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Aims: We aimed to investigate the independent associations between growth differentiation factor 15 (GDF‐15) level at admission and cardiovascular (CV) death, thrombotic events, heart failure (HF), and bleeding outcomes in patients with coronary artery disease (CAD). Methods and results: We measured the plasma concentrations of GDF‐15 centrally in patients from the BIomarker‐based Prognostic Assessment for patients with Stable angina and acute coronary Syndrome (BIPass) registry, which consecutively enrolled patients with CAD from November 2017 to September 2019 at five tertiary hospitals in China. The outcomes included CV death, thrombotic events [myocardial infarction (MI) and ischaemic stroke], HF events [acute HF during hospitalization and hospitalization for HF post‐discharge (A/H HF) and cardiogenic shock], and bleeding outcomes [non‐coronary artery bypass grafting‐related major bleeding and clinically significant bleeding (CSB)] during the 12 month follow‐up period after hospitalization. Among 6322 patients with CAD {65.4% male, median age 63.7 [inter‐quartile range (IQR)] 56.0–70.1 years}, the median concentration of plasma GDF‐15 at admission was 1091 (IQR 790.5–1635.0) ng/L. Higher concentrations of GDF‐15 were associated with an increased risk of CV death [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.35–2.88, P < 0.001], A/H HF (HR 2.69, 95% CI 1.92–3.77, P < 0.001), cardiogenic shock (HR 1.46, 95% CI 1.04–2.05, P = 0.029), and CSB (HR 1.48, 95% CI 1.22–1.79, P < 0.001), but not for MI or stroke, after adjusting for clinical risk factors and prognostic biomarkers. Adding GDF‐15 to the model with risk factors and biomarkers improved the net reclassification for CV death, A/H HF, cardiogenic shock, and CSB. Conclusions: In patients with CAD, admission levels of GDF‐15 were associated with an increased 1 year risk of CV death, HF, and bleeding outcomes, but not with thrombotic events. GDF‐15 may be a prognostic biomarker for CV death, HF, and bleeding outcomes and could be used to refine the risk assessment of these specific clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT04044066 [ABSTRACT FROM AUTHOR]

Objective: Smoking and obesity are established risk factors of dyslipidemia, however, the interplay between them has not been well studied. This study aims to explore the joint effect of smoking and body mass index (BMI) on serum lipid profiles. Methods: The study consisted of 9846 Chinese adults (mean age = 49.9 years, 47.6% males, 31.2% ever smokers), based on the China Health and Nutrition Survey. Serum lipid profiles included total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (APO-A), and apolipoprotein B (Apo-B). The joint effect of smoking and BMI on serum lipids were examined by the four-way decomposition analysis and multivariate linear regression models. Results: The four-way decomposition showed that the interplay between smoking and BMI was complicated. There was only indirect effect (the mediated effect) between smoking and BMI on TC, LDL-C and APO-B. The pure indirect effect was -0.023 for TC, -0.018 for LDL-C, and -0.009 for APO-B. For TG, HDL-C and APO-A, the interaction effect was dominant. The reference interaction (the interactive effect when the mediator is left to what it would be in the absence of exposure) was 0.474 (P < 0.001) for TG, -0.245 (P = 0.002) for HDL-C, and -0.222 (P < 0.001) for APO-A, respectively. The effect of BMI on TG, HDL-C and APO-A were significantly higher in smokers than in nonsmokers (TG: 0.151 in smokers versus 0.097 in nonsmokers, HDL-C: -0.037 versus -0.027, APO-A: -0.019 versus -0.009, P for difference < 0.001 for all). Conclusion: These findings illustrate the joint effects of smoking and BMI on serum lipid profiles. There were significant interaction effects of smoking and BMI on TG, HDL-C and APO-A, while BMI maybe a mediator for the association of smoking with TC, LDL-C and APO-B. The effects between them were rather complex. Smoking cessation is necessary, especially for those overweight. [ABSTRACT FROM AUTHOR]

This paper aims to report complex bursting patterns in a parametrically and externally excited Jerk circuit system. Typically, the common compound bursting with two clusters in each period can be observed in this system. By the fast-slow analysis, we find that the active states related to this type of bursting are created by supercritical Hopf bifurcations. Interestingly, with the increase of parametric excitation amplitude, the common bursting pattern evolves into the ones that display complex structures. We show that the parametric excitation amplitude plays a vital role in influencing the dynamical behaviors, which is apparent from the two-parameters analysis. Then, a rich variety of dynamical phenomena including period-doubling and inverse period-doubling cascades in orbits of period 2, 4, and 8 can be observed with the increase of parametric excitation amplitude, thereby leading to complex bursting patterns with multiple-periodically active states. Besides, as a result of the period-doubling cascades, chaotic attractors are eventually discovered, which can be corroborated by the maximal Lyapunov exponent. In particular, periodic windows with period-doubling and inverse period-doubling cascades also emerge in the chaotic region when the parametric excitation amplitude increases to higher values. These give rise to the complex bursting patterns with chaotically active states. Based on this, two types of bursting patterns with complex structures, i.e., bursting patterns with multiple-periodically active states and bursting patterns with chaotically active states are revealed. Our results enrich the routes to complex bursting and deepen the understanding of bursting patterns with complex structures. [ABSTRACT FROM AUTHOR]

Pulse-shaped explosion (PSE), characterized by pulse-shaped sharp quantitative changes in relation to the variation of system parameters, is a novel dynamical mechanism underlying the occurrence of bursting oscillations. In previous works, the generation of PSE was found to be related to a fold bifurcation of the critical escape transitions. In this paper, we report a new route to PSE based on the externally and parametrically excited Rayleigh system. We show that the forward and reverse C-shaped equilibrium curves, exhibiting two symmetrical fold points, can be observed in the fast subsystem. In particular, we find that the two opposite C-shaped equilibrium curves are tangent at the fold point of fold curves, which leads to an X-shaped equilibrium curve that is extremely steep near the tangent point. With the disappearance of the fold point of fold curves, the X-shaped equilibrium curve splits into two separate branches, both of which show pulse-shaped quantitative changes. As a result, two symmetrical PSEs are created. Based on this, a new route to PSE by the fold bifurcation of fold curves is presented. Finally, we briefly investigate bursting dynamics induced by the PSE and the effects of parametric excitation amplitude on bursting dynamics. [ABSTRACT FROM AUTHOR]

The pulse-shaped explosion (PSE), characterized by the pulse-shaped quantitative of system solutions varying dramatically, is a special route to bursting oscillations reported recently. This paper reports interesting dynamical behaviors related to the PSE of equilibria, and based on that, the complex bursting dynamics is investigated in a van der Pol–Mathieu–Duffing system with multiple-frequency slow-varying excitations. We find that bifurcations can be observed in a narrow parameter interval within PSE. We also show that two groups of bifurcations are symmetrically arranged on both sides of PSE, and each of which determines a different bursting part. Based on this, two compound bursting patterns, i.e. compound Hopf/Hopf bursting oscillation and compound subHopf/fold cycle bursting oscillation, and a novel type of relaxation oscillation (bursting oscillation of point/point) independent of bifurcations, are revealed. Our results enrich the knowledge of dynamical behaviors related to PSE as well as the possible routes to complex bursting dynamics. [ABSTRACT FROM AUTHOR]

Dear Editor, Endoscopy with iodine staining was widely used for esophageal cancer (EC) screening in high-incidence area.1,2 Most endoscopy screening-positive population was found to develop esophageal epithelium lesion, and therefore endured higher risk for developing esophageal squamous cell carcinoma (ESCC) than normal population.3,4 However, endoscopic screening may be too costly and invasive for large-scale population, and non-invasive biomarkers may be more applicable and cost effective for population-based screening.5,6 In this population-based screening study, we aim to identify potential metabolic biomarkers for early screening of ESCC, and establish the optimal early ESCC screening model. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was used to explore ESCC screening related metabolic biomarkers and profile difference between ESCC screening-positive subjects and normal population. [Extracted from the article]

Background: Long-term smoking exposure will increase the risk of esophageal squamous cell carcinoma (ESCC), whereas the mechanism is still unclear. We conducted a cross-sectional study to explore whether serum metabolites mediate the occurrence of ESCC caused by cigarette smoking.Methods: Serum metabolic profiles and lifestyle information of 464 participants were analyzed. Multiple logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of smoking exposure to ESCC risk. High-dimensional mediation analysis and univariate mediation analysis were performed to screen potential intermediate metabolites of smoking exposure for ESCC.Results: Ever smoking was associated with a 3.11-fold increase of ESCC risk (OR = 3.11, 95% CI 1.63-6.05), and for each cigarette-years increase in smoking index, ESCC risk increased by 56% (OR = 1.56, 95% CI 1.18-2.13). A total of 5 metabolites were screened as mediators by high-dimensional mediation analysis. In addition, glutamine, histidine, and cholic acid were further proved existing mediation effects according to univariate mediation analysis. And the proportions of mediation of histidine and glutamine were 40.47 and 30.00%, respectively. The mediation effect of cholic acid was 8.98% according to the analysis of smoking index.Conclusions: Our findings suggest that cigarette smoking contributed to incident ESCC, which may be mediated by glutamine, histidine and cholic acid. [ABSTRACT FROM AUTHOR]

This paper investigates bursting dynamics of a Rayleigh oscillator with multiple-frequency slow excitations, in which two different bursting patterns related to the bistable pulse-shaped explosion (PSE) are obtained. Typically, the PSE, a novel sharp transition behavior reported recently, can be observed in the Rayleigh oscillator. We show that if there is an initial phase difference - π 2 between the slow excitations, two coexisting solution branches exhibiting PSE, which we call bistable PSE, may be created in the fast subsystem. Then, the route to bursting by the bistable PSE is analyzed, and two different bursting patterns, i.e., bursting of point–point type and bursting of cycle–cycle type, are obtained. Our findings show that the initial phase difference of excitations may have great effects on PSE, which thus plays an important role in transitions to different attractors and complex bursting dynamics. [ABSTRACT FROM AUTHOR]