Isolation and neuronal apoptosis inhibitory property of bacoside-A3 via downregulation of ß-amyloid induced inflammatory response.

Alzheimer's disease is one of the neurodegenerative disorders caused by neuronal degeneration and apoptosis in brain. Bacoside A and B isolated from the Bacopa monniera plant are responsible for cognitive effects. These compounds repair damaged neurons by promoting activity of kinases, synaptic activity restoration, and improvement of nerve transmission. The present study explored the effect of bacoside-A3 on ß-amyloid-induced reduction of U87MG cell viability, generation of oxidative radicals, and activation of nuclear factor-κB. The U87MG cells were stimulated with ß-amyloid (10 µM) after 24 h of bacoside-A3 pretreatment or without pretreatment to induce characteristics of Alzheimer disease in vitro. Sulforhodamine B (SRB) assay was used to count viable cells and ELISA kit for analysis of PGE2 secretion. The pretreatment with bacoside-A3 prevented ß-amyloid-mediated suppression of U87MG cell proliferation. Pretreatment of U87MG cells with bacoside-A3 prior to ß-amyloid stimulation suppressed generation of ROS in a concentration-based manner. The ß-amyloid-mediated formation of iNOS in U87MG cells was suppressed by bacoside-A3 in a dose-based manner. The ß-amyloid-mediated PGE2 secretion was suppressed by bacoside-A3 pretreatment in U87MG cells in the dose-based manner. The overexpression of COX-2 by ß-amyloid stimulation was suppressed in bacoside-A pretreated cells in the dose-based manner. The bacoside-A3 pretreatment prevented nuclear translocation of NF-κB in U87MG cells in the dose-based manner. In summary, bacoside-A3 prevented ß-amyloid-mediated suppression of U87MG cell viability, inhibited generation of oxidative radicals, PGE2, and synthesis of iNOS. Therefore, bacoside-A3 has therapeutic potential for Alzheimer disease and further in vivo studies need to be performed.

Epigenome-Wide Association Study Indicates Hypomethylation of MTRNR2L8 in Large-Artery Atherosclerosis Stroke.

Background and Purpose- Ischemic stroke, a complex and heterogeneous disease, is the second leading cause of death worldwide. Genetic factors and epigenetic modification contribute to the pathogenesis of this disease. However, the effects of epigenetic factors on this disease have not been systematically investigated. Our study was designed to identify methylation alterations in large-artery atherosclerotic stroke. Methods- We conducted an epigenome-wide association analysis of large-artery atherosclerotic stroke using an Infinium HumanMethylation450 array (cases:controls=12:12), and the differentially methylated loci were validated in 2 cohorts (cases:controls, 110:122 and 191:191, respectively) using a Sequenom EpiTYPER assay. Results- In the screening stage, 1012 differentially methylated CpG sites annotated in 672 genes were found to be significantly associated with large-artery atherosclerotic stroke (mean methylation difference >5%, P<0.01). Disease, Gene Ontology, and pathway analysis highlighted the enrichment of these differentially methylated genes in cardiovascular, metabolic, neurological and immune-related functional gene clusters ( P<0.05). We identified a differentially methylated region in the promoter of a humanin gene ( MTRNR2L8, mean methylation difference=-13.01%, P=8.86×10-14). We constructed a diagnostic prediction model that was based on the mean number of significantly changed CpG loci in MTRNR2L8 and showed high diagnostic specificity and sensitivity ( P<0.0001, area under the curve=0.774). Conclusions- Together, these findings demonstrate that DNA methylation plays an important role in large-artery atherosclerotic stroke and that methylation of MTRNR2L8 is a potential therapeutic target and diagnostic biomarker for stroke.

Recombinant Tissue-Type Plasminogen Activator Study of Wake-Up Ischemic Strokes Guided by Rapid MRI.

BACKGROUND: rt-PA intravenous thrombolytic therapy and its efficacy have been widely recognized and proved for strokes. However, for patients with wake-up ischemic stroke (WUIS), they lose the opportunity to receive rt-PA intravenous thrombolytic therapy because of the difficulty of determining the onset time window. AIM: This study is aimed at investigating the intravenous thrombolytic therapy of WUIS guided by rapid MRI. METHODS: Data were collected from patients with acute ischemic stroke within 4.5 h and from WUIS patients with uncertain onset time window, who received the treatment of rt-PA intravenous thrombolytic therapy in our hospital from November 2006 to April 2018. The improved Rankin scale was used to evaluate neurological function recovery. According to the Rankin scale score, patients were divided into two groups: those with good prognosis (modified Rankin scale [mRS] score 0-1) and those with poor prognosis (mRS score 2-6). RESULTS: A total of 253 patients received rt-PA intravenous thrombolysis after head MRI evaluation; this included 177 cases of acute ischemic stroke and 76 cases of WUIS (which contains 2 death cases, 0.8% mortality; 3 cases of symptomatic bleeding, 1.2% bleeding rate; and 5 cases of aggravation, 2.0% aggravation rate). There was no statistical difference between the baseline data from the acute ischemic stroke patients with 4.5 h onset time window and the baseline data from the WUIS patients with undetermined onset time window, when the treatment was guided by rapid MRI. There were also no significant statistical differences in National Institutes of Health Stroke Scale score, Rankin scale score, symptomatic bleeding, death and aggravation of the disease between the 2 groups at 24 h, 3 days, and 7 days after admission (p < 0.05). CONCLUSION: According to the characteristic of undetermined onset time window of WUIS, more WUIS patients would be benefited from the rt-PA intravenous thrombolytic treatment when it is conducted under the guidance of rapid MRI.

Quercetin improves endothelial insulin sensitivity in obese mice by inhibiting Drp1 phosphorylation at serine 616 and mitochondrial fragmentation.

Studies have shown that endothelial insulin resistance induced by oxidative stress contributes to vascular dysfunction in metabolic disorders. Quercetin, a natural antioxidant, has been recently shown to exert protective effects on endothelial function. However, the effects of quercetin on endothelial insulin resistance and its underlying mechanism are unclear. Here, we found that chronic oral treatment of obese mice with quercetin increased vascular endothelial insulin sensitivity, accompanied by alleviated mitochondrial fragmentation as revealed by confocal imaging. In addition, western blot analysis showed that quercetin treatment suppressed the levels of dynamin-related protein 1 (Drp1) and phosphorylation at serine 616 in endothelial cells of obese mice. Mechanistically, quercetin specifically suppressed Drp1 phosphorylation at serine 616, whereas it showed little effects on the Drp1 level and its phosphorylation at serine 637 in cultured endothelial cells under oxidative stress. Furthermore, our results also showed that quercetin suppressed Drp1 phosphorylation at serine 616 by inhibiting PKCδ as revealed by western blot analysis. Knockdown of PKCδ with siRNA alleviated the protective effects of quercetin on endothelial-mitochondrial dynamics and insulin sensitivity. These results suggest that chronic oral treatment with quercetin exerts endothelial protective effects through inhibition of PKCδ and the resultant mitochondrial fragmentation.

Evaluating the Efficacy of Atorvastatin on Patients with Carotid Plaque by an Innovative Ultrasonography.

BACKGROUND: The present study aimed to explore the efficacy of atorvastatin on patients with carotid plaque, applying superb microvascular imaging (SMI), and contrast-enhanced ultrasound (CEUS) for evaluating carotid intraplaque neovascularization. METHODS: A total of 82 patients (82 carotid plaques) who were randomized into treatment group and control group underwent conventional ultrasound, CEUS, and SMI examinations. Patients in treatment group received a dose of 20 mg atorvastatin per day for 6 months while those in control group received placebo instead. Lipid parameters were assessed and intraplaque neovascularization were evaluated by CEUS and SMI before and 6 months after atorvastatin treatment. RESULTS: No significant differences were found between the 2 groups at the study entry. Patients with atorvastatin treatment received marked improvement in total cholesterol, triglyceride, and LDL-cholesterol compared with those in control group (P < .001). In treatment group, SMI-detected intraplaque neovascularization reduced from 69.23% to 48.72% while CEUS-detected ones reduced from 76.92% to 69.23%. By contrast, the percentage of intraplaque neovascularization in control group did not change too much either by SMI (65.12%, 67.44%) or CEUS (74.41%, 74.41%). The consistency between CEUS and SMI was above .75 at all assessments (P < .001). CONCLUSIONS: Atorvastatin treatment works for patients with carotid plaque by reducing LDL-cholesterol and improving plaque regression. Second, the consistency between SMI and CEUS in visualizing intraplaque neovascularization is good. That indicates a high possibility to identify carotid plaque instability by a safer and cheaper ultrasonography without contrast agent.

Prognostic Value of Diffusion-Weighted Imaging (DWI) Apparent Diffusion Coefficient (ADC) in Patients with Hyperacute Cerebral Infarction Receiving rt-PA Intravenous Thrombolytic Therapy.

BACKGROUND The aim of this study was to investigate the potential value of apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) in the prognosis of patients with hyperacute cerebral infarction (HCI) receiving intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA). MATERIAL AND METHODS From June 2012 to June 2015, 58 cases of HCI (<6 h) undergoing rt-PA intravenous thrombolytic therapy (thrombolysis group) and 70 cases of HCI (<6 h) undergoing conventional antiplatelet and anticoagulant therapy (control group) in the same period were collected. DWI was conducted on all the subjects, and ADC maps were generated with Functool software to quantify ADC value. The clinical outcomes of HCI patients were observed for 3 months, and prognostic factors were analyzed. RESULTS Before thrombolysis treatment, the lesion area presented high signal intensity on DWI map and low signal intensity on ADC map, and gradually weakened signal intensity on DWI map and gradually enhanced signal intensity on ADC map were observed after thrombolysis. The ADC values of the thrombolysis group were significantly higher than those of the control group after treatment (24 h, 7 d, 30 d, and 90 d) (all P<0.05), and the ADC and rADC values in the thrombolysis group gradually increased over time (all P<0.05). Multiple logistic regression analysis showed that baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline rADC value, and stroke history were the independent factors for the prognosis of HIC patients with thrombolysis (all P<0.05). CONCLUSIONS The values of ADC and rADC may provide guidance in the prognosis of HCI patients receiving rt-PA, and the baseline rADC value is the protective factor for the prognosis of HCI patients receiving rt-PA.

Ginsenoside Represses Symptomatic Intracerebral Hemorrhage after Recombinant Tissue Plasminogen Activator Therapy by Promoting Transforming Growth Factor-ß1.

BACKGROUND: Currently, the most effective treatment for brain ischemic stroke is recombinant tissue plasminogen activator (rt-PA); however, increased incidence of symptomatic intracerebral hemorrhage severely reduced its favorable treatment outcome. METHODS: We aimed to investigate the effect of ginsenoside (Gs) on symptomatic intracerebral hemorrhage after rt-PA treatment. Stroke patients were randomly divided into 2 treatment groups, one receiving rt-PA + placebo (Pc) and the other rt-PA + Gs. Twenty-four hours after the treatment, outcomes were assessed with transcranial Doppler (TCD) ultrasonography and National Institutes of Health Stroke Scale (NIHSS), and plasma levels of transforming growth factor-ß1 (TGF-ß1), matrix metalloproteinase (MMP)-2, and MMP-9 were also measured. After initial cotreatment, the patients were continuously administered with either Pc or Gs, and the treatment outcomes at 7 days were assessed with TCD, NIHSS, modified Rankin scale (MRS), and Glasgow outcome scale (GOS). RESULTS: Cotreatment of rt-PA with Gs significantly improved outcomes in patients compared to the Pc group, as indicated by improved TCD and NIHSS scores and reduced incidence of symptomatic intracerebral hemorrhage, which could be attributed to a Gs-induced increase in TGF-ß1 and a decrease in both MMP-2 and MMP-9 serum levels. Seven days of Gs treatment also significantly improved outcomes in patients compared to the Pc group, assessed by TCD, NIHSS, MRS, and GOS. CONCLUSION: Our study supports the clinical use of Gs as a potential supplement with rt-PA treatment, which reduces symptomatic intracerebral hemorrhage, therefore improving the treatment outcome of stroke patients.

Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: the Chinese Intracranial Atherosclerosis (CICAS) Study.

BACKGROUND AND PURPOSE: We aimed to establish the prevalence, characteristics, and outcomes of intracranial atherosclerosis (ICAS) in China by a large, prospective, multicenter study. METHODS: We evaluated 2864 consecutive patients who experienced an acute cerebral ischemia<7 days after symptom onset in 22 Chinese hospitals. All patients underwent magnetic resonance angiography, with measurement of diameter of the main intracranial arteries. ICAS was defined as ≥50% diameter reduction on magnetic resonance angiography. RESULTS: The prevalence of ICAS was 46.6% (1335 patients, including 261 patients with coexisting extracranial carotid stenosis). Patients with ICAS had more severe stroke at admission and stayed longer in hospitals compared with those without intracranial stenosis (median National Institutes of Health Stroke Scale score, 3 versus 5; median length of stay, 14 versus 16 days; both P<0.0001). After 12 months, recurrent stroke occurred in 3.27% of patients with no stenosis, in 3.82% for those with 50% to 69% stenosis, in 5.16% for those with 70% to 99% stenosis, and in 7.27% for those with total occlusion. Cox proportional hazards regression analyses showed that the degree of arterial stenosis, age, family history of stroke, history of cerebral ischemia or heart disease, complete circle of Willis, and National Institutes of Health Stroke Scale score at admission were independent predictors for recurrent stroke at 1 year. The highest rate of recurrence was observed in patients with occlusion with the presence of ≥3 additional risk factors. CONCLUSIONS: ICAS is the most common vascular lesion in patients with cerebrovascular disease in China. Recurrent stroke rate in our study was lower compared with those of previous clinical trials but remains unacceptably high in a subgroup of patients with severe stenosis.

Comparison of fast MRI-based individual thrombolysis therapy for patients with superacute infarction.

BACKGROUND: The aim of this study is to investigate the outcomes of magnetic resonance imaging (MRI)-based individual thrombolysis therapy using recombinant tissue plasminogen activator (rt-PA) in patients with superacute infarction, comparing the outcome in 1 group of patients treated within 4.5 hours compared with 4.5- to 12-hour window treatment group. METHODS: We studied 135 patients stratified to 2 different groups based on whether they presented with stroke symptoms within 4.5 hours (4.5-hour group, 72 patients) or between 4.5 and 12 hours (4.5- to 12-h group, 63 patients). All patients were treated with rt-PA after MRI confirmed superacute ischemic stroke (hyperintense in diffusion-weighted imaging but no hypointense change in T2-weighted image (T2WI) or fluid-attenuated inversion recovery). Clinical neurologic deficit was evaluated using the National Institutes of Health Stroke Scale on admission, at 24 hours, and 7 days later. A 90-day clinical outcome was assessed using the modified Rankin Scale (mRS). RESULTS: There was no significant difference in the clinical outcome between the patients treated with thrombolysis within the first 4.5 hours and those treated between 4.5 and 12 hours. The 2 groups both had recanalization, mRS, and favorable outcome at 90 days (P > .05). CONCLUSIONS: Our study suggested that fast MR-based thrombolysis using rt-PA was safe and reliable in superacute infarction within 4.5 hours and 4.5-12 hours poststroke.

Classification of Glioblastoma Associated with Immune Checkpoints and Tumor Microenvironment based on Immunogenomic Profiling.

BACKGROUND: Immune microenvironment is involved in tumor initiation and progression, and its effect on glioblastoma (GBM) is still unknown. OBJECT: We sought to investigate the association between immune status and GBM. METHODS: Transcriptome data and the relevant clinical data were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases, and we identified two immune subtypes based on 29 immune-associated gene sets. RESULTS: Through single-sample gene set enrichment analysis (ssGSEA), we found that the high-immunity subtype had the most tumor-infiltrating immune cells and immune checkpoint molecules in GBM patients. Furthermore, we could more effectively identify immune signature pathways in GBM. CONCLUSION: After validation with the GEO dataset, we conclude that the identified GBM high-immune subtypes may be amenable to the application of novel immune therapy for GBM.

Identification and Prognostic Value of m6A-Related Genes in Glioblastoma.

BACKGROUND: N6-methyladenosine (m6A) is one of the most common forms of mRNA modification, which is dynamically regulated by the m6A-related genes; however, its effect in glioblastoma (GBM) is still unknown. OBJECTIVE: We sought to investigate the association between m6A-related genes (m6A-RGs) and GBM. METHODS: Transcriptome data and the relevant clinical data were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. The m6A-RGs were identified from differently expressed genes, and COX and lasso regression models were applied to locate the prognosis-related genes. RESULTS: We identified 15 out of 19 m6A-RGs differentially expressed between GBM and nontumor tissues. We identified two subgroups of GBM (clusters 1 and 2) by applying consensus clustering. Compared with the cluster 1 subgroup, the cluster 1 subgroup correlates with a poorer prognosis, and most of the 19 m6A-RGs are higher expressed in cluster 1. Through univariate Cox and lasso regression model, we identified three m6A-RGs, namely HNRNPC, ALKBH5, and FTO, which were used to construct a Cox regression risk model to predict the prognosis of GBM patients. CONCLUSION: We identified a valuable m6A model for predicting the prognosis of GBM patients, which can provide useful epigenetic biomarkers.

Alternative Splicing in Glioblastoma and its Clinical Implication in Outcome Prediction.

BACKGROUND AND OBJECTIVE: Alternative splicing (AS) offers an important mechanism to form protein polymorphism. A growing body of evidence indicates the correlation between splicing abnormality and carcinoma. Nevertheless, an overall analysis of AS signatures in glioblastoma (GBM) is absent and urgently needed. METHODS: TCGA SpliceSea data was used to evaluate the AS profiles and further classified into different AS events. The survival analysis was based on these AS events, and AS-related genes were identified and performed with enrichment analysis. At last, the splicing factor-AS regulatory network was established in Cytoscape. RESULTS: Eight hundred forty-two splicing events were confirmed as prognostic molecular events in GBM. Furthermore, the final prognostic signature constructed by seven AS events gave good result with an area under the curve (AUC) of receiver operating characteristic (ROC) curve up to 0.935 for five years, showing high potency in predicting patients' outcome. We built the splicing regulatory network to show the internal relationship of splicing events in GBM. PC4 and SFRS1 interacting protein 1 (PSIP1) and histone H4 acetylation may play a significant part in the prognosis induced by splicing events. CONCLUSION: In our study, a high-efficiency prognostic prediction model was built for GBM patients based on AS events, which could become potential prognostic biomarkers for GBM. Meanwhile, PSIP1 may be a critical target for pharmaceutical treatment.

A Pan-Cancer Analysis of the Oncogenic Role of Methyltransferase-Like 1 in Human Tumors.

BACKGROUND AND OBJECT: Although emerging cell- or animal-based evidence supports the relationship between methyltransferase-like 1 (METTL1) and cancers, no pan-cancer analysis is available. METHODS: We thus first explored the potential oncogenic roles of METTL1 across 33 tumors based on the datasets of The Cancer Genome Atlas and Gene Expression Omnibus. RESULTS: METTL1 is highly expressed in most cancers, and distinct associations exist between METTL1 expression and prognosis of tumor patients. METTL1 level is related with the dendritic and B-cell infiltration levels in most tumors. Moreover, RNA processing- and RNA metabolism-associated functions were involved in the functional mechanisms of METTL1. CONCLUSION: Our pan-cancer study offers a relatively comprehensive understanding of the oncogenic roles of METTL1 across different tumors.

Novel Immune-Related LncRNA Pairs are Associated with Immunol Infiltration and Survival Status in Glioblastoma.

Background: Immune-related lncRNA is involved in tumor initiation and progression, while its effect in glioblastoma (GBM) is still unknown. Objective: We sought to investigate the association between immune-related lncRNA (ir-lncRNA) and GBM. Methods: Transcriptomic and clinical data were obtained from the TCGA dataset, and we found 2008 ir-lncRNA differentially expressed between GBM and adjacent brain tissues. Results: Appling the univariate Cox and Lasso regression model, we found 30 prognosis-related ir-lncRNA pairs to construct a Cox regression risk model to associate the outcome of GBM patients. Furthermore, with this risk model, we can identify the tumor immune infiltration status, the expression of immunosuppressive biomarkers, and chemical sensitivity in GBM patients. Conclusions: We constructed an immunologic risk model with lncRNA to associate the survival outcome of GBM patients, which can provide useful biomarkers.

Blood-Brain Barrier Dysfunction and the Potential Mechanisms in Chronic Cerebral Hypoperfusion Induced Cognitive Impairment.

Chronic cerebral hypoperfusion (CCH) is a major cause of vascular cognitive impairment and dementia (VCID). Although the underlying mechanisms have not been fully elucidated, the emerging data suggest that blood-brain barrier (BBB) dysfunction is one of the pivotal pathological changes in CCH. BBB dysfunction appears early in CCH, contributing to the deterioration of white matter and the development of cognitive impairment. In this review, we summarize the latest experimental and clinical evidence implicating BBB disruption as a major cause of VCID. We discuss the mechanisms of BBB dysfunction in CCH, focusing on the cell interactions within the BBB, as well as the potential role of APOE genotype. In summary, we provide novel insights into the pathophysiological mechanisms underlying BBB dysfunction and the potential clinical benefits of therapeutic interventions targeting BBB in CCH.

MRI-guided thrombolysis for lenticulostriate artery stroke within 12 h of symptom onset.

Stroke thrombolysis treatment is generally administered within 4.5 h, but a greater time window may be permitted depending upon the ischemic penumbra on neuroimaging. This observational cohort study investigated the outcomes of thrombolysis given within 12 h after symptom onset of lenticulostriate artery stroke. The population comprised 160 patients. Thrombolysis was administered via tissue plasminogen activator, alteplase (TPA). Thrombolysis was indicated by a mismatch between diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI), that is, an acute ischemic lesion on DWI without a corresponding lesion on T2WI. Demographics and medical history were compared with the modified Rankin scale (mRS) score, to reflect outcome. Patients with a favorable clinical outcome (mRS 0-1) had significantly lower hypertension, baseline NIH Stroke Scale (NIHSS) score, and admission systolic/diastolic blood pressure compared with patients with mRS 2-6. Lower admission systolic blood pressure and NIHSS score were significantly associated with favorable outcome. In patients either with IV-TPA within 4.5 h, or between 4.5 and 12 h, lower admission systolic blood pressure and/or NIHSS score similarly independently predict favorable outcome. However, in all groups, the onset-to-treatment time did not significantly influence the outcomes. We conclude that in our cohort higher admission systolic blood pressure and higher baseline NIHSS and not time were associated with poor outcome in patients with magnetic resonance-guided thrombolysis within 12 h of isolated lenticulostriate artery stroke, therefore loosening the traditionally perceived dependency of outcome on time.

Integrated single-cell multiomics reveals novel immune candidate markers for post-traumatic coagulopathy.

Introduction: Post-traumatic coagulopathy (PTC) is a critical pathology in traumatic brain injury (TBI), however, its potential mechanism is not clear. To explore this in peripheral samples, we integrated single cell RNA-sequencing and T cell repertoire (TCR)-sequencing across a cohort of patients with TBI. Methods: Clinical samples from patients with more brain severity demonstrated overexpression of T cell receptor-encoding genes and less TCR diversity. Results: By mapping TCR clonality, we found patients with PTC have less TCR clones, and the TCR clones are mainly distributed in cytotoxic effector CD8+T cell. In addition, the counts of CD8+ T cell and natural killer (NK) cells are associated with the coagulation parameter by WGCNA, and the granzyme and lectin-like receptor profiles are also decreased in the peripheral blood from TBI patients, suggesting that reduced peripheral CD8+ clonality and cytotoxic profiles may be involved in PTC after TBI. Conclusion: Our work systematically revealed the critical immune status in PTC patients at the single-cell level.

Effectiveness and Predictors of Poor Prognosis Following Intravenous Thrombolysis in Patients with Wake-Up Ischemic Stroke Guided by Rapid MRI.

PURPOSE: Our aim was to investigate the effectiveness and predictors of poor prognosis in WUIS patients who received alteplase thrombolysis under the guidance of diffusion-weighted imaging (DWI)-T2-weighted imaging (T2WI) mismatch. PATIENTS AND METHODS: We recruited patients within 4.5 h of acute ischemic stroke (AIS) and WUIS patients with uncertain onset times from two stroke centers. To evaluate effectiveness, we compared National Institutes of Health Stroke Scale (NIHSS) scores between the two groups at admission and at 24 h, 3 days, and 1 week thereafter. We also compared the two groups with respect to the modified Rankin Scale (mRS) score at 90 days after thrombolysis. The WUIS patients were divided into a favorable prognosis group (mRS score: 0-1 points) and a poor prognosis group (mRS score ≥2 points). Data were compared between the two subgroups to identify factors that influence poor prognoses. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of factors related to poor prognosis. RESULTS: A total of 114 patients with WUIS and 316 patients with AIS were enrolled in the study. There were no significant differences between the two groups in terms of NIHSS or 90-day mRS scores (p > 0.05). Baseline NIHSS score (odds ratio [OR] = 1.490, 95% confidence interval [CI] 1.248-1.779, p < 0.001) and atrial fibrillation (OR = 3.825, 95% CI 1.218-12.016, p = 0.022) were identified as independent predictors of poor prognosis following thrombolysis in WUIS patients. The combined ROC diagnosis of these two variables had an area under the curve of 0.850. CONCLUSION: The DWI-T2WI sequence is an effective method to guide intravenous thrombolytic therapy for WUIS. Baseline NIHSS score and atrial fibrillation were identified as independent predictors of poor prognosis following thrombolysis in WUIS patients.

Neonatal microglia and proteinase inhibitors-treated adult microglia improve traumatic brain injury in rats by resolving the neuroinflammation.

Microglia participate in the regulation of neuroinflammation caused by traumatic brain injury (TBI). This research aimed to explore the repair effects of intracranial injection of neonatal microglia or protease-treated adult microglia on TBI in rat model. Lateral fluid percussion injury was used to establish rat brain injury model. E64 and serpinA3N were employed for the treatment of adult microglia. Cleaved caspase-3 level was analyzed through immunoblotting assay. Enzyme-linked immunosorbent assay was employed to analyze cytokine and chemokine levels. Astrocytosis and microgliosis were shown by immunofluorescence. The cognitive function of rats was analyzed by water maze. The injection of neonatal microglia inhibited cell apoptosis, reduced astrocytosis and microgliosis, decreased the level of chemokines and cytokines in cortex and ipsilateral hippocampus, and improved cognitive function of TBI rat model. The transplantation of peptidase inhibitors-treated adult microglia also inhibited cell apoptosis, reduced astrocytosis and microgliosis, and improved cognitive function of rats with TBI. The transplantation of either neonatal microglia or peptidase inhibitors-treated adult microglia significantly inhibited the pathogenesis of TBI in rat model, while untreated adult microglia showed no significant effect.

Associations of Abdominal Visceral Fat Content and Plasma Adiponectin Level With Intracranial Atherosclerotic Stenosis: A Cross-Sectional Study.

Background: Abdominal obesity and adipocytokines are closely related to atherosclerosis, and adiponectin level is considered one of the important clinical indicators. This study aimed to analyze the associations of abdominal visceral fat content and adiponectin level with intracranial atherosclerotic stenosis (ICAS). Methods: A total of 186 patients were enrolled in this study. Patients were distributed into ICAS and non-ICAS by the degree of artery stenosis. Plasma adiponectin levels and the ratio of visceral adipose tissue (VAT) to subcutaneous adipose tissue (SAT) were measured. The related factors of intracranial atherosclerotic stenosis were determined using multivariable logistic regression analysis. Results: The VAT/SAT ratio (OR, 26.08; 95% CI, 5.92-114.83; p < 0.001) and adiponectin (OR, 0.61; 95% CI, 0.44-0.84; p = 0.002) were found to be the independent predictors of ICAS in a multivariable logistic regression analysis. The prevalence of ICAS increased (T1: 27.4%; T2: 50.0%; T3: 75.8%) as the VAT/SAT ratio tertile increased (p < 0.001). The prevalence of ICAS decreased (T1: 72.6%; T2: 54.8%; T3: 25.8%) as the adiponectin tertile increased (p < 0.001). In ROC curves analysis, VAT/SAT ratio had a sensible accuracy for the prediction of ICAS. The optimal cut-off value of VAT/SAT ratio to predict ICAS in this study was 1.04 (AUC: 0.747; p < 0.001; sensitivity: 67.4%; specificity: 74.7%). The optimal adiponectin cutoff was 3.03 ug/ml (AUC: 0.716; p < 0.001; sensitivity:75.8%; specificity: 61.5%). Conclusion: Higher VAT/SAT ratio and lower plasma adiponectin levels were closely related to the increased risk of intracranial atherosclerotic stenosis.