Guoqing Zhao

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.

Background: Inhalational 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.Methods: Six-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.Results: After 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.Conclusion: Multiple 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.

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.

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.

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.

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.

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.

Depression is a common psychiatric disease caused by various factors, manifesting with continuous low spirits, with its precise mechanism being unclear. Early life stress (ELS) is receiving more attention as a possible cause of depression. Many studies focused on the mechanisms underlying how ELS leads to changes in sex hormones, neurotransmitters, hypothalamic pituitary adrenocortical (HPA) axis function, and epigenetics. The adverse effects of ELS on adulthood are mainly dependent on the time window when stress occurs, sex and the developmental stage when evaluating the impacts. Therefore, with regard to the exact sex differences of adult depression, we found that ELS could lead to sex-differentiated depression through multiple mechanisms, including 5-HT, sex hormone, HPA axis, and epigenetics.