Reliable in vitro neuronal models are essential for studying neuronal development and neurological diseases. Although SH-SY5Y cells, derived from human neuroblastoma, are widely used for neuronal differentiation, their efficiency varies markedly with experimental conditions, and standardized quantitative evaluation methods remain lacking. Here, we systematically optimized glutamatergic differentiation of SH-SY5Y cells by modulating serum concentration, extracellular matrix growth factors, induction duration, and basal medium composition. Reduced serum levels promoted neurite outgrowth, while growth factor-enriched Matrigel and nutrient-rich media enhanced neurite complexity and expression of neuronal markers. Prolonged induction further augmented glutamatergic differentiation. To enable objective and quantitative assessment, we developed a Neuronal Differentiation Score (NDS) by integrating morphological and molecular features via principal component analysis. The NDS strongly correlated with neuronal architecture and marker expression, allowing reliable classification of differentiation grades (high-grade defined as NDS > -0.0967). These findings provide an optimized protocol for reproducible glutamatergic differentiation of SH-SY5Y cells and a validated, quantitative tool for assessing neuronal maturation, facilitating more reliable in vitro modeling of neurodevelopment and disease.

Introduction:Observational studies suggest a potential association between asthma and frailty, but the causal relationship remains unclear. This study aimed to explore this association and determine its causal nature, with implications for targeted interventions that could improve patient management and quality of life. Material and methods:This study analyzed cross-sectional data from the National Health and Nutrition Examination Survey and included 29,589 participants. Multivariate logistic regression was used to assess the association between asthma and frailty, with propensity score matching for reliability. Bidirectional Mendelian randomization (MR) was used, with genetic variants associated with asthma and frailty obtained from the FinnGen database and a large GWAS meta-analysis. Causal effects were estimated using inverse variance weighting, with sensitivity analyses for robustness. Results:Cross-sectional analysis found a significant association between asthma and frailty (OR = 2.16; 95% CI: 2.01-2.31; p < 0.001). After adjusting for confounders using multiple methods, this association remained significant, with ORs ranging from 1.60 to 2.04, all p < 0.001. MR analysis revealed a bidirectional causal relationship: Genetically predicted asthma was significantly associated with an increased risk of frailty, with an OR of 1.091 (95% CI: 1.061-1.123). In the reverse direction analysis, genetic liability to frailty was also significantly associated with an increased risk of asthma, with an OR of 2.264 (95% CI: 1.503-3.409). Conclusions:This study suggests a bidirectional causal association between asthma and frailty. Routine screening for frailty in asthma patients is recommended, and further research is needed to explore the underlying mechanisms.

Postoperative neurocognitive impairment (PNCI) significantly affects the recovery and long-term outcomes of elderly patients, with central nervous system (CNS) inflammation serving as the key pathogenic driver of its development. As the resident immune cells of the CNS, microglia play a crucial role in regulating perioperative inflammation and maintaining homeostasis. However, the contribution, phenotypic heterogeneity, and communication network of perioperative microglia in the development of PNCI remain insufficiently characterized. 18-month-old mice underwent surgery and developed PNCI. The hippocampi of mice in both control and surgery groups were dissected 24 h postoperatively for single-cell RNA sequencing. Immunofluorescence coupled with fluorescence in situ hybridization was used to verify the number of subpopulations and the expression levels of target RNA transcripts in the hippocampus. Cognitive function tests were conducted to evaluate the effects of the TNF inhibitor etanercept in PNCI model. Eight microglial subpopulations and six astrocytic subpopulations were identified in the hippocampus. Postoperatively, the percentage of microglial subpopulations underwent dramatic changes, with inflammation associated microglia (IAM) increasing more than 14-fold and transition state microglia (TSM) increasing more than 33-fold. These alterations were accompanied by a marked enhancement of intercellular communications among glial cells, particularly driven by the activation of TNF signaling pathway in IAM. This pathway, along with its associated regulatory network, critically modulated the function of astrocytes and endothelial cells, thereby playing a pivotal role in CNS inflammation and the subsequent development of PNCI. Notably, administration of TNF inhibitor etanercept attenuated IAM activation and glial network communication in the hippocampus, which was associated with improved cognitive performance in PNCI mice. These results highlight the pivotal role of TNF signaling activation in IAM and its associated glial cell communication as the fundamental mechanism driving hippocampal CNS inflammation, which subsequently contributes to the onset and progression of PNCI.

This study analyzes research trends in anesthesiology over the past decade (2013-2023) by conducting a systematic keyword analysis of articles published in leading anesthesia journals, including Anesthesia, British Journal of Anesthesia, Anesthesiology, Journal of Clinical Anesthesia, and Anesthesia & Analgesia. Using the Bibliometrix software package (R version 3.5.6), we identified temporal patterns and journal-specific preferences in research themes. Early trends emphasized pain management, neuromuscular blockade, and perioperative physiology, while the COVID-19 pandemic shifted focus toward respiratory management and pandemic-related concerns. In recent years, research priorities have increasingly highlighted perioperative brain health, including postoperative cognitive dysfunction and delirium, alongside the integration of artificial intelligence to optimize perioperative care. These findings reflect the evolving landscape of anesthesiology, with a growing emphasis on mitigating postoperative complications and addressing the cognitive outcomes of surgical patients-issues of relevance to aging populations. By bridging gaps between research innovations and clinical application, this study underscores the importance of multidisciplinary collaboration to enhance patient outcomes and inform public health strategies in the perioperative setting.

AIMS:The rapidly growing scale and complexity of single-cell transcriptomic data in brain research make it increasingly difficult for traditional methods to extract meaningful insights efficiently, highlighting the need for artificial intelligence. MATERIALS AND METHODS:We presented the Hybrid Learning-based Brain single-cell Prediction Framework (HL-BscPF), designed to automate cell type classification and reveal disease-related pathways in the brain. HL-BscPF integrates ItClust and TOSICA models, combining autoencoder-based dimensionality reduction with transformer architecture to enhance predictive accuracy. HL-BscPF was evaluated using brain scRNA-seq datasets representing various neuropathological states, and its predictive performance was benchmarked against ground-truth annotations. KEY FINDINGS:Applied to four brain-specific single-cell datasets, including aging, Alzheimer's disease, postoperative cognitive dysfunction, and stroke, HL-BscPF accurately classified cell types and uncovered key functional alterations in neuronal and glial populations. TOSICA showed higher accuracy in large-scale datasets due to its multi-head self-attention capabilities, whereas ItClust performed optimally in cases with lower cell diversity, demonstrating their complementary strengths. By providing precise cell identification and novel insights into brain-specific pathway dysregulation, HL-BscPF offers a powerful tool for extracting meaningful insights from vast single-cell datasets, enabling a deeper understanding of the complex neuropathologies. SIGNIFICANCE:HL-BscPF demonstrates exceptional accuracy and interpretability in cell type annotation and functional analysis, uncovering critical disease-related mechanisms. This framework offers a powerful tool for advancing single-cell research in brain pathologies.

Background: The reciprocal nexus between sleep and pain is well -documented, with the deleterious impact of operative trauma potentially playing a pivotal role in the dysregulation of this interplay, which could significantly contribute to the manifestation of postoperative delirium (POD). Studies have investigated the effect of adding dexmedetomidine (DEX) to patientcontrolled intravenous analgesia (PCIA) pumps on postoperative pain -sleep interaction cycle and POD, but conclusions remained uncertain. The objective of this investigation is to perform a meta -analysis that thoroughly assesses the impact of integrating DEX into PCIA, focusing on analgesic effectiveness, sleep quality, and the incidence of delirium in postoperative patients. Methods: PubMed, Embase, Cochrane Library, SinoMed, and Wanfang Data Knowledge Service Platform were searched, for publications in any language, from database inception to September 2023. Our analysis encompassed randomized controlled trials (RCTs) that examine the therapeutic efficacy and risk profile of adding DEX to the PCIA on the postoperative pain -sleep interaction cycle, by focusing on changes in postoperative analgesia (Visual analog scale (VAS) score), sleep efficiency, sleep structure, subjective sleep score (Assen insomnia scale and numerical rating scale) and adverse event rate. Results: 34 RCTs (4324 patients) were analyzed. This study shows DEX improved analgesia and reduced VAS scores at 6, 12, and 24 h after surgery. Sleep efficiency was enhanced on the 1st and 2nd postoperative night. DEX improved sleep structure at the 1st postoperative night by reducing non -rapid eye movement stage 1 (N1) sleep and increasing non -rapid eye movement stage 2 (N2) and non -rapid eye movement stage 3 (N3) sleep. At the 2nd night, DEX reduced N1 sleep and increased N2 sleep, but not N3 sleep. Data from AIS and NRS showed improvement in subjective sleep scores on the 1st postoperative night and 2nd night. Additionally, DEX decreased the occurrence of POD on the 24 h and first -three days.

Background Perioperative neurocognitive disorders (PND) refer to neurocognitive abnormalities during perioperative period, which are a great challenge for elderly patients and associated with increased morbidity and mortality. Our studies showed that long non-coding RNAs (lncRNAs) regulate mitochondrial function and aging-related pathologies in the aged hippocampus after anesthesia, and lncRNAs are associated with multiple neurodegenerations. However, the regulatory role of lncRNAs in PND-related pathological processes remains unclear. Methods A total of 18-month mice were assigned to control and surgery (PND) groups, mice in PND group received sevoflurane anesthesia and laparotomy. Cognitive function was assessed with fear conditioning test. Hippocampal RNAs were isolated for sequencing, lncRNA and microRNA libraries were constructed, mRNAs were identified, Gene Ontology (GO) analysis were performed, and lncRNA-microRNA-mRNA networks were established. qPCR was performed for gene expression verification. Results A total of 312 differentially expressed (DE) lncRNAs, 340 DE-Transcripts of Uncertain Coding Potential (TUCPs), and 2,003 DEmRNAs were identified in the hippocampus between groups. The lncRNA-microRNA-mRNA competing endogenous RNA (ceRNA) network was constructed with 29 DElncRNAs, 90 microRNAs, 493 DEmRNAs, 148 lncRNA-microRNA interaction pairs, 794 microRNA-mRNA interaction pairs, and 110 lncRNA-mRNA co-expression pairs. 795 GO terms were obtained. Based on the frequencies of involved pathological processes, BP terms were divided into eight categories: neurological system alternation, neuronal development, metabolism alternation, immunity and neuroinflammation, apoptosis and autophagy, cellular communication, molecular modification, and behavior changes. LncRNA-microRNA-mRNA ceRNA networks in these pathological categories were constructed, and involved pathways and targeted genes were revealed. The top relevant lncRNAs in these ceRNA networks included RP23-65G6.4, RP24-396L14.1, RP23-251I16.2, XLOC_113622, RP24-496E14.1, etc., and the top relevant mRNAs in these ceRNA networks included Dlg4 (synaptic function), Avp (lipophagy), Islr2 (synaptic function), Hcrt (regulation of awake behavior), Tnc (neurotransmitter uptake). Conclusion In summary, we have constructed the lncRNA-associated ceRNA network during PND development in mice, explored the role of lncRNAs in multiple pathological processes in the mouse hippocampus, and provided insights into the potential mechanisms and therapeutic gene targets for PND.

Background: Dexmedetomidine is known for its selective action on α2-adrenoceptor sites and is recognized for its neuroprotective capabilities. It can improve postoperative cognitive function. Commonly used anesthetics, such as sevoflurane and propofol, have been reported to affect postoperative cognitive function. Therefore, it could be valuable to explore dexmedetomidine-led anesthesia strategy. This study was designed to assess the performance, safety, and effective infusion rate in anesthesia maintenance, to explore a feasible dexmedetomidine-led anesthesia maintenance protocol, and to provide a foundation for potential combined anesthesia. Methods: Thirty patients aged 18–60 years, classified as ASA I or II, undergoing abdominal surgery were involved. The anesthesia maintenance was achieved with dexmedetomidine, remifentanil and rocuronium. Dixon up-and-down sequential methodology was utilized to ascertain the ED50 of dexmedetomidine for maintaining Patient State Index (PSI) 25–40 (depth of stage III anesthesia). Intraoperative HR, BP and depth of anesthesia were monitored and controlled. The wake-up time from anesthesia, the incidence of intraoperative awareness and postoperative delirium, and the patients’ satisfaction were assessed. Results: The results indicated that dexmedetomidine-led anesthesia could maintain the depth of stage III anesthesia during abdominal surgery. The ED50 and ED95 of dexmedetomidine infusion rates during anesthesia maintenance were 2.298 μg/kg·h (95%CI: 2.190–2.404 μg/kg·h) and 3.765 μg/kg·h (95%CI: 3.550–4.050 μg/kg·h). Continuous infusion of dexmedetomidine and 0.1–0.3 μg/kg·min remifentanil could maintain PSI 25–40, and provide appropriate anesthesia depth for abdominal surgery. Perioperative bradycardia and hypertension could be rapidly corrected with atropine and nitroglycerin. The median wake-up time after anesthesia was 4.8 min, the perioperative maximum HR had significant correlation with wake-up time and intraoperative dexmedetomidine dose. No intraoperative awareness and postoperative delirium occurred; the patients were satisfied with dexmedetomidine-led anesthesia. Conclusions: dexmedetomidine-led strategy could maintain stable depth of anesthesia throughout surgery, and the ED50 of dexmedetomidine infusion rates was 2.298 μg/kg·h. Intraoperative HR, BP and depth of anesthesia require monitoring, the bradycardia and hypertension could be rapidly corrected.

Glia-neuron interaction is a crucial feature in aged hippocampus during the occurrence of postoperative cognitive impairment. However, the regulatory effects of microglia, astrocytes, and oligodendrocytes in this glia-neuron interaction, the potential mechanisms and gene targets are still to be elucidated. Here, single-cell RNA sequencing was performed to detect the perioperative genomic expression characteristics of neuroglial system in the hippocampus of aged mice, and to investigate the potential cross-cellular mechanisms and valuable treatment options for glia-neuron interaction-related cognitive impairment. We found that postoperative neurons and glia cells exhibited protein dysmetabolism and mitochondrial electron misrouting. Impaired autophagy and circadian rhythm worsened microglia activation/neuroinflammation, and exacerbated these metabolic alterations. Reactive microglia also aggravated astrocyte and oligodendrocyte cytotoxicity through the PGD2/DP and complement pathways, altering glutamate level and synaptic function via the "tripartite synapses" model, and affecting neuronal myelination. Ligand-receptor communication also indicated these synaptic and axonal dysfunctions via enhanced MDK and PTN pathways. Additionally, we found that anesthetic dexmedetomidine hold therapeutic potential within the disrupted neuroglial system. It enhanced neuronal metabolic rebalance (Atf3-related) and reduced neuroinflammation from a multicellular perspective, therefore improving postoperative cognitive impairment. Together, our study proposes an aged hippocampal cell atlas and provides insights into the role of disrupted glia-neuron cycle in postoperative cognitive impairment. Our findings also elucidate the therapeutic potential and mechanism of dexmedetomidine intervention.

BackgroundRemimazolam is a new ultrashort-acting benzodiazepine for sedation and anesthesia. The effects of remimazolam and the mechanism by which it functions in cancer cells have not been determined. This research aimed to explore the mechanism of remimazolam action in colon cancer treatment, using bioinformatics analysis and in vitro experiments.MethodsCell cycle progression, colony formation, self-renewal capacity, and apoptosis detection were performed in HCT8 cells treated with or without remimazolam. Transcriptome sequencing, Gene Ontology, Kyoto Encyclopedia of Genes and Genome, Protein–Protein Interaction, Gene Set Enrichment Analysis, Western blotting, and qPCR were performed to investigate the mechanism of action of remimazolam in HCT8 colon cancer cells.ResultsRemimazolam promoted proliferation and cell-cycle progression of HCT8 cells. After remimazolam treatment, a total of 1,096 differentially expressed genes (DEGs) were identified: 673 genes were downregulated, and 423 genes were upregulated. The DEGs were enriched mainly in “DNA replication“, “cell cycle”, and “G1/S transition” related pathways. There were 15 DEGs verified by qPCR, and representative biomarkers were detected by Western Bloting. The remimazolam-mediated promotion of cell proliferation and cell cycle was reversed by G1T28, a CDK4/6 inhibitor.ConclusionRemimazolam promoted cell-cycle progression and proliferation in HCT8 colon cancer cells, indicating that the long-term use of remimazolam has potential adverse effects in the anesthesia of patients with colon cancer.

Background Surgical pain affects postoperative sleep quality, and they jointly form a vicious cycle of mutual influence. The cycle of postoperative pain and sleep disorders could lead to delirium, cardiovascular disease, and hyperalgesia, which significantly affect patients' postoperative recovery. Thus, exploring this phenomenon is of great importance for surgical patients, and warrants further investigation. Objective By employing bibliometric methods, this study systematically analyzes the publications on postoperative pain-sleep disorders, identifies research trends and field dynamics, and ultimately provides insights for further progress in this research area. Methods In this study, we searched the Web of Science database for studies on postoperative pain and sleep disorders from 2013 to 2023, and analyzed the number of publications, journals, authors, institutions, country regions, and keywords by utilizing CiteSpace, VOSviewer, and Bibliometrix. Results The 1894 retrieved publications showed a trend of increasing number of publications and correlations between postoperative pain and sleep disorders from 2013 to 2023. The top countries for publications included the USA, China, etc., establishing a global collaborative network centered around the USA, China, and Europe. The top institutions for publications included University of California System, Harvard University, etc. The top authors include Christine Miaskowski, Steven M. Paul, Qiuling Shi, etc. These publications involved multiple disciplines including surgery, neurology, and anesthesiology, and various research funds including NIH, HHS, NSFC, etc. The top journals for publications included the European Archives of Oto-Rhino-Laryngology, etc. Keywords that appear most frequently in this field include "pain", "surgery", "quality of life", "sleep", "depression", and "outcomes". The thematic map indicated that the hot topics in this area include obstructive sleep apnea, tonsillectomy, children, pain, quality of life, and sleep. The undeveloped topics with research potential included postoperative pain, analgesia and dexmedetomidine, breast cancer, fatigue, and lung cancer. Conclusion The increased number of publications and correlations between postoperative pain and sleep disorders, and the collaborative network across the USA, China, and Europe indicate a growing global interest in this area. This study also provides valuable insights into the trend of hot topics and frontiers and shows that this is an evolving and dynamic research area.

BackgroundDexmedetomidine (DEX) is a sedative with greater preservation of cognitive function, reduced respiratory depression, and improved patient arousability. This study was designed to investigate the performance of DEX during anesthesia induction and to establish an effective DEX induction strategy, which could be valuable for multiple clinical conditions.MethodsPatients undergoing abdominal surgery were involved in this dose-finding trial. Dixon's up-and-down sequential method was employed to determine the effective dose of DEX to achieve the state of “loss of consciousness”, and an effective induction strategy was established with continuous infusion of DEX and remifentanil. The effects of DEX on hemodynamics, respiratory state, EEG, and anesthetic depth were monitored and analyzed.ResultsThrough the strategy mentioned, the depth of surgical anesthesia was successfully achieved by DEX-led anesthesia induction. The ED50 and ED95 of the initial infusion rate of DEX were 0.115 and 0.200 μg/kg/min, respectively, and the mean induction time was 18.3 min. The ED50 and ED95 of DEX to achieve the state of “loss of consciousness” were 2.899 (95% CI: 2.703–3.115) and 5.001 (95% CI: 4.544–5.700) μg/kg, respectively. The mean PSI on the loss of consciousness was 42.8 among the patients. During anesthesia induction, the hemodynamics including BP and HR were stable, and the EEG monitor showed decreased α and β powers and increased θ and δ in the frontal and pre-frontal cortices of the brain.ConclusionThis study indicated that continuous infusion of combined DEX and remifentanil could be an effective strategy for anesthesia induction. The EEG during the induction was similar to the physiological sleep process.

Postoperative cognitive dysfunction (POCD) is a serious and common complication induced by anesthesia and surgery. Neuronal apoptosis induced by general anesthetic neurotoxicity is a high-risk factor. However, a comprehensive analysis of general anesthesia-regulated gene expression patterns and further research on molecular mechanisms are lacking. Here, we performed bioinformatics analysis of gene expression in the hippocampus of aged rats that received sevoflurane anesthesia in GSE139220 from the GEO database, found a total of 226 differentially expressed genes (DEGs) and investigated hub genes according to the number of biological processes in which the genes were enriched and performed screening by 12 algorithms with cytoHubba in Cytoscape. Among the screened hub genes, Agt, Cdkn1a, Ddit4, and Rhob are related to the neuronal death process. We further confirmed that these genes, especially Ddit4, were upregulated in the hippocampus of aged mice that received sevoflurane anesthesia. NMDAR, the core target receptor of sevoflurane, rather than GABAAR, mediates the sevoflurane regulation of DDIT4 expression. Our study screened sevoflurane-regulated DEGs and focused on the neuronal death process to reveal DDIT4 as a potential target mediated by NMDAR, which may provide a new target for the treatment of sevoflurane neurotoxicity.

BACKGROUND:Propofol is a common sedative-hypnotic drug used for general anesthesia. Recent studies have drawn attention to the antitumor effects of propofol, but the potential mechanism by which propofol suppresses colon cancer stemness and epithelial-mesenchymal transition (EMT) has not been fully elucidated. METHODS:For the in vitro experiments, we used propofol to treat LOVO and SW480 cells and Cell Counting Kit-8 (CCK-8) to detect proliferation. Self-renewal capacity, cell invasion and migration, flow cytometry analysis, qPCR and Western blotting were performed to detect the suppression of propofol to colon cancer cells and the underlying mechanism. Tumorigenicity and immunohistochemistry experiments were performed to confirm the role of propofol in vivo. RESULT:We observed that propofol could suppressed stem cell-like characteristics and EMT-related behaviors, including self-renewal capacity, cell invasion and migration in colon cancer cells, and even suppressed tumorigenicity in vivo. Furthermore, investigations of the underlying mechanism revealed that propofol treatment downregulated SIRT1. SIRT1 overexpression or knockdown affected the stemness and EMT of colon cancer cells. Additionally, propofol reversed stemness and EMT in cells with overexpressing SIRT1 and subsequently inhibited the Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways. Wnt/β-catenin pathway inhibitor and PI3K/AKT/mTOR pathway inhibitor blocked the propofol-induced reduction of sphere-formation and cell invasion-migration. CONCLUSION:Propofol inhibits LOVO and SW480 cell stemness and EMT by regulating SIRT1 and the Wnt/β-catenin and PI3K/AKT/mTOR signaling pathways. Our findings indicate that propofol inhibits SIRT1 in cancer and is advantageous in colon cancer surgical treatment of patients with high SIRT1 expression.

Circular RNAs are highly stable single-stranded circular RNAs and enriched in the brain. Previous studies showed that circRNAs, as part of competing endogenous RNAs (ceRNAs) network, play an important role in neurodegenerative and psychiatric diseases. However, the mechanism of circRNA-related ceRNA networks in postoperative cognitive dysfunction (POCD) has not been elucidated yet. POCD usually occurs in elderly patients and is characterized by hippocampal dysfunction. Here, aged C57BL/6 mice were subjected to exploratory laparotomy under sevoflurane anesthesia, and this POCD model was verified by Morris water maze test. Whole-transcriptome sequencing was performed on the hippocampus of control group (Con) and surgery group. One hundred and seventy-seven DEcircRNAs, 221 DEmiRNAs and 2,052 DEmRNAs were identified between two groups. A ceRNA network was established with 92 DEcircRNAs having binding sites with 76 DEmiRNAs and 549 target DEmRNAs. In functional enrichment analysis, a pathological pattern of POCD was highlighted in the ceRNA network: Abnormal metabolic process in neural cells, including oxygen metabolism, could promote apoptosis and then affect the synaptic function, which may undermine the neural plasticity and eventually lead to changes in cognitive function and other behavioral patterns. In conclusion, this specific ceRNA network of circRNAs-miRNAs-mRNAs has provided novel insights into the regulatory mechanisms of POCD and revealed potential therapeutic gene targets.

Postoperative cognitive impairment is more likely to occur in elderly patients and in those with neurodegenerative diseases. The mechanisms underlying this impairment include neuroinflammation and oxidative stress. The increase in reactive oxygen species during oxidative stress causes cellular and molecular injury to neurons, including DNA damage, which aggravate brain dysfunction. Vitamin C has antioxidant effects and improves cognitive function in patients with Alzheimer's disease. However, it is unclear whether it can ameliorate surgery-induced cognitive impairment by inhibiting oxidative stress. In this study, 6-month-old mice overexpressing mutant amyloid precursor protein and presenilin-1 (APP/PS1) were subjected to laparotomy. The open field and fear conditioning tests were used to assess cognitive function. Mice that underwent surgery showed cognitive impairment without changes in spontaneous locomotor activity. Oxidative stress, DNA damage and inflammatory mediators were increased in the hippocampus after surgery. The expression levels of non-homologous end-joining DNA repair-associated proteins, including Ku heterodimer, DNA-dependent protein kinase catalytic subunit, X-ray repair cross complementing 4 (XRCC4) and XRCC4-like factor, were increased after surgery. Vitamin C pretreatment effectively attenuated cognitive dysfunction induced by surgery and reduced oxidative stress and DNA damage. Our findings suggest that DNA damage plays an important role in surgery-induced cognitive dysfunction, and that vitamin C pretreatment may have therapeutic potential as a preventative approach for the cognitive impairment.

急救复苏的实施关系着抢救的成功率,是临床医师的必备技能和住院医师规范化培训中的必备项目.受临床诊治条件的限制,急救复苏的培训科目难以直接开展.医学模拟教学可以模拟急救情景,为受训人员提供实践急救诊治和技术的机会,使急救复苏实践培训的开展成为可能.本文探讨了急救复苏培训工作的临床价值和现状,在医学生教育、住院医师培训和医学继续教育中实践急救模拟教学的方案和重点.以我们的急救模拟培训为基础,结合国内外的培训经验,论述医学模拟教学在急救复苏培训中的实践构想和设计方案,包括建立急救病例库和教学培训团队,资源共享和远程模拟教学模式.同时,探讨了急救模拟培训的推广策略,为急救复苏规范化培训在国内的开展提供了理论基础和实践方法.

AIM:Perioperative neurocognitive disorders (PND) occur frequently after surgery and anesthesia, especially in aged patients. Previous studies have shown multiple PND related mechanisms in the hippocampus; however, their relationships remain unclear. Meanwhile, the perioperative neuropathological processes are sophisticated and changeable, single period study could not reveal the accurate mechanisms. Thus, multiperiod whole-transcriptome study is necessary to elucidate the gene expression patterns during perioperative period.METHODS:Aged C57BL/6 mice were subjected to exploratory laparotomy under sevoflurane anesthesia. Whole-transcriptome sequencing (RNA-seq analysis) was performed on the hippocampi from control condition (Con), 30 min (Day0), 2 days (Day2), and 7 days (Day7) after surgery. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analyses, quantitative real-time PCR, immunofluorescence, and fear conditioning test were also performed to elucidate the pathological processes and modulation networks during the period.RESULTS:Through RNA-seq analysis, 328, 3597, and 4179 differentially expressed genes (DEGs) were screened out in intraoperative period (Day0 vs. Con), early postoperative period (Day2 vs. Day0), and late postoperative period (Day7 vs. Day2). The involved GO biological processes were divided into 9 categories, and positive-regulated processes were more than negative-regulated ones. Seventy-four transcription factors were highlighted. The potential synaptic and neuroinflammatory pathways were constructed for Neurotransmitter, Synapse and Neuronal alteration categories with 9 genes (Htr1a, Rims1, and Ezh2, etc.). The metabolic and mitochondrial pathways were constructed for metabolism, oxidative stress, and biological rhythm categories with 9 genes (Gpld1, Sirt1, and Cry2, etc.). The blood-brain barrier and neurotoxicity related pathways were constructed for blood-brain barrier, neurotoxicity, and cognitive function categories with 10 genes (Mmp2, Itpr1, and Nrf1, etc.).CONCLUSION:The results revealed gene expression patterns and modulation networks in the aged hippocampus during perioperative period, which provide insights into overall mechanisms and potential therapeutic targets for prevention and treatment of perioperative central nervous system diseases, such as PND, from the genetic level.

BACKGROUND:Ewing's sarcoma of the adrenal gland with inferior vena cava (IVC) and right atrium thrombus is extremely rare. Here, we report a case of giant adrenal Ewing's sarcoma with IVC and right atrium tumor thrombus and summarize the anesthesia and perioperative management.CASE SUMMARY:A young female was admitted to the Department of Urology with intermittent pain under the right costal arch for four months. Enhanced abdominal computed tomography revealed a large retroperitoneal mass (22 cm in diameter), which may have originated from the right adrenal gland and was closely related to the liver. Transthoracic echocardiography showed a strong echogenic filling measuring 70 mm extended from the IVC into the right atrium and ventricle. After preoperative preparation with cardiopulmonary bypass, sufficient blood products, transesophageal echocardiography and multiple monitoring, tumor and thrombus resection by IVC exploration and right atriotomy were successfully performed by a multidisciplinary team. Intraoperative hemodynamic stability was the major concern of anesthesiologists and the status of tumor thrombus and pulmonary embolism were monitored continuously. During transfer of the patient to the intensive care unit (ICU), cardiac arrest occurred without external stimulus. Cardiopulmonary resuscitation was performed immediately and cardiac function was restored after 1 min. In the ICU, extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) were provided to maintain cardiac, liver and kidney function. Histopathologic examination confirmed the diagnosis of Ewing's sarcoma. After postoperative treatments and rehabilitation, the patient was discharged from the urology ward.CONCLUSION:An adrenal Ewing's sarcoma with IVC and right atrium thrombus is extremely rare, and its anesthesia and perioperative management have not been reported. Thus, this report provides significant insights in the perioperative management of patients with adrenal Ewing's sarcoma and IVC tumor thrombus. Intraoperative circulation fluctuations and sudden cardiovascular events are the major challenges during surgery. In addition, postoperative treatments including ECMO and CRRT provide essential support in critically ill patients. Moreover, this case report also highlights the importance of multidisciplinary cooperation during treatment of the disease.

OBJECTIVES:Single-injection erector spinae plane block (ESPB) provides good control of pain relief after open thoracotomy surgeries. However, the duration of pain relief does not last long. For this purpose, we hypothesized that adding α2-adrenoceptor agonist, dexmedetomidine, for interfascial nerve blockade may increase the duration of analgesia. There are only few studies using dexmedetomidine for interfasical nerve blocks in humans. In this study, our aim is to investigate whether addition of dexmedetomidine to ropivacaine for ESPB could effectively prolong the duration of postoperative analgesia and reduce opioid consumption after open thoracotomy.MATERIALS AND METHODS:Sixty patients with esophageal cancer were randomized to receive ESPB using 28 mL of 0.5% ropivacaine, with 2 mL of normal saline (group R) or 0.5 µg/kg dexmedetomidine in 2 mL (group RD) administered interfascially. ESPB was performed at the fifth thoracic level under ultrasound guidance. The primary outcome was the duration of analgesia. The secondary outcomes were total postoperative sufentanil consumption, Numeric Rating Scale pain scores, Ramsay Sedation Scale scores and adverse effects.RESULTS:The duration of analgesia in group RD (505.1±113.9) was longer than that in group R (323.2±75.4) (P<0.001). The total postoperative sufentanil consumption was lower in group RD (23.3±10.0) than in group R (33.8±13.8) (P=0.001). There was no significant difference in the incidence of adverse effects between the 2 groups.CONCLUSION:After open thoracotomy, addition of dexmedetomidine to ropivacaine for ESPB effectively prolonged the duration of postoperative analgesia and reduced opioid consumption without increasing additional incidence of adverse effects.