Stress hyperglycemia is common in critical and severe diseases. However, few studies have examined the association between stress hyperglycemia and the functional outcomes of patients with anterior circulation stroke, after mechanical thrombectomy (MT), in different diabetes status. This study therefore aimed to determine the relationship between stress hyperglycemia and the risk of adverse neurological functional outcomes in anterior circulation stroke patients with and without diabetes after MT.Data of 408 patients with acute anterior circulation stroke treated with MT through the green-channel treatment system for emergency stroke at the First Affiliated Hospital of Jinan University between January 2016 and December 2020 were reviewed retrospectively. The stress hyperglycemia ratio (SHR) was calculated as fasting plasma glucose (mmol/L) divided by glycosylated hemoglobin (%). The patients were stratified into four groups by quartiles of SHR (Q1-Q4). The primary outcome was an excellent (nondisabled) functional outcome at 3 months after admission (modified Rankin Scale score of 0-1). The relationship between stress hyperglycemia and neurological outcome after stroke was assessed using multivariate logistic regression.After adjusting for potential confounders, compared with patients in Q1, those in Q4 were less likely to have an excellent outcome at 3 months (odds ratio [OR], 0.32, 95% confidence interval [CI], 0.14-0.66, p = 0.003), a good outcome at 3 months (OR, 0.41, 95% CI, 0.20-0.84, p = 0.020), and major neurological improvement (OR, 0.38, 95% CI, 0.19-0.73, p = 0.004). Severe stress hyperglycemia increased risks of 3-months all-cause mortality (OR, 2.82, 95% CI, 1.09-8.29, p = 0.041) and ICH (OR, 2.54, 95% CI, 1.21-5.50, p = 0.015).Stress hyperglycemia was associated with a reduced rate of excellent neurological outcomes, and increased mortality and ICH risks in patients with anterior circulation stroke after MT regardless of diabetes status.
Background and purpose: Admission hyperglycemia is associated with 3-month and/or 6-month poor outcomes after aneurysmal subarachnoid hemorrhage, but the effect of prolonged hyperglycemia on long-term outcomes is not very clear. We studied the relationship between 14 th day fasting glucose and 1-year outcome after aneurysmal subarachnoid hemorrhage. Methods: A prospective study of aneurysmal subarachnoid hemorrhage from August 2007 to August 2010 was used to analyze the effect of fasting glucose on admission and 14 th day respectively on 1-year outcome assessed with the modified Rankin scale. Onset to admission longer than 14 days were excluded from analysis, as well as patients died within the first 14 days post-onset. A total of 322 patients (female 54.7%, average age: 53.9±11.6 yr, 310 patients admitted within 7 days) were used to assess the relationship between poor outcomes and fasting glucose, and medical history, Fisher scale, Hunt and Hess grade, Glasgow Coma Scores. Poor outcome (death and dependency) was defined as modified Rankin scale 3-6 at 1 year. Multivariate Cox regression analysis was performed to assess risk factors for 1-year outcome. Results: The mean fasting glucose on 14 th day of poor outcome patients was higher than that of good outcome patients [(7.11±3.35) vs. (5.43±1.55) mmol/L, p <0.001]. Fasting glucose at admission in poor outcome patients was also higher than that of good outcome ones[(6.90±2.61) vs. (5.92±1.74) mmol/L, p =0.005]. After adjusting for Hunt and Hess grade, history of hypertension and Fisher scale, fasting glucose on 14 th day was an independent predictor of poor outcome (odds ratio, 1.278; 95% CI, 1.098 to 1.487; P =0.0016). Meanwhile, glucose level on 14 th day was found to be associated with 1-year death (adjusted HR, 1.183; 95%CI, 1.087 to 1.288) after adjusting for Fisher scale, Glasgow Coma Scale and treatment methods. However, fasting glucose at admission wasn’t independent predictor of 1-year death and dependency in Logistic regression and death in Cox regression. Conclusions: After aneurysmal subarachnoid hemorrhage, the fasting glucose levels on 14 th day are associated with an increased risk of 1-year death and dependency. Further studies are needed to confirm these results.
The previous studies on the association between marital status and stroke outcomes were rare. Furthermore, the existing studies mostly focused on the protective effect of marriage on survival. We conducted the study to evaluate the association between marital status and adverse stroke outcomes in patients with AIS based on China national stroke registry. This was a multicenter, prospective cohort study of patients with AIS. Patients were classified into two groups based on marital status at admission: married and unmarried. The primary outcomes included all-cause mortality, stroke recurrence, combined endpoint, and stroke disability. Stroke disability was defined as modified Rankin Scale of 2–6. Of 12,118 patients, 1220 were unmarried and 10,898 married. Unmarried patients had higher proportion of 1-year post-stroke events than married patients did. As compared with being unmarried, the adjusted odds ratios with 95% confidence interval of being married for outcomes were as follows: 0.70 (0.58–0.84) for all-cause mortality, 0.78 (0.66–0.91) for stroke recurrence, 0.77 (0.66–0.90) for combined endpoint, and 0.75 (0.65–0.88) for stroke disability. Interactions between marital status and education were significant for all outcomes except for stroke disability. Marital status was associated with all adverse stroke outcomes in patients with acute ischemic stroke, especially in those with middle-school education.
Background and Purpose: Ischemic stroke (IS) is one of the most common causes of human death worldwide, but the molecular mechanisms of IS are still unclear. To explore the key genes and pathways involved in the pathogenic process of IS, we did a bioinformatics analysis of high throughput sequencing data of IS for the first time, which compared the expression profiles of brain tissues in IS patients and health controls. Methods: The dataset SRP040622 analyzed of expression profiling in 13 samples by deep sequencing in the platform of Illumina HiSeq 2000, including seven cortical ischemic stroke tissues and six control cortex tissues. These data from SRP040622 were downloaded from Sequence Read Archive (SRA) by using Prefech. We adopted fastq-dump, Hisat2, samtools, HTseq and DEseq2 to get the quantification of gene expression from raw data. The differentially expressed genes (DEGs) were identified by limma package, and function enrichment analyses were performed in DAVID website. In addition, the protein-protein interaction (PPI) network was constructed by using STRING and Cytoscape. Results: A total 880 DEGs were identified, including 350 up-regulated genes and 530 down-regulated genes. These DEGs enriched in biological processes(BP) mainly associated with signal transduction, multicellular organism development, positive regulation of cell proliferation, protein phosphorylation, cell-cell adhesion and angiogenesis. And KEGG pathway which DEGS were mainly enriched in is PI3K-Akt signaling pathway, Focal adhesion and Ras signaling pathway. In addition, 34 hub genes were selected by using CytoHubba with degrees >10. Conclusions: Our data reflects that PI3K-Akt signaling pathway, Focal adhesion and Ras signaling pathway may play significant roles in IS, and the hub genes among DEGs(including KDR, ESR1, MMP2, CAV1, PTK2, VWF) may be the potential targets for diagnosis and treatment of IS.
Sperm whale myoglobin (Mb) has weak dehaloperoxidase activity and catalyzes the peroxidative dehalogenation of 2,4,6-trichlorophenol (TCP) to 2,6-dichloroquinone. Crystals of Mb and of its more active G65T variant were used to study the binding of TCP, 4-iodophenol (4-IP) and phenol. The structures of crystals soaked overnight in a 10 mM solution of phenol revealed that a phenol molecule binds in the proximal cavity, forming a hydrogen bond to the hydroxyl of Tyr146 and hydrophobic contacts which include interactions with Cβ and Cγ of the proximal histidine His93. The phenol position corresponds to the strongest xenon binding site, Xe1. It appears that the ligand enters the proximal cavity through a gate formed by the flexible loops 79-86 and 93-103. TCP and 4-IP do not bind to Mb in this manner under similar conditions; however, it appears to be likely that dimethyl sulfoxide (DMSO), which was used at a concentration of 0.8 M to facilitate 4-IP dissolution, binds in the phenol/Xe1 binding site. In this structure, a water molecule coordinated to the heme iron was replaced by an oxygen molecule, reflecting the reduction of the heme. Crystals of Mb and G65T Mb soaked for 5-10 min did not show bound phenol. Kinetic studies of TCP dechlorination showed that phenol has a dual effect: it acts as a competitive inhibitor that is likely to interfere with TCP binding at the heme edge and as a weak activator, likely through binding in the proximal cavity. The lack of phenol bound at the heme edge in the crystal structures suggests that its inhibitory binding only takes place when the heme is activated by hydrogen peroxide.
Background: Stroke is a leading cause of death in China. Yet the adherence to guideline-recommended stroke performance metrics was suboptimal in the past decade. We sought to determine whether adherence changed after the implementation of the China National Quality Management Initiatives. Methods and Results: Data were obtained from the China National Stroke Registries (CNSR), and included 132 hospitals (12 173 patients) participated in CNSR Phase I (2007-2008) vs. 219 hospitals (19 604 patients) in CNSR Phase II (2012-2013). The overall adherence increased over time, as reflected by the higher composite score of 0.76 in 2012-2013 as compared with 0.63 in 2007-2008, and the increase in 9 of 13 individual metrics, including dysphagia screening, carotid imaging, rehabilitation evaluation, antithrombotics, lipid-lowering, antihypertensive medications, antidiabetic medications at discharge, smoking cessation, and stroke education). However, there were no significant improvements in the intravenous thrombolytic therapy, early antithrombotics, deep vein thrombosis prophylaxis, and anticoagulation for atrial fibrillation. Multivariate analysis suggested that there was a 1.17-fold increase in the odds of fulfilling care opportunities. Conclusions: Adherence to stroke performance metrics increased recently, but significant opportunities remain for further improvement. Continuous stroke quality improvement program should be developed as a national priority in China.
To determine the relationship of glycated albumin (GA) and the recurrence of stroke in patients on either dual or single antiplatelet therapy.The Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events trial randomized minor ischemic stroke or TIA patients to antiplatelet therapy of clopidogrel plus aspirin or aspirin alone. A subgroup of 3,044 consecutive patients with baseline GA levels from 73 (64%) prespecified clinical sites was analyzed. Patients were categorized into 2 groups based on GA level of 15.5%, the cut point for development of diabetes. The primary outcome was stroke recurrence during 90-day follow-up. Cox proportional hazards models were used to assess the interaction of GA with randomized antiplatelet therapy on their risk of recurrent stroke.Significant interaction of GA levels with the 2 antiplatelet therapy groups was found after adjustment for age, sex, and other conventional confounding factors (p = 0.009). The interaction remained consistent after further adjustment for history of diabetes (p = 0.010). In patients with lower GA level, stroke occurred in 5.5% of patients in the clopidogrel-aspirin group, and 12.7% in the aspirin group (adjusted hazard ratio [HR] 0.40; 95% confidence interval [CI] 0.26-0.61; p < 0.001). Furthermore, in patients with elevated GA level, stroke occurred in 9.2% of patients in the clopidogrel-aspirin group, and 11.4% in the aspirin group (adjusted HR 0.79; 95% CI 0.60-1.05; p = 0.103).GA could be a potential biomarker to predict the effects of dual and single antiplatelet therapy in patients with minor stroke or TIA.
Agents inhibiting microglial activation are attracting attention as candidate drugs for neuroprotection in neurodegenerative diseases. Recently, researchers have focused on the immunosuppression induced by rifampicin. Our previous study showed that rifampicin inhibits the production of lipopolysaccharide (LPS)-induced pro‑inflammatory mediators and improves neuron survival in inflammation; however, the mechanism through which rifampicin inhibits microglial inflammation and its neuroprotective effects are not completely understood. In this study, we examined the effects of rifampicin on morphological changes induced by LPS in murine microglial BV2 cells. Then we investigated, in BV2 microglia, the effects of rifampicin on two signaling pathway componentss stimulated by LPS, the Toll‑like receptor-4 (TLR-4) and the nuclear factor-κB (NF-κB). In addition, we co-cultured BV2 microglia and neurons to observe the indirect neuroprotective effects of rifampicin. Rifampicin inhibited LPS-stimulated expression of the TLR-4 gene. When neurons were co-cultured with LPS-stimulated BV2 microglia, pre-treatment with rifampicin increased neuronal viability and reduced the number of apoptotic cells. Taken together, these findings suggest that rifampicin, with its anti-inflammatory properties, may be a promising agent for the treatment of neurodegenerative diseases.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
'/%3e%3c/g%3e%3cuse xlink:href='%23d' x='45.714'/%3e%3cuse xlink:href='%23e' transform='matrix(-1 0 0 1 479.792 0)'/%3e%3cg id='f' fill='%23fff'%3e%3cpath fill='%23039' d='M232.636 202.406v.005c0 2.212.85 4.227 2.212 5.69 1.365 1.466 3.245 2.377 5.302 2.377 2.067 0 3.944-.905 5.303-2.365 1.358-1.459 2.202-3.472 2.202-5.693v-10.768l-14.992-.013-.028 10.766'/%3e%3ccircle cx='236.074' cy='195.735' r='1.486'/%3e%3ccircle cx='244.392' cy='195.742' r='1.486'/%3e%3ccircle cx='240.225' cy='199.735' r='1.486'/%3e%3ccircle cx='236.074' cy='203.916' r='1.486'/%3e%3ccircle cx='244.383' cy='203.905' r='1.486'/%3e%3c/g%3e%3cuse xlink:href='%23f' y='-26.016'/%3e%3cuse xlink:href='%23f' x='-20.799'/%3e%3cuse xlink:href='%23f' x='20.745'/%3e%3cuse xlink:href='%23f' y='25.784'/%3e%3c/svg%3e)