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Aim: To explore the association between the neutrophil-to-platelet ratio (NPR) and futile recanalization (FR) in patients with acute ischemic stroke due to large vascular occlusions after endovascular therapy (EVT). Methods: FR after EVT was defined as a poor 90-day prognosis (modified Rankin scale [mRS] score ≥3) despite successful reperfusion (modified thrombolysis in cerebral infarction grade 2b-3). Patients were divided into high NPR (>35; n = 115) and low NPR (≤35; n = 81) groups. Results: The FR rate was significantly higher in the high NPR group than low NPR group (81.74 vs 55.56%; p = 0.000). NPR was independently associated with FR (odds ratio: 2.107; 95% CI: 1.017-4.364; p = 0.045). Conclusion: High NPR was associated with the risk of FR in patients with acute ischemic stroke due to large vascular occlusions.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular Isquémico/complicaciones , Neutrófilos , Procedimientos Endovasculares/efectos adversos , Resultado del Tratamiento , Isquemia Encefálica/complicaciones , Estudios RetrospectivosRESUMEN
PURPOSE: To evaluate the physical and cognitive functions of patients with stroke who underwent either direct or bridging thrombectomy within 6 hours of stroke onset. MATERIALS AND METHODS: Patients with large vessel occlusion in anterior circulation treated with direct (direct group) or bridging thrombectomy (bridging group) were prospectively analyzed between June 2020 and February 2022. The efficacy outcome was the 3-month modified Rankin Scale (mRS) score, the safety outcome was symptomatic intracranial hemorrhage (sICH), and cognitive function was assessed using the Clinical Dementia Rating (CDR) scale at 6 months after stroke. RESULTS: A total of 125 patients (direct group, n = 75; bridging group, n = 50) who had completed follow-up at 3 months by telephone call were included. No significant differences were observed between the direct and bridging groups in terms of an mRS score of 0-2 (25.3% vs 22.0%, respectively; P = .83), an mRS score of 0-3 (37.3% vs 44.0%, respectively; P = .58), sICH (17.3% vs 14.0%, respectively; P = .80), or 3-month all-cause mortality (36.3% vs 30.0%, respectively; P = .34). Sixty-nine patients (direct group, n = 38; bridging group, n = 31) completed the CDR assessment at 6 months after stroke. There was no significant difference in poststroke dementia, defined as a CDR score of ≥1 point between the direct group (42.1%) and bridging group (22.6%) (P = .12). Ordinal regression analyses showed that the CDR score at 6 months was not associated with treatment type (direct thrombectomy vs bridging thrombectomy). CONCLUSIONS: With regard to physical and cognitive functions at 3 and 6 months, direct thrombectomy was comparable with bridging thrombectomy in patients who were treated within 6 hours of stroke onset.
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Isquemia Encefálica , Accidente Cerebrovascular , Humanos , Estudios Prospectivos , Resultado del Tratamiento , Trombectomía/efectos adversos , Hemorragias Intracraneales/etiología , Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Terapia Trombolítica/efectos adversosRESUMEN
BACKGROUND: Previous cross-sectional studies have identified a possible link between Helicobacter pylori (H. pylori) infection and dementia. However, the association of H. pylori infection with longitudinal cognitive decline has rarely been investigated. OBJECTIVE: This cohort study aims to demonstrate the effects of H. pylori infection on longitudinal cognitive decline. METHODS: This cohort study recruited 268 subjects with memory complaints. Among these subjects, 72 had a history of H. pylori infection, and the rest 196 subjects had no H. pylori infection. These subjects were followed up for 24 months and received cognitive assessment in fixed intervals of 12 months. RESULTS: At baseline, H. pylori infected, and uninfected participants had no difference in MMSE scores. At 2 years of follow-up, H. pylori infected participants had lower MMSE scores than uninfected participants. H. pylori infection was associated with an increased risk of longitudinal cognitive decline, as defined by a decrease of MMSE of 3 points or more during follow-up, adjusting for age, sex, education, APOEÉ4 genotype, hypertension, diabetes, hyperlipidemia, and smoking history (HR: 2.701; 95% CI: 1.392 to 5.242). H. pylori infection was associated with larger cognitive decline during follow-up, adjusting for the above covariates (standardized coefficient: 0.282, pâ<â0.001). Furthermore, H. pylori infected subjects had significantly higher speed of cognitive decline than uninfected subjects during follow-up, adjusting for the above covariates. CONCLUSION: H. pylori infection increases the risk of longitudinal cognitive decline in older subjects with memory complaints. This study is helpful for further understanding the association between infection and dementia.
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Disfunción Cognitiva , Demencia , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Anciano , Estudios de Seguimiento , Estudios de Cohortes , Factores de RiesgoRESUMEN
It has been assumed that patients with strict immunosuppressive treatment after solid organ transplantation have only marginal risk in developing autoimmune encephalitis. We reported a woman in her late 40 s who presented with generalized convulsions and loss of consciousness. After detailed history review, neuropsychological tests, metagenomic next-generation sequencing of serum and cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) brain, and electroencephalogram, she was diagnosed as anti-CASPR2 encephalitis based on the positive anti-CASPR2 auto-antibody in serum and CSF. The patient underwent liver transplantation and has taken lenvatinib for 2 months, in addition to tacrolimus, mycophenotale mofetil, and entecavir administered for half a year. This case was the first report of anti-CASPR2 encephalitis in post-organ transplantation patients. Together with the reports of other encephalitis cases in organ transplantation, it warns the possibility of developing immune-oriented encephalitis in patients undergoing immunosuppression, especially in combination with other treatments of immunomodulatory activity.
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Autoanticuerpos , Encefalitis , Femenino , Humanos , Encefalitis/tratamiento farmacológico , Encefalitis/etiología , Terapia de Inmunosupresión/efectos adversos , HígadoRESUMEN
INTRODUCTION: To evaluate the predictors for efficacy and safety of patients with acute ischemic stroke (AIS) and Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) ï¼6 undergoing endovascular therapy (EVT). METHODS: This study retrospectively analyzed consecutive patients presented between December 2020 and December 2021 with large vessel occlusions (LVO) within the anterior circulation and an ASPECTS ï¼6, followed by EVT. The efficacy outcome was 90-day functional independence, defined as modified Rankin Scale (mRS) score 0-3. The primary safety outcome was symptomatic intracranial hemorrhage (sICH). Secondary safety outcomes included 90-day all-cause mortality and 24-hour any ICH. RESULTS: A total of 22 patients were included. The percentage of patients with mRS 0-3 at 90â¯days was 36.4% (8/22). The occurrence of sICH was 22.7% (5/22). The occurrence of any ICH was 45.5% (10/22). The 90-day all-cause mortality was 36.4% (8/22). Median (interquartile range, IQR) cerebral blood volume (CBV) index was 0.5 (0.4-0.7). CBV index in mRS 0-3 group (nâ¯=â¯8) was higher than mRS 4-5 group (nâ¯=â¯14) (Pï¼0.05). There was no significant difference of age, gender, comorbidities, baseline National Institutes of Health Stroke Scale (NIHSS) score, mismatch ratio, CBV index, interval between stroke onset and re-perfusion, good re-perfusion rate between sICH group (nâ¯=â¯5) and non-sICH group (nâ¯=â¯17). CONCLUSIONS: AIS patients with low ASPECTS can still benefit from EVT and gain good functional outcome, especial those had higher CBV index on pre-EVT computed tomography perfusion (CTP). Further studies with larger sample size are needed to validate our findings.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Alberta , Volumen Sanguíneo Cerebral , Humanos , Hemorragias Intracraneales , Estudios Retrospectivos , Trombectomía , Resultado del TratamientoRESUMEN
Background: This study aims to assess the efficacy and safety of different doses of intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke (AIS) by adopting a network meta-analysis (NMA). Methods: Studies comparing different doses of tPA in AIS were identified by retrieving electronic databases. NMAs of outcome measures included favorable functional outcome with a modified Rankin scale score (mRS) of 0 or 1 at 3 months after treatment (3M-FF), the functional independence with a mRS of 0, 1, or 2 at 3 months (3M-FI), symptomatic intracranial hemorrhage (sICH) and 3-month all-cause mortality (3M-M). Symptomatic intracranial hemorrhage (sICH) and 3-month all-cause mortality (3M-M) were assessed. Probability-based ranking and surface under cumulative ranking (SUCRA) were performed to identify the best dose of tPA. Inconsistency was evaluated by node-splitting analysis and a loop-specific approach. Publication bias was analyzed by funnel plots. Results: A total of 14 studies were included in the quantitative synthesis. The NMA results revealed no difference among low (<0.7 mg/kg), moderate (0.8 mg/kg), and standard (0.9 mg/kg) doses of tPA with regard to efficacy and safety. The SUCRAs of 3M-FF and 3M-FI showed that the standard dose ranked first, the moderate dose ranked second, and the low dose ranked third. The SUCRA of sICH showed that the standard dose ranked first (78.1%), the low dose ranked second (61.0%), and the moderate dose ranked third (11.0%). The SUCRAs of 3-month mortality showed that the standard dose ranked first (73.2%), the moderate dose ranked second (40.8%), and the low dose ranked third (36.1%). No significant inconsistency was shown by node-splitting analysis and no publication bias was shown in funnel plots. Conclusion: Lower dose tPA was comparable to the standard dose with regard to efficacy and safety. Based on the SUCRA results and American Heart Association/American Stroke Association (AHA/ASA) guidelines, the standard dose was still the optimal selection for AIS.
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Background: Recent evidence of genetics and metabonomics indicated a potential role of apolipoprotein M (ApoM) in the pathogenesis of Alzheimer's disease (AD). Here, we aimed to investigate the association between plasma ApoM with AD. Methods: A multicenter, cross-sectional study recruited patients with AD (n = 67), age- and sex-matched cognitively normal (CN) controls (n = 73). After the data collection of demographic characteristics, lifestyle risk factors, and medical history, we examined and compared the plasma levels of ApoM, tau phosphorylated at threonine 217 (p-tau217) and neurofilament light (NfL). Multivariate logistic regression analysis was applied to determine the association of plasma ApoM with the presence of AD. The correlation analysis was used to explore the correlations between plasma ApoM with cognitive function [Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)], activities of daily living (ADL), and the representative blood-based biomarkers (plasma p-tau217 and NfL). Receiver operating characteristic (ROC) analysis and Delong's test were used to determine the diagnostic power of plasma ApoM. Results: Plasma ApoM and its derived indicators (ratios of ApoM/TC, ApoM/TG, ApoM/HDL-C, and ApoM/LDL-C) were significantly higher in AD group than those in CN group (each p < 0.0001). After adjusted for the risk factors of AD, the plasma ApoM and its derived indicators were significantly associated with the presence of AD, respectively. ApoM (OR = 1.058, 95% CI: 1.027-1.090, p < 0.0001), ApoM/TC ratio (OR = 1.239, 95% CI: 1.120-1.372, p < 0.0001), ApoM/TG ratio (OR = 1.064, 95% CI: 1.035-1.095, p < 0.0001), ApoM/HDL-C ratio (OR = 1.069, 95% CI: 1.037-1.102, p < 0.0001), and ApoM/LDL-C ratio (OR = 1.064, 95% CI:1.023-1.106, p = 0.002). In total participants, plasma ApoM was significantly positively correlated with plasma p-tau217, plasma NfL, and ADL (each p < 0.0001) and significantly negatively correlated with MMSE and MoCA (each p < 0.0001), respectively. In further subgroup analyses, these associations remained in different APOEϵ 4 status participants and sex subgroups. ApoM/TC ratio (ΔAUC = 0.056, p = 0.044) and ApoM/TG ratio (ΔAUC = 0.097, p = 0.011) had a statistically remarkably larger AUC than ApoM, respectively. The independent addition of ApoM and its derived indicators to the basic model [combining age, sex, APOEϵ 4, and body mass index (BMI)] led to the significant improvement in diagnostic power, respectively (each p < 0.05). Conclusion: All the findings preliminarily uncovered the association between plasma ApoM and AD and provided more evidence of the potential of ApoM as a candidate biomarker of AD.
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ß-Hydroxybutyl acid (ßOHB), the most prevalent type of ketone in the human body, is involved in the pathogenesis of cognitive disorders, especially Alzheimer's dementia (AD), through a variety of mechanisms, such as enhancing mitochondrial metabolism, regulating signaling molecule, increasing histone acetylation, affecting the metabolism of Aß and Tau proteins, inhibiting inflammation and lipid metabolism, and regulating intestinal microbes. Based on the above findings, clinical drug development in AD has begun to focus on ßOHB.
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Enfermedad de Alzheimer , Ácido 3-Hidroxibutírico/metabolismo , Ácido 3-Hidroxibutírico/farmacología , Acetilación , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Cognición , Humanos , Mitocondrias/metabolismoRESUMEN
INTRODUCTION: C1q tumor necrosis factor (TNF)-related protein 9 (CTRP9) is a novel member of the C1q/TNF superfamily. According to our previous review, CTRP9 plays a vital role in the process of cardiovascular diseases, including regulating energy metabolism, modulating vasomotion, protecting endothelial cells, inhibiting platelet activation, inhibiting pathological vascular remodeling, stabilizing atherosclerotic plaques, and protecting the heart. We proposed that CTRP9 could play multiple positive and beneficial roles in vascular lesions in ischemic stroke (IS). Here, we aimed to study the relationship between serum CTRP9 and the etiology, severity, and prognosis of IS patients. METHODS: A total of 302 patients with IS and 173 non-stroke controls were selected from the same hospital, and all patients with IS were followed up 12 months after stroke onset. Stroke etiology was classified according to the Trial of ORG 10172 in Acute Stroke Treatment classification. Symptomatic severity was determined using the National Institutes of Health Stroke Scale score. The lesion volume of acute cerebral ischemia was measured using magnetic resonance imaging (MRI). The unfavorable functional outcome was a combination of death or major disability 12 months after stroke onset. Receiver operating characteristic (ROC) curves and integrated discrimination improvement (IDI) and net reclassification improvement (NRI) statistics were applied in the statistical analysis. RESULTS: We found that serum CTRP9 levels and the ratios of CTRP9/total cholesterol (TC), CTRP9/triglyceride (TG), CTRP9/low-density lipoprotein cholesterol (LDL-C), and CTRP9/high-density lipoprotein cholesterol (HDL-C) were associated with the presence of IS. Moreover, the serum CTRP9 concentration was positively associated with the severity of IS. Incorporation of CTRP9/LDL-C levels into a fully adjusted model for IS-cardioembolic (CE) improved discrimination and calibration, and significantly improved reclassification. In addition, CTRP9 was a predictor of unfavorable functional outcomes. CONCLUSIONS: All the findings indicated that serum CTRP9 could be a promising blood-derived biomarker for the early evaluation and prognosis assessment of IS. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800020330.
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BACKGROUND: Subjective cognitive impairment (SCI) is common after acute ischemic stroke and adversely affects the quality of life. SCI is associated with an increased risk of developing mild cognitive impairment and dementia. Identifying biomarkers which could predict long-term cognitive outcomes of post-stroke SCI is of importance for early intervention. This study aims to investigate the association between circulating neurofilament light (NfL) and long-term cognitive function in patients with post-stroke SCI. METHODS: This longitudinal study recruited 304 patients with post-stroke SCI, and serum NfL levels were determined at baseline. These patients were followed up for 12 months for the observation of cognitive change. Cognitive performances were assessed by a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) scale. RESULTS: The patients were divided into a progression group (as determined by decreased TICS-40 scores) and a stable group (as determined by increased or unchanged TICS-40 scores). The progression group had significantly higher serum NfL levels than the stable group at baseline. Serum NfL levels were predictive for longitudinal cognitive decline during follow-up. CONCLUSION: These findings imply that circulating NfL could predict the long-term cognitive change of patients with post-stroke SCI.
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We propose a scheme for quantum geometric computation on a fiber-cavity-fiber system, in which two atoms are located in two single-mode cavities, respectively, connected with each other by optical fiber. This scheme not only has the feature of virtual excitation of photons in the cavity quantum electrodynamics (CQED) that can reduce the effect of decay effectively but also has the advantage of geometric phase to withstand noises due to its built-in noise-resilience feature and robust merit. Specifically, our proposal combined with optimized-control-technology (OCT) can reduce gate operation error by adjusting the time-dependent amplitude and phase of the resonant field which further enhances the robustness of the quantum operation. The robustness against decoherence is demonstrated numerically and the scheme may be applied in the remote quantum information processing tasks and quantum computation.
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BACKGROUND: Mental health problems after acute ischemic stroke (AIS) have caused wide public concerns, and the study on early identification of these disorders is still an open issue. This study aims to investigate the predictive effect of circulating neurofilament light (NfL) on long-term mental health status of AIS patients. METHODS: This study collected demographic information and mental health measurements from 304 AIS patients from May 1, 2016 to Dec 31, 2019. Baseline serum neurofilament light (NfL) was determined within 2 h since patient admission. Six months after AIS onset, the degree of symptoms of depression, anxiety, and insomnia was assessed by the Chinese versions of the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder scale (GAD-7), the 7-item Insomnia Severity Index (ISI), respectively. Subjects were divided into the high NfL group and the low NfL group. Multivariate logistic regression analysis was performed to identify factors associated with these mental health problems. RESULTS: The high NfL group had significantly higher PHQ-9, GAD-7, and ISI scores than the low NfL group. The prediction of serum NfL for major depression generated a sensitivity of 70.27%, a specificity of 67.79% and an AUC of 0.694. The prediction of serum NfL for anxiety generated a sensitivity of 69.23%, a specificity of 64.02%, and an AUC of 0.683. The prediction of serum NfL for insomnia generated a sensitivity of 75.00%, a specificity of 66.43% and an AUC of 0.723. Higher serum NfL was a risk factor of post-AIS depression [ORs (95% CI): 4.427 (1.918, 10.217)], anxiety [ORs (95% CI): 3.063 (1.939, 6.692)], and insomnia [ORs (95% CI): 4.200 (1.526, 11.562)]. CONCLUSIONS: These findings imply that circulating NfL might be a potential biomarker of long-term mental health problems after AIS.
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Atorvastatin is a member of the statin class of drugs, which competitively inhibit the activity of 5hydroxy3methylglutarylcoenzyme A reductase. The aim of the present study was to assess whether atorvastatin may protect BV2 microglia and hippocampal neurons against oxygenglucose deprivation (OGD)induced neuronal inflammatory injury and to determine the underlying mechanisms by which its effects are produced. Cell viability and apoptotic ability were assessed using an MTT assay and annexin Vfluorescein isothiocyanate/propidium iodide double staining followed by flow cytometry, respectively. The expression of inflammation and apoptosisassociated mRNAs and proteins were assessed using reverse transcriptionquantitative polymerase chain reaction and western blotting, and the expression of inflammatory factors was determined using ELISA. The results of the current study revealed that atorvastatin treatment suppressed the viability of OGD BV2 microglia and hippocampal neurons. Furthermore, atorvastatin treatment reduced the expression of proinflammatory factors in OGD BV2 microglia. Additionally, it was demonstrated to downregulate the tolllike receptor 4 (TLR4)/tumor necrosis factor receptorassociated factor 6 (TRAF6)/nuclear factorκB (NFκB) pathway in OGD BV2 microglia. Atorvastatin also inhibited the apoptosis of OGD hippocampal neurons by regulating the expression of apoptosisassociated proteins. It was concluded that atorvastatin treatment may protect BV2 microglia and hippocampal neurons from OGDinduced neuronal inflammatory injury by suppressing the TLR4/TRAF6/NFκB pathway. This may provide a potential strategy for the treatment of neuronal injury.
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Atorvastatina/farmacología , Glucosa/deficiencia , Hipocampo/metabolismo , Microglía/metabolismo , FN-kappa B/metabolismo , Neuronas/metabolismo , Transducción de Señal/efectos de los fármacos , Factor 6 Asociado a Receptor de TNF/metabolismo , Receptor Toll-Like 4/metabolismo , Animales , Hipoxia de la Célula/efectos de los fármacos , Femenino , Hipocampo/patología , Masculino , Ratones , Microglía/patología , Neuronas/patologíaRESUMEN
BACKGROUND: Blood pressure (BP) variability has been shown to be an independent risk factor of stroke and target organ damage because of hypertension, but so far, there have been very few studies investigating the impact of BP variability on cerebrovascular atherosclerosis. METHODS: A total of 409 participants were enrolled and classified according to patterns of cerebrovascular atherosclerosis (i.e. large or small artery atherosclerosis; extracranial; or intracranial artery atherosclerosis). Coefficient of variation (CV) was used as a marker of BP variability. Multivariate binary logistical regression was used to analyze the associations between BP variability and the risk of different patterns of cerebrovascular atherosclerosis. RESULTS: The risk of large artery atherosclerosis and extracranial arterial stenosis, respectively, had a dose-responsive positive relationship with the tertiles of awake systolic blood pressure (SBP) CVs [large artery atherosclerosis, the second tertile, adjusted odds ratio (OR)=2.839, 95% confidence interval (CI) 1.593-5.059, P<0.001; the third tertile, adjusted OR=4.010, 95% CI 1.859-8.651, P<0.001; extracranial arterial stenosis, the second tertile, adjusted OR=2.274, 95% CI 1.189-4.348, P=0.013; the third tertile, adjusted OR=2.568, 95% CI 1.230-5.360, P=0.012, when referenced to the first tertile], but not with those of mean awake SBP. The third tertile of awake SBP CVs indicated a significantly higher risk of intracranial arterial stenosis (adjusted OR=2.253, 95% CI 1.118-4.538, P=0.023) and advanced intracranial arterial stenosis (adjusted OR=5.073, 95% CI 2.064-12.466, P<0.001) when referenced to the first tertile. CONCLUSION: In Chinese patients with acute atherosclerotic stroke, higher awake BP variability (measured in the subacute stage) might be associated with a higher risk of large artery atherosclerosis.
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Presión Sanguínea , Isquemia Encefálica , Arteriosclerosis Intracraneal , Accidente Cerebrovascular , Vigilia , Anciano , Isquemia Encefálica/etiología , Isquemia Encefálica/fisiopatología , Femenino , Humanos , Arteriosclerosis Intracraneal/complicaciones , Arteriosclerosis Intracraneal/fisiopatología , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/fisiopatologíaRESUMEN
BACKGROUND: Many studies have revealed apolipoproteins are risk factors for ischemic stroke, but the influence of apolipoproteins on onset age of first-ever atherosclerotic stroke has not been well investigated. METHODS: We recruited 357 qualified participants from consecutive patients with acute ischemic stroke who came to the stroke registry center in Sichuan Provincial People's Hospital, Chengdu, China. Patients were stratified into tertiles according to the distributions of apoB levels for large artery atherosclerosis (LAA) and small artery atherosclerosis (SAA) groups. The onset age of stroke was analyzed tripartitely in terms of early-onset group, the middling-onset group and the late-onset group. Multinomial logistical regression was used to analyze the associations between the two. RESULTS: The risk of early-onset stroke increased monotonically with higher apoB levels (the second tertile, adjusted OR = 2.61, 95% CI 1.18-5.79 (p = 0.018); the third tertile, adjusted OR = 19.52, 95% CI 5.93-64.31 (p < 0.001)), and patients with the highest tertile of apoB levels had a 9.20 times (95% CI, 2.97-28.53, p < 0.001) increased risk of middling-onset stroke in reference to late onset of stroke. CONCLUSIONS: The present study suggests the higher the apolipoprotein B levels are, the earlier an atherosclerotic stroke might occur in a Chinese population.
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Apolipoproteínas B/sangre , Aterosclerosis/complicaciones , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/etiología , Edad de Inicio , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To observe the expression of aquaporin-4 (AQP-4) mRNA and study the relationship between AQP-4, brain edema, pathological changes and ultrastructure of peri-hematoma tissue in intracerebral hemorrhage (ICH) patients. METHODS: Intracranial operation was performed via nonfunctional area with a funnel-like approach on 30 ICH patients. The brain tissue which must be removed 1 cm away the hematoma was removed within 12 hours for observation as normal brain tissue and taken as the control group (7 patients), and which of the brain tissue within 1 cm around hematoma was taken as the study specimens. The experimental group was subdivided into five groups according to the time interval after ICH: <6 hours (6 cases), 6-12 hours (7 cases), 12-24 hours (5 cases), 24-72 hours (6 cases), and >72 hours ( 6 cases ). Expression of the AQP-4 mRNA, brain edema, pathological and ultrastructural changes were observed with reverse transcription-polymerase chain reaction (RT-PCR), light microscope and electron microscope. RESULTS: The expression of the AQP-4 mRNA was not remarkable, the morphology and construction were basically normal in control group. The expression of AQP-4 mRNA was mild (1.17+/-0.41)and there was edema of neuroglia in the <6 hours group. After 6 hours, besides neuroglial edema, the expression of the AQP-4 mRNA was gradually obvious, capillary endothelial cells began to swell too, and tight junctions gradually began to loosen. In the 12-72 hours group the expression of the AQP-4 mRNA reached its peak (3.50+/-0.55, 3.60+/-0.55, both P<0.01), and brain edema was most prominent, and electron microscopy showed that neurons, neuroglia, and capillary endothelial cells were markedly deformed. After 72 hours, the expression of AQP-4 mRNA gradually recovered, and brain cells showed less damage. On the 5th day the damage began to repair, and on the 8th day, the damage was basically repaired. The correlation analysis showed that there was a remarkable positive correlation between the expression of the AQP-4 mRNA and the degree of brain edema and the size of hematoma (r(1)=0.67, P<0.01; r(2)=0.44, P<0.05) . CONCLUSION: Secondary edema and brain damage may correlate with the expression of the AQP-4 mRNA in the peri-hematoma brain edema area. Removal of hematoma will help decrease the AQP-4 mRNA expression and brain edema damage in the early stage.
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Acuaporina 4/metabolismo , Edema Encefálico/etiología , Encéfalo/metabolismo , Hemorragia Cerebral/metabolismo , Adulto , Anciano , Acuaporina 4/genética , Encéfalo/patología , Encéfalo/ultraestructura , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/patología , Femenino , Hematoma/metabolismo , Hematoma/patología , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/genéticaRESUMEN
OBJECTIVE: To investigate the relationship between inflammatory response and cell apoptosis in the perihematoma region in patients with intracerebral hemorrhage (ICH). METHODS: Surgical specimens were obtained from the area 1 cm adjacent to the hematoma. Thirty patients with ICH were divided into five groups: 6, 7, 5, 6, 6 patients in surgery<6 hours, 6-12 hours, 12-24 hours, 24-72 hours and >72 hours groups after the onset, respectively. The control group specimens were obtained from the brain tissues distant to the hematoma in the process of craniotomy in the patients of two former groups. Sections were stained with hematoxylin and eosin (HE) for the examination of pathological changes. Immunohistochemistry, terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) and reverse transcription-polymerase chain reaction (RT-PCR) were applied to determine apoptosis cells, Bax and Bcl-x protein and mRNA. RESULTS: The tissues from perihematoma region were almost normal in control group and <6 hours group. They were slightly damaged in 6-12 hours group, became worse in 12-24 hours group and most severe in 24-48 hours group, and they became better latter and were similar to the control group on 8th day. Infiltration of neutrophils, macrophages and lymphocyte appeared gradually at 6-12 hours, and became much more prominent at 12-24 hours (all P<0.01). The reactive gliosis began to appear at 24-72 hours, and enhanced after 72 hours (all P<0.01). The expression of the apoptosis and Bax protein increased gradually after 6 hours, reaching the peak at 12-24 hours (P<0.05 or P<0.01), and decreased gradually later. The changes in the levels of Bax mRNA were similar to that of the result of immunohistochemistry. Although the expression of Bcl-x protein and mRNA seemed to be increased at 12-72 hours, there was no significant difference between groups (P>0.05). The correlation analysis showed that the infiltration of neutrophils, macrophages and lymphocyte was positively correlated to the TUNEL positive cells and expression of Bax protein and mRNA (P<0.05 or P<0.01), and showed no correlation to Bcl-x protein and mRNA (all >0.05). CONCLUSION: There is a close relationship between inflammatory response and apoptosis and tissue damage in the perihematoma area in ICH.