MiR-325-3p Alleviates Acute Pancreatitis via Targeting RIPK3.

BACKGROUND AND AIMS: Acute pancreatitis (AP) is an acute inflammatory disease that can lead to death. Mir-325-3p is strongly and abnormally expressed in many diseases, necessitating exploration of its function and mechanism in AP. METHODS: Blood samples from AP patients and mice were analyzed. The expression levels of miR-325-3p in AP patients and mouse were detected. Whether miR-325-3p targets RIPK3 gene was predicted by TargetScan online database and dual luciferase reporter assay. In vitro experiments verified the effect of miR-325-3p overexpression on caerulein-induced MPC83 pancreatic acinar cancer cell line. In vivo experiments verified the effect of overexpression of miR-325-3p on the disease degree of pancreatic tissues in AP mice. RESULTS: Analysis of blood samples from AP patients and experiments in mice demonstrated that expression of miR-325-3p was significantly reduced during the process of AP in humans and mice. Predicted using the TargetScan online database and through dual luciferase reporter assay detection, miR-325-3p directly targets the RIPK3 gene. In vitro experiments revealed that overexpression of miR-325-3p reversed caerulein-induced apoptosis and necroptosis in MPC83 pancreatic acinar cancer cell line. We used Z-VAD-FMK to assess necroptosis and demonstrated that miR-325-3p targets necroptosis to reduce cell damage. In subsequent experiments in mice, we verified that overexpression of miR-325-3p reduces inflammation, edema, hemorrhage, and necrosis in acute pancreatitis. Characteristic western blot, immunohistochemistry, and transmission electron microscopy results revealed that overexpression of miR-325-3p reduces the severity of acute pancreatitis by inhibiting pancreatic necroptosis in AP mice. CONCLUSIONS: The current research results indicate that miR-325-3p directly targets RIPK3 and exerts a protective role in mouse AP. Necroptosis is still the primary mechanism of RIPK3 regulation. MiR-325-3p inhibits acute pancreatitis by targeting RIPK3-dependent necroptosis, which may represent a novel treatment method for acute pancreatitis.

Characteristics of and risk factors for biliary pathogen infection in patients with acute pancreatitis.

BACKGROUND: Infection in patients with acute pancreatitis, especially severe acute pancreatitis patients, is a common and important phenomenon, and the distributions and drug resistance profiles of bacteria causing biliary infection and related risk factors are dynamic. We conducted this study to explore the characteristics of and risk factors for bacterial infection in the biliary tract to understand antimicrobial susceptibility, promote the rational use of antibiotics, control multidrug-resistant bacterial infections and provide guidance for the treatment of acute pancreatitis caused by drug-resistant bacteria. METHODS: The distribution of 132 strains of biliary pathogenic bacteria in patients with acute pancreatitis from January 2016 to December 2020 were analyzed. We assessed drug resistance in the dominant Gram-negative bacteria and studied the drug resistance profiles of multidrug-resistant bacteria by classifying Enterobacteriaceae and nonfermentative bacteria. We then retrospectively analyzed the clinical data and risk factors associated with 72 strains of Gram-negative bacilli, which were divided into multidrug-resistant bacteria (50 cases) and non-multidrug-resistant bacteria (22 cases). RESULTS: The main bacteria were Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli had a 66.67% detection rate. Acinetobacter baumannii had more than 50.00% drug resistance to carbapenems, ESBL-producing Klebsiella pneumoniae had 100.00% drug resistance, and Pseudomonas aeruginosa had 66.67% resistance to carbapenems. Multivariate logistic regression analysis suggested that the administration of third- or fourth-generation cephalosporins was an independent risk factor for Gram-negative multidrug-resistant biliary bacterial infection in acute pancreatitis patients. CONCLUSION: Drug resistance among biliary pathogens in acute pancreatitis patients remains high; therefore, rational antimicrobial drug use and control measures should be carried out considering associated risk factors to improve diagnosis and treatment quality in acute pancreatitis patients.

The impacts of infectious complications on outcomes in acute pancreatitis: a retrospective study.

BACKGROUND: The occurrence of infectious complications characterizes the more severe forms of acute pancreatitis (AP) and is associated with high mortality. We investigated the effects of infection at different sites in patients with AP, including those with necrotizing pancreatitis (NP). METHODS: We conducted a retrospective analysis of 285 patients who met the inclusion criteria for AP and were admitted to Tianjin Nankai Hospital between January 2016 and September 2019. According to the source of the culture positivity during hospitalization, patients were divided into four groups: sterile group(n = 148), pancreatic infection group(n = 65), extrapancreatic infection group(n = 22) and combined infection group(n = 50). The source of infection, microbiology, biochemical parameters and prognostic indicators were analyzed. RESULTS: In terms of baseline characteristics, the four groups were similar in age, sex, aetiology, previous pancreatitis and diabetes. Compared with the severity of the disease in the other groups, the APACHE II scores(9.91 ± 4.65, 9.46 ± 5.05, respectively) and organ failure rate (40.9 and 50%, respectively)were higher in the extrapancreatic infection group and the combined infection group (P < 0.05). The frequency of surgical intervention and hospitalization time in patients with NP complicated with extrapancreatic infection was greatly increased (P < 0.05). Regarding the primary outcome, patients in the combined infection group had longer hospital stays (68.28 ± 51.80 vs 55.58 ± 36.24, P < 0.05) and higher mortality (24.0% vs 9.2%, P < 0.05) than patients in the pancreatic infection group. In addition, patients in the extrapancreatic infection group also showed high intensive care utilization (59.1%) and mortality rates (18.2%). Among the 137 AP patients with infection complications, 89 patients exhibited multidrug-resistant (MDR) microorganisms, and the mortality rate of patients with MDR bacterial infection was higher than that of patients with non-MDR bacterial infection (24.7% vs 3.6%, P = 0.001). CONCLUSION: Clinicians should be aware that extrapancreatic infection (EPI) significantly aggravates the main outcome in pancreatic infection patients. Infection with MDR bacteria is also associated with AP mortality.