Elevated serum FGF21 levels predict heart failure during hospitalization of STEMI patients after emergency percutaneous coronary intervention.

Background: Fibroblast growth factor 21 (FGF21) has multiple cardioprotective effects including modulation of glucolipid metabolism, anti-inflammation, and anti-oxidative stress, but its association with the heart failure during hospitalization in patients with ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI) has not been reported. Methods: A total of 348 STEMI patients treated with emergency PCI were included from January 2016 to December 2018. Relevant biochemical indicators were measured by central laboratory. Serum FGF21 levels were measured by ELISA. The occurrence of heart failure during hospitalization was recorded. Patients' cardiac function was assessed by echocardiography. Results: Serum FGF21 levels were significantly higher in the STEMI group with heart failure than in the group without heart failure (249.95 ± 25.52 vs. 209.98 ± 36.35, P < 0.001). Serum FGF21 levels showed a strong positive correlation with N-terminal precursor B-type natriuretic peptide (NT-proBNP) in STEMI patients (r = 0.749, P < 0.001). FGF21 was found to be an independent risk factor for the development of heart failure during hospitalization in STEMI patients by binary logistic regression analysis. The area under curve (AUC) for FGF21 to predict the development of heart failure during hospitalization in STEMI patients was 0.816 (95% CI [0.770-0.863]) according to the receiver operating characteristic (ROC) curve analysis. Conclusion: Elevated serum FGF21 levels have been shown to be a strong predictor of heart failure during hospitalization in patients with STEMI after emergency PCI.

Elevated serum FGF21 predicts the major adverse cardiovascular events in STEMI patients after emergency percutaneous coronary intervention.

BACKGROUND: Although there have been several studies related to serum fibroblast growth factor 21 (FGF21) levels and acute myocardial infarction, the value of serum FGF21 levels in ST-segment elevation myocardial infarction (STEMI) patients after emergency percutaneous coronary intervention (PCI) has not been previously investigated. METHODS: A total of 348 STEMI patients who underwent emergency PCI were enrolled from January 2016 to December 2018. The primary endpoint was the occurrence of major adverse cardiovascular events (MACEs), with a median follow-up of 24 months. Eighty patients with stable angina (SA) who underwent selective PCI served as the control group. Serum FGF21 levels were measured by ELISA. RESULTS: Serum FGF21 levels were significantly higher in the STEMI group than in the SA group (225.03 ± 37.98 vs. 135.51 ±  34.48, P < 0.001). Multiple linear regression analysis revealed that serum FGF21 levels were correlated with NT-proBNP (P < 0.001). According to receiver operating characteristic (ROC) analysis, the areas under the ROC curve (AUCs) of FGF21 and NT-proBNP were 0.812 and 0.865, respectively. The Kaplan-Meier curves showed that STEMI patients with lower FGF21 levels had an increased MACE-free survival rate. Cox analysis revealed that high FGF21 levels (HR: 2.011, 95% CI: [1.160-3.489]) proved to be a powerful tool in predicting the risk of MACEs among STEMI patients after emergency PCI. CONCLUSION: Elevated FGF21 levels on admission have been shown to be a powerful predictor of MACEs for STEMI patients after emergency PCI.

Catalyst-Free Four-Component Polymerization of Propiolic Acids, Benzylamines, Organoboronic Acids, and Formaldehyde toward Functional Poly(propargylamine)s.

Multicomponent polymerizations (MCPs) are a group of fascinating polymer synthesis approaches that are developed rapidly in the recent decade. As a popular alkyne-based MCP, the A3 -polycouplings of alkynes, aldehydes, and amines are developed for the synthesis of poly(propargylamine)s under the catalysis of metal catalysts. In this work, through the design of carboxylic acid group-activated alkyne monomers, a catalyst-free, four-component polymerization of propiolic acids, benzylamines, organoboronic acids, and formaldehyde is reported under mild condition at 45 °C in dichloroethane. This four-component polymerization is applicable to different monomer structures, which can afford seven poly(propargylamine)s with up to 94% yields and molecular weights of up to 13 900 g mol-1 . Moreover, the poly(propargylamine)s demonstrate good solubility and processibility, high thermal stability and light refractivity, unique photophysical property, and so on. The simple monomers, mild condition, low cost, high efficiency, and procedure simplicity of this catalyst-free four-component polymerization demonstrates an elegant example of functional polymer synthesis.

Correlations and Prognostic Roles of the Nutritional Status and Neutrophil-to-lymphocyte Ratio in Elderly Patients with Acute Myocardial Infarction Undergoing Primary Coronary Intervention.

The prognostic capacities of nutritional status and inflammation in patients with acute myocardial infarction (AMI) have attracted increasing interest. However, the combined usefulness of the Controlling Nutritional Status (CONUT) score and neutrophil-to-lymphocyte ratio (NLR) in predicting adverse outcomes has not been investigated. The aim of our study was to investigate the relationship between the CONUT score and the NLR in patients with AMI and assessing the potential of these factors as prognostic markers.In this retrospective study, we reviewed the medical records of consecutive patients aged 65 years or older who were diagnosed with AMI and who underwent primary coronary intervention. We assessed the nutritional and inflammatory statuses using the CONUT score and the NLR, respectively. The NLR and CONUT score in the major adverse cardiovascular event (MACE) (+) patients were significantly higher than those in the MACE (-) patients. The areas under the receiver operating characteristic curves of the NLR and CONUT score were 0.71 and 0.77, respectively. The Kaplan-Meier analysis showed that patients with a high NLR (≥6.07) and CONUT score (≥3.5) had the worst prognoses. The multivariate Cox proportional hazards analyses suggested that the CONUT score was an independent predictor.The CONUT score was proven to be a significant prognostic factor of clinical outcomes in patients with AMI. However, further research in this area is needed to more fully understand the relationship among nutritional status, inflammation, and cardiovascular diseases, which might help reduce MACEs in patients with AMI.

Metal-Free Multicomponent Tandem Polymerizations of Alkynes, Amines, and Formaldehyde toward Structure- and Sequence-Controlled Luminescent Polyheterocycles.

Sequence-controlled polymers, including biopolymers such as DNA, RNA, and proteins, have attracted much attention recently because of their sequence-dependent functionalities. The development of an efficient synthetic approach for non-natural sequence-controlled polymers is hence of great importance. Multicomponent polymerizations (MCPs) as a powerful and popular synthetic approach for functional polymers with great structural diversity have been demonstrated to be a promising tool for the synthesis of sequence-controlled polymers. In this work, we developed a facile metal-free one-pot multicomponent tandem polymerization (MCTP) of activated internal alkynes, aromatic diamines, and formaldehyde to successfully synthesize structural-regulated and sequence-controlled polyheterocycles with high molecular weights (up to 69 800 g/mol) in high yields (up to 99%). Through such MCTP, polymers with the in situ generated multisubstituted tetrahydropyrimidines or dihydropyrrolones in the backbone and inherent luminescence can be easily obtained with high atom economy and environmental benefit, which is inaccessible by other synthetic approaches.

Effect of ionic interaction on the mechanochromic properties of pyridinium modified tetraphenylethene.

A pyridinium modified tetraphenylethene-based salt shows aggregation-induced emission enhancement properties and irreversible mechanochromic behaviours.

PQ-69, a novel and selective adenosine A1 receptor antagonist with inverse agonist activity.

Potent and selective adenosine A1 receptor (A1AR) antagonists with favourable pharmacokinetic properties used as novel diuretics and antihypertensives are desirable. Thus, we designed and synthesized a series of novel 4-alkylamino substitution-2-arylpyrazolo[4,3-c]quinolin-3-one derivatives. The aim of the present study is to characterize the biological profiles of the optimized compound, PQ-69. In vitro binding assay revealed a K i value of 0.96 nM for PQ-69 in cloned hA1 receptor, which was 217-fold more selective compared with hA2A receptors and >1,000-fold selectivity for hA1 over hA3 receptor. The results obtained from [(35)S]-GTPγS binding and cAMP concentration assays indicated that PQ-69 might be an A1AR antagonist with inverse agonist activity. In addition, PQ-69 displayed highly inhibitory activities on isolated guinea pig contraction (pA2 value of 8.99) induced by an A1AR agonist, 2-chloro-N6-cyclopentyl adenosine. Systemic administration of PQ-69 (0.03, 0.3, 3 mg/kg) increased urine flow and sodium excretion in normal rats. Furthermore, PQ-69 displayed better metabolic stability in vitro and longer terminal elimination half-life (t 1/2) in vivo compared with 1,3-dipropyl-8-cyclopentylxanthine. These findings suggest that PQ-69 exhibits potent antagonist effects on A1AR in vitro, ex vivo and in vivo, it might be a useful research tool for investigating A1AR function, and it could be developed as a potential therapeutic agent.

Evidence-based study on antithrombotic therapy in patients at risk of a stroke with paroxysmal atrial fibrillation.

The aim of the present study was to determine the optimal intensity of anticoagulation therapy in elderly patients with paroxysmal atrial fibrillation (PAF), using aspirin and varied concentrations of warfarin. Elderly patients with PAF (n=1,162) who met the inclusion criteria of the study and were at middle or high-risk of a stroke were investigated. Patients were divided into six groups (four high-risk groups and two middle-risk groups). Patients were treated with aspirin or varied concentrations of warfarin. The primary endpoint events, secondary endpoint events, major bleeding events and minor bleeding events were observed and compared. In high-risk elderly patients, warfarin significantly reduced primary and secondary endpoint events, total primary events and total events compared with aspirin. In middle-risk elderly patients, for all the events warfarin demonstrated no significant difference compared with aspirin. In high-risk patients with PAF, when the concentration of warfarin was adjusted to target international normalized ratio (INR) range 1.7-2.5, the primary and secondary endpoint events, total primary events and total events were significantly lower (P<0.05), compared with aspirin and warfarin at INR 1.2-1.6. When the intensity of warfarin was adjusted to the target INR 2.6-3.0, the primary and secondary endpoint events were significantly lower (P<0.05) compared with aspirin and warfarin INR at 1.2-1.6. This study determined that in high-risk elderly patients with PAF, warfarin is recommended for anticoagulation with an optimal INR range of 1.7-2.5. In patients at a middle-risk of a stroke, aspirin is the recommended treatment as an antithrombotic as results have indicated that there is limited benefit in the use of warfarin.

Olmesartan attenuates the impairment of endothelial cells induced by oxidized low density lipoprotein through downregulating expression of LOX-1.

Oxidized low density lipoprotein (ox-LDL) and its receptor, lectin-Like ox-LDL receptor-1 (LOX-1), play important roles in the development of endothelial injuries. Olmesartan can protect endothelial cells from the impairment caused by various pathological stimulations. In the present study we investigated whether olmesartan decreased the impairment of endothelial cells induced by ox-LDL by exerting its effects on LOX-1 both in vitro and in vivo. Incubation of cultured endothelial cells of neonatal rats with ox-LDL for 24 h or infusion of ox-LDL in mice for 3 weeks led to the remarkable impairment of endothelial cells, including increased lactate dehydrogenase synthesis, phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK) and expression of apoptotic genes such as B-cell leukemia/lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-3. Simultaneously, the cell vitality and expression of Bcl-2 gene were greatly reduced. All these effects, however, were significantly suppressed by the treatment with olmesartan. Furthermore, ox-LDL promoted up-regulation of LOX-1 expression either in cultured endothelial cells or in the aortas of mice, which was reversed with the administration of olmesartan. Our data indicated that olmesartan may attenuate the impairment of endothelial cell via down-regulation of the increased LOX-1 expression induced by ox-LDL.

Design, synthesis, and biological evaluation of novel 4-alkylamino-1-hydroxymethylimidazo[1,2-a]quinoxalines as adenosine A(1) receptor antagonists.

A series of 4-alkylamino-1-hydroxymethylimidazo[1,2-a]quinoxalines have been synthesized and evaluated for their adenosine A(1) receptor inhibitory activity in the radioligand binding assays. The compounds were tested for the inhibition percent (IP) and the affinity toward A(1)AR (K(i)) that IP were more than 90% in the nanomolar range. 4-Cyclopentylamino-7,8-dichloro-1-hydroxymethylimidazo[1,2-a]quinoxaline 18 is the most potent compound in this series, having K(i)=7nM, which is remarkably higher than that of IRFI-165 (K(i)=48). 1-Hydroxymethyl groups of the tricyclic heteroarmatic compounds displayed the potent affinities toward A(1)AR.