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1.
J Am Heart Assoc ; 8(20): e012052, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31595836

RESUMO

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.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31627895

RESUMO

Myocardial infarction due to coronary artery occlusion leads to adverse cardiac remodeling and heart failure. Apoptotic loss of cardiomyocytes near the ischemia area enlarges infarct area and promotes cardiac remodeling. Protein arginine methyltransferase 4 (PRMT4), a type I protein arginine methyltransferase, is involved in many cellular processes. Here we aimed to investigate the role of PRMT4 in cardiomyocyte apoptosis and myocardial infarction. We found that PRMT4 expression was markedly increased in ischemic heart and hypoxic cardiomyocytes. In vivo, cardiac-specific overexpression of PRMT4 in mice resulted in decreased survival rate, reduced left ventricular function, and aggravated cardiac remodeling following myocardial infarction. Mechanistically, PRMT4 overexpression promoted hypoxia-induced cardiomyocytes apoptosis, while its inhibition abolished these effects. Taken together, our work suggested an essential role of PRMT4 in myocardial infarction and cardiomyocyte apoptosis.

3.
Stroke ; : STROKEAHA119026872, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31597550

RESUMO

Background and Purpose- Stroke and Alzheimer disease are 2 major causes of neurological disability in aged people and shared overlapping predictors. In recent prospective studies, high Lp(a) [lipoprotein(a)] level is associated with high risk of stroke but low risk of Alzheimer disease. Whether this reflects a causal association remains to be established. The aim of this study is to examine the causal associations of Lp(a) concentrations on ischemic stroke, ischemic stroke subtypes, and Alzheimer disease. Methods- We used 9 single-nucleotide polymorphisms associated with Lp(a) concentrations as instrumental variables. Summary-level data on ischemic stroke and its subtypes were obtained from the Multiancestry Genome-Wide Association Study of Stroke consortium with European individuals ≤446 696 individuals. Summary-level data on Alzheimer disease were obtained from the International Genomics of Alzheimer Project With European individuals ≤54 162 individuals. Two-sample Mendelian randomization (MR) estimates were calculated with inverse-variance weighted, penalized inverse-variance weighted, simple median, weighted median, and MR Pleiotropy Residual Sum and Outlier approaches, and MR-Egger regression was used to explore pleiotropy. Results- Genetically predicted 1-SD log-transformed increase in Lp(a) concentrations was associated with a substantial increase in risk of large artery stroke (odds ratio, 1.20; 95% CI, 1.11-1.30; P<0.001) and a reduce in risk of small vessel stroke (odds ratio, 0.92; 95% CI, 0.88-0.97; P=0.001) and Alzheimer disease (odds ratio, 0.94; 95% CI, 0.91-0.97; P<0.001) using inverse-variance weighted method. No significant association was observed for total ischemic stroke or cardioembolic stroke. MR-Egger indicated no evidence of pleiotropic bias. Results were broadly consistent in sensitivity analyses using penalized inverse-variance weighted, simple median, weighted median, and MR Pleiotropy Residual Sum and Outlier approaches accounting for potential genetic pleiotropy or outliers. Conclusions- This study provides evidence to support that high Lp(a) concentrations was causally associated with an increased risk of large artery stroke but a decreased risk of small vessel stroke and Alzheimer disease. The mechanism underlying the double-edged sword effect of Lp(a) concentrations on neurological system requires further investigation.

4.
Fish Shellfish Immunol ; 93: 517-530, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31386908

RESUMO

Rearing density and disease management are considered as pivotal factors determining shrimp farm productivity and profitability. To systematically investigate the potential mechanisms for density-related differences between disease susceptibility and rearing densities, we conducted comparative transcriptome analysis of the molecular differences between hepatopancreas and intestine of Litopenaeus vannamei under two different rearing densities (800- and 400- shrimp/m3) for 15 d and further analyzed the differences in immune response to Vibrio parahaemolyticus E1 (VPE1) raised under two density conditions. Totally 45 different expression genes (DEGs) were identified in the hepatopancreas under two different rearing densities, the DEGs were grouped into four processes or pathways related to animal immune system. Then, exposure to the VPE1 resulted in 639 DEGs, involved into fourteen immune related processes or pathways. In the intestine, seventeen processes or pathways related to the immune system were identified among the 5470 DEGs under two different rearing densities. 279 DEGs were identified post VPE1 challenge, classified into five processes or pathways associated with the immune system. Meanwhile, the results of growth performance, histopathology and the activities of antioxidant enzymes in the hepatopancreas and intestines of shrimp showed that high density decreased weight gain rate (63.20 ±â€¯1.67% and 18.73 ±â€¯3.35% in the high and low rearing density groups, respectively), severely destroyed the histopathology and inhibited the antioxidant enzymes activities. This study demonstrated that rearing density in L. vannamei significantly impacts susceptibility to the VPE1, via altered transcriptional challenge responses, and thus higher mortality due to disease.

5.
Environ Int ; 132: 105080, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31465951

RESUMO

The well-documented energy balance dynamics within forest ecosystems are poorly implemented in studies of the biophysical effects of forests. This results in limitations to the accurate quantification of forest cooling/warming on local air temperature. Taking into consideration the forest air space, this study proposes a three-layered (canopy, forest air space and soil [CAS]) land surface energy balance model to simulate air temperature within forest spaces (Taf) and subsequently to evaluate its biophysical effects on forest cooling/warming, i.e., the air temperature gradient (∆Ta) between the Taf and air temperature of open spaces (Tao) (∆Ta = Taf - Tao). We test the model using field data for 23 sites across 10 cities worldwide; the model shows satisfactory performance with the test data. High-latitude forests show greater seasonal dynamics of ∆Ta, generating considerable cooling of local air temperatures in warm seasons but minimal cooling or even warming effects during cool seasons, while low-latitude tropical forests always exert cooling effects with less interannual variability. The interannual dynamics of ∆Ta are significantly related to the seasonality of solar geometry and canopy leaf phenology. The differences between forest canopy temperature (Tc) and Tao, which are the two most important terms attributed by the CAS model in impacting Taf, explain a large part of forest cooling and warming (May-July: R2 = 0.35; November-January: R2 = 0.51). The novel CAS model provides a feasible way to represent the energy balance within forest ecosystems and to assess its impacts on local air temperatures globally.

6.
World J Pediatr ; 15(5): 499-505, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31456156

RESUMO

BACKGROUND: Mumps is a common type of respiratory infectious disease caused by mumps virus (MuV), and can be effectively prevented by vaccination. In this study, a reverse genetic system of MuV that can facilitate the rational design of safer, more efficient mumps vaccine candidates is established. METHODS: MuV-S79 cDNA clone was assembled into a full-length plasmid by means of the GeneArt™ High-Order Genetic Assembly System, and was rescued via reverse genetic technology. RT-PCR, sequencing, and immunofluorescence assays were used for rMuV-S79 authentication. Viral replication kinetics and in vivo experimental models were used to evaluate the replication, safety, and immunogenicity of rMuV-S79. RESULTS: A full-length cDNA clone of MuV-S79 in the assembly process was generated by a novel plasmid assemble strategy, and a robust reverse genetic system of MuV-S79 was successfully established. The established rMuV-S79 strain could reach a high virus titer in vitro. The average viral titer of rMuV-S79 in the lung tissues was 2.68 ± 0.14 log10PFU/g lung tissue, and rMuV-S79 group did not induce inflammation in the lung tissues in cotton rats. Neutralizing antibody titers induced by rMuV-S79 were high, long-lasting and could provide complete protection against MuV wild strain challenge. CONCLUSION: We have established a robust reverse genetic system of MuV-S79 which can facilitate the optimization of mumps vaccines. rMuV-S79 rescued could reach a high virus titer and the safety was proven in vivo. It could also provide complete protection against MuV wild strain challenge.

7.
Hypertens Res ; 42(11): 1776-1782, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31451721

RESUMO

Blood pressure (BP) fluctuates widely during the acute phase of stroke. Compared to single BP assessment, patterns of BP over time may have greater power in predicting stroke outcome. This study aims to investigate the effect of BP fluctuation patterns on stroke outcomes in acute ischemic stroke (IS) patients. IS patients within 24 h of onset registered in the BOSS registry between 2012 and 2014 were analyzed. Fluctuation of BP was predefined as the change trend in systolic BP (SBP) from Day 1 to Day 7 after onset and was used to divide patients into groups with sustained high SBP (≥160 mmHg) during the first 7 days (C1); rapid (C2: within the first 2 days) or delayed (C3: after 2 days) decline from high (≥160 mmHg) to low (<160 mmHg); consistently low SBP (C4); and elevation from low to high (C5). The primary stroke outcome was defined as a modified Rankin Scale score ≥3 at 3 months after onset. Of 1,095 IS patients, C1 (n = 90) had the highest risk of poor outcome (23.3%), while C2 (n = 198, risk = 11.6%) and C4 (n = 650, risk = 12.2%) had the lowest risk. C2 and C4 had a significant reduction in poor outcome risk when compared to C1, even after adjustment for average BP and BP variability (BPV) during the first 7 days (adjusted odds ratio[OR]C2 = 0.32, 95% CI: 0.12-0.80; ORC4 = 0.37, 95% CI: 0.14-0.97). The BP fluctuation pattern in the acute phase of IS might be a useful predictive parameter for functional outcome independent of average BP and BPV.

8.
J Clin Hypertens (Greenwich) ; 21(10): 1534-1541, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31468708

RESUMO

Using data from the Blood Pressure and Clinical Outcome in TIA or Ischemic Stroke (BOSS) study, we aim to test the applicability and feasibility of stroke secondary prevention recommendations from the 2017 American College of Cardiology/American Heart Association guideline. Patients were categorized based on their blood pressure (BP) status at 3 months. The nonhypertension group was defined as those without a diagnosis of hypertension. The other patients were further divided into three subgroups according to office BP measured at 3-month visit (BP <130/80, 130-139/80-89, and ≥140/90 mm Hg). The primary outcome was any stroke within one year. The associations between BP status and 1-year prognosis (recurrent stroke, recurrent stroke/TIA, and poor functional outcome [modified Rankin scale score 3-6]) were estimated. Among 2341 IS/TIA patients, additional 1056 patients were classified as uncontrolled hypertension at the 90-day visit according to the new guidelines. Adjusted hazard/odds ratios (95% confidence intervals [CI]) for recurrent stroke in BP <130/80, 130-139/80-89, and ≥140/90 compared with nonhypertension group were 2.42 (95% CI: 0.87-6.76), and 4.30 (95% CI: 1.73-10.70), respectively. The prevalence of hypertension and uncontrolled BP among BOSS study population was substantially higher based on the new guidelines. BP of 130-139/80-89 did not show the worsened clinical outcomes compared with people without hypertension. Our study adds to the growing uncertainty about secondary prevention BP goal for IS/TIA patients.

9.
JAMA Neurol ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31424481

RESUMO

Importance: Dual antiplatelet therapy with clopidogrel and aspirin is effective for secondary prevention after minor ischemic stroke or transient ischemic attack (TIA). Uncertainties remained about the optimal duration of dual antiplatelet therapy for minor stroke or TIA. Objective: To obtain precise estimates of efficacy and risk of dual antiplatelet therapy after minor ischemic stroke or TIA. Design, Setting, and Participants: This analysis pooled individual patient-level data from 2 large-scale randomized clinical trials that evaluated clopidogrel-aspirin as a treatment to prevent stroke after a minor stroke or high-risk TIA. The Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) trial enrolled patients at 114 sites in China from October 1, 2009, to July 30, 2012. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial enrolled patients at 269 international sites from May 28, 2010, to December 19, 2017. Both were followed up for 90 days. Data analysis occurred from November 2018 to May 2019. Interventions: In the 2 trials, patients with minor stroke or high-risk TIA were randomized to clopidogrel-aspirin or aspirin alone within 12 hours (POINT) or 24 hours (CHANCE) of symptom onset. Main Outcomes and Measures: The primary efficacy outcome was a major ischemic event (ischemic stroke, myocardial infarction, or death from ischemic vascular causes). The primary safety outcome was major hemorrhage. Results: The study enrolled 5170 patients (CHANCE) and 4881 patients (POINT). Analysis included individual data from 10 051 patients (5016 in the clopidogrel-aspirin treatment group and 5035 in the control group) with a median age of 63.2 (interquartile range, 55.0-72.9) years; 6106 patients (60.8%) were male. Clopidogrel-aspirin treatment reduced the risk of major ischemic events at 90 days compared with aspirin alone (328 of 5016 [6.5%] vs 458 of 5035 [9.1%]; hazard ratio [HR], 0.70 [95% CI, 0.61-0.81]; P < .001), mainly within the first 21 days (263 of 5016 [5.2%] vs 391 of 5035 [7.8%]; HR, 0.66 [95% CI, 0.56-0.77]; P < .001), but not from day 22 to day 90. No evidence of heterogeneity of treatment outcome across trials or prespecified subgroups was observed. Major hemorrhages were more frequent in the clopidogrel-aspirin group, but the difference was nonsignificant. Conclusions and Relevance: In this analysis of the POINT and CHANCE trials, the benefit of dual antiplatelet therapy appeared to be confined to the first 21 days after minor ischemic stroke or high-risk TIA.

10.
Chin Med J (Engl) ; 132(17): 2053-2058, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31403970

RESUMO

BACKGROUND: Both cortical and cortical-subcortical (cortex-involved) lesions are typically associated with embolic stroke, of which atrial fibrillation (AF) is the common cause. The aim of this study was to find out the associations between cortex-involved stroke, vascular risk factors, and the subtypes (discovery time and duration) of AF. METHODS: This was an imaging study of the China Atrial Fibrillation Screening in Acute Ischemic Stroke Patients (CRIST) trial. Between October 2013 and June 2015, 1511 acute ischemic stroke or transient ischemic attack (TIA) patients within 7 days after stroke onset at 20 Chinese hospitals were enrolled in this prospective, multicenter cohort, cross-sectional study. The final analysis of this sub-study included 243 patients with AF with required magnetic resonance imaging (MRI) sequences. AF was diagnosed by 6-day Holter monitoring and classified by duration of 24 h. Two stroke specialists blinded to the clinical information reviewed MRI (diffusion-weighted MRI). The third stroke specialists, also blinded to the clinical information, assessed the conflicts. Adjusted large artery atherosclerosis as confounding factor, the associations between cortex-involved lesions, vascular risk factors, and the subtype of AF were evaluated by univariate and multivariate regression analyses. RESULTS: Of 243 acute ischemic stroke patients with AF, 190 were known AF and 53 were newly detected AF. There were 28 patients with AF persistent >24 h and 25 persistent ≤24 h in newly detected AF. Patients with newly detected AF were likely to have a fewer history of stroke or TIA (16.98% vs. 36.31%, P = 0.008) and lower fasting blood glucose (5.91 ±â€Š1.83 mmol/L vs. 6.75 ±â€Š3.83 mmol/L, P = 0.030) than patients with known AF. Among these 243 patients, 102 (41.98%) patients were with cortex-involved lesions. Cortex-involved lesions were significantly related to newly detected AF persistent >24 h (odds ratio [OR]: 4.517, 95% confidence interval [CI]: 1.490-13.696, P = 0.008), proteinuria (OR: 3.431, 95% CI: 1.530-7.692, P = 0.021), and glycosylated hemoglobin (OR: 0.632, 95% CI: 0.464-0.861, P = 0.004). CONCLUSIONS: Compared to previously known AF, newly detected AF persistent >24 h was associated with cortex-involved ischemic stroke. CLINICAL TRIAL REGISTRATION: NCT02156765, https://clinicaltrials.gov/ct2/show/record/NCT02156765.

11.
Aging (Albany NY) ; 11(15): 5807-5816, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31422381

RESUMO

In this study we tested whether vascular aging is associated with the risk of first stroke in the Kailuan cohort, a community-based Chinese cohort. For participants aged ≥ 50 years, healthy vascular aging (HVA) was defined as an absence of hypertension and a brachial-ankle pulse wave velocity < the mean + 2 standard deviations, which was determined from a reference sample of healthy participants aged < 30 years. The primary outcome was first stroke (ischemic or hemorrhagic). In total, 11,474 participants were enrolled. The prevalence of HVA decreased from 36.0% in participants aged 50-59 years to 4.7% in those aged ≥ 70 years. During a median follow-up of 3.3 years, the incidence of first stroke was 0.5% in the HVA group but was 2.6% in the Non-HVA group. After adjusting for confounding variables, HVA was associated with a 0.32-fold lower risk of first stroke compared to the Non-HVA group (95% confidence interval, 0.18-0.56; p < 0.001). It thus appears that HVA reduced the risk of first stroke in a community-based Chinese population. This suggests that evaluation of vascular aging as part of public health screening may be useful for stroke risk assessment.

12.
JAMA Netw Open ; 2(7): e198103, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31365109

RESUMO

Importance: Clinical trials have generally shown a neutral effect of early blood pressure (BP) decreases on clinical outcomes after acute ischemic stroke. Whether the effect of early antihypertensive therapy differs for patients with ischemic stroke with or without prior hypertension is unclear. Objective: To investigate the association between immediate antihypertensive treatment and patient outcomes according to the presence or absence of hypertension before stroke onset. Design, Setting, and Participants: This study was a prespecified subgroup analysis of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS), a multicenter, single-blind, blinded end-points randomized clinical trial of 4071 patients with acute ischemic stroke and elevated systolic BP. Patients were recruited from August 2009 to May 2013, and this statistical analysis was performed using the intention-to-treat population from January to October 2018. Interventions: Participants were randomly assigned to receive antihypertensive treatment (aimed at decreasing systolic BP by 10%-25% within the first 24 hours after randomization, achieving systolic BP <140 mm Hg and diastolic BP <90 mm Hg within 7 days, and maintaining this level during hospitalization) or to the control arm (discontinued all antihypertensive medications). Main Outcomes and Measures: Primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3; range 0-6, with higher values indicating greater disability) at 14 days or hospital discharge. Results: In total, 2038 patients were randomized to receive antihypertensive treatment, and 2033 patients were randomized to the control group. The mean (SD) age was 62.0 (10.9) years, and 2604 participants (64.0%) were men. At day 14 or hospital discharge, the primary outcome was not different between the treatment and control groups among patients with or without prior hypertension (P = .97 for homogeneity): odds ratios (ORs) associated with treatment were 1.00 (95% CI, 0.87-1.16) for patients with prior hypertension and 1.00 (95% CI, 0.75-1.32) for patients without. Early antihypertensive treatment was associated with different rates of 3-month recurrent stroke (patients with hypertension: OR, 0.44; 95% CI, 0.25-0.77 vs without hypertension: OR, 3.43; 95% CI, 0.94-12.55; P = .005 for homogeneity) and vascular events (patients with hypertension: OR, 0.66; 95% CI, 0.43-1.02 vs those without hypertension: OR, 1.91; 95% CI, 0.75-4.83; P = .04 for homogeneity) by hypertension history. Conclusions and Relevance: Among patients with acute ischemic stroke, early antihypertensive treatment was not associated with different death and major disability outcomes by hypertension history. However, early antihypertension therapy was associated with a decreased rate of recurrent stroke among patients with a history of hypertension and may inform future studies in the optimal approach to hypertension management in the setting of acute ischemic stroke. Trial Registration: ClinicalTrials.gov identifier: NCT01840072.

13.
World J Pediatr ; 15(5): 511-515, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31377975

RESUMO

BACKGROUND: To describe mumps virus (MuV) used as a vector to express enhanced green fluorescent protein (EGFP) or red fluorescent protein (RFP) genes. METHODS: Molecular cloning technique was applied to establish the cDNA clones of recombinant mumps viruses (rMuVs). rMuVs were recovered based on our reverse genetic system of MuV-S79. The properties of rMuVs were determined by growth curve, plaque assay, fluorescent microscopy and determination of fluorescent intensity. RESULTS: Three recombinant viruses replicated well in Vero cells and similarly as parental rMuV-S79, expressed heterologous genes in high levels, and were genetically stable in at least 15 passages. CONCLUSION: rMuV-S79 is a promising platform to accommodate foreign genes like marker genes, other antigens and immunomodulators for addressing various diseases.

14.
Neurol Res ; 41(10): 893-899, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31328681

RESUMO

Objectives: Although statin therapy is associated with lower recurrence in patients with acute ischaemic stroke, data-evaluating associations between inpatient statin use and stroke recurrence in diabetic patients after acute stroke onset are limited. Methods: This study was based on population data from the Chinese National Stroke Registry. Patients with acute ischaemic stroke and no history of statin therapy were selected. Individuals treated regularly with any type or dosage of statins during acute hospitalization were defined as having inpatient statin therapy. The subjects were divided into two groups according to statin use status during acute hospitalization. Multivariate logistic regression analysis was used to analyse the associations between statin use and stroke recurrence in patients with or without diabetes. Results: A total of 11,429 patients, 2341 (20.48%) with diabetes, were selected for analysis. Statin therapy during hospitalization was documented in 4982 (43.59%). Logistic analysis showed no significant associations between inpatient statin use and stroke recurrence in diabetic subjects at 3 months (OR = 0.90, 95% CI = 0.69-1.16, P = 0.40) or 1 year (OR = 0.92, 95% CI = 0.74-1.16, P = 0.48), but statin use was significantly associated with lower recurrence in non-diabetic patients at both 3 months (OR = 0.80, 95% CI = 0.69-0.92, P = 0.002) and 1 year (OR = 0.82, 95% CI = 0.72-0.93, P = 0.002) after discharge. Conclusion: Inpatient statin use was associated with lower stroke recurrence in non-diabetic patients after acute ischaemic stroke, but no definite association between inpatient statin use and stroke recurrence in patients with diabetes mellitus was found.

15.
J Clin Hypertens (Greenwich) ; 21(8): 1108-1114, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31256446

RESUMO

High blood pressure (BP) is frequent in acute ischemic stroke (IS). However, the impact of BP change patterns during acute phase on clinical outcomes is not conclusive. This study aims to investigate the association between the acute-phase BP trajectories and clinical outcomes in IS patients with high admission BP. The cohort consisted of 316 IS patients with admission systolic BP (SBP) ≥160 mm Hg. SBP trajectories during the first 7 days after onset were characterized using a random effects model. The patients were classified into three groups based on the SBP trajectory curve parameters: sustained high SBP (T1), moderate decrease (T2), and rapid decrease in SBP (T3). Poor outcomes were defined as modified Rankin scale score ≥3 in 3 months after onset. The relationship between SBP trajectory groups and the outcome was examined in multivariable logistic regression models. The decreasing trend was greater in the favorable than in the poor outcome group (P = 0.028 for difference in linear slopes). The incidence of poor outcomes was 25.9%, 13.5%, and 9.8% in T1 (n = 54), T2 (n = 170), and T3 (n = 92) groups, respectively. Compared with T1 group, the decrease in SBP in T2 and T3 groups was significantly associated with lower risk of the poor outcome (odds ratio = 0.25, 95% confidence interval = 0.10-0.67, P = 0.006). These findings suggest that a decrease in BP in the acute phase is predictive of favorable outcomes in IS patients. BP trajectories have a greater power to detect the association than individual BP values at one time-point.

16.
Int J Stroke ; 14(7): 670-677, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31226919

RESUMO

OBJECTIVE: To investigate the comparative efficacy and safety of the low-dose versus standard-dose alteplase using real-world acute stroke registry data from Asian countries. METHODS: Individual participant data were obtained from nine acute stroke registries from China, Japan, Philippines, Singapore, South Korea, and Taiwan between 2005 and 2018. Inverse probability of treatment weight was used to remove baseline imbalances between those receiving low-dose versus standard-dose alteplase. The primary outcome was death or disability defined by modified Rankin Scale scores of 2 to 6 at 90 days. Secondary outcomes were symptomatic intracerebral hemorrhage and death. Generalized linear mixed models with the individual registry as a random intercept were performed to determine associations of treatment with low-dose alteplase and outcomes. RESULTS: Of the 6250 patients (mean age 66 years, 36% women) included in these analyses, 1610 (24%) were treated with low-dose intravenous alteplase. Clinical outcomes for low-dose alteplase were not significantly different to those for standard-dose alteplase, adjusted odds ratios for death or disability: 1.00 (0.85-1.19) and symptomatic intracerebral hemorrhage 0.87 (0.63-1.19), except for lower death with borderline significance, 0.77 (0.59-1.01). CONCLUSIONS: The present analyses of real-world Asian acute stroke registry data suggest that low-dose intravenous alteplase has overall comparable efficacy for functional recovery and greater potential safety in terms of reduced mortality, to standard-dose alteplase for the treatment of acute ischemic stroke.

17.
Cancer Lett ; 460: 108-118, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31226409

RESUMO

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.

18.
BMJ ; 365: l2211, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171523

RESUMO

OBJECTIVE: To test the hypothesis that ticagrelor plus aspirin is safe and superior to clopidogrel plus aspirin for reducing high platelet reactivity at 90 days and stroke recurrence in patients with minor stroke or transient ischaemic attack, particularly in carriers of the CYP2C19 loss-of-function allele and patients with large artery atherosclerosis. DESIGN: Open label, blinded endpoint, randomised controlled phase II trial. SETTING: Prospective studies conducted at 26 centres in China, August 2015 to March 2017. PARTICIPANTS: 675 patients with acute minor stroke or transient ischaemic attack. INTERVENTION: Ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 mg loading dose, 75 mg daily thereafter) on a background of aspirin (100 mg daily for the first 21 days) within 24 hours of symptom onset. MAIN OUTCOME MEASURES: Primary outcome was the proportion of patients with high platelet reactivity at 90 days. High platelet reactivity was defined as P2Y12 reaction units of more than 208. Secondary outcomes included high platelet reactivity at 90 days (7 days either way) in patients carrying genetic variants that would affect clopidogrel metabolism, and any stroke (ischaemic or haemorrhagic) recurrence at 90 days (7 days either way), six months, and one year. RESULTS: At 90 days, high platelet reactivity occurred in 35 (12.5%) of 280 patients in the ticagrelor/aspirin group and 86 (29.7%) of 290 patients in the clopidogrel/aspirin group (risk ratio 0.40; 95% confidence interval 0.28 to 0.56; P<0.001), and in 10.8% versus 35.4% (0.31; 0.18 to 0.49; P<0.001) of patients carrying CYP2C19 loss-of-function alleles. Stroke occurred in 21 (6.3%) of 336 patients in the ticagrelor/aspirin group and 30 (8.8%) of 339 patients in the clopidogrel/aspirin group (hazard ratio 0.70; 95% confidence interval 0.40 to 1.22; P=0.20). Patients with large artery atherosclerosis in the ticagrelor/aspirin group had a lower stroke recurrence at 90 days than those in the clopidogrel/aspirin group (6.0% v 13.1%; hazard ratio 0.45, 95% confidence interval 0.20 to 0.98; P=0.04). No difference was seen in the rates of major or minor haemorrhagic events between the ticagrelor/aspirin and clopidogrel/aspirin groups (4.8% v 3.5%; P=0.42). CONCLUSION: Patients with minor stroke or transient ischaemic attack who are treated with ticagrelor plus aspirin have a lower proportion of high platelet reactivity than those who are treated with clopidogrel plus aspirin, particularly for those who are carriers of the CYP2C19 loss-of-function allele. The results of this study should be evaluated further in large scale, phase III trials and in different populations. TRIAL REGISTRATION: Clinicaltrials.gov NCT02506140.


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Ataque Isquêmico Transitório/tratamento farmacológico , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Ticagrelor/uso terapêutico , Adulto , Idoso , Plaquetas/efeitos dos fármacos , China , Quimioterapia Combinada , Feminino , Humanos , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/fisiologia , Estudos Prospectivos , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento
19.
Stroke ; 50(8): 2007-2015, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31238826

RESUMO

Background and Purpose- Traditional risk factors for ischemic stroke are body stressors that are related to autonomic autonomic system (ANS) dysfunction. The value of ABCD2 score (age, blood pressure, clinical features, duration of symptoms, diabetes) to predict ischemic stroke after transient ischemic attack is compromised by the inclusion of a limited number of stressors. We aimed to assess whether markers of ANS function and stress could predict the occurrence of secondary ischemic events after transient ischemic attack or minor stroke. Methods- This is a prospective cohort study in which 201 patients were recruited within 48 hours after initial transient ischemic attack or minor stroke and followed for 90 days to assess the development of secondary ischemic events. ABCD2 score, heart rate variability (HRV) parameters as markers of ANS function, and psychological stress were assessed. Logistic regression and area under the curve (AUC) were used to assess the models' predictive ability. Results- Morning high frequency (HF) HRV power and changes in HF HRV from morning to afternoon (daytime HF changes) were the most useful HRV predictors for both ischemic events (AUC=0.61 and 0.70) and ischemic stroke (AUC=0.62 and 0.72). Compared with ABCD2 score, 2 HRV-based stress models showed higher predictive ability for ischemic events (AUC=0.82 versus 0.63, 0.76 versus 0.63; P<0.05) and ischemic stroke (AUC=0.87 versus 0.64, 0.82 versus 0.64; P<0.05). Conclusions- Assessing the effects of stress on the ANS may be an innovative way to stratify the risk of ischemic events after transient ischemic attack or minor stroke. New risk stratification by assessing the dynamic features of ANS dysfunction and stress may help identify high-risk sub-populations that may benefit from added management.

20.
Ann Neurol ; 86(3): 419-426, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31237713

RESUMO

OBJECTIVE: Dual antiplatelet therapy (DAT) with clopidogrel plus aspirin has been suggested by American Heart Association/American Stroke Association guidelines for minor stroke (MS) and transient ischemic attack (TIA) patients. The purpose of this study was to find the potential subgroups that benefit from DAT. We aimed to compare the efficacy of clopidogrel-aspirin therapy with that of aspirin therapy in MS/TIA patients stratified by CYP2C19 genotype and risk profiles. METHODS: CYP2C19 loss-of-function allele (LoFA) carriers were defined as patients with LoFA of either *2 or *3. Low- and high-risk profile was defined as Essen Stroke Risk Score (ESRS) <3 and ≥3, respectively. Stroke recurrence at 1 year was considered primary outcome. RESULTS: Of a total 2,933 MS/TIA patients, there were 1,726 (58.8%) LoFA carriers and 1,068 (36.4%) patients at high risk (ESRS ≥3). No significant difference for stroke recurrence between the clopidogrel-aspirin group and aspirin alone group was found in LoFA carriers (11.2% vs 13.3%, hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.64~1.09). In stratified analyses by CYP2C19 genotype and ESRS, HRs (95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 1.00 (0.70~1.42), 0.63 (0.41~0.97), 0.62 (0.40~0.96), and 0.52 (0.31~0.88) among subgroups of LoFA carriers at low risk, LoFA carriers at high risk, LoFA noncarriers at low risk, and LoFA noncarriers at high risk, respectively, with p = 0.021 for interaction. INTERPRETATION: Overall, LoFA carriers do not benefit from DAT, but there is significant benefit for LoFA carriers who are at high risk. The benefit of clopidogrel in Chinese MS/TIA patients depends on CYP2C19 genotype and risk profile. ANN NEUROL 2019;86:419-426.

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