Association of Cardiac Biomarkers in Combination With Cognitive Impairment After Acute Ischemic Stroke.

BACKGROUND: Poststroke cognitive impairment is a severe and common clinical complication that constitutes a substantial global health burden. We aimed to evaluate the association of 3 cardiac biomarkers in combination with poststroke cognitive impairment and their prognostic significance. METHODS AND RESULTS: This prospective study included 566 patients with ischemic stroke. Cardiac biomarkers, including sST2 (soluble suppression of tumorigenicity-2 receptor), GDF-15 (growth differentiation factor-15), and NT-proBNP (N-terminal pro-B-type natriuretic peptide), were measured. Cognitive impairment was defined as a Mini-Mental State Examination score of <27 or a Montreal Cognitive Assessment score of <25 at 3 months after ischemic stroke. Odds of cognitive impairment 3 months after ischemic stroke increased with the number of elevated cardiac biomarkers (sST2, GDF-15, and NT-proBNP; Ptrend<0.001). The multivariable adjusted odds ratios (95% CIs) of cognitive impairment defined by the Mini-Mental State Examination and Montreal Cognitive Assessment were 2.45 (1.48-4.07) and 1.86 (1.10-3.14) for the participants with ≥2 elevated cardiac biomarkers, respectively, compared with those without any elevated cardiac biomarker. Additionally, higher cardiac biomarker scores were associated with an increased risk of cognitive impairment (Ptrend<0.05). Simultaneously adding all 3 cardiac biomarkers to the basic model with traditional risk factors significantly improved the risk prediction of Mini-Mental State Examination-defined cognitive impairment (net reclassification improvement=34.99%, P<0.001; integrated discrimination index=2.67%, P<0.001). Similar findings were observed using the Montreal Cognitive Assessment scores. CONCLUSIONS: An increased number of elevated novel cardiac biomarkers were associated with an increased odds of poststroke cognitive impairment, suggesting that a combination of these cardiac biomarkers may improve the risk prediction of cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

Efficacy of Immediate Antihypertensive Treatment in Patients With Acute Ischemic Stroke With Different Blood Pressure Genetic Variants.

BACKGROUND: It remains unclear whether blood pressure (BP) genetic variants could modify the efficacy of immediate antihypertensive treatment after acute ischemic stroke. We conducted a secondary analysis of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) to investigate the effect of early antihypertensive treatment on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants. METHODS: The CATIS randomized 4071 patients with acute ischemic stroke with elevated systolic BP to receive antihypertensive treatment or discontinue all antihypertensive agents during hospitalization. Randomization was conducted centrally and was stratified by participating hospitals and use of antihypertensive medications. Five BP-associated single nucleotide polymorphisms (rs16849225, rs17030613, rs1173766, rs6825911, and rs35444 in FIGN-GRB14, ST7L-CAPZA1, NPR3, ENPEP, and near TBX3, respectively) were genotyped among 2590 patients. The primary outcome was a combination of death and major disability at 14 days or hospital discharge. A weighted BP genetic risk score was constructed by the 5 single nucleotide polymorphisms. RESULTS: At 14 days or hospital discharge, the primary outcome was not significantly different between antihypertensive treatment and control groups based on genotype subgroups for all 5 single nucleotide polymorphisms (all P>0.05 for interaction). In addition, the BP genetic risk score did not modify the effect of antihypertensive treatment. The odds ratios (95% CIs) for the primary outcome were 0.95 (0.71-1.26), 1.08 (0.80-1.44), and 0.91 (0.69-1.22) in patients with low, intermediate, and high BP genetic risk score, respectively (P=0.88 for interaction). CONCLUSIONS: Early antihypertensive treatment had a neutral effect on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

Gas chromatography-mass spectrometry pilot study to identify volatile organic compound biomarkers of childhood obesity with dyslipidemia in exhaled breath.

Objectives: Childhood obesity affects multiple organs in the body and is associated with both significant morbidity and ultimately premature mortality. Childhood obesity, especially dyslipidemia, can lead to early atherosclerosis and premature cardiovascular disease (CVD) in adulthood. The detection of exhaled volatile organic compounds (VOCs) in the breath offers the opportunity for the discovery of novel disease-specific biomarkers. This study aimed to identify VOCs that correlate with childhood obesity accompanied by dyslipidemia. Methods: A total of 82 overweight or obese children between the ages of 8 and 12 years were recruited from the exercise on obesity adolescents in Peking (EXCITING) study (NCT04984005). The breath VOCs of the participants were measured by gas chromatography-mass spectrometry (GC-MS). The classification was performed using principal component analysis (PCA) of the relative abundance of VOCs. The difference between the obese and overweight groups with or without dyslipidemia was analyzed. Results: Among the 82 children, 25 were overweight, of whom 10 had dyslipidemia. The other 57 children were obese, and 17 of them had dyslipidemia. Obese children with dyslipidemia had higher triglycerides and elevated non-high-density lipoprotein-cholesterol compared to overweight children without dyslipidemia. We confirmed 13 compounds based on database well matches (average score > 80) for mass spectra and refractive index. These 13 VOCs were grouped into three chemical functional groups: saturated hydrocarbons, aromatic hydrocarbons and unsaturated aldehydes. For obese children with dyslipidemia, the PCA scatter plot of the three chemical groups was obviously separated from the other groups. Some of the candidates, including heptadecane, naphthalene, and cis-6-nonnenol, were significantly higher in obese children with dyslipidemia than in overweight groups with or without dyslipidemia. Conclusion: A suite of VOCs from three chemical function groups, saturated hydrocarbons, aromatic hydrocarbons, and unsaturated aldehydes, were separated in the obese children with dyslipidemia. Heptadecane, naphthalene, and cis-6-nonenol were significantly elevated in obese children with dyslipidemia. Our findings underscore the potential value of the candidate VOCs for future risk categorization.

Osteoprotegerin and Ischemic Stroke Prognosis: A Prospective Multicenter Study and Mendelian Randomization Analysis.

BACKGROUND: Osteoprotegerin was implicated in vascular injury and inflammatory responses, but its prognostic value in ischemic stroke remained unclear. We aimed to prospectively investigate the association between plasma osteoprotegerin and ischemic stroke prognosis combined with a Mendelian randomization analysis. METHODS: Our prospective study follows the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) reporting guideline. We measured baseline plasma osteoprotegerin levels for 3490 ischemic stroke patients recruited between August 2009 and May 2013 in 26 hospitals across China. The primary outcome was a composite outcome of death and major disability at 3 months after ischemic stroke. RESULTS: After adjustment for age, sex, admission National Institutes of Health Stroke Scale score, and other important covariates, elevated osteoprotegerin levels were associated with increased risks of primary outcome (odds ratio, 1.40 [95% CI, 1.05-1.88]), death (hazard ratio, 2.05 [95% CI, 1.04-4.08]), and composite outcome of death and vascular events (hazard ratio, 2.00 [95% CI, 1.15-3.48]) when 2 extreme quartiles were compared. Each 1-SD higher log-osteoprotegerin was associated with a 18% (95% CI, 6%-32%) increased risk of primary outcome, 69% (95% CI, 31%-118%) increased risk of death, and 53% (95% CI, 24%-89%) increased risk of composite outcome of death and vascular events, respectively. Multiple-adjusted spline regression model showed a linear association of osteoprotegerin with primary outcome (P for linearity <0.001). Adding osteoprotegerin to conventional risk factors did not significantly improve discriminatory power (C statistics, 0.817 versus 0.818; P=0.232) but did slightly improve the risk reclassification of primary outcome (net reclassification improvement: 13.68%, P<0.001; integrated discrimination improvement: 0.23%, P=0.039). In Mendelian randomization analysis, genetically determined high plasma osteoprotegerin was associated with increased risk of primary outcome (odds ratio, 5.74 [95% CI, 1.12-29.44]; P=0.036). CONCLUSIONS: Elevated plasma osteoprotegerin was associated with poor prognosis of ischemic stroke, and genetically determined high plasma osteoprotegerin was associated with an increased risk of primary outcome in Mendelian randomization analysis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01840072.

Plasma sDPP4 (Soluble Dipeptidyl Peptidase-4) and Cognitive Impairment After Noncardioembolic Acute Ischemic Stroke.

BACKGROUND: DPP4 (dipeptidyl peptidase-4) inhibitors have been proven to promote neuronal regeneration, reverse the development of cognitive deficits. However, the association of circulating soluble form (sDPP4 [soluble DPP4]) with poststroke cognitive impairment (PSCI) is unclear. We aimed to investigate the association between plasma sDPP4 levels and PSCI in patients with ischemic stroke. METHODS: A total of 600 noncardioembolic stroke patients were included based on a preplanned ancillary study from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). We used the Montreal Cognitive Assessment to evaluate cognitive function at 3 months follow-up after ischemic stroke. Binary logistic regression analyses were performed to investigate the association of plasma sDPP4 levels with subsequent PSCI. We further calculated integrated discrimination improvement and category-free net reclassification improvement to investigate the incremental prognostic effect of plasma sDPP4 beyond the basic model with conventional risk factors. RESULTS: Plasma sDPP4 was inversely associated with PSCI after ischemic stroke, and the adjusted odds ratio (95% CI) for the highest versus lowest quartile of sDPP4 was 0.49 (0.29-0.81; P for trend=0.011). Each 1-SD increase of logarithm-transformed plasma sDPP4 concentration was associated with 17% (odds ratio, 0.83 [95% CI, 0.70-0.99]) lower risk of PSCI. Adding plasma sDPP4 to the basic model notably improved risk reclassification for PSCI, as shown by a category-free net reclassification improvement of 19.10% (95% CI, 2.52%-35.68%; P=0.03) and integrated discrimination improvement of 0.79% (95% CI, 0.13%-1.46%; P=0.02). CONCLUSIONS: Higher plasma sDPP4 levels were associated with decreased risk of cognitive impairment after noncardioembolic ischemic stroke.

Plasma choline and betaine and risks of cardiovascular events and recurrent stroke after ischemic stroke.

BACKGROUND: Choline and betaine have been suggested to play a pivotal role in neurotransmitter synthesis, cell membrane integrity, and methyl-group metabolism, exerting neuroprotective effects in patients with various neurological disorders. However, population-based evidence on choline and betaine with subsequent cardiovascular events after stroke is rare. OBJECTIVES: We aimed to prospectively investigate the relationships of circulating choline and betaine with cardiovascular events and recurrent stroke in patients with ischemic stroke. METHODS: We performed a nested case-control study within the China Antihypertensive Trial in Acute Ischemic Stroke. A total of 323 cardiovascular events (including 264 recurrent strokes) and 323 controls (free of recurrent cardiovascular events) matched for age (±1 y), sex, and treatment group were included. The primary endpoint was a composite of cardiovascular events after ischemic stroke. Plasma choline and betaine were measured at baseline by ultra-high-performance LC-MS/MS. Conditional logistic regression models were applied, and discrimination, reclassification, and calibration of models with choline pathway metabolites were evaluated. RESULTS: Plasma choline and betaine were inversely associated with cardiovascular events and recurrent stroke after ischemic stroke. Specifically, in fully adjusted models, each additional SD of choline and betaine was associated with 35% (95% CI: 20%-48%) and 30% (95% CI: 14%-43%) decreased risks of subsequent cardiovascular events, respectively, and 34% (95% CI: 16%-48%) and 29% (95% CI: 12%-43%) decreased risks of recurrent stroke, respectively. In addition, both choline and betaine offered substantial risk discrimination and reclassification improvement for cardiovascular events and recurrent stroke beyond traditional risk factors, as evidenced by an increase in C statistics, the net reclassification index, and integrated discrimination improvement. CONCLUSIONS: Plasma choline pathway metabolites, including choline and betaine, were associated with decreased risks of cardiovascular events and recurrent stroke and provided incremental value in risk discrimination and stratification in patients with ischemic stroke. This nested case-control study was based on the China Antihypertensive Trial in Acute Ischemic Stroke, which is registered at clinicaltrials.gov as NCT01840072.

Serum ß-klotho is a potential biomarker in the prediction of clinical outcomes among patients with NSCLC.

BACKGROUND: We aimed to investigate the ß-klotho (KLB) expression in non-small cell lung cancer (NSCLC) and to determine its value as a novel molecular target for survival prognosis in patients with NSCLC. METHODS: The serum KLB concentrations in 50 patients with NSCLC and the 20 healthy persons were measured by enzyme-linked immunosorbent assay (ELISA) methods. The relationship between serum KLB level, including the level change after therapy, and the progression-free survival (PFS) and overall survival (OS) were analyzed. The KLB expression in A549 cells was measured by real-time polymerase chain reaction (RT-PCR) and western blotting. The function of cells was revealed by in vitro studies. RESULTS: The concentrations of serum KLB in patients with NSCLC were obviously lower than those in healthy subjects. KLB expression was significantly increased in patients after chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted therapy. In addition, expression of KLB was positively related with PFS and OS. Compared with 16-human bronchial epithelial (HBE) cells, the expression level of KLB was significantly decreased in A549 cells. Overexpression of KLB suppressed the proliferation of A549 cells, along with G1-to-S phase arrest and apoptosis induction. CONCLUSIONS: KLB plays an anti-tumorigenic role in NSCLC. KLB may be a candidate target for the diagnosis and treatment of NSCLC and may serve a potentially significant role in future clinical applications.

Soluble ST2 and risk of cognitive impairment after acute ischemic stroke: a prospective observational study.

BACKGROUND: Soluble suppression of tumorigenesis-2 (sST2) was reported to be associated with cognitive performance and risk of incident stroke. However, the impact of sST2 on cognitive function after ischemic stroke is unclear. We aimed to assess the association of sST2 and cognitive impairment at 3 months in acute ischemic stroke patients. METHODS: Baseline plasma sST2 levels were measured in 619 ischemic stroke patients (mean age: 60.0 ± 10.5 years) from 7 participating hospitals of the China Antihypertensive Trial in Acute Ischemic Stroke. Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to assess cognitive status. Cognitive impairment was defined as a MoCA score < 23 or MMSE score < 27. The association between sST2 and cognitive impairment was evaluated by logistic regression analysis. RESULTS: 325 (52.5%) or 323 (52.2%) participants developed cognitive impairment according to MoCA or MMSE. After adjustment for age, sex, education, and other covariates, the odds ratio for the highest vs lowest quartile of sST2 was 2.38 (95% CI, 1.42-4.00) and 1.82 (95% CI 1.09-3.03) risk of cognitive impairment defined by MoCA and MMSE score, respectively. Incorporation sST2 into a model containing conventional risk factors significantly improved reclassification. CONCLUSIONS: Elevated plasma sST2 levels were significantly associated with post-stroke cognitive impairment.

Plasma soluble suppression of tumorigenicity 2 and depression after acute ischemic stroke.

BACKGROUND AND PURPOSE: Soluble suppression of tumorigenicity 2 (sST2) might be related to stroke and depression, but the association of sST2 with poststroke depression (PSD) is unclear. The study aimed to prospectively assess the association between plasma sST2 levels and PSD. METHODS: A total of 635 acute ischemic stroke patients with sST2 measurements from the China Antihypertensive Trial in Acute Ischemic Stroke were included in this analysis. We used the 24-item Hamilton Rating Scale for Depression to assess depression at 3 months, and PSD was defined as a score of ≥8. Logistic regression analysis was performed to estimate the risk of PSD associated with sST2, and net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to assess the predictive value of sST2. RESULTS: Two hundred fifty (39.4%) patients developed depression at 3 months after ischemic stroke. Patients with PSD had higher sST2 levels than patients without PSD (172.7 vs. 153.8 pg/ml; p = 0.003). After adjustment for age, sex, education, National Institutes of Health Stroke Scale score, and other covariates, the odds ratio for the highest quartile of sST2 compared with the lowest quartile was 1.84 (95% confidence interval, 1.10-3.08) for PSD. Adding sST2 to a conventional model notably improved risk prediction for PSD (category-free NRI = 19.34%, 95% confidence interval = 4.39%-34.28%, p = 0.017; IDI = 1.20%, 95% confidence interval = 0.25%-2.15%, p = 0.014). CONCLUSIONS: Increased plasma sST2 levels in the acute phase of ischemic stroke were significantly associated with the increased risk of PSD, independently of conventional risk factors.

Predictive Value of Cystatin C for Stroke Recurrence in Patients With Acute Ischemic Stroke.

BACKGROUND: This study explored the value of cystatin C (CysC) in predicting stroke recurrence in patients with acute ischemic stroke.Methods and Results:This was a post hoc analysis of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) on 3,474 acute ischemic stroke patients with documented serum CysC and high-sensitivity C-reactive protein (hsCRP) concentrations. Study outcomes included stroke recurrence and combined vascular events within 2 years after stroke. In stroke patients with higher (i.e., ≥4.8ng/mL), but not lower, hsCRP concentrations, a higher CysC concentration (i.e., ≥0.78 mg/L) was associated with a 2.48-fold increase in the risk of recurrent stroke (95% confidence interval [CI] 1.37-4.51; P=0.003) and a 2.04-fold increase in the risk of vascular events (95% CI 1.27-3.28; P=0.003). Serum hsCRP concentrations significantly modified the association of serum CysC with recurrent stroke (Pinteraction=0.001) and vascular events (Pinteraction=0.007). Moreover, CysC may improve reclassification of stroke recurrence (net reclassification improvement [NRI] 42.9%, P=0.001; integrated discrimination improvement [IDI] 1.2%, P=0.001) and vascular events (NRI 35.8%, P=0.001; IDI 1.1%, P=0.004). CONCLUSIONS: In ischemic stroke patients with high hsCRP concentrations, higher CysC concentrations increased the risk of stroke recurrence and vascular events. This indicates that the predictive value of CysC on stroke recurrence may depend on the inflammation status of patients.

Ipilimumab plus nivolumab for patients with metastatic uveal melanoma: a multicenter, retrospective study.

BACKGROUND: Uveal melanoma (UM) is the most common intraocular malignancy in adults. In contrast to cutaneous melanoma (CM), there is no standard therapy, and the efficacy and safety of dual checkpoint blockade with nivolumab and ipilimumab is not well defined. METHODS: We conducted a retrospective analysis of patients with metastatic UM (mUM) who received treatment with ipilimumab plus nivolumab across 14 academic medical centers. Toxicity was graded using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier methodology. RESULTS: 89 eligible patients were identified. 45% had received prior therapy, which included liver directed therapy (29%), immunotherapy (21%), targeted therapy (10%) and radiation (16%). Patients received a median 3 cycles of ipilimumab plus nivolumab. The median follow-up time was 9.2 months. Overall response rate was 11.6%. One patient achieved complete response (1%), 9 patients had partial response (10%), 21 patients had stable disease (24%) and 55 patients had progressive disease (62%). Median OS from treatment initiation was 15 months and median PFS was 2.7 months. Overall, 82 (92%) of patients discontinued treatment, 34 due to toxicity and 27 due to progressive disease. Common immune-related adverse events were colitis/diarrhea (32%), fatigue (23%), rash (21%) and transaminitis (21%). CONCLUSIONS: Dual checkpoint inhibition yielded higher response rates than previous reports of single-agent immunotherapy in patients with mUM, but the efficacy is lower than in metastatic CM. The median OS of 15 months suggests that the rate of clinical benefit may be larger than the modest response rate.

Plasma S100A8/A9 Concentrations and Clinical Outcomes of Ischemic Stroke in 2 Independent Multicenter Cohorts.

BACKGROUND: S100A8/A9 is implicated in inflammation mechanisms related to atherosclerosis and plaque vulnerability, but it remains unclear whether S100A8/A9 is associated with the prognosis of ischemic stroke. The aim of this study was to investigate these associations in 2 independent multicenter cohorts. METHODS: Plasma S100A8/A9 concentrations at baseline were measured among 4785 patients with ischemic stroke from 2 independent cohorts: Infectious Factors, Inflammatory Markers, and Prognosis of Acute Ischemic Stroke (IIPAIS) and China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a composite outcome of death or major disability at 3 months after ischemic stroke. Secondary outcomes were major disability, death, and a composite outcome of death or vascular events. RESULTS: Among the combined participants of IIPAIS and CATIS, the adjusted odds ratios associated with the highest quartile of plasma S100A8/A9 were 2.11 (95% CI, 1.66-2.68) for the primary outcome and 1.62 (95% CI, 1.27-2.07) for the secondary outcome of major disability; adjusted hazard ratios were 4.14 (95% CI, 2.10-8.15) for the secondary outcome of death and 2.08 (95% CI, 1.38-3.13) for the composite outcome of death or vascular events. Each SD increase of log-transformed S100A8/A9 was associated with 28% (95% CI, 18%-39%; P < 0.001) increased risk of the primary outcome. Multivariable-adjusted spline regression analyses showed a linear association between plasma S100A8/A9 concentrations and primary outcome (P < 0.001 for linearity). Subgroup analyses further confirmed these associations. CONCLUSIONS: High plasma S100A8/A9 concentrations at baseline were independently associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that S100A8/A9 might have a role as a prognostic marker of ischemic stroke.

The association between the socioeconomic status and body pain: A nationwide survey.

Pain is a significant burden among different communities, but little is known regarding the epidemiology of pain, particularly with respect to socioeconomic status (SES).The aim of the study was to estimate the prevalence of body pain and to identify risk factors of pain in middle-aged and older Chinese.The data were extracted from the 2008 Chinese Suboptimal Health Study that consisted of 18,316 Chinese subjects aged 18 to 65 years. Information on SES including occupation and education levels and body pain were collected. A Likert scale was used to evaluate reported body pain. We used the multiple logistic regression model to examine the association between SES and body pain.Overall, 65.34% reported body pain (male: 60.93%; female: 69.73%). After adjustments based on sex, age, education, area of residence, marital status, smoking, drinking and health status, the results showed that students (odds ratio [OR] = 1.51; 95% confidence interval [CI]: 1.32-1.74) and professionals (OR = 1.22; 95% CI: 1.08-1.37) had significant high risk for body pain, compared with civil servants and farmers (OR = 0.64; 95% CI: 0.55-0.75) who significantly lower risk of body pain. The study demonstrates there is a significant negative association between education and reported body pain.The results indicated an association between SES and body pain within the Chinese community. Body pain varied among different Chinese occupation-related population and people with higher education level are less like to have body pain.

Serum cystatin C levels are negatively correlated with post-stroke cognitive dysfunction.

Stroke is the leading cause of death and long-term disability worldwide, and cognitive impairment and dementia are major complications of ischemic stroke. Cystatin C (CysC) has been found to be a neuroprotective factor in animal studies. However, the relationship between CysC levels and cognitive dysfunction in previous studies has revealed different results. This prospective observational study investigated the correlation between serum CysC levels and post-stroke cognitive dysfunction at 3 months. Data from 638 patients were obtained from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE) at 3 months after stroke. According to the MMSE score, 308 patients (52.9%) had post-stroke cognitive dysfunction. After adjusting for potential confounding factors, the odds ratio (95% CI) of post-stroke cognitive dysfunction for the highest quartile of serum CysC levels was 0.54 (0.30-0.98), compared with the lowest quartile. The correlation between serum CysC and cognitive dysfunction was modified by renal function status. We observed a negative linear dose-response correlation between CysC and cognitive dysfunction in patients with normal renal function (Plinearity = 0.044), but not in those with abnormal renal function. Elevated serum CysC levels were correlated with a low risk of 3-month cognitive dysfunction in patients with acute ischemic stroke, especially in those with normal renal function. The current results suggest that CysC is a protective factor for post-stroke cognitive dysfunction, and could be used to treat post-stroke cognitive dysfunction. The CATIS study was approved by the Institutional Review Boards at Soochow University from China (approval No. 2012-02) on December 30, 2012, and was registered at ClinicalTrials.gov (identifier No. NCT01840072) on April 25, 2013.

Simple Renal Cysts Are Associated With 24-Month Prognosis of Patients With Type B Aortic Dissection and Hypertension.

BACKGROUND: The association of simple renal cyst (SRC) with type B aortic dissection (BAD) has recently been established. However, no studies have examined adverse events after BAD hospitalization among patients with SRC. In this study, we assessed the prognostic value of SRC in BAD patients with hypertension after thoracic endovascular aortic repair (TEVAR). METHODS: We studied all BAD patients with hypertension who were admitted for TEVAR (n = 238; age 56.1 ± 9.8 years, 84.0% male). Aortic-related adverse events (ARAE) were evaluated as outcomes at 3 months and 24 months after TEVAR. RESULTS: Among the total number of patients, 104 (43.7%) had at least 1 SRC. Patients with SRC were significantly older than those without (59.6 ± 8.8 vs 53.3 ± 9.7; P < 0.001). Patients with SRC were also more likely to suffer from peripheral arterial disease (55.8% vs 40.3%; P = 0.018) and cerebrovascular accidents (47.1% vs 29.9%; P = 0.006) than those without. Median follow-up for the 238 patients was 18.5 (range 6.4-24.0) months. Cumulative ARAE-free rates were 94.5 ± 1.5% at the 3-month follow-up and 81.5 ± 2.8% at the 24-month follow-up. Independent predictors of 3-month ARAE were found to be insertion of ≥ 2 stents (hazard ratio [HR] 3.977, 95% confidence interval [CI] 1.224-12.920; P = 0.022). For 24-month follow-up, SRC (HR 1.962, 95% CI 1.023-3.764; P = 0.043) was evaluated as the only independent predictive factor. SRC (HR 8.841, 95% CI 1.726-45.294; P = 0.009) was also evaluated as an independent predictive factor for 24-month ARAEs in the chronic group, but not in the acute or the subacute group. CONCLUSIONS: SRC could predict 24-month ARAE in BAD patients with hypertension after TEVAR, especially in the chronic group.

Socioeconomic status and self-rated health in China: Findings from a cross-sectional study.

To investigate whether socioeconomic status is associated with the self-rated health (SRH) status among Chinese.A cross sectional study including a national sample was conducted among Chinese adults in 2008. In total, 3225 participants were selected by a multistage cluster sampling method. Both general self-rated health and time-comparative self-rated health were measured by a standardized questionnaire. Logistic regression models were used to estimate the odds ratios (ORs) (95% confidence intervals, CIs) of occupation with SRH by occupation, and adjusted for age, sex, education, area, marriage, smoking, drinking, and health status.Overall, 34.4% of study participants reported "good" on the general SRH (male: 35.8%; female: 32.9%) and 26.2% reported "good" on the time-comparative SRH (male: 27.2%; female: 25.3%). The prevalence of "good" general SRH varied from 28.8% to 52.8% and the prevalence of time-comparative SHR varied from 21.7% to 33.9% in different occupations. The adjusted OR (Odd Ratio) for "good" on the general SRH was 1.35 (95% CI: 1.20-1.52) for the occupation of civil servants, 2.23 (95% CI: 1.96-2.54) for farmers, and 1.15 (95%CI: 1.01-1.31) for businessmen. The full adjusted OR of "good" on the time-comparative SRH was 1.36 (95% CI: 1.17-1.58) for students and was 1.25 (95% CI: 1.10-1.42) for civil servants.In presented study, 34.4% of the participants reported "good" on the general SRH, and 26.2% participants reported "good" on the time-comparative SRH. The prevalence of "good" general SRH and "good" time-comparative SRH varied among occupations.

SNPs rs10224002 in PRKAG2 may disturb gene expression and consequently affect hypertension.

Genome-wide association studies have identified a large number of genetic loci for blood pressure in European populations. The associations in other populations are needed to determine. The purpose of this study was to examine the associations between the single nucleotide polymorphisms (SNPs) identified in European populations and hypertension in the Chinese Han population, and highlight the potential roles. Seven tag-SNPs were genotyped in 857 hypertension cases and 927 controls to test the associations. The intronic SNP rs10224002 (PRKAG2) which could affect DNase and regulatory motif was associated with hypertension (P = 0.024). This SNP was also found to be associated with coronary artery disease and stroke. We searched for potential functional variants by bioinformatics analysis and found various kinds of variants such as missense mutations, phosphorylation-related SNPs and SNPs that have regulatory potentials in the blood pressure loci. We performed expression quantitative trait locus (eQTL) and differential expression analyses for the identified variants and genes. eQTL analysis found that rs10224002 was associated with PRKAG2 gene expression in peripheral blood (P = 0.0016). PRKAG2 was differentially expressed between hypertension cases and controls (P = 0.0133), coronary artery disease cases and controls (P = 0.02112) and stroke cases and controls (P = 0.0059). Our study demonstrated that SNPs rs10224002 may be associated with hypertension in the Chinese Han population and PRKAG2 may play a role in the etiology of hypertension and cardiovascular diseases.

Ginsenoside Rg1 protects against H2O2­induced neuronal damage due to inhibition of the NLRP1 inflammasome signalling pathway in hippocampal neurons in vitro.

Oxidative stress and neuroinflammation are important in the pathogenesis of ageing and age­related neurodegenerative diseases, including Alzheimer's disease. NADPH oxidase 2 (NOX2) is a major source of reactive oxygen species (ROS) in the brain. The nucleotide­binding oligomerisation domain (NOD)­like receptor protein 1 (NLRP1) inflammasome is responsible for the formation of pro­inflammatory molecules in neurons. Whether the NOX2­NLRP1 inflammasome signalling pathway is involved in neuronal ageing and age­related damage remains to be elucidated. Ginsenoside Rg1 (Rg1) is a steroidal saponin found in ginseng. In the present study, the primary hippocampal neurons were treated with H2O2 (200 µM) and Rg1 (1, 5 and 10 µM) for 24 h to investigate the protective effects and mechanisms of Rg1 on H2O2­induced hippocampal neuron damage, which mimics age­related damage. The results showed that H2O2 treatment significantly increased ROS production and upregulated the expression of NOX2 and the NLRP1 inflammasome, and led to neuronal senescence and damage to hippocampal neurons. Rg1 decreased ROS production, reducing the expression of NOX2 and the NLRP1 inflammasome in H2O2­treated hippocampal neurons. Furthermore, Rg1 and tempol treatment significantly decreased neuronal apoptosis and the expression of ß­galactosidase, and alleviated the neuronal senescence and damage induced by H2O2. The present study indicates that Rg1 may reduce NOX2­mediated ROS generation, inhibit NLRP1 inflammasome activation, and inhibit neuronal senescence and damage.

Smoking modifies the effect of two independent SNPs rs5063 and rs198358 of NPPA on central obesity in the Chinese Han population.

Obesity is the third most risk factors of death in the middle-income and high-income countries. Whether DNA polymorphisms in CORIN and NPPA genes were associated with obesity, and if these associations could be modified by smoking in the Chinese Han population were unknown, hence a group of 1507 participants were recruited and genotyped for 12 tag single-nucleotide polymorphisms (SNPs) of CORIN and NPPA genes. Regression models were used to test the associations of SNPs with obesity. The potential SNP-smoking interactions were detected in regression models. NPPA SNPs rs5063 and rs198358 were associated with the body mass index (BMI) (P = 0.0053 and 0.0037, respectively). Rs198358 was associated with obesity in both univariate- and multivariable-adjusted analyses (P = 0.0138 and 0.0173, respectively). Rs5063 was associated with central obesity in both univariate- and multivariable-adjusted analyses (P = 0.0454 and 0.0361, respectively). Significant interactions between cigarette smoking and rs5063 and rs198358 were detected (P = 0.0019 and 0.0006, respectively). In subgroup analyses, rs5063 and rs198358 were associated with central obesity in smokers (P = 0.0081 and 0.0037, respectively). The results of our study demonstrated that the effect of NPPA SNPs rs5063 and rs198358 on central obesity might be modified by smoking in the Chinese Han population. Further studies are needed to confirm the associations and elucidate the underlying mechanisms.

Prognostic significance of serum cystatin C in acute ischemic stroke patients according to lipid component levels.

BACKGROUND AND AIMS: Serum cystatin C (CysC) is associated with the risk of ischemic stroke and may predict cardiovascular events and death after ischemic stroke onset. However, the association between serum CysC and functional outcome in ischemic stroke patients remains unclear, and whether lipid component level influences the relationship between them has not been studied. METHODS: A total of 3348 ischemic patients from China Antihypertensive Trial in Acute Ischemic Stroke were included in the study. Serum CysC was used to calculate estimated glomerular filtration rate (eGFRCysC) at baseline. The primary outcome was poor functional outcome (modified Rankin Scale score ≥3) at one year after ischemic stroke. Secondary outcomes were death, stroke recurrence, vascular events and combination of the aforementioned outcomes. RESULTS: The association between eGFRCysC and primary outcome was appreciably modified by low-density lipoprotein cholesterol (LDL-C) (pinteraction = 0.048). Low eGFRCysC was associated with primary outcome only in ischemic stroke patients with LDL-C ≥4.14 mmol/l rather than all patients. The multivariable adjusted odds ratio (95% confidence interval) of poor functional outcome associated with low eGFRCysC was 3.94 (1.04-14.98) and a positive linear dose-response relationship between them was observed among patients with LDL-C ≥4.14 mmol/l (p for linearity = 0.021). Subgroup analyses further confirmed these associations. There was no association between eGFR based on serum creatinine and poor functional outcome of stroke. CONCLUSIONS: Low eGFRCysC may be an independent predictor for 1-year poor functional outcome in ischemic stroke patients with LDL-C ≥4.14 mmol/l. Further studies are needed to replicate our findings and to clarify the potential mechanisms.