BACKGROUND:Early-life exposure to sevoflurane is considered an important risk factor for abnormal neurodevelopment and may lead to impaired myelination and neurobehavioral deficits in neonatal mice. Sodium butyrate (NaB), a short-chain fatty acid (SCFA) with epigenetic regulatory activity, has shown neuroprotective effects in various neurological disorders. However, the role of NaB in sevoflurane-induced myelination impairment and the underlying molecular mechanisms remain unclear. METHODS:An in vivo neonatal mouse model of sevoflurane exposure was established to investigate its effects on myelination and neurobehavioral function. NaB intervention was then administered to evaluate its potential to ameliorate sevoflurane-induced myelination impairment and neurobehavioral deficits. In vitro, human oligodendrocyte precursor cells (HOPCs) were directly treated with different concentrations of NaB to examine its effects on cell proliferation, migration, differentiation, and related molecular signaling pathways. RESULTS:Repeated exposure to sevoflurane during the critical period of brain development in neonatal mice inhibited the proliferation and differentiation of oligodendrocyte precursor cells (OPCs), impaired myelination, and led to neurobehavioral deficits. NaB intervention ameliorated sevoflurane-induced myelination impairment and neurobehavioral dysfunction by regulating histone H3 lysine 9 acetylation (H3K9ac), upregulating brain-derived neurotrophic factor (BDNF) expression, promoting tropomyosin receptor kinase B (TrkB) phosphorylation, and increasing phosphorylated TrkB (p-TrkB) levels. CONCLUSIONS:Repeated sevoflurane exposure in neonatal mice inhibited OPC proliferation and differentiation, impaired myelination, and caused neurobehavioral deficits. NaB ameliorated these impairments by regulating H3K9ac modification and increasing BDNF and p-TrkB levels.

Diabetes-associated cognitive dysfunction represents a global health challenge, yet the mechanisms by which anesthetics modulate cognitive function in diabetic states remain poorly understood. We systematically compared the effects of 2-hour brief exposure to sevoflurane (SEV) and propofol (PRO) on cognitive function and neuropathology in streptozotocin (STZ) -induced diabetic mice. Morris water maze and Y-maze tests revealed that SEV significantly exacerbated spatial memory and learning deficits in mice, while PRO showed no significant effects. Additionally, diabetic mice exhibited reduced NeuN+ neurons, increased β-amyloid deposition, and decreased SYN expression in the hippocampal CA1 region as examined by Immuno-fluorescence staining. Neither short-term SEV nor PRO exposure aggravated neuronal structural damage. Further transcriptomics revealed both anesthetics affected hippocampal neuron differentiation, but SEV uniquely perturbed fatty acid metabolism pathways. Metabolomics identified SEV-induced disruptions in lipid metabolism, marked by elevated hippocampal free fatty acids, phospholipids, as well as reduced lysophospholipids and acylcarnitine. Integrated multi-omics analysis demonstrated that SEV impaired cognition by suppressing fatty acid oxidation and dysregulating glycerophospholipid metabolism. These findings highlight the critical impact of anesthetic selection in diabetic populations.

Perioperative neurocognitive disorders (PNDs) encompass a spectrum of cognitive impairments that may affect patients before, during, or after surgical procedures, with significant implications for patient outcomes, and healthcare expenditures. This comprehensive review examines the evolution of PND terminology, clinical manifestations, diagnostic criteria, incidence rates, risk factors, underlying mechanisms, preventive measures, management strategies, and future research directions. The authors emphasize the importance of early diagnosis and intervention to enhance postoperative recovery and underscore the necessity of a multidisciplinary approach to patient care.

BackgroundInhalational anesthetic sevoflurane is commonly used in pediatric anesthesia. Multiple exposures to sevoflurane in early postnatal life have been associated with long-term abnormalities in myelin development and cognitive and memory impairments, although the underlying mechanisms remain incompletely elucidated. Disruption of gut microbiota is recognized as an important contributor to neurological diseases. Here, we explore the potential mechanisms underlying the abnormal myelin development induced by multiple sevoflurane exposures in neonatal rats by analyzing gut homeostasis.MethodsSix-day-old (P6) C57BL/6 mice were exposed to 3% sevoflurane for 2 hours per day for three consecutive days. Mice exposed to a mixture of 60% nitrogen and oxygen under the same conditions and duration served as controls. Behavioral tests were conducted between P32 and P42. At P9 (24 hours after the last sevoflurane exposure) and P42 (after the completion of behavioral tests), intestinal and brain examinations were performed to investigate the effects of sevoflurane exposure during the lactation and adolescent periods on gut homeostasis and myelin development in mice. Subsequently, the ameliorative effects of butyrate supplementation on sevoflurane-induced abnormalities in myelin development and cognitive and memory impairments were observed.ResultsAfter repeated exposure to sevoflurane, neonatal mice developed persistent gut microbiota imbalance accompanied by a decrease in short-chain fatty acids. Short-term intestinal inflammation emerged, with damage to the mucus layer and barrier function. In the hippocampus and prefrontal cortex, the expression of genes and transcription factors related to oligodendrocyte differentiation and myelin development was significantly affected, and these changes persisted even after the exposure ended. There was a reduction in proteins associated with oligodendrocytes and myelin formation, which had a certain impact on memory and cognitive behavior. This study also explored the potential connections between microbiota, metabolism, the gut, the brain, and behavior. Timely supplementation with butyrate could effectively reverse these changes, indicating that gut homeostasis is crucial for brain neurodevelopment.ConclusionMultiple exposures to sevoflurane in neonatal mice disrupt gut homeostasis and affect oligodendrocyte differentiation and myelin development in the hippocampus and prefrontal cortex, inducing cognitive and memory impairments. Supplementation with butyrate can alleviate these changes.

Abstract Blood group is a potential genetic element in coronary artery disease. Nevertheless, the relationship between different ABO blood groups and myocardial injury after non-cardiac surgery (MINS) is poorly understood. This study verified whether ABO blood group is a potential MINS influencing factor. This retrospective cohort study included 1201 patients who underwent elective non-cardiac surgery and a mandatory troponin test on postoperative days 1 and 2 from 2019 to 2020 at a university-affiliated tertiary hospital. The primary outcome was associations between ABO blood groups and MINS, assessed using univariate and multivariate logistic-regression analyses. Path analysis was used to investigate direct and indirect effects between blood group and MINS. MINS incidence (102/1201, 8.5%) was higher in blood-type B patients than in non-B patients [blood-type B: 44/400 (11.0%) vs. non-B: 58/801 (7.2%); adjusted odds ratio = 1.57 (1.03–2.38); p = 0.036]. In the confounding factor model, preoperative hypertension and coronary artery disease medical history were associated with MINS risk [adjusted odds ratio: 2.00 (1.30–3.06), p = 0.002; 2.81 (1.71–4.61), p < 0.001, respectively]. Path analysis did not uncover any mediating role for hypertension, diabetes, or coronary artery disease between blood type and MINS. Therefore, blood-type B is associated with higher MINS risk; potential mediators of this association need to be investigated.

Isoflurane, a widely used inhalation anesthetic in clinical practice, is associated with an increased risk of neuronal injury. Heat shock protein 90 (HSP90) plays a crucial role in maintaining neuronal homeostasis under stress conditions; however, its role during isoflurane exposure remains poorly understood. In this study, we aimed to investigate the protective effects of HSP90 inhibition and explore the regulatory mechanisms underlying these effects during isoflurane exposure. We found that the HSP90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17 AAG) has great protective effects in mitigating isoflurane-induced ferroptosis of mouse hippocampus and cultured neuronal cells. We focused on the activity of the crucial protein GPX4 in ferroptosis and found that 17 AAG exerted protective effects, preserving the physiological GPX4 activity under isoflurane exposure; further, 17 AAG restored the protein level of GPX4. Further, we observed that the chaperone-mediated autophagy (CMA) pathway was activated; 17 AAG also mediated GPX4 degradation under isoflurane exposure. Additionally, it interfered with the formation of complexes between HSP90 and Lamp-2a, inhibiting CMA activity, followed by the blockade of GPX4 degradation, further affecting the isoflurane-induced ferroptosis. Based on these findings, we proposed HSP90 inhibition as a protective mechanism against isoflurane-induced ferroptosis in neurons.

臂丛神经损伤(BPI)是一种严重的上肢神经损伤,伤后上肢尤其手部运动的恢复极为困难.恢复程度主要取决于伤后治疗是否及时,故BPI的早期诊断就显得尤为重要[1].早期的臂丛神经重建术对于损伤神经的恢复具有重要意义,然而,对损伤的早期诊断、分级以及手术方法的选择依旧困难重重[2].

Introduction Stellate ganglion block (SGB) is usually used in the department of algiatry. But preoperative SGB may reduce adverse cardiovascular events in high-risk patients, although evidence remains sparse. Therefore, we aim to determine whether a single-shot postoperative SGB can reduce the incidence of myocardial injury after non-cardiac surgery (MINS) and improve recovery in patients undergoing laparoscopic radical resection for colorectal cancer.Methods and analysis This is an investigator-initiated, single-centre, randomised, two-arm clinical trial enrolling patients aged over 45 years and scheduled for elective laparoscopic radical colorectal surgery with at least one risk factor for MINS. A total of 950 eligible patients will be randomised into a routine or block groups. The primary outcome is the incidence of MINS. The secondary outcomes include the Visual Analogue Scale of pain during rest and movement, the incidence of delirium, quality of recovery (QOR) assessed by QOR-15, and sleep quality assessed by Richards Campbell Sleep Questionnaire. Tertiary outcomes include time to first flatus, gastrointestinal complications such as anastomotic leak or ileus, length of hospital stay, collapse incidence of severe cardiovascular and cerebrovascular complications of myocardial infarction, cardiac arrest, ischaemic or haemorrhagic stroke, and all-cause mortality within 30 days after the operation.Ethics and dissemination The protocol was approved by Medical Ethics Committee of the China-Japan Union Hospital, Jilin University (Approval number: 2021081018) prior to recruitment. The study will be performed according to the guidelines of the Declaration of Helsinki. The findings of this study will be published and presented through various scientific forums.Trial registration number ChiCTR2200055319.

Postoperative pain occurs immediately after surgery. The most common perioperative analgesic methods are nerve block, patient-controlled intravenous analgesia, and patient-controlled epidural analgesia. However, overuse of opioid analgesics can cause many adverse reactions including excessive sedation, respiratory inhibition, postoperative nausea, and vomiting. In recent years, many clinical trials have shown that perioperative acupuncture has unique advantages in patients. Perioperative acupuncture can relieve intraoperative pain, improve postoperative pain management, reduce postoperative nausea and vomiting, and shorten the length of hospital stay. This study aimed to confirm the analgesic effect of perioperative acupuncture by reviewing studies on the different methods of perioperative acupuncture and their analgesic effects. The cited literature was searched in English and Chinese from PubMed, China National Knowledge Infrastructure, and Wanfang data, using the following keywords: "perioperative pain," "acupuncture," "electroacupuncture," and "perioperative analgesia." Studies published from 2005 to 2023 were included. All retrieved papers were read in detail. Perioperative acupuncture has benefits in reducing postoperative pain and opioid need. Although analgesic drugs are still the primary means of postoperative pain control, acupuncture provides a safe analgesic supplement or alternative. This review aimed to assist practitioners in choosing appropriate perioperative acupuncture methods by summarizing the recent literature on the role of different acupuncture approaches for perioperative pain management.

Perioperative neurocognitive disorders (PNDs) are some of the most common postoperative complications among the elderly and susceptible individuals, which significantly worsens the clinical outcome of patients. However, the prevention and treatment strategies of PNDs are difficult to determine and implement since the pathogenesis of PNDs is not well understood. The development of living organisms is associated with active and organized cell death, which is essential for maintaining the homeostasis of life. Ferroptosis is a programmed cell death (different from apoptosis and necrosis) mainly caused by an imbalance in the generation and degradation of intracellular lipid peroxides due to iron overload. Pyroptosis is an inflammatory cell death characterized by the creation of membrane holes mediated by the gasdermin (GSDM) family, followed by cell lysis and the release of pro-inflammatory cytokines. Ferroptosis and pyroptosis are involved in the pathogenesis of various central nervous system (CNS) diseases. Furthermore, ferroptosis and pyroptosis are closely associated with the occurrence and development of PNDs. This review summarizes the main regulatory mechanisms of ferroptosis and pyroptosis and the latest related to PNDs. Based on the available evidence, potential intervention strategies that can alleviate PNDs by inhibiting ferroptosis and pyroptosis have also been provided.

This article discusses the effects and mechanisms of Parkin-mediated mitophagy in oxaliplatin-induced peripheral nerve pain (OIPNP) from both in vivo and in vitro. We believe that our study makes a significant contribution to the literature because OIPNP has always been the focus of clinical medicine, and mitochondrial quality regulation mechanisms especially Parkin-mediated mitophagy, have been deeply studied in recent years. We use a variety of molecular biological techniques and animal experiments to support our argument.

Background To compare the effect of different amounts of fresh oxygen flow on oxygen reserve in patients undergoing general anesthesia. Methods Seventy-two patients were enrolled in this quasi-experimental study. Patients were randomly divided into experimental groups with a fresh oxygen flow of 1 L/min, 2 L/min, 4 L/min, and 8 L/min (denoted as G1, G2, G3, and G4, respectively) for 2 min of mask-assisted ventilation. Safe apnea time (SAT) was the primary endpoint; SAT was defined as the time from the cessation of ventilation to the time the patient’s pulse oxygen saturation (SpO 2 ) decreased to 90%. Ventilation indicators such as end-tidal oxygen concentration (EtO 2 ), end-tidal carbon dioxide partial pressure (EtCO 2 ), SpO 2, and carbon dioxide (CO 2 ) elimination amount, during mask-assisted ventilation, were the secondary endpoints. Results The SAT of G1, G2, G3, and G4 were 305.1 ± 97.0 s, 315 ± 112.5 s, 381.3 ± 118.6 s, and 359 ± 104.4 s, respectively ( p > 0.05). The EtO 2 after 2 min of mask-assisted ventilation in groups G1, G2, G3, and G4 were 69.7 ± 8.8%, 75.2 ± 5.0%, 82.5 ± 3.3%, and 86.8 ± 1.5%, respectively ( p < 0.05). Also, there was a moderate positive correlation between the fresh oxygen flow and EtO 2 (correlation coefficient r = 0.52, 95% CI 0.31–0.67, p < 0.0001). The CO 2 elimination in the G1 and G2 groups was greater than that in the G4 group ( p < 0.05). There was no significant difference in other indicators among the groups (all p > 0.05). Conclusion The amount of fresh oxygen flow during mask-assisted ventilation was positively correlated with EtO 2 . Also, even though there was no significant difference, the patients’ oxygen reserves increased with the increase in fresh oxygen flow.

Iso�urane is one of the most popular inhalation anesthetics in the clinical practice but presenting an increased risk of neuronal injury. Hsp90 has been indicated to present an important role for maintaining neuronal homeostasis under the stress. However, the effect of hsp90 during iso�urane exposure is poorly understood. Here in this study, we aimed to observe the protect effect of hsp90 inhibition, and investigate the potential regulatory mechanism after iso�urane exposure. We found that hsp90 inhibitor, 17AAG, showed a great protective effect in maintaining isourane-induced ferroptosis of mice hippocampus and cultured neuronal cells. We focus on the crucial protein GPX4 activity in ferroptosis, and found that the 17 AAG contributed its protect effect to preserve physiological level of GPX4 activity under iso�urane exposure, although 17AAG could restored the protein level of GPX4. Further, we observed CMA pathway was activated and then mediated GPX4 degradation under iso�urane exposure. And 17AAG could interfere the complex between hsp90 and lamp2a to inhibit CMA activity, followed by blocking GPX4 degradation, which further affected the isourane-induced ferroptosis. Based on these �ndings, we proposed that hsp90 inhibition as a protective mechanism against isourane-induced ferroptosis in neurons.

Postoperative neurocognitive disorders are common neurological complications following surgery that are generally characterized by varying degrees of cognitive impairment. Postoperative neurocognitive disorders can exhibit as short-term postoperative delirium and/or long-term postoperative cognitive dysfunction. In addition, postoperative neurocognitive disorders may result in poor outcomes in patients, and are a leading cause of postoperative morbidity and mortality, particularly in elderly patients. Recently, there has been a heightened interest in mechanisms and clinical treatments for postoperative neurocognitive disorders. Though some influencing factors and mechanisms of postoperative neurocognitive disorders have been revealed, they remain troublesome problems in clinical departments. Dexmedetomidine is a commonly used anesthetic adjuvant that may help improve postoperative cognitive impairment, especially the conditions of a postoperative acute event (postoperative delirium, within 1 week after operation) and delayed neurocognitive recovery (postoperative cognitive dysfunction, up to 30 days). In the recent literature, dexmedetomidine has been shown to exert positive effects on cognitive impairment in clinical and animal studies, especially for postoperative neurocognitive disorders. However, not all clinical findings support this efficacy. Though some mechanisms of dexmedetomidine on postoperative neurocognitive disorders have been proposed, such as signaling pathways associated with inflammation and apoptosis, this evidence is fragmentary and disputed in the literature. Therefore, this article aims to review the potential biological mechanisms underlying dexmedetomidine's effects on postoperative neurocognitive disorders, providing a reference for future studies.

氯普鲁卡因(CP )属酯类局部麻醉剂,是将普鲁卡因的对氨基苯甲酸的二位上用氯原子取代,使其具有作用快,效果好,恢复快,毒性低等特点.CP的麻醉持续时间可达 60分钟,麻醉强度为普鲁卡因的2 倍,代谢速度快 4 倍,不良反应降低一半[1],适用于椎管内麻醉,周围神经阻滞和局部浸润麻醉.本文将综述 CP 的作用机制、不良事件概况以及应用进展.

Purpose Neuropathic pain causes great distress among patients; however, its response to traditional analgesia techniques remains sub-optimal. There has been progress in stem cell research for neuropathic pain treatment; however, effective homing remains problematic. This study aimed to establish Fe3O4@polydopamine(PDA)-labeled mesenchymal stem cells (MSCs); moreover, we aimed to guide MSCs using a magnetic field to the spinal cord segments showing pain-related responses to allow MSC homing and gathering, in advance, in order to fully employ their repair function. Materials and Methods Fe3O4@PDA-labeled MSCs were characterized using transmission electron microscopy. We analyzed the characteristics of MSCs, as well as the nanoparticle effects on MSC activity, differentiation, and proliferation, using the CCK-8 method, flow cytometry, and staining. Using rats, we performed behavioral tests of mechanical and thermal pain hypersensitivity. Serum inflammatory markers were detected using ELISA. Finally, changes in proteins associated with spinal cord pain were detected through quantitative reverse transcription PCR, histology, and immunohistochemistry. Results Fe3O4@PDA did not affect the characteristics and viability of MSCs. The magnetic field guidance improved the therapeutic effect of Fe3O4@PDA-labeled MSCs as indicated by the paw withdrawal threshold. Fe3O4@PDA-labeled MSCs decreased spinal nerve demyelination and c-Fos expression (a pain molecule); moreover, they inhibited microglia and astrocyte activation. Conclusion Fe3O4@PDA-labeled MSCs showed better homing to the spinal cord under magnetic field guidance. Moreover, they inhibited microglial and astrocyte activation, as well as played an early and continuous role in neuropathic pain treatment.

BACKGROUND:Bone cement implantation syndrome (BCIS) is characterized by hypotension, arrhythmia, diffuse pulmonary microvascular embolism, shock, cardiac arrest, any combination of these factors, or even death following bone cement implantation.CASE SUMMARY:An 80-year-old patient with pemphigus and Parkinson's disease underwent total hip replacement under spinal subarachnoid block and developed acute pulmonary embolism after bone cement implantation. The patient received mask mechanical ventilation with a continuous intravenous infusion of adrenaline (2 μg/mL) at a rate of 30 mL/h. Subsequently, the symptoms of BCIS were markedly alleviated, and the infusion rate of adrenaline was gradually reduced until the infusion was completely stopped 45 min later. The patient was then transferred to the Department of Orthopedics, and anticoagulation therapy began at 12 h postoperatively. No other complications were observed.CONCLUSION:This is a rare case of BCIS in a high-risk patient with pemphigus and Parkinson's disease.

BACKGROUND:Postoperative pain management is crucial for patients undergoing total knee arthroplasty (TKA). There have been many recent clinical trials on post-TKA peripheral nerve block; however, they have reported inconsistent findings. In this meta-analysis, we aimed to comprehensively analyze studies on post-TKA analgesia to provide evidence-based clinical suggestions.METHODS:We performed a computer-based query of PubMed, Embase, the Cochrane Library, and the Web of Science to retrieve related articles using neurothe following search terms: nerve block, nerve blockade, chemodenervation, chemical neurolysis, peridural block, epidural anesthesia, extradural anesthesia, total knee arthroplasty, total knee replacement, partial knee replacement, and others. After quality evaluation and data extraction, we analyzed the complications, visual analogue scale (VAS) score, patient satisfaction, perioperative opioid dosage, and rehabilitation indices. Evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation approach.RESULTS:We included 16 randomized controlled trials involving 981 patients (511 receiving peripheral nerve block and 470 receiving epidural block) in the final analysis. Compared with an epidural block, a peripheral nerve block significantly reduced complications. There were no significant between-group differences in the postoperative VAS score, patient satisfaction, perioperative opioid dosage, and rehabilitation indices.CONCLUSIONS:Our findings demonstrate that the peripheral nerve block is superior to the epidural block in reducing complications without compromising the analgesic effect and patient satisfaction. Therefore, a peripheral nerve block is a safe and effective postoperative analgesic method with encouraging clinical prospects.

Depression is a common psychological and mental disorder, characterized by low mood, slow thinking and low will, and even suicidal tendencies in severe cases. It imposes a huge mental and economic burden on patients and their families, and its prevention and treatment have become an urgent public health problem. It is worth noting that there is a significant gender difference in the incidence of depression. Studies have shown that females are far more likely to suffer from depression than males, confirming a close relationship between estrogen and the onset of depression. Moreover, recent studies suggest that the brain-derived neurotrophic factor- (BDNF-) mammalian target of rapamycin complex-1 (mTORC1) signaling pathway is a crucial target pathway for improving depression and mediates the rapid antidepressant-like effects of various antidepressants. However, it is not clear whether the BDNF-mTORC1 signaling pathway mediates the regulation of female depression and how to regulate female depression. Hence, we focused on the modulation of estrogen-BDNF-mTORC1 signaling in depression and its possible mechanisms in recent years.