Activation of GPR81 aggravated intestinal ischemia/reperfusion injury-induced acute lung injury via HMGB1-mediated neutrophil extracellular traps formation.

INTRODUCTION: Intestinal ischemia/reperfusion (II/R) injury is a life-threatening situation accompanied by severe organ injury, especially acute lung injury (ALI). A great body of evidence indicates that II/R injury is usually associated with hyperlactatemia. G-protein-coupled receptor 81 (GPR81), a receptor of lactate, has been recognized as a regulatory factor in inflammation, but whether it was involved in II/R injury-induced ALI is still unknown. METHODS: To establish the II/R injury model, the superior mesenteric artery of the mice was occluded gently by a microvascular clamp for 45 min to elicit intestinal ischemia and then a 90-min reperfusion was performed. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the lung injury after II/R. The pulmonary histopathological alteration was evaluated by H&E staining. The concentration of proteins, the number of infiltrated cells, and the level of IL-6 were measured in BALF. The formation of neutrophil extracellular traps (NETs) was evaluated by the level of double-stranded DNA (dsDNA) and myeloperoxidase- double-stranded DNA (MPO-dsDNA) complex in BALF, and the content of citrullinated histone H3 (Cit-H3) in lung tissue. The level of HMGB1 in the BALF and plasma was measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Administration of the GPR81 agonist 3,5-dihydroxybenzoic acid (DHBA) aggravated II/R injury-induced lung histological abnormalities, upregulated the concentration of proteins, the number of infiltrated cells, and the level of IL-6 in BALF. In addition, DHBA treatment increased the level of dsDNA and MPO-dsDNA complex in BALF, and promoted the elevation of Cit-H3 in lung tissue and the release of HMGB1 in BALF and plasma. CONCLUSION: After induction of ALI by II/R, the administration of DHBA aggravated ALI through NETs formation in the lung.

Sodium butyrate activates HMGCS2 to promote ketone body production through SIRT5-mediated desuccinylation / 医学前沿

Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD+/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.

Effects of PDCA method on improving the accuracy of the Autar Deep Venous Thrombosis Scale / 中国实用护理杂志

Objective:To investigate the effects of PDCA method on improving the accuracy of the Autar Deep Venous Thrombosis (DVT) Scale used by nurses to assess the risk of deep venous thrombosis in surgical patients.Methods:Applied the way of PDCA, namely, raising questions, analyzing reasons, implementing measures, feeding back effects to professional explanate the difficulty in using the scale, moreover, training the nurses used level education method between August 2017 and December2018.The accuracy and consistency of the scale were compared before and after interventions.Results:A total 396 patients were evaluated in the study. There were significant differences in the consistency of evaluation among hospitalized, post-operative and discharged patients after intervention compared with before intervention ( P< 0.0167).The consistency of assessment of team members and responsible nurses increased from 68 to 120 cases, and the consistency of assessment reached 90.91%. The Kappa consistency of assessment of responsible nurses and team members increased from 0.354 before intervention to 0.879 after intervention. The effect was remarkable. Conclusions:PDCA cycle method is based on the problems found in clinical practice. It clarifies the professional terms and rules used in the scale, improves the accuracy and consistency of the Autar DVT scale used by nurses, correctly reflects the risk of thrombosis, ensures the safety of patients, and is worthy of promotion and reference.