Perioperative neurocognitive disorders (PND), highly prevalent in geriatric surgical populations, constitute a major postoperative clinical challenge associated with prolonged hospital stays and adverse surgical outcomes. Although substantial research efforts have been devoted to investigating etiology, the precise molecular mechanisms of PND remains elusive, thereby hindering the development of effective therapeutic interventions. To address this gap, we conducted single-nucleus RNA sequencing on 119,109 hippocampal cells isolated from 18-month-old PND mice and age-matched controls, alongside performing complementary Western blotting and electrophysiological experiments. We propose that hippocampal neuronal excitation-inhibition (E/I) imbalance serves as a key mechanism underlying PND, which is associated with dysregulated inhibitory control of excitatory plasticity in PND pathology. Furthermore, we identified PND-associated astrocytes and oligodendrocytes—distinct from those in other cognitive disorders and linked to E/I imbalance. These cell types played distinct roles in the pathological process of PND. Our study proposes that E/I imbalance, associated with dysregulated inhibitory control of excitatory plasticity, underlies the pathogenesis of PND, providing new insights for therapeutic interventions.
BACKGROUND:Although interscalene nerve block is considered as the standard analgesic method for arthroscopic shoulder surgery, it is not indicated for patients with respiratory comorbidity. Periarticular infiltration is usually used for postoperative analgesia following orthopedic surgery, with uncertain analgesic effects. Infraspinatus-teres minor interfascial (ITM) block is an innovative method used in arthroscopic shoulder surgery. We supposed that ITM block combined with periarticular infiltration could provide adequate analgesia for patients undergoing arthroscopic shoulder surgery. METHODS:This is a randomized, parallel-controlled, prospective, single-center study. Fifty-six patients scheduled for arthroscopic shoulder surgery will be randomized into two groups: ITM block combined with periarticular infiltration group (ITM group) and periarticular infiltration group (PAI group). Periarticular infiltration will be administered to all patients following surgery. The primary outcome is the time from the end of surgery to the first press of the patient-controlled analgesia pump (PCA) in the two groups. Secondary outcomes are the following: intraoperative remifentanil and propofol consumption, hemodynamic changes, VAS scores, frequency of PCA compression, remedy analgesic consumption, length of hospital stay, patients satisfaction score, and adverse reactions. DISCUSSION:This study will demonstrate the analgesic efficacy of ITM block combined with periarticular infiltration in arthroscopic shoulder surgery. TRIAL REGISTRATION:Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ ) ChiCTR2400088821. Registered on 27 August 2024.
Perioperative neurocognitive disorders (PND) are cognitive dysfunctions that usually occur in elderly patients after anesthesia and surgery. Microglial overactivation is a key underlying mechanism. Interleukin-33 (IL-33) is a member of the IL-1 family that orchestrates microglial function. In the present study, we explored how IL-33, which regulates microglia, contributes to cognitive improvement in a male mouse model of PND. An exploratory laparotomy was performed to establish a PND model. The expression levels of IL-33 and its receptor ST2 were evaluated using western blot. IL-33/ST2 secretion, microglial density, morphology, phagocytosis of synapse, and proliferation, and dystrophic microglia were assessed using immunofluorescence. Synaptic plasticity was measured using Golgi staining and long-term potentiation. The Morris water maze and open field test were used to evaluate cognitive function and anxiety. Hippocampal expression of IL-33 and ST2 were elevated on postoperative day 3. We confirmed that IL-33 was secreted by astrocytes and neurons, whereas ST2 mainly colocalized with microglia. IL-33 treatment induced microgliosis after anesthesia and surgery. These microglia had larger soma sizes and shorter and fragmented branches. Compared to the Surgery group, IL-33 treatment reduced the synaptic phagocytosis of microglia and increased microglial proliferation and dystrophic microglia. IL-33 treatment also reversed the impaired synaptic plasticity and cognitive function caused by anesthesia and surgery. In conclusion, these results indicate that IL-33 plays a key role in regulating microglial state and synaptic phagocytosis in a PND mouse model. IL-33 treatment has a therapeutic potential for improving cognitive dysfunction in PND.
Objective To explore the status and influencing factors of postoperative anxiety in patients undergoing non-cardiac surgery.Methods A total of 299 non-cardiac surgery patients from Beijing Chaoyang Hospital,Capital Medical University from August 2019 to January 2020 were selected,the perioperative data were collected,and multivariate logistic regression equation was used to analyze the influencing factors of postoperative anxiety in patients undergoing non-cardiac surgery.Results Among the 299 patients,there were 134 males and 165 females,aged from 20 to 85 years,with an average age of(55.2±14.0)years.The incidence of postoperative anxiety was 12.70%(38/299).Multivariate logistic regression analysis showed that preoperative anxiety(OR=5.512,95%CI:2.206-13.776,P=0.001),preoperative depressive symptoms(OR=3.523,95%CI:1.436-8.644,P=0.006)and first day postoperative pain(OR=1.405,95%CI:1.125-1.756,P=0.003)were risk factors for postoperative anxiety in patients undergoing non-cardiac surgery.Conclusions In non-cardiac surgery,pre-screening and intervention for patients with preoperative anxiety and depression,and actively relieving postoperative pain can significantly reduce the incidence of postoperative anxiety.
Perioperative neurocognitive disorder (PND) is a common complication of surgery and anesthesia, especially among older patients. Microglial activation plays a crucial role in the occurrence and development of PND and transforming growth factor beta 1 (TGF-β1) can regulate microglial homeostasis. In the present study, abdominal surgery was performed on 12–14 months-old C57BL/6 mice to establish a PND model. The expression of TGF-β1, TGF-β receptor 1, TGF-β receptor 2, and phosphor-smad2/smad3 (psmad2/smad3) was assessed after anesthesia and surgery. Additionally, we examined changes in microglial activation, morphology, and polarization, as well as neuroinflammation and dendritic spine density in the hippocampus. Behavioral tests, including the Morris water maze and open field tests, were used to examine cognitive function, exploratory locomotion, and emotions. We observed decreased TGF-β1 expression after surgery and anesthesia. Intranasally administered exogenous TGF-β1 increased psmad2/smad3 colocalization with microglia positive for ionized calcium-binding adaptor molecule 1. TGF-β1 treatment attenuated microglial activation, reduced microglial phagocytosis, and reduced surgery- and anesthesia-induced changes in microglial morphology. Compared with the surgery group, TGF-β1 treatment decreased M1 microglial polarization and increased M2 microglial polarization. Additionally, surgery- and anesthesia-induced increase in interleukin 1 beta and tumor necrosis factor-alpha levels was ameliorated by TGF-β1 treatment at postoperative day 3. TGF-β1 also ameliorated cognitive function after surgery and anesthesia as well as rescue dendritic spine loss. In conclusion, surgery and anesthesia induced decrease in TGF-β1 levels in older mice, which may contribute to PND development; however, TGF-β1 ameliorated microglial activation and cognitive dysfunction in PND mice.
目的 通过SPOC的翻转课堂教学方式,探索针对留学生可行而有效的临床麻醉学见习教学模式.方法 选取某院2020年10月1日-2020年31日30名留学生开展基于SPOC的翻转课堂教学.随机将留学生分为5个小班,每个小班6人.利用课程资料库、在线测验系统、在线答疑平台,进行在线课程,线上随堂测试和出科测试,向学生发放调查问卷,对教学效果及实施教学过程进行评价.结果 随堂测试及出科测试,留学生的及格率波动在80%~86.7%之间,学生的随堂测试和出科考试成绩在81.4~86.2.研究人员发送调查问卷30份,回收30份,回收率100%.问卷调查显示:76.7%的留学生们对麻醉科基于SPOC的翻转课堂内容设置和教学模式等都非常满意;认为该模式能提高自己的自学能力的占73.3%、能够提高学习兴趣的占83.3%;认为对自己能力有帮助的占83.3%;对教学方式非常满意的为86.7%.结论 基于SPOC的翻转课堂不仅能提高留学生麻醉科见习中获取知识的能力,还有助于学生创新思维能力的培养,对提高留学生的临床麻醉技能具有重要的推动作用.
经食管超声心动图( transesophageal echocardiography, TEE)是监测并诊断围术期心血管系统结构和功能的一种重要手段[1].学习TEE理论知识和操作技能,对于熟练掌握TEE技术至关重要[2-3].既往的培训和学习方式一直处于"传—帮—带"模式,学习曲线长,且心脏的解剖结构还需学员具备立体思维和丰富的想象力.随着超声技术的快速发展,各个学科已经或正在建立和完善自身的教育培训模式,但是,仍然缺乏有针对性的教学培训大纲.因此,如何对无超声基础的麻醉医师进行高效率的教学成为难点,培训效果无法保证难度,使得TEE技术的推广受到一定的限制.本研究的目的是探讨比较TEE模拟器教学与传统临床实践麻醉科医师TEE教学培训中的效果.
BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model.Materials and methodsExploratory laparotomy was performed in mice aged 12–14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM).ResultsSirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration.ConclusionThis study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD.
Postoperative cognitive dysfunction (POCD) are a common complication of the central nervous system following surgery and anesthesia. The specific pathogenesis and effective therapeutics of POCD need to be further studied. Ginkgolide B (GB), a platelet-activating factor receptor-specific antagonist, has been suggested to have strong anti-inflammatory effects. Here we tested the effects and mechanism of GB on POCD of aged rats. Neurobehavioral tests were used to investigate the effect of GB pretreatment on POCD. The hippocampus were harvested to test the expression of proinflammatory cytokines by ELISA. The expression of the microglial marker ionized calcium-binding adaptor molecule-1 (Iba-1) in the hippocampus was evaluated by western blot assay and immunohistochemistry. A Nissl staining experiment was used to detect the neuronal numbers in the hippocampus. Surgery might result in the overexpression of platelet activating factor (PAF) in the plasma and hippocampus and might cause hippocampus-dependent memory impairment. GB pretreatment, inhibited the activation of microglia, reduced the levels of IL-1β and TNF-α, decreased the loss of neurons after surgery, and prevented POCD in aged rats. Our findings suggested that PAF was involved in the development of POCD. Improvement of POCD by PAF antagonist GB was associated with the inhibition of microgliosis-mediated neuroinflammation and neuronal apoptosis in aged rats.
Background Perioperative neurocognitive disorders (PNDs) are common complications of surgical patients, which can lead to prolonged hospitalization, increased complications, and decreased independence and quality of life. However, the underlying molecular mechanisms of PND remain largely obscure. Microglia activation and synapse loss were observed in PND. Cluster of differentiation 47 (CD47), which can bind to its receptor signal regulatory protein alpha (SIRPα) and generate “do not eat me” signal, protects synapses from excessive pruning. Therefore, we aimed to evaluate the potential role of CD47–SIRPα signaling in PND. Methods The tibial fracture surgery was performed in aged C57BL/6 mice for PND model establishment. The expression of CD47 and SIRPα in the hippocampus was assessed. Synaptic plasticity, dendritic spine density, microglial engulfment, and hippocampal-dependent memory function were evaluated after model establishment and intervention with SIRPα overexpression. Results CD47 and SIRPα expression in the hippocampus were both decreased after the surgery. SIRPα overexpression showed reduced engulfment within host microglia, but a total effect of excessive synapse engulfment decreased dendritic spine density and post-synaptic density protein 95 (PSD95) expression. SIRPα overexpression could not improve the synaptic dysfunction and cognitive impairment in PND. In addition, SIRPα overexpression led to increased CD47 and Iba1 expression. Conclusion Anesthesia and surgery affect CD47–SIRPα signaling. SIRPα overexpression could not ameliorate the cognitive impairment in PND mice. One reason may be that the increased Iba1 expression leads to a total effect of excessive synapse engulfment, which results in decreased dendritic spine density and PSD95 expression.
阻塞性睡眠呼吸暂停是上呼吸道阻塞引起的憋醒、打鼾,并伴有呼吸表浅和呼吸暂停等的一种临床症状,可致慢性缺氧、局部和全身炎症反应增加及内皮功能障碍、激活交感神经活性、间歇性低氧血症和高碳酸血症.近年来,认知功能损害已被证实是阻塞性睡眠呼吸暂停的一个不可忽视的重要并发症.本文回顾了近几年有关阻塞性睡眠呼吸暂停与认知功能损害之间相关性的文献,从阻塞性睡眠呼吸暂停与认知功能的特征、阻塞性睡眠呼吸暂停及认知功能损害相关性、阻塞性睡眠呼吸暂停损害认知的病理机制等方面作一综述.
Postoperative cognitive dysfunction (POCD) is a neurological complication of surgery especially common in elderly patients. In this study, we investigated the role of NONMMUT055714 in POCD via regulation of miR-7684-5p. In a POCD mouse model, we induced overexpression of NONMUTT055714 via transfection of lentivrus into the hippocampus, and used the Morris water maze for assessment of cognitive function. Silencing of NONMUTT055714 and miR-7684-5p was induced in primary hippocampal neurons to observe the effects of these regulatory RNAs on cellular processes. Bioinformatics analysis and a double luciferase reporter experiment were performed to further explore the relationship between NONMMUT055714, miR-7684-5p, and SORLA. Cell and animal rescue experiments were performed to verify the ability of miR-7684-5p to reverse the protective effects of NONMMUT055714 overexpression in POCD. We observed that NONMMUT055714 has decreased expression in the POCD mouse model. Overexpression of NONMMUT055714 protected against cognitive impairment of the POCD mouse model in vivo. We identified miR-7684-5p as a NONMMUT055714-related miRNA and in turn as an upstream regulator of SORLA. We found that NONMMUT055714 downregulation is associated with decreased SORLA, increased Aβ and p-tau expression, increased inflammatory biomarkers, increased markers of oxidative stress, and increased neuronal apoptosis in vitro. The effects of NONMMUT055714 downregulation were reversed by silencing miR-7684-5p in vitro and in vivo. Taken together, our findings suggest that NONMMUT055714 is protective against the development of POCD via its function as a ceRNA (or miRNA sponge) in the regulation of miR-7684-5p and SORLA. We therefore propose NONMMUT055714 as a novel target for the investigation and prevention of POCD.
In this article, we conduct a systematic review of the literature to explore the specific role of dexmedetomidine (DEX) on postoperative sleep and its associated mechanisms at present. The electronic database Embase, MEDLINE/PubMed, the Cochrane Library, Web of Science, and Google Scholar were searched. The restriction terms included "dexmedetomidine", "sleep" and "surgery". The inclusion criteria were as following: 1) patients 18 years old or older; 2) DEX used in the perioperative period not just for critically ill patients in the intensive care unit (ICU); 3) prospective or retrospective studies. The review articles, conference abstracts, and animal studies were excluded. Out of the 22 articles which met the above criteria, 20 of them were randomized controlled studies and 2 of them were retrospective cohort studies. Infusion of DEX including during the surgery and after surgery at a low or high dose was shown to improve subjective and objective sleep quality, although 2 studies showed there is no evidence that the use of DEX improves sleep quality and 1 showed less sleep efficiency and shorter total sleep time in the DEX group. Other postoperative outcomes evaluated postoperative nausea and vomiting, pain, postoperative delirium bradycardia and hypotension. Outcomes of our systematic review showed that DEX has advantages in improving patients' postoperative sleep quality. Combined with the use of general anesthetic, DEX provides a reliable choice for procedural sedation.
A tracheal diverticulum (TD) is a rare disease that is usually diagnosed as an incidental finding on thoracic computed tomography or bronchoscopy. TDs can be classified as congenital or acquired. In patients undergoing surgery, TDs can result in difficult intubation, difficult ventilation, pneumothorax, and other complications. We herein report a case of anesthetic management of thoracoscopic pulmonary wedge resection in a patient with a giant TD in the carina. Intraoperative double-lumen intubation and single-lung ventilation were challenging to perform. Fiberoptic-guided intubation was helpful, and intraoperative management was tailored to avoid diverticulum rupture. In this report, we also review complications related to TD in surgical patients undergoing mechanical ventilation. Ventilation is one of the most prominent anesthetic challenges. The close collaboration of the entire medical team was a key factor in the successful management of this rare case.
Background The mental diseases especially anxiety, depression, and insomnia are common in patients at perioperative period. This study aims to investigate the association of preoperative mental diseases with acute postoperative pain of patients undergoing non-cardiac surgery. Method: The patients undergoing non-cardiac surgery from August 1, 2019 to January 23, 2020 at Capital Medical University, Beijing Chao-Yang Hospital were included in this retrospective study. The demographics, clinical data and assessments of depression, anxiety, and insomnia by Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) were collected and analyzed. The patients with any of depression, anxiety or insomnia were divided into mental disease group, and others were in non-mental disease group according to the. We compared the postoperative visual analog score between patients in mental diseases group with propensity score matching cohort from patients in non-mental diseases. The primary outcome was acute postoperative pain according to the Visual Analog Scale (VAS) 24h after surgery. Secondary outcomes included VAS at other time points and incidence of postoperative nausea and vomiting (PONV), rescue analgesia, and length of hospital stay (LOS). Results The analysis included 397 patients (274 in the group and 123 in the mental disease group). Patients in mental disease group (anxiety, depression and insomnia) were associated with higher VAS scores and increased times of rescue analgesia. Each of the 3 mental diseases was associated with higher VAS scores independently. Conclusion In this retrospective study, preoperative anxiety, depression and insomnia were associated with increased the level of acute postoperative pain and increased times of rescue analgesia of patients undergoing non-cardiac surgery.
Abstract In this article, we conduct a systematic review of the literature to explore the specific role of dexmedetomidine (DEX) on postoperative sleep and its associated mechanisms at present. The electronic database Embase, MEDLINE/PubMed, the Cochrane Library, Web of Science, and Google Scholar were searched. The restriction terms included “dexmedetomidine”, “sleep” and “surgery”. The inclusion criteria were as following: 1) patients 18 years old or older; 2) DEX used in the perioperative period not just for critically ill patients in the intensive care unit (ICU); 3) prospective or retrospective studies. The review articles, conference abstracts, and animal studies were excluded. Out of the 22 articles which met the above criteria, 20 of them were randomized controlled studies and 2 of them were retrospective cohort studies. Infusion of DEX including during the surgery and after surgery at a low or high dose was shown to improve subjective and objective sleep quality, although 2 studies showed there is no evidence that the use of DEX improves sleep quality and 1 showed less sleep efficiency and shorter total sleep time in the DEX group. Other postoperative outcomes evaluated postoperative nausea and vomiting, pain, postoperative delirium bradycardia and hypotension. Outcomes of our systematic review showed that DEX has advantages in improving patients’ postoperative sleep quality. Combined with the use of general anesthetic, DEX provides a reliable choice for procedural sedation.
Patients in the perioperative period usually present with different types and degrees of sleep disorders, which can severely affect their post-operative outcomes. Multiple risk factors may lead to the occurrence of perioperative sleep disorders, including personal factors, psychological factors, surgery factors, and environmental factors. In this review, we summarize the potential risk factors for perioperative sleep disorders during hospitalization. And it also provides an overview of perioperative outcomes and potential therapeutic prevention of perioperative sleep disorders. However, the further search is necessary to investigate the effectiveness and safety of preventions in the clinical practice and push forward the therapies.
Objective:To investigate the effects of preoperative insomnia on postoperative pain in patients undergoing non-cardiac surgery.Methods:A total of 400 patients who underwent non-cardiac surgery in Beijing Chaoyang Hospital, Capital Medical University from September 2019 to January 2020 were enrolled and their clinical data were retrospectively analyzed. The Insomnia Severity Index (ISI) was used to evaluate preoperative insomnia, and 43 patients with a score of 8-14 points were set as a mild insomnia group. Meanwhile, the propensity score was used and 42 patients were set as a control group. Then, their general information, anesthesia information during surgery, the Visual Analogue Scale (VAS) scores 1, 24, 36, 48, 60, 72 h, and 84 h after surgery and postoperative nausea and vomiting were collected.Results:Compared with the control group, the mild insomnia group presented significant increased VAS scores 1, 24, 60 h after surgery, and VAS score and ISI score were positively correlated 1 h after surgery ( r=0.223, P<0.05) and 24 h after surgery ( r=0.342, P<0.05). There was no statistical difference in VAS score between the two groups at other time points ( P>0.05). There was no statistical difference in intraoperative medication, postoperative analgesia and rescue analgesia between the two groups ( P>0.05). The wild insomnia group showed a remarkably increased incidence of postoperative vomiting (11.6%), compared with the control group (0) ( P<0.05). Conclusions:Preoperative mild insomnia may aggregate postoperative pain, and VAS score is associated with ISI score..
Perioperative neurocognitive dysfunction (PND) is a prevalent neurological complication after anesthesia and surgery. Ginkgolide B (GB) has been suggested to improve lipopolysaccharide-induced learning and memory impairment. The present study aimed to investigate whether GB serves a protective role against PND by inhibiting inducible nitric oxide synthase (iNOS) and nitric oxide (NO). Abdominal surgery was performed on 10- to 12-week-old male C57BL/6 mice under isoflurane anesthesia. Prior to surgery, 1400W (a specific iNOS inhibitor) and GB were administered via intraperitoneal injection. Open field and fear conditioning tests were conducted to assess cognitive function on postoperative days 1 and 3. Biochemical assays were performed to evaluate alterations in NO, malondialdehyde (MDA) and superoxide dismutase (SOD) levels. Western blotting was performed to measure iNOS expression in the hippocampus on postoperative day 1. In addition, hematoxylin and eosin staining was performed to detect the neuronal morphology in the hippocampus. Following treatment with 1400W or GB, surgery-induced cognitive dysfunction was improved. Compared with the control group, the surgery group exhibited significant overproduction of iNOS and MDA in the hippocampus on postoperative day 1. Higher levels of NO were also detected in the hippocampus and prefrontal cortex of the surgery group on postoperative day 1. Furthermore, pretreatment with 1400W or GB significantly inhibited the surgery-induced elevation of NO and MDA in brain tissues. Moreover, GB pretreatment significantly inhibited surgery-induced downregulation of SOD and upregulation of iNOS. Surgery-induced increases in neuronal loss and the Bax/Bcl-2 ratio in the hippocampus were significantly inhibited by pretreatment with GB. Collectively, the results of the present study demonstrated that the therapeutic effects of GB on PND were associated with inhibition of iNOS-induced NO production, increased SOD, and the alleviation of neuronal loss and apoptosis.
围术期神经认知障碍(PND)是一种常见的围术期神经系统并发症,表现为注意力不集中,学习能力下降和记忆受损,可影响患者术后短期功能恢复及预后,延长患者的住院时间.目前PND的发生机制仍存在争议.补体系统是一种生物级联反应体系,已被证实在多种神经退行性疾病的发生发展过程中起着重要作用.麻醉及手术刺激可激活中枢神经系统中的补体系统,影响神经炎症反应、突触功能、血脑屏障、血脑脊液屏障,引起或加重PND.本文章就补体系统对围术期神经认知功能的影响做一系统综述,以期为PND的潜在药物靶点和治疗提供参考.