Soluble ST2 for predicting heart failure, atrial fibrillation and death in patients with coronary heart disease with or without renal insufficiency.

Background: This study aimed to investigate the relationship between baseline soluble suppression of tumorigenesis-2 (sST2) concentration and the outcomes of heart failure (HF), atrial fibrillation (AF) or death in patients with coronary heart disease (CHD) with or without renal insufficiency (RI). Methods: Between March 2011 and December 2015, 3454 patients with CHD from the Chinese PLA General Hospital were enrolled in this cohort study. The patients were followed up until October 2021. AF, HF, and death events were recorded. Associations between baseline sST2 concentrations and clinical outcomes were assessed using Kaplan-Meier (K-M) curves, and Cox regression and generalised additive models. Subgroup analysis were carried out between RI and non-RI groups. Results: Among the patients with CHD (61.5 ± 11.8 years; 78.6 % men), 415 (12.02 %) had RI. During a median follow-up of 8.37 years, HF and AF were reported in 216 (6.25 %) and 174 (5.04 %) patients, respectively, and 297 (8.60 %) died. The K-M curves indicated that patients in the higher quartiles of sST2 concentrations were correlated with a poor survival rate of HF, AF, or death (all Ps < 0.001). Generalised additive model (GAM) demonstrated a nonlinear positive association between sST2 concentration and the risk of HF, AF, and death in CHD patients. The cut-off value of sST2 for predicting HF, AF and death were 32.1, 25.4 and 28.6 ng/mL, respectively. CHD patients with sST2 higher than the cut-off value had higher risks of HF (HR: 3.02, 95%CI: 2.24-4.05), AF (HR: 2.86; 95%CI: 2.10-3.90), and death (HR:2.11, 95%CI: 1.67-2.67). Furthermore, in patients with RI (12.02 %, n = 415), the prognostic value of sST2 over the cut-off value for HF and death remained unchanged (HR: 3.21 and 2.35; P < 0.05). In patients with CHD with or without RI, sST2 improved the area under the curve (AUC) of traditional risk models for predicting clinical endpoint events. Conclusions: The biomarker sST2 may be useful for predicting HF, AF, and death in patients with CHD. The predicted value was not affected by renal function.

Effects of Banxia Baizhu Tianma Decoction in alleviating atherosclerosis based on the regulation of perivascular adipose.

ETHNOPHARMACOLOGICAL RELEVANCE: The occurrence and development of atherosclerosis, a common chronic inflammatory vascular disease, are closely related to cardiovascular and cerebrovascular diseases. Banxia Baizhu Tianma Decoction (BBTD) is a representative traditional Chinese medicine formula that resolves phlegm, disperses wind, invigorates the spleen and eliminates dampness and is also a commonly used clinical medication for treating vascular diseases. AIM OF THE STUDY: To explore the pharmacological mechanisms of BBTD in alleviating atherosclerosis, the present study was carried out by conducting an integrative analysis of aortic and perivascular adipose tissue (PVAT) proteomics and metabolomics. MATERIALS AND METHODS: Eight-week-old ApoE-/- mice were randomly divided into the BBTD group and the model group, and nine age-matched C57BL/6J (C57) mice were used as the control group (n = 9). The C57 mice were fed a standard diet, while the ApoE-/- mice were fed a high-fat, high-cholesterol diet for 12 weeks. Mice in the BBTD group were transgastrically administered BBTD at a dose of 17.8 g/kg/day for 8 weeks, while the model group and control group mice received an equivalent volume of saline by gavage. Histomorphology of the aortas and PVAT was assessed by HE staining, oil red O staining, Masson staining, and α-SMA and CD68 immunohistochemical methods. An integrative analysis of aortic proteomics, PVAT proteomics and PVAT metabolomics was conducted to study the pharmacological mechanisms of BBTD. RESULTS: Compared to the model group, mice treated with BBTD had thicker fibrous caps, increased collagen content, less erosion of smooth muscle cells and infiltration of macrophages, as well as a relatively low inflammatory response level, suggesting that BBTD treatment reduced plaque vulnerability. Omics analysis suggested that BBTD treatment demonstrated anti-atherosclerotic effects and increased plaque stability in the aorta by activating the TGF-beta pathway. Simultaneously, BBTD inhibited PVAT inflammation levels (decreased the levels of MCP and IL-6). Proteomics and metabolomics of PVAT suggested that the targets of BBTD included upregulation of the α-linolenic acid metabolic pathway and downregulation of multiple inflammatory pathways, such as the NF-kappa B signalling pathway, primary immunodeficiency and Th17 cell differentiation in PVAT. CONCLUSIONS: BBTD reduces the vulnerability of atherosclerotic plaques and inhibits the inflammatory phenotype of perivascular adipose tissue.

Association between allostatic load and adverse outcomes among older patients with heart failure with preserved ejection fraction.

BACKGROUND: The allostatic load (AL) refers to the cumulative weakening of multiple physiological systems caused by repeated adaptation of the body to stressors There are still no studies have focused on the association between AL and the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). The present study aimed to investigate the association between AL and adverse outcomes, including mortality and HF admission, among elderly male patients with HFpEF. METHODS: We conducted a prospective cohort study of 1111 elderly male patients with HFpEF, diagnosed between 2015 and 2019 and followed up through 2021. We constructed an AL measure using a combination of 12 biomarkers. The diagnosis of HFpEF was made according to the 2021 European Society of Cardiology guidelines. A Cox proportional hazards model was used to determine the associations between AL and adverse outcomes. RESULTS: In multivariate analysis, AL was significantly associated with increased risk of all-cause mortality (medium AL: adjusted hazard ratio [HR] = 2.53; 95% confidence interval [CI] 1.37-4.68; high AL: HR = 4.21; 95% CI 2.27-7.83; per-score increase: HR = 1.31; 95% CI 1.18-1.46), cardiovascular mortality (medium AL: HR = 2.67; 95% CI 1.07-6.68; high AL: HR = 3.13; 95% CI 1.23-7.97; per-score increase: HR = 1.20; 95% CI 1.03-1.40), non-cardiovascular mortality (medium AL: HR = 2.45; 95% CI 1.06-5.63; high AL: HR = 5.81; 95% CI 2.55-10.28; per-score increase: HR = 1.46; 95% CI 1.26-1.69), and HF admission (medium AL: HR = 2.68; 95% CI 1.43-5.01; high AL: HR = 3.24; 95% CI 1.69-6.23; per-score increase: HR = 1.24; 95% CI 1.11-1.39). Consistent results were found in multiple subgroup analyses. CONCLUSIONS: A higher AL was associated with poor prognosis in elderly men with HFpEF. AL relies on information that is easily obtained in physical examinations and laboratory parameters and can be assessed in various care and clinical settings to help risk stratification of HFpEF patients.

Association of blood pressure variability and CT-based Leiden score in hypertension patients.

Background: Blood pressure variability (BPV) obtained from ambulatory blood pressure monitoring (ABPM) has been demonstrated to accurately predict the risk of cerebrovascular events and death in hypertension patients, however, the association between BPV and the severity of coronary atherosclerotic plaque remains unclear. Methods: Patients with hypertension combined with suspected coronary artery disease (CAD) were collected, who underwent both ABPM and coronary computed tomographic angiography (CCTA) from December 2017 to March 2022. Patients were divided into three groups according to the Leiden score: low-risk group (Leiden score <5), medium-risk group (Leiden score 5-20), and high-risk group (Leiden score >20). The clinical characteristics of patients were collected and analyzed. Univariate Pearson correlation and multivariate Logistics regression were used to determine the association between BPV and the severity of coronary atherosclerotic plaque. Results: A total of 783 patients were included, with the average age of (62.85 ± 10.17) years and 523 males. Patients in the high-risk group had higher mean systolic blood pressure (SBP), nighttime mean SBP and SBP variability (P < 0.05). Leiden score with low risk was associated with 24 h-SBP variability (r = 0.35, P = 0.006) and 24 h-diastolic blood pressure (DBP) loading (r = -0.18, P = 0.027). Leiden score with medium and high risk was associated with nighttime mean SBP (r = 0.23, P = 0.005), 24 h-SBP variability (r = 0.32, P = 0.003), and the decrease of nighttime SBP (r = 0.24, P = 0.019). Multivariate Logistic analysis showed that smoking [odds ratio (OR) = 1.014, 95% confidential interval (CI): 1.0-1.07, P = 0.03], diabetes (OR = 1.43, 95% CI: 1.10-2.26, P = 0.01) and 24 h-SBP variability (OR = 1.35, 95% CI: 1.01-2.46, P = 0.01) were independently associated with Leiden score with medium and high risk. Conclusion: Larger SBP variability in hypertensive patients indicates the higher Leiden score and consequently the more serious coronary atherosclerotic plaque. Monitoring SBP variability has certain significance for predicting the severity of coronary atherosclerotic plaque and preventing its progression.

Preliminary clinical observation of double C-arm digital subtraction angiography guidance during transjugular intrahepatic portosystemic shunt placement.

BACKGROUND: This study aimed to investigate the safety, preliminary clinical experience, and technical advantages of double C-arm digital subtraction angiography -assisted portal vein puncture for transjugular intrahepatic portosystemic shunt. METHODS: Clinical data of 25 patients with portal hypertension caused by liver cirrhosis were retrospectively analyzed from January 2021 to June 2022. The fluoroscopy time, puncture time, mean portosystemic pressure gradient, dose area product, and intraoperative and postoperative complications were recorded. RESULTS: Transjugular intrahepatic portosystemic shunt was performed in all 25 patients, with a success rate of 100%. The fluoroscopy time, puncture time, and dose area product were 33.6 ± 8.5 min, 9.1 ± 5.7 min, and 126 ± 53 Gy·cm2, respectively. The mean portosystemic pressure gradient decreased from 22.5 ± 6.3 mmHg to 10.5 ± 2.3 mmHg (p < 0.01). No serious intraoperative and postoperative complications were found. CONCLUSION: Double C-arm digital subtraction angiography-assisted portal vein puncture is safe and feasible in transjugular intrahepatic portosystemic shunt operation. It can reduce the difficulty of the operation and possesses evident technical advantages.

Design of NiS@Ni3S2/CdS heterostructure with intimate contact interface for sensitive photoelectrochemical detection of lincomycin.

Owing to their internal electric field effect and abundant photo-induced carriers, photoactive heterostructured materials are considered a feasible approach to improve the sensitivity of a photoelectrochemical (PEC) sensor. Herein, a novel NiS@Ni3S2/CdS heterostructure composite is derived from Ni-loaded zeolitic imidazolate framework (Ni-ZIF). The PEC experiments showed the NiS@Ni3S2/CdS composite exhibits superior photocurrent response than NiS@Ni3S2 and CdS. This is attributed to the fact that the type II heterojunction of NiS@Ni3S2/CdS with a tightly connected interface reduces the transport distance of carriers and facilitates electron-hole separation. Next, using the NiS@Ni3S2/CdS modified electrode, an aptamer/glutaraldehyde/chitosan/NiS@Ni3S2/CdS/ITO PEC biosensor is developed, which exhibits excellent sensitivity for lincomycin (Lin) detection with a wide linear range (0.0001 âˆ¼ 1.25 nM) and a low detection limit of 0.067 pM. The prepared sensor is further employed to monitor Lin in the actual milk. The results confirm that the prepared sensing electrode displays good selectivity, repeatability and stability.

Revealing the Critical Regulators of Modulated Smooth Muscle Cells in Atherosclerosis in Mice.

Background: There are still residual risks for atherosclerosis (AS)-associated cardiovascular diseases to be resolved. Considering the vital role of phenotypic switching of smooth muscle cells (SMCs) in AS, especially in calcification, targeting SMC phenotypic modulation holds great promise for clinical implications. Methods: To perform an unbiased and systematic analysis of the molecular regulatory mechanism of phenotypic switching of SMCs during AS in mice, we searched and included several publicly available single-cell datasets from the GEO database, resulting in an inclusion of more than 80,000 cells. Algorithms implemented in the Seurat package were used for cell clustering and cell atlas depiction. The pySCENIC and SCENIC packages were used to identify master regulators of interested cell groups. Monocle2 was used to perform pseudotime analysis. clusterProfiler was used for Gene Ontology enrichment analysis. Results: After dimensionality reduction and clustering, reliable annotation was performed. Comparative analysis between cells from normal artery and AS lesions revealed that three clusters emerged as AS progression, designated as mSMC1, mSMC2, and mSMC3. Transcriptional and functional enrichment analysis established a continuous transitional mode of SMCs' transdifferentiation to mSMCs, which is further supported by pseudotime analysis. A total of 237 regulons were identified with varying activity scores across cell types. A potential core regulatory network was constructed for SMC and mSMC subtypes. In addition, module analysis revealed a coordinate regulatory mode of regulons for a specific cell type. Intriguingly, consistent with gain of ossification-related transcriptional and functional characteristics, a corresponding small set of regulators contributing to osteochondral reprogramming was identified in mSMC3, including Dlx5, Sox9, and Runx2. Conclusion: Gene regulatory network inference indicates a hierarchical organization of regulatory modules that work together in fine-tuning cellular states. The analysis here provides a valuable resource that can provide guidance for subsequent biological experiments.

Correlation Between Plasma Proteomics and Adverse Outcomes Among Older Men With Chronic Coronary Syndrome.

Background: Chronic coronary syndrome (CCS) is a newly proposed concept and is hallmarked by more long-term major adverse cardiovascular events (MACEs), calling for accurate prognostic biomarkers for initial risk stratification. Methods: Data-independent acquisition liquid chromatography tandem mass spectrometry (DIA LC-MS/MS) quantitative proteomics was performed on 38 patients with CCS; 19 in the CCS events group and 19 in the non-events group as the controls. We also developed a machine-learning-based pipeline to identify proteins as potential biomarkers and validated the target proteins by enzyme-linked immunosorbent assay in an independent prospective cohort. Results: Fifty-seven differentially expressed proteins were identified by quantitative proteomics and three final biomarkers were preliminarily selected from the machine-learning-based pipeline. Further validation with the prospective cohort showed that endothelial protein C receptor (EPCR) and cholesteryl ester transfer protein (CETP) levels at admission were significantly higher in the CCS events group than they were in the non-events group, whereas the carboxypeptidase B2 (CPB2) level was similar in the two groups. In the Cox survival analysis, EPCR and CETP were independent risk factors for MACEs. We constructed a new prognostic model by combining the Framingham coronary heart disease (CHD) risk model with EPCR and CETP levels. This new model significantly improved the C-statistics for MACE prediction compared with that of the Framingham CHD risk model alone. Conclusion: Plasma proteomics was used to find biomarkers of predicting MACEs in patients with CCS. EPCR and CETP were identified as promising prognostic biomarkers for CCS.

Impact of the CYP2D6 Genotype on Metoprolol Tolerance and Adverse Events in Elderly Chinese Patients With Cardiovascular Diseases.

The latest consensus has changed CYP2D6 genotyping among Chinese population, while its impact on metoprolol tolerance and adverse events in elderly Chinese patients with cardiovascular diseases remains unclear. In this study, we prospectively included elderly patients who started metoprolol treatment for cardiovascular indications. According to the latest consensus on CYP2D6 genotype-to-phenotype translation, the patients were categorized as normal, intermediate, or poor metabolizers (NMs, IMs, or PMs, respectively) by detecting the presence of the CYP2D6*1, *2, *5, *10, and *14. Logistic regression model was used to analyze the correlation between the CYP2D6 phenotype and incidence of adverse events, which were assessed over a 12-week period. In this study, there were 651 (62.7%) NMs, 385 (37.1%) IMs, and 3 (0.3%) PMs. After 12 weeks of follow-up, compared with NMs, IMs had the lower maintenance dose [50.0 (25.0-50.0) mg/day vs. 25.0 (25.0-50.0) mg/day, p < 0.001] and lower weight-adjusted maintenance doses (0.52 ± 0.25 mg/day/kg vs. 0.42 ± 0.22 mg/day/kg, p < 0.001), and had higher incidence of postural hypotension (6.0% vs. 10.9%, p = 0.006), bradycardia (21.5% vs. 28.6%, p = 0.011), asystole (0.8% vs. 3.1%, p = 0.009) and syncope (2.0% vs. 6.2%, p = 0.001). In logistic regression model, the overall incidence of adverse events was 1.37-fold larger in IMs than in NMs (odds ratio = 1.37, 95% confidence interval = 1.05-1.79, p = 0.021). We conclude that IMs have lower tolerance and higher incidence of metoprolol-related adverse events than NMs in elderly Chinese patients with cardiovascular diseases. CYP2D6 genotyping is justifiable in elderly patients to minimize the risk of adverse events and ensure the benefits of metoprolol.

The Relationship between Exercise and Mental Health Outcomes during the COVID-19 Pandemic: From the Perspective of Hope.

The unexpected outbreak of COVID-19 triggered fear and anxiety in the general population. Exercise was one of the most widely promoted methods to improve body function when socially restricted. This study aims to examine the role of exercise in relieving stressful mental health outcomes (anxiety and depressive symptoms) during the COVID-19 pandemic and explore the underlying mechanism from the perspective of hope, using a combination of goal-directed planning (pathways) and motivation (agency). A cross-sectional online survey recruiting 2390 Chinese participants was conducted during the COVID-19 pandemic in China. A series of questions and scales, including the self-designed exercise questionnaire, the Adult Dispositional Hope Scale, the Generalized Anxiety Disorder Scale-7 and the Patient Health Questionnaire-9, were used to measure exercise, hope, anxiety symptoms and depressive symptoms, respectively. A structural equation model was constructed to test the hypothesis that exercise benefits mental health outcomes through the mediating role of hope. Our results showed that exercise relieved stressful mental health outcomes via three paths: one direct path (ß = −0.077, 95% CI = (−0.138, −0.017), p < 0.01), one indirect path through hope of pathways thinking (ß = −0.046, 95% CI = (−0.064, −0.027), p < 0.001) and another indirect path through hope of agency thinking (ß = −0.060, 95% CI = (−0.081, −0.039), p < 0.001). Our results showed that exercise could alleviate stressful mental health outcomes by promoting both hope of pathway thinking and agency thinking. It provided practical insights into psychological prevention and intervention by means of exercise during the COVID-19 pandemic.

Associations of falls and severe falls with blood pressure and frailty among Chinese community-dwelling oldest olds: The Chinese Longitudinal Health and Longevity Study.

INTRODUCTION: Falls are a leading cause of death among Chinese oldest olds. However, studies on Chinese community-dwelling older adults are lacking. We aimed to identify the associations of falls and severe falls with blood pressure and frailty among Chinese community-dwelling oldest olds. METHODS: Cross-sectional analyses were conducted with 6,595 community-dwelling oldest olds (aged ≥80 years) from 22 Chinese provinces from the Chinese Longitudinal Health and Longevity Study (CLHLS). Systolic BP (SBP) and diastolic BP (DBP) were measured twice at participants' homes, and a 38-item frailty index was used to assess the frailty status of participants. Falls and severe falls were confirmed through face-to-face interviews. Multivariate logistic regression was used to investigate the associations of BP and frailty with falls and severe falls. RESULTS: The mean participant age was 91.0 years, and 56.1% were female. In total, 24.2% participants had a history of fall and 8.3% had a history of severe falls. The multivariate-adjusted odds ratio (OR) for falls among the oldest old with SBP ≥140 mm Hg compared to those with an SBP of 120-129 mm Hg was 1.20 (95% confidence interval [CI], 1.01-1.44). The adjusted OR for falls among frail participants compared to robust participants was 1.39 (95% CI, 1.02-1.89). DBP and pre-frailty were not associated with falls after multivariate adjustment. SBP, DBP, and frailty status were not associated with severe falls after multivariate adjustment. CONCLUSIONS: SBP and frailty but not DBP and pre-frailty are associated with increased odds of falls among Chinese community-dwelling oldest olds.

Waist to height ratio is associated with an increased risk of mortality in Chinese patients with heart failure with preserved ejection fraction.

BACKGROUND: Abdominal obesity as a predominant comorbidity has played a key role in the incidence and worsening of heart failure with preserved ejection fraction (HFpEF), and waist-to-height ratio (WHtR) behaves better than waist circumference or body mass index in evaluating abdominal obesity. While the association between WHtR and all-cause death in Chinese patients with HFpEF remains unclear. METHODS: Patients with stable HFpEF (N = 2041) who presented to our hospital from January 2008 to July 2019 were divided into low-WHtR (< 0.5, N = 378) and high-WHtR (≥ 0.5, N = 1663). Multivariable Cox proportional-hazard models were used to examine the association of WHtR with all-cause death. RESULTS: The average age was 76.63 ± 11.44 years, and the mean follow-up was 4.53 years. During follow-up, 185 patients (9.06%) reached the primary outcome of all-cause death. As for the secondary outcome, 79 patients (3.87%) experienced cardiovascular death, 106 (5.19%) had non-cardiovascular death, and 94 (4.61%) had heart failure rehospitalization. After multivariable adjustment, a higher WHtR was significantly associated with the increased risks of all-cause death [adjusted hazard ratios (HR) 1.91, 95% confidence interval (CI) 1.06-3.45, p = 0.032], cardiovascular death (adjusted HR 2.58; 95% CI 1.01-6.67, p = 0.048), and HF rehospitalization (adjusted HR 3.04; 95% CI 1.26-7.31, p = 0.013). CONCLUSIONS: Higher WHtR is an independent risk factor for all-cause death in Chinese patients with HFpEF.

Prognostic value of soluble suppression of tumorigenesis-2 (sST2) for cardiovascular events in coronary artery disease patients with and without diabetes mellitus.

BACKGROUND: Soluble suppression of tumorigenesis-2 (sST2) is implicated in myocardial overload and has long been recognized as an inflammatory marker related to heart failure and acute coronary syndrome, but data on the prognostic value of sST2 in patients with coronary artery disease (CAD) remain limited. This study sought to investigate the prognostic value of sST2 in patients with established CAD and its predictive value in CAD patients with and without type 2 diabetes mellitus (T2DM). METHODS: A total of 3641 consecutive patients were included in this prospective cohort study. The primary end point was major adverse cardiovascular events (MACEs). The secondary end point was all-cause death. The association between sST2 and outcomes was investigated using multivariable Cox regression. RESULTS: During a median follow-up of 6.4 years, MACEs occurred in 775 patients, and 275 patients died. Multiple Cox regression models showed that a higher level of sST2 was an independent predictor of MACEs development (HR = 1.36, 95% CI 1.17-1.56, p < 0.001) and all-cause death (HR = 2.01, 95% CI 1.56-2.59, p < 0.001). The addition of sST2 to established risk factors significantly improved risk prediction of the composite outcome of MACEs and all-cause death (C-index, net reclassification index, and integrated discrimination improvement, all p < 0.05). In subgroup analysis depending on diabetes status, the diabetes group had a significantly higher level of sST2, which remained a significant predictor of MACEs and all-cause death in patients with and without T2DM in multivariable models. The area under the curve (AUC) of CAD patients with diabetes mellitus was significantly higher than that of those without T2DM. For MACEs, the AUC was 0.737 (patients with T2DM) vs 0.620 (patients without T2DM). For all-cause death, the AUC was 0.923 (patients with T2DM) vs 0.789 (patients without T2DM). CONCLUSIONS: A higher level of sST2 is significantly associated with long-term MACEs and all-cause death in CAD patients with and without T2DM. sST2 has strong predictive value for cardiovascular adverse events in CAD patients with T2DM, and these results provide new evidence for the role of sST2.

Growth differentiation factor-15 is associated with cardiovascular outcomes in patients with coronary artery disease.

BACKGROUND: Growth differentiation factor-15 (GDF-15) is a marker of inflammation, oxidative stress and it is associated with adverse prognosis in cardiovascular disease. The aim of the present cohort study is to investigate the prognostic value of GDF-15 in patients with coronary artery disease (CAD) during long-term follow up. METHODS: A total of 3641 consecutive patients with CAD were prospectively enrolled into the study and followed up for major adverse cardiovascular events (MACEs) and all-cause death up to 5.3-7.6 years. Plasma GDF-15 was measured and clinical data and long-term events were registered. The patients were subsequently divided into three groups by the levels of GDF-15 and the prognostic value of GDF-15 level with MACEs and all-cause death was evaluated. RESULTS: After a median follow-up at 6.4 years later, 775 patients (event rate of 21%) had developed MACEs and 275 patients died (event rate of 7.55%). Kaplan-Meier analysis indicated that the patients with GDF-15 > 1800 ng/L were significantly associated with an increased risk of MACEs and all-cause death. Cox regression analysis indicated that GDF-15 > 1800 ng/L were independently associated with the composite of MACEs (HR 1.74; 95% CI 1.44-2.02; P < 0.001) and all-cause death (HR 2.04; 95% CI 1.57-2.61; P < 0.001). For MACEs, GDF-15 significantly improved the C-statistic (area under the curve, 0.583 [95% CI 0.559-0.606] to 0.628 [0.605-0.651]; P < 0.001), net reclassification index (0.578; P = 0.031), and integrated discrimination index (0.021; P = 0.027). For all-cause death, GDF-15 significantly improved the C-statistic (0.728 [95% CI 0.694-0.761] to 0.817 [0.781-0.846]; P < 0.001), net reclassification index (0.629; P = 0.001), and integrated discrimination index (0.035; P = 0.002). CONCLUSIONS: In the setting of CAD, GDF-15 is associated with long-term MACEs and all-cause death, and provides incremental prognostic value beyond traditional risks factors.

Cadmium-induced endoplasmic reticulum stress in chicken neutrophils is alleviated by selenium.

Cadmium (Cd) decreases immune function and induces apoptosis of immune cells. Selenium (Se) can antagonize some metal element toxicity including Cd. To evaluate the cytotoxicity of Cd and the chemoprotective role of Se on bird neutrophils in vitro, we incubated chicken neutrophils cells with Cadmium chloride (CdCl2) (10-6M), Sodium selenite (Na2SeO3) (10-7M), and with a mixture of Na2SeO3 (10-7M) and CdCl2 (10-6M) for 12, 24, 36, and 48h. We found that Interleukin 1ß (IL-1ß), Interleukin 10 (IL-10), and interferon gamma (IFN-γ) increased and interleukin 17 (IL-17), interleukin 4 (IL-4) decreased significantly in the chicken neutrophils of the Cd treatment groups. Cd significantly increased the mRNA expression levels of nuclear factor kappaB (NF-κB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE2) and the nitric oxide (NO) content. In addition, we demonstrated that Cd induced the apoptosis of chicken neutrophils and increased mRNA level of Bak, Cysteine-aspartic protease (Caspase)-3, Caspase-9, Caspase-12, glucose-regulated protein 78 (GRP78) and activating transcription factor 6 (ATF6), decreased mRNA level of Bcl-xl, and Ca/calmodulin-dependent protein (CaM). Moreover, the expression of NF-κB and Caspase-12 protein increased significantly in the Cd treatment groups. Se pretreatment significantly protected neutrophils against Cd-caused alterations. Our work suggested that Cd-induced immune suppression, inflammatory response, and apoptosis via endoplasmic reticulum stress (ERS). Moreover, these factors played critical roles in Se-mediated chemoprevention against Cd-induced immunotoxicity.

Bis[methyl 2-(2-pyridylmethyl-idene)hydrazinecarbodithio-ato]zinc(II).

In the title compound, [Zn(C(8)H(8)N(3)S(2))(2)], the Zn atom is coordinated by the two ligands in a tridentate manner, via the pyridyl N, the azomethine N and the thiol-ate S atom; the coordination geometry is distorted octa-hedral, with the two ligands in the mer configuration (two S atoms and two pyridyl N atoms are cis with respect to each other and the azomethine N atoms is trans). The mol-ecules are linked by C-H⋯S hydrogen bonds, forming a three-dimensional network structure.