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Objective:To evaluate the relationship between hippocampal macrophage polarization and perioperative neurocognitive disorders in mice with tibial fractures.Methods:Forty-five clean-grade healthy male C57/BL6 mice, aged 5-7 months, were divided into 3 groups ( n=15 each) using the random number table method: control group (group C), anesthesia group (group A) and anesthesia surgery group (group AS). Group C received no treatment. Group A was anesthetized with isoflurane inhaled for 15 min. In AS group, intramedullary nail fixation of tibial fracture was performed under anesthesia through inhalation of 2% isoflurane. Morris water maze test and open field test were performed before anesthesia/on 1 day before surgery and after anesthesia/on 1, 3 and 7 days after operation. Five mice were randomly selected after the behavioral experiments were completed at each time point, and hippocampal tissues were taken after the animals were sacrificed for determination of the expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, chemokine (c-c motif) ligand 12 (CCL2), CCL5, CCL8, iNOS and Arg-1 mRNA (by quantitative real-time polymerase chain reaction), expression of iNOS and Arg-1 proteins (by Western blot), and percentage of CD11b, CD45, CD86 and CD206 cells in hippcampal area (by immunofluorescence staining). Results:Compared with group C, the escape latency was significantly prolonged after operation, the number of crossing the platform was reduced after operation, the expression of TNF-ɑ, IL-6, CCL5 and CCL8 mRNA and iNOS protein and mRNA was up-regulated, the expression of Arg-1 protein and mRNA was down-regulated, the percentages of CD11b + CD45 + cells and CD11b + CD86 + cells in the hippocampus were increased, and the percentages of CD11b + CD206 + cells were decreased in AS group ( P<0.05), and no significant change was found in the parameters mentioned above in group A ( P>0.05). Compared with group A, the escape latency was significantly prolonged after surgery, the frequency of crossing the platform was reduced after surgery, the expression of iNOS mRNA was up-regulated, the percentages of CD11b + CD45 + cells and CD11b + CD86 + cells were increased, and the percentages of CD11b + CD206 + cells were decreased in AS group ( P<0.05). Conclusions:The occurrence of PND may be related to increased polarization to M1 macrophages in the hippocampus and decreased polarization to M2 macrophages in mice with tibial fracture, which further leads to central inflammatory responses.
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Objective:To evaluate the changes in proteome in hippocampus and bioinformatics analysis in mice with perioperative neurocognitive disorders (PND).Methods:Clean-grade healthy male C57BL/6 mice, aged 15 months, weighing 30-35 g, were divided into 2 groups ( n=9 each) using a random number table method: control group (group C) and group PND.The model of PND was established by performing open tibial fracture with intramedullary fixation under isoflurane anesthesia in anesthetized mice.The Morris water maze test, open field test and fear conditioning test were performed at 1 day before operation and at 1, 3 and 7 days after operation.At 1, 3 and 7 days after operation, 3 mice with worst cognitive performance in each cognitive function assessments were sacrificed in group P, and three mice were randomly sacrificed in group C. The hippocampal tissues were then obtained, the expression of differentially expressed proteins was identified by high-performance liquid chromatography-mass spectrometry, and Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to analyze the differentially expressed proteins. Results:Compared with group C, the escape latency at different time points was significantly prolonged, and the percentage of time spend on target quadrant and the percentage of freezing time in fear conditioning test were decreased in group P ( P<0.05). There were 21 differentially expressed proteins, of which 12 proteins showed up-regulated expression and 9 proteins showed down-regulated expression.The GO functional analysis showed that the differentially expressed proteins were involved in the process such as the metabolism, signal transmission, regulation of biological processes, formed cell components such as synapses and organelles, and were related to molecular function such as binding and transportation.KEGG signaling pathway analysis showed that there were also differences in MAPK signaling pathway, ErbB signaling pathway, AMPK signaling pathway and the transport of SNARE protein in vesicle and etc. Conclusion:There are 21 differentially expressed proteins in the hippocampus of PND mice, and these proteins are involved in the pathophysiological process probably related to PND such as neuroinflammatory responses, abnormal synaptic structure, mitochondrial dysfunction and decreased autophagy.
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Objective:To investigate the relationship between preoperative subjective cognitive decline (SCD) and postoperative delirium (POD) in elderly patients.Methods:A total of 292 elderly patients of both sexes, aged 65-90 yr, weighing 50-90 kg, of American Society of Anesthesiologists physical status Ⅰ-Ⅱ, with Mini-Mental State Examination (MMSE) score>23 and Montreal Cognitive Assessment (MoCA) score > 26 at 1 day before operation, underwent total knee/hip arthroplasty under combined spinal-epidural block in our hospital from January to December 2020, were collected.The development of SCD was evaluated using subjective cognitive decline scale at 1 day before operation.Cerebrospinal fluid (CSF) was extracted after successful spinal-epidural anesthesia puncture, the concentrations of β-amyloid protein 40 (Aβ 40), Aβ 42, total tau (t-tau) and phosphorylated tau (p-tau) were determined by enzyme-linked immunosorbent assay.The incidence of POD was evaluated using confusion assessment method during post-anesthesia care unit and at 1-7 days after operation (or before discharge). Patients were divided into POD group and non-POD group according to whether POD occurred within 7 days after operation.The risk factors of which P values were less than 0.05 would enter the logistic regression analysis to stratify the risk factor for incidence of POD. Results:A total of 205 patients were enrolled and 53 patients developed POD (25.8%). The results of logistic regression analysis showed that preoperative SCD, and increased CSF p-tau and t-tau concentrations were risk factors for POD of elderly patients, and increased CSF Aβ 42 concentration and Aβ 40/p-tau, Aβ 40/t-tau, Aβ 42/p-tau and Aβ 42/t-tau were the protective factors for POD in elderly patients ( P<0.05). After correction of the confounding factors such as age, sex, body weight, education, the history of smoking and drinking, hypertension, diabetes and coronary heart disease, family history of dementia, Pittsburgh sleep quality index (PSQI), MMSE and MoCA score at 1 day before operation, duration of surgery, duration of anesthesia, intraoperative volume of infusion and blood loss and postoperative pain score, SCD, and increased CSF p-tau and t-tau concentrations were still the risk factors for POD in elderly patients, and increased CSF Aβ 42 concentration and Aβ 40/p-tau, Aβ 40/t-tau, Aβ 42/p-tau and Aβ 42/t-tau were still the protective factors for POD in elderly patients ( P<0.05). Conclusion:Preoperative SCD is the risk factor for POD in elderly patients.
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Objective:To evaluate the value of cerebrospinal fluid (CSF) nerve injury-related proteins levels in predicting postoperative delirium (POD) in patients.Methods:A total of 1 000 patients of both sexes, aged 40-90 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, with Mini-Mental State Examination score>24 at 1 day before operation, undergoing elective knee/hip arthroplasty under spinal-epidural anesthesia , were enrolled in this study.Cubital venous blood samples were drawn before anesthesia for detection of the concentrations of plasma total cholesterol, high-density lipoprotein, low-density lipoprotein and triglyceride.CSF 2ml was extracted after successful spinal-epidural anesthesia puncture for measurement of concentrations of α-synuclein (α-syn), β-amyloid protein 1-40 (Aβ 1-40), Aβ 1-42, total-Tau (t-Tau), phosphorylated Tau (p-Tau), progranulin (PGRN) and soluble myeloid cell triggering receptor 2 (sTREM2) (by enzyme-linked immunosorbent assay). The Confusion Assessment Method was used at 1, 3 and 7 days after surgery to evaluate the occurrence of POD.The patients were divided into POD group and non-POD group according to whether POD occurred after operation.Logistic regression analysis was used to analyze the variables of which P values were less than 0.05 to analyze the risk factors for POD.The receiver operating characteristic (ROC) curve was drawn and area (AUC) under the curve was calculated to evaluate the accuracy of the related risk factors in predicting POD. Results:A total of 964 patients were enrolled in the study, and 108 patients were diagnosed with POD, and the incidence was 11.2%.The results of logistic regression analysis found that age and and increased α-syn in CSF concentration were risk factors for POD, and decreased PGRN in CSF concentration and Aβ 1-42/p-Tau in CSF were the protective factors for POD ( P<0.05). ROC curve analysis showed that α-syn (AUC 0.69, 95% confidence interval (CI) 0.634-0.748, sensitivity 57.41%, specificity 82.10%, Youden Index 0.3951), PGRN in CSF concentration (AUC 0.695, 95%CI 0.637-0.750, sensitivity 59.26%, specificity 80.86%, Youden Index 0.4012) and Aβ 1-42/p-Tau in CSF (AUC 0.635, 95%CI 0.574-0.692, sensitivity 93.52%, specificity 30.25%, Youden Index 0.2377) could predict the occurrence of POD. Conclusion:PGRN, α-syn concentration and Aβ 1-42/p-Tau in CSF can predict the occurrence of POD in patients.
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Acute ischemic stroke with large vessel occlusion (AIS-LVO) refers to ischemic stroke caused by large vessel occlusion of internal carotid artery, middle cerebral artery and vertebrobasilar artery, which has the characteristics of large infarct, relatively poor outcome, higher disability and mortality. Therefore, early vascular recanalization and rescue of ischemic penumbra are the key to improve the outcome of patients with AIS-LVO. Mechanical thrombectomy (MT) has a definite effect on AIS-LVO. The current guidelines recommend that MT should be performed on the basis of IVT for AIS-LVO patients without contraindications of intravenous thrombolysis (IVT), the so-called bridging therapy. IVT can increase the risk of bleeding to a certain extent, delay MT and increase the cost of hospitalization. However, there are still many controversies about whether the patients with AIS-LVO can directly perform MT. This article reviews the comparative study of direct MT and bridging therapy in patients with anterior circulation AIS-LVO, hoping to provide reference for clinicians in the treatment of AIS-LVO.
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Objective To provide more reference base for the prevention and treatment of acute cerebral infarction through the correlation study between the onset of acute cerebral infarction and meteorological factors during the same period in Dalian area.Methods From January 1,2015 to December 31,2015,the data of hospitalized medical records and meteorological data during the same period in 3 5 7 8 consecutive patients with acute cerebral infarction admitted to three tertiary hospitals in Dalian were analyzed retrospectively.The seasonal regularity of acute cerebral infarction in Dalian area was analyzed descriptively.A single retrospective 1 ∶ 1 matched case-crossover study design was used to analyze the effect of mean air temperature lag 0-3 days on the onset of acute cerebral infarction.Pearson correlation analysis was used to analyze the influence of meteorological factors of the day on the onset of acute cerebral infarction,at the same time,the relationship between stroke subtypes and meteorological factors was investigated.Results (1) The incidence of acute cerebral infarction was higher in winter (December,January,and February) and it was lower in summer (from June to August).(2) Hysteresis analysis:when the temperature was reduced by 1 ℃each time,the OR values of acute cerebral infarction lagging behind 0 and 1 d were 1.034 (95％ CI 1.012-1.056) and 1.025 (95％ CI 1.008-1.042) respectively.There was significant difference (all P ＜ 0.05).The correlation between the temperature of the day of onset and the onset of acute cerebral infarction was the highest.(3) The onset of cerebral infarction was negatively correlated with the average temperature of the day and hours of sunshine (r =-0.392,-0.260,all P ＜ 0.01),and it was positively correlated with the daily average air pressure (r =0.403,P ＜ 0.01).Among them,the correlation of the type of cardiogenic embolism and each meteorological factor was the highest.The correlation coefficients of daily average temperature,daily air pressure,and hours of sunshine were-0.836,0.733,and-0.629,respectively (all P ＜ 0.01).Conclusion A cold and high air pressure may trigger the onset of acute cerebral infarction,especially cardiogenic cerebral infarction.
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Mild stroke refers to ischemic stroke with mild neurological defects.In recent years,its incidence rate has increased gradually.However,there is no standardized definition for mild stroke,and there is a great controversy about whether to conduct thrombolytic therapy for mild stroke.The conventional wisdom holds that the patients with mild stroke should not be treated with intravenous thrombolysis;however,many studies have indicated that the short-term and medium-term outcomes are poor in patients with mild stroke without receiving thrombolytic therapy,and many patients with mild stroke may benefit from thrombolytic therapy.This article summarizes about the definition of mild stroke and the clinical studies of thrombolytic therapy in recent years,hoping to provide reference for clinicians in order to make better clinical decisions.
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Objective To investigate MR findings and analysis of misdiagnosis of atypical invasive pituitary adenoma.Methods The MR findings of twenty cases of atypical invasive pituity adenomas confirmed by pathology were reviewed ,which were misdiag-nosed as chordomas or meningiomas.Results All the twenty cases showed iso-or slightly hypo-signal on T1 WI,iso-or slightly hy-per-signal on T2 WI;Enhanced scan displayed heterogeneous enhancement.The dynamic enhancement curve showed rapid enhance-ment phase.The bilateral cavernous sinuswere infringed in nine cases,in which the pituity and pituity stalk were not well seen. Among the twenty cases,twelve cases with suprasellar and anterior cranial fossa extension were misdiagnosed as meningiomas;eight cases with clival destruction were misdiagnosed as chordomas.Conclusion The MR features of atypical invasive pituity adenomas are various.In order to avoid misdiagnosis,a comprehensive analysis should be based on a variety of signs.