Purpose: Postoperative delirium (POD) is a prevalent and severe complication in elderly patients undergoing major surgery, associated with increased morbidity and mortality. This randomized controlled trial aimed to investigate the effects of low-dose esketamine on the incidence of POD in elderly patients underwent total hip or knee arthroplasty. Patients and Methods: Two hundred and sixty elderly participants were randomly assigned to either the esketamine group (Group E) (0.20mg/kg loading, 0.125mg/kg/h infusion, 0.5 mg/kg for postoperative analgesia) or the placebo group (Group P) (received normal saline). The primary outcome was the incidence of POD, with secondary outcomes including delirium subtypes, duration, intraoperative analgesic consumption, operative and anesthesia times, hemodynamic changes, postoperative pain scores, sleep quality, and common postoperative adverse events. Results: There was no significant difference in the incidence of POD between Group E (8.5%) and Group P (10.8%). No significant differences were observed for the time of delirium onset, duration of delirium, and delirium subtype between the two groups. Patients in the esketamine group had more stable hemodynamic profile after induction and reduced the pain score of motion on the first two days postoperatively but increased the incidence of postoperative dizziness. Conclusion: The repeated infusion of low-dose esketamine did not reduce the incidence of POD during the initial three postoperative days in elderly patients following total hip or knee arthroplasty.

Background: Traumatic brain injury (TBI) is a kind of acquired brain injury, which is caused by external mechanical forces. Moreover, the neuroprotective role of sevoflurane (Sevo) has been identified in TBI. Therefore, this research was conducted to figure out the mechanism of Sevo in TBI via FGF2. Methods: The key factors of neuroprotective effects of Sevo in TBI rats were predicted by bioinformatics analysis. A TBI model was induced on rats that then inhaled Sevo for 1 h and grouped via lentivirus injection. Modified Neurological Severity Score was adopted to evaluate neuronal damage in rats, followed by motor function and brain water content measurement. FGF2, EZH2, and HES1 expression in brain tissues was evaluated by immunofluorescence staining, and expression of related genes and autophagy factors by RT-qPCR and Western blot analysis. Methylation-specific PCR was performed to assess HES1 promoter methylation level, and ChIP assay to detect the enrichment of EZH2 in the HES1 promoter. Neuronal damage was assessed by cell immunofluorescence staining, and neuronal apoptosis by Nissl staining, TUNEL staining, and flow cytometry. Results: Sevo diminished brain edema, improved neurological scores, and decreased neuronal apoptosis and autophagy in TBI rats. Sevo preconditioning could upregulate FGF2 that elevated EZH2 expression, and EZH2 bound to the HES1 promoter to downregulate HES1 in TBI rats. Also, FGF2 or EZH2 overexpression or HES silencing decreased brain edema, neurological deficits, and neuronal autophagy and apoptosis in Sevo-treated TBI rats. Conclusions: Our results provided a novel insight to the neuroprotective mechanism of Sevo in TBI rats by downregulating HES1 via FGF2/EZH2 axis activation.

Sleep is crucial for human health, insufficient sleep or poor sleep quality may negatively affect sleep function and lead to a state of sleep deprivation. Sleep deprivation can result in various health problems, including chronic pain. The intricate relationship between sleep and pain is complex and intertwined, with daytime pain affecting sleep quality and poor sleep increasing pain intensity. The article first describes the influence of sleep on the onset and development of pain, and then explores the impact of daytime pain intensity on nighttime sleep quality and subsequent pain thresholds. However, the primary emphasis is placed on the pivotal role of oxidative stress in this bidirectional relationship. Although the exact mechanisms underlying sleep and chronic pain are unclear, this review focuses on the role of oxidative stress. Numerous studies on sleep deprivation have demonstrated that it can lead to varying degrees of increased pain sensitivity, while chronic pain leads to sleep deprivation and further exacerbates pain. Further research on the role of oxidative stress in the mechanism of sleep deprivation-induced pain sensitization seems reasonable. This article comprehensively reviews the current research on the interrelationship between sleep deprivation, pain and the crucial role of oxidative stress.

Sleep is essential for the body’s repair and recovery, including supplementation with antioxidants to maintain the balance of the body’s redox state. Changes in sleep patterns have been reported to alter this repair function, leading to changes in disease susceptibility or behavior. Here, we recruited healthy male physicians and measured the extent of the effect of overnight sleep deprivation (SD) and recovery sleep (RS) on nociceptive thresholds and systemic (plasma-derived) redox metabolism, namely, the major antioxidants glutathione (GSH), catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD). Twenty subjects underwent morning measurements before and after overnight total SD and RS. We found that one night of SD can lead to increased nociceptive hypersensitivity and the pain scores of the Numerical Rating Scale (NRS) and that one night of RS can reverse this change. Pre- and post-SD biochemical assays showed an increase in MDA levels and CAT activity and a decrease in GSH levels and SOD activity after overnight SD. Biochemical assays before and after RS showed a partial recovery of MDA levels and a basic recovery of CAT activity to baseline levels. An animal study showed that SD can cause a significant decrease in the paw withdrawal threshold and paw withdrawal latency in rats, and after 4 days of unrestricted sleep, pain thresholds can be restored to normal. We performed proteomics in the rat medial prefrontal cortex (mPFC) and showed that 37 proteins were significantly altered after 6 days of SD. Current findings showed that SD causes nociceptive hyperalgesia and oxidative stress, and RS can restore pain thresholds and repair oxidative stress damage in the body. However, one night of RS is not enough for repairing oxidative stress damage in the human body.