Potential preservative mechanisms of cardiac rehabilitation pathways on endothelial function in coronary heart disease.

Cardiac rehabilitation, a comprehensive exercise-based lifestyle and medical management, is effective in decreasing morbidity and improving life quality in patients with coronary heart disease. Endothelial function, an irreplaceable indicator in coronary heart disease progression, is measured by various methods in traditional cardiac rehabilitation pathways, including medicinal treatment, aerobic training, and smoking cessation. Nevertheless, studies on the effect of some emerging cardiac rehabilitation programs on endothelial function are limited. This article briefly reviewed the endothelium-beneficial effects of different cardiac rehabilitation pathways, including exercise training, lifestyle modification and psychological intervention in patients with coronary heart disease, and related experimental models, and summarized both uncovered and potential cellular and molecular mechanisms of the beneficial roles of various cardiac rehabilitation pathways on endothelial function. In exercise training and some lifestyle interventions, the enhanced bioavailability of nitric oxide, increased circulating endothelial progenitor cells (EPCs), and decreased oxidative stress are major contributors to preventing endothelial dysfunction in coronary heart disease. Moreover, the preservation of endothelial-dependent hyperpolarizing factors and inflammatory suppression play roles. On the one hand, to develop more endothelium-protective rehabilitation methods in coronary heart disease, adequately designed and sized randomized multicenter clinical trials should be advanced using standardized cardiac rehabilitation programs and existing assessment methods. On the other hand, additional studies using suitable experimental models are warranted to elucidate the relationship between some new interventions and endothelial protection in both macro- and microvasculature.

Inflammatory marker profiles and in-hospital neurological deterioration in patients with acute minor ischemic stroke.

AIM: The aim of the study was to analyze the association between inflammatory marker profiles and in-hospital neurological deterioration (ND) in acute ischemic stroke (AIS) patients. METHODS: Data from patients with minor AIS from the Third China National Stroke Registry were analyzed. Inflammatory cytokine levels within 24 h of admission were measured. The primary outcome was in-hospital ND (an increase in National Institutes of Health Stroke Scale score ≥4 from admission to discharge). Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression models. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to evaluate incremental predictive values. RESULTS: A total of 4031 patients (1246 women, 30.9%) with a median age of 62 years were included. In-hospital ND occurred in 121 patients (3%). Each standard-deviation increase in interleukin (IL)-6 (OR, 1.17 [95% CI, 1.06-1.31]) and high-sensitivity C-reactive protein (hsCRP) (OR, 1.43 [95% CI, 1.24-1.66]) levels was associated with increased in-hospital ND risk. Incremental predictive values for adding IL-6 (IDI, 0.012; NRI, 0.329) but not hsCRP levels to the conventional risk factors were found. CONCLUSION: In minor AIS, hsCRP and IL-6 levels were associated with in-hospital ND, including IL-6 levels in prognostic models improved risk classification.

High-resolution magnetic resonance imaging-based radiomic features aid in selecting endovascular candidates among patients with cerebral venous sinus thrombosis.

OBJECTIVES: Cerebral venous sinus thrombosis (CVST) can cause sinus obstruction and stenosis, with potentially fatal consequences. High-resolution magnetic resonance imaging (HRMRI) can diagnose CVST qualitatively, although quantitative screening methods are lacking for patients refractory to anticoagulation therapy and who may benefit from endovascular treatment (EVT). Thus, in this study, we used radiomic features (RFs) extracted from HRMRI to build machine learning models to predict response to drug therapy and determine the appropriateness of EVT. MATERIALS AND METHODS: RFs were extracted from three-dimensional T1-weighted motion-sensitized driven equilibrium (MSDE), T2-weighted MSDE, T1-contrast, and T1-contrast MSDE sequences to build radiomic signatures and support vector machine (SVM) models for predicting the efficacy of standard drug therapy and the necessity of EVT. RESULTS: We retrospectively included 53 patients with CVST in a prospective cohort study, among whom 14 underwent EVT after standard drug therapy failed. Thirteen RFs were selected to construct the RF signature and CVST-SVM models. In the validation dataset, the sensitivity, specificity, and area under the curve performance for the RF signature model were 0.833, 0.937, and 0.977, respectively. The radiomic score was correlated with days from symptom onset, history of dyslipidemia, smoking, fibrin degradation product, and D-dimer levels. The sensitivity, specificity, and area under the curve for the CVST-SVM model in the validation set were 0.917, 0.969, and 0.992, respectively. CONCLUSIONS: The CVST-SVM model trained with RFs extracted from HRMRI outperformed the RF signature model and could aid physicians in predicting patient responses to drug treatment and identifying those who may require EVT.

Mediation effect of stroke recurrence in the association between post-stroke interleukin-6 and functional disability.

AIM: Post-stroke inflammation increases the risk of functional disability through enlarged cerebral infarct size directly and follow-up stroke event indirectly. We aimed to use post-stroke proinflammatory cytokine interleukin-6 (IL-6) as a marker of inflammatory burden and quantify post-stroke inflammation's direct and indirect effect on functional disability. METHODS: We analyzed patients with acute ischemic stroke admitted to 169 hospitals in the Third China National Stroke Registry. Blood samples were collected within 24 h of admission. Stroke recurrence and functional outcome measured by the modified Rankin scale (mRS) were assessed via face-to-face interviews at 3 months. Functional disability was defined as an mRS score ≥2. Mediation analyses under the counterfactual framework were performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between IL-6 and functional outcome. RESULTS: Among the 7053 analyzed patients, the median (interquartile range [IQR]) NIHSS score was 3 (1-5), and the median (IQR) level of IL-6 was 2.61 (1.60-4.73) pg/mL. Stroke recurrence was observed in 458 (6.5%) patients, and functional disability was seen in 1708 (24.2%) patients at the 90-day follow-up. Per stand deviation (4.26 pg/mL) increase in the concentration of IL-6 was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.19; 95% CI, 1.09-1.29) and disability (aOR, 1.22; 95% CI, 1.15-1.30) within 90 days. Mediation analyses revealed that 18.72% (95% CI, 9.26%-28.18%) of the relationship between IL-6 and functional disability was mediated by stroke recurrence. CONCLUSIONS: Stroke recurrence mediates less than 20% of the association between IL-6 and functional outcome at 90 days among patients with acute ischemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes directly.

Temporal trends and rural-urban disparities in cerebrovascular risk factors, in-hospital management and outcomes in ischaemic strokes in China from 2005 to 2015: a nationwide serial cross-sectional survey.

BACKGROUND: Stroke is the leading cause of mortality in China, with limited evidence of in-hospital burden obtained from nationwide surveys. We aimed to monitor and track the temporal trends and rural-urban disparities in cerebrovascular risk factors, management and outcomes from 2005 to 2015. METHODS: We used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005, 2010 and 2015. We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach. We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015. RESULTS: We analysed 28 277 ischaemic stroke admissions from 189 participating hospitals. From 2005 to 2015, the estimated national hospital admission rate for ischaemic stroke per 100 000 people increased (from 75.9 to 402.7, Ptrend<0.001), and the prevalence of risk factors, including hypertension, diabetes, dyslipidaemia and current smoking, increased. The composite score of diagnostic tests for stroke aetiology assessment (from 0.22 to 0.36, Ptrend<0.001) and secondary prevention treatments (from 0.46 to 0.70, Ptrend<0.001) were improved. A temporal decrease was found in discharge against medical advice (DAMA) (from 15.2% (95% CI 13.7% to 16.7%) to 8.6% (8.1% to 9.0%); adjusted Ptrend=0.046), and decreases in in-hospital mortality (0.7% in 2015 vs 1.8% in 2005; adjusted OR (aOR) 0.52; 95% CI 0.32 to 0.85) and the composite outcome of in-hospital mortality or DAMA (8.4% in 2015 vs 13.9% in 2005; aOR 0.65; 95% CI 0.47 to 0.89) were observed. Disparities between rural and urban hospitals narrowed; however, disparities persisted in in-hospital management (brain MRI: rural-urban difference from -14.4% to -11.2%; cerebrovascular assessment: from -20.3% to -16.7%; clopidogrel: from -2.1% to -10.3%; anticoagulant for atrial fibrillation: from -10.9% to -8.2%) and in-hospital outcomes (DAMA: from 2.7% to 5.0%; composite outcome of in-hospital mortality or DAMA: from 2.4% to 4.6%). CONCLUSIONS: From 2005 to 2015, improvements in hospital admission and in-hospital management for ischaemic stroke in China were found. A temporal improvement in DAMA and improvements in in-hospital mortality and the composite outcome of in-hospital mortality or DAMA were observed. Disparities between rural and urban hospitals generally narrowed but persisted.

Pre-stroke dementia and in-hospital outcomes in the Chinese Stroke Center Alliance.

Background: Little is known about the impact of prevalent dementia on in-hospital outcomes of patients with incident stroke in China. Using data from the Chinese Stroke Center Alliance (CSCA), we aim to quantify the prevalence of pre-stroke dementia and whether this group is at higher risk of adverse in-hospital outcomes compared to those without pre-stroke dementia. Methods: We used multivariable logistic regression models to assess the associations between pre-stroke dementia and ambulation by day 2, in-hospital mortality, in-hospital complications, and being discharged home. Covariates included age, sex, comorbidities [dyslipidemia, atrial fibrillation, peripheral vascular disease (PVD), smoking, and alcohol use], medication history (antiplatelet drugs or lipid-lowering drugs), stroke severity [measured by the National Institute of Health Stroke Scale (NIHSS)], administration of intravenous tissue plasminogen activator (IV tPA) within 4.5 hours of stroke onset, and receipt of deep vein thrombosis (DVT) prophylaxis if indicated. Results: In the final analytic sample of 559,070 ischemic stroke patients with no prior stroke history enrolled across 1,476 hospitals, those with pre-stroke dementia (n=1,511; 0.3%) were older and more likely to be female. Despite having received similar treatment, patients with pre-stroke dementia had lower odds of ambulating by day 2 [odds ratio (OR) =0.69; 95% confidence interval (CI): 0.62-0.78], higher odds of in-hospital mortality (OR =2.01; 95% CI: 1.35-2.99) or complications (OR =2.17; 95% CI: 1.93-2.44), and lower odds of being discharged home compared to those without pre-stroke dementia (OR =0.71; 95% CI: 0.62-0.83). Conclusions: Worse in-hospital outcomes among patients with pre-stroke dementia may be explained by pre-existing cognitive impairment that limited their ability to advocate for care needs. Further research is needed to determine whether a different care pathway or additional attention from clinicians is necessary for patients with pre-stroke dementia.

Sex differences in vascular risk factors, in-hospital management, and outcomes of patients with acute ischemic stroke in China.

BACKGROUND: Previous assessments of sex differences for patients with acute ischemic stroke were limited in a specific region or population, narrow scope, or small sample size. METHODS: Patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals were analyzed. Absolute standardized differences (ASDs) were used to assess sex differences in vascular risk factors, guideline-recommended in-hospital management measures and outcomes, including stroke severity (National Institutes of Health Stroke Scale≥16), death/discharge against medical advice, major adverse cardiovascular events, pneumonia, and disability (modified Rankin Scale≥3). RESULTS: Of 838,229 patients analyzed, 524351 (62.6%) were men and 313,878 (37.4%) were women. Compared with men, women were older (68.6 vs. 64.7 years), had higher prevalence of hypertension (67.7% vs. 62.4%), diabetes (24.7% vs. 19.5%), and atrial fibrillation (7.1% vs. 4.3%), but lower prevalence of smoking (4.5% vs. 56.6%) and drinking (2.6% vs 35.8%) (ASDs >10%). No sex differences were seen in guideline-directed management measures, indicated by risk-adjusted individual measures and the all-or-null summary measure (34.5% vs 34.9%, ASD = 1.0%). Compared to men, women tended to have strokes that were more severe at presentation (6.5% vs. 4.5%, ASD = 8.8%) and more disabilities at discharge (34.9% vs 30.5%, ASD =9.4%). However, all sex-related differences in outcomes were attenuated to null after risk adjustments (ASDs<2%). CONCLUSIONS: Compared to male patients, female patients had more vascular risk factors and received similar in-hospital care. They had strokes that were more severe at presentation and more disabilities at discharge, both of which may be explained by worse vascular risk profiles.

Guideline-directed low-density lipoprotein management in high-risk ischemic stroke or transient ischemic attack admissions in China from 2015 to 2019.

BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) is crucial for secondary stroke prevention in stroke patients with preexisting cardiovascular diseases (CVD) or cerebrovascular diseases (CeVD). However, data on attainment of guideline-recommended LDL-C levels are lacking. METHODS: We analyzed data from the Chinese Stroke Center Alliance (CSCA) program for patients with ischemic stroke and transient ischemic attack (TIA) hospitalized between August 2015 and July 2019. Participants were classified into different disease groups according to preexisting CeVD (stroke/TIA) or CVD [coronary heart disease (CHD) or myocardial infarction (MI)]. RESULTS: Of 858,509 patients presenting with an acute stroke/TIA, 251,176 (29.3%) had a preexisting CeVD, 44,158 (5.1%) had preexisting CVD, 33,070 (3.9%) had concomitant preexisting CeVD and CVD, and 530,105 (61.7%) had no documented history of CeVD/CVD. Overall, only 397,596 (46.3%) met the target for LDL-C <2.6 mmol/L, 128,177 (14.9%) for LDL-C <1.8 mmol/L and 55,275 (6.4%) for LDL-C <1.4 mmol/L, and patients with concomitant CeVD and CVD had higher attainment rates than other disease groups (P<0.001). Despite improvements over time in the proportion of patients who attain LDL-C targets (P for trend <0.05), it remains suboptimal. Younger age, women, having a history of hypertension or dyslipidemia, current smoking or drinking, and being admitted to hospitals located in eastern China were associated with lower odds of meeting the LDL-C goals. CONCLUSIONS: Overall attainment of guideline LDL-C targets in a population of stroke/TIA patients is low and indicates the need for better management of dyslipidemia, particularly for high-risk stroke patients with pre-existing CeVD or CVD.

Synergism of rMV-Hu191 with cisplatin to treat gastric cancer by acid sphingomyelinase-mediated apoptosis requiring integrity of lipid raft microdomains.

BACKGROUND: DDP-based chemotherapy is one of the first-line treatment in GC. However, the therapeutic efficacy of DDP is limited due to side effects. Therefore, it is of great significance to develop novel adjuvants to synergize with DDP. We had demonstrated previously that rMV-Hu191 had antitumor activity in GC. Here we examined the synergism of rMV-Hu191 with DDP in vitro and in vivo. METHODS: Cellular proliferation, the synergistic effect and cell apoptosis were evaluated by CCK-8 assay, ZIP analysis and flow cytometry, respectively. The protein levels and location of ASMase were monitored by western blot and immunofluorescence assay. shRNA and imipramine were used to regulate the expression and activity of ASMase. MßCD was administrated to disrupt lipid rafts. Mice bearing GC xenografts were used to confirm the synergism in vivo. RESULTS: From our data, combinational therapy demonstrated synergistic cytotoxicity both in resistant GC cell lines from a Chinese patient and drug-nonresistant GC cell lines, and increased cell apoptosis, instead of viral replication. Integrity of lipid rafts and ASMase were required for rMV-Hu191- and combination-induced apoptosis. The ASMase was delivered to the lipid raft microdomains at the initial stage of rMV-Hu191 treatment. In vivo GC mice xenografts confirmed the synergism of combinational treatment, together with increased apoptosis and trivial side-effects. CONCLUSIONS: This is the first study to demonstrate that rMV-Hu191 combined with DDP could be used as a potential therapeutic strategy in GC treatment and the ASMase and the integrity of lipid rafts are required for the synergistic effects.

A recombinant Chinese measles virus vaccine strain rMV-Hu191 inhibits human colorectal cancer growth through inducing autophagy and apoptosis regulating by PI3K/AKT pathway.

The potential therapeutic effects of oncolytic measles virotherapy have been verified against plenty of malignancies. However, the oncolytic effects and underlying mechanisms of the recombinant Chinese measles virus vaccine strain Hu191 (rMV-Hu191) against human colorectal cancer (CRC) remain elusive. In this study, the antitumor effects of rMV-Hu191 were evaluated in CRC both in vitro and in vivo. From our data, rMV-Hu191 induced remarkably caspase-dependent apoptosis and complete autophagy in vitro. In mice bearing CRC xenografts, tumor volume was remarkably suppressed and median survival was prolonged significantly with intratumoral treatment of rMV-Hu191. To gain further insight into the relationship of rMV-Hu191-induced apoptosis and autophagy, we utilized Rapa and shATG7 to regulate autophagy. Our data suggested that autophagy was served as a protective role in rMV-Hu191-induced apoptosis in CRC. PI3K/AKT signaling pathway as one of the common upstream pathways of apoptosis and autophagy was activated in CRC after treatment with rMV-Hu191. And inhibition of PI3K/AKT pathway using LY294002 was accompanied by enhanced apoptosis and decreased autophagy which suggested that PI3K/AKT pathway promoted rMV-Hu191-induced autophagy and inhibited rMV-Hu191-induced apoptosis. This is the first study to demonstrate that rMV-Hu191 could be used as a potentially effective therapeutic agent in CRC treatment. As part of the underlying cellular mechanisms, apoptosis and autophagy were involved in the oncolytic effects generated by rMV-Hu191. And the cross-talk between these two processes and the PI3K/AKT signaling pathway was well identified.

China Stroke Statistics 2019: A Report From the National Center for Healthcare Quality Management in Neurological Diseases, China National Clinical Research Center for Neurological Diseases, the Chinese Stroke Association, National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention and Institute for Global Neuroscience and Stroke Collaborations.

China faces the greatest challenge from stroke in the world. The death rate for cerebrovascular diseases in China was 149.49 per 100 000, accounting for 1.57 million deaths in 2018. It ranked third among the leading causes of death behind malignant tumours and heart disease. The age-standardised prevalence and incidence of stroke in 2013 were 1114.8 per 100 000 population and 246.8 per 100 000 person-years, respectively. According to the Global Burden of Disease Study 2017, the years of life lost (YLLs) per 100 000 population for stroke increased by 14.6%; YLLs due to stroke rose from third highest among all causes in 1990 to the highest in 2017. The absolute numbers and rates per 100 000 population for all-age disability-adjusted life years (DALYs) for stroke increased substantially between 1990 and 2017, and stroke was the leading cause of all-age DALYs in 2017. The main contributors to cerebrovascular diseases include behavioural risk factors (smoking and alcohol use) and pre-existing conditions (hypertension, diabetes mellitus, dyslipidaemia and atrial fibrillation (AF)). The most prevalent risk factors among stroke survivors were hypertension (63.0%-84.2%) and smoking (31.7%-47.6%). The least prevalent was AF (2.7%-7.4%). The prevalences for major risk factors for stroke are high and most have increased over time. Based on the latest national epidemiological data, 26.6% of adults aged ≥15 years (307.6 million adults) smoked tobacco products. For those aged ≥18 years, age-adjusted prevalence of hypertension was 25.2%; adjusted prevalence of hypercholesterolaemia was 5.8%; and the standardised prevalence of diabetes was 10.9%. For those aged ≥40 years, the standardised prevalence of AF was 2.31%. Data from the Hospital Quality Monitoring System showed that 3 010 204 inpatients with stroke were admitted to 1853 tertiary care hospitals during 2018. Of those, 2 466 785 (81.9%) were ischaemic strokes (ISs); 447 609 (14.9%) were intracerebral haemorrhages (ICHs); and 95 810 (3.2%) were subarachnoid haemorrhages (SAHs). The average age of patients admitted was 66 years old, and nearly 60% were male. A total of 1555 (0.1%), 2774 (0.6%) and 1347 (1.4%) paediatric strokes (age <18 years) were identified among IS, ICH and SAH, respectively. Over one-third (1 063 892 (35.3%)) of the patients were covered by urban resident basic medical insurance, followed by urban employee basic medical insurance (699 513 (23.2%)) and new rural cooperative medical schema (489 361 (16.3%)). The leading risk factor was hypertension (67.4% for IS, 77.2% for ICH and 49.1% for SAH), and the leading comorbidity was pneumonia or pulmonary infection (10.1% for IS, 31.4% for ICH and 25.2% for SAH). In-hospital death/discharge against medical advice rate was 8.3% for stroke inpatients, ranging from 5.8% for IS to 19.5% for ICH. The median and IQR of length of stay was 10.0 (7.0-14.0) days, ranging from 10.0 (7.0-13.0) in IS to 14.0 (8.0-22.0) in SAH. Data from the Chinese Stroke Center Alliance demonstrated that the composite scores of guideline-recommended key performance indicators for patients with IS, ICH and SAH were 0.77±0.21, 0.72±0.28 and 0.59±0.32, respectively.

The Occurrence and Longitudinal Changes of Cognitive Impairment After Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: More and more evidence suggests that cognitive impairment (CI) after stroke is closely related to the quality of life of stroke patients. The primary aim of this study is to investigate the occurrence and longitudinal changes of CI at different stages after acute ischemic stroke (AIS) in Chinese patients. METHODS: The data of this study come from the impairment of cognition and Sleep after acute ischemic stroke or transient ischemic attack in Chinese patients study (ICONS), a nationwide multicenter prospective registry that recruited consecutive AIS or transient ischemic attack in-hospital patients within 7 days after onset. Patients were followed for Montreal Cognitive Assessment (MoCA) scale at 2-week (2w), 3 months (3m) and 12 months (12m). CI was defined as MoCA score≦22. No cognitive impairment (NCI) was defined as MoCA score>22. RESULTS: A total of 2432 AIS patients were enrolled in this study. Overall, 72.94% of patients were male and the average age was 60.95 years. Median National Institutes of Health Stroke Scale score was 3. The occurrence rate of CI was 52.38%, 35.55% and 34.16% at 2w, 3m and 12m. Among patients with CI at 2w and 3m, 39.9% and 27.9% of patients returned to NCI at next follow-up point. At 3m and 12m follow-up, there were also 9.6% and 12.7% new CI patients. The two cognitive items with the highest abnormal rate were "Delayed recall" (89.35%, 83.33% and 82.80%) and "Visuospatial/executive" (78.91%, 73.42% and 70.08%). The cognitive item with the highest percentage of improved patients was "Orientation" (60.91-76.68%), and the cognitive item with the lowest percentage of improved patients was "Language" (35.85-44.50%). CONCLUSION: CI had a relatively high occurrence at 2w to 12m after AIS. CI at 3m and 12m was significantly lower than that at 2w after stroke. The occurrence of abnormalities and recovery probability for different cognitive items also differed greatly.

Renal Dysfunction and In-Hospital Outcomes in Patients With Acute Ischemic Stroke After Intravenous Thrombolytic Therapy.

Background The impact of estimated glomerular filtration rate (eGFR) on clinical short-term outcomes after stroke thrombolysis with tissue plasminogen activator remains controversial. Methods and Results We analyzed 18 320 ischemic stroke patients who received intravenous tissue plasminogen activator at participating hospitals in the Chinese Stroke Center Alliance between June 2015 and November 2017. Multivariate logistic regression models were used to evaluate associations between eGFR (<45, 45-59, 60-89, and ≥90 mL/min per 1.73 m2) and in-hospital mortality and symptomatic intracerebral hemorrhage, adjusting for patient and hospital characteristics and the hospital clustering effect. Of the 18 320 patients receiving tissue plasminogen activator, 601 (3.3%) had an eGFR <45, 625 (3.4%) had an eGFR 45 to 59, 3679 (20.1%) had an eGFR 60 to 89, and 13 415 (73.2%) had an eGFR ≥90. As compared with eGFR ≥90, eGFR values <45 (6.7% versus 0.9%, adjusted odds ratio, 3.59; 95% CI, 2.18-5.91), 45 to 59 (4.0% versus 0.9%, adjusted odds ratio, 2.00; 95% CI, 1.18-3.38), and 60 to 89 (2.5% versus 0.9%, adjusted odds ratio, 1.67; 95% CI, 1.20-2.34) were independently associated with increased odds of in-hospital mortality. However, there was no statistically significant association between eGFR and symptomatic intracerebral hemorrhage. Conclusions eGFR was associated with an increased risk of in-hospital mortality in acute ischemic stroke patients after treatment with tissue plasminogen activator. eGFR is an important predictor of poststroke short-term death but not of symptomatic intracerebral hemorrhage.

A recombinant measles virus vaccine strain rMV-Hu191 has oncolytic effect against human gastric cancer by inducing apoptotic cell death requiring integrity of lipid raft microdomains.

Live-attenuated strain of measles virus (MV) has oncolytic effect. In this study, the antitumor effect of rMV-Hu191, a recombinant Chinese Hu191 MV generated in our laboratory by efficient reverse genetics system, was evaluated in gastric cancer (GC). From our data, rMV-Hu191 induced cytopathic effects and inhibited tumor proliferation both in vitro and in vivo by inducing caspase-dependent apoptosis. In mice bearing GC xenografts, tumor size was reduced and survival was prolonged significantly after intratumoral injections of rMV-Hu191. Furthermore, lipid rafts, a type of membrane microdomain with specific lipid compositions, played an important role in facilitating entry of rMV-Hu191. Integrity of lipid rafts was required for successful viral infection as well as subsequent cell apoptosis, but was not required for viral binding and replication. CD46, a MV membrane receptor, was found to be partially localized in lipid rafts microdomains. This is the first study to demonstrate that Chinese Hu191 MV vaccine strain could be used as a potentially effective therapeutic agent in GC treatment. As part of the underlying cellular mechanism, the integrity of lipid rafts is required for viral entry and to exercise the oncolytic effect.

Integrated analysis of lncRNA-mRNA co-expression networks in the α-particle induced carcinogenesis of human branchial epithelial cells.

PURPOSE: To identify the mRNA and long noncoding RNA (lncRNA) expression profiles and explore the lncRNA-mRNA co-expression networks associated with the carcinogenesis induced by α-particles. MATERIALS AND METHODS: Immortalized human bronchial epithelial cell line, BEP2D, and its two malignant transformed cell lines, BERP35T-1 and BERP35T-4, were investigated. The lncRNA and mRNA expression profiles of BEP2D, BERP35T-1 and BERP35T-4 were generated. lncRNAs and mRNAs co-expression analysis was performed. RESULTS: The microarray identified 668 lncRNAs in BERP35T-1 cells and 555 in BERP35T-4 cells that were differentially expressed compared to BEP2D cells. The GO terms and KEGG pathway annotation data indicated that mitotic cell cycle, DNA repair, apoptotic processes, and RNA splicing functional pathways were significantly associated with the α-particle induced cell carcinogenesis. Co-expression network analysis revealed 8902 interactions between 495 differentially expressed mRNAs and 430 corresponding lncRNAs in BERP35T-1 cells compared with BEP2D cells. The genes, situated at the important nodes of the co-expression network, include B3GNT5, RAD23, YWHAZ (14-3-3ζ), FBXW11, TGFBR2, LRP6, PSMD11, MYL12A, etc. Conclusions: This pilot study is the first to explore epigenetic mechanisms of α-particle induced carcinogenesis of human bronchial epithelial cells. It provides basic information for further investigation into the detail mechanisms underlying radiation-induced lung cancer.

The Relationship between Cerebral White Matter Integrity and Cognitive Function in Mild Stroke with Basal Ganglia Region Infarcts.

Mild stroke is a known risk factor for dementia. The relationship between cerebral white matter (WM) integrity and cognitive impairment (CI) in mild stroke patients with basal ganglia region infarcts is unknown. Total of 33 stroke patients and 19 age-matched controls underwent diffusion tensor imaging scans and a formal neuropsychological test battery. CI was defined as having a performance score 1.5 SD below the established norm. We compared the differences in Z-scores and Fraction Anisotropy (FA) values among controls, stroke with no CI (NCI) and stroke with CI groups. Multiple linear regressions were performed between FA values in affected regions and neuropsychological tests in stroke patients. The majority of stroke patients were in their 50s (56.90 ± 9.23 years). CI patients exhibited a significantly decreased Z score in visual delayed memory and remarkably decreased FA values in the right external capsule and right fornix (FWE-corrected) compared with NCI patients and controls. In stroke patients, the FA value in the right fornix was positively correlated with delayed visual memory. Mild stroke with basal ganglia region infarcts may be related to widespread abnormality of WM integrity. The lower WM integrity in the right fornix may be a marker of impaired delayed visual memory.

Autophagy Inhibition in Childhood Nephroblastoma and the Therapeutic Significance.

BACKGROUND: Autophagy is a physiological pathway characterized by lysosomedependent self-digestion to recycle damaged or superfluous cellular content. Deregulation of autophagy hampers the maintenance of cellular homeostasis and contributes to tumorigenesis. However, during anticancer therapy, autophagy activation contributes to development of resistance. Thus autophagy has been recognized as an important pathway and a therapeutic target in cancer. Nephroblastoma (Wilm's tumor) is a common childhood malignancy. The role of autophagy in nephroblastoma is largely uninvestigated. OBJECTIVE: This study is to investigate the change of autophagy level in nephroblastoma, and whether autophagy could be a therapeutic target in anaplastic nephroblastoma. METHOD: In clinical samples of childhood nephroblastoma, autophagy activity was evaluated by the expressions of selected autophagy markers as well as the presence of autophagosome ultrastructure. Use of autophagy inhibitors alone and in combination with conventional chemotherapeutics, was studied both in vivo and in vitro. RESULTS: In nephroblastoma, there was decrease in the Beclin 1 level and the number of autophagosomes, suggesting autophagy inhibition. Furthermore, in two anaplastic nephroblastoma cell lines, G401 and SK-NEP1, autophagy inhibitors further enhanced the efficacy of conventional chemotherapeutics including vincristine and cisplatin. In G401 tumor model established in nude mice, combinational use of chloroquine, an inhibitor of autophagy degradation, further decreased the tumor mass compared with single use of the chemotherapeutics vindesine, although no statistical significance was achieved. CONCLUSION: Our results suggest that autophagy deregulation is involved in nephroblastoma, and targeting autophagy can serve as a potential adjuvant strategy for the highly malignant cases.

[Concentrations and Component Profiles PAHs in Surface Soils and Wheat Grains from the Cornfields Close to the Steel Smelting Industry in Handan, Hebei Province].

In this study, paired surface soil and mature wheat grain samples were collected in the cornfields near the large Handan Steel Manufacturer; and the total concentrations and compositional profiles of the parent PAHs were measured, then the spatial distribution characteristics and correlation with total organic carbon fractions in soil were determined. Accordingly, a preliminary source identification was performed, and the association between PAHs in surface soil and wheat grain was briefly discussed. The median concentration of total PAHs in surface soils from the cornfields of Handan was 398.9 ng x g(-1) (ranged from 123.4 ng x g(-1) to 1626.4 ng x g(-1), where around 18% and 10% of all the studied soil samples were over the corresponding quality criteria for total PAHs and B [a] P in soils, respectively. The MMW and HMW species were the main components in the compositional profiles of surface soils. Based on the specific isomeric ratios of PAHs species, coal/biomass combustion and transportation fuel (tail gas) were the dominant mixed sources for the local PAHs emission. The fractions of surface soil TOC had significant positive correlations with the total PAHs and also with the individual components with different rings. In addition, the median concentration of total PAHs in wheat grains collected in the cornfields near the Handan Steel Manufacture was 27.0 ng x g(-1) (ranged from 19.0-34.0 ng x g(-1)). The levels in wheat grains were not high, and lower than the related hygienic standards of food proposed by EU and China. The LMW and MMW PAHs with 2 to 4 rings occupied a larger proportion, more than 84% of the total PAHs, which was largely different from the component profiles in surface soils. This situation suggested that the local sources of PAHs in wheat grains may originate not only from surface soil via root absorption and internal transportation, but also from ambient air through dry and wet deposition on the leaf surface (stoma).

The Management of LDL Cholesterol and Predictors of Goal Achievement in Stroke Patients in China: A Cross-Sectional Study.

OBJECTIVE: To assess the management of low-density lipoprotein cholesterol (LDL-C) in patients suffering from ischemic stroke within 6-12 months and explore the predictors of the achievement of LDL-C target. METHODS: This study was a nation-wide, multicenter, cross-sectional study conducted from July 2013 to August 2013 in mainland China. Patients who had an ischemic stroke within 6-12 months and were more than 18 year old were consecutively included into this study. All data referred to personal information, medical history, medication and results from laboratory tests were collected by face-to-face questionnaires, physical examination and blood tests. The predictors for the achievement of LDL-C target (<1.8 mmol/L or <70 mg/dL) were analyzed by the multivariate analysis. RESULTS: A total of 3956 cases from 56 centers who suffered from ischemic stroke within 6-12 months were finally included into this study. The average serum level of LDL-C in all patients was 2.42 ± 0.91 mmol/L with a median of 2.30 mmol/L and the total LDL-C goal achievement rate was 27.4% (95% CI: 26.0%-28.8%). Lipid-lowering therapy (odds ratio [OR] = 3.54, 95% CI: 2.879-4.388) was the most significant predictor for LDL-C target achievement and female (OR = 0.64, 95% CI: 0.526-0.777), current smoking (OR = 0.714, 95% CI: 0.571-0.892), and the history of dyslipidemia (OR = 0.577, 95% CI: 0.497-0.668) were other three important negative factors for the LDL-C goal achievement. CONCLUSION: Although lipid modulation is recommended as an important intervention for stroke patients in the international guidelines, the goal achievement of LDL-C is still very low in this population in mainland China. The modifiable predictors including the use of lipid-lowering medication and smoking cessation should be improved in secondary prevention of stroke.

EWSR1 regulates mitosis by dynamically influencing microtubule acetylation.

EWSR1, participating in transcription and splicing, has been identified as a translocation partner for various transcription factors, resulting in translocation, which in turn plays crucial roles in tumorigenesis. Recent studies have investigated the role of EWSR1 in mitosis. However, the effect of EWSR1 on mitosis is poorly understood. Here, we observed that depletion of EWSR1 resulted in cell cycle arrest in the mitotic phase, mainly due to an increase in the time from nuclear envelope breakdown to metaphase, resulting in a high percentage of unaligned chromosomes and multipolar spindles. We also demonstrated that EWSR1 is a spindle-associated protein that interacts with α-tubulin during mitosis. EWSR1 depletion increased the cold-sensitivity of spindle microtubules, and decreased the rate of spindle assembly. EWSR1 regulated the level of microtubule acetylation in the mitotic spindle; microtubule acetylation was rescued in EWSR1-depleted mitotic cells following suppression of HDAC6 activity by its specific inhibitor or siRNA treatment. In summary, these results suggest that EWSR1 regulates the acetylation of microtubules in a cell cycle-dependent manner through its dynamic location on spindle MTs, and may be a novel regulator for mitosis progress independent of its translocation.