Development and validation of cardiovascular risk prediction equations in 76 000 people with known cardiovascular disease.

AIMS: Multiple health administrative databases can be individually linked in Aotearoa New Zealand, using encrypted identifiers. These databases were used to develop cardiovascular risk prediction equations for patients with known cardiovascular disease (CVD). METHODS AND RESULTS: Administrative health databases were linked to identify all people aged 18-84 years with known CVD, living in Auckland and Northland, Aotearoa New Zealand, on 1 January 2014. The cohort was followed until study outcome, death, or 5 years. The study outcome was death or hospitalization due to ischaemic heart disease, stroke, heart failure, or peripheral vascular disease. Sex-specific 5-year CVD risk prediction equations were developed using multivariable Fine and Gray models. A total of 43 862 men {median age: 67 years [interquartile range (IQR): 59-75]} and 32 724 women [median age: 70 years (IQR: 60-77)] had 14 252 and 9551 cardiovascular events, respectively. Equations were well calibrated with good discrimination. Increasing age and deprivation, recent cardiovascular hospitalization, Mori ethnicity, smoking history, heart failure, diabetes, chronic renal disease, atrial fibrillation, use of blood pressure lowering and anti-thrombotic drugs, haemoglobin A1c, total cholesterol/HDL cholesterol, and creatinine were statistically significant independent predictors of the study outcome. Fourteen per cent of men and 23% of women had predicted 5-year cardiovascular risk <15%, while 28 and 24% had ≥40% risk. CONCLUSION: Robust cardiovascular risk prediction equations were developed from linked routine health databases, a currently underutilized resource worldwide. The marked heterogeneity demonstrated in predicted risk suggests that preventive therapy in people with known CVD would be better informed by risk stratification beyond a one-size-fits-all high-risk categorization.

Using regionwide New Zealand health databases, methods of predicting hospitalization risk in patients with existing heart disease were developed. Using only data from health databases, it was possible to predict the risk accurately.Among patients with existing heart disease, the predicted risk varied markedly which could help improve preventive strategies.

Vehicular visible light communications noise analysis and modeling.

Vehicular visible light communications (VVLC) is promising intelligent transportation systems technology with the utilization of light-emitting diodes. The main degrading factor for the performance of VVLC systems is noise. Traditional VVLC systems noise modeling is based on the additive white Gaussian noise assumption in the form of shot and thermal noise. In this paper, to investigate both time correlated and white noise components of the VVLC channel noise, we propose a noise analysis based on Allan variance, which provides a time-series analysis method to identify noise from the data. The results show that white noise and random walk are observed in the VVLC systems. We also propose a motion detection algorithm based on the adaptive Gaussian mixture (GM) model to generate a double Gaussian model of VVLC channel noise. We further present a study on the error performance of a VVLC system considering channel noise to be a mixture of Gaussian components. We derive the analytical expressions of probability of error for binary phase-shift keying and quadrature phase-shift keying constellations. It has been observed that, in the presence of GM noise, the system performance degrades significantly from the usual one expected in a Gaussian noise environment and becomes a function of the mixing coefficients of the GM distribution.

SIRT6 Knockdown in Buffalo Fetal Fibroblasts Exacerbates Premature Senescence Caused by DNA and Telomere Damage.

As a gene with antiaging functions, sirtuin6 (SIRT6) belonging to the sirtuin family plays a vital role in DNA repair, telomerase function, and cellular senescence, as well as maintains epigenomic stability and promotes longevity. However, its role in cell senescence in large animals, such as buffaloes, remains unknown. Fibroblasts are commonly used for somatic reprogramming, and their physiological characteristics affect the efficiency of this process. We aimed to elucidate the role of SIRT6 in cellular senescence and proliferation and analyze its effect on the biological function of buffalo fibroblasts to help improve the efficiency of buffalo somatic cell reprogramming. The expression of SIRT6 and related DNA damage was measured in buffalo fibroblasts obtained at different developmental stages (in the fetus and at 3 and 10 years of age), and the effect of SIRT6 knockdown on the senescence of buffalo fetal fibroblast was investigated. An inverse relationship was observed between SIRT6 expression and senescence in buffalo fibroblasts obtained from animals of various ages. This was accompanied by decreased cell growth, viability, and increased DNA damage. Short hairpin RNA-mediated SIRT6 knockdown accelerated the senescence of buffalo fetal fibroblasts. It blocked the cell cycle during in vitro cell culture, which further enhanced DNA damage, particularly with respect to the telomeres. Collectively, our findings suggest that SIRT6 expression was closely associated with buffalo senescence in fibroblasts. These findings serve as a foundation to better understand the cellular functions of SIRT6 and also aid in selecting donor cells for buffalo somatic cell reprogramming.

Validation and comparison of cardiovascular risk prediction equations in Chinese patients with Type 2 diabetes.

AIMS: For patients with diabetes, the European guidelines updated the cardiovascular disease (CVD) risk prediction recommendations using diabetes-specific models with age-specific cut-offs, whereas American guidelines still advise models derived from the general population. We aimed to compare the performance of four cardiovascular risk models in diabetes populations. METHODS AND RESULTS: Patients with diabetes from the CHERRY study, an electronic health records-based cohort study in China, were identified. Five-year CVD risk was calculated using original and recalibrated diabetes-specific models [Action in Diabetes and Vascular disease: PreterAx and diamicroN-MR Controlled Evaluation (ADVANCE) and the Hong Kong cardiovascular risk model (HK)] and general population-based models [Pooled Cohort Equations (PCE) and Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR)]. During a median 5.8-year follow-up, 46 558 patients had 2605 CVD events. C-statistics were 0.711 [95% confidence interval: 0.693-0.729] for ADVANCE and 0.701 (0.683-0.719) for HK in men, and 0.742 (0.725-0.759) and 0.732 (0.718-0.747) in women. C-statistics were worse in two general population-based models. Recalibrated ADVANCE underestimated risk by 1.2% and 16.8% in men and women, whereas PCE underestimated risk by 41.9% and 24.2% in men and women. With the age-specific cut-offs, the overlap of the high-risk patients selected by every model pair ranged from only 22.6% to 51.2%. When utilizing the fixed cut-off at 5%, the recalibrated ADVANCE selected similar high-risk patients in men (7400) as compared to the age-specific cut-offs (7102), whereas age-specific cut-offs exhibited a reduction in the selection of high-risk patients in women (2646 under age-specific cut-offs vs. 3647 under fixed cut-off). CONCLUSION: Diabetes-specific CVD risk prediction models showed better discrimination for patients with diabetes. High-risk patients selected by different models varied significantly. Age-specific cut-offs selected fewer patients at high CVD risk especially in women.

This large electronic health records-based real-world study indicated that the diabetes-specific cardiovascular risk models had better discriminative abilities than the models derived from the general population in Chinese patients with Type 2 diabetes.Current guidelines-recommended models, i.e. ADVANCE, PCE, and China-PAR, selected significantly different high-risk groups with various observed cardiovascular risks, indicating the potential considerable misclassification of risk stratification in clinical decision-making for preventive interventions.Compared with the fixed cut-off, the influence of the age-specific cut-offs for high risk of cardiovascular disease was different in men and women: age-specific cut-offs selected ∼27% fewer high-risk patients in women but similar in men.

Evaluation of Atherosclerotic Cardiovascular Risk Prediction Models in China: Results From the CHERRY Study.

Background: Updated American or Chinese guidelines recommended calculating atherosclerotic cardiovascular disease (ASCVD) risk using the Pooled Cohort Equations (PCE) or Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) models; however, evidence on performance of both models in Asian populations is limited. Objectives: The authors aimed to evaluate the accuracy of the PCE or China-PAR models in a Chinese contemporary cohort. Methods: Data were extracted from the CHERRY (CHinese Electronic health Records Research in Yinzhou) study. Participants aged 40 to 79 years without prior ASCVD at baseline from 2010 to 2016 were included. ASCVD was defined as nonfatal or fatal stroke, nonfatal myocardial infarction, and cardiovascular death. Models were assessed for discrimination and calibration. Results: Among 226,406 participants, 5362 (2.37%) adults developed a first ASCVD event during a median of 4.60 years of follow-up. Both models had good discrimination: C-statistics in men were 0.763 (95% confidence interval [CI]: 0.754-0.773) for PCE and 0.758 (95% CI: 0.749-0.767) for China-PAR; C-statistics in women were 0.820 (95% CI: 0.812-0.829) for PCE and 0.811 (95% CI: 0.802-0.819) for China-PAR. The China-PAR model underpredicted risk by 20% in men and by 40% in women, especially in the highest-risk groups. However, PCE overestimated by 63% in men and inversely underestimated the risk by 34% in women with poor calibration (both P < 0.001). After recalibration, observed and predicted risks by recalibrated PCE were better aligned. Conclusions: In this large-scale population-based study, both PCE and China-PAR had good discrimination in 5-year ASCVD risk prediction. China-PAR outperformed PCE in calibration, whereas recalibration equalized the performance of PCE and China-PAR. Further specific models are needed to improve accuracy in the highest-risk groups.

Underwater blue-green LED communication using a double-layered, curved compound-eye optical system.

Optical receiving systems with single-lens structures have problems such as low receiving efficiency and small field of view when applied to underwater optical wireless communication systems. In this study, a design scheme for a double-layered fly-eye-lens optical system with wide-angle focusing is proposed. Based on the analysis of the LED light source transmission model and seawater channel, the optical-power receiving equation of the fly-eye lens system is deduced. The fly-eye-lens receiving system was designed and simulated using Zemax according to the geometrical optics principle of the lens array. An experimental device for measuring the insertion loss and receiving efficiency of an underwater blue-green LED communication system was built, and the optical power of the receiving optical system was experimentally measured. For the link distances of 1, 3, and 5 m, the received optical power of the double-layered-compound eye system was higher than that of the single-layered system, with a power increase of 72%, 65%, and 60%, respectively. The results show that the double-layered fly-eye-lens receiving antenna can significantly improve the optical power received by the receiving end; therefore, this antenna structure has strong practicability and good development prospects in the field of underwater optical wireless communication.

Associations between short-term exposure of PM2.5 constituents and hospital admissions of cardiovascular diseases among 18 major Chinese cities.

Previous studies showed different risk effects on exposure of fine particulate matter (PM2.5) mass for cardiovascular disease (CVD) globally, which is likely due to different constituents of PM2.5. This study aimed to investigate the association between short-term exposure of PM2.5 constituents and hospital admissions of CVD. Daily counts of city-specific hospital admissions for CVD in 18 cities in China between 2014 and 2017 were extracted from the national Urban Employee Basic Medical Insurance database and the Beijing Municipal Commission of Health and Family Planning Information Center database. Directly measured PM2.5 constituents, including ions and polycyclic aromatic hydrocarbons, were collected by the Chinese Environmental Public Health Tracking system. We used the time-stratified case-crossover design to estimate the association between PM2.5 constituents and hospital admissions of CVD. Concentrations of ions accounted for the majority of the detected constituents. Excess risk (ER) of average ions concentrations for CVD was highest as 2.30% (95% CI: 1.62-2.99%) for NH4+, whose major sources are residential and agricultural emissions. This was followed by 1.85% (1.30-2.41%) for NO3- (generally from vehicles), 0.95% (0.28-1.63%) for SO42- (often from fossil fuel burning) respectively. The association for ions were generally consistent with ischemic heart disease (IHD) and ischemic stroke, e.g., NH4+ was associated with IHD (2.50%; 1.52-3.48%) and ischemic stroke (1.77%; 0.65-2.9%). For polycyclic aromatic hydrocarbons (PAHs), mainly from coal and vehicle-related oil combustion, the constituents were all associated with ischemic stroke but not for IHD. The ER for ischemic stroke was highest at 1.69% (0.99-2.39%) for indeno (123-cd) pyrene. Thus, in terms of the subtypes of CVD, the risks of hospital admissions varied with exposure to different PM2.5 constituents. Exposed to NH4+ had the highest risk to IHD and ischemic stroke, whereas PAHs were predominately associated with ischemic stroke only.

Long-term exposure to ozone and cardiovascular mortality in a large Chinese cohort.

BACKGROUND: Evidence for the association between long-term exposure to ozone (O3) and cause-specific cardiovascular disease (CVD) mortality is inconclusive, and this association has rarely been evaluated at high O3 concentrations. OBJECTIVES: We aim to evaluate the associations between long-term O3 exposure and cause-specific CVD mortality in a Chinese population. METHODS: From 2009 to 2018, 744,882 subjects (median follow-up of 7.72 years) were included in the CHinese Electronic health Records Research in Yinzhou (CHERRY) study. The annual average concentrations of O3 and fine particulate matter (PM2.5), which were estimated using grids with a resolution up to 1 × 1 km, were assigned to the community address for each subject. The outcomes were deaths from CVD, ischemic heart disease (IHD), myocardial infarction (MI), stroke, and hemorrhagic/ischemic stroke. Time-varying Cox model adjusted for PM2.5 and individual-level covariates was used. RESULTS: The mean of annual average O3 concentrations was 68.05 µg/m3. The adjusted hazard ratio per 10 µg/m3 O3 increase was 1.22 (95% confidence interval [CI]: 1.13-1.33) for overall CVD mortality, 1.08 (0.91-1.29) for IHD, 1.21 (0.90-1.63) for MI, 1.28 (1.15-1.43) for overall stroke, 1.39 (1.16-1.67) for hemorrhagic stroke and 1.22 (1.00-1.49) for ischemic stroke, respectively. The study showed that subjects without hypertension had a higher risk for CVD mortality associated with long-term O3 exposure (1.66 vs. 1.15, p = 0.01). CONCLUSIONS: We observed the association between long-term exposure to high O3 concentrations and cause-specific CVD mortality in China, independent of PM2.5 and other CVD risk factors. This suggested an urgent need to control O3 pollution, especially in developing countries.

Whole-Transcriptome Analysis of LncRNAs Mediated ceRNA Regulation in Granulosa Cells Isolated From Healthy and Atresia Follicles of Chinese Buffalo.

Granulosa cells (GCs) are the main supporting cells in follicles and play an important role in the regulation of oocyte maturation and follicular atresia. Accumulating evidence indicates that non-coding RNAs participate in regulation of the physiological function of GCs. However, whole-transcriptome analysis for GCs of buffalo has yet to be reported. In this study, healthy follicles (HFs) and atretic follicles (AFs) were defined according to the apoptosis rate of GCs and the hormone level in follicular fluid. GCs were collected from HFs and AFs (n = 15, 5 < n < 8 mm) for whole-transcriptome analysis using second-generation high-throughput sequencing. A total of 1,861 and 1,075 mRNAs, 159 and 24 miRNAs, and 123 and 100 lncRNAs, were upregulated and downregulated between HFs and AFs, respectively. Enrichment of functions and signaling pathways of these differentially expressed (DE) genes showed that most of DEmRNAs and targets of DEmiRNAs were annotated to the categories of ECM-receptor interaction and focal adhesion, as well as PI3K-AKT, mTOR, TGF-beta, Rap1, and estrogen signaling pathways. The competing endogenous RNA (CeRNA) network was also constructed based on the ceRNA theory which further revealed regulatory roles of these DERNAs in GCs of buffalo follicles. Finally, we validated that lnc4040 regulated the expression of Hif1a as miR-709 sponge in a ceRNA mechanism, suggesting their critical functions in GCs of buffalo follicles. These results show that lncRNAs are dynamically expressed in GCs of HFs and AFs, and interacting with target genes in a ceRNA manner, suggesting their critical functions in buffalo follicular development and atresia.

Rationale, design and population description of the CREDENCE study: cardiovascular risk equations for diabetes patients from New Zealand and Chinese electronic health records.

The cardiovascular risk equations for diabetes patients from New Zealand and Chinese electronic health records (CREDENCE) study is a unique prospectively designed investigation of cardiovascular risk in two large contemporary cohorts of people with type 2 diabetes from New Zealand (NZ) and China. The study was designed to derive equivalent cardiovascular risk prediction equations in a developed and a developing country, using the same epidemiological and statistical methodology. Two similar cohorts of people with type 2 diabetes were identified from large general population studies in China and New Zealand, which had been generated from longitudinal electronic health record systems. The CREDENCE study aims to determine whether cardiovascular risk prediction equations derived in patients with type 2 diabetes in a developed country are applicable in a developing country, and vice versa, by deriving and validating equivalent diabetes-specific cardiovascular risk prediction models from the two countries. Baseline data in CREDENCE was collected from October 2004 in New Zealand and from January 2010 in China. In the first stage of CREDENCE, a total of 93,207 patients (46,649 from NZ and 46,558 from China) were followed until December 31st 2018. Median follow-up was 7.0 years (New Zealand) and 5.7 years (China). There were 5926 (7.7% fatal) CVD events in the New Zealand cohort and 3650 (8.8% fatal) in the Chinese cohort. The research results have implications for policy makers, clinicians and the public and will facilitate personalised management of cardiovascular risk in people with type 2 diabetes worldwide.

Highly nitrogen-doped porous carbon transformed from graphitic carbon nitride for efficient metal-free catalysis.

Nitrogen-doped carbon materials are proposed as promising metal-free catalysts for persulfate-mediated catalytic oxidation process, yet the nitrogen content in the final carbon products is typically low. Moreover, controversies remain in the unambiguous identification of active sites in nitrogen-doped carbons for persulfate activation. Here we report the facile synthesis of nitrogen-doped carbon material via one-step pyrolysis of urea and D-mannitol, which simultaneously combine ultrahigh nitrogen content (up to 33.75 at%) with apparent porous structure via transformation from graphitic carbon nitride. With this strategy, the highly nitrogen-doped porous carbon (NC1.0) exhibits excellent catalytic activity toward peroxymonosulfate (PMS) activation for oxidation of organic pollutants. Both experiments and density functional theory (DFT) calculations, for the first time, revealed that the electron-rich graphitic N and electron-deficient carbon atom adjacent to graphitic N in NC1.0 served as active sites for PMS reduction and oxidation toward the generation of hydroxyl radical (OH) and singlet oxygen (1O2), respectively, in which PMS oxidation was the main reaction in the course of PMS activation rendering 1O2 the dominant reactive oxygen species (ROS) in the NC1.0/PMS system. More importantly, NC1.0 presents robust stability in PMS activation, superior to most reported nitrogen-doped carbon-based catalysts, offering great promise for practical environmental remediation.

SQLE Promotes Differentiation and Apoptosis of Bovine Skeletal Muscle-Derived Mesenchymal Stem Cells.

In this study, Squalene epoxidase (SQLE) overexpression vector was transfected into bovine skeletal muscle-derived mesenchymal stem/stromal cells (MSCs) to study the molecular mechanism of SQLE regulating meat quality through myogenesis. We initially profiled the expression of SQLE in cattle embryos and adults, in the muscle tissue of four different cattle varieties, and in 11 different tissues/organs of Guangxi cattle variety. Subsequently, we isolated and cultured bovine skeletal muscle-derived MSCs and detected the expression of SQLE during cell proliferation and differentiation. Then, we constructed a bovine SQLE overexpression vector and transfected it into bovine skeletal muscle-derived MSCs by liposome transfection. Cell Counting Kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), flow cytometry, immunofluorescence, and quantitative polymerase chain reaction assays were used to characterize cell proliferation and differentiation in detail. The results showed that the relative expression level of bovine SQLE gene in brain tissue was the highest, and in adult muscle tissue was significantly higher than that in embryonic stage. Especially, the expression of SQLE was significantly upregulated in cell differentiation stage. Furthermore, the proliferation, cell cycle, apoptosis, and myoblast differentiation assays indicated that SQLE significantly promoted the differentiation and apoptosis of bovine skeletal muscle-derived MSCs, but inhibited their proliferation. In conclusion, our study reveals the role of SQLE in myoblast differentiation. These results will provide new clues for the regulation network of bovine muscle development.

Oneself is more important: Exploring the role of narcissism and fear of negative evaluation in the relationship between subjective social class and dishonesty.

Previous studies have found that high social class individuals are more dishonest than low social class ones. However, the underlying mechanism of this phenomenon is still unclear. The "ignoring negative consequences" hypothesis suggests that belonging to a high social class makes individuals ignore the negative consequences of dishonesty, whereas the "self-focused" hypothesis suggests that belonging to a high social class makes individuals focus more on the self and self-interests. The present study aims to examine these two hypotheses by measuring participants' subjective social class, narcissism, fear of negative evaluation, and tendency to be dishonest. To this end, an online survey was conducted. Results provide evidence for the self-focused hypothesis by showing that subjective social class positively predicts the tendency to be dishonest, and narcissism plays a mediating role in this relationship.

Predictive factors for acute renal failure in crush injuries in the Sichuan earthquake.

INTRODUCTION: The Sichuan earthquake caused a large number of crush injuries and many of them developed acute renal failure (ARF). A retrospective study was performed on victims with crush injuries of West China Hospital to investigate the predictive factors for acute renal failure (ARF) in crush injuries. PATIENTS AND METHODS: Medical records of injured victims treated in West China Hospital within the first week after the Sichuan earthquake were retrospectively reviewed and 101 patients with crush injury were enrolled in the study. We divided them into an ARF group and a non-ARF group. The clinical data of included patients were extracted and analysed. RESULTS: Patients with ARF accounted for 42% of the included population. Patients younger than 20 made up the biggest age category (45%), and the entrapped time under the debris (22 [IQR 3.5-38]h) was longer than previous reports. In univariate analysis, male gender, multiple crush injuries, medical comorbidities, surgical interventions and infections were more frequent in patients with ARF than in those without ARF. Mean arterial pressure was higher in the ARF group. Besides, the risk of ARF was increased by creatine kinase >14,494.5IU/L most significantly, followed by time under the rubble >4h, aspartate transaminase >453.5IU/L, albumin <27.15g/L and white blood cell >11.8×10(9)/L. In multivariate analysis, male gender, time under the rubble, multiple crush injuries, surgical interventions, infections and creatine kinase level were independently associated with ARF in crush injuries. CONCLUSIONS: The entrapped time under the debris, multiple crush injuries, male gender, infections, and creatine kinase level are predictive factors for ARF in crush injuries.

Effect of high glucose levels on the calcification of vascular smooth muscle cells by inducing osteoblastic differentiation and intracellular calcium deposition via BMP-2/Cbfα-1 pathway.

In this paper, we investigate the effect and the possible mechanism of high glucose levels on the calcification of human aortic smooth muscle cells (HASMCs). HASMCs were divided into four groups: normal glucose group (NG), osmolality control group (OC), high glucose group (HG, HASMCs culture medium containing 30 mmol/L glucose), and high glucose plus recombinant human Noggin protein (bone morphogenetic protein-2 (BMP-2) antagonist) group (HN). The mRNA levels and the protein expressions of BMP-2 and core binding factor alpha-1 (Cbfα-1) were measured by real-time quantitative polymerase chain reaction (PCR) and Western blot. After induced by 10 mmol/L ß-glycerol phosphoric acid, cells were harvested for assessments of alkaline phosphatase (ALP) activities at Days 1, 2, and 3, and intracellular calcium contents at Days 7 and 14, respectively. High glucose levels increased the mRNA levels and the protein expressions of BMP-2 and Cbfα-1 (P<0.05). The expression of Cbfα-1 was partially blocked by Noggin protein (P<0.05), while BMP-2 was not (P>0.05). After being induced by ß-glycerol phosphoric acid, high glucose levels increased the ALP activity [(48.63±1.03) vs. (41.42±2.28) U/mg protein, Day 3; P<0.05] and the intracellular calcium content [(2.76±0.09) vs. (1.75±0.07) µmol/mg protein, Day 14; P<0.05] in a time-dependent manner when compared with the NG group, while the ALP activity could not be blocked by Noggin protein [(48.63±1.03) vs. (47.37±0.97) U/mg protein, Day 3; P>0.05]. These results show that high glucose levels can evoke the calcification of HASMCs by inducing osteoblastic trans-differentiation and intracellular calcium deposition via the BMP-2/Cbfα-1 pathway, which can be partially blocked by Noggin protein.