Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models.

BACKGROUND: Acute pancreatitis (AP) encompasses a spectrum of pancreatic inflammatory conditions, ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure. Given the challenges associated with obtaining human pancreatic samples, research on AP predominantly relies on animal models. In this study, we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models. AIM: To investigate the shared molecular changes underlying the development of AP across varying severity levels. METHODS: AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide (LPS). Additionally, using Ptf1α to drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J- hM3/Ptf1α(cre) mice were administered Clozapine N-oxide to induce AP. Subsequently, we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus (GEO) database. RESULTS: Caerulein-induced AP showed severe inflammation and edema, which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis. Compared with the control group, RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model. Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway, TLR signaling pathway, and NF-κB signaling pathway, alongside elevated levels of apoptosis-related pathways, such as apoptosis, P53 pathway, and phagosome pathway. The significantly elevated genes in the TLR and NOD-like receptor signaling pathways, as well as in the apoptosis pathway, were validated through quantitative real-time PCR experiments in animal models. Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood, while TLR1, TLR7, RIPK3, and OAS2 genes exhibited marked elevation in human AP. The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP. The transgenic mouse model hM3/Ptf1α(cre) successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway, indicating that these pathways represent shared pathological processes in AP across different models. CONCLUSION: The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP, notably the MYD88 gene. Apoptosis holds a central position in the necrotic processes of AP, with TUBA1A and GADD45A genes exhibiting prominence in human AP.

Etiological Changes and Prognosis of Hospitalized Patients with Acute Pancreatitis Over a 15-Year Period.

BACKGROUND: The worldwide incidence of acute pancreatitis (AP) is increasing, but the dominant etiology of AP may vary by country. Mixed etiologies are involved in the increase in the number of AP patients. AIMS: This study was to analyze the etiological changes and prognosis of AP patients and explore the prognosis of AP patients with mixed etiologies. METHODS: Using a retrospective analysis method, AP patients hospitalized from January 2007 to December 2021 were selected from a pancreatic center in Nanchang, China. Trends in the main etiologies were analyzed, and the severity and prognosis of different etiologies were compared. RESULTS: A total of 10,071 patients were included. Cholelithiasis (56.0%), hyperlipidemia (25.3%), and alcohol (6.5%) were the top three etiologies. The proportion of acute biliary pancreatitis (ABP) showed a decreasing trend, while the proportion of hypertriglyceridemic pancreatitis (HTGP) and alcoholic AP showed an increasing trend (all ptrend < 0.001). The incidence of organ failure and necrotizing pancreatitis was higher in patients with HTGP than in those with AP induced by other etiologies (all p < 0.05). There was no statistically significant difference in mortality among patients with different etiologies. Patients with AP due to a mixed hypertriglyceridemia-alcoholic etiology had higher ICU admission rates and were more severe than those with AP induced by other mixed etiologies. CONCLUSION: In the past 15 years, the proportion of ABP has trended downward, while those of HTGP and alcoholic AP have risen. Among patients with mixed etiologies, those with a mixed hypertriglyceridemia-alcoholic etiology had a worse prognosis.

Gastrointestinal Fistulas in Necrotizing Pancreatitis Receiving a Step-Up Approach Incidence, Risk Factors, Outcomes and Treatment.

Purpose: Necrotizing pancreatitis (NP) complicated by gastrointestinal fistula is challenging and understudied. As the treatment of necrotizing pancreatitis changed to a step-up strategy, we attempted to evaluate the incidence, risk factors, clinical outcomes and treatment of gastrointestinal fistulas in patients receiving a step-up approach. Methods: Clinical data from 1274 patients with NP from 2014-2022 were retrospectively analyzed. Multivariable logistic regression analysis was conducted to identify risk factors and propensity score matching (PSM) to explore clinical outcomes in patients with gastrointestinal fistulas. Results: Gastrointestinal fistulas occurred in 8.01% (102/1274) of patients. Of these, 10 were gastric fistulas, 52 were duodenal fistulas, 14 were jejunal or ileal fistulas and 41 were colonic fistulas. Low albumin on admission (OR, 0.936), higher CTSI (OR, 1.143) and invasive intervention prior to diagnosis of gastrointestinal fistula (OR, 5.84) were independent risk factors for the occurrence of gastrointestinal fistula, and early enteral nutrition (OR, 0.191) was a protective factor. Patients who developed a gastrointestinal fistula were in a worse condition on admission and had a poorer clinical outcome (p<0.05). After PSM, both groups of patients had similar baseline information and clinical characteristics at admission. The development of gastrointestinal fistulas resulted in new-onset persistent organ failure, increased open surgery, prolonged parenteral nutrition and hospitalization, but not increased mortality. The majority of patients received only conservative treatment and minimally invasive interventions, with 7 patients (11.3%) receiving surgery for upper gastrointestinal fistulas and 11 patients (26.9%) for colonic fistulas. Conclusion: Gastrointestinal fistulas occurred in 8.01% of NP patients. Independent risk factors were low albumin, high CTSI and early intervention, while early enteral nutrition was a protective factor. After PSM, gastrointestinal fistulas resulted in an increased proportion of NP patients receiving open surgery and prolonged hospitalization. The majority of patients with gastrointestinal fistulas treated with step-up therapy could avoid surgery.

Elevated CK-MB levels are associated with adverse clinical outcomes in acute pancreatitis: a propensity score-matched study.

Aim: Cardiac injury, reflected by the measured concentrations of chemicals released from injured cardiac muscle, is common in acute pancreatitis (AP). However, there is no adequate evidence assessing the impact of cardiac injury on AP-related outcomes. Creatine kinase-myocardial band (CK-MB) mainly exists in the myocardium. Therefore, we sought to evaluate the relationship between the increase in CK-MB and the adverse clinical outcomes of AP. Methods: This propensity score-matched study analyzed AP patients admitted to the Department of Gastroenterology in the First Affiliated Hospital of Nanchang University from June 2017 to July 2022. Propensity score matching and multivariate logistic regression analysis were used to explore the relationship between CK-MB elevation and AP outcome variables. Results: A total of 5,944 patients were screened for eligibility, of whom 4,802 were ultimately enrolled. Overall, 896 (18.66%) of AP patients had elevated (>24 U/ml) CK-MB levels, and 895 (99.89%) were paired with controls using propensity score matching. The propensity score-matched cohort analysis demonstrated that mortality (OR, 5.87; 95% CI, 3.89-8.84; P < 0.001), severe acute pancreatitis (SAP) (OR, 2.74; 95% CI, 2.23-3.35; P < 0.001), and infected necrotizing pancreatitis (INP) (OR, 3.40; 95% CI, 2.34-4.94; P < 0.001) were more frequent in the elevated CK-MB (>24 U/ml) group than in the normal CK-MB (≤ 24 U/ml) group. Using the multivariate logistic regression analysis, elevated CK-MB levels were independently associated with increased mortality (OR, 2.753, 95% CI, 2.095-3.617, P < 0.001), SAP incidence (OR, 2.223, CI, 1.870-2.643, P < 0.001), and INP incidence (OR, 1.913, 95% CI, 1.467-2.494, P < 0.001). CK-MB elevation was an independent risk factor for adverse clinical outcomes in AP patients. Conclusion: CK-MB elevation was significantly related to adverse outcomes in AP patients, which makes it a potentially useful laboratory parameter for predicting adverse clinical outcomes of AP.

Hepatic Krüppel-like factor 14 regulates lipid metabolism in nonalcoholic steatohepatitis mice.

Excessive lipid accumulation is a critical characteristic in the development of nonalcoholic steatohepatitis (NASH). The underlying molecular mechanism, however, is unclear. In this study, we explored whether and how Krüppel-like factor 14 (KLF14) affects hepatic lipid metabolism in NASH. KLF14 expression was detected in NASH patients and mice fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Adeno-associated viruses and adenoviruses were used to alter hepatic KLF14 expression in vivo or in vitro to investigate how KLF14 functions in lipid regulation. The molecular mechanisms were explored using RNA-seq, luciferase reporter, and ChIP assays. The fatty liver phenotype was analyzed histopathologically, and serum and hepatocyte biochemical parameters were measured. The NASH mouse model developed quickly in C57BL/6J mice fed a CDAHFD for 8 weeks. We found that KLF14 expression was decreased in NASH patients and CDAHFD mice. Oleic acid and palmitic acid treatment also reduced KLF14 levels in hepatocytes. KLF14 knockdown downregulated the genes involved in fatty acid oxidation, promoting the progression of hepatic steatosis. In contrast, hepatic KLF14 overexpression alleviated lipid accumulation and oxidative stress in CDAHFD mice. These effects resulted from direct activation of the PPARα signaling pathway. PPARα inhibition diminished the KLF14 overexpression-reduced protective effects against steatosis in OA&PA-treated MPHs and AAV-KLF14-infected CDAHFD mice. These data reveal that hepatic KLF14 regulates lipid accumulation and oxidative stress through the KLF14-PPARα pathway as NASH progresses. KLF14 may be a novel therapeutic target for hepatic steatosis.

The severity and infection of acute pancreatitis may increase the risk of bleeding in patients undergoing EUS-guided drainage and endoscopic necrosectomy: a large retrospective cohort.

BACKGROUND: There has been great progress in the use of endoscopic ultrasound (EUS)-guided drainage in acute pancreatitis patients using a novel lumen-apposing metal stent (LAMS) in the last decade, but some patients experience bleeding. Our research analyzed the preprocedural risk factors for bleeding. METHODS: From July 13, 2016 to June 23, 2021, we retrospectively analyzed all patients who received endoscopic drainage by the LAMS in our hospital. Univariate and multivariate statistical analyses were used to identify the independent risk factors. We plotted ROC curves based on the independent risk factors. RESULTS: A total of 205 patients were analyzed and 5 patients were excluded. A total of 200 patients were included in our research. Thirty (15%) patients presented with bleeding. In the multivariate analysis, computed tomography severity index score (CTSI) score [odds ratio (OR), 2.66; 95% CI: 1.31-5.38; P = 0.007], positive blood cultures [odds ratio (OR), 5.35; 95% CI: 1.31-21.9; P = 0.02], and Acute Physiology and Chronic Health Evaluation II (APACHE II) score [odds ratio (OR), 1.14; 95% CI: 1. 01-1.29; P = 0.045] were associated with bleeding. The area under the ROC curve of the combined predictive indicator was 0.79. CONCLUSION: Bleeding in endoscopic drainage by the LAMS is significantly associated with the CTSI score, positive blood cultures, and APACHE II score. This result could help clinicians make more appropriate choices.

One hundred most cited articles related to Endoscopic retrograde cholangiopancreatography: A bibliometric analysis.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) has developed over the past few decades into a reliable technology for diagnostic and therapeutic purposes. Through a bibliometric analysis, this research attempted to evaluate the characteristics of the top 100 articles on ERCP that had the most citations. Methods: We extracted pertinent publications from the Web of Science Core Collection (WoSCC) on July 9, 2022. The top 100 ERCP articles with the most citations were identified and analyzed. The following data were extracted: publication year, country/region, organization, total citation times, annual citation times, research type and research field, etc. To implement the network's visual analysis, a bibliographic coupling network based on keywords was built using the VOSviewer 1.6.17 program. Results: The journal with the most publications were GASTROINTESTINAL ENDOSCOPY, with 45 articles. Most of the top 100 articles came from the United States (n = 47) and Italy (n = 14). Indiana University and the University of Amsterdam were among the most important institutions in ERCP research. ML Freeman of the University of Minnesota contributed the highest number (n = 9) and the most highly cited paper. The age of the paper and article type is closely related to citation frequency. Of the 100 most-cited articles, clinical application in the field of ERCP has focused on three aspects: diagnosis, treatment, and complications. Clinical use of ERCP has shifted from diagnosis to treatment. Post-ERCP pancreatitis is the focus of attention, and the clinical application of technically complex therapeutic ERCP is the future development trend. Conclusion: This study lists the most influential articles in ERCP by exposing the current state of the field, and showing the evolution of research trends to provide perspective for the future development of ERCP.

Dynamic Changes and Nomogram Prediction for Sinistral Portal Hypertension in Moderate and Severe Acute Pancreatitis.

Objectives: To investigate the dynamic changes in gastric varices in patients with acute pancreatitis (AP) and to develop a novel nomogram for the early prediction of sinistral portal hypertension (SPH). Methods: This was a retrospective, case-control study with an analysis of the quantitative, dynamic computed tomography imaging results of SPH in patients with moderate and severe AP with a long-term follow-up. Multivariate logistic regression analysis and nomogram were employed. Results: The SPH group (n = 94) and non-SPH group (n = 94) were matched. The dynamic changes showed an increasing trend in the diameter of gastric fundus, short gastric, gastric coronary, and gastroepiploic veins, which did not recover during the one-year follow-up. Multivariate analysis showed that male (adjusted odds ratio (adjOR), 8.71; 95% confidence interval (CI), 2.86-26.53; P < 0.001), body mass index ≥27.5 kg/m2 (adjOR, 5.49; 95% CI, 1.85-16.29; P = 0.002), prothrombin time ≥12.6 s (adjOR, 2.82; 95% CI, 1.11-7.17; P = 0.03), and the patency of splenic vein [stenosis (adjOR, 8.48; 95% CI, 2.13-33.71; P = 0.002), and occlusion (adjOR, 34.57; 95% CI, 10.87-110.00; P < 0.001)] were independently associated with the development of SPH. The nomogram incorporating these factors demonstrated good discrimination, calibration and clinical utility. The area under the curve was as high as 0.92 (95% CI, 0.87-0.95). Conclusion: The dynamic changes in varices in SPH are long-term and slowly progressing. Males and obese patients with abnormal splenic veins and coagulopathies are at high risk for developing SPH. A simple nomogram tool helps in the early, accurate prediction of SPH.

microRNA-16-5p suppresses cell proliferation and angiogenesis in colorectal cancer by negatively regulating forkhead box K1 to block the PI3K/Akt/mTOR pathway.

MicroRNAs (miRNAs/miRs) have aroused increasing attention in colorectal cancer (CRC) therapy. This study is designed for a detailed analysis of the roles of miR-16-5p and forkhead box K1 (FOXK1) in cell angiogenesis and proliferation during CRC in addition to their underlying mechanisms. CRC tissues and colon cancer cell lines (SW620 and HCT8) were investigated. qRT-PCR and Western blot were utilized to evaluate miR-16-5p and FOXK1 expression. Following gain- and loss-of-function assays on miR-16-5p or FOXK1, the effects of miR-16-5p and FOXK1 were assessed on cell angiogenesis and proliferation in CRC cells. A dual-luciferase reporter assay was employed to evaluate the binding relationship of miR-16-5p and FOXK1. Western blot was used to determine the effects of miR-16-5p and FOXK1 on key molecules of the PI3K/Akt/mTOR pathway. Highly expressed FOXK1 and lowly expressed miR-16-5p were observed in CRC cells and tissues. miR-16-5p overexpression or FOXK1 knockdown reduced CRC cell proliferation and angiogenesis of human umbilical vein endothelial cells co-cultured with the supernatant of CRC cells, whereas miR-16-5p silencing or FOXK1 upregulation caused opposite trends. Additionally, miR-16-5p negatively modulated FOXK1 expression. The blockade of the PI3K/Akt/mTOR pathway was triggered by miR-16-5p overexpression or FOXK1 silencing. In conclusion, miR-16-5p hampers cell angiogenesis and proliferation during CRC by targeting FOXK1 to block the PI3K/Akt/mTOR pathway.

Study on the Mechanism of MicroRNA551b-5p in Severe Acute Pancreatitis Capillary Leakage Syndrome.

Objective: This study focused on investigating the effects of microRNA551b-5p (miR-551b-5p) on severe acute pancreatitis. Methods: Initially, quantitative real-time polymerase chain reaction (qPCR) is employed to determine the expression of miR-551b-5p in differentiated human umbilical vein endothelial cells (HUVECs). Further, the effects of aberrantly expressed miR-551b-5p in HUVECs Transwell assay. The expressions of proteins associated with severe acute pancreatitis capillary leakage syndrome are determined by Western blot, FITC-phalloidin, and immunofluorescence stainings. Finally, the correlative factor and the target genes of miR-551b-5p, as well as their contributions, are assessed. Results: We observed that overexpression of miR-551b-5p distinctly promoted the expression of EGFR, AKT3, and AQP5, while it suppressed the expression of JAM3, AQP1, and occludin. Functionally, the cytoskeleton of the miR-551b-5p overexpression was relatively loose with apparent vacuoles, and overexpression of miR-551b-5p increased the permeability of HUVECs. Conclusion: miR-551b-5p overexpression promoted changes in vascular endothelial permeability via upregulation of the EGFR/AKT3 pathway and downregulation of occludin and JAM3.

Randomized controlled trial: neostigmine for intra-abdominal hypertension in acute pancreatitis.

BACKGROUND: Intra-abdominal hypertension (IAH) in acute pancreatitis (AP) is associated with deterioration in organ function. This trial aimed to assess the efficacy of neostigmine for IAH in patients with AP. METHODS: In this single-center, randomized trial, consenting patients with IAH within 2 weeks of AP onset received conventional treatment for 24 h. Patients with sustained intra-abdominal pressure (IAP) ≥ 12 mmHg were randomized to receive intramuscular neostigmine (1 mg every 12 h increased to every 8 h or every 6 h, depending on response) or continue conventional treatment for 7 days. The primary outcome was the percent change of IAP at 24 h after randomization. RESULTS: A total of 80 patients were recruited to neostigmine (n = 40) or conventional treatment (n = 40). There was no significant difference in baseline parameters. The rate of decrease in IAP was significantly faster in the neostigmine group compared to the conventional group by 24 h (median with 25th-75th percentile: -18.7% [- 28.4 to - 4.7%] vs. - 5.4% [- 18.0% to 0], P = 0.017). This effect was more pronounced in patients with baseline IAP ≥ 15 mmHg (P = 0.018). Per-protocol analysis confirmed these results (P = 0.03). Stool volume was consistently higher in the neostigmine group during the 7-day observational period (all P < 0.05). Other secondary outcomes were not significantly different between neostigmine and conventional treatment groups. CONCLUSION: Neostigmine reduced IAP and promoted defecation in patients with AP and IAH. These results warrant a larger, placebo-controlled, double-blind phase III trial. Trial registration Clinical Trial No: NCT02543658 (registered August /27, 2015).

Risk factors for bleeding in patients with acute necrotizing pancreatitis undergoing endoscopic necrosectomy.

BACKGROUND: This study investigated risk factors for bleeding in patients with acute necrotizing pancreatitis (ANP) undergoing endoscopic necrosectomy (EN) and the effect of endoscopic haemostasis. METHODS: 145 patients with ANP who underwent EN were recruited from January 2014 to December 2018. Patients with and without bleeding were allocated to the bleeding and nonbleeding groups, respectively. Multivariable logistic regression models were used to assess independent risk factors for bleeding. RESULTS: 39 patients (26.9%) experienced bleeding. The body mass index and culture-confirmed infectious pancreatic necrosis (IPN), renal failure and continuous renal replacement therapy rates were significantly higher in the bleeding group (all P < 0.01). In addition, the number of debridement procedures was significantly higher in the bleeding group (P = 0.004), accompanied by a higher mortality rate and greater hospitalization costs (all P < 0.05). Most cases of bleeding during EN were successfully stopped by endoscopic haemostasis (94.1%), but this was difficult to achieve after EN. Multivariate analysis revealed that renal failure (odds ratio [OR]: 3.77, P = 0.02), culture-confirmed IPN (OR: 3.19, P = 0.02), and ≥3 debridement procedures (OR: 12.92, P = 0.001) were associated with an increased bleeding risk. CONCLUSION: Renal failure, culture-confirmed IPN, and multiple debridement procedures were independent risk factors for bleeding in patients with ANP who underwent EN.

Efficacy and Safety of Faecal Microbiota Transplantation for Acute Pancreatitis: A Randomised, Controlled Study.

Aims: We investigated whether faecal microbiota transplantation (FMT) decreases intra-abdominal pressure (IAP) and improves gastrointestinal (GI) dysfunction and infectious complications in acute pancreatitis (AP). Methods: In this first randomised, single-blind, parallel-group, controlled study, we recruited and enrolled consecutive patients with AP complicated with GI dysfunction. Eligible participants were randomly assigned to receive faecal transplant (n = 30) or normal saline (n = 30) via a nasoduodenal tube once and then again 2 days later. The primary endpoint was the rate of IAP decline; secondary endpoints were GI function, infectious complications, organ failure, hospital stay and mortality. Analyses were based on intention to treat. Results: We enrolled 60 participants and randomly assigned them to the FMT (n = 30) or control (n = 30) group. Baseline characteristics and disease severity were similar for both groups. IAP decreased significantly 1 week after intervention in both groups, with no difference in the IAP decline rate between FMT and Control group [0.1 (-0.6, 0.5) vs. 0.2 (-0.2, 0.6); P = 0.27]. Normal gastrointestinal failure (GIF) scores were achieved in 12 (40%) patients in the FMT group and 14 (47%) in the control group, with no significant difference (P = 0.60). However, D-lactate was significantly elevated in the FMT group compared to the control group, as calculated by the rate of decline [-0.3 (-3.7, 0.8) vs. 0.4 (-1.1, 0.9); P = 0.01]. Infectious complications occurred in 15 (50%) and 16 (53.33%) patients in the FMT and control groups, respectively (P = 0.80). However, interleukin-6 (IL-6) was significantly elevated in the FMT group compared to the control group, as calculated by the rate of decline [0.4 (-3.6, 0.9) vs. 0.8 (-1.7, 1.0); P = 0.03]. One participant experienced transient nausea immediately after FMT, but no serious adverse events were attributed to FMT. Conclusion: FMT had no obvious effect on IAP and infectious complications in AP patients, though GI barrier indictors might be adversely affected. Further multi-centre studies are needed to confirm our findings. The study was registered at https://clinicaltrials.gov (NCT02318134).

Effects of Snake-Derived Phospholipase A2 Inhibitors on Acute Pancreatitis: In vitro and in vivo Characterization.

OBJECTIVE: We aimed to investigate the effects of snake-derived phospholipase A2 inhibitor (PLA2) from Sinonatrix percarinata and Bungarus multicinctus on acute pancreatitis in vivo and in vitro and assess the mechanisms. METHODS: The levels of platelet-activating factor (PAF) and tumor necrosis factor (TNF)-α were detected by ELISA, and the characteristics of autophagy were detected by transmission electron microscopy and Western blotting (LC3, p62, and ATG5). RESULTS: In vitro experiments showed that PLA2 treatment caused obvious formation of autophagic bodies. By contrast, Sinonatrix and Bungarus peptides reduced the number of autophagic bodies. The concentrations of PAF and TNF-α, and the expressions of p62, autophagy-related 5 (ATG5), and microtubule-associated protein 1A/1B-light chain 3 (LC3)II/LC3I in the PLA2-treated group were significantly higher than in the control group (P<0.05). The concentrations of PAF and TNF-α, and the expressions of p62, ATG5, and LC3II/LC3I in the Sinonatrix or Bungarus peptide treatment groups were significantly lower than in the PLA2-treated cells (P<0.05). In the pancreatic tissue, autophagic bodies were observed in the model group; autophagic bodies were remarkably reduced in Sinonatrix or Bungarus peptide-treated groups compared with the model group. In vivo experiments also showed that the levels of PAF and TNF-α, and the expressions of p62, ATG5, and LC3II/LC3I were significantly higher in the model group than in the control group (P<0.05). The levels of PAF and TNF-α in the model group, and the expressions of p62, ATG5, and LC3II/LC3I in Sinonatrix or Bungarus peptide-treated groups were significantly lower than in the model group (P<0.05). CONCLUSION: Sinonatrix or Bungarus peptide could ameliorate the features of acute pancreatitis, likely through regulating autophagy.

Matrine Suppresses Pancreatic Fibrosis by Regulating TGF-ß/Smad Signaling in Rats.

PURPOSE: This study aimed to elucidate the molecular mechanisms of the anti-pancreatic fibrosis effects of matrine in rats. MATERIALS AND METHODS: Trinitrobenzene sulfonic acid was administrated to rats to establish a pancreatic fibrosis model. Rats were divided into four groups: Control, Sham, Model, and Matrine (n=8). Hematoxylin-eosin staining, Masson staining, and Azan staining were performed to evaluate pancreatic fibrosis. Expression of transforming growth factor-ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), and collagen I in pancreatic tissues was evaluated by immunohistochemical staining. mRNA and protein levels of TGF-ß receptor 1 (TßR1), TßR2, and Smad2 in pancreatic tissues were determined by RT-PCR and Western blot, respectively. RESULTS: In the model group, hyperplasia of glandules around the glandular ducts, mitochondrial swelling of acinous cells, and severe fibrosis were found. Interestingly, in the Matrine group, mitochondrial swelling was only found in a small number of acinous cells, and the fundamental structures of pancreatic tissues were intact. Moreover, pancreatic fibrosis was markedly alleviated. Comparing to the Sham group, expression of α-SMA, TGF-ß1, and collagen I was sharply elevated in the Model group (p<0.05); however, their expressions were much lower in the Matrine group, compared to the Model group (p<0.05). Compared with the Sham group, mRNA and protein levels of Smad2, TßR1, and TßR2 in the Model group were notably raised (p<0.05). However, their high expression was significantly downregulated in the Matrine group (p<0.05). CONCLUSION: Matrine suppressed pancreatic fibrosis by regulating TGF-ß/Smad signaling in rats.

Double-catheter lavage combined with percutaneous flexible endoscopic debridement for infected pancreatic necrosis failed to percutaneous catheter drainage.

BACKGROUND: Infected pancreatic necrosis (IPN) is a serious local complication of acute pancreatitis, with high mortality. Minimally invasive therapy including percutaneous catheter drainage (PCD) has become the preferred method for IPN instead of traditional open necrosectomy. However, the efficacy of double-catheter lavage in combination with percutaneous flexible endoscopic debridement after PCD failure is unknown compared with surgical necrosectomy. METHODS: A total of 27 cases of IPN patients with failure PCD between Jan 2014 and Dec 2015 were enrolled in this retrospective cohort study. Fifteen patients received double-catheter lavage in combination with percutaneous flexible endoscopic debridement, and 12 patients underwent open necrosectomy. The primary endpoint was the composite end point of major complications or death. The secondary endpoint included mortality, major complication rate, ICU admission length of stay, and overall length of stay. RESULTS: The primary endpoint occurrence rate in double-catheter lavage in combination with percutaneous flexible endoscopic debridement group (8/15, 53%) was significantly lower than that in open necrosectomy group (11/12, 92%) (RR = 1.71, 95% CI = 1.04 - 2.84, P < 0.05). Though the mortality between two groups showed no statistical significance (0% vs. 17%, P = 0.19), the rate of new-onset multiple organ failure and ICU admission length of stay in the experimental group was significantly lower than that in open necrosectomy group (13% vs. 58%, P = 0.04; 0 vs. 17, P = 0.02, respectively). Only 40% of patients required ICU admission after percutaneous debridement, which was markedly lower than the patients who underwent surgery (83%; P < 0.05). CONCLUSIONS: Double-catheter lavage in combination with percutaneous flexible endoscopic debridement showed superior effectiveness, safety, and convenience in patients with IPN after PCD failure as compared to open necrosectomy.

miR-551b-5p increases intracellular Ca2+ concentration but does not alter c-Kit expression in rat interstitial cells of Cajal.

OBJECTIVE: To investigate the effect of the severe acute pancreatitis (SAP)-related miR-551b-5p on intracellular Ca2+ concentration and c-Kit expression and distribution in rat interstitial cells of Cajal (ICCs) in vitro. METHODS: ICCs were isolated from 5-10-day-old rats and cultured in vitro. The cultured ICCs were divided into five groups: a normal control group; a group transfected with an miR-551b-5p mimic; a group transfected with an miR-551b-5p inhibitor; a group transfected with a negative control for the miR-551b-5p mimic; and a group transfected with a negative control for the miR-551b-5p inhibitor. After transfection, real-time PCR was used to detect miR-551b-5p and c-Kit expression. A Western blot analysis was used to determine the expression of c-Kit protein. Confocal microscopy combined with immunofluorescence and Fluo 3-acetoxymethyl (AM) fluorescence were used to determine the localization of c-Kit and intracellular Ca2+ concentration, respectively. RESULTS: Transfection with the miR-551b-5p mimic or inhibitor resulted in overexpression or downregulation of miR-551b-5p in ICCs, respectively. The overexpression or downregulation of miR-551b-5p had no significant influence on c-Kit mRNA or protein levels. The overexpression of miR-551b-5p significantly increased the intracellular Ca2+ concentration, and the downregulation of miR-551b-5p significantly decreased the intracellular Ca2+ concentration. CONCLUSION: miR-551b-5p increases intracellular Ca2+ concentration but does not alter c-Kit expression in rat ICCs, suggesting that it functions in ICCs by regulating the intracellular Ca2+ concentration downstream or independently of c-Kit signaling.

Identification of serum microRNAs as diagnostic and prognostic biomarkers for acute pancreatitis.

BACKGROUND/OBJECTIVES: To identify serum microRNA (miRNA) as diagnostic and prognostic biomarkers for acute pancreatitis (AP). MATERIALS AND METHODS: Sera microRNA expression was profiled from 12 AP patients with varying disease severity and three healthy controls. Differentially expressed miRNAs were validated in a larger cohort of patients and controls. The diagnostic and prognostic potentials of differentially expressed miRNAs were evaluated using receiver operating characteristic (ROC) curve analysis and compared to that of classic prognostic markers for AP. RESULTS: miRNA microarray analyses identified 205 differentially expressed miRNAs between sera from AP patients and that from controls. Nine miRNAs were differentially expressed between severe and mild AP patients. Further validation confirmed the down-regulation of miR-92b, miR-10a, and miR-7 in AP patients, and ROC analysis revealed that these miRNAs can differentiate AP from health cases. Furthermore, the serum miR-551b-5p level was significantly higher in patients with disease complications or a low plasma calcium level. ROC analysis showed that the serum miR-551b-5p level can distinguish between severe and mild AP. CONCLUSION: The expressions of miR-92b, miR-10a, and miR-7 in AP might be used for the early diagnosis of AP and miR-551b-5p may be used for predicting AP severity.