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Aims: To compare the performance of logistic regression and machine learning methods in predicting postoperative delirium (POD) in elderly patients. Method: This was a retrospective study of perioperative medical data from patients undergoing non‐cardiac and non‐neurology surgery over 65 years old from January 2014 to August 2019. Forty‐six perioperative variables were used to predict POD. A traditional logistic regression and five machine learning models (Random Forest, GBM, AdaBoost, XGBoost, and a stacking ensemble model) were compared by the area under the receiver operating characteristic curve (AUC‐ROC), sensitivity, specificity, and precision. Results: In total, 29,756 patients were enrolled, and the incidence of POD was 3.22% after variable screening. AUCs were 0.783 (0.765–0.8) for the logistic regression method, 0.78 for random forest, 0.76 for GBM, 0.74 for AdaBoost, 0.73 for XGBoost, and 0.77 for the stacking ensemble model. The respective sensitivities for the 6 aforementioned models were 74.2%, 72.2%, 76.8%, 63.6%, 71.6%, and 67.4%. The respective specificities for the 6 aforementioned models were 70.7%, 99.8%, 96.5%, 98.8%, 96.5%, and 96.1%. The respective precision values for the 6 aforementioned models were 7.8%, 52.3%, 55.6%, 57%, 54.5%, and 56.4%. Conclusions: The optimal application of the logistic regression model could provide quick and convenient POD risk identification to help improve the perioperative management of surgical patients because of its better sensitivity, fewer variables, and easier interpretability than the machine learning model. [ABSTRACT FROM AUTHOR]

Background: Lymphocyte activation gene 3 (LAG-3) is one of the immune checkpoint molecules, negatively regulating the T-cell reactions. The present study investigated the role of LAG-3 in sepsis-induced T-lymphocyte disability.Methods: Mice sepsis was induced by cecal ligation and puncture (CLP). LAG-3 expression on some immune cells were detected 24 hours after CLP. LAG-3 knockout and anti-LAG-3 antibody were applied to investigate the effects on the survival, bacterial clearance. Cytokine levels, T-cell counts, and the presence of apoptosis (in blood, spleen, and thymus) were also determined. In vitro T-cell apoptosis, interferon γ secretion, and proliferation were measured. The expression of interleukin 2 receptor on T cells was also determined after CLP.Results: LAG-3 was up-regulated on CD4+/CD8+ T, CD19+ B, natural killer, CD4+CD25+ regulatory T cells and dendritic cells. Both LAG-3 knockout and anti-LAG-3 antibody had a positive effect on survival and on blood or peritoneal bacterial clearance in mice undergoing CLP. Cytokine levels and T-cell apoptosis decreased in anti-LAG-3 antibody-treated mice. Induced T-cell apoptosis decreased, whereas interferon γ secretion and proliferation were improved by anti-LAG-3 antibody in vitro. Interleukin 2 receptor was up-regulated on T cells in both wild-type and LAG-3-knockout mice undergoing CLP.Conclusions: LAG-3 knockout or anti-LAG-3 antibody blockade protected mice undergoing CLP from sepsis-associated immunodysfunction and may be a new target for the treatment. [ABSTRACT FROM AUTHOR]

Propofol postconditioning (P‑PostC) offers cardioprotection in mice, and the upregulation of autophagy protects cardiac cells against ischemia/reperfusion injury. The present study aimed to examine the effects of P‑PostC on the induction of autophagy and its potential roles in hypoxia/reoxygenation (H/R) injury. Rat heart‑derived H9c2 cells were exposed to H/R, comprising 6 h of hypoxia followed by 4 h of reoxygenation, as well as postconditioning with various concentrations of propofol at the onset of reperfusion. Lactate dehydrogenase (LDH) activity and the rate of cell apoptosis were measured to evaluate the degree of cardiomyocyte H/R injury. The induction of autophagy in myocytes subjected to H/R injury and P‑PostC was detected by western blotting and immunofluorescence. Furthermore, the activation of c‑Jun N‑terminal kinase (JNK) in cells treated with P‑PostC with or without co‑treatment with SP600125, an inhibitor of JNK, was also determined by western blotting. P‑PostC reduced the activity of LDH in the culture medium and the percentage of apoptotic cells compared with cells in the untreated H/R group. In addition, P‑PostC induced autophagy and promoted survival signaling in H9c2 cardiac myoblast cells. The inhibition of autophagy by 3‑methyladenine treatment diminished the cardioprotective effects of P‑PostC. These results indicated that propofol postconditioning promoted cell survival through the induction of autophagy in H9c2 cardiac cells, and that the stress‑activated protein kinase/JNK survival pathway may be partly involved in P‑PostC‑induced autophagy. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To characterize the expression profiles of genes in purified monocytes from septic patients during systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS), and then to investigate the potential mechanism of monocyte deactivation. Methods: Lipopolysaccharides (LPS)-induced cytokine responses, phagocytosis assay and migration assay were performed in monocytes from SIRS patients, CARS patients and healthy volunteers (n = 8). After functional assays, each pair of samples from the same group was pooled into one for gene expression analysis. All new samples (n = 4) were hybridized on NimbleGen human gene expression 12 × 135 K microarrays, and selected genes were validated by real-time polymerase chain reaction. Pathway analysis and Gene Ontology analysis were performed on differentially expressed genes using Agilent GeneSpring (version 11.0). Results: A set of genes related to pro-inflammation, phagocytosis, chemotaxis, antigen presentation, and anti-apoptosis were significantly down-regulated, while some genes associated with pro-apoptosis and anti-inflammation were up-regulated instead on monocytes from CARS patients compared with SIRS patients and healthy volunteers. Monocytes from CARS patients showed impaired production of TNF-α and IL-6, and increased release of IL-10 when stimulated by LPS. Functional analysis confirmed reduced phagocytosis and migratory activity of monocytes from CARS patients. Human leukocyte antigen-DR (HLA-DR) measurements demonstrated decreased expression of HLA-DR on monocytes from CARS patients. Conclusion: Monocytes from CARS patients exhibited significant changes in mRNA expression of genes associated with phagocytosis, antigen presentation, inflammatory response, cell migration, and apoptosis, which might cause deactivation of monocytes during CARS. [ABSTRACT FROM AUTHOR]