IL-17A/p38 Signaling Pathway Induces Alveolar Epithelial Cell Pyroptosis and Hyperpermeability in Sepsis-Induced Acute Lung Injury by Activating NLRP3 Inflammasome.

Sepsis is a syndrome with poor prognosis. Nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and T helper 17 (Th17) cells are involved in the pathogenesis of inflammatory diseases. This study aims to explore their roles and underlying mechanisms in sepsis. The blood and bronchoalveolar lavage fluid are collected from sepsis patients and healthy donors. A sepsis mice model is established by cecal ligation puncture (CLP). The contents of cytokines are detected by ELISA. The amounts of Th17 cells, IL-17A, IL-1ß, IL-18, and lipopolysaccharide is significantly elevated in sepsis patients. The increased differentiation of Th17 cells can promote lung cell pyroptosis and induce hyperpermeability via activating NLRP3 inflammasome and p38 pathway. The inhibitors targeting Th17 cells, NLRP3 inflammasome, and p38 pathway can significantly alleviate lung injury in sepsis mice. Th17 cells can secrete IL-17A to activate NLRP3 inflammasome via p38 signaling pathway, which contributes to the development of sepsis-induced acute lung injury.

[Effect of Xuebijing injection on rabbits ischemia/reperfusion injury induced by femoral arterial disease].

OBJECTIVE: To investigate the changes in serum malondialdehyde (MDA), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), aspartate aminotransferase (AST) and creatinine (Cr) after the reproduction of ischemia/reperfusion (I/R) injury model, and the protective effects of liver and kidney with Xuebijing injection on acute I/R injury in rabbits. METHODS: Sixty rabbits were divided into six groups with a random number: A, normal group; B, sham operated group; C, model group, and D, E, F groups (Xuebijing low, middle, high dosage treatment groups). I/R injury model was reproduced (after a 4-hour ischemia, the femoral vessels were reperfusion). Physiological saline (2 ml/kg) or 0.33, 0.66 and 1.32 g/kg Xuebijing injection were given at 0, 12, 36, 60 hours after operation via ear vein. MDA, IL-1ß, TNF-α, AST and Cr were determined at 6, 12, 24 and 72 hours after reperfusion in each group. RESULTS: MDA, IL-1ß, TNF-α at different time points, AST and Cr at 72 hours after reperfusion in C group were significantly higher than those in A group and B group. Compared with the C group, the above indexes were gradually decreased with does-dependence, the values of MDA (µmol/L), IL-1ß (ng/L) and TNF-α (µg/L) in serum of group F at 6, 12, 24 and 72 hours after reperfusion were significantly lower (MDA: 9.74 ± 3.71 vs. 12.35 ± 4.64, 11.26 ± 4.14 vs. 12.82 ± 3.85, 9.72 ± 2.25 vs. 13.30 ± 2.83, 9.12 ± 2.72 vs. 13.10 ± 2.72; IL-1ß: 83.49 ± 12.79 vs. 100.09 ± 17.53, 85.10 ± 11.75 vs. 102.64 ± 19.64, 75.97 ± 11.29 vs. 99.24 ± 14.62, 81.96 ± 14.81 vs. 99.59 ± 12.05; TNF-α: 8.95 ± 1.13 vs. 9.94 ± 1.29, 8.79 ± 1.80 vs. 9.56 ± 0.89, 8.27 ± 1.83 vs. 9.51 ± 1.32, 7.23 ± 1.39 vs. 9.23 ± 1.05, P < 0.05 or P < 0.01). The values of AST(U/L) and Cr (µmol/L) in serum of groups D, E and F at 24 hours and 72 hours after reperfusion were significantly lower (AST 24 hours: 24.00 ± 1.27, 23.80 ± 1.11, 22.90 ± 1.65 vs. 39.50 ± 1.73, 72 hours: 32.15 ± 1.95, 32.90 ± 1.77, 32.25 ± 2.25 vs. 52.86 ± 2.43; Cr 24 hours: 273.78 ± 17.04, 267.07 ± 19.59, 265.25 ± 15.59 vs. 347.60 ± 18.83, 72 hours: 437.38 ± 18.48, 343.77 ± 16.79, 351.48 ± 20.22 vs. 437.50 ± 19.86, all P < 0.01). CONCLUSIONS: It is demonstrated that I/R injury could dramatically lead to systemic inflammatory response and oxygen free radical injury. Xuebijing injection in higher dosage can reduce the systemic inflammatory response significantly, and also MDA level in serum. Xuebijing injection in low dosage, middle dosage and high dosage can produce protective effects against the damages to liver and kidney function.

The efficacy of parenteral fish oil in critical illness patients with sepsis: a prospective, non-randomized, observational study.

BACKGROUND AND OBJECTIVES: To investigate the clinical outcomes in septic patients receiving parenteral fish oil. METHODS AND STUDY DESIGN: A prospective, non-randomized, observational clinical study was carried out in 112 patients with sepsis from March, 2013 to May, 2015 in the surgical intensive care unit (SICU) of a tertiaryreferral hospital. The patients were put into one of two groups; either the control or the study group. Patients received the standard treatment of sepsis based on guidelines in the control group. In the study group, patients received parenteral nutrition (PN) containing fish oil. The Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, the length of ICU and hospital stay, duration of mechanical ventilation, mortality, and readmission into the ICU were recorded. Tumor necrosis factor (TNF)-α and procalcitonin (PCT) levels were also evaluated. RESULTS: The study group showed a significant reduction for all-cause mortality (20.0% vs 10.0% in study and control groups, p=0.034) and APACHE II score on day 5 (p=0.015), day 7 (p=0.036) and day out of SICU (p=0.045) compared with the control group. The study group tended to show a shortened length of stay in the ICU compared to the control group. However, TNF-α and PCT level, 28 d mortality, the length of hospital stay and the duration of mechanical ventilation did not show statistical differences between the two groups. There were no drug-related adverse effects shown during the study. CONCLUSIONS: PN with fish oil is probably safe and may improve clinical outcome in critical ill patients with sepsis.

Low molecular weight heparin once versus twice for thromboprophylaxis following esophagectomy: a randomised, double-blind and placebo-controlled trial.

BACKGROUND: Venous thromboembolism (VTE) remained common complication following surgical resection of esophageal cancer. In this prospective randomized double-blind placebo-controlled trial (NCT01267305), we aim to compare the safety and efficacy between low molecular weight heparin (LMWH) once-daily (QD) and twice-daily (BID) for the prophylaxis of VTE following esophagectomy. METHODS: During August 2012 to July 2013, patients underwent esophagectomy were randomly assigned to nadroparin calcium QD (4,100 AxaIU qd + placebo qd, group QD), or nadroparin calcium BID (4,100 AxaIU q12h, group BID) in the prophylaxis of VTE. All patients received thrombelastography (TEG) before and 0/24/48/72 hours after operation. Daily vascular ultrasound of lower extremities was followed during the first 7 postoperative days to confirm the suspected deep venous thrombosis (DVT). Cumulatively postoperative chest drainage at 72 hours after the surgery was collected to identify the difference in volume and red blood cell (RBC) counts between the two groups. Any bleeding events and thromboembolic events were also documented. RESULTS: A total of 117 patients were enrolled in this study, and 111 eligible patients were randomly assigned (group QD: 55 patients; group BID: 56 patients). Patients' clinical features were close between the two groups. TEG analysis [R time, K time, alpha angel and maximum amplitude (MA)] before and instantly after operation showed nearly identical results. However, compared with group QD, all TEG measurements of 24/48/72 hours postoperatively showed significantly prolonged R time and K time, and decreased alpha angel in group BID. In ultrasound follow-ups, a total of four cases of DVT (four cases in group QD and no case in group BID) were found in this cohort (7.27% versus 0%, P=0.046), and one case of pulmonary embolism (PE) (in group QD) was observed. The incidence of VTE was lower in group BID (9.09% versus 0%, P=0.032). At 72 hours after surgery, the cumulative volume of chest drainage were close between these two groups (1,001.39±424.58 versus 1,133.61±513.93 mL, P=0.406). RBC counts in chest drainage were also identical between two groups [(2.56±1.98)×10(5) versus (2.71±4.67)×10(5), P=0.61]. No patient died due to VTE or bleeding events. CONCLUSIONS: For the prophylaxis of VTE, BID LMWH provided more potent efficacy and equal safety when compared to QD LMWH in patients undergoing selective esophagectomy. Further study based on larger population is required to confirm these findings.