Sepsis-induced neuroinflammation plays an important role in sepsis-related brain dysfunction. However, the molecules that are targeted during neuroinflammation resulting from sepsis-induced brain dysfunction remain unclear. Herein, we tried to investigate the expression and roles of NMDA receptor subunits during sepsis-related brain dysfunction. Sepsis was induced by cecal ligation and perforation (CLP) or by a single intraperitoneal injection of lipopolysaccharide (LPS, 8 mg/kg) in C57BL/6J mice. The NMDA receptor co-agonist D-serine was injected intraperitoneally for 3 days (500 mg/kg/day) to compensate for the loss of NMDA receptors. The behaviors of mice were tested in the Barnes maze and in the open field test. The mice were euthanized at the indicated time points. The brains were collected to detect the following: the levels of synaptophysin and NMDA receptor subunits GluN2A, GluN2B and GluN1 (by Western blot and RT-PCR); the number of CA1 neurons (by Nissl staining); neuronal activity (by p-CREB staining); neuroinflammation (by staining of Iba-1 and inflammatory factors IL-1β, TNF-α, NLRP3); and the levels of oxidative stress [by dihydroethidium (DHE)]. Sepsis selectively decreased the protein and mRNA levels of GluN2A, GluN2B and GluN1 but not the levels of synaptophysin or the neuronal number in the hippocampus of mice in either of the classic CLP-induced or LPS-induced sepsis models during the first 7 days after sepsis. Intraperitoneal injection of D-serine obviously limited the lipopolysaccharide-induced changes, including the impairment of learning and memory, the loss of NMDA receptor subunits, robust neuroinflammation, the levels of ROS stress and the decrease of p-CREB in the hippocampus of mice. These data suggest that the sepsis-induced selective loss of NMDA receptors modulates hippocampal neuropathology in the mice that survived sepsis, and the data show that NMDA receptors are potential targets for the improvement of brain dysfunction in sepsis survivors.

Depression is a major public health problem worldwide and is closely related with systemic inflammatory responses. Additionly, physical activity (PA) is thought to be associated with lower levels of depression and inflammatory markers. This study aimed to elucidate the complex interactions between PA, depression, and inflammatory markers. Based on the National Health and Nutrition Examination Survey (NHANES), various logistic regression were applied to analyze the pairwise correlations among the three. Restrictive cubic splines were constructed to explore the nonlinear relationship between PA and depression. Mediation models were used to identify the mediating role of inflammatory markers. The findings revealed a positive link between depression and inflammatory marker, whereas PA was inversely correlated with both inflammatory marker and depression. Particularly, we noticed the greatest reduction in the risk of depression when the level of PA was between 1200 and 1722 MET-min/week. Besides, we demonstrated that inflammatory markers mediate the potential effects of physical inactivity on depression, ranging from 1.72 % to 6.25 %. In conclusion, PA appear to protect against depression, in which inflammatory markers may play a mediating role. Moreover, we determined the optimal dosage of PA to minimize the likelihood of depression, thereby offering valuable guidance for managing depression.

Background: Previous studies have shown that high-density lipoprotein cholesterol (HDL-C) levels are positively associated with cognitive function across a range of concentrations. However, recent studies have suggested that very high HDL-C levels may lead to poorer outcomes. Therefore, we aimed to investigate the relationship between different concentrations of HDL-C and cognitive impairment risk. Methods: We collected data from 3632 participants aged over 60 years from the U.S. National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014 to assess the relationship between HDL-C and cognitive function. Cognitive function was evaluated with the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test, the animal fluency test (AFT), and the digit symbol substitution test (DSST). We used restricted cubic spline models and logistic regression to examine the association between HDL-C and cognitive function. Results: A U-shaped was observed between HDL-C and cognitive outcomes, individuals with higher risk in those with both low and very high HDL-C levels compared with those with midrange values. Very high HDL-C levels (≥ 2.50 mmol/L) were associated with increased risk of cognitive impairment (OR = 2.19; 95% CI, 1.12–4.28) compared with those with HDL-C levels in the range of 1.50 to 1.99 mmol/L in older adults after adjustment for confounding factors. Interaction test demonstrated that relationship between very high HDL-C and the risk of cognitive impairment was not changed in different sex and race group (P for interaction > 0.05). Conclusions: Very high HDL-C levels were associated with an increased risk of cognitive impairment. HDL-C may not be a protective factor for maintaining brain health in older adults at very high levels.

Background: This study aims to investigate the risk factors of perioperative neurocognitive disorders (PNDs) mainly including postoperative cognitive dysfunction (POCD) in elderly patients with gastrointestinal tumors, and evaluate its predictive value. Methods: A total of 222 eligible elderly patients (≥65 years) scheduled for elective gastroenterectomy under general anesthesia were enrolled. The cognitive function assessment was carried out 1 day before surgery and 7 days after surgery. Receiver operating characteristic curve analysis was performed to evaluate the predictive value of risk factors for early POCD. The risk factors for POCD were analyzed using univariate and multivariate logistic regression model. Results: Of all the 222 enrolled patients, 91 (41.0%) developed early POCD and 40 (18.0%) were identified as major POCD within 7 days after the surgery. Visual analogue score (VAS, 1st day, resting) ≥4 (OR = 7.618[3.231–17.962], P < 0.001) and alcohol exposure (OR = 2.398[1.174–4.900], P = 0.016) were independent risk factors for early POCD. VAS score (1st, resting) ≥4 (OR = 13.823[4.779–39.981], P < 0.001), preoperative white blood cell (WBC) levels ≥10 × 10*9/L (OR = 5.548[1.128–26.221], P = 0.035), blood loss ≥500 ml (OR = 3.317[1.094–10.059], P = 0.034), history of hypertension (OR = 3.046[1.267–7.322], P = 0.013), and neutrophil–lymphocyte ratio (NLR) ≥2 (OR = 3.261[1.020–10.419], P = 0.046) were independent risk factors for major POCD. Receiver operating characteristic curve analysis indicated that VAS score (1st day, resting) was a significant predictor for major POCD with a cut-off value of 2.68 and an area under the curve of 0.860 (95% confidence interval: 0.801–0.920, P < 0.001). Conclusions: The risk factors for early POCD after gastroenterectomy included high VAS score (1st day, resting) and alcohol exposure. High VAS score, preoperative WBC levels ≥10 × 10*9/L, blood loss ≥500 ml, NLR ≥2, and history of hypertension were independent risk factors for major POCD. Among them, VAS score was one of the important predictors.

Background: Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients following surgery. The preventive and/or treatment strategies for the incidence remain limited.Objective: This study aimed to investigate the preventive effect of perioperative probiotic treatment on POCD in elderly patients undergoing hip or knee arthroplasty.Methods: After obtaining ethical approval and written informed consent, 106 patients (age ≥60 years) were recruited, who scheduled elective hip or knee arthroplasty, from 16 March 2021 to 25 February 2022 for this randomized, double-blind, and placebo-controlled trial. They were randomly assigned with a 1:1 ratio to receive either probiotics or placebo treatment (four capsules, twice/day) from hospital admission until discharge. Cognitive function was assessed with a battery of 11 neuropsychological tests on the admission day and the seventh day after surgery, respectively.Results: A total of 96 of 106 patients completed the study, and their data were finally analyzed. POCD occurred in 12 (26.7%) of 45 patients in the probiotic group and 29 (56.9%) of 51 patients in the placebo group (relative risk [RR], 0.47 [95% confidence interval [CI], 0.27 to 0.81]; P = 0.003). Among them, mild POCD occurred in 11 (24.4%) in the probiotic group and 24 (47.1%) in the placebo group (RR, 0.52 [95% CI, 0.29 to 0.94]; P = 0.022). No significant difference in severe POCD incidence was found between the two groups (P = 0.209). Compared with the placebo group, the verbal memory domain cognitive function was mainly improved in the probiotic group.Conclusion: Probiotics may be used perioperatively to prevent POCD development and improve verbal memory performance in elderly patients receiving hip or knee arthroplasty.Clinical trial registration: www.chictr.org.cn, identifier: ChiCTR2100045620.