Lipid profiles and the risk of new-onset hypertension in a Chinese community-based cohort.

BACKGROUND AND AIMS: Dyslipidemia and hypertension, key risk factors for cardiovascular disease, may share similar pathophysiological processes. A longitudinal association was reported between dyslipidemia and new-onset hypertension, but few data were published in Asian. We aimed to investigate the association of lipid profiles with new-onset hypertension in a Chinese community-based non-hypertensive cohort without lipid-lowering treatment (n = 1802). METHODS AND RESULTS: New-onset hypertension was defined as any self-reported history of hypertension, systolic blood pressure ≥140 mmHg, or diastolic blood pressure ≥90 mmHg, or receiving antihypertensive medications at follow-up. Logistic regression models were used to evaluate the associations. Participants were aged 53.97 ± 7.49 years, 31.19% were men, and 64.54% with dyslipidemia. During a median of 2.30 years follow-up, the incidence of new-onset hypertension was 12.99%. Multivariate adjusted risks of new-onset hypertension increased with triglyceride increases (odds ratio [OR] = 1.14, 95% confidence interval [CI]: 1.03-1.27) and high-density lipoprotein cholesterol (HDL-C) decreases (OR = 0.47, 95% CI: 0.29-0.76) for one unit. However, threshold effects were observed for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-HDL-C. Compared with subjects with hyperlipidemia, in those with normal concentrations of TC, LDL-C, and non-HDL-C increased risks of new-onset hypertension were observed with OR (95% CI) of 1.65 (1.10-2.46), 1.58 (1.07-2.33), and 1.57 (1.15-2.15) for one unit increasement, respectively, after adjusting for all covariates. CONCLUSION: Higher TG and lower HDL-C increased the risk of new-onset hypertension, but for TC, LDL-C and non-HDLC, the risk of new-onset hypertension was increased only at normal concentrations in a Chinese community-based cohort.

An Extended Kalman Filter and Back Propagation Neural Network Algorithm Positioning Method Based on Anti-lock Brake Sensor and Global Navigation Satellite System Information.

Telematics box (T-Box) chip-level Global Navigation Satellite System (GNSS) receiver modules usually suffer from GNSS information failure or noise in urban environments. In order to resolve this issue, this paper presents a real-time positioning method for Extended Kalman Filter (EKF) and Back Propagation Neural Network (BPNN) algorithms based on Antilock Brake System (ABS) sensor and GNSS information. Experiments were performed using an assembly in the vehicle with a T-Box. The T-Box firstly use automotive kinematical Pre-EKF to fuse the four wheel speed, yaw rate and steering wheel angle data from the ABS sensor to obtain a more accurate vehicle speed and heading angle velocity. In order to reduce the noise of the GNSS information, After-EKF fusion vehicle speed, heading angle velocity and GNSS data were used and low-noise positioning data were obtained. The heading angle speed error is extracted as target and part of low-noise positioning data were used as input for training a BPNN model. When the positioning is invalid, the well-trained BPNN corrected heading angle velocity output and vehicle speed add the synthesized relative displacement to the previous absolute position to realize a new position. With the data of high-precision real-time kinematic differential positioning equipment as the reference, the use of the dual EKF can reduce the noise range of GNSS information and concentrate good-positioning signals of the road within 5 m (i.e. the positioning status is valid). When the GNSS information was shielded (making the positioning status invalid), and the previous data was regarded as a training sample, it is found that the vehicle achieved 15 minutes position without GNSS information on the recycling line. The results indicated this new position method can reduce the vehicle positioning noise when GNSS information is valid and determine the position during long periods of invalid GNSS information.

Novel non-trimethoxylphenyl piperlongumine derivatives selectively kill cancer cells.

Piperlongumine (PL) is a natural alkaloid with broad biological activities. Twelve analogues have been designed and synthesized with non-substituted benzyl rings or heterocycles in this work. Most of the compounds showed better anticancer activities than the parent PL without apparent toxicity in normal cells. Elevation of cellular ROS levels was one of the main anticancer mechanisms of these compounds. Cell apoptosis and cell cycle arrest for the best compound ZM90 were evaluated and similar mechanism of action with PL was demonstrated. The SAR was also characterized, providing worthy directions for further optimization of PL compounds.

The prognostic value of Forkhead box P3 regulatory T cells in biliary tract cancer: A systematic review and meta-analysis.

BACKGROUND: This study aimed to explore the value of tumor-infiltrating Forkhead box P3(FoxP3+) regulatory T cells (Tregs) in evaluating the prognosis of biliary tract cancer. METHODS: Four electronic databases were searched using 2 computers: PubMed, Embase, Web of Science, and Cochrane Library. The vocabulary and syntax were adapted according to the database. Two researchers independently selected the studies, collected information, and assessed the risk of bias. The Meta-analysis was performed using STATA 17.0, and HR and its corresponding 95% CI were used to evaluate the correlation between FoxP3+ Tregs and the overall survival of patients with biliary tract cancer. In addition, the quality of the included studies was evaluated. RESULTS: Ten articles were included in this study. The results of the meta-analysis showed that patients with high FoxP3+ Tregs infiltration had worse overall survival (OS) (HR = 1.34,95% CI 1.16 to 1.71; P < .001). Subgroup analysis of gallbladder carcinoma and cholangiocarcinoma showed that the high infiltration of FoxP3+ Tregs was significantly correlated with the OS of the former (HR = 1.55,95% CI 1.11 to 2.00; P < .001), but not with the OS of the latter (HR = 1.00,95% CI 0.62 to 1.38; P > .05). CONCLUSIONS: Our meta-analysis reveals that high infiltration of FoxP3 + Tregs is significantly associated with reduced overall survival in gallbladder carcinoma, endorsing their use as a prognostic biomarker for this subtype. In contrast, no significant prognostic correlation was identified for FoxP3+ Tregs in cholangiocarcinoma, indicating the need for subtype-specific evaluation of their prognostic relevance in biliary tract cancers.

Heart Rate Predicts the Risk of New-Onset Peripheral Arterial Disease in a Community-Based Population in China.

INTRODUCTION: Elevated heart rate is linked with poor prognosis and has been shown to accelerate the progress of atherosclerosis. However, the association between heart rate and new-onset PAD is unknown. METHODS: A total of 3463 participants without PAD at baseline from a community-based cohort in Beijing were included and followed up for 2.3 years. PAD was defined as ankle-brachial index (ABI) ≤0.9. We used multivariate logistic regression models to investigate the association of heart rate and the risk of new-onset PAD. RESULTS: Participants were 56.67 ± 8.54 years old, and 36.12% were men. The baseline ABI was 1.11 ± 0.08, and the incidence of new-onset PAD was 2.97%. Multivariate regression models, adjusted for sex, age, risk factor of atherosclerosis, medications, and baseline ABI, showed that heart rate was significantly associated with incidence of PAD (odds ratio [OR] = 1.22, 95% confidence interval [CI]: 1.03-1.43, P = 0.020); every increase of 10 heart beats per minute (bpm) was associated with a 22% increase in the odds of developing new-onset PAD. Respondents in the higher-heart rate group (≥80 bpm) had an increased risk of new-onset PAD, compared with those in the lower-heart rate group (<80 bpm) (OR = 1.73, 95% CI: 1.14-2.63, P = 0.010). Subgroup analyses revealed no significant heterogeneity among the analyzed subgroups. CONCLUSION: Elevated heart rate was independently associated with the risk of new-onset PAD in a community-based population in Beijing. Heart rate management should be considered for the purpose of PAD prevention.

Association of depressive symptoms with the progression of carotid intima-media thickness in a community-based cohort in Beijing, China.

OBJECTIVES: To determine the relationship between depressive symptoms and progression of carotid intima-media thickness (cIMT) in a Beijing community-based population. DESIGN: Prospective cohort study between 2014 and 2018. SETTING: Dwellers without cardiovascular disease, hypertension or diabetes from a Beijing community. PARTICIPANTS: 3849 Chinese community-dwelling individuals who underwent baseline screening for depressive symptoms were invited to participate in the study in 2014 and follow-up visit in 2018. Among them, 2124 participants completed carotid ultrasound examination both at baseline and a follow-up visit. After further excluding patients with a history of stroke, myocardial infarction or lower extremity arterial stenosis and those with a diagnosis of hypertension or diabetes and ankle-brachial index ≤0.9 at baseline, 1011 eligible participants were finally included. PRIMARY OUTCOME MEASURE: The rate of mean cIMT change. RESULTS: Over a median follow-up period of 4.40 years, the overall rate of mean cIMT change was 2.23% (-5.64% to 9.51%). After adjustment for 13 covariates, there was an increase of 2.36% (ß=2.36, 95% CI: 0.37 to 4.36, p=0.020) for the rates of mean cIMT change in the depressive group compared with the control group. Furthermore, this association was modified by drinking status (ß=3.22, 95% CI: 1.25 to 5.19, P-interaction=0.006). CONCLUSION: Depressive symptoms were independently associated with progression of mean cIMT in a community-based cohort in Beijing, China. Furthermore, this relationship was modified by drinking status.

Brachial-ankle pulse wave velocity is independently associated with urine albumin-to-creatinine ratio in a Chinese community-based cohort.

PURPOSE: Arterial stiffness is important in the development of albuminuria. The brachial-ankle pulse wave velocity (baPWV) acts as an indicator of arterial stiffness and may be associated with cardiovascular disease morbidity and mortality. The urine albumin-to-creatinine ratio (UACR) is a metric used to diagnose albuminuria and has also been shown to be associated with cardiovascular disease. Here, we aim to elucidate the relationship between the baPWV and UACR in the Chinese community. METHODS: A community-based cohort of 3669 subjects was selected for the analysis. The BaPWV and UACR were measured from each subject. UACR ≥ 30 mg/g was defined as pathological albuminuria. RESULTS: The mean baPWV was 1536.59 ± 305.89 cm/s, and the median UACR value was 6.11 mg/g (interquartile range 4.17, 10.68). A threshold-effect analysis was conducted, and the results showed that the cut-off value for the baPWV was 1269 cm/s. In subjects with baPWV values lower than 1269 cm/s, the prevalence of microalbuminuria and macroalbuminuria was not significantly associated with the baPWV (odds ratio 0.77, 95% confidence interval 0.57-1.03, P = 0.08). However, in participants with baPWV ≥ 1269 cm/s, the prevalence of microalbuminuria and macroalbuminuria increased with increasing baPWV 100 cm/s (odds ratio 1.16, 95% confidence interval 1.11-1.22, P < 0.001). CONCLUSIONS: These findings suggest that, in this Chinese community-based cohort, elevated baPWV is independently associated with pathological albuminuria with a cut-off value of 1269 cm/s as determined by threshold-effect analysis.

Kidney function predicts the risk of asymptomatic peripheral arterial disease in a Chinese community-based population.

PURPOSE: Lower-extremity peripheral arterial disease (PAD) can predict the risk of subsequent cardiovascular disease (CVD) and all-cause mortality. Chronic kidney disease (CKD) as a precursor of CVD has been proven to be independently associated with PAD. However, few data exist regarding the prediction value of kidney function for incident asymptomatic PAD in community-based populations. We aimed to investigate the predicting value of estimated glomerular filtration rate (eGFR) for incident asymptomatic PAD in a Chinese community-based population. A total of 3549 subjects without PAD and eGFR > 30 ml/min/1.73 m2 were included. METHODS: PAD was defined by an ankle-brachial index (ABI) ≤ 0.9. Multivariate regression models were used to evaluate the associations. RESULTS: Subjects were 56.69 ± 8.56 years old and 35.9% were males. After 2.36 years of follow-up, the incidence of asymptomatic PAD was 3.1%. The risk of incident PAD was graded related to the categories of eGFR. Compared to participants with normal kidney function, the multivariate adjusted OR [95% CI] for new PAD was 1.31 (0.81-2.12) for those with mildly decreased kidney function, 4.13 (1.73-9.89) for those with grades 3 CKD (P for trend: 0.014). Baseline eGFR was significantly and linearly associated with incident PAD (OR [95% CI] for each 5 mL/min/1.73 m2 decrease of eGFR: 1.23 [1.09-1.38]) in participants with baseline eGFR < 90 mL/min/1.73 m2 but not in those with baseline eGFR ≥ 90 mL/min/1.73 m2 after adjustment for covariates. CONCLUSION: Kidney function was an independent risk factor for development of incident PAD in community-based population with baseline eGFR ≤ 90 mL/min/1.73 m2.

Metabolic Syndrome Is Associated With Rapid Estimated Glomerular Filtration Rate Decline In A Chinese Community-Based Population.

PURPOSE: This study aimed to determine the relationship between the metabolic syndrome (MetS) and rapid estimated glomerular filtration rate (eGFR) decline in a Chinese community-based population. PATIENTS AND METHODS: A total of 3108 participants were recruited between December 2011 and July 2014 from an observational study cohort designed for the study of atherosclerotic diseases in Beijing, China. The outcome was a rapid eGFR decline. Subgroup and interaction analyses were performed with respect to a number of covariates. RESULTS: Over a median follow-up period of 2.34 (IQR: 2.29-2.41) years, the overall incidence of rapid eGFR decline was 7.24%. We found that the MetS was significantly associated with the risk of rapid eGFR decline (odds ratio [OR]=1.69, 95% confidence interval [CI]: 1.28-2.23, p<0.001) in a model adjusted for age, sex, and eGFR, and this relationship remained significant after adjustment for smoking, drinking, and low-density lipoprotein-cholesterol (OR=1.78, 95% CI: 1.34-2.35, p<0.001). Waist circumference (OR=1.38, 95% CI: 1.04-1.83, p=0.027), triglycerides (OR=1.40, 95% CI: 1.05-1.86, p=0.022), blood pressure (OR=2.05, 95% CI: 1.49-2.82, p<0.001), and fasting plasma glucose (OR=2.12, 95% CI: 1.57-2.85, p<0.001), but not high-density lipoprotein-cholesterol (OR=1.26, 95% CI: 0.94-1.69, p=0.117), were positively associated with the risk of rapid eGFR decline. Similarly, an increase in the number of MetS components present was associated with an increase in the risk of rapid eGFR decline. Furthermore, this association was modified by smoking status (OR=3.78, 95% CI: 1.68-8.49, p-interaction=0.030). CONCLUSION: The MetS independently predicted rapid eGFR decline in a Chinese community-based cohort recruited for the study of atherosclerosis. The relationship between the MetS and the risk of rapid eGFR decline was modified by smoking status.

Small molecules inhibiting Keap1-Nrf2 protein-protein interactions: a novel approach to activate Nrf2 function.

Oxidative stress is well recognized to contribute to the cause of a wide range of diseases, such as cancer, diabetes, Alzheimer's disease, arteriosclerosis, and inflammation. The Keap1-Nrf2-ARE pathway plays a critical regulatory role and can protect cells from oxidative stress through activating Nrf2 to induce its downstream phase II enzymes. Nrf2 activation through the covalent inactivation of Keap1 may cause unpredictable side effects. Non-covalent disruption of the Keap1-Nrf2 protein-protein interactions is an alternative strategy for Nrf2 activation, potentially with reduced risk of toxicity. Efforts have been made in recent years to develop peptide- and small molecule-based Keap1-Nrf2 PPI inhibitors via different approaches, including high-throughput screening, target-based virtual screening, structure-based optimization, and fragment-based drug design. This review aims to highlight the recently discovered small-molecule inhibitors as well as their therapeutic potential.

Concentration-Dominated Temperature-Dependence of Upconversion Luminescence in Gd6WO12 Nanophosphor Co-Doped with Er3+ and Yb3+.

Nanosized Gd6WO12 phosphors containing various Er3+ concentrations and fixed Yb3+ concentration were synthesized by a co-precipitation method. The crystal structure and microscopic morphology of the obtained nanophosphors were characterized by means of X-ray diffraction (XRD) and field emission scanning electron microscopy (FE-SEM). Two-photon processes for both the green and red upconversion (UC) emissions were confirmed by analyzing the dependence of UC intensities on 980 nm laser working current. UC emission intensity changing with temperature displays different trends for the samples with different Er3+ concentrations. The experimental results indicated that thermal quenching behavior of UC luminescence could not be simply explained by crossover mechanism. The enhancement for green UC emission in the sample with higher Er3+ concentration was discussed. Finally, the ErS+ concentration dependence of UC luminescence was experimentally observed, and its mechanisms were analyzed.