Higher versus lower mean arterial pressure target management in older patients having non-cardiothoracic surgery: A prospective randomized controlled trial.

STUDY OBJECTIVE: This study aimed to evaluate the effects of low versus high mean arterial pressure (MAP) levels on the incidence of postoperative delirium during non-cardiothoracic surgery in older patients. DESIGN: Multicenter, randomized, parallel-controlled, open-label, and assessor-blinded clinical trial. SETTING: University hospital. PATIENTS: Three hundred twenty-two patients aged ≥65 with an American Society of Anesthesiologists physical status of I-II who underwent non-cardiothoracic surgery with general anaesthesia. INTERVENTIONS: Participants were randomly assigned into a low-level MAP (60-70 mmHg) or high-level MAP (90-100 mmHg) group during general anaesthesia. The study was conducted from November 2016 to February 2020. Participants were older patients having non-cardiothoracic surgery. The follow-up period ranged from 1 to 7 days after surgery. The primary outcome was the incidence of postoperative delirium. MAIN RESULTS: In total, 322 patients were included and randomized; 298 completed in-hospital delirium assessments [median (interquartile range) age, 73 (68-77) years; 173 (58.1%) women]. Fifty-four (18.1%) patients total, including 36 (24.5%) and 18 (11.9%) in the low-level and high-level MAP groups [relative risk (RR) 0.48, 95% confidence interval (CI) 0.25 to 0.87, P = 0.02], respectively, experienced postoperative delirium. The adjusted RR was 0.34 (95% CI 0.16 to 0.70, P < 0.01) in the multiple regression analysis. High-level MAP was associated with a shorter delirium span and a higher intraoperative urine volume than low-level MAP. CONCLUSIONS: In older patients during non-cardiothoracic surgery, high-level blood pressure management might help reduce the incidence of postoperative delirium.

Lipoxin A4 Ameliorates Lipopolysaccharide-Induced A549 Cell Injury through Upregulation of N-myc Downstream-Regulated Gene-1.

BACKGROUND: Lipoxin A4 (LXA4) can alleviate lipopolysaccharide (LPS)-induced acute lung injury (ALI) and acute respiratory distress syndrome through promoting epithelial sodium channel (ENaC) expression in lung epithelial cells. However, how LXA4 promote ENaC expression is still largely elusive. The present study aimed to explore genes and signaling pathway involved in regulating ENaC expression induced by LXA4. METHODS: A549 cells were incubated with LPS and LXA4, or in combination, and analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) of ENaC-α/γ. Candidate genes affected by LXA4 were explored by transcriptome sequencing of A549 cells. The critical candidate gene was validated by qRT-PCR and Western blot analysis of A549 cells treated with LPS and LXA4 at different concentrations and time intervals. LXA4 receptor (ALX) inhibitor BOC-2 was used to test induction of candidate gene by LXA4. Candidate gene siRNA was adopted to analyze its influence on A549 viability and ENaC-α expression. Phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was utilized to probe whether the PI3K signaling pathway was involved in LXA4 induction of candidate gene expression. RESULTS: The A549 cell models of ALI were constructed and subjected to transcriptome sequencing. Among candidate genes, N-myc downstream-regulated gene-1 (NDRG1) was validated by real-time-PCR and Western blot. NDRG1 mRNA was elevated in a dose-dependent manner of LXA4, whereas BOC-2 antagonized NDRG1 expression induced by LXA4. NDRG1 siRNA suppressed viability of LPS-treated A549 cells (treatment vs. control, 0.605 ± 0.063 vs. 0.878 ± 0.083, P = 0.040) and ENaC-α expression (treatment vs. control, 0.458 ± 0.038 vs. 0.711 ± 0.035, P = 0.008). LY294002 inhibited NDRG1 (treatment vs. control, 0.459 ± 0.023 vs. 0.726 ± 0.020, P = 0.001) and ENaC-α (treatment vs. control, 0.236 ± 0.021 vs. 0.814 ± 0.025, P < 0.001) expressions and serum- and glucocorticoid-inducible kinase 1 phosphorylation (treatment vs. control, 0.442 ± 0.024 vs. 1.046 ± 0.082, P = 0.002), indicating the PI3K signaling pathway was involved in regulating NDRG1 expression induced by LXA4. CONCLUSION: Our research uncovered a critical role of NDRG1 in LXA4 alleviation of LPS-induced A549 cell injury through mediating PI3K signaling to restore ENaC expression.