Background: Postoperative delirium (POD) is a serious and common complication. The aim of present study is to investigate the diurnal variation of POD and the effects of esketamine in elderly patients. Methods: A randomized, double-blind, placebo-controlled clinical trial with factorial design was conducted. Patients (aged 65 to 85 years) with normal Mini-Mental State Examination (MMSE) score were stratified by age (≤70 vs. >70) and American Society of Anesthesiologists physical status classification (Ⅱ vs. Ⅲ), then randomly assigned to either morning (08:00–12:00) or afternoon (14:00–18:00) noncardiac operation under general anesthesia with or without esketamine administration (0.2 mg/kg). The primary outcome was the incidence of POD (3-Minute Diagnostic Interview for Confusion Assessment Method-defined Delirium, 3D-CAM) on postoperative days 1, 3, and 7. The secondary outcomes were the scores of MMSE and Hospital Anxiety and Depression Scale. The intention-to-treat analysis of the outcomes were performed by generalized estimating equation. Results: Six patients who did not receive an intervention because of canceled operation were excluded after randomization. The datasets containing 426 cases were analyzed following the intention-to-treat principle after handling missing data via multiple imputation method. The incidence of POD declined from about 55% on postoperative day 1 to 31 and 18% on postoperative days 3 and 7, respectively. Afternoon operation [B=−0.583, OR (95% CI) 0.558 (0.319–0.976); P=0.041], but not esketamine, significantly decreased the incidence of POD. Both esketamine and operation time failed to significantly affect MMSE, HAD, and NRS score. There was no interaction among operation time, esketamine, and follow up time. Conclusion: Elderly patients undergoing elective noncardiac surgery in the afternoon displayed lower POD incidence than those operated in the morning. A single low-dose of esketamine before general anesthesia induction failed to significantly decrease the risk of POD but decrease the risk of intraoperative hypotension and emergence agitation.

Intestinal ischemia‒reperfusion (IIR) injury is a common complication of surgery, but clear molecular insights and valuable therapeutic targets are lacking. Mitochondrial calcium overload is an early sign of various diseases and is considered a vital factor in ischemia‒reperfusion injury. The mitochondrial calcium uniporter (MCU), which is located on the inner mitochondrial membrane, is the primary mediator of calcium ion entry into the mitochondria. However, the specific mechanism of MCU in IIR injury remains to be clarified. In this study, we generated an IIR model using C57BL/6 mice and Caco-2 cells and found increases in the calcium levels and MCU expression following IIR injury. The specific inhibition of MCU markedly attenuated IIR injury. Moreover, MCU knockdown alleviates mitochondrial dysfunction by reducing oxidative stress and apoptosis. Mechanistically, MCU knockdown substantially reduced the translocation of Drp1 and thus its binding to Fis1 receptors, resulting in decreased mitochondrial fission. Taken together, our findings demonstrated that MCU is a novel upstream regulator of Drp1 in ischemia‒reperfusion and represents a predictive and therapeutic target for IIR.

Background: Intestinal ischemia reperfusion (IIR) is a challenging and life-threatening clinical condition, with disease progression closely linked to excessive inflammatory responses. As a potent activator of innate immunity, the mechanism underlying mitochondrial DNA (mtDNA) release across the mitochondrial membrane remains incompletely elucidated. Methods: In this study, an in vivo IIR model was established by clamping the superior mesenteric artery in male mice, and an in vitro hypoxia reoxygenation (HR) model was constructed using Caco-2 cells. Combining multiple techniques including RNA sequencing, subcellular organelle isolation, laser confocal imaging, siRNA transfection, protein cross-linking, Western blotting, enzyme-linked immunosorbent assay (ELISA), and quantitative real-time PCR (qPCR), the regulatory mechanisms of mtDNA release and its biological effects in IIR were systematically verified. Results: We found that IIR significantly induced an increase in cytosolic and circulating mtDNA levels, correlating with inflammatory cytokine production. Mechanistic studies revealed that calcium overload mediated by the mitochondrial calcium uniporter (MCU) triggered the opening of the mitochondrial permeability transition pore (mPTP). Meanwhile, the pro-apoptotic protein BAX was recruited to mitochondria and interacted with BAK to form outer mitochondrial membrane oligomeric pores. Notably, although mPTP opening was independent of the BAX/BAK pathway, the two pathways exhibited sequential synergistic effects during mtDNA release. Inhibition of either pathway significantly reduced mtDNA release, decreased inflammatory cytokine levels, and alleviated intestinal tissue injury caused by IIR. Conclusions: These findings identify mtDNA as a potential biomarker for IIR and highlight the MCU-mPTP-BAX/BAK axis as a therapeutic target. Graphical

After the extubation of endotracheal tubes or removal of laryngeal masks in patients who underwent general anesthesia, complications such as hoarseness often occur, potentially leading to serious adverse effects on patients. Therefore, this study aimed to analyze the causes of hoarseness to provide improved prevention and treatment options. We conducted a retrospective analysis of patients who underwent general anesthesia at the Renmin Hospital of Wuhan University from January 2017 to December 2021, excluding patients under 18 years of age, over 80 years old, with preoperative hoarseness and undergoing multiple surgeries. The incidence, duration, influencing factors and causes of hoarseness after tracheal intubation were analyzed. The study found that the incidence of hoarseness after tracheal intubation was 11.77%. Of those patients experiencing hoarseness immediately after the operation, 79.56% could recover on the same day, 15.37% of patients could recover on the day after operation, 4.23% could recover within 3 days of the operation, and 0.83% of patients might need 5 or more days to recover. Patients aged 50 years and older, with an intubation time of more than 3 h, who underwent neck and cardiothoracic surgery, with a low BMI and with difficult airways exhibited a higher incidence of hoarseness after tracheal intubation. The main causes of hoarseness were vocal cord paralysis and arytenoid joint dislocation, with the number of patients at 8.97% (1106) and 7.32% (902) respectively. The incidences of hoarseness caused by psychological stress accounted for 4.15% of the cases. with a total of 512 patients affected. Age, intubation time, surgical site, low BMI and difficult airway were important factors affecting hoarseness after intubation. The vocal cord paralysis and arytenoid joint dislocation were major causes of hoarseness.