Cucurbit[8]uril-based supramolecular theranostics.

Different from most of the conventional platforms with dissatisfactory theranostic capabilities, supramolecular nanotheranostic systems have unparalleled advantages via the artful combination of supramolecular chemistry and nanotechnology. Benefiting from the tunable stimuli-responsiveness and compatible hierarchical organization, host-guest interactions have developed into the most popular mainstay for constructing supramolecular nanoplatforms. Characterized by the strong and diverse complexation property, cucurbit[8]uril (CB[8]) shows great potential as important building blocks for supramolecular theranostic systems. In this review, we summarize the recent progress of CB[8]-based supramolecular theranostics regarding the design, manufacture and theranostic mechanism. Meanwhile, the current limitations and corresponding reasonable solutions as well as the potential future development are also discussed.

Dynamically assembled nanomedicine based on host-guest molecular recognition for NIR laser-excited chemotherapy and phototheranostics.

Nanomedicines combining multimodal therapeutic modalities supply opportunities to eliminate tumors in a safe and efficient manner. However, the rigid encapsulation and covalent conjugation of different therapeutic reagents suffer from the complicated preparation process, premature drug leakage and severe adverse events. Herein, we report a self-enhanced supramolecular nanomedicine (SND) based on the host-guest molecular recognition between ß-cyclodextrin (ß-CD) and camptothecin (CPT) for trimodal synergistic chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT) using a single 670 nm near-infrared (NIR) laser. Thioketal bond and polyethylene glycol (PEG) segment are introduced into the structure of CPT-tk-PEG prodrug, thus the premature release of CPT is efficiently inhibited and the specific drug release is realized at tumor site where singlet oxygen (1O2)-generated PDT is performed. A boron dipyrromethene (BODIPY) theranostic agent is anchored onto ß-CD, endowing SND with capabilities of fluorescence imaging, PDT and PTT. Benefiting from the supramolecular assembly, not only the solubility of CPT is improved by 40 times, but also the blood circulation time and tumor accumulation of SND are greatly promoted. In vivo, SND can effectively induce the immunogenic cell death (ICD) of tumor cells, thus performing prominent inhibition against both primary and distal tumors, and even anti-metastasis effect against liver without causing obvious systemic toxicity. STATEMENT OF SIGNIFICANCE: Although nanomedicines supply opportunities to eliminate tumors in an efficient manner, they usually suffer from premature drug leakage, complicated preparation process and severe side effects owing to the rigid encapsulation or covalent conjugation. Based on the host-guest molecular recognition, we developed a self-enhanced SND for synergistic chemotherapy, photodynamic therapy and photothermal therapy. Introduction of thioketal bond in CPT prodrug avoided the premature drug release, and the specific drug release was realized in the tumor cells. Profiting from the facile supramolecular assembly strategy, SND not only displayed a primary anticancer efficacy with a low systemic toxicity, but also efficiently inhibited the growth of distal tumors, contributing a vaccine-like function to eradicate the recurrent and metastatic tumors.

Tranexamic acid for acute intracerebral haemorrhage growth based on imaging assessment (TRAIGE): a multicentre, randomised, placebo-controlled trial.

BACKGROUND: Studies show tranexamic acid can reduce the risk of death and early neurological deterioration after intracranial haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in intracerebral haemorrhage patients susceptible to haemorrhage expansion. METHODS: We did a prospective, double-blind, randomised, placebo-controlled trial at 10 stroke centres in China. Acute supratentorial intracerebral haemorrhage patients were eligible if they had indication of haemorrhage expansion on admission imaging (eg, spot sign, black hole sign or blend sign), and were treatable within 8 hours of symptom onset. Patients were randomly assigned (1:1) to receive either tranexamic acid or a matching placebo. The primary outcome was intracerebral haematoma growth (>33% relative or >6 mL absolute) at 24 hours. Clinical outcomes were assessed at 90 days. RESULTS: Of the 171 included patients, 124 (72.5%) were male, and the mean age was 55.9±11.6 years. 89 patients received tranexamic acid and 82 received placebo. The primary outcome did not differ significantly between the groups: 36 (40.4%) patients in the tranexamic acid group and 34 (41.5%) patients in the placebo group had intracranial haemorrhage growth (OR 0.96, 95% CI 0.52 to 1.77, p=0.89). The proportion of death was lower in the tranexamic acid treatment group than placebo group (8.1% vs 10.0%), but there were no significant differences in secondary outcomes including absolute intracranial haemorrhage growth, death and dependency. CONCLUSIONS: Among patients susceptible to haemorrhage expansion treated within 8 hours of stroke onset, tranexamic acid did not significantly prevent intracerebral haemorrhage growth. Larger studies are needed to assess safety and efficacy of tranexamic acid in intracerebral haemorrhage patients.

Benefit and risk of early intravenous heparin after thrombolysis in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: We performed a retrospective analysis of the "Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China)" registry to explore the benefit and risk of intravenous thrombolysis (IVT) followed by intravenous heparin (IVH) in acute ischemic stroke (AIS) patients. METHODS: In the TIMS-China database, the patients who received IVH immediately after IVT (Early IVH group) and those who initiated antithrombotic therapy (ATT) until 24 hr after IVT (Standard ATT group) were screened for this comparison. Propensity score (PS) matching was performed between both groups. The logistic regression analysis was performed in the matched population to compare all the efficacy and safety outcomes. RESULTS: Of 1,437 patients in this study, 119 received early IVH and 1,318 cases initiated standard ATT. After PS matching (1:2), 117 pairs were identified. The early IVH group had higher proportions of neurological improvement at 24 hr (OR = 2.24, 95% CI = 1.42-3.53) and 7 days (OR = 1.92, 95% CI = 1.22-3.03), better chance of excellent recovery (OR = 1.69, 95% CI = 1.07-2.67) and functional independence (OR = 1.77, 95% CI = 1.13-2.78) at 90 days, and a lower 90-day mortality (OR = 0.44, 95% CI = 0.21-0.92) than standard ATT group. Additionally, early IVH did not increase the risk of symptomatic intracranial hemorrhage (OR = 0.92, 95% CI = 0.34-2.48). CONCLUSIONS: IVH immediately after thrombolysis seems to be safe and potentially more effective as compared with standard ATT delay of 24 hr for a subset of AIS patients.

Ticagrelor plus aspirin versus clopidogrel plus aspirin for platelet reactivity in patients with minor stroke or transient ischaemic attack: open label, blinded endpoint, randomised controlled phase II trial.

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.

Association of Cardioembolism and Intracranial Arterial Stenosis with Outcomes of Mechanical Thrombectomy in Acute Ischemic Stroke.

OBJECTIVE: To estimate the association of different etiologies of cardioembolism (CE), intracranial arterial stenosis (ICAS), or the combination of these conditions with outcomes of mechanical thrombectomy in acute ischemic stroke. METHODS: Data from the intervention group of the Endovascular therapy for Acute ischemic Stroke Trial (EAST) were analyzed. In 140 patients, the presence of CE, ICAS, neither CE nor ICAS, or both conditions was assessed. The primary outcome was a favorable outcome at 90 days (modified Rankin Scale score 0-2); secondary outcomes included successful reperfusion (modified Thrombolysis In Cerebral Infarction grade 2b-3), symptomatic intracerebral hemorrhage, and 90-day mortality. RESULTS: Of 140 patients, 47 had neither CE nor ICAS, 35 had ICAS but not CE, 46 had CE but not ICAS, and 12 had both CE and ICAS. The rate of favorable outcome was 67.1% in the no CE and no ICAS group, 74.3% in the ICAS without CE group, 41.3% in the CE without ICAS group, and 33.3% in the CE and ICAS group. The CE and ICAS group had poor outcomes (odds ratio = 0.20 after adjusting for age, sex, and National Institutes of Health Stroke Scale score; 95% confidence interval, 0.04-0.95; P = 0.043). No significant differences were observed in secondary outcomes. CONCLUSIONS: The presence of both CE and ICAS was associated with poor outcome in patients with anterior circulation large-vessel occlusion treated with endovascular thrombectomy. Future studies are warranted to further explore this association.

Oxidized low-density lipoprotein predicts recurrent stroke in patients with minor stroke or TIA.

OBJECTIVE: To investigate the association between oxidized low-density lipoprotein (oxLDL) and recurrent stroke in patients with minor stroke or TIA. METHODS: In the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial, baseline oxLDL levels were blindly measured in plasma with the 4E6 antibody in the core laboratory. The primary outcome was any stroke within 90 days. The secondary outcomes included any stroke within 1 year and ischemic stroke and combined vascular events within 90 days and 1 year. The associations of oxLDL with recurrent stroke were analyzed by Cox proportional hazards. RESULTS: Among 3,019 patients included in this study, the median (interquartile range) of oxLDL was 13.96 (6.65-28.81) µg/dL. After adjustment for conventional confounding factors, patients in the highest oxLDL quartile (≥28.81 µg/dL) had a higher risk of recurrent stroke within 90 days (hazard ratio 1.43, 95% confidence interval 1.03-1.98) compared to those in the lowest oxLDL quartile (<6.65 µg/dL). Similar results were found for secondary outcomes. We also found a J-shaped association between oxLDL and risk of each outcome. There were no significant interactions between oxLDL and low-density lipoprotein and use of dual antiplatelet, antihypertensive, antidiabetic, and statins agents. CONCLUSIONS: Elevated oxLDL levels can independently predict recurrent stroke in patients with minor stroke or TIA. CLINICALTRIALSGOV IDENTIFIER: NCT00979589.

Identification of CSF biomarkers by proteomics in Guillain-Barré syndrome.

The purpose of the present study was to screen for differentially expressed proteins in the cerebrospinal fluid (CSF) of patients with Guillain-Barré syndrome (GBS). The identification of differentially expressed protein can provide new targets for understanding the pathogenic mechanism, early clinical diagnosis, prognosis and for measuring the effectiveness of interventions. We enrolled 50 GBS patients and 50 meningitis patients (control group) to compare protein expression in CSF. The GBS cases included 28 cases of acute inflammatory demyelinating polyneuropathy (AIDP) and 22 cases of acute motor axonal neuropathy (AMAN). We then performed two-dimensional differential in-gel electrophoresis combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to identify the differentially expressed proteins. The expression levels were validated by ELISA, and their accuracy, sensitivity, and specificity in GBS diagnosis were analyzed by the receiver operating characteristic curve. Three differentially expressed proteins were identified, including the upregulated haptoglobin (Hp) and heat shock protein 70 (Hsp70), and downregulated cystatin C. There were no significant differences between the AIDP and AMAN patients in the positive rates and quantitative expression levels of the three differentially expressed proteins. The accuracy of Hp in the diagnosis of GBS was 0.835, sensitivity was 86.7%, and specificity was 88.2%. The accuracy of cystatin C in the diagnosis of GBS was 0.827, sensitivity was 85.5%, and specificity was 89.7%. The accuracy of Hsp70 in the diagnosis of GBS was 0.841, its sensitivity was 87.8%, and its specificity was 92.3%. Hp and Hsp70 are significantly increased, and cystatin C is downregulated in CSF of GBS patients, which provides important biomarkers for early GBS diagnosis, although these proteins cannot distinguish AIDP and AMAN.

High SBP trajectories are associated with risk of all-cause death in general Chinese population.

OBJECTIVE: This study aimed to investigate whether long-term trajectories of high SBP can further predict risk of all-cause death in Chinese adults. METHODS: We used a community-based cohort of 84 363 participants without myocardial infarction, stroke, or cancer, in 2010. SBP trajectories used latent mixture modeling with data from 2006, 2008, and 2010. Cox proportional hazards models were used to examine the association between SBP trajectories and risk of all-cause death in 2010-2015. RESULTS: We identified five distinct SBP trajectory patterns based on the 2006 status and the pattern of change during 2006-2010. Each pattern was labeled according to the SBP levels and pattern over time: low-stable (n = 21 249), moderate-stable (n = 39 390), moderate-increasing (n = 9634), elevated-decreasing (n = 9094) and elevated-stable (n = 4996). During 5.24 ±â€Š1.04 years of follow-up, we documented 4131 deaths. After adjusting for potential confounding factors and using the low-stable group as a reference, hazard ratios [95% confidence interval (CI)] of all-cause death for the moderate-stable, moderate-increasing, elevated-decreasing, and elevated-stable groups were 1.32 (1.12-1.56), 1.60 (1.26-2.04), 1.69 (1.38-2.07), and 1.75 (1.33-2.32), respectively. Although the moderate-stable trajectory exhibited SBP ranges within the 'normal' range (126.90-130.09 mmHg) in 2006-2010, this group had higher all-cause death risk relative to the low-stable trajectory group (109.86-112.46 mmHg) (adjusted hazard ratio = 1.32, 95% CI 1.12-1.56). CONCLUSION: High SBP trajectories are independent risk factors for all-cause death. Our findings suggest increasing SBP trajectories within the currently designated 'normal' range may still increase risk of all-cause death.

The relationship between oxidized low-density lipoprotein and the NIHSS score among patients with acute ischemic stroke: The SOS-Stroke Study.

BACKGROUND AND AIMS: Oxidized low-density lipoprotein (oxLDL) has a defined role in the genesis and development of atherosclerosis, however, whether it is related to severity of neurological deficits is rarely reported. The aim of our study was to investigate the potential association between oxLDL and the National Institutes of Health Stroke Scale (NIHSS) score among patients with acute ischemic stroke. METHODS: Between January 2014 and October 2014, we recruited 4111 patients with acute ischemic stroke (AIS), who were admitted within 7 days-43 hospitals in China, and participated in the SOS-Stroke Study. We collected detailed clinical data and then tested the relationship between oxLDL and the NIHSS score using a multivariate linear regression analysis. RESULTS: After adjusting for age, gender, ethnicity, marriage and other confounding variables, the elevated NIHSS score was significantly associated with increased oxLDL levels, and each 1-µg/dL elevation in oxLDL concentration resulted in an increase of 0.027 in the NIHSS score. CONCLUSIONS: A positive correlation was found between plasma levels of oxLDL and the NIHSS score in patients with acute ischemic stroke. Higher plasma levels of oxLDL potentially suggest a worse prognosis in AIS patients.

Estimated Glomerular Filtration Rate, Proteinuria, and Risk of Cardiovascular Diseases and All-cause Mortality in Diabetic Population: a Community-based Cohort Study.

Data about associations between estimated glomerular filtration rate (eGFR) and proteinuria with cardiovascular diseases (CVDs) and all-cause mortality among diabetic population is less described. We aimed to describe these associations in Chinese diabetic population, and investigate the difference between sexes. The study was based on 8,301 diabetic participants in the Kailuan study, who was free of CVDs at baseline. We used Cox proportional hazard models to examine the associations of eGFR and proteinuria with CVDs and all-cause mortality. A stratified analysis by gender was performed. During a median follow-up of 8.05 years, 917 deaths and 813 incident CVDs occurred. Adjusted for all potential confounders, eGFR was associated with all-cause mortality, but not associated with incidence of CVDs. Compared to those with eGFR ≥ 90 ml/min/1.73 m2, Participants with eGFR <45 ml/min/1.73 m2 had 1.50 fold higher risk of all-cause mortality. Adjusted for all potential confounders, proteinuria was associated with risk of both CVDs and all-cause mortality. Additionally, the risk of all-cause mortality by proteinuria was greater in women than that in men. Both lower eGFR and proteinuria are independent risk factors for all-cause mortality in the Chinese diabetic population. Proteinuria conferred excessive risk for CVDs, and especially in women.

Effects of puerarin combined with conventional therapy on ischemic stroke.

This study evaluated the use of conventional therapy combined with puerarin on ischemic stroke. Eighty patients with ischemic stroke admitted to Tangshan Gongren Hospital from March 2014 to September 2015 were randomly divided into two groups. The control group was treated with conventional therapy. The observation group was treated with an additional puerarin injection of 400 mg/day. The patients in both groups were examined for clinical neurological signs and symptoms. The levels of biochemical markers as well as changes in hemorheology were measured after the intervention and compared among the groups. Our results indicate that the language expression was significantly better in the observation group after the intervention (p<0.05). Additionally, the aphasia quotient was higher (p<0.05), the neurological deficit score was lower (p<0.05), and the functional ability score was higher (p<0.05). The plasma S-100B and NSE levels were lower (p<0.05), the whole blood viscosity and plasma viscosity were lower (p<0.05), and the levels of corticotropin-releasing hormone, corticotropin, cortisol, adrenaline and norepinephrine were lower (p<0.05). Our findings led to the conclusion that the use of puerarin can effectively improve the language function, reduce neurological damage, reduce blood viscosity, reduce stress response and improve quality of life.

High On-Treatment Platelet Reactivity to Adenosine Diphosphate Predicts Ischemic Events of Minor Stroke and Transient Ischemic Attack.

BACKGROUND: This study aimed to evaluate the relationship between thromboelastography adenosine diphosphate maximum amplitude (TEG-ADPMA) and recurrent ischemic events in patients with minor ischemic stroke or high-risk transient ischemic attack (TIA). METHODS: A total of 265 patients received dual antiplatelet therapy were consecutively enrolled. High on-treatment platelet reactivity (HTPR) to ADP was assessed by TEG-ADPMA and detected the CYP2C19 genotype; recurrent ischemic events were followed up for 90 days after onset. The difference of recurrent ischemic events was analyzed with or without HTPR to ADP by the Kaplan-Meier, and further to determine the difference of recurrent ischemic events in each group according to TEG-ADPMA-based tertile distribution. RESULTS: A total of 23 (8.6%) patients had recurrent ischemic events. TEG-ADPMA greater than or equal to 48 mm had good predictive value. Whether these patients were divided into 2 groups or 3 groups, the HTPR to ADP group had higher risk of recurrent ischemic events than the normal on-treatment platelet reactivity to ADP group by the Kaplan-Meier (all, P < .05). The tertile distribution map showed that the results of recurrent ischemic events were statistically significant in the third tertile group compared with the other two groups (all, P < .03); also, the third tertile group had a higher rate of carriers of at least 1 CYP2C19 reduced-function allele than the other two groups (P < .05). CONCLUSIONS: In patients with minor ischemic stroke and high-risk TIA, the TEG-ADPMA could predict recurrent ischemic events and has auxiliary effect on clinical decision-making.

The association between high on-treatment platelet reactivity and early recurrence of ischemic events after minor stroke or TIA.

OBJECTIVES: To evaluate the role of HTPR in predicting early recurrence of ischemic events in patients with minor ischemic stroke or high-risk TIA. METHODS: From January 2014 to September 2014, a single center continuously enrolled patients with minor ischemic stroke or high-risk TIA and gave them antiplatelet therapy consisting of aspirin with clopidogrel. HTPR was assessed by TEG after 7 days of antiplatelet therapy and detected CYP2C19 genotype. The incidence of recurrent ischemic events was assessed 3 months after onset. The incidence of recurrent ischemic events was compared between the HTPR and NTPR groups with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to determine the risk factors associated with recurrent ischemic events. RESULTS: We enrolled 278 eligible patients with minor ischemic stroke or high-risk TIA. Through TEG testing, patients with HTPR were 22.7%, and carriers were not associated with HTPR to ADP by TEG-ADP(%) (p = 0.193). A total of 265 patients completed 3 months of follow-up, and Kaplan-Meier analysis showed that patients with HTPR had a higher percentage of recurrent ischemic events compared with patients with NTPR (p = 0.002). In multivariate Cox proportional hazards models, history of ischemic stroke or TIA (HR 4.45, 95% CI 1.77-11.16, p = 0.001) and HTPR (HR 3.34, 95% CI 1.41-7.91, p = 0.006) was independently associated with recurrent ischemic events. DISCUSSION: In patients with minor stroke or TIA, the prevalence of HTPR was 22.7%, and HTPR was independently associated with recurrent ischemic events.

Effect of ticagrelor with clopidogrel on high on-treatment platelet reactivity in acute stroke or transient ischemic attack (PRINCE) trial: Rationale and design.

Rationale and aim Little is known about the safety and efficacy of the combination of ticagrelor and aspirin in acute ischemic stroke. This study aimed to evaluate whether the combination of ticagrelor and aspirin was superior to that of clopidogrel and aspirin in reducing the 90-day high on-treatment platelet reactivity for acute minor stroke or transient ischemic attack, especially for carriers of cytochrome P450 2C19 loss-of-function allele. Sample size and design This study was designed as a prospective, multicenter, randomized, open-label, active-controlled, and blind-endpoint, phase II b trial. The required sample size was 952 patients. It was registered with ClinicalTrials.gov (NCT02506140). Study outcomes The primary outcome was the proportion of patients with high on-treatment platelet reactivity at 90 days. High on-treatment platelet reactivity is defined as the P2Y12 reaction unit >208 measured using the VerifyNow P2Y12 assay. Conclusion The Platelet Reactivity in Acute Non-disabling Cerebrovascular Events study explored whether ticagrelor combined with aspirin could reduce further the proportion of patients with high on-treatment platelet reactivity at 90 days after acute minor stroke or transient ischemic attack compared with clopidogrel and aspirin.

Association of Oxidized Low-Density Lipoprotein With Prognosis of Stroke and Stroke Subtypes.

BACKGROUND AND PURPOSE: The association between oxidized low-density lipoprotein (oxLDL) and the long-term prognosis of stroke is unclear. The aim of this study is to investigate whether oxLDL levels contribute to the prognosis of stroke and stroke subtypes. METHODS: All patients with ischemic stroke were recruited from the SOS-Stroke (Study of Oxidative Stress in Patients With Acute Ischemic Stroke) and classified into 5 different subtypes, according to the TOAST criteria (Trial of Org 10172 in Acute Stroke Treatment). We measured oxLDL levels and followed up with patients at 1 year after stroke onset. We analyzed the association between oxLDL and the clinical outcomes of death and poor functional outcome (modified Rankin Scale score of 3-6) of stroke and different stroke subtypes. RESULTS: Among the 3688 patients included in this study, 293 (7.94%) were deceased at the 1-year follow-up and 1020 (27.66%) had a poor functional outcome. Patients in the highest oxLDL quartile had a higher risk of 1-year stroke mortality (hazard ratio, 1.61; 95% confidence interval, 1.10-2.33; P<0.001) and a poor functional outcome (odds ratio, 1.48; 95% confidence interval, 1.15-1.89; P<0.001) compared with the lowest oxLDL quartile. In the subgroup analyses, oxLDL was only significantly associated with death and poor functional outcome in the large-artery atherosclerosis subgroup (P<0.05) and small-artery occlusion subgroup (P<0.05). CONCLUSIONS: High levels of oxLDL were associated with the high risk of death and poor functional outcome within 1 year after stroke onset, especially in large-artery atherosclerosis and small-artery occlusion stroke subtypes.

Cumulative systolic blood pressure exposure in relation to cognitive function in middle-aged and elderly adults: A prospective, population-based study.

The association between systolic blood pressure (SBP) and cognitive function is controversial in elderly adults. In addition, few studies focused on the cumulative effect of SBP. We aimed to investigate the association between cumulative SBP exposure and cognitive function among middle-aged and elderly adults.The analysis was based on the Asymptomatic Polyvascular Abnormalities Community (APAC) study. The primary predictor was the cumulative SBP calculated by consecutive SBP values measured through baseline (2006-2007) up to the fourth examination (2012-2013). The cognitive function was estimated by mini-mental state examination (MMSE) in the fourth examination. Linear regression and logistic regression analyses were used to investigate the association between cumulative SBP and cognitive function.Among 2211 participants (41.4% female, aged 40-94 years), 167 (7.55%) were diagnosed with cognitive impairment (MMSE score < 24). Higher cumulative exposure to SBP (per SD increment) was independently associated with poor cognitive performance after controlling for multiple factors (P < 0.001). We observed nondifferential association between men and women. However, higher cumulative SBP in the adults aged ≥60 years had a stronger association with poor cognitive performance compared with that in adults aged 40 to 60 years.Greater exposure to cumulative SBP is associated with worse cognitive performance among middle-aged and elderly adults. This association is similar between men and women, but stronger in elderly adults.

The prevalence of carotid plaque with different stability and its association with metabolic syndrome in China: The Asymptomatic Polyvascular Abnormalities Community study.

Few studies have investigated the prevalence of carotid plaque with different stability in Chinese. As is well known, carotid atherosclerosis is tightly associated with metabolic syndrome (MetS); however, the data about the association between the presence of carotid plaque with different stability and MetS was limited. The aim of our study was to investigate the prevalence of carotid plaque with different stability and its potential association with MetS in general Chinese population.The Asymptomatic Polyvascular Abnormalities Community study is a community-based study to investigate the epidemiology of asymptomatic polyvascular abnormalities in Chinese adults. A total of 5393 participants were finally eligible and included in this study. The carotid plaque and its stability were assessed using ultrasonography. The MetS was defined using the criteria from US National Cholesterol Education Program-Adult Treatment Panel III. Data were analyzed with multivariate logistic regression models.Of the 5393 subjects, 1397 (25.9%) participants had stable carotid plaque, 1518 (28.1%) had unstable carotid plaque in participants, and 1456 (27.0%) had a MetS. MetS was, respectively, significantly associated with the prevalence of carotid plaque (odds ratio [OR]: 1.25; 95% confidence interval [CI]: 1.07, 1.47), stable carotid plaque (OR: 1.23; 95% CI: 1.02,1.48), and unstable carotid plaque (OR: 1.27; 95% CI: 1.03,1.56) after adjusting for age, gender, level of education, income, smoking, drinking, physical activity, body mass index, low-density lipoprotein, and high-sensitivity C-reactive protein. With the number of MetS components, the prevalence of carotid plaque, stable carotid plaque, and unstable carotid plaque significantly increased (P for trend <0.0001), respectively.In summary, the prevalence of carotid plaque was 54.1%, stable carotid plaque was 25.9%, and unstable carotid plaque was 28.1%. Our study revealed that the prevalence of carotid plaque, stable carotid plaque, and unstable carotid plaque was, respectively, significantly associated with MetS in the general population.

Carotid intima-media thickness and cognitive function in a middle-aged and older adult community: a cross-sectional study.

The relationship between atherosclerosis and cognitive function is less well studied in Chinese populations. In addition, the results among middle-aged adults have been mixed. We aimed to investigate the association of atherosclerosis measured by carotid intima-media thickness (CIMT) and cognitive function in middle-aged and older adults from a Chinese community. Participants in the Asymptomatic Polyvascular Abnormalities in Community study (APAC) who had completed the CIMT detection and cognitive function measurements in 2012/2013 were included. Cognitive function was measured using the Mini-Mental State Examination (MMSE). Multivariate linear regression analysis was used to analyze the association between CIMT and MMSE. Then, a stratified analysis was performed separately in middle-aged and older adults. A total of 3227 participants were included in this study (mean age 57.9 years, range 43-93 years); 56.6 % of them were men, 66.0 % were middle-aged adults. After adjusting for potential confounders, larger CIMT was associated with lower MMSE scores, with a 0.75-point decrease in MMSE score for every 1-mm increase in CIMT (ß = - 0.75, P = 0.0020). The association remained statistically significant in middle-aged adults (ß = - 0.57, P = 0.0390), and was stronger in older adults and adults with low education levels. There is a significant association between CIMT and cognitive function among middle-aged and older adults sampled from a Chinese population. This association was stronger in older adults and adults with low education levels.

The Oxfordshire Community Stroke Project classification system predicts clinical outcomes following intravenous thrombolysis: a prospective cohort study.

BACKGROUND: The Oxfordshire Community Stroke Project (OCSP) classification system is a simple stroke classification system that can be used to predict clinical outcomes. In this study, we compare the safety and efficacy of intravenous thrombolysis in Chinese stroke patients categorized using the OCSP classification system. PATIENTS AND METHODS: We collected data from the Thrombolysis Implementation and Monitoring of Acute Ischemic Stroke in China registry. A total of 1,115 patients treated with intravenous thrombolysis with alteplase within 4.5 hours of stroke onset were included. Symptomatic intracranial hemorrhage (SICH), mortality, and 90-day functional outcomes were compared between the stroke patients with different stroke subtypes. RESULTS: Of the 1,115 patients included in the cohort, 197 (17.67%) were classified with total anterior circulation infarct (TACI), 700 (62.78%) with partial anterior circulation infarct, 153 (13.72%) with posterior circulation infarct, and 65 (5.83%) with lacunar infarct. After multivariable adjustment, compared to the patients with non-TACI, those with TACI had a significantly increased risk of SICH (odds ratio [OR] 8.80; 95% confidence interval [CI] 2.84-27.25, P<0.001), higher mortality (OR 5.24; 95% CI 3.19-8.62; P<0.001), and poor functional independence (OR 0.38; 95% CI 0.26-0.56; P<0.001) at 3-month follow-up. CONCLUSION: After thrombolysis, the patients with TACI exhibited greater SICH, a higher mortality rate, and worse 3-month clinical outcomes compared with the patients with non-TACI. The OCSP classification system may help clinicians predict the safety and efficacy of thrombolysis.