Prognostic Impact of Fasting Plasma Glucose on Mortality and Re-Hospitalization in Patients with Acute Heart Failure / 中华医学杂志(英文版)

Background@#The impact of fasting plasma glucose (FPG) on survival outcomes in patients with acute heart failure (HF) is unclear, and the relationship between intensity of glycemic control of FPG in diabetes mellitus (DM) patients and HF prognosis remains uncertain. This retrospective study aimed to evaluate the prognostic impact of FPG in patients with acute HF.@*Methods@#A total of 624 patients hospitalized with acute HF from October 2000 to April 2014 were enrolled in this study. All patients were stratified by three groups according to their admission FPG levels (i.e., DM, impaired fasting glucose [IFG], and non-DM). All-cause and cardiovascular mortality was the primary end point, and HF re-hospitalization was the secondary end point during follow-up period.@*Results@#A total of 587 patients were included in final analysis. The all-cause mortality rates of patients with DM, IFG, and non-DM were 55.5%, 40.3%, and 39.2%, with significant difference (P = 0.001). Moreover, compared with those with IFG (34.3%) and non-DM (32.6%), patients with DM had significantly higher rate of cardiovascular mortality (45.1%). Multiple Cox regression analysis showed that DM as well as IFG was related to all-cause mortality (DM: hazard ratio [HR] = 1.936, P < 0.001; IFG: HR = 1.672, P = 0.019) and cardiovascular mortality (DM: HR = 1.739, P < 0.001; IFG: HR = 1.817, P = 0.013). However, they were both unrelated to HF re-hospitalization. DM patients with strictly controlled blood glucose (FPG <3.9 mmol/L) had higher all-cause mortality than patients with non-DM, IFG, and DM patients with moderately controlled glucose (3.9 mmol/L≤ FPG <7.0 mmol/L). Likewise, both the primary end point and secondary end point were found to be worse in DM patients with poorly controlled blood glucose (FPG ≥7.0 mmol/L).@*Conclusions@#IFG and DM were associated with higher all-cause mortality and cardiovascular mortality in patients with acute HF. The association between mortality and admission FPG in DM patients with acute HF appeared U-shaped.

IL-33 promotes IL-10 production in macrophages: a role for IL-33 in macrophage foam cell formation

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and site-specific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the −2000 to −1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the −1997 to −1700 and −1091 to −811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.

Role of Circulating Fibrocytes in Cardiac Fibrosis / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>It is revealed that circulating fibrocytes are elevated in patients/animals with cardiac fibrosis, and this review aims to provide an introduction to circulating fibrocytes and their role in cardiac fibrosis.</p><p><b>DATA SOURCES</b>This review is based on the data from 1994 to present obtained from PubMed. The search terms were "circulating fibrocytes " and "cardiac fibrosis ".</p><p><b>STUDY SELECTION</b>Articles and critical reviews, which are related to circulating fibrocytes and cardiac fibrosis, were selected.</p><p><b>RESULTS</b>Circulating fibrocytes, which are derived from hematopoietic stem cells, represent a subset of peripheral blood mononuclear cells exhibiting mixed morphological and molecular characteristics of hematopoietic and mesenchymal cells (CD34+/CD45+/collagen I+). They can produce extracellular matrix and many cytokines. It is shown that circulating fibrocytes participate in many fibrotic diseases, including cardiac fibrosis. Evidence accumulated in recent years shows that aging individuals and patients with hypertension, heart failure, coronary heart disease, and atrial fibrillation have more circulating fibrocytes in peripheral blood and/or heart tissue, and this elevation of circulating fibrocytes is correlated with the degree of fibrosis in the hearts.</p><p><b>CONCLUSIONS</b>Circulating fibrocytes are effector cells in cardiac fibrosis.</p>

Effect of Metabolic Syndrome on Risk Stratification for Left Atrial or Left Atrial Appendage Thrombus Formation in Patients with Nonvalvular Atrial Fibrillation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Metabolic syndrome (MS) is a risk factor for stroke and thromboembolism event. Left atrial or LA appendage (LA/LAA) thrombus is a surrogate of potential stroke. The relationship between MS and atrial thrombus remains unclear. In this study, we sought to investigate the effect of MS on risk stratification of LA/LAA thrombus formation in patients with nonvalvular atrial fibrillation (NVAF).</p><p><b>METHODS</b>This cross-sectional study enrolled 294 consecutive NVAF patients without prior anticoagulant and lipid-lowering therapies. LA/LAA thrombus was determined by transesophageal echocardiography. Risk assessment of LA/LAA thrombus was performed using the CHADS2 , CHA2DS2 -VASc, MS, CHADS2 -MS, and CHA2DS2 -VASc-MS scores. Logistic regression analyses were performed to determine which factors were significantly related to LA/LAA thrombus. Odds ratio (OR) including 95% confidence interval was also calculated. The predictive powers of different scores for the risk of LA/LAA thrombus were represented by C-statistics and compared by receiver operating characteristic (ROC) analysis.</p><p><b>RESULTS</b>LA/LAA thrombi were identified in 56 patients (19.0%). Logistic analysis showed that MS was the strongest risk factor for LA/LAA thrombus in NVAF patients (OR = 14.698, P < 0.001). ROC curve analyses revealed that the C-statistics of CHADS2 -MS and CHA2DS2 -VASc-MS was significantly higher than those of CHADS2 and CHA2DS2 -VASc scores (CHADS2 -MS vs. CHADS2 , 0.807 vs. 0.726, P = 0.0019). Furthermore, MS was helpful for identifying individuals with a high risk of LA/LAA thrombus in the population with a low risk of stroke (CHADS2 or CHA2DS2 -VASc score = 0).</p><p><b>CONCLUSIONS</b>MS is associated with LA/LAA thrombus risk in patients with NVAF. In addition to the CHADS2 and CHA2DS2 -VASc scores, the CHADS2 -MS and CHA2DS2 -VASc-MS scores provide additional information on stroke risk assessment.</p>

Carbon Monoxide Releasing Molecule Accelerates Reendothelialization after Carotid Artery Balloon Injury in Rat / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>This study was aimed to investigate the effects of carbon monoxide releasing molecule (CORM-2), a novel carbon monoxide carrier, on the reendothelialization of carotid artery in rat endothelial denudation model.</p><p><b>METHODS</b>Male rats subjected to carotid artery balloon injury were treated with CORM-2, inactive CORM-2 (iCORM-2) or dimethyl sulfoxide (DMSO). The reendothelialization capacity was evaluated by Evans Blue dye and the immunostaining with anti-CD31 antibody. The number of circulating endothelial progenitor cells (EPCs) was detected by flow cytometry. The proliferation, migration, and adhesion of human umbilical vein endothelial cells (HUVECs) were assessed by using [3H]thymidine, Boyden chamber and human fibronectin respectively. The expressions of protein were detected by using western blot analysis.</p><p><b>RESULTS</b>CORM-2 remarkably accelerated the re-endothelialization 5 d later and inhibited neointima formation 28 d later. In addition, the number of peripheral EPCs significantly increased in CORM-2-treated rats than that in iCORM-2 or DMSO-treated rats after 5 d later. In vitro experiments, CORM-2 significantly enhanced the proliferation, migration and adhesion of HUVECs. The levels of Akt, eNOS phosphorylation, and NO generation in HUVECs were also much higher in CORM-2 treated group. Blocking of PI3K/Akt/eNOS signaling pathway markedly suppressed the enhanced migration and adhesion of HUVECs induced by CORM-2.</p><p><b>CONCLUSION</b>CORM-2 could promote endothelial repair, and inhibit neointima formation after carotid artery balloon injury, which might be associated with the function changes of HUVECs regulated by PI3K/Akt/eNOS pathway.</p>

Triple antithrombotic therapy versus double antiplatelet therapy after percutaneous coronary intervention with stent implantation in patients requiring chronic oral anticoagulation: a meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Whether an addition of OAC to double antiplatelet therapy for patients with an indication of chronic oral anticoagulation undergoing PCI-S may improve clinical outcomes is still debated. This meta-analysis aimed to update and re-compare the benefits and risks of triple antithrombotic therapy (TT) with double anti-platelet therapy (DAPT) after in patients who requiring oral anticoagulation after percutaneous coronary interventions with stenting (PCI-s).</p><p><b>METHODS</b>Ten reports of observational retrospective or prospective studies were retrieved, including a total of 6296 patients, follow-up period ranging from 1 year to 2 years.</p><p><b>RESULTS</b>Baseline characteristics were similar in both groups. The main finding of this study is the overall incidence of major adverse cardiovascular events (MACE), myocardial infarction (MI) and stent thrombosis was comparable between two groups. Patients with TT was associated with significant reduction in ischemic stroke (OR: 0.27; 95%CI: 0.13 - 0.57; P = 0.0006) as compared to DAPT. We reaffirmed triple therapy significantly increased the risk of major bleeding (OR: 1.47; 95%CI: 1.22 - 1.78; P < 0.0001) and minor bleeding (OR: 1.55; 95%CI: 1.07 - 2.24; P = 0.02).</p><p><b>CONCLUSIONS</b>Triple therapy is more efficacious in reducing the occurrence of ischemic stroke in PCI-s patients with an indication of chronic oral anticoagulation (OAC), compared with DAPT. However, it significantly increased major and minor risk of bleeding. It is imperative that further prospective randomized controlled trials are required to defne the best therapeutic strategy for patients with an indication of chronic OAC undergoing PCI-s.</p>

Serum uric acid levels correlate with recurrence of paroxysmal atrial fibrillation after catheter ablation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recently there has been a great deal of interest in the role of serum uric acid (SUA) in atrial fibrillation (AF). The objective of this study was to establish whether there is a relationship between levels of SUA and recurrence of paroxysmal AF after catheter ablation.</p><p><b>METHODS</b>Three hundred and thirty patients diagnosed with paroxysmal AF were analyzed. Patients were categorized into quartiles on the basis of their pre-operative SUA measurement and follow-up, and Kaplan-Meier estimation with a Log-rank test was used for the analysis of the influence of SUA on the recurrence of AF. Pre-procedural clinical variables were correlated with the clinical outcome after ablation using multivariate Logistic analysis. A Cox proportional hazards model was used to estimate the relationship between SUA and the recurrence of AF.</p><p><b>RESULTS</b>After a mean follow-up of (9.341 ± 3.667) (range 3.0 - 16.3) months, recurrence rates from the lowest SUA quartile to the highest SUA quartile were 16.0%, 26.4%, 28.3%, and 29.3% respectively (P = 0.014). After adjustment for gender, body mass index (BMI), hypertension, serum levels of high sensitivity C-reactive protein (hsCRP), triglyceride (TG), left atrial diameter (LA), estimated glomerular filtration rate (eGFR), and SUA, there was an increased risk of recurrence in subjects in the highest SUA quartile compared with those in the lowest quartile (hazard ratio 2.804, 95% confidence interval 1.466 - 5.362, P = 0.002). Following multivariate Logistical analysis, SUA was found to be an independent predictor of recurrence (hazard ratio 1.613, 95% confidence interval 1.601 - 1.625, P = 0.014).</p><p><b>CONCLUSION</b>In a retrospective study of patients with paroxysmal AF undergoing catheter ablation, elevated preoperative SUA levels were associated with a higher rate of recurrence of AF.</p>

Impact of insulin resistance on prognosis in non-diabetic patients with acute coronary syndromes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the impact of insulin resistance (IR) on prognosis in non-diabetic acute coronary syndrome patients.</p><p><b>METHODS</b>In this prospective study, we enrolled 332 non-diabetic patients suffering from acute coronary syndrome. The patients were divided into three groups by HOMA-IR which calculated by formula: low HOMA-IR group (HOMA-IR < 2), 44 cases; moderate HOMA-IR group (2 ≤ HOMA2-IR < 6), 99 cases; high HOMA-IR group (HOMA ≥ 6) with HOMA index, 179 cases. The in-hospital medical records of patients were compared, and all patients were followed up for one year after discharge.</p><p><b>RESULTS</b>Incidence of hypertension (P = 0.013), dyslipidemia (P < 0.001), faster resting heart rate (P < 0.001) and number of triple vessel coronary artery disease (P = 0.017) in high HOMA-IR group were significantly higher than in low and moderate HOMA-IR group. During follow-up, the major end-point events increased in proportion to IR grade: 64.3% (26/44) in the high HOMA-IR group, 54.7% (52/99) in moderate HOMA-IR group and 41.3% (74/199) in low HOMA-IR group (P = 0.034). Multivariable logistic regression analysis showed that high sensitivity C reactive protein (OR = 1.012, 95%CI:1.002-1.022, P = 0.022), HOMA-IR (OR = 1.250, 95%CI:1.043-1.497, P = 0.015) , triple vessel coronary artery disease (OR = 5.914, 95%CI:2.947-11.868, P < 0.001) , ischemic changes on ECG (OR = 5.495, 95%CI:2.925-10.324, P < 0.001) and low left ventricular ejection fraction (LVEF ≤ 40%) (OR = 13.205, 95%CI:5.000-34.661, P < 0.001) were independent risk factor for major end-point events during follow-up.</p><p><b>CONCLUSIONS</b>Increased insulin resistance is linked with poor prognosis of non-diabetic patients with acute coronary syndrome.</p>

Increased expression of granulocyte colony-stimulating factor mediates mesenchymal stem cells recruitment after vascular injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent studies indicate that bone marrow-derived cells may significantly contribute to atherosclerosis, post-angioplasty restenosis and transplantation-associated vasculopathy. The responsible bone marrow (BM) cells and mechanisms regulating the mobilization of these cells are currently unclear. The purpose of this study was to investigate the expression of granulocyte colony-stimulating factor (G-CSF) on injured arteries and its effects on mesenchymal stem cells (MSCs) differentiation into vascular smooth muscle cells (VSMCs) in the process of vascular remodeling.</p><p><b>METHODS</b>Balloon-mediated vascular injury was established in female rats (n = 100) which received radioprotective whole female BM cells by tail vein injection and male MSCs through a tibial BM injection after lethal irradiation. The injured and contralateral carotid arteries were harvested at 3, 7, 14 and 28 days after treatment.</p><p><b>RESULTS</b>Morphometric analysis indicated that intima to media area-ratio (I/M ratio) significantly increased at 28 days, 0.899 ± 0.057 (P < 0.01), compared with uninjured arteries. Combining fluorescence in situ hybridization (FISH) and immunohistochemical analysis showed that a significant number of the neointimal cells derived from MSCs, (45.2 ± 8.5)% at 28 days (P = 0.01), compared with (23.5 ± 6.3)% at 14 days. G-CSF was induced in carotid arteries subject to balloon angioplasty (fold mRNA change = 8.67 ± 0.63 at three days, relative G-CSF protein = 0.657 ± 0.011 at three days, P < 0.01, respectively, compared with uninjured arteries). G-CSF was chemotactic for MSCs but did not affect the differentiation of MSCs into smooth-muscle-like cells.</p><p><b>CONCLUSION</b>Increased expression of G-CSF by injured arteries plays an essential role in contribution to recruitment and homing of MSCs to the site of the arterial lesion.</p>

Potential proarrhythmic effect of cardiac resynchronization therapy during perioperative period: data from a single cardiac center / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cardiac resynchronization therapy (CRT) could improve heart function, symptom status, quality of life and reduce hospitalization and mortality in patients with severe heart failure (HF) with optimal medical management. However, the possible adverse effects of CRT are often ignored by clinicians.</p><p><b>METHOD</b>A retrospective analysis of CRT over a 6-year period was made in a single cardiac center.</p><p><b>RESULTS</b>Fifty-four patients were treated with CRT(D) device, aged (57 ± 11) years, with left ventricular ejection fraction of (32.1 ± 9.8)%, of which 4 (7%) developed ventricular tachycardia/ventricular fibrillation (VT/VF) or junctional tachycardia after operation. Except for one with frequent ventricular premature beat before operation, the others had no previous history of ventricular arrhythmia. Of the 4 patients, 3 had dilated cardiomyopathy and 1 had ischemic cardiomyopathy, and tachycardia occurred within 3 days after operation. Sustained, refractory VT and subsequent VF occurred in one patient, frequent nonsustained VT in two patients and nonparoxysmal atrioventricular junctional tachycardia in one patient. VT was managed by amiodarone in two patients, amiodarone together with beta-blocker in one patient, and junctional tachycardia was terminated by overdrive pacing. During over 12-month follow-up, except for one patient's death due to refractory heart and respiratory failure in hospital, the others remain alive and arrhythmia-free.</p><p><b>CONCLUSIONS</b>New-onset VT/VF or junctional tachycardia may occur in a minority of patients with or without prior history of tachycardia after biventricular pacing. Arrhythmia can be managed by conventional therapy, but may require temporary discontinuation of pacing. More observational studies should be performed to determine the potential proarrhythmic effect of CRT.</p>

R25G mutation in exon 1 of LMNA gene is associated with dilated cardiomyopathy and limb-girdle muscular dystrophy 1B / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mutations of the LMNA gene encoding lamin A and C are associated with dilated cardiomyopathy (DCM), conduction system defects and skeletal muscle dystrophy. Here we report a family with a mutation of the LMNA gene to identify the relationship between genotype and phenotype.</p><p><b>METHODS</b>All 30 members of the family underwent clinical and genetic evaluation. A mutation analysis of the LMNA gene was performed. All of the 12 exons of LMNA gene were extended with polymerase chain reaction (PCR) and the PCR products were screened for gene mutation by direct sequencing.</p><p><b>RESULTS</b>Ten members of the family had limb-girdle muscular dystrophy (LGMD) and 6 are still alive. Two patients suffered from DCM. Cardiac arrhythmias included atrioventricular block and atrial fibrillation; sudden death occurred in 2 patients. The pattern of inheritance was autosomal dominant. Mutation c.73C > G (R25G) in exon 1 encoding the globular domains was confirmed in all of the affected members, resulting in the conversion of arginine (Arg) to glycine (Gly).</p><p><b>CONCLUSIONS</b>The mutation R25G in exon 1 of LMNA gene we reported here in a Chinese family had a phenotype of malignant arrhythmia and mild LGMD, suggesting that patients with familial DCM, conduction system defects and skeletal muscle dystrophy should be screened by genetic testing for the LMNA gene.</p>

Effect of AP-1 decoy oligodeoxynucleotides on neonatal rat cardiac fibroblast proliferation and collagen synthesis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the inhibitory effects of AP-1 decoy oligodeoxynucleotides (ODNs) on angiotensin II (AngII)-induced proliferation and collagen synthesis in neonatal rat cardiac fibroblasts (CFs).</p><p><b>METHODS</b>The CFs of neonatal SD rats were cultured in serum-free medium for 24 h and stimulated with 10(-7) mol/L AngII in the presence of AP-1 decoy ODNs or mutational AP-1 decoy ODNs at varied concentrations. MTT assay was employed for quantitative evaluation of the CF proliferation. Collagen synthesis in the CFs was assessed with hydroxyproline, and the cell cycle distribution determined with flow cytometry (FCM).</p><p><b>RESULTS</b>With the increase of the concentration of AP-1 decoy ODNs, the absorbance at 490 nm (OD490) of the CFs decreased gradually as shown by MTT assay. Treatment with 100 or 200 nmol/L AP-1 decoy ODNs resulted in significantly lowered OD490 of the CFs as compared with that of AngII group. The concentration of hydroxyproline increased significantly after treatment with 10(-7) mol/L AngII in comparison with the control group (P<0.05). Hydroxyproline concentration in cells treated with 100 or 200 nmol/L AP-1 decoy ODNs was significantly lower than that in the 10(-7) mol/L AngII-treated cells. AP-1 decoy ODNs decreased the cell percentage in S phase and increased hydroxyproline concentration, but increased the percentage of cells in G0/G1 phase. AP-1 decoy ODNs at 100 and 200 nmol/L did not obviously affect AngII-induced CF proliferation and collagen synthesis (P<0.01).</p><p><b>CONCLUSION</b>AP-1 decoy can inhibit AngII-induced rat CF proliferation and collagen synthesis possibly by affecting the cell cycle distribution.</p>

The Effect of Activator Protein-1 Decoy Oligodeoxynucleotides on the Collagen Ⅰ and Ⅲ Expression in Rat Cardiac Fibroblast Cells Induced by Angiotension Ⅱ / 中华高血压杂志

Objective To investigate the effects of activator protein-1(AP-1)decoy oligodeoxynucleotides (ODNs)on the myocardial fibrosis induced by angiotension Ⅱ(Ang Ⅱ)in vitro.Methods CFs of neonatal Spra- gue-Dawley(SD)rats were isolated by trypsin digestion method.CFs were co-cultured with 10~(-7)mol/L Ang Ⅱ in the presence of different concentration of activator protein-1(AP-1)decoy ODNs or mutational AP-1 decoy ODNs for 24 h.Collagen synthesis was assessed by hydroxyproline and the mRNA expression of collagen Ⅰ,collagen Ⅲ.Results The concentration of hydroxyproline increased significantly after treated by 10~(-7)mol/L Ang Ⅱ;decoy ODNs on the range of 10-200 nmol/L dose dependently decrease synthesis of collagen;Ang Ⅱ stimulates mRNA expression of collagen Ⅲ(1.04?0.07 vs 1.63?0.071,n=3,P