Current severe acute pancreatitis (SAP) murine models face significant limitations. The sodium taurocholate method consistently induces pancreatic necrosis but demands intricate surgical procedures, leading to high variability and infection risks. In contrast, the arginine approach causes acinar cell damage without fully mimicking clinical injury pathways. Furthermore, the caerulein-lipopolysaccharide (CAE-LPS) model, while operationally straightforward, fails to replicate persistent organ failure due to LPS’s rapid clearance, thereby inadequately capturing the lethal trajectory observed in clinical SAP patients who succumb to the disease. To address these gaps, we developed a SAP mouse model by integrating two key pathogenic mechanisms: trypsin-driven complement activation and sustained complement hyperactivation as drivers of multiple organ failure. The SAP model was established by combining CAE-induced pancreatic injury with zymosan (ZYM)-mediated complement activation. Dosing and combination protocols were meticulously optimized and were followed by a comprehensive longitudinal analysis during the acute phase (0–12 days), with comparisons to the CAE-LPS model. The optimized protocol involved nine intraperitoneal CAE injections (100 μg/kg each) followed by a single ZYM dose (1000 mg/kg). This regimen triggered pancreatic necrosis, inflammatory infiltration, and multi-organ damage (liver, kidney, intestine). Notably, the model demonstrated sustained complement activation and a mortality pattern in non-survivors that more closely aligned with clinical SAP outcomes than the CAE-LPS model. This novel model offers a robust platform for advancing SAP research, bridging the divide between preclinical studies and clinical translation.

Abstract Mesenchymal stem cells (MSCs) have a moderate impact on the therapy of severe acute pancreatitis. This study seeks to improve the therapeutic effectiveness of MSCs. By preconditioning them via the upregulation of critical anti‐inflammatory molecules, so diminishing immune rejection, we are creating a path for more effective treatments. Aloe emodin (AE), a natural active monomer with low‐toxicity, in conjunction with interferon gamma (IFN‐γ) (I‐AE), markedly upregulated immunosuppressive molecules indoleamine 2,3‐dioxygenase and programmed cell death‐Ligand 1 in MSCs, thereby pharmacologically modulating the inhibition of CD4 − T cell activation in vitro effectively. Transient transfection of small interfering RNA silenced the class II transactivator (CIITA) gene expression of umbilical cord mesenchymal stem cells (UMSCs) interfering with human leukocyte antigen class II expression to avert immune rejection. AE‐loaded nanoparticles efficiently maintained proliferation inhibition of MSCs within a manageable range by sustained release. UMSCs pretreated by I‐AE with CIITA silencing preserved pancreatic structure as evidenced by diminished acinar cell death, reduced pancreatic edema and inflammation, and significantly lowered serum amylase levels The encouraging potential of UMSCs with CIITA gene silencing combined with AE and IFN‐γ pretreatment offers optimism for clinical application in pancreatitis therapy.

PURPOSE:Pancreatic intraductal papillary mucinous neoplasms (IPMN) are precursors to pancreatic cancer, with an increasing incidence due to advances in imaging techniques. This study aimed to identify risk factors for malignant transformation in IPMN and develop a predictive model using data from a large medical center in western China. METHODS:Patients with IPMN admitted to West China Hospital between January 2010 and February 2022 were included in this study. They were divided into benign and malignant. Characteristic parameters and laboratory results were collected. The training set and test set were randomly divided at a ratio of 7:3. Least absolute shrinkage and selection operator regression was used to select potential prognostic factors. A nomogram was developed by logistic regression. Receiver operating characteristic curves and calibration curves were used to evaluate the model's predictive performance. RESULTS:We retrospectively analyzed 182 patients, identifying six independent predictors of malignancy: classification, cyst wall thickening, abrupt changes in main pancreatic duct caliber, maximum tumor diameter, maximum main pancreatic duct diameter, and lnCA19-9. We developed a nomogram with an area under the curve of 0.86 in the training set and 0.81 in the test set. The model showed strong predictive ability, providing a valuable tool for clinicians to guide preoperative decision-making. CONCLUSION:Our study offers the first predictive model for malignant IPMN in western China and highlights the importance of comprehensive risk assessment, incorporating clinical, imaging, and laboratory data.

INTRODUCTION:Gastrointestinal fistula (GIF) is a rare but severe complication in patients with necrotizing pancreatitis (NP), significantly prolonging disease course and increasing morbidity and mortality. Its subtle and nonspecific early symptoms often delay diagnosis and intervention. Despite its clinical significance, the low incidence of GIF in NP has resulted in limited research and a lack of consensus on optimal diagnostic and therapeutic strategies. AREAS COVERED:This review focuses on the epidemiology, pathophysiology, diagnostic approaches, and therapeutic management of GIF in NP patients. Imaging techniques, such as contrast-enhanced computed tomography and endoscopy, have been integral to early diagnosis. Advances in interventional and surgical techniques provide new avenues for treatment, but variability in clinical practice highlights the need for standardized protocols. EXPERT OPINION:Recent advances in diagnostic imaging have improved the detection of GIF, while innovations in interventional and surgical treatments show promise. Current research is still insufficient and varied. Future research should focus on developing diagnostic methods and treatment measures for such complications. By improving early diagnosis and offering insights into effective management strategies, it is hoped that patient outcomes can be improved.

Acute pancreatitis (AP) is a prevalent gastrointestinal disorder. The immune response plays a crucial role in AP progression. However, the impact of immune regulatory checkpoint PD-L1 on severe acute pancreatitis (SAP) remains uncertain. Hence, this study aimed to examine the influence of PD-L1 on SAP. We assessed PD-L1 expression in neutrophils and monocytes obtained from SAP patients. We induced SAP in C57BL/6J mice, PD-L1 gene-deficient mice, and PD-L1 humanized mice using intraperitoneal injections of cerulein plus lipopolysaccharide. Prior to the initial cerulein injection, a PD-L1 inhibitor was administered. Pancreatic tissues were collected for morphological and immunohistochemical evaluation, and serum levels of amylase, lipase, and cytokines were measured. Flow cytometry analysis was performed using peripheral blood cells. The expression of PD-L1 in neutrophils and monocytes was significantly higher in SAP patients compared to healthy individuals. Likewise, the expression of PD-L1 in inflammatory cells in the peripheral blood of SAP-induced C57BL/6J mice was notably higher than in the control group. In mice with PD-L1 deficiency, SAP model exhibited lower pancreatic pathology scores, amylase, lipase, and cytokine levels compared to wild-type mice. PD-L1 deletion resulted in reduced neutrophil apoptosis, leading to an earlier peak in neutrophil apoptosis. Furthermore, it decreased early monocyte apoptosis and diminished the peak of T lymphocyte apoptosis. Within the SAP model, administration of a PD-L1 inhibitor reduced pancreatic pathology scores, amylase, lipase, and cytokine levels in both C57BL/6J mice and PD-L1 humanized mice. These findings suggest that inhibiting PD-L1 expression can alleviate the severity of SAP.

Background and aims: Partial pancreatectomy, commonly used for chronic pancreatitis, or pancreatic lesions, has diverse impacts on endocrine and metabolism system. The study aims to determine the global prevalence of new-onset, worsening, and resolution of diabetes following partial pancreatectomy. Methods: The authors searched PubMed, Embase, Web of Science, and Cochrane Library from inception to October, 2023. DerSimonian-Laird random-effects model with Logit transformation was used. Sensitivity analysis, meta-regression, and subgroup analysis were employed to investigate determinants of the prevalence of new-onset diabetes. Results: A total of 82 studies involving 13 257 patients were included. The overall prevalence of new-onset diabetes after partial pancreatectomy was 17.1%. Univariate meta-regression indicated that study size was the cause of heterogeneity. Multivariable analysis suggested that income of country or area had the highest predictor importance (49.7%). For subgroup analysis, the prevalence of new-onset diabetes varied from 7.6% (France, 95% CI: 4.3-13.0) to 38.0% (UK, 95% CI: 28.2-48.8, P<0.01) across different countries. Patients with surgical indications for chronic pancreatitis exhibited a higher prevalence (30.7%, 95% CI: 21.8-41.3) than those with pancreatic lesions (16.4%, 95% CI: 14.3-18.7, P<0.01). The type of surgical procedure also influenced the prevalence, with distal pancreatectomy having the highest prevalence (23.7%, 95% CI: 22.2-25.3, P<0.01). Moreover, the prevalence of worsening and resolution of preoperative diabetes was 41.1 and 25.8%, respectively. Conclusions: Postoperative diabetes has a relatively high prevalence in patients undergoing partial pancreatectomy, which calls for attention and dedicated action from primary care physicians, specialists, and health policy makers alike.

Objectives To assess the feasibility of estimating an EQ-5D-5L value set using a small study design in cancer patients and to compare the EQ-5D-5L values based on the preferences of cancer patients with those of the general public. Methods Patients with clinically diagnosed cancers were recruited from two hospitals in Shanghai, China. In face-to-face interviews using the EQ-PVT survey, health states were valued by cancer patients using both cTTO and DCE methods. cTTO data was modelled alone or jointly with DCE data. Forty-eight models using different model specifications (cross-attribute level effect [CALE] and additive models), random/fixed effects model assumptions, data heteroscedasticity and censoring were estimated. The best performed model was identified in terms of monotonicity of estimated model coefficients and out-of-sample prediction accuracy. Results Data collected from 221 cancer patients who participated in the study were included. The hybrid CALE model using both TTO and DCE data performed best in terms of prediction accuracy (Lin’s concordance coefficient = 0.989; root mean squared error = 0.058) and suggested that pain/discomfort and anxiety/depression were the most undesirable health problems. Compared to values based on general Chinese public’s health preferences, the values based on cancer patients’ preferences were much higher and lower for health states characterized by extreme mobility problems and severe/extreme pain or discomfort, respectively. Conclusion This study demonstrated the feasibility of using a small design to develop EQ-5D-5L value sets based on cancer patients’ health preferences. Since there were signs of differences between preferences of patients and general population, it may be valuable to develop patient-specific value sets and use them in clinical decision making and economic evaluations.

Laparoscopic central pancreatectomy (LCP) has been implemented in pancreatic surgery; however, open surgery is still the predominant approach for central pancreatectomy (CP). Our objective was to compare LCP with open CP (OCP). Data were collected from patients with tumours located in the pancreatic neck and proximal body who underwent CP in the Department of Pancreatic Surgery West China Hospital from January 1, 2010, to June 30, 2019. A comparison between the LCP and OCP groups was performed. Fifteen patients underwent CP via the laparoscopic approach, and 96 patients underwent CP via the open approach. Using 1:2 propensity score matching (PSM), 12 patients in the LCP group were matched to 21 in the OCP group. Regarding safety, postoperative pancreatic fistula (POPF) was not significantly different between the two groups (13.3

目的 评价蔗糖铁注射液、多糖铁胶囊及其他口服铁补充制剂治疗血液透析患者肾性贫血方案的成本-效果,为临床药物选择提供参考.方法 通过对肾性贫血临床治疗结果进行单组率Meta分析获得各干预措施的临床治疗有效率,并建立决策树模型对其成本与效果进行经济学评价,并对参数不确定性进行单因素敏感性分析.结果 共纳入 670 例患者进行成本-效果分析.结果 显示,在多糖铁胶囊有效率较低的情况下,意愿支付＞22590.61 元,蔗糖铁静脉注射液具有最好的成本-效果.而在其他口服补铁制剂中,多糖铁胶囊治疗血液透析患者肾性贫血最具经济学效益.结论 血液透析患者肾性贫血首选静脉补铁治疗.静脉补铁副作用较大或需长期用药情况下,口服铁剂治疗肾性贫血首选多糖铁胶囊.

Single-minded homolog 2 (SIM2) has been identified as a potential contributor to the development of solid tumors. Despite this, there is a lack of comprehensive research regarding its biological role and underlying mechanism within pancreatic cancer (PC), as well as its prognostic impact. This study systematically evaluated the expression level and clinical significance of SIM2 in patients with PC using various databases, including The Cancer Genome Atlas, KM Plotter, and gene expression profiling interactive analysis. To investigate the relationship between SIM2 expression and immune cell infiltration, we conducted ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) analyses. Single-minded homolog 2 was up-regulated in patients with PC. Pancreatic cancer patients with higher SIM2 expression had poorer overall survival rates. Gene set enrichment analysis results suggested that SIM2 may have a significant impact on the progression of PC and the regulation of immune responses. According to the ssGSEA algorithm, SIM2 has a negative correlation with the levels of infiltrating TFH, mast cells, and pDC. Our study demonstrated that SIM2 serves as a biomarker, and is associated with both prognosis and immune infiltration in PC. This provides a solid foundation for future investigations into the precise role of SIM2 in the carcinogenesis and progression of PC.

Some acute inflammatory diseases are often exacerbated during or after hospitalization, leading to some severe manifestations like systemic inflammatory response syndrome, multiple organ failure, and high mortality. Early clinical predictors of disease severity are urgently needed to optimize patient management for better prognosis. The existing clinical scoring system and laboratory tests cannot circumvent the problems of low sensitivity and limited specificity. Extracellular vesicles (EVs) are heterogeneous nanosecretory vesicles containing various biomolecules related to immune regulation, inflammation activation, and inflammation-related complications. This review provides an overview of EVs as inflammatory mediators, inflammatory signaling pathway regulators, promoters of inflammatory exacerbation, and markers of severity and prognosis. Currently, although relevant biomarkers are clinically available or are in the preclinical research stage, searching for new markers and detection methods is still warranted, as the problems of low sensitivity/specificity, cumbersome laboratory operation and high cost still plague clinicians. In-depth study of EVs might open a door in the search for novel predictors.

Abstract Inflammation is a prevalent pathological process that accompanies the onset and progression of numerous acute and chronic diseases including rheumatoid arthritis, sepsis, pancreatitis, atherosclerosis, ischaemic brain/heart disease and so forth. However, conventional anti‐inflammatory drugs have certain disadvantages such as nonspecific tissue distribution, low bioavailability, and a short half‐life, resulting in off‐target side effects and limited efficacy in disease control. To address these issues, nanoparticles have emerged as a novel therapeutic paradigm in this field to attain inflammation targeting and improve drug pharmacokinetic properties via the well‐recognized enhanced permeability and retention (EPR) effect at the inflammatory site. Existing reviews are predominantly centered on inflammatory pathology introduction and vector design. As a necessary complement, this review mainly elaborates on the introduction of inflammation core events, the history of the drug delivery system for anti‐inflammatory drugs, the action mechanism of inflammation targeting vectors, nanoparticle classification based on targeting moiety, methods to combine targeting moiety with core nanoparticles, techniques to assess targetability in vitro and in vivo and finally the challenges and prospects in this field. The information provided herein offers practical guidance to researchers seeking to develop and evaluate inflammation targeting vectors rationally.

BACKGROUND The severity of acute pancreatitis in pregnancy (APIP) is correlated with higher risks of maternal and fetal death. AIM To develop a nomogram that could predict moderately severe and severe acute pancreatitis in pregnancy (MSIP). METHODS Patients with APIP admitted to West China Hospital between January 2012 and December 2018 were included in this study. They were divided into mild acute pancreatitis in pregnancy (MAIP) and MSIP. Characteristic parameters and laboratory results were collected. The training set and test set were randomly divided at a ratio of 7:3. Least absolute shrinkage and selection operator regression was used to select potential prognostic factors. A nomogram was developed by logistic regression. A random forest model was used to validate the stability of the prediction factors. Receiver operating characteristic curves and calibration curves were used to evaluate the model's predictive performance. RESULTS A total of 190 patients were included in this study. A total of 134 patients (70.5%) and 56 patients (29.5%) were classified as having MAIP and MSIP, respectively. Four independent predictors (lactate dehydrogenase, triglyceride, cholesterol, and albumin levels) were identified for MSIP. A nomogram prediction model based on these factors was established. The model had areas under the curve of 0.865 and 0.853 in the training and validation sets, respectively. The calibration curves showed that the nomogram has a good consistency. CONCLUSION A nomogram including lactate dehydrogenase, triglyceride, cholesterol, and albumin levels as independent predictors was built with good performance for MSIP prediction.

Cancer associated fibroblasts (CAFs) support tumors via multiple mechanisms, including maintaining the immunosuppressive tumor microenvironment and limiting infiltration of immune cells. The prolyl isomerase Pin1, whose overexpression in CAFs has not been fully profiled yet, plays critical roles in tumor initiation and progression. To decipher effects of selective Pin1 inhibition in CAFs on pancreatic cancer, here we formulate a DNA-barcoded micellular system (DMS) encapsulating the Pin1 inhibitor AG17724. DMS functionalized with CAF-targeting anti-FAP-α antibodies (antiCAFs-DMS) can selectively inhibit Pin1 in CAFs, leading to efficacious but transient tumor growth inhibition. We further integrate DNA aptamers (AptT), which can engage CD8+ T lymphocytes, to obtain a bispecific antiCAFs-DMS-AptT system. AntiCAFs-DMS-AptT inhibits tumor growth in subcutaneous and orthotopic pancreatic cancer models.

Background: With uncontrolled inflammatory progression, acute pancreatitis (AP) can progress to severe acute pancreatitis (SAP). Inflammation and parenchymal cell death are key pathologic responses of AP. Toll-like receptor 4 (TLR4) plays a pro-inflammatory role in AP. Myeloid differentiation primary response protein 88 (MyD88) is the most essential utilized adaptor of TLR4, but its role in AP remains unclear. We investigated the potential role of MyD88 in the pathogenesis of AP.Methods: An AP model was induced by administering either cerulein or L-arginine to wild-type or MyD88-deficient mice. Additionally, receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 (Nec-1) was administered to the MyD88-/- mice. The severity of AP was determined by measuring serum amylase and lipase activities, quantifying pancreatic myeloperoxidase (MPO) activity, and histological examination. The effects of MyD88 deletion on cell death and the inflammatory response were determined by measuring apoptosis, necrosis, and inflammatory cytokines. Western blot was used to assess the necrotic mediators, RIP1 and RIP3.Results: The deletion of MyD88 resulted in more severe acute experimental pancreatitis as assessed by increased amylase and lipase activities, increased pancreatic MPO activity, a reduced anti-inflammatory response, reduced apoptosis, and increased necrosis. Additionally, Nec-1 treatment significantly reduced necrosis in the MyD88-/- mice.Conclusions: The deletion of MyD88 inhibited the TLR4/MyD88-dependent pathway mediated protective immune defense response and enhanced TLR4/MyD88-independent TRIF pathway-mediated pancreatic necrosis, which in turn aggravated the severity of AP. The critical role of MyD88 in immune defense response and cell death indicates that MyD88 represents a potential therapeutic target in the management of AP.

Background: Sever acute pancreatitis (SAP) is a critical disease with high mortality, and lack of clinically available treatments with specificity and effectiveness. Bone marrow derived mesenchymal stem cells (BMSCs) exhibited moderate effect on AP which needs further improvement.Methods: Pancreatic infiltrating lymphocytes were analyzed to demonstrate the intervention of BMSCs on inflammatory cell infiltration of AP. Gene silencing with siRNA and small molecule inhibitor were utilized to determine the key effector molecule of BMSCs on AP. Pharmacological regulation and nanotechnology were introduced to further ameliorate BMSCs action.Results: It was revealed that BMSCs prevent the progression of acute pancreatitis (AP) by reducing recruitment of macrophages, neutrophils and CD4 thorn T cells in the lesion site. The pivotal role of chemokine-iNOS-IDO axis for BMSCs to intervene AP was confirmed. Compared with any single drug, Chloroquine/Tamoxifen combination together with IFN-gamma pronouncedly up-regulated the transcription of several MSC immune regulators such as COX 2, PD-L1, HO-1 especially iNOS/IDO. As expected, BMSCs and human umbilical cord mesenchymal stem cells (UMSCs) pretreated with CQ/TAM/IFN-gamma exerted enhanced intervention in AP and SAP mice. Moreover, pretreatment with CQ-LPs/TAM-NPs combination not only counteracted MSCs proliferation inhibition induced by free drugs but also enhanced their efficacy.Conclusion: Under the background of rapid progress in MSCs clinical translation, this study focuses on the urgent clinical issue and initiates an original mechanism-based strategy to promote intervention on severity progression of SAP, which promises its clinical translation in future.

Background: LncRNA GAS8-AS1 inhibits thyroid carcinoma, but its function in other malignancies is unknown. The present study aimed to investigate the involvement of GAS8-AS1 in pancreatic cancer (PC). Methods: The present study included 68 PC patients (38 males and 30 females, 42-66 years, 52.1 ± 4.5) and 62 healthy volunteers (28 males and 24 females, 43-67 years, 52.3 ± 4.9). Real-time quantitative PCR, transient cell transfection, and in vitro cell migration and invasion assays were applied for the research. Results: The study showed that plasma GAS8-AS1 was lower in PC patients than in healthy controls. Downregulation of plasma GAS8-AS1 distinguished early-stage PC patients from healthy controls. Patients with low GAS8-AS1 plasma levels showed a significantly lower 5-year overall survival rate. Plasma miR-1179 levels were also significantly lower in PC patients than in healthy controls and were positively correlated with plasma GAS8-AS1 levels in PC patients but not healthy controls. GAS8-AS1 overexpression upregulated miR-1179, and MiR-1179 overexpression increased GAS8-AS1 level. Overexpression of both GAS8-AS1 and miR-1179 inhibited PC cell migration and invasion. Conclusion: GAS8-AS1 may promote PC by positively interacting with miR-1179.