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.

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.

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.

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.

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.

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。

Effects of propofol, dexmedetomidine, and midazolam on postoperative cognitive dysfunction in elderly patients: a randomized controlled preliminary trial

Background: Postoperative cognitive dysfunction (POCD) is a serious complication after surgery, especially in elderly patients. The anesthesia technique is a potentially modifiable risk factor for POCD. This study assessed the effects of dexmedetomidine, propofol or midazolam sedation on POCD in elderly patients who underwent hip or knee replacement under spinal anesthesia. Methods: The present study was a prospective randomized controlled preliminary trial. From July 2013 and December 2014, a total of 164 patients aged 65 years or older who underwent hip or knee arthroplasty at China-Japan Friendship Hospital and 41 non-surgical controls were included in this study. Patients were randomized in a 1:1:1 ratio to 3 sedative groups. All the patients received combined spinal-epidural anesthesia (CSEA) with midazolam, dexmedetomidine or propofol sedation. The sedative dose was adjusted to achieve light sedation (bispectral index[BIS] score between 70 and 85). All study participants and controls completed a battery of 5 neuropsychological tests before and 7 days after surgery. One year postoperatively, the patients and controls were interviewed over the telephone using the Montreal cognitive assessment 5-minute protocol. Results: In all, 60 of 164 patients (36.6%) were diagnosed with POCD 7 days postoperatively, POCD incidence in propofol group was significantly lower than that in dexmedetomidine and midazolam groups (18.2% vs. 40.0%, 51.9%, χ^2 6.342 and 13.603, P= 0.012 and < 0.001). When the patients were re-tested 1 year postoperatively, the incidence of POCD was not significantly different among the 3 groups (14.0%, 10.6% vs. 14.9%, χ^2 0.016 and 0.382, P= 0.899 and 0.536). Conclusion: Among dexmedetomidine, propofol and midazolam sedation in elderly patients, propofol sedation shows a significant advantage in term of short-term POCD incidence.

Comparing the effects of different drugs on postoperative cognitive dysfunction in elderly patients

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.

Serum proteomics of early postoperative cognitive dysfunction in elderly patients

Background Studies on postoperative cognitive dysfunction （POCD） have attracted extensive attention and achieved significant progress. However, the diagnosis of POCD is not very satisfactory as no specific biomarkers have been classified. The aim of the present study was to evaluate differences in serum protein composition between POCD and Non-POCD patients, identify potential biomarkers associated with early POCD, and study the mechanism underlying POCD. Methods Sixty-eight elderly patients （age 〉65 years） received isoflurane inhalation anesthesia for arthroplasty surgeries. One day before and seven days after the surgery, these patients were subjected to a neuropsychological test and venous blood sample collection. Postoperative cognitive dysfunction was determined using Z test scores. Based on the results, the patients were divided into POCD and non-POCD groups. Twenty-five randomly chosen blood samples obtained seven days after the surgery from each group were analyzed on a Bruker ultraFlexTM time of flight （TOF）/TOF mass spectrophotometer. The resulting peptide fingerprints were compared with those from the pre-surgery samples to identify differences in serum protein composition. The model designed to distinguish between a non-POCD group and a POCD group were established and validated. Three proteins with the most significant changes were selected for further characterization. Results Thirty-three cases were diagnosed as POCD. Using the Clinprotools software, 58 polypeptides were found to display differential expression （P 〈0.05）. Using a support vector algorithm method, seven differential peaks were isolated to establish a diagnostic model to distinguish POCD patients from normal individuals. The prediction rate and recognition rate were 96.89% and 100%, respectively. Validation of this model showed that the accuracy rates were 100% and 85% using samples from the POCD and non-POCD groups, respectively. Protein analysis also led to the identification of fibrinopeptide A （FPA） as a potential biomarker for POCD. Conclusions Arthroplastic surgery under isoflurane inhalation anesthesia causes differential serum protein expression in elderly patients. These differentially expressed proteins may contribute to the diagnosis of early POCD, which may provide a basis for identifying the underlying mechanism of POCD development.

Investigation of one-lung ventilation postoperative cognitive dysfunction and regional cerebral oxygen saturation relations

Objective： To explore the relationship of postoperative cognitive dysfunction （POCD） in one-lung ventilation （OLV） patients and regional cerebral oxygen saturation （rSO2）. Methods： Twenty-nine male and twenty-one female cases of OLV received thoracic surgery, with American Standards Association （ASA） physical status being at Grades Ⅰ-Ⅲ. Neuropsychological tests were performed on the day before operation and 7 d after operation, and there was an intraoperative continuous monitoring of rSO2. The values of rSO2 before anesthesia induction （t1）, at the beginning of OLV （t2）, and at the time of OLV 30 min （t3）, OLV 60 min （t4）, the end of OLV （t5）, and the end of surgery （t6） were recorded. The intraoperative average of rSO2 （ rSO2 ）, the intraoperative minimum value of rSO2 （rSO2, rn=n）, and the reduced maximum percentage of rSO2 （rSO2, %max） when compared with the baseline value were calculated. The volume of blood loss, urine output, and the amount of fluid infusion was recorded. Results： A total of 14 patients （28%） in the 50 cases suffered from POCD. The values of mini-mental state examination （MMSE）, the digit span and the digit symbol on the 7th day after the operation for POCD in OLV patients were found to be significantly lower than those before the operation （P〈0.05）. The values of MMSE and vocabulary fluency scores were significantly lower than those in the non-POCD group （P〈0.05）. The values of rSO2 in the POCD group of OLV patients at t2 and t3 and the values of rSO2 in the non-POCD group at t2 were found to be significantly higher than those at tl （P〈0.05）. The values of rSO2, %max in the POCD group were significantly higher than those in the non-POCD group （P〈0.05）. When the value of rSO2, %max is more than 10.1%, it may act as an early warning index for cognitive function changes, Conclusions： POCD after OLV may be associated with a decline in rSO2.

持续输注超低剂量右美托咪定对老年CAS患者血流动力学和术后认知功能的影响

目的探讨持续输注超低剂量右美托咪定对行颈动脉支架置入术(CAS)的老年患者血流动力学稳定性和术后认知功能的影响。方法选取106例于首都医科大学附属北京世纪坛医院择期行CAS的老年患者,随机分为右美托咪定组(D组,n=52)和对照组(C组,n=54)。观察2组患者麻醉诱导前15 min(T0)、麻醉诱导后5 min(T1)、置入支架前5 min(T2)、置入支架后5 min(T3)、气管拔管后5 min(T4)的血流动力学和脑灌注变化;计算平均动脉压(MAP)、心率(HR)和脑氧饱和度(rSO_(2))的标准差(SD),分别记作SD_(MAP)、SD_(HR)和SD_(rSO_(2))。应用蒙特利尔认知评估量表(MoCA)对患者进行认知功能评估,比较患者术前、术后认知功能的变化,评价2组患者术后认知功能障碍(POCD)的发生情况。结果D组患者SD_(MAP)、SD_(HR)和SD_(rSO_(2))均明显低于C组(P<0.05);D组麻醉药及血管活性药使用量明显低于C组(P<0.05);D组拔管时间明显短于C组(P<0.05);D组术后1 d MoCA评分明显高于C组,术后30 d POCD发生率明显低于C组(P<0.05)。结论持续输注超低剂量右美托咪定可维持血流动力学和脑灌注稳定,减少麻醉药物用量,促进术后认知功能恢复。

全基因组关联分析老年患者体外循环心脏手术后POCD易感性研究

目的 筛查老年患者体外循环心脏手术后发生认知功能障碍的易感基因位点。方法 选取120名计划进行体外循环心脏手术患者,麻醉诱导前收集患者5 mL血液,在术前1 d以及术后7 d对患者进行认知功能检测,通过简易智能状态评定表判断患者是否发生术后认知功能障碍(POCD),随机抽取36例发生POCD的患者和36例未发生POCD的患者,运用病例对照的研究方法通过全基因组关联分析筛选体外循环心脏手术后发生POCD的易感基因。结果 将发生POCD患者序列与未发生POCD患者序列通过高通量测序筛选得出370 384个单核苷酸多态性(SNP)位点,其中104个SNP位点(P<0.05)与体外循环心脏手术后POCD的发生相关联,这些SNP位点主要集中于1号、2号、7号、11号、13号、15号染色体,以内含子变异和上游基因突变为其主要突变类型,生物信息学分析发现参与的生物进程与功能主要包括离子稳态和激素合成分泌等。结论 POCD患者与正常人群存在易感基因差异。

Clinical Effect of Electroacupuncture Baihui and Neiguan Acupoint on Cognitive Function Recovery in Elderly Patients after General Anesthesia

Objective:To study and analyze the clinical effect of electroacupuncture at Baihui and Neiguan Points on cognitive function recovery of elderly patients after general anesthesia.Methods:The subjects were 80 elderly patients who received general anesthesia from January 2019 to February 2021.According to different anesthesia methods,they were divided into research group(electroacupuncture at Baihui and Neiguan combined with conventional drug anesthesia)and control group(simple drug anesthesia).The postoperative cognitive function recovery of the two groups was observed and compared.Results:Compared with the control group,the MMSE score and POCD incidence of research group were significantly better.There was significant difference between the two groups(P<0.05).Conclusion:Conclusion electroacupuncture at Baihui and Neiguan combined with conventional drug anesthesia can promote the recovery of cognitive function and prevent cognitive dysfunction in elderly patients under general anesthesia.