Emotion regulation is a vital life skill, and cognitive reappraisal (CR) is the most effective emotion regulation strategy, which plays a key role in healthy aging. In memory clinic patients, problems with emotion regulation difficulties and cognitive impairment are very common, often accompanied by signs of cerebral small vessel disease (CSVD) on their magnetic resonance imaging (MRI). Is there a correlation among cognitive reappraisal failure, cognitive impairment, and CSVD in these older adults? This study aims to investigate the question. A standardized emotion regulation task was used to measure CR ability. A total of 170 older adults were included in statistical analysis, of which 78 were considered as cognitive reappraisal failure (CR-Failure). All participants completed the emotion regulation task, neuropsychiatric assessments, and MRI scans, with traditional CSVD markers being evaluated. Our analysis indicated that CR ability is negatively correlated with scores on the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale. Additionally, logical memory and executive function are significant factors in CR utilization. A higher burden of CSVD or presence of cognitive impairment is an independent risk factor for cognitive reappraisal failure in memory clinic older adults. Furthermore, cognitive impairment significantly mediates the relationship between greater CSVD burden and CR failure.

OBJECTIVESTo evaluate the reliability and validity of the computer-aided cognitive test (CACT).METHODS219 Subjects of Tongji Hospital's Brain Health cohort (115 cases of Mild Cognitive Impairment (MCI) patients and 104 cases of normal controls) were enrolled, of which 24 cases received a retest after 2 weeks. Finally, the reliability and validity of the scale were tested and analyzed.RESULTS(1) Reliability: (a) the internal consistency reliability of the total score of the scale was 0.645; (b) the retest reliability correlation coefficient of the total score of the scale was 0.900; (c) the Guttman Split-Half coefficient was 0.631; (2) Validity: (a) construct validity analysis showed that the correlation coefficient between each section score was between 0.036 and 0.408, and the correlation coefficient between each section score and the total score was between 0.468 and 0.781; (b) criterion validity analysis showed that the correlation coefficient between the total score of CACT and that of the Mini Mental State Examination (MMSE) was 0.733, and the coefficient between the total score of CACT and that of the basic version of the Montreal Cognitive Assessment (MoCA) was 0.763; (c) the area under the ROC curve of the CACT to distinguish between MCI patients and controls was 0.920, with an optimal diagnostic threshold of 20, a sensitivity of 88.5%, and a specificity of 80.9%.CONCLUSIONThe CACT is little influenced by education level. It has good reliability and validity, which can be used for early clinical screening of cognitive dysfunction.

T lymphocytes are involved in the pathogenesis of Parkinson’s disease (PD), while the heterogeneity of T-cell subpopulations remains elusive. In this study, we analyzed up to 22 subpopulations of T lymphocytes in 115 PD patients and 60 matched healthy controls (HC) using flow cytometry. We found that PD patients exhibited decreased naïve CD8+ T cells (CD3+ CD8+ CD45RA+ CD45RO−) and increased late-differentiated CD4+ T cells (CD3+ CD4+ CD28− CD27−), compared to HC, which were not affected by anti-parkinsonism medication administration. The proportion of naïve CD8+ T cells in PD patients was positively correlated with their severity of autonomic dysfunction and psychiatric complications, but negatively associated with the severity of rapid eye movement and sleep behavior disorder. The proportion of late-differentiated CD4+ T cells was negatively correlated with the onset age of the disease. We further developed individualized PD risk prediction models with high reliability and accuracy on the base of the T lymphocyte subpopulations. These data suggest that peripheral cellular immunity is disturbed in PD patients, and changes in CD8+ T cells and late-differentiated CD4+ T cells are representative and significant. Therefore, we recommend naïve CD8 + and late-differentiated CD4+ T cells as candidates for multicentric clinical study and pathomechanism study of PD.

Structurally, botulinum toxin type A (BTX-A) is composed of neurotoxin and nontoxic complexing proteins (CPs), and the neurotoxin has the function of blocking acetylcholine release from the neuromuscular junction and therefore paralyzing muscles. Nowadays, a novel botulinum toxin A free of CPs (chinbotulinumtoxin A, A/Chin) is produced, and the present study comprehensively evaluated the dynamic paralytic effect of A/Chin on the gastrocnemius muscle of rats. Different doses (0.01, 0.1, 0.5, 1, 2, and 4 U) of A/Chin and other BTX-As with and without CPs were administered to the gastrocnemius muscles of rats and muscle strength was measured and compared at different postinjection timepoints (from day 0 to 84). With the dose increased, time-to-peak paralytic effect of other BTX-As varied from day 3 to day 14, while A/Chin groups showed rapid and steady time to peak on day 3. At the lowest dose of 0.01 U, A/Chin showed significantly better peak paralytic effect than the others on day 3. When the dose increased to 0.5 U and more, A/Chin group also showed significant paralytic effect when the paralytic effect of other BTX-As was worn off. Moreover, the paralytic effect of A/Chin was confirmed as muscle atrophy while hematoxylin-eosin staining was performed. In conclusion, compared with other BTX-As, A/Chin showed rapid and steady time-to-peak paralytic effect and long-term paralytic efficacy at the same dose level. And it might lay a solid foundation for further wide application of A/Chin in both clinical and cosmetic areas.

Background The clinical nomogram is a popular decision-making tool that can be used to predict patient outcomes, bringing benefits to clinicians and patients in clinical decision-making. This study established a simple and effective clinical prediction model to predict the 3-month prognosis of acute ischemic stroke (AIS), and based on the predicted results, improved clinical decision-making and improved patient outcomes. Methods From 18 December 2021 to 8 January 2022, a total of 146 hospitalized patients with AIS confirmed by brain MR were collected, of which 132 eligible participants constituted a prospective study cohort. The least absolute shrinkage and selection operator (LASSO) regression was applied to a nomogram model development dataset to select features associated with poor prognosis in AIS for inclusion in the logistic regression of our risk scoring system. On this basis, the nomogram was drawn, evaluated for discriminative power, calibration, and clinical benefit, and validated internally by bootstrap. Finally, the optimal cutoff point for each independent risk factor and nomogram was calculated using the Youden index. Results A total of 132 patients were included in this study, including 85 men and 47 women. Good outcome was found in 94 (71.212%) patients and bad outcome in 38 (28.788%) patients during the follow-up period. A total of eight (6.061%) deaths were reported over this period, of whom five (3.788%) died during hospitalization. Five factors affecting the 3-month prognosis of AIS were screened by LASSO regression, namely, age, hospital stay, previous stroke, atrial fibrillation, and NIHSS. Further multivariate logistic regression revealed three independent risk factors affecting patient outcomes, namely, age, previous stroke, and NIHSS. The area under the curve of the nomogram was 0.880, and the 95% confidence interval was 0.818–0.943, suggesting that the nomogram model has good discriminative power. The p -value for the calibration curve is 0.925, indicating that the nomogram model is well-calibrated. According to the decision curve analysis results, when the threshold probability is >0.01, the net benefit obtained by the nomogram is the largest. The concordance index for 1,000 bootstrapping calculations is 0.869. The age cutoff for predicting poor patient outcomes using the Youden index was 76.5 years (specificity 0.777 and sensitivity 0.684), the cutoff for the NIHSS was 7.5 (specificity 0.936, sensitivity 0.421), and the cutoff for total nomogram score was 68.8 (sensitivity 81.6% and specificity 79.8%). Conclusion The nomogram model established in this study had good discrimination, calibration, and clinical benefits. A nomogram composed of age, previous stroke, and NIHSS might predict the prognosis of stroke after AIS. It might intuitively and individually predict the risk of poor prognosis in 3 months of AIS and provide a reference basis for screening the treatment plan of patients.

Objective To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. Methods A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. Results A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). Conclusion The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969)

Introduction We evaluated the efficacy of brain–computer interface (BCI) training to explore the hypothesized beneficial effects of physiotherapy alone in chronic stroke patients with moderate or severe paresis. We also focused on the neuroplastic changes in the primary motor cortex (M 1 ) after BCI training. Methods In this study, 18 hospitalized chronic stroke patients with moderate or severe motor deficits participated. Patients were operated on for 20 sessions and followed up after 1 month. Functional assessments were performed at five points, namely, pre1-, pre2-, mid-, post-training, and 1-month follow-up. Wolf Motor Function Test (WMFT) was used as the primary outcome measure, while Fugl-Meyer Assessment (FMA), its wrist and hand (FMA-WH) sub-score and its shoulder and elbow (FMA-SE) sub-score served as secondary outcome measures. Neuroplastic changes were measured by functional near-infrared spectroscopy (fNIRS) at baseline and after 20 sessions of BCI training. Pearson correlation analysis was used to evaluate functional connectivity (FC) across time points. Results Compared to the baseline, better functional outcome was observed after BCI training and 1-month follow-up, including a significantly higher probability of achieving a clinically relevant increase in the WMFT full score (ΔWMFT score = 12.39 points, F = 30.28, and P < 0.001), WMFT completion time (ΔWMFT time = 248.39 s, F = 16.83, and P < 0.001), and FMA full score (ΔFMA-UE = 12.72 points, F = 106.07, and P < 0.001), FMA-WH sub-score (ΔFMA-WH = 5.6 points, F = 35.53, and P < 0.001), and FMA-SE sub-score (ΔFMA-SE = 8.06 points, F = 22.38, and P < 0.001). Compared to the baseline, after BCI training the FC between the ipsilateral M 1 and the contralateral M 1 was increased ( P < 0.05), which was the same as the FC between the ipsilateral M 1 and the ipsilateral frontal lobe, and the FC between the contralateral M 1 and the contralateral frontal lobe was also increased ( P < 0.05). Conclusion The findings demonstrate that BCI-based rehabilitation could be an effective intervention for the motor performance of patients after stroke with moderate or severe upper limb paresis and represents a potential strategy in stroke neurorehabilitation. Our results suggest that FC between ipsilesional M 1 and frontal cortex might be enhanced after BCI training. Clinical Trial Registration www.chictr.org.cn , identifier: ChiCTR2100046301.

Background: Atherosclerosis is the leading cause of cardiovascular disease worldwide, including in China. Primary prevention, through lipid-lowering, could avert development of atherosclerosis. Carotid intima-media thickness (CIMT) is a well-validated measure of atherosclerosis used in intervention studies as the primary outcome and alternative end point for cardiovascular disease events. Methods: This randomized, double-blind, placebo-controlled, multicenter, parallel-group study assessed the effects of rosuvastatin 20 mg/d compared with placebo on progression of CIMT over 104 weeks in Chinese people with subclinical atherosclerosis. The primary end point was the annualized rate of change in mean of the maximum CIMT measurements taken 7× over the study period from each of 12 carotid artery sites (near and far walls of the right and left common carotid artery, carotid bulb, and internal carotid artery). Secondary end points included CIMT changes at different artery sites and lipid-parameter changes. Safety was also assessed. Results: Participants were randomized (1:1) to receive rosuvastatin (n=272) or placebo (n=271). Baseline characteristics were well balanced between groups. The change in mean of the maximum CIMT of the 12 carotid sites was 0.0038 mm/y (95% CI, −0.0023–0.0100) for the rosuvastatin group versus 0.0142 mm/y (95% CI, 0.0080–0.0204) for the placebo group, with a difference of −0.0103 mm/y (95% CI, −0.0191 to −0.0016; P =0.020). For the CIMT secondary end points, the results were generally consistent with the primary end point. There were clinically relevant improvements in lipid parameters with rosuvastatin. We observed an adverse-event profile consistent with the known safety profile of rosuvastatin. Conclusions: Rosuvastatin 20 mg/d significantly reduced the progression of CIMT over 2 years in Chinese adults with subclinical atherosclerosis and was well tolerated. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02546323.

Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) is a rare mitochondrial disorder associated with mutations in the POLG gene, which encodes the DNA polymerase gamma catalytic subunit. A few POLG-related SANDO cases have been reported, but the genotype–phenotype correlation remains unclear. Here, we report a patient with SANDO carrying two novel missense variants (c.2543G>C, p.G848A and c.452 T>C, p.L151P) in POLG. We also reviewed previously reported cases to systematically evaluate the clinical and genetic features of POLG-related SANDO. A total of 35 distinct variants in the coding region of POLG were identified in 63 patients with SANDO. The most frequent variant was the p.A467T variant, followed by the p.W748S variant. The clinical spectrum of SANDO is heterogeneous. No clear correlation has been observed between the mutation types and clinical phenotypes. Our findings expand the mutational spectrum of POLG and contribute to clinical management and genetic counseling for POLG-related SANDO.

Mutations in VPS16 have been identified to be responsible for generalized dystonia. We screened VPS16 variants in 53 unrelated subjects with isolated dystonia via whole-exome sequencing. A novel pathogenic frameshift mutation p.R643fs* was found in a patient with early-onset multifocal dystonia with prominent oromandibular and bulbar involvement. Our findings expanded the spectrum of VPS16-related dystonia and suggested that mutations in VPS16 should be considered in patients with progressive early-onset dystonia.

雷诺现象(Raynaud's phenomenon ,RP)是首次由巴黎医生提出的风湿科一种常见的自身免疫性疾病,其典型表现为手指或(和)足趾等部位在寒冷或情绪激动等因素诱发下出现的三相颜色变化:变白(缺血),然后变成紫(蓝)色(发绀),然后变成红色(再灌注),常常反复发作,病程呈自限性,患病率为3％ ～5％[1 ] ,女性多见,女:男约为9:1 ,通常发生在15～40岁,年轻成人比中老年人更易患病[2].雷诺现象可以持续几分钟到几小时,每天发作数次,通常伴有疼痛、麻木和肿胀等症状,严重者可出现溃疡、坏疽或致残,患者的手部功能及日常活动受到严重影响.目前尚缺乏有效的治疗方法,近年来多项研究提示局部注射肉毒毒素后患者手指温度升高、血流改善、甚至溃疡愈合.本研究就局部注射肉毒毒素治疗雷诺现象进展做一综述.

大脑功能减退的临床表现复杂多样,而传统认知量表评估内容单一,忽略了很多行为细节,在痴呆诊断中具有局限性.随着人工智能与医学交叉的研究不断增加,不断有新的评估方法出现,语音、书写过程、步态、眼动等特征分析及虚拟现实(virtual reality,VR)技术、可穿戴设备在认知评估中的探索成为热点.本文重点对以上认知评估新技术在认知评估中的探索和运用进行综述,并讨论认知评估新技术相对于传统量表评估的优势及前景,为今后此类评估方法在临床应用中的探索提供指导.

Visual working memory (VWM), the core process inherent to many advanced cognitive processes, deteriorates with age. Elderly individuals usually experience defects in the processing of VWM. The dorsolateral prefrontal cortex is a key structure for the top-down control of working memory processes. Many studies have shown that repeated transcranial magnetic stimulation (rTMS) improves VWM by modulating the excitability of neurons in the target cortical region, though the underlying neural mechanism has not been clarified. Therefore, this study sought to assess the characteristics of brain memory function post-rTMS targeting the left dorsolateral prefrontal cortex. The study stimulated the left dorsolateral prefrontal cortex in elderly individuals by performing a high-frequency rTMS protocol and evaluated behavioral performance using cognitive tasks and a VWM task. Based on the simultaneously recorded electroencephalogram signals, event-related potential and event-related spectral perturbation analysis techniques were used to investigate the variation characteristics of event-related potential components' (N2PC and CDA) amplitudes and neural oscillations in elderly individuals to elucidate the effect of high-frequency rTMS. The results found that rTMS enhanced VWM performance and significantly improved attention and executive function in elderly individuals with subjective cognitive decline. We therefore speculate that rTMS enhances VWM by increasing the N2PC and CDA amplitude, alongside increasing β oscillation activity. This would improve the attention and allocation of resources in elderly individuals such as to improve an individual's VWM.

Chronic hypertension alters cerebrovascular function, which can lead to neurovascular pathologies and increased susceptibility to neurological disorders. The purpose of this study was to utilize in vivo MRI methods with corroborating immunohistology to evaluate neurovascular dysfunction due to progressive chronic hypertension. The spontaneously hypertensive rat (SHR) model at different stages of hypertension was studied to evaluate: i) basal cerebral blood flow (CBF), ii) cerebrovascular reactivity (CVR) assessed by CBF and blood-oxygenation level dependent (BOLD) signal changes to hypercapnia, iii) neurovascular coupling from CBF and BOLD changes to forepaw stimulation, and iv) damage of neurovascular unit (NVU) components (microvascular, astrocyte and neuron densities). Comparisons were made with age-matched normotensive Wistar Kyoto (WKY) rats. In 10-week SHR (mild hypertension), basal CBF was higher (p < 0.05), CVR trended higher, and neurovascular coupling response was higher (p < 0.05), compared to normotensive rats. In 40-week SHR (severe hypertension), basal CBF, CVR, and neurovascular coupling response were reversed to similar or below normotensive rats, and were significantly different from 10-week SHR (p < 0.05). Immunohistological analysis found significantly reduced microvascular density, increased astrocytes, and reduced neuronal density in SHR at 40 weeks (p < 0.05) but not at 10 weeks (p > 0.05) in comparison to age-matched controls. In conclusion, we observed a bi-phasic basal CBF, CVR and neurovascular coupling response from early to late hypertension using in vivo MRI, with significant changes prior to changes in the NVU components from histology. MRI provides clinically relevant data that might be useful to characterize neurovascular pathogenesis on the brain in hypertension.

Introduction: This study aimed to build the supervised learning model to predict the state of cognitive impairment, Alzheimer's Disease (AD) and cognitive domains including memory, language, action, and visuospatial based on Digital Clock Drawing Test (dCDT) precisely. Methods: 207 normal controls, 242 Mild Cognitive Impairment (MCI) patients, 87 dementia patients, including 53 AD patients, were selected from Shanghai Tongji Hospital. The electromagnetic tablets were used to collect the trajectory points of dCDT. By combining dynamic process and static results, different types of features were extracted, and the prediction models were built based on the feature selection approaches and machine learning methods. Results and Discussion: The optimal AUC of cognitive impairment's screening, AD's screening and differentiation are 0.782, 0.919 and 0.818, respectively. In addition, the cognitive state of the domains with the best prediction result based on the features of dCDT is action with the optimal AUC 0.794, while the other three cognitive domains got the prediction results between 0.744-0.755. Conclusion: By extracting dCDT features, cognitive impairment and AD patients can be identified early. Through dCDT feature extraction, a prediction model of single cognitive domain damage can be established.

Parkinson's disease (PD) is slowly progressive. Due to the lack of specific and sensitive biomarkers, the majority of PD patients are in the advanced stages when diagnosed. This study aimed to investigate biomarkers for early PD diagnosis. We first selected differential mRNAs by analysis of a Gene Expression Omnibus (GEO) data set. Next, we performed RNA sequencing to select differential mRNAs. After an integrated analysis of GEO and RNAseq data, we identified the PD early diagnosis biomarkers associated with oxidative stress. By function analysis, cellular response to hormone stimulus and response to the oxygen-containing compound was involved in the top Gene Set Enrichment Analysis (GSEA)s of the two cohorts. Moreover, SOCS7 was included in these GSEAs coincidentally. Further, by analyzing SOCS7 and its physical interactors, we found they mainly participate in immunity and redox homeostasis related processes, which might play a significant role in PD. Thus, our results suggest SOCS7 might be the potential diagnostic marker for PD.

目的 探讨急性缺血性卒中(acute ischemic stroke,AIS)患者脑小血管病(cerebral small vessel dis-ease,CSVD)总体负荷在不同严重程度AIS静脉溶栓中的应用价值并寻找最优人群.方法 回顾性纳入2016年3月-2020年1月188名就诊于常熟市第二人民医院神经内科接受阿替普酶静脉溶栓治疗的急性缺血性卒中患者.根据头部MRI评估CSVD总体负荷(CSVD总负荷评分),使用多因素Logistic回归分析AIS静脉溶栓患者90 d预后不良(mRS评分≥3分)的独立影响因素.应用受试者工作特征(receiver operating characteristic,ROC)曲线比较评分量表对不同人群的预测价值.结果 多因素回归分析发现,糖尿病(OR=2.828,95％CI 1.009～7.924,P=0.048)、吸烟(OR=9.396,95％CI 2.690～32.823,P<0.001)、心房颤动(OR=8.160,95％CI 2.167～30.729,P=0.002)、基线NIHSS评分(每增加1分:OR=1.379,95％CI 1.241～1.532,P<0.001)、CSVD总负荷评分≥3分(OR=5.448,95％CI 1.720～17.260,P=0.004)是AIS患者静脉溶栓预后不良的独立危险因素.ROC曲线分析提示CSVD总负荷评分对8≤NIHSS≤15人群预测效果最好(C值=0.828).结论 CSVD总负荷评分≥3分是静脉溶栓患者90 d不良预后的独立危险因素,对中重度AIS静脉溶栓患者90 d预后的预测价值最高.

BackgroundLate-onset depression (LOD) is often difficult to recognize when there is an absence of a family history of depression and less severe psychopathology. Increasing evidence has shown that the development and course of LOD symptomatology are associated with cerebrovascular comorbidities and cerebral microvascular lesions. This study was designed to evaluate the associations of LOD with macrovascular and microvascular changes in the brain by using a multi-imaging method, including computed tomography angiography (CTA), CT perfusion (CTP), and magnetic resonance imaging (MRI), to explore the course and pathomechanism of LOD.MethodsA total of 116 participants were divided into two groups. Participants older than 60 years who met the diagnostic criteria of depression [International Classification of Diseases (ICD), 10th Edition] were enrolled in the LOD group, and the remainder were age- and sex-matched into the control group. The cognitive/mood status of all participants was evaluated by an experienced neuropsychologist. Global and regional mean cerebral blood flow (CBF) were measured by CT cerebrovascular perfusion imaging; the stenosis of the bilateral intracranial large arteries (internal carotid artery, anterior cerebral artery, middle cerebral artery, posterior cerebral artery, and vertebral artery) was recorded by CTA; regional white matter hyperintensity (WMH) loads were evaluated by fluid-attenuated inversion recovery (FLAIR) MRI; and the Hamilton Depression Scale (HAMD) was used to evaluate depression status.ResultsOur key findings were the following: (I) participants in the LOD group were more prone to intracranial arterial stenosis (81.1% vs. 74.6%), had more severe stenotic arteries compared with controls (Z=2.024, P<0.05), and significantly more participants with LOD had severe stenosis of the middle cerebral artery (MCA) (9.4% vs. 0%, P<0.05); (II) there was a significant difference in hypoperfusion of the frontal and parietal lobes superposed on global cerebral hypoperfusion between the two groups (P<0.001); (III) and there was a significant difference in high WMH loads in deep white matter (DWM) between the two groups (P<0.05).ConclusionsA low global or regional perfusion state, moderate-to-severe stenosis of MCAs, and high WMH loads could be used as imaging biomarkers to indicate diffuse or localized cerebral macrovascular and microvascular pathology in LOD.

BACKGROUND:Cardiogenic cerebral embolism is one of the most common causes of ischemic stroke. In general, cardioembolic stroke is associated with more severe neurological deficits and higher early mortality, as well as a worse functional outcome. Oral anticoagulant (OAC) therapy could reduce the risk of stroke significantly. However, several limitations have led to it being underused, which raises the failure of anticoagulant therapy. This study aimed to investigate the patients with atrial fibrillation presented cardioembolic stroke who underwent OAC therapy, and to assess treatment efficacy, and outcomes, especially the international normalized ratio (INR) value in the acute phase.METHODS:Clinical data of 306 patients with cardioembolic stroke and etiology of atrial fibrillation were retrospectively analyzed, and demographics, cardiovascular risk factors, embolic cardiopathy, CHADS2 and CHA2DS2-VASc score, HAS-BLED score, INR value, TOAST subtypes, OCSP classification, modified Rankin Scale (mRS) scores and prognosis were evaluated.RESULTS:The median score on the CHADS2 and CHA2DS2-VASc scales was 3 and 4, respectively; The median score on the HAS-BLED scale was 2. Only 33 patients (10.8%) were in therapeutic INR range at the onset of stroke. In the acute phase, 233 patients (76.1%) continued to use OAC therapy, and 73 patients were suspended. Eighteen patients (24.7%) resumed treatment after an average of 32 days. Thirty-nine of 251 survivors with nonvalvular atrial fibrillation were modified to novel oral anticoagulants (NOACs). At 3 months follow-up, patients with INR ≥1.7 had significantly better prognosis than those with INR <1.7, both in the percentage of patients with functional independence (78.9% vs. 41.2%) and in mortality (7.0% vs. 25.0%) (P<0.001).CONCLUSIONS:Patients presented cardioembolic stroke despite being treated with OAC, especially those with a subtherapeutic INR value, raises the failure of anticoagulant therapy. Despite the ineffectiveness of the OAC, the prognosis is better when the INR ≥1.7 at the initiation of the stroke.

Methylene blue (MB) has a protective effect on cognitive decline caused by chronic hypoperfusion, but the specific mechanism is not clear. This article aims to determine whether MB protects vascular neurons through PI3K/Akt and plays a role in improving cognitive impairment. Molecular biological methods, the hippocampal neuronal density test, the hippocampal vascular network density test, and dynamic enhanced magnetic resonance imaging (MRI) were used to detect the blood–brain barrier permeability and Evans blue leakage rate in the hippocampus. We also observed and evaluated the changes in the above results after administration of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway protein inhibitor LY294002. There were significant differences for cerebral blood flow (CBF) between the chronic cerebral hypoperfusion (CCH) + MB group (100 ml/100 g/min) and the CCH group (60 ml/100 g/min, P < 0.05). After using LY294002, the CBF of the CCH + MB + LY294002 group dropped to 82 ml/100 g/min. The vascular density in the CCH + MB group was 23%, which is significantly higher than that in the CCH group (15.1%) (P < 0.05). The vascular density (17.5%) in the CCH + MB + LY294002 group was significantly higher than that in the CCH group but lower than that in the CCH + MB group. Western blotting results showed that one week after intraperitoneal injection of MB, the expression of t-Akt and p-Akt in the CCH + MB group was increased after CCH, and LY294002 partially blocked this up-regulation effect (CCH + MB + LY294002 group). MB is a potential therapy for the relief of mild cognitive impairment associated with CCH, vascular dementia, and Alzheimer’s disease.