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We conducted a non-inferiority study to assess the postoperative quality of recovery (QoR) in elderly patients receiving ciprofol or propofol total intravenous anesthersia(TIVA)after elective laparoscopic major abdominal surgery, with QoR-15 scores as the main measure. A prospective, double-blind, randomized non-inferiority trial was conducted in the theater, post-anesthesia care unit (PACU), and the ward. 144 elderly patients (age ≥ 65 years) were randomly assigned to either the ciprofol group or the propofol group. The ciprofol group received continuous infusion of ciprofol with remifentanil, and the propofol group received infusion of propofol with remifentanil. The primary outcome was the QoR-15 on the first postoperative day (POD1), assessed in both intention-to-treat and per-protocol populations, with the mean difference between groups compared to a non-inferiority threshold of −8. Additional assessments included QoR-15 scores on POD2, 3, and 5 for both analysis sets. Other evaluated perioperative value factors included hemodynamic parameters and injection discomfort in the intention-to-treat analysis. A linear mixed model was utilized to examine the impact of group-time interactions on hemodynamic data and QoR-15. The QoR-15 scores on POD1 in the ciprofol group were non-inferior to those in the propofol group both in intention-to-treat set (mean [95 %CI], 95.9[93.7–98.2] vs. 95.6 [93.3–97.8]; mean difference [95 % CI], 0.4 [−2.8–3.5]; P<0.001 for noninferiority) and per-protocol set (mean [95 %CI], 96.7 [94.4–99.0] vs. 95.7 [93.4–98.0]; mean difference [95 % CI], 1.0 [−2.2–4.3]; P<0.001 for noninferiority). Comparable outcomes were noted on postoperative days 2, 3, and 5 following the procedure in both analysis sets. Additionally: compared with propofol group, the occurrence of injection pain was lower (2.8 % vs. 27.8 %, P < 0.001); the hypotension was less frequent (33.3 % vs. 54.2 %, P = 0.012); the bradycardia was more common (38.9 % vs. 23.6 %, P = 0.048). Ciprofol is not inferior to propofol in QoR. Ciprofol can be suitably administered to elderly patients undergoing elective laparoscopic major abdominal surgery. •Ciprofol is a novel intravenous anesthetic agent.•Ciprofol offers a comparable quality of recovery to propofol, with reduced injection pain, more stable intraoperative hemodynamics.•For elderly patients with cardiovascular diseases undergoing major laparoscopic surgery, ciprofol may be preferable to propofol.

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.

Background Postoperative pain is common in pediatric urological surgery. The study assess the impact of perioperative intravenous infusion of low-dose esketamine on postoperative pain in pediatric urological surgery. Methods Pediatric patients ( n  = 80) undergoing urological surgery were randomized into four groups. Patients in the control group were administered an analgesic pump containing only hydromorphone at a dose of 0.1 mg/kg (Hydromorphone Group 1, H1) or 0.15 mg/kg (Hydromorphone Group 2, H2). Patients in the experimental group were injected intravenously with 0.3 mg/kg of esketamine (Esketamine group 1, ES1) or equal volume of saline (Esketamine Group 2, ES2) during anesthesia induction. Esketamine 1.0 mg/kg and hydromorphone 0.1 mg/kg were added to the analgesic pump. Face, Leg, Activity, Crying, and Comfort (FLACC) scale or the Numerical Rating Scale (NRS) and adverse effects were recorded at 2, 6, 24, and 48 h postoperatively. Additionally, total and effective PCA button presses were recorded. Results In comparison to the H1 group, the pain scores were notably reduced at all postoperative time points in both the ES1 and H2 groups. The ES2 group exhibited lower pain scores only at 24 and 48 h postoperatively. When compared to the H2 group, there were no significant differences in pain scores at various postoperative time points in the ES2 group. However, the ES1 group demonstrated significantly lower pain scores at 6, 24 and 48 h postoperatively, and these scores were also significantly lower than those observed in the ES2 group. The total and effective number of PCA button presses in the ES1, ES2 and H2 group were lower than that in the H1 group ( P  < 0.001). The incidence of adverse effects within 48 h after surgery was 15% in ES1, 22% in ES2, 58% in H1, and 42% in H2, respectively ( P  = 0.021). Conclusions The use of low-dose esketamine infusion in analgesia pump can effectively alleviates postoperative pain in pediatric urological patients, leading to a significant reduction in the number of analgesic pump button press. The combined approach of perioperative anesthesia induction and analgesia pump administration is recommended for optimal pain management in these patients. Trial registration Chinese Clinical Trial Registry - ChiCTR2300073879 (24/07/2023).

Postoperative thoracic surgery is often accompanied by severe pain, and opioids are a cornerstone of postoperative pain management, but their use may be limited by many adverse events. Several studies have shown that the perioperative application of esketamine adjuvant therapy can reduce postoperative opioid consumption. However, whether esketamine has an opioid-sparing effect after thoracic surgery is unclear. To explore the opioid-sparing effect of different doses of esketamine infusion during thoracic surgery and its impact on patient recovery. Randomized controlled study. A single-center study with a total of 120 patients. Patients were randomly allocated to 1 or 3 groups receiving intraoperative intravenous infusions of esketamine 0.15 mg · kg-1· h-1 (group K1), esketamine 0.25 mg · kg-1· h-1(group K2), or placebo (group C). Postoperative opioid consumption, and postoperative indicators like extubation time, PACU stay time, and adverse events were recorded for each group. The consumption of hydromorphone during the first 24 and 48 postoperative hours was significantly reduced in patients of group K2 compared to those of group C and group K1. The time to extubation and post anesthesia care unit (PACU) stay were significantly shorter in group K2 than in group K1 and group C. The time to first feed and off the bed time after surgery were shorter in groups K1 and K2 than in group C. Patients in group K2 were significantly satisfied with patient controlled intravenous analgesia (PCIA) than in groups K1 and C. The sample size calculation was based mainly on the index of hydromorphone consumption. Intraoperative intravenous esketamine at 0.25 mg · kg-1 · h-1 reduced postoperative opioids consumption by 34% in postoperative 24 hours and 30% in postoperative 48 hours in patients undergoing thoracic surgery. It also improved the quality of perioperative recovery.

Sleep is crucial for sustaining normal physiological functions, and sleep deprivation has been associated with increased pain sensitivity. The histone deacetylases (HDACs) are known to significantly regulate in regulating neuropathic pain, but their involvement in nociceptive hypersensitivity during sleep deprivation is still not fully understood. Utilizing a modified multi-platform water environment technique to establish a sleep deprivation model. We measured the expression levels of HDAC1/2 in the medial prefrontal cortex (mPFC) through immunoblotting and real-time quantitative PCR. The presence of pyroptosis was determined using a TUNEL assay. Suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor employed clinically, was injected into the peritoneal cavity to inhibit HDAC2 expression. Animal pain behaviors were evaluated by measuring paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs). Our findings indicate that sleep deprivation leads to increased nociceptive hypersensitivity, an upregulation of HDAC2 expression in the mPFC, a downregulation of the expression of nuclear factor erythroid 2-related factor 2 (NRF2), and changes in markers of oxidative stress in rats. SAHA, the HDAC inhibitor, enhanced NRF2 expression by inhibiting HDAC2, which consequently ameliorated oxidative stress and mitigated nociceptive hypersensitivity in rats. The incidence of apoptosis was found to be higher in the mPFC tissues of sleep deprivation rats, and the intraperitoneal administration of SAHA decreased this apoptosis. The co-injection of SAHA and the NRF2 inhibitor ML385 into sleep deprivation rats negated the beneficial effects of SAHA. In conclusion, HDAC2 is implicated in the induction of oxidative stress and apoptosis by suppressing NRF2 levels, thereby exacerbating nociceptive hypersensitivity in sleep deprivation rats.

Purpose: Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the E[D.sub.50] of ciprofol in elderly patients. Patients and Methods: A total of 26 non-frail patients and 28 frail patients aged 65-78 years, with BMI ranging from 15 to 28 kg/[m.sup.2], and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS<4), frail patients (CFS[greater than or equal to]4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient's dose was dependent on the previous patient's response. Demographic information, heart rate (HR), oxygen saturation (Sp[O.sub.2]), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded. Results: The calculated E[D.sub.50] (95% confidence interval [CI]) and E[D.sub.95] (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250-0.284) and 0.301 mg/kg (95% CI 0.284-0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244-0.281) and 0.302 mg/kg (95% CI 0.283-0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia. Conclusion: Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients. Keywords: ciprofol, median effective dose, elderly patients, frailty, loss of consciousness

Purpose: Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED50 of ciprofol in elderly patients.Patients and Methods: A total of 26 non-frail patients and 28 frail patients aged 65– 78 years, with BMI ranging from 15 to 28 kg/m2, and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS< 4), frail patients (CFS≥ 4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient’s dose was dependent on the previous patient’s response. Demographic information, heart rate (HR), oxygen saturation (SpO2), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded.Results: The calculated ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250– 0.284) and 0.301 mg/kg (95% CI 0.284– 0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244– 0.281) and 0.302 mg/kg (95% CI 0.283– 0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia.Conclusion: Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.

Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED of ciprofol in elderly patients. A total of 26 non-frail patients and 28 frail patients aged 65-78 years, with BMI ranging from 15 to 28 kg/m , and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS<4), frail patients (CFS≥4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient's dose was dependent on the previous patient's response. Demographic information, heart rate (HR), oxygen saturation (SpO ), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded. The calculated ED (95% confidence interval [CI]) and ED (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250-0.284) and 0.301 mg/kg (95% CI 0.284-0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244-0.281) and 0.302 mg/kg (95% CI 0.283-0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia. Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.

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.

Alzheimer’s disease (AD) is a degenerative neurological illness for which effective therapy alternatives are currently lacking. Photothermal therapy (PTT) employs the localized thermal effects of nano-photothermal agents (NPTAs) under near-infrared (NIR) light for the treatment of diverse conditions. PTT presents numerous benefits for AD therapy, including operational flexibility, non-invasiveness, spatiotemporal modulation, and synergistic multimodal treatment approaches. The primary mechanisms of PTT for AD treatment encompass the following facets: Initially, localized heat impacts may transiently disrupt the blood-brain barrier (BBB), facilitating the trans-BBB transport of therapeutic medicines. Secondly, the photothermal action can efficiently dissociate Aβ aggregates and Tau protein while inhibiting Aβ aggregation, hence diminishing neurotoxicity and reinstating cognitive function. Third, during PTT, NPTAs can achieve imaging of biomarkers such as Aβ and Tau at the site of AD lesions and actively monitor the therapy process. Despite being in its nascent stages for AD treatment and encountering numerous challenges, such as poor biocompatibility, inadequate penetration of deep brain tissue by NIR light, and cumulative toxicity risks, PTT remains a promising therapeutic strategy to overcome the limitations of AD treatment. This study elucidates the pathophysiology of AD, the processes by which NPTAs enter the brain, and the mechanism of NPTAs in AD theranostics, with a particular focus on current developments in NIR-activated NPTAs for AD treatment. It further discusses the challenges in this emerging field and proposes future research directions, thereby facilitating the clinical translation of PTT-based strategies in AD treatment. Graphical Abstract Nano-photothermal agents (NPTAs) serve as an innovative trident weapon for Alzheimer's disease (AD) theranostics.