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Objective To investigate the potential function of GSDMD in lipopolysaccharide (LPS) induced acute lung injury (ALI) during the inflammatory reaction and lung tissue damage. Methods Twenty wild-type C57BL/6 mice and twenty GSDMD knockout C57BL/6 mice were randomized into the WT-sham group, WT-ALI group, Knockout (KO)-sham group and KOALI group. The ALI was induced by intratracheal injection of LPS (1 mg/kg), using PBS as the treatment control. To examine the inflammatory reaction and tissue damage in the lung, the lung tissue and bronchoalveolar lavage fluid (BALF) were collected. HE staining of lung tissue and the semi-quantitative score of lung injury were performed. The wet/dry ratio of lung tissue and the total protein concentration in BALF were measured by BCA. The levels of TNF-α, IL-1β, and IL-6 in BALF were detected by ELISA. The expression of pyroptosis-related proteins in BALF and lung tissues were detected by Western blotting. Results Compared with the WT-ALI group, the lung injury pathological score, wet/dry ratio, and total protein concentration were all significantly lower in KO-ALI group (P

Objective To investigate the effects of necroptosis induced by vibrio vulnificus cytolysin (VVc) on immortalized bone marrow-derived macrophage cell line (iBMDM) and its mechanism. Methods The iBMDM were divided into five groups, control group, VVc(2μg/ml) group, VVc(4μg/ml) group, Necrostatin-1 (Nec-1)+VVc(2μg/ml) group, Nec-1+VVc(4μg/ml) group based on the concentration of VVc and whether the cells received receptor interacting protein 1 (RIP1). In the RIP1 inhibited groups, iBMDM was pretreated with Nec-1 (5μmol/L) before stimulation with VVc. Cells and culture supernatant were harvested at 2h after the challenge by cytolysin. Lactate dehydrogenase (LDH) activity in cell-culture supernatant following VVc stimulation was determined to evaluate cell death. The cell state was detected by flow cytometry with Annexin V/propidium iodide staining, and the expression of phosphorylated mixed lineage kinase domain-like (MLKL) and pyroptosis- and necroptosis-related proteins (caspase-1, caspase-11, gasdermin D) were detected by Western blotting. Results The LDH level in the culture supernatant was increased in the groups stimulated by VVc and could also be inhibited by pretreatment with Nec-1 (P＜0.05). Compared with control and RIP1- inhibited groups, the VVc-treatment induced a high amount of the double positive staining cells in the VVc group (P＜0.05). In the RIP1 inhibited groups, Nec-1 pretreatment could significantly decrease the levels of pMLKL (P＜0.05), compared with VVc group. None of the cleaved pyroptosis-related protein was detected by Western blotting. Conclusion Necroptosis induced by RIP1 may play an important role in VVc injury model of iBMDM, furthermore, Nec-1 could reduce the degree of injury after VVc challenge. DOI: 10.11855/j.issn.0577-7402.2018.05.11

Objective To evaluate the effect of intracarotid cold saline infusion (ICSI) on neurological outcomes in canines with cardiac arrest (CA) introduced by severe hypothermia. Methods Restoration of spontaneous circulation (ROSC) after hypothermic CA was induced in 10 Beagle dogs. These 10 dogs were randomly divided into 2 groups (5 each). Dogs in control group were rewarmed using warn water bath, and dogs in experimental group received the bath rewarming plus ICSI for 6 hours to maintain the brain temperature

Objective To observe the influences of regional citrate or systemic heparin anticoagulation on acid-base balance, coagulation, electrolytes, serum creatinine, alanine aminotransferase (ALT) and cardiac index (CI) during continuous renal replacement therapy (CRRT) rewarming in accidental hypothermia dogs. Methods Nineteen adult beagles were given abdominal trauma coupled with deep hypothermia [(28±0.5)℃] induced by seawater immersion for establishing animal model of trauma. According to rewarming ways, the animal models were randomly divided into three groups, comparison group (warm bath rewarming, n=5), CRRT rewarming-systemic heparin anticoagulation group (heparin anticoagulation group, n=7) and CRRT rewarming-regional citrate anticoagulation group (citrate anticoagulation group, n=7). During the rewarming routine blood examination was performed, and blood chemistry, coagulation function, blood gas and hemodynamic status were assayed, at the same time the mortality was recorded. Results During the rewarming, the mortality was 14.3% (1/7) in heparin anticoagulation group, 40.0% (2/5) in warm bath group and 0 in regional citrate anticoagulation group. Blood temperature in creased to 38℃, the heparin anticoagulation group showed a significant decrease of platelet compared with citrate anticoagulation group and comparison group (P0.05). Conclusions CRRT plus warm bath rewarming have better effect on improving metabolic acidosis than warm bath rewarming alone in accidental hypothermia dogs. In comparison with systemic heparin anticoagulation, regional citrate anticoagulation has smaller influences on coagulation system and platelet when CRRT rewarming performed in accidental hypothermia dogs. DOI: 10.11855/j.issn.0577-7402.2016.10.05

Objective To investigate the effect of the small intestinal decompression on intra -abdominal hypertension(IAH) in critically ill patients. Methods Fourteen IAH patients received small intestinal decompression under the X ray in Navy General Hospital of PLA from August 2013 to August 2015, and the heart rate, mean arterial pressure, breathing rate, abdominal perimeter, urea nitrogen, creatinine, urine output per hour, 24-h intra-abdominal pressure after decompression, and lactic acid before and after the decompression were examined and recorded. Results After decompression all the patients' heart rate, breathing rate, abdominal perimeter, intra-abdominal pressure significantly decreased (P0.05). Conclusion Transnasal small intestinal decompression is safe and effective for the critically ill patients with intra-abdominal hypertension. DOI: 10.11855/j.is sn.0577-7402.2016.07.13

Objective To estimate and compare the efficacy and safety of midazolam, propofol and dexmedetomidine combined with propofol in sedation for mechanically ventilated patients. Methods Seventy-six patients with mechanical ventilation time >24h in ICU of Navy General Hospital of PLA from Mar. 2012 to Sep. 2014 were randomly divided into midazolam group (n=23), propofol group (n=27) and dexmedetomidine combined with propofol group (n=26), and they were given corresponding drugs for sedation. The proportions in each group which reached the target score of Richmond agitation-sedation scale (RASS) and the nonverbal pain assessment scale (Critical-Care Pain Observation Tool, CPOT) were accounted and recorded, and the positive rate of delirium was assessed with the confusion assessment method in the intensive care unit (CAM-ICU). The mechanical ventilation time and the effectiveness of sedation among the 3 groups were compared, the frequency of adverse cardiovascular events was recorded, and the frequency of controlled ventilation, daily mean arterial pressure as well as the heart rate range were analyzed. Results The proportion of reaching the target score of RASS was higher in dexmedetomidine combined with propofol group (86.54%) than that in midazolam group (69.32%, P0.05). The proportion of reaching the target score of CPOT was higher in dexmedetomidine combined with propofol group (63.1%) than in midazolam group (51.2%) and propofol group (49.5%, P0.05). The positive rate of delirium and the proportion of controlled ventilation were lower, and the time of mechanical ventilation is shorter in dexmedetomidine combined with propofol group than in the other two groups (P0.05). Conclusion The efficacy and safety of dexmedetomidine combined with propofol is higher than the individual use of midazolam or propofol in producing sedation for mechanically ventilated patients. DOI: 10.11855/j.issn.0577-7402.2015.06.12