulating gut microbiota and has become a potential method for treating intestinal microbiota imbalance in SAP. The article reviews the research progress of traditional Chinese medicine in treating SAP from the perspective of gut microbiota. [ABSTRACT FROM AUTHOR]

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Background: Guidelines must be interpreted comprehensively and correctly to standardize the clinical process. However, this process is challenging and requires interpreters to have a medical background and qualifications. In this study, the accuracy of ChatGPT3.5 in answering clinical questions related to the 2019 guidelines for severe acute pancreatitis was evaluated. Methods and results: An observational study was conducted using the 2019 guidelines for severe acute pancreatitis. The study compared the accuracy of ChatGPT3.5 in English versus Chinese and found that it was more accurate in English (71%) than in Chinese (59%) (P value: 0.203). Additionally, the study assessed the accuracy of ChatGPT3.5 in answering short-answer questions versus true/false questions and found that it was more accurate in answering short-answer questions (76%) than in answering true/false questions (60%) (P value: 0.405). Conclusions: For clinicians managing severe acute pancreatitis, ChatGPT3.5 may have potential value. However, it should not be relied upon excessively for clinical decision making. [ABSTRACT FROM AUTHOR]

Background/Objectives: Early identification of patients at risk of developing severe acute pancreatitis (SAP) is still an issue. Dynamic assessment of clinical and laboratory parameters within the first 48 h of admission may offer valuable insights into the prediction of unfavorable outcomes such as SAP and death. Methods: A prospective observational study was conducted on a cohort of patients admitted for AP at a tertiary referral hospital. Clinical and laboratory data were collected on admission and at 48 h. Patients were classified based on the Revised Atlanta classification. Logistic regression analysis was performed to identify independent risk factors for SAP. Likelihood ratios and post-test probabilities were calculated to assess the clinical usefulness of predictive markers. Results: 227 patients were included, with biliary etiology being the most common and a prevalence of SAP and death of 10.7% and 5.7%, respectively. BISAP ≥ 2 on admission, presence of SIRS after 48 h, rise in heart rate over 20 bpm, and any increase in BUN after 48 h were independent risk factors for SAP. The combination of these factors increased the post-test probability of SAP and death, with BISAP ≥ 2 combined with the presence of SIRS after 48 h showing the highest probability (82% and 73%, respectively). Conclusions: Dynamic assessment of BUN, heart rate, and SIRS within the first 48 h of admission can aid in predicting the development of SAP and death in patients with AP. These findings underscore the importance of continuous monitoring, although multicenter studies are warranted to refine predictive models for SAP. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis is a newly recognized form of regulatory cell death characterized by severe lipid peroxidation triggered by iron overload and the production of reactive oxygen species (ROS). However, the role of ferroptosis in severe acute pancreatitis(SAP) has not been fully elucidated. Methods: We established four severe acute pancreatitis models of rats including the sham control group, the SAP group, the Fer -1-treated SAP (SAP + Fer-1) group, the 3-MA-treated SAP (SAP + 3-MA) group. The SAP group was induced by retrograde injection of sodium taurocholate into the pancreatic duct. The other two groups were intraperitoneally injected with ferroptosis inhibitor (Fer-1) and autophagy inhibitor (3-MA), respectively. The model of severe acute pancreatitis with amylase crest-related inflammatory factors was successfully established. Then we detected ferroptosis (GPX4, SLC7A1 etc.) and autophagy-related factors (LC3II, p62 ect.) to further clarify the relationship between ferroptosis and autophagy. Results: Our study found that ferroptosis occurs during the development of SAP, such as iron and lipid peroxidation in pancreatic tissues, decreased levels of reduced glutathione peroxidase 4 (GPX 4) and glutathione (GSH), and increased malondialdehyde(MDA) and significant mitochondrial damage. In addition, ferroptosis related proteins such as GPX4, solute carrier family 7 member 11(SLC7A11) and ferritin heavy chain 1(FTH1) were significantly decreased. Next, the pathogenesis of ferroptosis in SAP was studied. First, treatment with the ferroptosis inhibitor ferrostatin-1(Fer-1) significantly alleviated ferroptosis in SAP. Interestingly, autophagy occurs during the pathogenesis of SAP, and autophagy promotes the occurrence of ferroptosis in SAP. Moreover, 3-methyladenine (3-MA) inhibition of autophagy can significantly reduce iron overload and ferroptosis in SAP. Conclusions: Our results suggest that ferroptosis is a novel pathogenesis of SAP and is dependent on autophagy. This study provides a new theoretical basis for the study of SAP. [ABSTRACT FROM AUTHOR]

Purpose: There is a lack of adequate models specifically designed for elderly patients with severe acute pancreatitis (SAP) to predict the risk of death. This study aimed to develop a nomogram for predicting the overall survival of SAP in elderly patients. Methods: Elderly patients diagnosed with SAP between January 1, 2017 and December 31, 2022 were included in the study. Risk factors were identified through least absolute shrinkage and selection operator regression analysis. Subsequently, a novel nomogram model was developed using multivariable logistic regression analysis. The predictive performance of the nomogram was evaluated using metrics such as the receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). Results: A total of 326 patients were included in the analysis, with 260 in the survival group and 66 in the deceased group. Multivariate logistic regression indicated that age, respiratory rate, arterial pH, total bilirubin, and calcium were independent prognostic factors for the survival of SAP patients. The nomogram demonstrated a performance comparable to sequential organ failure assessment (P = 0.065). Additionally, the calibration curve showed satisfactory predictive accuracy, and the DCA highlighted the clinical application value of the nomogram. Conclusion: We have identified key demographic and laboratory parameters that are associated with the survival of elderly patients with SAP. These parameters have been utilized to create a precise and user-friendly nomogram, which could be an effective and valuable clinical tool for clinicians. [ABSTRACT FROM AUTHOR]

As the mortality of severe acute pancreatitis (SAP) is significantly higher than those with mild or moderate severity, it is of clinical significance to identify patients most likely to develop SAP at the time of emergency department (ED) presentation. The aim of this study was to compare the performance of the Bedside Index for Severity in Acute Pancreatitis (BISAP) and the Emergency Department SpO 2 , Age and SIRS (ED-SAS) scoring systems as early risk assessment tools for identifying patients at high-risk of developing SAP. We retrospectively reviewed adult patients with AP presented to ED between January 2019–September 2022. We calculated the scores of each patient with the parameters of the initial data. The primary outcome was SAP. The secondary outcomes were 30-day mortality, intensive care admission, and identifying low-risk patients without complications. Of 415 patients, 34 (8.2%) developed SAP and 15 (3.6%) died. With regard to predicting SAP, BISAP and ED-SAS scores had similar discriminative ability with area under the curves (AUCs) of 0.84 (95% confidence interval [CI]:0.80–0.88) and 0.83 (95% CI:0.79–0.86), respectively (p = 0.642). At a cut-off score of ≥2 for SAP, sensitivity/specificity values were 73.5%/82.4% for BISAP, 76.5%/83.2% for ED-SAS. BISAP and ED-SAS scores of ≥3, yielded sensitivity/specificity values of 50%/95.8% and 35.3%/95.5%, respectively. BISAP and ED-SAS were also similar in predicting mortality (AUCs of 0.92 vs. 0.90, respectively) and intensive care unit admission (AUCs 0.91 vs. 0.91). The BISAP and ED-SAS scores performed similarly in predicting SAP, mortality, and intensive care unit admission. As an easily calculated tool early in the ED, ED-SAS may be helpful in disposition decisions for emergency physicians. [ABSTRACT FROM AUTHOR]

Background: Severe acute pancreatitis (SAP) is a potential fatal gastrointestinal disease that is usually complicated by myocardial injury and dysfunction. Due to the lack of understanding of the mechanism of SAP-associated cardiac injury (SACI), there is still no complete treatment. Aims: To explore the alleviative effect and anti-ferroptosis mechanism against SACI of glycyrrhizin (GL), an inhibitor of oxidative stress. Methods: The SAP model was established by perfusing 5% sodium taurocholate into biliopancreatic duct in rats. H&E staining and serum assays were used to assess the injury changes of pancreas and heart. Echocardiography was used to evaluate the cardiac function. Transmission electron microscopy (TEM) and oxidative stress assays were used to investigate the ferroptosis-related morphological and biochemical changes. Western blot and immunofluorescence were performed to analyzed the expression of ferroptosis-related proteins. Results: Significant myocardial impairment was found in SAP rats according to increased histopathological scores, serum creatine kinase-MB (CK-MB) and cardiac troponin-I (cTnI) levels, and a decreased fractional shortening and ejection fraction. The decreased mitochondrial cristae and significant expression changes of ferroptosis-related proteins confirmed the presence of ferroptosis in SACI. GL treatment attenuated above-mentioned cardiac tissues damage by inhibiting ferroptosis via restoring the expression of Nrf2 and HO-1 in vivo and in vitro. Treating with ML385 (a Nrf2 inhibitor) or transfecting with siRNA-Nrf2 reversed the protective effect of GL. Conclusions: Our findings demonstrate the involvement of ferroptosis in SACI and suggest a potential role for GL in the treatment of SACI by supressing ferroptosis via Keap1/Nrf2/HO-1 pathway. [ABSTRACT FROM AUTHOR]

Background: Severe acute pancreatitis (SAP) is a potentially lethal inflammatory pancreatitis condition that is usually linked to multiple organ failure. When it comes to SAP, the lung is the main organ that is frequently involved. Many SAP patients experience respiratory failure following an acute lung injury (ALI). Clinicians provide insufficient care for compounded ALI since the underlying pathophysiology is unknown. The mortality rate of SAP patients is severely impacted by it. Objective: The study aims to provide insight into immune cells, specifically their roles and modifications during SAP and ALI, through a comprehensive literature review. The emphasis is on immune cells as a therapeutic approach for treating SAP and ALI. Findings: Immune cells play an important role in the complicated pathophysiology ofSAP and ALI by maintaining the right balance of pro‐ and anti‐inflammatory responses. Immunomodulatory drugs now in the market have low thepeutic efficacy because they selectively target one immune cell while ignoring immune cell interactions. Accurate management of dysregulated immune responses is necessary. A critical initial step is precisely characterizing the activity of the immune cells during SAP and ALI. Conclusion: Given the increasing incidence of SAP, immunotherapy is emerging as a potential treatment option for these patients. Interactions among immune cells improve our understanding of the intricacy of concurrent ALI in SAP patients. Acquiring expertise in these domains will stimulate the development of innovative immunomodulation therapies that will improve the outlook for patients with SAP and ALI. [ABSTRACT FROM AUTHOR]

Severe acute pancreatitis (SAP) is the most serious type of acute pancreatitis (AP) and a common critical disease in clinic. With the continuous improvement of medical level, the mortality rate in the early stage of SAP has decreased significantly, and the peak of death is mainly concentrated in the later stage of the disease and the main cause of death in the later stage is secondary sepsis after infection of pancreatic or peripancreatic necrosis. If the risk of secondary sepsis in SAP can be predicted early it can guide the medical staff to carry out appropriate early monitoring and intervention to improve the clinical outcome of patients, The article reviewed the application progress of blood markers to predict secondary sepsis in SAP. [ABSTRACT FROM AUTHOR]

Objective To explore the therapeutic effects of Dahuang Fuzi decoction (DHFZT) on severe acute pancreatitis (SAP) in mice through the establishment of mouse model with SAP. Methods The SPF mice were randomly divided into three groups: control group, model group, and DHFZT group, with 8 mice in each group. Except for the control group, the rat SAP models were established in each group by intraperitoneal injection of L-arginine. Mice in the the DHFZT group received oral administration of 1.5 mL DHFZT at 6 and 12 h after modeling, while mice in the control and model groups received oral administration of 1.5 mL normal saline. Following the final oral administration, anesthesia was ad⁃ ministered to collect eye samples from all mice for ELISA detection of SAP markers such as amylase (AMS) and lipase (LPS), as well as inflammatory response markers including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Tissue samples from pancreas, lungs, and colon were collected for histological observation and calculation of histological scores. Immunohistochemistry and Western blotting were used to detect α-defensin 6 (DEFA6) protein and glucose regulator protein 78 (GRP78) in small intestine tissues, respectively; immunofluorescence staining was performed to detect lysozyme in the small intestine tissues. Results Serum AMS, LPS, TNF-α, IL-6 level were as follows: model group > DHFZT group > control group (all P<0. 05). In the control group, the tissue structures of pancreas, lung and colon were intact, and no inflammatory cell infiltration was observed. In the model group, the tissue structures of pancreas, lung and colon were destroyed, and red blood cell exudation and inflammatory cell infiltration were observed. The histopathology of DHFZT group was improved compared with that of the model group. The histopathological scores of pancreas, lung and colon were as follows: model group > DHFZT group > control group (all P<0. 05). Small intestine DEFA6 protein expression was as follows: model group < DHFZT group < control group, GRP78 protein expression was in the following order: model group > DHFZT group > control group, and the relative fluorescence intensity of lysozyme was as follows: model group < DHFZT group < control group (all P<0. 05). Conclusion The intragastric administration of DHFZT exhibits specific therapeutic effects on SAP in mice, potentially by inhibiting endoplasmic reticulum stress in Paneth cells, enhancing the secretion of antibacterial molecules, and thus improving intestinal barrier function. [ABSTRACT FROM AUTHOR]

Background Aims Design and Methods Results Conclusions Relevance to Clinical Practice The complexity of severe acute pancreatitis (SAP) and the stress caused by the disease is associated with a high incidence of feeding intolerance. However, the factors influencing feeding incontinence in patients with SAP are diverse.To systematically analyse relevant studies that investigate the occurrence of feeding intolerance in patients with SAP, identify the relevant factors of feeding intolerance in such patients and provide a reference for nursing staff to develop relevant intervention measures.This scoping review followed the approach proposed by Arksey and O'Malley. Seven electronic databases were searched from their establishment until August 2023. This included research on the factors influencing feeding intolerance in patients with SAP, determining research questions, completing literature screening and quality evaluation, extracting data and summarizing and analysing the data. The PRISMA extension for scoping reviews (PRISMA‐ScR) statement has also been included.A total of 23 articles were included. The factors influencing feeding intolerance in patients with SAP included the patient's condition, disease, treatment, feeding management and follow‐up care.The factors affecting feeding intolerance in patients with SAP are multifaceted. A personalized nursing care plan should be developed based on relevant risk factors to improve feeding tolerance and comfort in patients with SAP and shorten hospitalization time.Intensive care nurses should identify the risk factors for feeding intolerance in patients with SAP and implement appropriate interventions. To identify the risk factors, nurses must be updated with courses and training. Moreover, a systematic feeding intolerance prediction program can help intensive care nurses effectively identify the risk factors for feeding. [ABSTRACT FROM AUTHOR]

Severe acute pancreatitis (SAP) is characterized by rapid onset and progression, complex clinicopathological changes, and a mortality rate of as high as 20%—30%. Long-term clinical practice and basic research have shown that relying solely on Western medicine for the treatment of SAP may not achieve satisfactory outcomes, and integrated traditional Chinese and Western medicine therapy has a marked clinical effect and significant advantages. Based on evidence-based medicine and with reference to related guidelines and clinical practice in China and globally, these guidelines summarize 28 clinical questions after widely soliciting opinions and suggestions from experts. This document specifically elaborates on the etiology, pathogenesis, and diagnostic criteria of SAP, as well as the key points of integrated traditional Chinese and Western medicine typing, disease staging, treatment methods, and therapies, so as to standardize the integrated traditional Chinese and Western medicine diagnostic criteria and treatment principles of SAP. [ABSTRACT FROM AUTHOR]

Objectives: Acute pancreatitis (AP) is an inflammatory disease of the pancreas, and the prognosis of severe AP (SAP) is poor. The study aimed to identify promising biomarkers for predicting the occurrence and survival outcome of SAP patients. Materials and Methods: Two hundred and forty AP patients were retrospectively recruited, in which 72 cases with SAP. Blood test was done for collection of laboratory indicators. After treatment, the mortality of patients was recorded. Results: Patients in the SAP group had higher intensive care unit admissions and longer hospital stays (p <.001). Among laboratory parameters, significantly high values of C‐reactive protein (CRP), triglycerides and glucose (TyG) index, Von willebrand factor antigen (vWF:Ag) and D‐dimer were found in SAP groups relative to non‐SAP ones. Receiver operating characteristic curve indicated the good performance of CRP, TyG index, vWF:Ag and D‐dimer in SAP diagnosis. Among all SAP cases, 51 survived while 21 died. TyG index (odds ratio [OR] = 6.914, 95% confidence interval [CI] = 1.193–40.068, p =.028), vWF:Ag (OR = 7.441, 95% CI = 1.236–244.815, p =.028), and D‐dimer (OR = 7.987, 95% CI = 1.251–50.997, p =.028) were significantly related to survival outcome of SAP patients by multiple logistic regression analysis. Both TyG index and vWF showed favorable efficiency in predicting overall prognosis. The area under the curve for the multivariate model (PRE = −35.908 + 2.764 × TyG + 0.021 × vWF:Ag) was 0.909 which was greater than 0.9, indicating its excellent performance in prognosis prediction. Conclusion: CRP, TyG index, vWF:Ag, and D‐dimer values on admission may be potential clinical predictors of the development of SAP. Moreover, TyG index and vWF:Ag may be helpful to predict survival outcome. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic accuracy of abdominal contrast-enhanced multi-slice spiral CT after oral diluted iodide in a time segment (post-ODI ACE-MSCT) for gastrointestinal fistula (GIF) in severe acute pancreatitis (SAP). Materials and methods: Patients with SAP who underwent both post-ODI ACE-MSCT and endoscopy/surgery from 2017 to 2023 were continuously retrospectively involved. Their demographic information and clinical features were recorded prospectively in an in-hospital database. Using endoscopy/surgery results as the reference standard, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of post-ODI ACE-MSCT for diagnosing GIF in SAP were calculated by a four-cell table. The consistency of the two diagnostic methods was evaluated by the Kappa test and McNemar's test. Results: Using endoscopy/surgery as the reference standard, a total of 86 cases were divided into the GIF group (N = 52) and the non-GIF group (N = 34). Among the 52 cases of GIF, 88.5% (46/52) cases had a positive result and 11.5% (5/52) cases had a negative result of post-ODI ACE-MSCT for GIF. Among the 34 cases of non-GIF, 2.9% (1/34) case had a positive result and 97.1% (33/34) cases had a negative result of post-ODI ACE-MSCT for GIF. Post-ODI ACE-MSCT had a sensitivity of 88.5% (95% CI 75.9%–95.2%), a specificity of 97.1% (95% CI 82.9%–99.8%), a positive predictive value of 97.9% (95% CI 87.3%–99.9%), a negative predictive value of 84.6% (95% CI 68.8%–93.6%), and an accuracy of 91.9% (83.4%–96.4%). The kappa value was 0.834, and P < 0.001 by McNemar's test. There were no significant differences in diagnostic test characteristics between the two modalities. Conclusion: Post-ODI ACE-MSCT can diagnose GIF in SAP in a simple, noninvasive, and accurate way, and can provide earlier imaging evidence for clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Severe acute pancreatitis (SAP) is a serious gastrointestinal disease that is facilitated by pancreatic acinar cell death. The protective role of human placental mesenchymal stem cells (hP-MSCs) in SAP has been demonstrated in our previous studies. However, the underlying mechanisms of this therapy remain unclear. Herein, we investigated the regularity of acinar cell pyroptosis during SAP and investigated whether the protective effect of hP-MSCs was associated with the inhibition of acinar cell pyroptosis. Methods: A mouse model of SAP was established by the retrograde injection of sodium taurocholate (NaTC) solution in the pancreatic duct. For the hP-MSCs group, hP-MSCs were injected via the tail vein and were monitored in vivo. Transmission electron microscopy (TEM) was used to observe the pyroptosis-associated ultramorphology of acinar cells. Immunofluorescence and Western blotting were subsequently used to assess the localization and expression of pyroptosis-associated proteins in acinar cells. Systemic inflammation and local injury-associated parameters were evaluated. Results: Acinar cell pyroptosis was observed during SAP, and the expression of pyroptosis-associated proteins initially increased, peaked at 24 h, and subsequently showed a decreasing trend. hP-MSCs effectively attenuated systemic inflammation and local injury in the SAP model mice. Importantly, hP-MSCs decreased the expression of pyroptosis-associated proteins and the activity of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in acinar cells. Conclusions: Our study demonstrates the regularity and important role of acinar cell pyroptosis during SAP. hP-MSCs attenuate inflammation and inhibit acinar cell pyroptosis via suppressing NLRP3 inflammasome activation, thereby exerting a protective effect against SAP. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of honokiol (HON) and the role of high-mobility group protein B1 (HMGB1) on the pathogenesis of severe acute pancreatitis (SAP). Methods: Thirty mice were numbered according to weight, and randomly divided into 5 groups using a random number table, including control, SAP, SAP and normal saline (SAP+NS), SAP and ethyl pyruvate (SAP+EP), or SAP+HON groups, 6 mice in each group. Samples of pancreas, intestine, and blood were collected 12 h after SAP model induction for examination of pathologic changes, immune function alterations by enzyme linked immunosorbent assay (ELISA), and Western blot. In vitro experiments, macrophages were divided into 5 groups, the control, lipopolysaccharide (LPS), LPS+DMSO (DMSO), LPS+anti-HMGB1 monoclonal antibody (mAb), and LPS+ HON groups. The tight connection level was determined by transmission electron microscopy and fluorescein isothiocyanate-labeled. The location and acetylation of HMGB1 were measured by Western blot. Finally, pyridone 6 and silencing signal transducer and activator of the transcription 1 (siSTAT1) combined with honokiol were added to determine whether the Janus kinase (JAK)/ STAT1 participated in the regulation of honokiol on HMGB1. The protein expression levels of HMGB1, JAK, and STAT1 were detected using Western blot. Results: Mice with SAP had inflammatory injury in the pancreas, bleeding of intestinal tissues, and cells with disrupted histology. Mice in the SAP+HON group had significantly fewer pathological changes. Mice with SAP also had significant increases in the serum levels of amylase, lipase, HMGB1, tumor necrosis factor- α, interleukin-6, diamine oxidase, endotoxin-1, and procalcitonin. Mice in the SAP+HON group did not show these abnormalities (P<0.01). Studies of Caco-2 cells indicated that LPS increased the levels of occludin and claudin-1 as well as tight junction permeability, decreased the levels of junctional adhesion molecule C, and elevated intercellular permeability (P<0.01). HON treatment blocked these effects. Studies of macrophages indicated that LPS led to low nuclear levels of HMGB1, however, HON treatment increased the nuclear level of HMGB1 (P<0.01). HON treatment also inhibited the expressions of JAK1, JAK2, and STAT1 (P<0.01) and increased the acetylation of HMGB1 (P<0.05). Conclusion: HON prevented intestinal barrier dysfunction in SAP by inhibiting HMGB1 acetylation and JAK/STAT1 pathway. [ABSTRACT FROM AUTHOR]

BackgroundSevere acute pancreatitis (SAP) is accompanied with acute onset, rapid progression, and complicated condition. Sepsis is a common complication of SAP with a high mortality rate. This research aimed to identify the shared hub genes and key pathways of SAP and sepsis, and to explore their functions, molecular mechanism, and clinical value.MethodsWe obtained SAP and sepsis datasets from the Gene Expression Omnibus (GEO) database and employed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to identify the shared differentially expressed genes (DEGs). Functional enrichment analysis and protein–protein interaction (PPI) was used on shared DEGs to reveal underlying mechanisms in SAP-associated sepsis. Machine learning methods including random forest (RF), least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) were adopted for screening hub genes. Then, receiver operating characteristic (ROC) curve and nomogram were applied to evaluate the diagnostic performance. Finally, immune cell infiltration analysis was conducted to go deeply into the immunological landscape of sepsis.ResultWe obtained a total of 123 DEGs through cross analysis between Differential expression analysis and WGCNA important module. The Gene Ontology (GO) analysis uncovered the shared genes exhibited a significant enrichment in regulation of inflammatory response. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the shared genes were primarily involved in immunoregulation by conducting NOD-like receptor (NLR) signaling pathway. Three machine learning results revealed that two overlapping genes (ARG1, HP) were identified as shared hub genes for SAP and sepsis. The immune infiltration results showed that immune cells played crucial part in the pathogenesis of sepsis and the two hub genes were substantially associated with immune cells, which may be a therapy target.ConclusionARG1 and HP may affect SAP and sepsis by regulating inflammation and immune responses, shedding light on potential future diagnostic and therapeutic approaches for SAP-associated sepsis.

Objective To investigate the risk factors of acute kidney injury （AKI） in patients with severe acute pancreatitis （SAP）. Methods Clinical data of 66 patients with SAP were collected in this retrospective study. All patients were divided into the AKI and non-AKI groups according to whether they were complicated with AKI. The risk factors of AKI in patients with SAP were identified by using Logistic regression analysis and receiver operating characteristic （ROC） curve. Results The overall age and Acute Physiology and Chronic Health Evaluation （APACHE） Ⅱscore of SAP patients complicated with AKI were higher than those without AKI， but diabetes mellitus was more common in non-AKI patients （all P < 0.05）. Patients in the AKI group had higher levels of hypersensitive C-reactive protein （CRP）， systemic inflammatory response index （SIRI）， creatinine （Scr）， CRP/Albumin （Alb） index and D-dimer （DDI） upon admission， whereas had lower fasting triglyceride and glucose simple index （TyG）， Alb， total cholesterol， high density lipoprotein cholesterol （HDL-C） and blood calcium levels compared with their counterparts without AKI， and the differences were statistically significant （all P < 0.05）. Stepwise regression analysis showed that increased APACHEⅡ score， increased SIRI index， increased PLR index， decreased SII index and decreased blood calcium were the independent risk factors for SAP patients complicated with AKI （all P < 0.05）. ROC curve results showed that in addition to Scr， APACHEⅡ score， SIRI index and blood calcium had certain diagnostic value in SAP patients complicated with AKI， among which the area under the ROC curve （AUC） of APACHEⅡ score was 0.880 （95% CI 0.787-0.974， optimal cutoff value 11.50）， 0.662 （95% CI 0.521-0.804， optimal cutoff value 10.89） for SIRI index， and 0.754 （95% CI 0.627-0.881， optimal cutoff value 2.07 mmol/L） for blood calcium level （all P < 0.05）. The combination of the above three indexes with Scr could further improve the diagnostic value for AKI in SAP patients， among which the AUC of Scr + blood calcium was the largest， reaching 0.969 （95% CI 0.929-1.000， P < 0.05）. Conclusions APACHEⅡ score， SIRI index， PLR index， SII index and blood calcium level are the independent risk factors of AKI in SAP patients. APACHEⅡ score， SIRI index and blood calcium have diagnostic value in SAP patients complicated with AKI. The combination of these three indexes with Scr can significantly improve the diagnostic efficiency for AKI， providing a novel diagnostic approach for AKI in SAP patients.

Abstract Background Macrophage proinflammatory activation contributes to the pathology of severe acute pancreatitis (SAP) and, simultaneously, macrophage functional changes, and increased pyroptosis/necrosis can further exacerbate the cellular immune suppression during the process of SAP, where cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) plays an important role. However, the function and mechanism of cGAS–STING in SAP-induced lung injury (LI) remains unknown. Methods Lipopolysaccharide (LPS) was combined with caerulein-induced SAP in wild type, cGAS −/− and sting −/− mice. Primary macrophages were extracted via bronchoalveolar lavage and peritoneal lavage. Ana-1 cells were pretreated with LPS and stimulated with nigericin sodium salt to induce pyroptosis in vitro. Results SAP triggered NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation-mediated pyroptosis of alveolar and peritoneal macrophages in mouse model. Knockout of cGAS/STING could ameliorate NLRP3 activation and macrophage pyroptosis. In addition, mitochondrial (mt)DNA released from damaged mitochondria further induced macrophage STING activation in a cGAS- and dose-dependent manner. Upregulated STING signal can promote NLRP3 inflammasome-mediated macrophage pyroptosis and increase serum interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α levels and, thus, exacerbate SAP-associated LI (SAP-ALI). Downstream molecules of STING, IRF7, and IRF3 connect the mtDNA–cGAS–STING axis and the NLRP3–pyroptosis axis. Conclusions Negative regulation of any molecule in the mtDNA–cGAS–STING–IRF7/IRF3 pathway can affect the activation of NLRP3 inflammasomes, thereby reducing macrophage pyroptosis and improving SAP-ALI in mouse model.

Yinan Cao,1– 3,&ast; Fan Li,1– 3,&ast; Zhenxuan Sun,1– 3 Jin Liu,1– 3 Jie Liu,1– 3 Qi Yang,1– 3 Peng Ge,1– 3 Yalan Luo,1– 3 Hailong Chen1– 3 1Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 2Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116044, People’s Republic of China; 3Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yalan Luo; Hailong Chen, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Zhongshan Road 222, Dalian, 116011, Liaoning, People’s Republic of China, Tel +86-411-83635963, Fax +86-411-83622844, Email luoyalanxueshu@163.com; chenhailong@dmu.edu.cnPurpose: Explore the therapeutic effects and regulatory mechanism of Qingyi Decoction (QYD) on severe acute pancreatitis (SAP) associated acute lung injury (ALI).Methods: We identified the constituents absorbed into the blood of QYD based on a network pharmacological strategy. The differentially expressed genes from the GEO database were screened to identify the critical targets of QYD treatment of SAP-ALI. The SAP-ALI rat model was constructed.Some methods were used to evaluate the efficacy and mechanism of QYD in treating SAP-ALI. LPS-stimulated pulmonary microvascular endothelial cell injury simulated the SAP-induced pulmonary endothelial injury model. We further observed the therapeutic effect of QYD and CDK5 plasmid transfection on endothelial cell injury.Results: 18 constituents were absorbed into the blood, and 764 targets were identified from QYD, 25 of which were considered core targets for treating SAP-ALI. CDK5 was identified as the most critical gene. The results of differential expression analysis showed that the mRNA expression level of CDK5 in the blood of SAP patients was significantly up-regulated compared with that of healthy people. Animal experiments have demonstrated that QYD can alleviate pancreatic and lung injury inflammatory response and reduce the upregulation of CDK5 in lung tissue. QYD or CDK5 inhibitors could decrease the expression of NFAT5 and GEF-H1, and increase the expression of ACE-tub in SAP rat lung tissue. Cell experiments proved that QYD could inhibit the expression of TNF-α and IL-6 induced by LPS. Immunofluorescence results suggested that QYD could alleviate the cytoskeleton damage of endothelial cells, and the mechanism might be related to the inhibition of CDK5-mediated activation of NFAT5, GEF-H1, and ACE-tub.Conclusion: CDK5 has been identified as a critical target for pulmonary endothelial injury of SAP-ALI. QYD may partially alleviate microtubule disassembly by targeting the CDK5/NFAT5/GEF-H1 signaling pathway, thus relieving SAP-induced pulmonary microvascular endothelial cell injury. Keywords: Qingyi decoction, severe acute pancreatitis, acute lung injury, CDK5, microtubule

Objective To establish an early prediction model for the diagnosis of severe acute pancreatitis based on the improved machine learning models, and to analyze its clinical value. Methods A case-control study was conducted on 352 patients with acute pancreatitis admitted to the Gastroenterology and Hepatobiliary Surgery Departments of the Army Medical Center of PLA and Emergency and Critical Care Medicine Department of No.945 Hospital of Joint Logistics Support Force of PLA from January 2014 to August 2023.According to the severity of the disease, the patients were divided into the severe group (n=88) and the non-severe group (n=264).The RUSBoost model and improved Archimead optimization algorithm was used to analyze 39 routine laboratory biochemical indicators within 48 h after admission to construct an early diagnosis and prediction model for severe acute pancreatitis.The task of feature screening and hyperparameter optimization was completed simultaneously.The ReliefF algorithm feature importance rank and multivariate logistic analysis were used to analyze the value of the selected features. Results In the training set, the area under curve (AUC) of the improved machine learning model was 0.922.In the testing set, the AUC of the improved machine learning model reached 0.888.The 4 key features of predicting severe acute pancreatitis based on the improved Archimedes optimization algorithm were C-reactive protein, blood chlorine, blood magnesium and fibrinogen level, which were consistent with the results of ReliefF algorithm feature importance ranking and multivariate logistic analysis. Conclusion The application of improved machine learning model analyzing the laboratory examination results can help to early predict the occurrence of severe acute pancreatitis.

Abstract Kaempferol (KA), an natural antioxidant of traditional Chinese medicine (TCM), is extensively used as the primary treatment for inflammatory digestive diseases with impaired redox homeostasis. Severe acute pancreatitis (SAP) was exacerbated by mitochondrial dysfunction and abundant ROS, which highlights the role of antioxidants in targeting mitochondrial function. However, low bioavailability and high dosage of KA leading to unavoidable side effects limits clinical transformation. The mechanisms of KA with poor bioavailability largely unexplored, hindering development of the efficient strategies to maximizing the medicinal effects of KA. Here, we engineered a novel thioketals (TK)-modified based on DSPE-PEG2000 liposomal codelivery system for improving bioavailability and avoiding side effects (denotes as DSPE-TK-PEG2000-KA, DTM@KA NPs). We demonstrated that the liposome exerts profound impacts on damaging intracellular redox homeostasis by reducing GSH depletion and activating Nrf2, which synergizes with KA to reinforce the inhibition of inadequate fission, excessive mitochondrial fusion and impaired mitophagy resulting in inflammation and apoptosis; and then, the restored mitochondrial homeostasis strengthens ATP supply for PAC renovation and homeostasis. Interestingly, TK bond was proved as the main functional structure to improve the above efficacy of KA compared with the absence of TK bond. Most importantly, DTM@KA NPs obviously suppresses PAC death with negligible side effects in vitro and vivo. Mechanismly, DTM@KA NPs facilitated STAT6-regulated mitochondrial precursor proteins transport via interacting with TOM20 to further promote Drp1-dependent fission and Pink1/Parkin-regulated mitophagy with enhanced lysosomal degradation for removing damaged mitochondria in PAC and then reduce inflammation and apoptosis. Generally, DTM@KA NPs synergistically improved mitochondrial homeostasis, redox homeostasis, energy metabolism and inflammation response via regulating TOM20-STAT6-Drp1 signaling and promoting mitophagy in SAP. Consequently, such a TCM’s active ingredients-based nanomedicine strategy is be expected to be an innovative approach for SAP therapy. Graphical Abstract

Abstract Background Compared with other types of acute pancreatitis (AP), hypertriglyceridemic acute pancreatitis (HTG-AP) is younger, recurrent and more prone to exacerbation. Severe HTG-AP has a high fatality rate. Early and accurate prediction of the severity is crucial. However, there is currently a lack of a specific scoring system for the severity of HTG-AP. Aim/Purpose To construct a risk prediction model that can accurately predict severe HTG-AP in the early stage and evaluate its clinical value. Methods The clinical data of 1768 patients with AP admitted to the Second Affiliated Hospital of Anhui Medical University from January 2020 to May 2023 were analyzed retrospectively, and 136 HTG-AP patients were finally selected. Univariate and multivariate analysis were performed for the early onset indicators to identify the independent risk factors for developing SAP in the patients of HTG-AP. Logistic regression was then utilized to establish a risk prediction model for the severity of HTG-AP, which was subsequently evaluated for its performance through discrimination and calibration analysis. Results Of the 136 patients with HTG-AP, 39 patients (28.7%) progressed to severe acute pancreatitis (SAP). Multivariate analysis revealed that CRP, RDW/SC, and D-dimer were independent risk factors for developing SAP in the patients of HTG-AP. The logistic regression analysis to establish prediction model was: Logit P = − 8.101 + 0.008 × CRP + 0.425 × D-dimer + 0.743 × RDW/SC. The receiver-operating characteristics (ROC) curve showed that area under curve (AUC) value of CRP, RDW/SC, D-dimer, and the prediction model were 0.831, 0.843, 0.874, and 0.915, respectively. Moreover, the AUC value of the prediction model and commonly used scoring systems of AP were compared: prediction model (AUC = 0.915) > Ranson (AUC = 0.900) > SOFA (AUC = 0.899) > CTSI (AUC = 0.889) > BISAP (AUC = 0.887). Conclusion CRP, RDW/SC and D-dimer were independent risk factors for SAP in the patients of HTG-AP. Compared with commonly used scoring systems of AP, the prediction model had good clinical prediction ability, providing reference for early identification of the patients developing severe HTG-AP and active intervention.

Background: Severe acute pancreatitis (SAP) is an inflammatory disorder affecting the gastrointestinal system. Intestinal injury plays an important role in the treatment of severe acute pancreatitis. In this study, we mainly investigated the role of S1PR2 in regulating macrophage pyroptosis in the intestinal injury of severe acute pancreatitis. Methods: The SAP model was constructed us ing cerulein and lipopolysaccharide, and the expression of S1PR2 was inhibited by JTE-013 to detect the degree of pancreatitis and intestinal tissue damage in mice. Meanwhile, the level of pyroptosis-related protein was detected by western blot, the level of related mRNA was detected by PCR, and the level of serum inflammatory factors was detected by ELISA. In vitro experiments, LPS+ATP was used to construct the pyroptosis model of THP-1. After knockdown and overexpression of S1PR2, the pyroptosis proteins level was detected by western blot, the related mRNA level was detected by PCR, and the level of cell supernatant inflammatory factors were detected by ELISA. A rescue experiment was used to verify the sufficient necessity of the RhoA/ROCK pathway in S1PR2-induced pyroptosis. Meanwhile, THP-1 and FHC were cocultured to verify that cytokines released by THP-1 after damage could regulate FHC damage. Results: Our results demonstrated that JTE-013 effectively attenuated intestinal injury and inflammation in mice with SAP. Furthermore, we observed a significant reduction in the expression of pyroptosis-related proteins within the intestinal tissue of SAP mice upon treatment with JTE-013. We confirmed the involvement of S1PR2 in THP-1 cell pyroptosis in vitro. Specifically, activation of S1PR2 triggered pyroptosis in THP-1 cells through the RhoA/ROCK signaling pathway. Moreover, it was observed that inflammatory factors released during THP-1 cell pyroptosis exerted an impact on cohesin expression in FHC cells. Conclusion: The involvement of S1PR2 in SAP-induced intestinal mucosal injury may be attributed to its regulation of macrophage pyroptosis. [ABSTRACT FROM AUTHOR]

Objective To investigate the role and mechanism of Rho-related GTP-binding protein F (RhoF)-mediated Th17 polarization in the development of severe acute pancreatitis (SAP). Methods RhoF transgenic mice were randomly divided into control group (n = 10), SAP group (n = 10) and SAP+Y-27632 group (n = 10), and WT mice were randomly divided into control group (n = 10), SAP group (n = 10) and SAP+Y-27632 group (n = 10). SAP models were established in all groups except the control group. The SAP+Y-27632 group was infused with Y-27632 via tail vein after model establishment. T cells in mouse blood samples were isolated for RhoF, p-MYPT1 protein detection and ROCK activity determination, and the percentage of lymphoid CD4+T cells producing IL-17 was analyzed by flow cytometry. Results The expression of RhoF and p-MYPT1 was increased in T cells in the SAP group compared with that in the control group (P < 0.01), and the level of RhoF was closely correlated with that of p-MYPT1 (P = 0.018). The expression of RhoF protein level in T cells of mice in the RhoF group increased by approximately 30% compared to that in the WT group, and the level of spontaneous IL-17 production by CD4+ T cells was significantly increased (P = 0.003). Compared with WT mice, the histological score of pancreatic injury, the expression of RhoF and p-MYPT1 in T cells, the number of IL-17+ T cells and serum IL-17 level in RhoF transgenic mice were significantly increased (P < 0.05). The histological score, RhoF and p-MYPT1 expression of T cells, IL-17+ T cell numbers and serum IL-17 level were significantly lower in the SAP+Y-27632 group than those in the SAP group (P < 0.05). Conclusion RhoF/ROCK signaling pathway-mediated polarization of Th17 cells is involved in the pathogenesis of SAP. [ABSTRACT FROM AUTHOR]

The aim of this study is to explore the risk factors for parenteral nutrition-associated liver disease (PNALD) in patients with severe acute pancreatitis by establishing a verification risk model. A total of 176 patients with severe acute pancreatitis from January 2019 to August 2021, were assigned into the observation group (n = 88) and control group (n = 88) based on the diagnostic results of PNALD, randomly. Their clinical data were recorded. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and alkaline phosphatase (ALP), etc., were detected. The logistic model and desicion tree model were used to analyze the risk factors. Patients in the observation group had higher levels of ALT, AST, TBIL, and lower level of ALP than those of control group (P < 0.05). Multivariate logistic regression analysis revealed that alcohol intake history, ALT ≥69.65 U/L, AST ≥71.27 U/L, TBIL ≥26.27 μmol/L and ALP ≤45.11 U/L were risk factors for PNALD. The levels of ALT and AST in observation group were two times as high as those in the control group, which conformed to the Danan's criteria and accorded with the results of univariate analysis. The regression model showed high consistency with the decision tree model in the prediction of risk factors. Alcohol intake history, ALT ≥69.65 U/L, AST ≥71.27 U/L, TBIL ≥26.27 μmol/L and ALP ≤45.11 U/L are risk factors for PNALD. [ABSTRACT FROM AUTHOR]

Severe acute pancreatitis (SAP) is a life-threatening gastrointestinal emergency. The study aimed to identify biomarkers and investigate molecular mechanisms of SAP. The GSE194331 dataset from GEO database was analyzed using bioinformatics. Differentially expressed genes (DEGs) associated with SAP were identified, and a protein–protein interaction network (PPI) was constructed. Machine learning algorithms were used to determine potential biomarkers. Gene set enrichment analysis (GSEA) explored molecular mechanisms. Immune cell infiltration were analyzed, and correlation between biomarker expression and immune cell infiltration was calculated. A competing endogenous RNA network (ceRNA) was constructed, and biomarker expression levels were quantified in clinical samples using RT-PCR. 1101 DEGs were found, with two modules most relevant to SAP. Potential biomarkers in peripheral blood samples were identified as glutathione S-transferase 1 (MGST1) and glutamyl peptidyltransferase (QPCT). GSEA revealed their association with immunoglobulin regulation, with QPCT potentially linked to pancreatic cancer development. Correlation between biomarkers and immune cell infiltration was demonstrated. A ceRNA network consisting of 39 nodes and 41 edges was constructed. Elevated expression levels of MGST1 and QPCT were verified in clinical samples. In conclusion, peripheral blood MGST1 and QPCT show promise as SAP biomarkers for diagnosis, providing targets for therapeutic intervention and contributing to SAP understanding. [ABSTRACT FROM AUTHOR]

Background: Macrophage proinflammatory activation contributes to the pathology of severe acute pancreatitis (SAP) and, simultaneously, macrophage functional changes, and increased pyroptosis/necrosis can further exacerbate the cellular immune suppression during the process of SAP, where cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) plays an important role. However, the function and mechanism of cGAS–STING in SAP-induced lung injury (LI) remains unknown. Methods: Lipopolysaccharide (LPS) was combined with caerulein-induced SAP in wild type, cGAS −/− and sting −/− mice. Primary macrophages were extracted via bronchoalveolar lavage and peritoneal lavage. Ana-1 cells were pretreated with LPS and stimulated with nigericin sodium salt to induce pyroptosis in vitro. Results: SAP triggered NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation-mediated pyroptosis of alveolar and peritoneal macrophages in mouse model. Knockout of cGAS/STING could ameliorate NLRP3 activation and macrophage pyroptosis. In addition, mitochondrial (mt)DNA released from damaged mitochondria further induced macrophage STING activation in a cGAS- and dose-dependent manner. Upregulated STING signal can promote NLRP3 inflammasome-mediated macrophage pyroptosis and increase serum interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α levels and, thus, exacerbate SAP-associated LI (SAP-ALI). Downstream molecules of STING, IRF7, and IRF3 connect the mtDNA–cGAS–STING axis and the NLRP3–pyroptosis axis. Conclusions: Negative regulation of any molecule in the mtDNA–cGAS–STING–IRF7/IRF3 pathway can affect the activation of NLRP3 inflammasomes, thereby reducing macrophage pyroptosis and improving SAP-ALI in mouse model. [ABSTRACT FROM AUTHOR]

Objectives: As a serious complication of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), infected pancreatic necrosis (IPN) can lead to a prolonged course of interventional therapy. Most predictive models designed to identify such patients are complex or lack validation. The aim of this study was to develop a predictive model for the early detection of IPN in MSAP and SAP. Methods: A total of 594 patients with MSAP or SAP were included in the study. To reduce dimensionality, least absolute shrinkage and selection operator regression analysis was used to screen potential predictive variables, a nomogram was then constructed using logistic regression analysis. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical efficacy of the model. External data were also obtained to further validate the constructed model. Results: There were 476, 118, and 82 patients in the training, internal validation, and external validation cohorts, respectively. Platelet count, hematocrit, albumin/globulin, severity of acute pancreatitis, and modified computed tomography severity index score were independent factors for predicting IPN in MSAP and SAP. The area under the ROC curves were 0.923, 0.940, and 0.817, respectively, in the three groups. There was a good consistency between the actual probabilities and the predicted probabilities. DCA revealed excellent clinical utility. Conclusion: The constructed nomogram is a simple and feasible model that has good clinical predictive value and efficacy in clinical decision‐making for IPN in MSAP and SAP. [ABSTRACT FROM AUTHOR]

Kaempferol (KA), an natural antioxidant of traditional Chinese medicine (TCM), is extensively used as the primary treatment for inflammatory digestive diseases with impaired redox homeostasis. Severe acute pancreatitis (SAP) was exacerbated by mitochondrial dysfunction and abundant ROS, which highlights the role of antioxidants in targeting mitochondrial function. However, low bioavailability and high dosage of KA leading to unavoidable side effects limits clinical transformation. The mechanisms of KA with poor bioavailability largely unexplored, hindering development of the efficient strategies to maximizing the medicinal effects of KA. Here, we engineered a novel thioketals (TK)-modified based on DSPE-PEG2000 liposomal codelivery system for improving bioavailability and avoiding side effects (denotes as DSPE-TK-PEG2000-KA, DTM@KA NPs). We demonstrated that the liposome exerts profound impacts on damaging intracellular redox homeostasis by reducing GSH depletion and activating Nrf2, which synergizes with KA to reinforce the inhibition of inadequate fission, excessive mitochondrial fusion and impaired mitophagy resulting in inflammation and apoptosis; and then, the restored mitochondrial homeostasis strengthens ATP supply for PAC renovation and homeostasis. Interestingly, TK bond was proved as the main functional structure to improve the above efficacy of KA compared with the absence of TK bond. Most importantly, DTM@KA NPs obviously suppresses PAC death with negligible side effects in vitro and vivo. Mechanismly, DTM@KA NPs facilitated STAT6-regulated mitochondrial precursor proteins transport via interacting with TOM20 to further promote Drp1-dependent fission and Pink1/Parkin-regulated mitophagy with enhanced lysosomal degradation for removing damaged mitochondria in PAC and then reduce inflammation and apoptosis. Generally, DTM@KA NPs synergistically improved mitochondrial homeostasis, redox homeostasis, energy metabolism and inflammation response via regulating TOM20-STAT6-Drp1 signaling and promoting mitophagy in SAP. Consequently, such a TCM's active ingredients-based nanomedicine strategy is be expected to be an innovative approach for SAP therapy. [ABSTRACT FROM AUTHOR]