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Research progress on the effects and mechanisms of anesthetics on neural stem cells 麻醉药对神经干细胞的作用及其机制的研究进展
Pub Date : 2022-11-07 DOI: 10.1002/ibra.12071
Ji Zhang, Quan-Yuan Chang, Loris Rizzello, You Wu

Exposure to anesthetic drugs has been proven to seriously affect developing animals in terms of neural stem cells' (NSCs') proliferation, differentiation, and apoptosis. This can severely hamper the development of physiological learning and memory skills. Studies on the effects of anesthetics on NSCs' proliferation and differentiation are thus reviewed here, with the aim to highlight which specific drug mechanisms are the least harmful to NSCs. PubMed has been used as the preferential searching database of relevant literature to identify studies on the effects and mechanisms of NSCs' proliferation and differentiation. It was concluded that propofol and sevoflurane may be the safest options for NSCs during pregnancy and in pediatric clinical procedures, while dexmedetomidine has been found to reduce opioid-related damage in NSCs. It was also found that the growth environment may impact neurodevelopment even more than narcotic drugs. Nonetheless, the current scientific literature available further highlights how more extensive clinical trials are absolutely required for corroborating the conclusion drawn here.

麻醉药物暴露已被证明会严重影响发育中的动物神经干细胞(NSCs)的增殖、分化和凋亡。这会严重阻碍生理学习和记忆技能的发展。因此,本文综述了麻醉药对NSCs增殖和分化影响的研究,旨在突出哪些特定药物机制对NSCs的危害最小。利用PubMed作为相关文献的优先检索数据库,对NSCs增殖分化的作用和机制进行研究。结论是,异丙酚和七氟醚可能是妊娠期和儿科临床过程中NSCs最安全的选择,而右美托咪定已被发现可以减少阿片类药物对NSCs的损伤。研究还发现,生长环境对神经发育的影响甚至比麻醉药物更大。尽管如此,现有的科学文献进一步强调,为了证实这里得出的结论,绝对需要更广泛的临床试验。
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引用次数: 0
Effects of gastrodin on the expression of brain aging-related genes in SAM/P-8 mice based on network pharmacology 基于网络药理学的天麻素对SAM/P-8小鼠脑衰老相关基因表达的影响。
Pub Date : 2022-11-06 DOI: 10.1002/ibra.12076
Nan Zhao, Rui Jiang, Jun-Jie Cheng, Qiu-Xia Xiao

Background

Gastrodin can reduce neuronal damage through multiple targets and pathways, and can be useful in preventing and treating degenerative lesions of the central nervous system, but the specific mechanism has not been elucidated.

Methods

The aging-related genes in the hippocampus and the frontal cortex were detected in adult and aged mice treated with gastrodin or not. In addition, we collected the target genes of gastrodin and aging from a network database, and a Venn diagram was created to obtain the intersection target genes of gastrodin and aging. Then, the String database was used to analyze the protein–protein interactions (PPIs) between aging-related genes and the target genes of gastrodin and aging. The “drug–disease–target–pathway” network was constructed using Cytoscape 3.7.2 software, and the main mechanism and pathway of key genes were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Finally, the reliability of these key genes was further verified by molecular docking technology.

Results

The results showed that 6 out of 10 genes related to brain aging were differentially expressed after gastrodin intervention. Moreover, there were 11 key genes between gastrodin and differentially expressed genes related to brain aging. GO and KEGG results suggested that material metabolism and carbohydrate digestion and absorption were associated with the pathological mechanism of gastrodin antiaging. Molecular docking results also confirmed the good binding activity of gastrodin to the key genes.

Conclusion

Gastrodin plays a potential role in antiaging by regulating substance metabolism and carbohydrate digestion and absorption.

背景:天麻素可以通过多种靶点和途径减少神经元损伤,并可用于预防和治疗中枢神经系统退行性病变,但其具体机制尚未阐明。方法:检测天麻素对成年和老龄小鼠海马和额叶皮层衰老相关基因的影响。此外,我们从网络数据库中收集了天麻素与衰老的靶基因,并创建了Venn图来获得天麻素与老化的交叉靶基因。然后,使用String数据库分析衰老相关基因与天麻素和衰老靶基因之间的蛋白质-蛋白质相互作用(PPIs)。使用Cytoscape 3.7.2软件构建“药物-疾病-靶向通路”网络,并通过京都基因与基因组百科全书(KEGG)和基因本体论(GO)分析关键基因的主要机制和通路。最后,通过分子对接技术进一步验证了这些关键基因的可靠性。结果:天麻素干预后,10个脑衰老相关基因中有6个差异表达。此外,天麻素与脑衰老相关的差异表达基因之间存在11个关键基因。GO和KEGG结果表明,物质代谢和碳水化合物的消化吸收与天麻素抗衰老的病理机制有关。分子对接结果也证实了天麻素与关键基因具有良好的结合活性。结论:天麻素通过调节物质代谢和碳水化合物的消化吸收,具有潜在的抗衰老作用。
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引用次数: 0
Thoracic epidural arteriovenous malformation causing rapidly progressive myelopathy and mimicking an acute transverse myelitis: A case report 胸硬膜外动静脉畸形引起快速进行性脊髓病和模拟急性横断面脊髓炎:1例报告
Pub Date : 2022-10-26 DOI: 10.1002/ibra.12070
Hao Yuan, Yu Pi, Hong-Su Zhou, Chong Wang, Wei Liu, Yong-Min Niu, Yang Lan, Dong Chen, Shi-Ran Liu, Shun-Wu Xiao

Clinical symptoms of spinal arteriovenous malformations (AVMs) combined with acute spontaneous hemorrhage lack specificity, which leads to misdiagnosis and delays treatment. The current study aimed to analyze the causes of misdiagnosis and review the key points of diagnosis and treatment. We presented an extremely rare case of a 25-year-old man whose clinical characteristics mimicked acute transverse myelitis, suffering from rapidly and repeatedly progressive myelopathy with a mass. The pathological diagnosis of the mass was AVM; symptom-based surgical treatment with posterior decompression and the removal of epidural AVMs during the postoperative 12-month follow-up period were performed. The manual muscle testing grade score of the proximal and distal muscles in both lower limbs improved from 1 to 5, and the American Spinal Injury Association motor and sensation grade score improved from B to E. In the case of sudden or progressive spinal cord injury of unknown cause and acute spinal cord dysfunction, there might be a misdiagnosis. The key to a differential diagnosis is to take into account AVMs, and spontaneous hemorrhages and hematomas should also be suspected. Angiography and magnetic resonance imaging are very important for the diagnosis of AVM, and we hope to enhance clinicians' understanding of and vigilance for such diseases.

脊髓动静脉畸形(AVMs)合并急性自发性出血的临床症状缺乏特异性,容易导致误诊和延误治疗。本研究旨在分析误诊原因,并对诊断和治疗要点进行综述。我们提出了一个极其罕见的病例,25岁的男子,其临床特征模拟急性横贯脊髓炎,患有快速和反复进行性脊髓病伴肿块。病理诊断为AVM;在术后12个月的随访期间进行以症状为基础的手术治疗,包括后路减压和硬膜外avm的移除。双下肢近端和远端肌肉手工肌肉测试分级由1分提高到5分,美国脊髓损伤协会运动和感觉分级由B分提高到e分。如果出现原因不明的突然或进行性脊髓损伤和急性脊髓功能障碍,可能存在误诊。鉴别诊断的关键是要考虑到动静脉畸形,同时也要怀疑自发性出血和血肿。血管造影和磁共振成像对AVM的诊断非常重要,我们希望能提高临床医生对此类疾病的认识和警惕。
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引用次数: 0
Efficacy of the lumbar sympathetic ganglion block in lower limb pain and its application prospects during the perioperative period 腰交感神经节阻滞治疗围手术期下肢疼痛的疗效及应用前景
Pub Date : 2022-10-09 DOI: 10.1002/ibra.12069
Jing-Han Zhang, Yan-Ping Deng, Min-Jian Geng

The sympathetic nervous system is involved in the physiological pathogenesis of many different types of chronic pain. Sympathetic blocks can interrupt the reflex control system by intercepting the noxious afferent fibers accompanying autonomic nerves, resulting in changes in peripheral or central sensory processing. A lumbar sympathetic ganglion block (LSGB), as a treatment method, refers to the injection of nerve blockers into the corresponding lumbar sympathetic nerve segments, usually requiring imaging assistance (CT, X-ray, ultrasound) to guide. At present, LSGB has been widely used in the clinical treatment of lower limb pain, such as neuropathic pain, lower limb ischemic pain, and so on. Its mechanism of action may be through inhibiting sympathetic nerve activity and dilating blood vessels, thereby alleviating pain and inhibiting stress response. However, there are few reports of LSGB during the perioperative period, especially in postoperative pain and gastrointestinal function. Therefore, by studying the literature about LSGB-related studies, this article reviews the anatomy of the lumbar sympathetic nerve (LSN), with its clinical application and possible mechanism. We reviewed the analgesic effect of LSGB in patients with lower limb pain and postoperative pain and the potential application prospects in the recovery of gastrointestinal function, finally providing a reference for its clinical application.

交感神经系统参与了许多不同类型慢性疼痛的生理发病机制。交感神经阻滞可以通过阻断伴随自主神经的有害传入纤维而中断反射控制系统,导致外周或中枢感觉处理的改变。腰椎交感神经节阻滞(LSGB)作为一种治疗方法,是指在相应的腰交感神经节段注射神经阻滞剂,通常需要影像学辅助(CT、x线、超声)引导。目前,LSGB已广泛应用于临床治疗下肢疼痛,如神经性疼痛、下肢缺血性疼痛等。其作用机制可能是通过抑制交感神经活动,扩张血管,从而减轻疼痛,抑制应激反应。然而,在围手术期,特别是在术后疼痛和胃肠功能方面,LSGB的报道很少。因此,本文通过对腰交感神经相关研究文献的梳理,对腰交感神经的解剖、临床应用及可能的机制进行综述。我们综述了LSGB在下肢疼痛和术后疼痛患者中的镇痛效果以及在胃肠功能恢复中的潜在应用前景,最终为其临床应用提供参考。
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引用次数: 1
Considering gene therapy to protect from X-linked deafness DFNX2 and associated neurodevelopmental disorders 考虑基因治疗以预防x连锁耳聋DFNX2和相关神经发育障碍
Pub Date : 2022-09-27 DOI: 10.1002/ibra.12068
Jean Defourny

Mutations and deletions in the gene or upstream of the gene encoding the POU3F4 transcription factor cause X-linked progressive deafness DFNX2 and additional neurodevelopmental disorders in humans. Hearing loss can be purely sensorineural or mixed, that is, with both conductive and sensorineural components. Affected males show anatomical abnormalities of the inner ear, which are jointly defined as incomplete partition type III. Current approaches to improve hearing and speech skills of DFNX2 patients do not seem to be fully effective. Owing to inner ear malformations, cochlear implantation is surgically difficult and may predispose towards severe complications. Even in cases where implantation is safely performed, hearing and speech outcomes remain highly variable among patients. Mouse models for DFNX2 deafness revealed that sensorineural loss could arise from a dysfunction of spiral ligament fibrocytes in the lateral wall of the cochlea, which leads to reduced endocochlear potential. Highly positive endocochlear potential is critical for sensory hair cell mechanotransduction and hearing. In this context, here, we propose to develop a therapeutic approach in male Pou3f4−/y mice based on an adeno-associated viral (AAV) vector-mediated gene transfer in cochlear spiral ligament fibrocytes. Among a broad range of AAV vectors, AAV7 was found to show a strong tropism for the spiral ligament. Thus, we suggest that an AAV7-mediated delivery of Pou3f4 complementary DNA in the spiral ligament of Pou3f4−/y mice could represent an attractive strategy to prevent fibrocyte degeneration and to restore normal cochlear functions and properties, including a positive endocochlear potential, before hearing loss progresses to profound deafness.

编码POU3F4转录因子的基因或上游基因的突变和缺失导致人类x连锁进行性耳聋DFNX2和其他神经发育障碍。听力损失可以是纯感音神经性的,也可以是混合性的,即既有传导性成分,也有感音神经性成分。受影响的男性表现为内耳解剖异常,共同定义为不完全分区III型。目前改善DFNX2患者听力和语言技能的方法似乎并不完全有效。由于内耳畸形,人工耳蜗植入术难度大,易发生严重并发症。即使在安全植入的情况下,患者的听力和语言结果仍然存在很大差异。小鼠DFNX2型耳聋模型显示,耳蜗外侧壁螺旋韧带纤维细胞功能障碍可引起感音神经丧失,导致耳蜗内电位降低。高度阳性的耳蜗电位对感觉毛细胞机械传导和听力至关重要。在此背景下,我们提出了一种基于腺相关病毒(AAV)载体介导的耳蜗螺旋韧带纤维细胞基因转移的雄性Pou3f4−/y小鼠的治疗方法。在广泛的AAV载体中,发现AAV7对螺旋韧带表现出强烈的趋向性。因此,我们认为aav7介导的Pou3f4互补DNA在Pou3f4−/y小鼠螺旋韧带中的传递可能是一种有吸引力的策略,可以在听力损失发展为深度耳聋之前防止纤维细胞变性,恢复正常的耳蜗功能和特性,包括耳蜗内电位的阳性。
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引用次数: 0
Knockdown of interleukin-6 plays a neuroprotective role against hypoxia-ischemia in neonatal rats via inhibition of caspase 3 and Bcl-2-associated X protein signaling pathway 白细胞介素-6的下调通过抑制caspase 3和bcl -2相关的X蛋白信号通路,对新生大鼠缺氧缺血具有神经保护作用
Pub Date : 2022-09-18 DOI: 10.1002/ibra.12067
Xiu Yang, Ke-Han Liao, Isaac B. Deng, Lan-Chun Zhang

This study aimed to investigate the role of interleukin-6 (IL-6) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (NHIE). Sprague-Dawley (SD) rats were used for the establishment of hypoxic-ischemic (HI) model. The Zea-Longa scoring was used to evaluate the extent of the neurological deficits. Triphenyl tetrazolium chloride (TTC) staining was used to measure the volume of infarction in the brain following HI protocol. The expression of IL-6 in the cortex and/or hippocampus at multiple time points after HI was examined by immunohistochemistry, western blotting and immunofluorescence. Moreover, small interfering RNAs (siRNA) were used to inhibit the expression of IL-6 in-vitro and in-vivo, and the concomitant expression of the Bcl-2 associated X protein (BAX) and caspase 3 was also measured. HI induced a significant brain damage, and these pathological changes were accompanied by IL-6 upregulation which was found localized in cortical neurons. The inhibition of IL-6 expression fostered neuronal and axonal growth, and a reduction in cellular apoptosis in cortical neuronal cultures, and cortex and hippocampus of neonatal rats. The expression of apoptotic markers such as BAX and caspase 3 was closely associated with IL-6. Downregulation of IL-6 could ameliorate HI-induced deficiencies by mediating the expression of caspase 3 and BAX.

本研究旨在探讨白细胞介素-6 (IL-6)在新生儿缺氧缺血性脑病(NHIE)发病机制中的作用。采用SD (Sprague-Dawley)大鼠建立缺血缺氧模型。Zea-Longa评分用于评估神经功能缺损的程度。采用三苯基氯化四氮唑(TTC)染色法测定脑梗死体积。免疫组织化学、免疫印迹和免疫荧光检测HI后多个时间点皮质和/或海马组织中IL-6的表达。此外,利用小干扰rna (small interfering RNAs, siRNA)抑制IL-6在体外和体内的表达,同时检测Bcl-2相关X蛋白(BAX)和caspase 3的表达。HI引起了明显的脑损伤,这些病理改变伴随着IL-6的上调,这种上调出现在皮质神经元中。抑制IL-6的表达可促进新生大鼠的神经元和轴突生长,减少皮质神经元培养物、皮层和海马的细胞凋亡。凋亡标志物BAX、caspase 3的表达与IL-6密切相关。下调IL-6可通过介导caspase 3和BAX的表达来改善hi诱导的缺陷。
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引用次数: 1
Predictors and occurrence of postoperative cognitive dysfunction in children undergoing noncardiac surgery: A prospective cohort study 接受非心脏手术的儿童术后认知功能障碍的预测因素和发生率:一项前瞻性队列研究。
Pub Date : 2022-09-10 DOI: 10.1002/ibra.12066
Fang-Fang Han, Xiu-Mei Wang, Hai-Jun Zhang, Jun-Ze Wang, Zhen-Xing Bao, Yu-Lan Li

In children after cardiac surgery, alterations in cognitive ability and behavior are increasingly common, but whether postoperative cognitive dysfunction (POCD) occurs in children undergoing noncardiac surgery is not known. The present study was performed to investigate the incidence rate and potential risk factors of early neurocognitive dysfunction in children after noncardiac surgery. Two hundred patients aged between 4 and 14 years old underwent elective noncardiac surgery and 100 healthy age-matched controls were enrolled in this prospective observational study. Wechsler Preschool and Primary Scale of Intelligence or Wechsler Intelligence Scale for Children-Revised were conducted 1 day before and 3 days after surgery. POCD was calculated and diagnosed as a combined Z score. Any factors that differed between POCD and non-POCD group (p < 0.10) were tested together by multivariate logistic regression analysis against the cognitive outcome of patients, to find out the independent risk factors of POCD. The general incidence of POCD was 15.6%. The univariate analysis revealed that POCD was associated with general anesthesia, surgical and anesthesia duration, early postoperative fever (EPF), and surgical history. However, only the history of surgery (p = 0.029), anesthesia duration (p = 0.010), and EPF (p < 0.001) were demonstrated to be independent risk factors for POCD. The occurrence rate of early POCD after noncardiac surgery in children is 15.6%. Children who had surgical history, longer anesthesia duration, or EPF are more prone to develop POCD.

在心脏手术后的儿童中,认知能力和行为的改变越来越常见,但接受非心脏手术的儿童是否会发生术后认知功能障碍(POCD)尚不清楚。本研究旨在调查儿童非心脏手术后早期神经认知功能障碍的发生率和潜在危险因素。200名年龄在4至14岁之间的患者接受了选择性非心脏手术,100名年龄匹配的健康对照组被纳入这项前瞻性观察性研究。韦氏学龄前和小学智力量表或韦氏儿童智力量表在手术前1天和手术后3天进行修订。计算POCD并将其诊断为综合Z评分。POCD组和非POCD组之间差异的任何因素(p p = 0.029)、麻醉持续时间(p = 0.010)和EPF(p
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引用次数: 0
Advances in the study of the relationship between Alzheimer's disease and the gastrointestinal microbiome 阿尔茨海默病与胃肠道微生物组关系的研究进展
Pub Date : 2022-09-08 DOI: 10.1002/ibra.12065
Xin-Yan Li, Hao-Yue Qin, Ting-Ting Li

There are many trillions of bacteria in the gastrointestinal microbiome (GM). Their ecological dysregulation can contribute to the development of certain neurodegenerative diseases, including Alzheimer's disease (AD). AD is common dementia and its incidence is increasing year by year. However, the relationship between GM and AD is unclear. Therefore, this review discusses the relationship between GM and AD, elaborates on the possible factors that can affect this relationship through the inflammation of the brain induced by blood−brain damage and accumulation of amyloid deposit, and proposes feasible ways to treat AD through GM-related substances, such as probiotics, Mega-3, and gut hormones, including their shortcomings as well.

胃肠道微生物群(GM)中有数万亿的细菌。它们的生态失调可能导致某些神经退行性疾病的发展,包括阿尔茨海默病(AD)。阿尔茨海默氏症是一种常见的痴呆症,其发病率呈逐年上升趋势。然而,GM和AD之间的关系尚不清楚。因此,本文讨论了转基因与AD的关系,阐述了可能通过血脑损伤引起的脑炎症和淀粉样蛋白沉积影响这种关系的因素,并提出了通过益生菌、Mega-3和肠道激素等转基因相关物质治疗AD的可行方法,以及它们的不足。
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引用次数: 1
Study of anxiety and job burnout, and awareness among young anesthetists during COVID-19 pandemic 新冠肺炎大流行期间年轻麻醉师焦虑、工作倦怠及意识的研究
Pub Date : 2022-08-27 DOI: 10.1002/ibra.12063
Xi Yang, Yunxia Zuo

To describe the psychological impact of coronavirus disease 2019 (COVID-19) on young doctors and their job burnout in the Department of Anesthesiology during the initial days of the pandemic and examine their awareness and familiarity with this pneumonia. We conducted a cross-sectional study in West China Hospital in February 2020. A self-designed questionnaire was sent to all young doctors working in the department of anesthesiology. Impact of Event Scale-Revised and Maslach Burnout Inventory General Survey were used to evaluate the psychological impact and degree of job burnout. Another questionnaire was conducted to explore the awareness and familiarity of COVID-19. All participants were divided into five groups according to the time of clinical practice: Postgraduate year (PGY) 0.5 (less than 0.5 year), 0.6–1 (0.6–1 year), 1–2 (1–2 years), 2–3 (2–3 years), 3 (more than 3 years) groups. The results were collected and analyzed subsequently. A total of 188 questionnaires were collected. There were significant differences in distress level between PGY 0.5 and PGY 0.6–1 (17.60 ± 12.53 vs. 12.05 ± 10.65; p = 0.029), and PGY 3 and PGY 0.6–1 (19.92 ± 11.88 vs. 12.05 ± 10.65; p = 0.031). As for job burnout, there were no differences among the five subgroups. Most participants (86.70%) were kept in good working condition, and 25 participants showed a mild level of job burnout. Although all of the respondents had high awareness of the basic elements of COVID-19, they had little knowledge about the details, such as lab tests, release criteria, and recommended therapy, and this result had no significant difference among the five groups. COVID-19 had caused a mild level of distress and work burnout in young anesthetists. Most of the participants were not clear about the diagnostic, release criteria, and therapeutic method, which will become key teaching points in the future.

描述2019冠状病毒病(COVID-19)在大流行最初几天对麻醉科年轻医生的心理影响及其工作倦怠,并检查他们对这种肺炎的认识和熟悉程度。我们于2020年2月在华西医院进行了横断面研究。一份自行设计的问卷发给所有在麻醉科工作的年轻医生。采用事件影响量表和Maslach职业倦怠量表测评工作倦怠的心理影响和程度。另一份调查问卷旨在了解患者对COVID-19的认知和熟悉程度。所有参与者根据临床实习时间分为5组:研究生一年(PGY) 0.5(少于0.5年)、0.6-1(0.6-1年)、1-2(1-2年)、2-3(2-3年)、3(超过3年)组。随后收集结果并进行分析。共收集问卷188份。PGY 0.5与PGY 0.6-1患者的痛苦程度差异有统计学意义(17.60±12.53∶12.05±10.65;p = 0.029), PGY 3和PGY 0.6 - 1(19.92±11.88和12.05±10.65;p = 0.031)。在工作倦怠方面,各亚组间无显著差异。大多数被试(86.70%)保持良好的工作状态,25名被试表现出轻度的工作倦怠。虽然所有受访者对COVID-19的基本要素都有较高的认识,但他们对实验室检查,释放标准和推荐治疗等细节知之甚少,并且这一结果在五组之间没有显着差异。新冠肺炎给年轻麻醉师造成了轻微的痛苦和工作倦怠。大多数学员对诊断、释放标准、治疗方法不清楚,这将成为今后教学的重点。
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引用次数: 1
Contralateral C7 nerve transfer in the treatment of central hemiplegia after stroke under general anesthesia: A case report 在全身麻醉下进行 C7 对侧神经转移以治疗中风后中枢性偏瘫:病例报告
Pub Date : 2022-08-24 DOI: 10.1002/ibra.12064
Qiu-Ying Zhang, Yi Guo, Yi-Nan Zhang

Similar reports in the past pay less attention to the anesthetic management of these patients. We reported a 46-year-old man who suffered from hypertensive cerebral apoplexy 5 months ago and accepted C7 nerve transfer to improve the central spastic paralysis in the right upper limb. After careful evaluation and anesthesia management before anesthesia, the operation was successfully completed under general anesthesia. The patient was cured and discharged without complications. The anesthesia management of C7 nerve transfer should choose appropriate operation opportunities for patients according to the type of stroke, improve the preoperative preparation, and form a multidisciplinary diagnosis and treatment.

过去的类似报道较少关注这些患者的麻醉管理。我们报告了一名 46 岁的男性患者,他在 5 个月前患上了高血压性脑中风,并接受了 C7 神经转移术来改善右上肢中枢性痉挛性瘫痪。经过麻醉前的仔细评估和麻醉管理,手术在全身麻醉下顺利完成。患者治愈出院,无并发症发生。C7神经转流术的麻醉管理应根据卒中类型为患者选择合适的手术时机,完善术前准备,形成多学科诊疗。
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引用次数: 0
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