Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.

Anesthesia,Anesthetics,and Postoperative Cognitive Dysfunction in Elderly Patients

Postoperative cognitive dysfunction(POCD)remains a major issue that worsens the prognosis of elderly surgery patients.This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients,aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols,ultimately reducing the incidence of POCD in elderly surgery patients.

Impact of thoracic paravertebral block and sufentanil on outcomes and postoperative cognitive dysfunction in thoracoscopic lung cancer surgery

BACKGROUND Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer(LC).This is achieved using either a thoracic paravertebral block(TPVB)or sufentanil(SUF)-based multimodal analgesia.However,the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction(POCD)remain unclear.AIM To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes.METHODS This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023.Patients receiving SUF-based multimodal analgesia(n=50)and patients receiving TPVB+SUF-based multimodal analgesia(n=57)were assigned to the control group and TPVB group,respectively.We compared the Ramsay Sedation Scale and visual analog scale(VAS)scores at rest and with cough between the two groups at 2,12,and 24 h after surgery.Serum levels of epinephrine(E),angio-tensin Ⅱ(Ang Ⅱ),norepinephrine(NE),superoxide dismutase(SOD),vascular endothelial growth factor(VEGF),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),and S-100 calcium-binding proteinβ(S-100β)were measured before and 24 h after surgery.The Mini-Mental State Examination(MMSE)was administered 1 day before surgery and at 3 and 5 days after surgery,and the occurrence of POCD was monitored for 5 days after surgery.Adverse reactions were also recorded.RESULTS There were no significant time point,between-group,and interaction effects in Ramsay sedation scores between the two groups(P>0.05).Significantly,there were notable time point effects,between-group differences,and interaction effects observed in VAS scores both at rest and with cough(P<0.05).The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased(P<0.05).The TPVB group had lower VAS scores than the control group at 2,12,and 24 h after surgery(P<0.05).The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group(P<0.05).The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery(P<0.05).Both groups had elevated serum E,Ang Ⅱ,and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels,with better indices in the TPVB group(P<0.05).Marked elevations in serum levels of VEGF,TGF-β1,TNF-α,and S-100β were observed in both groups at 24 h after surgery,with lower levels in the TPVB group than in the control group(P<0.05).CONCLUSION TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC,enhances analgesic effects,reduces postoperative stress response,and inhibits postoperative increases in serum VEGF,TGF-β1,TNF-α,and S-100β levels.This scheme also reduced POCD and had a high safety profile.

Evaluation of Efficacy and Safety of Electro-acupuncture Precondition on Postoperative Cognitive Dysfunction (POCD) Following Knee Replacement in Elderly: A Randomized Controlled Trial

OBJECTIVE: To investigate that whether electro-acupuncture(EA) precondition can reduce the incidence of postoperative cognitive dysfunction(POCD) following knee replacement and its safety in elderly. METHODS: A total of 60 participants met the inclusion criteria were enrolled in a randomized controlled trial with the ratio of 1:1, with 30 cases in the treatment group and 30 cases in the control group. The participants in the treatment group were provided with realEA therapy whereas participants in control group were provided with placebo-EA therapy. Interventions were offered 5 days prior to the surgery, once daily, and for a total of 5 days. The scores of Mini-Mental State Examination(MMSE), and contents of serumal inflammatory cytokines including interleukin 1β(IL-1β) and tumor necrosis factor-α(TNF-α) were observed at 24 hours prior-and posterior-to the surgery respectively for assessing the incidence of POCD among patients. Meanwhile, adverse effects were monitored and recorded. RESULTS:(1) After surgery, both treatment group and control group showed a significant decrease in MMSE global scores(P < 0.001, < 0.001, respectively), and the score in control group decreased more significantly than that in treatment group(P < 0.05);(2) Contents of serumal IL-1β and TNF-α were significantly increased in both groups after 24 hours posterior to the surgery(P < 0.001), and the contents in control group increased more significantly than that in treatment group(P < 0.001);(3) After surgery, the incidence of POCD was 20% in treatment group versus 36.67% in control group. There was no statistical difference between 2 groups(P > 0.05);(4) No serious adverse events were reported in this trial, except 1 patient from treatment group had a slight hematoma after receiving acupuncture. CONCLUSION: EA precondition might reduce cognitive impairments after 24 hours posterior to knee replacement surgery in elderly through inhibiting expression of inflammatory cytokines, including both IL-1β and TNF-α. However, there is insufficient evidence to support that EA precondition could reduce incidence of POCD.

Adaptive and regulatory mechanisms in aged rats with postoperative cognitive dysfunction

Inflammation may play a role in postoperative cognitive dysfunction. 5＇ Adenosine monophos- phate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-a are involved in inflammation. Therefore, these inflammatory mediators may be involved in postoperative cognitive dysfunction. Western immunoblot analysis revealed 5＇ adenosine mo- nophosphate-activated protein kinase and nuclear factor-kappa B in the hippocampus of aged rats were increased 1-7 days after splenectomy. Moreover, interleukin-1β and tumor necrosis fac- tor-α were upregulated and gradually decreased. Therefore, these inflammatory mediators may participate in the splenectomy model of postoperative cognitive dysfunction in aged rats.

Aspartic acid in the hippocampus:a biomarker for postoperative cognitive dysfunction

This study established an aged rat model of cognitive dysfunction using anesthesia with 2% iso- flurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethy- lacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid （100 μmol/L）. Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.

Small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells improve postoperative cognitive dysfunction in mice with diabetes

Postoperative cognitive dysfunction(POCD)is a common surgical complication.Diabetes mellitus(DM)increases risk of developing POCD after surgery.DM patients with POCD seriously threaten the quality of patients’life,however,the intrinsic mechanism is unclear,and the effective treatment is deficiency.Previous studies have demonstrated neuronal loss and reduced neurogenesis in the hippocampus in mouse models of POCD.In this study,we constructed a mouse model of DM by intraperitoneal injection of streptozotocin,and then induced postoperative cognitive dysfunction by transient bilateral common carotid artery occlusion.We found that mouse models of DM-POCD exhibited the most serious cognitive impairment,as well as the most hippocampal neural stem cells(H-NSCs)loss and neurogenesis decline.Subsequently,we hypothesized that small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells(iMSC-sEVs)might promote neurogenesis and restore cognitive function in patients with DM-POCD.iMSC-sEVs were administered via the tail vein beginning on day 2 after surgery,and then once every 3 days for 1 month thereafter.Our results showed that iMSC-sEVs treatment significantly recovered compromised proliferation and neuronal-differentiation capacity in H-NSCs,and reversed cognitive impairment in mouse models of DM-POCD.Furthermore,miRNA sequencing and qPCR showed miR-21-5p and miR-486-5p were the highest expression in iMSC-sEVs.We found iMSC-sEVs mainly transferred miR-21-5p and miR-486-5p to promote H-NSCs proliferation and neurogenesis.As miR-21-5p was demonstrated to directly targete Epha4 and CDKN2C,while miR-486-5p can inhibit FoxO1 in NSCs.We then demonstrated iMSC-sEVs can transfer miR-21-5p and miR-486-5p to inhibit EphA4,CDKN2C,and FoxO1 expression in H-NSCs.Collectively,these results indicate significant H-NSC loss and neurogenesis reduction lead to DM-POCD,the application of iMSC-sEVs may represent a novel cell-free therapeutic tool for diabetic patients with postoperative cognitive dysfunction.

Effects of ulinastatin combined with dexmedetomidine on cognitive dysfunction and emergence agitation in elderly patients who underwent total hip arthroplasty

BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture increases.Hip fracture is a common type of fracture in older people.Total hip arthroplasty(THA)has significant advantages in relieving chronic pain and promoting the recovery of hip joint function.AIM To investigate the effect of ulinastatin combined with dexmedetomidine(Dex)on the incidences of postoperative cognitive dysfunction(POCD)and emergence agitation in elderly patients who underwent THA.METHODS A total of 397 patients who underwent THA from February 2019 to August 2022.We conducted a three-year retrospective cohort study in Shaanxi Provincial People’s Hospital.Comprehensive demographic data were obtained from the electronic medical record system.We collected preoperative,intraoperative,and postoperative data.One hundred twenty-nine patients who were administered Dex during the operation were included in the Dex group.One hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin group.One hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex+ulinastatin group.The patients’perioperative conditions,hemodynamic indexes,postoperative Mini-Mental State Examination(MMSE)scores,Ramsay score,incidence of POCD,and serum inflammatory cytokines were evaluated.RESULTS There was a significant difference in the 24 h visual analogue scale score among the three groups,and the score in the Dex+ulinastatin group was the lowest(P<0.05).Compared with the Dex and ulinastatin group,the MMSE scores of the Dex+ulinastatin group were significantly increased at 1 and 7 d after the operation(all P<0.05).Compared with those in the Dex and ulinastatin groups,incidence of POCD,levels of serum inflammatory cytokines in the Dex+ulinastatin group were significantly decreased at 1 and 7 d after the operation(all P<0.05).The observer’s assessment of the alertness/sedation score and Ramsay score of the Dex+ulinastatin group were significantly different from those of the Dex and ulinastatin groups on the first day after the operation(all P<0.05).CONCLUSION Ulinastatin combined with Dex can prevent the occurrence of POCD and emergence agitation in elderly patients undergoing THA.

NP-23 Cascade Events for Delayed Postoperative Cognitive Dysfunction

Background:Postoperative cognitive dysfunction(POCD)can occur in patients with cardiac and non-cardiac surgeries.About 20%to 40%patients develop POCD at hospital discharge(a few days after surgery,acute POCD)and 10%elderly patients(>60 years old)have POCD at 3 months after surgery(delayed POCD).Age and degree of education are risk factors for delayed POCD.It has been shown that POCD is associated with increased mortality.Patients with POCD have a longer hospital stay and an increased rate of leaving job market.Thus,POCD is a very significant clinical syndrome during the perioperative period,which is recognized only in recent years.We and others have shown that neuroinflammation is a critical neuropathological process for POCD.However,neuroinflammation lasts for a few days after surgery.It is not known how such a short-lived neuropathological process lead to POCD a few months after surgery.To address this issue,a series of experiments were performed in my laboratory.Methods:Rats or mice were subjected to common carotid arterial exposure,a surgical component of carotid endarterectomy that is often performed in elderly patients.Their learning and memory were assessed at least one week after surgery.Their blood and brain tissues were harvested at various time after surgery for biochemical and structural analyses.Results:The surgery induced an increase of proinflammatory cytokines in the blood.The surgery also increased the expression of active matrix metallopeptidase 9(MMP-9)and its activity in the brain.This surgery induced POCD and neuroinflammation in wild-type mice but not in the MMP-9 knockout mice.P2X7 receptors and inflammasome were activated by the surgery.Inhibition of P2X7 receptors and P2X7 receptor knockout abolished POCD and neuroinflammation after surgery.The surgery decreased growth factor production and inhibition of neuroinflammation attenuated this decrease.The decreased growth factor expression occurred at 3 to 5 days after the surgery.Surgery increased histone deacetylase activity and inhibition of histone deacetylase attenuated the decrease of growth factor expression and the development of POCD.The surgery decreased neurogenesis in the hippocampus and application of growth factors to the brain attenuated this decrease and POCD.This decreased neurogenesis was observed 3 weeks after surgery.Finally,surgery impaired dendritic arborization that was assessed 3 weeks after surgery.Inhibition of histone deacetylases attenuated this impairment and POCD.Conclusion:Surgery induces a delayed POCD in rodents.Surgery results in systemic inflammation,which then activates MMP-9 to damage the brain-blood barrier to facilitate the systemic inflammation to be transmitted to the brain.Proinflammatory signals in the blood activate P2X7 receptors to induce neuroinflammation that inhibits growth factor expression through epigenetic regulation.Reduced growth factor expression results in decreased neurogenesis and dendritic arborization that then ultimately lead to the delayed POCD.Thus,surgery activates a series of cascade events to induce the delayed POCD.

Correlation Analysis Between BDNF and Postoperative Cognitive Dysfunction in Aged Rats

Objective:To investigate the relationship between BDNF and postoperative cognitive dysfunction among aged rats.Methods:36 SPF healthy aged male SD rats were randomly assigned to a control group and a model group,respectively,with 18 rats in each group.Abdominal exploration was performed on the rats in the model group after anesthesia,while the rats in the control group were not operated on after anesthesia.The escape latency and swimming distance of the two groups were analyzed on a day prior to surgery as well as on the first day,third day,and seventh day following surgery;the expression levels of BDNF protein in the hippocampus of rats in the two groups were compared on the first day,third day,and seventh day following surgery;the correlation between BDNF and escape latency and swimming distance was analyzed.Results:The escape latency and swimming distance of the rats in the control group on a day prior to surgery,the first day,third day,and seventh day following surgery did not differ significantly(p>0.05),but those in the model group had significant behavioral difference(p<0.05).On a day prior to surgery,the rats in both groups showed no significant behavioral difference in escape latency and swimming distance(p>0.05),but on the first day,third day,and seventh day following surgery,the escape latency and swimming distance of the rats in the model group were significantly longer than those in the control group(p<0.05).In the control group,there was no significant difference in the protein expression of BDNF in the hippocampus of rats on the first day,third day,and seventh day following surgery,but there was significant difference in the model group.On the first day,third day,and seventh day following surgery,the BDNF protein expression level in the rats’hippocampus of the control group was significantly higher than that of the model group(p<0.05).The data from Pearson correlation analysis confirmed that BDNF protein expression is negatively correlated with escape latency(r=-0.567,p<0.001)and swimming distance(r=-0.623,p<0.001).Conclusion:In aged rats,the BDNF protein expression level decreases,and the degree of cognitive dysfunction increases after surgery.

老年CPB下心脏手术患者的rSO_(2)监测及其与术后早期POCD的相关性

目的监测老年心肺转流术(CPB)下心脏手术患者的局部脑氧饱和度(rSO_(2))的变化,并分析其与术后认知功能障碍(POCD)发生的相关性。方法回顾性分析2022年9月至2023年12月于河南省胸科医院接受CPB下心脏手术的100例老年患者的临床资料,根据患者术后7 d内是否发生POCD分为POCD组39例和非POCD组61例。比较两组患者吸氧前rSO_(2)、CPB前期rSO_(2)平均值(rSO_(2mean))、CPB中期rSO_(2mean)、CPB后期rSO_(2mean)、术中最低rSO_(2),并采用Pearson法分析rSO_(2)与术后早期POCD发生的相关性。结果两组患者吸氧前的rSO_(2)、CPB前期rSO_(2mean)比较差异均无统计学意义(P>0.05);POCD组患者CPB中期rSO_(2mean)、CPB后期rSO_(2mean)、术中最低rSO_(2)分别为(64.00±5.37)%、(67.19±5.25)%、(60.07±5.99)%,明显低于非POCD组的(70.44±6.75)%、(72.38±5.70)%、(69.48±6.17)%,差异均有统计学意义(P<0.05);Pearson相关性分析结果显示,CPB中期rSO_(2mean)、CPB后期rSO_(2mean)、术中最低rSO_(2)与术后早期POCD均呈负相关(r=-0.453、-0.420、-0.605,P<0.05)。结论老年CPB下心脏手术患者术中rSO_(2)可出现降低,且CPB中期rSO_(2mean)、CPB后期rSO_(2mean)、术中最低rSO_(2)与术后早期POCD的发生均具有相关性,应受到临床关注。

Postoperative delirium:A tragedy for elderly cancer patients

In this editorial,we comment on the article by Hu et al entitled“Predictive modeling for postoperative delirium in elderly patients with abdominal malignancies using synthetic minority oversampling technique”.We wanted to draw attention to the general features of postoperative delirium(POD)as well as the areas where there are uncertainties and contradictions.POD can be defined as acute neurocognitive dysfunction that occurs in the first week after surgery.It is a severe postoperative complication,especially for elderly oncology patients.Although the underlying pathophysiological mechanism is not fully understood,various neuroinflammatory mechanisms and neurotransmitters are thought to be involved.Various assessment scales and diagnostic methods have been proposed for the early diagnosis of POD.As delirium is considered a preventable clinical entity in about half of the cases,various early prediction models developed with the support of machine learning have recently become a hot scientific topic.Unfortunately,a model with high sensitivity and specificity for the prediction of POD has not yet been reported.This situation reveals that all health personnel who provide health care services to elderly patients should approach patients with a high level of awareness in the perioperative period regarding POD.

Cognitive clarity in colon surgery: The dexmedetomidine advantage

Colon cancer is one of the most prevalent cancers globally,especially in the older age group.A large number of older patients undergoing surgery for colon cancer suffer from postoperative cognitive dysfunction(POCD).The trial by Bu et al demonstrated that dexmedetomidine(Dex)significantly reduced the incidence of POCD compared to placebo in individuals undergoing colon cancer surgery.Additionally,better cerebral oxygenation and lower cerebral injury markers were reported with the use of Dex.The trial has some limitations,such as a single-center design and a smaller sample size,and further studies with larger patient populations and robust multi-center designs are warranted to establish these findings.

体外循环术POCD患者血清GDNF、S100β和Aβ含量检测对病情评估的价值

目的分析研究体外循环术术后认知功能障碍(POCD)患者血清胶质细胞源性神经营养因子(GDNF)、S100β蛋白(S100β)、β淀粉样蛋白(Aβ)含量检测对病情评估的价值。方法选择2012年9月至2014年7月间接受体外循环术的心脏疾病患者176例作为研究对象,根据术后是否发生POCD分为对照组94例和POCD组82例。检测比较两组患者的血清GDNF、S100β、Aβ、兴奋性氨基酸[谷氨酸(GLU)、天冬氨酸(Asp)、甘氨酸(Gly)]水平。结果POCD组患者的体外循环术后1周血清GDNF(32.15±3.09)ng/ml,低于对照组患者的GDNF(67.92±5.88)ng/ml(P<0.05);POCD组患者的术后1周血清S100β(703.17±67.34)ng/L、Aβ(632.83±49.75)ng/L,均高于对照组患者的S100β(595.62±60.57)ng/L、Aβ(475.25±43.11)ng/L(P<0.05);POCD组患者的术后1周血清GLU(29.73±2.53)mmol/L、Asp(22.16±2.18)mmol/L、Gly(213.53±19.83)mmol/L,均高于对照组患者的GLU(23.61±2.09)mmol/L、Asp(17.32±1.85)mmol/L、Gly(181.62±18.99)mmol/L(P<0.05)。结论体外循环术POCD患者血清GDNF、S100β、Aβ、EAAs水平均可发生明显改变,上述指标有望成为评价病情的有效指标之一。

围术期保温对老年胸科手术患者POCD的影响

目的评价围术期保温对老年胸科手术患者术后认知功能障碍(POCO)及术后并发症的影响。方法收集2016年1月至2018年10月收治的80例老年胸科癌症患者的临床资料,患者随机分为围术期常规处理40例(常规组),围术期常规结合保温处理组40例(试验组)。2组患者麻醉诱导相同,维持采用瑞芬太尼0.1~0.3μg·kg-1·min-1和丙泊酚术中持续泵注。比较2组麻醉前(T1)、单肺通气(one-lung ventilation,OLV)开始(T2)、OLV 1 h(T3)、手术结束即刻(T4)的体温(temperature,Temp)、心率(heart rate,HR)与平均动脉压(mean arterial pressure,MAP),比较2组患者术前及术后3 d简易智力状态检查量表(Simple mental state examination scale,MMSE)、术后恢复质量评估量表(Post-operative quality recovery scale,PQRS)、蒙特利尔认知评估量表(Montreal Cognitive Assessment,MoCA)评分等,并分析2组术后并发症情况。结果Temp、HR及MAP在时间、组间及交互方面均有明显差异(P<0.05),试验组4个时间点两两比较差异均无统计学意义(P>0.05),常规组4个时间点两两比较比较均有显著差异(P<0.05)。T2、T3和T4时间点试验组的Temp均显著高于常规组(P<0.05),而HR与MAP均显著低于常规组(P<0.05);术前2组患者的MMSE、MoCA、PQRS评分差异均无统计学意义(P>0.05),术后3 d时,试验组MMSE、PQRS、MoCA评分均明显高于常规组(P<0.05)。术后3 d 2组间的POCD、术后谵妄发生率差异无统计学意义(P>0.05),而试验组的术后低体温及寒战发生率均显著低于常规组(均P<0.05)。结论围术期保温有利于维持老年胸科手术患者的生命体征稳定,并可有效地降低术后认知功能损伤。

POCD小鼠海马组织中差异表达miRNA的筛选、靶基因预测和生物信息学分析及其调控机制探讨

目的采用生物信息学方法分析术后认知功能障碍(POCD)小鼠海马组织中差异表达miRNA(DEMs)及其靶基因(DEGs),并构建POCD小鼠海马组织中差异表达miRNA-mRNA的调控网络图,探讨其机制。方法在GEO数据库中搜索下载POCD小鼠海马组织与正常小鼠海马组织基因表达谱芯片数据GSE95070,采用R软件lim⁃ma函数包筛选出差异表达的miRNA,即DEMs。将DEMs分别输入到miRTarBase、TargetScan、miRDB数据库中,三个数据库中皆存在的靶基因为差异表达的DEMs靶基因,即DEGs。使用R软件中的ggplot2、enrichplot函数包对DEGs进行了基因本体(GO)功能富集分析和KEGG信号通路分析。通过STRING在线工具构建DEGs蛋白互作网络(PPI),将蛋白间相互作用得分>0.4的节点输入到可视化工具Cytoscape软件中,利用cytoHubba插件筛选出节点度值排名前10的节点,即为可能参与小鼠POCD发生发展的枢纽基因。选取枢纽基因及其相应的DEMs,利用Cyto⁃scape软件构建POCD小鼠海马组织中差异表达miRNA-mRNA调控网络图。结果共筛选出19个显著差异表达的DEMs,得到448个DEGs。GO功能富集分析结果显示,DEGs在DNA结合的转录因子激活活性、特异性RNA聚合酶Ⅱ、微小GTP酶结合等分子功能中显著富集,在树突的形成以及调节、促进神经胶质细胞的增殖等生物学过程中显著富集,在突触膜的有机组成成分、细胞边缘以及囊泡运输等细胞组分中显著富集。KEGG信号通路分析结果显示,DEGs在Cushing综合征相关通路、cGMP-PKG信号通路、Hepatitis C信号通路、Apelin信号通路等通路中显著富集。小鼠POCD发生发展的10个枢纽基因分别为Gsk3β、Igf1、Cd34、Ubxn7、Smad2、Smarca4、Stat1、Grb2、Sin3a、Ncam1,相应的6个DEMs分别为mmu-miR-362-3p、mmu-miR-3065-5p、mmu-miR-592-3p、mmu-miR-28a-3p、mmu-miR-181c-5p、mmu-miR-351-5p,成功构建了POCD小鼠海马组织中差异表达miRNA-mRNA调控网络图,其中mmu-miR-362-3p调控Gsk3β的关系对、mmu-miR-3065-5p调控Igf1的关系对在调控网络中节点度最高。结论与正常小鼠海马组织相比,POCD小鼠海马组织中有19个差异表达的DEMs和448个DEGs;DEGs与树突的形成以及调节等有关,参与介导Cushing综合征相关通路、cGMP-PKG信号通路等。mmu-miR-362-3p、mmu-miR-3065-5p等差异表达的miRNA可能是通过调节Gsk3β、Igf1等靶基因的表达,影响POCD的发生发展。

前额叶及胼胝体膝部各项异性分数值预测老年患者早期POCD的价值

目的探讨前额叶(prefrontal cortex,PFC)及胼胝体(corpus callosum,CC)的磁共振弥散张量成像(diffusion tensor imaging,DTI)参数各向异性分数(fractional anisotropy,FA)值对老年患者早期POCD的预测价值。方法选取限期腹腔镜下胃癌或结肠癌根治术患者81例,男50例,女31例,年龄≥65岁,ASAⅢ级,根据术后是否发生POCD将患者分为两组:POCD组(n=21)和非POCD组(n=60)。患者于术前1d及术后7d接受DTI检查及认知功能评估,获得FA及神经心理学结果,根据Z计分法判定是否发生POCD,并借助受试者工作特征曲线(receiver operator characteristic curve,ROC)分析术前左、右PFC及CC膝部FA值诊断早期POCD的效能。结果早期POCD发生率为21例(25.93%)。POCD组术前、术后PFC及CC膝部FA值均明显低于非POCD组(P<0.05);术前左、右PFC及CC膝部FA值曲线下面积分别为0.757、0.764、0.698,分别明显高于术后FA值曲线下面积0.691、0.694、0.663(P<0.05)。结论早期POCD患者术前PFC及CC膝部FA值明显低于非POCD患者,且诊断效能明显高于术后,术前FA值有助于老年胃肠道手术患者早期POCD的预测与评估。

七氟烷和丙泊酚麻醉对老年患者POCD的影响

目的研究应用七氟烷和丙泊酚麻醉对老年患者的影响。方法选择全麻下行择期非心脏手术且年龄≥60岁的老年患者30例,随机分为丙泊酚(P组)和七氟烷(I组)麻醉组和对照组,根据需要输血-麻醉诱导:两组患者静脉注射丙泊酚1.5～2.0 ml/kg,芬太尼3～4μg/kg,维库溴铵0.1 mg/kg行麻醉诱导。结果患者术后1 h两组差异有显著性(P<0.05),术后4 h P组MMSE评分较术前有所下降,但差异无显著性(P>0.05),术后4 h P组差异无显著性(P>0.05),术后4 h差异有显著性(P<0.05)。术后24 h及48 h两组MMSE评分与术前比较差异无显著性(P>0.05)。结论接受丙泊酚或七氟烷麻醉的老年患者非心脏手术POCD降低。

单肺通气手术患者POCD危险因素分析

目的探讨单肺通气手术患者发生术后认知功能障碍(POCD)的患病率及其危险因素。方法选取60例42～83岁需单肺通气手术患者,于术前1 d和术后7 d分别接受简易智能状态检测,记录手术前后认知功能的改变,并分析围术期因素与患者发生POCD的关系。结果 14例患者发生POCD,患病率为23.3%。年龄增长与POCD的发生呈正相关,单肺通气后脑氧饱和度较基础值下降和乳酸升高值与患者POCD的发生呈正相关。结论单肺通气POCD的患病率为23.3%,年龄增长、乳酸值升高和脑氧饱和度较基础值下降是单肺通气的胸外科手术患者发生POCD的危险因素。

Klotho蛋白抑制POCD老年大鼠脑组织及小胶质细胞中FGF23/NF-κB p65的表达

目的以POCD老年大鼠及BV2小胶质细胞作为研究对象,探究Klotho蛋白对POCD的治疗作用及机制。方法SD老年大鼠45只,随机分为control组,七氟醚麻醉组(sevo组)、七氟醚麻醉手术组(sevo+surgery组)。采用水迷宫评估大鼠认知状态,HE、TUNEL染色和ELISA检测大鼠海马组织病变、凋亡及促炎介质的表达水平。Western blot检测大鼠海马组织和BV2细胞中相关蛋白表达。细胞免疫荧光检测BV2细胞中NF-κB p-P65表达。结果sevo组和sevo+surgery组老年大鼠出现明显认知障碍,海马区受损,炎症因子表达增加,大量神经元细胞凋亡,Klotho蛋白表达下调,而FGF23/NF-κB通路蛋白表达上调。LPS和七氟醚诱导BV2细胞炎症因子表达增加,FGF23/NF-κB通路蛋白表达上调,然而Klotho治疗降低了上述蛋白和炎症因子的表达。结论Klotho可能在POCD的防治中成为新的靶点,其机制可能与Klotho蛋白抑制小胶质细胞中FGF23/NF-κB的表达有关。