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 ...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.展开更多
Objective Post-operative cognitive dysfunction(POCD)and post-operative delirium(POD)are two common post-operative cerebral complications.The current meta-analysis was to systematically review the effects of penehyclid...Objective Post-operative cognitive dysfunction(POCD)and post-operative delirium(POD)are two common post-operative cerebral complications.The current meta-analysis was to systematically review the effects of penehyclidine hydrochloride(PHC)on POCD and POD in surgical patients.Methods Electronic databases were searched to identify all randomized controlled trials comparing PHC with atropine/scopolamine/placebo on POCD and POD in surgical patients.Primary outcomes of interest included the incidences of POCD and POD;the secondary outcomes of interest included peri-operative minimental state examination(MMSE)scores.Two authors independently extracted peri-operative data,including patients'baseline characteristics,surgical variables,and outcome data.For dichotomous data(POCD and POD occurrence),treatment effects were calculated as odds ratio(OR)and 95%confidential interval(Cl).Each outcome was tested for heterogeneity,and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity.For continuous variables(MMSE scores),treatment effects were calculated as weighted mean difference(WMD)and 95%CI.Statistical significance was defined as P<0.05.Results Our search yielded 33 studies including 4017 patients.Meta-analysis showed that,the incidence of POCD in PHC group was comparable to that in saline group(OR=0.97;95%Ck 0.S8-1.64;P=0.92),scopolamine group(OR=0.78;95%CI:0.48-1.27;P=0.32)and atropine group(0R=1.20;95%Ch 0.86-1.67;P=0.29).The incidence of POD in PHC group was comparable to that in saline group(OR=1.53;95%CI:0.81-2.90;P=0.19)and scopolamine group(OR=0.53;95%CI:0.06-4.56;P=0.56),but higher than that in atropine group(OR=4.49;95%CI:1.34-15.01;P=0.01).Conclusions PHC premedication was not associated with increased incidences of POCD or POD as compared to either scopolamine or placebo.展开更多
Permanent post-operative cognitive dysfunction (POCD) is a grim outcome to an estimated 6% of elderly surgical patients. Volatile anesthetics impact neuronal tissue independent of effects attributed to the physical tr...Permanent post-operative cognitive dysfunction (POCD) is a grim outcome to an estimated 6% of elderly surgical patients. Volatile anesthetics impact neuronal tissue independent of effects attributed to the physical trauma of the surgery itself. While it is recognized that all aspects related to surgery may contribute to cognitive loss in some manner, the present paper focuses on the role of volatile anesthetics in promoting POCD. There is an increased risk of onset and progression of Alzheimer’s disease (AD) from POCD, implying that the neuropathogenesis between the two is similar. Human studies, being ethically limited in scope, require animal models as a substitute. While the literature using rodent models contains valuable information, we believe that the accessible and practical zebrafish will greatly enhance our further understanding of the molecular mechanism of POCD as it relates to AD. Disease genes and fundamental neurobehaviors of these teleost fish mirror those of mammals and humans, validating their use as a core research model for AD. Since the gradual senescence seen in zebrafish also resembles that found in humans, we numerically correlated the two lifespans, offering researchers a computational tool. Zebrafish, being aquatic animals, necessitates the use of miscible compounds, such as trifluoroethanol, whose anesthetic potency we are presenting. We also review the rodent and zebrafish literature relevant to POCD. Continued research with the leading-edge zebrafish unlocks the possibility that, in the future, perioperative intervention will prevent POCD.展开更多
Objective： To investigate the relationship between post-operative cognitive dysfunction（POCD） and regional cerebral oxygen saturation（rSO2） and β-amyloid protein（Aβ） in patients undergoing laparoscopic pancre...Objective： To investigate the relationship between post-operative cognitive dysfunction（POCD） and regional cerebral oxygen saturation（rSO2） and β-amyloid protein（Aβ） in patients undergoing laparoscopic pancreaticoduodenectomy. Methods： Fifty patients undergoing elective laparoscopic pancreaticoduodenectomy received five groups of neuropsychological tests 1 d pre-operatively and 7 d post-operatively, with continuous monitoring of rSO2 intra-operatively. Before anesthesia induction（t0）, at the beginning of laparoscopy（t1）, and at the time of pneumoperitoneum 120 min（t2）, pneumoperitoneum 240 min（t3）, pneumoperitoneum 480 min（t4）, the end of pneumoperitoneum（t5）, and 24 h after surgery, jugular venous blood was drawn respectively for the measurement of Aβ by enzyme-linked immunosorbent assay（ELISA）. Results： Twenty-one cases of the fifty patients suffered from POCD after operation. We found that the maximum percentage drop in rSO2（rSO2, %max） was significantly higher in the POCD group than in the non-POCD group. The rSO2, %max value of over 10.2% might be a potential predictor of neurocognitive injury for those patients. In the POCD group, the plasma Aβ levels after 24 h were significantly higher than those of pre-operative values（P〈0.01）. After 24 h, levels of plasma Aβ in the POCD group were significantly higher than those in the non-POCD group（P〈0.01）. Conclusions： The development of POCD in patients undergoing laparoscopic pancreaticoduodenectomy is associated with alterations of rSO2 and Aβ. Monitoring of rSO2 might be useful in the prediction of POCD, and Aβ might be used as a sensitive biochemical marker to predict the occurrence of POCD.展开更多
To the Editor:In a randomized controlled preliminary trial comparing effects of propofol,dexmedetomidine,and midazolam on postoperative cognitive dysfunction(POCD)in elderly patients undergoing hip or knee arthroplast...To the Editor:In a randomized controlled preliminary trial comparing effects of propofol,dexmedetomidine,and midazolam on postoperative cognitive dysfunction(POCD)in elderly patients undergoing hip or knee arthroplasty with combined spinal-epidural anesthesia,Li et al[1]showed that intraoperative sedation with propofol compared to dexmedetomidine can significantly decrease risk of POCD.Given that POCD is associated with major adverse consequences,for example,an increased mortality rate,reduced quality of life,and delayed long-term recovery,[2]their findings have potential implications.However,we note that this finding is totally different from the results of a recent large randomized controlled study in elderly patients undergoing hip arthroplasty with the peripheral nerve block,in which patients sedated with dexmedetomidine have a lower risk of POCD than those sedated with propofol.展开更多
目的观察老年下肢手术患者围手术期血清神经元特异性烯醇化酶(neuron specific enolase,NSE)、S-100β变化,探讨术后认知功能障碍的(postoperative cognitive dysfunction,POCD)发生与NSE、S-100β变化的关系。方法择期行下肢手术的老...目的观察老年下肢手术患者围手术期血清神经元特异性烯醇化酶(neuron specific enolase,NSE)、S-100β变化,探讨术后认知功能障碍的(postoperative cognitive dysfunction,POCD)发生与NSE、S-100β变化的关系。方法择期行下肢手术的老年患者86例,分别于术前24h、术后6h以及48h进行老年认知功能量表(the scale of elderly congitive fuction,SECF)测定;同时检测术前24h、术后6h以及48h血清中NSE、S-100β蛋白水平。结果①术后共有21例患者被诊断为POCD。②NSE水平在术后6h以及48h均明显升高,与术前24h相比差异有显著统计学意义;③S-100β仅在术后6h显著升高,与术前24h相比差异有显著统计学意义;术后48h下降至术前水平。④发生POCD的患者,其术后NSE以及S-100β蛋白水平明显高于未发生者。结论老年患者术后NSE、S-100β蛋白水平明显升高,血清中NSE、S-100β蛋白水平的变化与POCD的发生有密切关系。展开更多
目的采用循证医学的方法系统评价右美托咪定在老年患者全麻术后认知功能障碍的影响。方法计算机检索Cochrane、Pub Med、Medline、知网、维普、万方数据库,均从建库到2015年7月发表的文献,对符合纳入与排除标准的研究进行资料提取,并采...目的采用循证医学的方法系统评价右美托咪定在老年患者全麻术后认知功能障碍的影响。方法计算机检索Cochrane、Pub Med、Medline、知网、维普、万方数据库,均从建库到2015年7月发表的文献,对符合纳入与排除标准的研究进行资料提取,并采用Rev Man 5.2软件进行Meta分析。结果最终纳入13个随机对照试验,共计854例患者。Meta分析结果显示:术后1 d右美托咪定组简易精神状态评价量表(MMSE评分)高于对照组,差异有统计学意义(P<0.05);右美托咪定组术后1 d POCD的发生率明显低于对照组(P<0.05),差异有统计学意义。结论老年患者全麻术中使用右美托咪定,能有效改善患者术后认知功能障碍,降低POCD的发生率。展开更多
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘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.
文摘Objective Post-operative cognitive dysfunction(POCD)and post-operative delirium(POD)are two common post-operative cerebral complications.The current meta-analysis was to systematically review the effects of penehyclidine hydrochloride(PHC)on POCD and POD in surgical patients.Methods Electronic databases were searched to identify all randomized controlled trials comparing PHC with atropine/scopolamine/placebo on POCD and POD in surgical patients.Primary outcomes of interest included the incidences of POCD and POD;the secondary outcomes of interest included peri-operative minimental state examination(MMSE)scores.Two authors independently extracted peri-operative data,including patients'baseline characteristics,surgical variables,and outcome data.For dichotomous data(POCD and POD occurrence),treatment effects were calculated as odds ratio(OR)and 95%confidential interval(Cl).Each outcome was tested for heterogeneity,and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity.For continuous variables(MMSE scores),treatment effects were calculated as weighted mean difference(WMD)and 95%CI.Statistical significance was defined as P<0.05.Results Our search yielded 33 studies including 4017 patients.Meta-analysis showed that,the incidence of POCD in PHC group was comparable to that in saline group(OR=0.97;95%Ck 0.S8-1.64;P=0.92),scopolamine group(OR=0.78;95%CI:0.48-1.27;P=0.32)and atropine group(0R=1.20;95%Ch 0.86-1.67;P=0.29).The incidence of POD in PHC group was comparable to that in saline group(OR=1.53;95%CI:0.81-2.90;P=0.19)and scopolamine group(OR=0.53;95%CI:0.06-4.56;P=0.56),but higher than that in atropine group(OR=4.49;95%CI:1.34-15.01;P=0.01).Conclusions PHC premedication was not associated with increased incidences of POCD or POD as compared to either scopolamine or placebo.
文摘Permanent post-operative cognitive dysfunction (POCD) is a grim outcome to an estimated 6% of elderly surgical patients. Volatile anesthetics impact neuronal tissue independent of effects attributed to the physical trauma of the surgery itself. While it is recognized that all aspects related to surgery may contribute to cognitive loss in some manner, the present paper focuses on the role of volatile anesthetics in promoting POCD. There is an increased risk of onset and progression of Alzheimer’s disease (AD) from POCD, implying that the neuropathogenesis between the two is similar. Human studies, being ethically limited in scope, require animal models as a substitute. While the literature using rodent models contains valuable information, we believe that the accessible and practical zebrafish will greatly enhance our further understanding of the molecular mechanism of POCD as it relates to AD. Disease genes and fundamental neurobehaviors of these teleost fish mirror those of mammals and humans, validating their use as a core research model for AD. Since the gradual senescence seen in zebrafish also resembles that found in humans, we numerically correlated the two lifespans, offering researchers a computational tool. Zebrafish, being aquatic animals, necessitates the use of miscible compounds, such as trifluoroethanol, whose anesthetic potency we are presenting. We also review the rodent and zebrafish literature relevant to POCD. Continued research with the leading-edge zebrafish unlocks the possibility that, in the future, perioperative intervention will prevent POCD.
基金Project supported by the Shandong Science and Technology Development Project(No.2011YD18070),China
文摘Objective： To investigate the relationship between post-operative cognitive dysfunction（POCD） and regional cerebral oxygen saturation（rSO2） and β-amyloid protein（Aβ） in patients undergoing laparoscopic pancreaticoduodenectomy. Methods： Fifty patients undergoing elective laparoscopic pancreaticoduodenectomy received five groups of neuropsychological tests 1 d pre-operatively and 7 d post-operatively, with continuous monitoring of rSO2 intra-operatively. Before anesthesia induction（t0）, at the beginning of laparoscopy（t1）, and at the time of pneumoperitoneum 120 min（t2）, pneumoperitoneum 240 min（t3）, pneumoperitoneum 480 min（t4）, the end of pneumoperitoneum（t5）, and 24 h after surgery, jugular venous blood was drawn respectively for the measurement of Aβ by enzyme-linked immunosorbent assay（ELISA）. Results： Twenty-one cases of the fifty patients suffered from POCD after operation. We found that the maximum percentage drop in rSO2（rSO2, %max） was significantly higher in the POCD group than in the non-POCD group. The rSO2, %max value of over 10.2% might be a potential predictor of neurocognitive injury for those patients. In the POCD group, the plasma Aβ levels after 24 h were significantly higher than those of pre-operative values（P〈0.01）. After 24 h, levels of plasma Aβ in the POCD group were significantly higher than those in the non-POCD group（P〈0.01）. Conclusions： The development of POCD in patients undergoing laparoscopic pancreaticoduodenectomy is associated with alterations of rSO2 and Aβ. Monitoring of rSO2 might be useful in the prediction of POCD, and Aβ might be used as a sensitive biochemical marker to predict the occurrence of POCD.
文摘To the Editor:In a randomized controlled preliminary trial comparing effects of propofol,dexmedetomidine,and midazolam on postoperative cognitive dysfunction(POCD)in elderly patients undergoing hip or knee arthroplasty with combined spinal-epidural anesthesia,Li et al[1]showed that intraoperative sedation with propofol compared to dexmedetomidine can significantly decrease risk of POCD.Given that POCD is associated with major adverse consequences,for example,an increased mortality rate,reduced quality of life,and delayed long-term recovery,[2]their findings have potential implications.However,we note that this finding is totally different from the results of a recent large randomized controlled study in elderly patients undergoing hip arthroplasty with the peripheral nerve block,in which patients sedated with dexmedetomidine have a lower risk of POCD than those sedated with propofol.
文摘目的观察老年下肢手术患者围手术期血清神经元特异性烯醇化酶(neuron specific enolase,NSE)、S-100β变化,探讨术后认知功能障碍的(postoperative cognitive dysfunction,POCD)发生与NSE、S-100β变化的关系。方法择期行下肢手术的老年患者86例,分别于术前24h、术后6h以及48h进行老年认知功能量表(the scale of elderly congitive fuction,SECF)测定;同时检测术前24h、术后6h以及48h血清中NSE、S-100β蛋白水平。结果①术后共有21例患者被诊断为POCD。②NSE水平在术后6h以及48h均明显升高,与术前24h相比差异有显著统计学意义;③S-100β仅在术后6h显著升高,与术前24h相比差异有显著统计学意义;术后48h下降至术前水平。④发生POCD的患者,其术后NSE以及S-100β蛋白水平明显高于未发生者。结论老年患者术后NSE、S-100β蛋白水平明显升高,血清中NSE、S-100β蛋白水平的变化与POCD的发生有密切关系。
文摘目的采用循证医学的方法系统评价右美托咪定在老年患者全麻术后认知功能障碍的影响。方法计算机检索Cochrane、Pub Med、Medline、知网、维普、万方数据库,均从建库到2015年7月发表的文献,对符合纳入与排除标准的研究进行资料提取,并采用Rev Man 5.2软件进行Meta分析。结果最终纳入13个随机对照试验,共计854例患者。Meta分析结果显示:术后1 d右美托咪定组简易精神状态评价量表(MMSE评分)高于对照组,差异有统计学意义(P<0.05);右美托咪定组术后1 d POCD的发生率明显低于对照组(P<0.05),差异有统计学意义。结论老年患者全麻术中使用右美托咪定,能有效改善患者术后认知功能障碍,降低POCD的发生率。
