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Thermoelectric materials can directly convert thermal energy into electrical energy, realizing the recovery of waste heat. Bismuth Telluride (Bi-Te) is considered as a perfect candidate thermoelectric material which has great potential in the field of refrigeration and temperature sensor. However, in the field of intelligent wearable devices and integrated circuits, traditional Bi-Te block material is difficult to be directly used due to its poor flexibility. In this paper, a series of Bi-Te thin films were prepared by a self-designed high-temperature thermal shock equipment. This equipment can heat up the reduced graphene oxide strip to 1750 K in 20 ms, which features both high heating rate (8.2 × 104 K/s) and cooling rate (1.5 × 104 K/s). Thermoelectric films on different substrates were prepared via high-temperature thermal shock. Through regulating the temperature of evaporation source, the particle size and composition of Bi-Te thin films can be precisely modulated, thus optimizing the Seebeck coefficient of the films. The Seebeck coefficient of copper foil (Cuf)-based Bi-Te film can reach 345.41 μV/K, which was prepared by thermal-shocking the Bi-Te powders for 30 s at 900°C.

In this work, we investigated the in vitro and in vivo functions of bisphosphonate of zoledronate (Zd) in hypoxia/reoxygenation (H/R) injured human embryonic stem cell-derived cardiomyocytes (hES-CMs). In the in vitro setting, the effects of Zd on hES-CM survival and differentiation were examined. We found that low and medium concentrations (2 µm) of Zd did not induce cell death of hES-CMs. 0.5 µm Zd protected H/R-induced hES-CM apoptosis but did not affect key differentiation proteins, including hcTnl, PECM-1 Cnx43 and Pan-Cadherin. In addition, Zd-induced TrkA/B phosphorylation and promoted VEGF to counter the apoptotic effect of H/R injury. In the in vivo animal model of myocardial infarction, Zd treatment promoted the survival of hES-CMs by inducing PECAM1 and hcTnl. Thus, we concluded that Zd protected H/R-induced hES-CM apoptosis in vitro and promoted hES-CM survival in vivo. These data may facilitate the development of human embryonic stem cells into clinical applications for patients with ischemic heart disease.

To investigate the expression level and clinical significance of Wilms' tumor 1 (WT1) in bone marrow of patients with myelodysplastic syndromes (MDS).The clinical data of 147 MDS patients who accepted real-time quantitative polymerase chain reaction (RT-PCR) to detect the expression level of WT1 in bone marrow before treated in Nanfang Hospital, Southern Medical University from January 2017 to April 2021 were retrospectively analyzed. According to the expression level of WT1, the patients were divided into WT1The positive rate of WT1 in 147 MDS patients was 82.3%. There were significant differences in bone marrow blast count, aberrant karyotypes, WHO 2016 classification, and IPSS-R stratification between WT1WT1 expression level directly reflects the disease progression, and it is also associated with prognosis of MDS patients.WT1基因在骨髓增生异常综合征患者骨髓中的表达及其临床意义.探究WT1基因在骨髓增生异常综合征（MDS）患者骨髓中的表达水平及其临床意义。.回顾性分析2017年1月至2021年4月在南方医科大学南方医院就诊的147例初发MDS患者的临床资料，应用实时荧光定量PCR检测骨髓WT1基因表达，根据其表 达水平分为WT1147例MDS患者WT1WT1基因表达水平可用于评估MDS患者病情，与MDS患者预后密切相关。.

There is scarce data on the long-term mortality and associated prognostic factors in patients with dilated cardiomyopathy (DCM). The study aimed to investigate the all-cause mortality up to 15 years (mean 7.9 ± 5.7 years) in such patients, and the independent prognostic factors influencing their long-term mortality.One hundred and sixty-six consecutive patients with DCM were prospectively enrolled from 2002 to 2003. The mean age of patients was 59.5 ± 10.4 years, and approximately 57% were male. They were followed up by telephone or outpatient visit at least every three months until 2019 or all-cause death occurred. Predictors of mortality were identified using multivariate logistic regression analysis.During the 15 years of follow-up, five patients were lost to follow-up, and the complete data records of 161 patients were included in the analysis. Patients were treated with angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin-receptor blocker (ARB), β-blockers, mineralocorticoid receptor antagonist (MRA), diuretics and digitalis from 2002 to 2004, and maintained at the maximum tolerated doses between 2004 and 2019. Our safety targets to maintain heart rate and blood pressure at 60-80 beats/min and 90-120/60-80 mmHg, respectively. All-cause mortality in the first five years was 55.9%. The independent risk factors for the 5-year mortality were age ≥ 70 years old (OR = 5.45,This study was the first to demonstrate the 15-year survival rate of 34% in DCM patients. The DCM patients' first five-year all-cause mortality decreased significantly after continuous standardized treatment and intensive management. The mortality then plateaued in the following 10 years. Age ≥ 70 years, LVEF ≤ 35%, and SBP120 mmHg were independent predictors of 15-year all-cause mortality.

A number of studies have suggested that autoantibodies against β1-adrenoreceptors (β1R-AAbs) have an important role in pathophysiological processes of heart failure. The aim of the present study was to determine whether β1R-AAbs are implicated in cardiac dysfunction following acute myocardial infarction (AMI) and their association with prognosis. A total of 33 cases with systolic heart failure (SHF), 49 with diastolic heart failure (DHF) and 44 with normal heart function following AMI were recruited. β1R-AAbs were detected by ELISA and major adverse cardiac events (MACEs) were recorded during the 5-year follow-up. The positive rate of β1R-AAbs in the SHF group (45.5%) was significantly higher compared with that in the DHF (22.4%; P

Resumo Fundamento: A fração de ejeção (FE) tem sido utilizada em análises fenotípicas e na tomada de decisões sobre o tratamento de insuficiência cardíaca (IC). Assim, a FE tornou-se parte fundamental da prática clínica diária. Objetivo: Este estudo tem como objetivo investigar características, preditores e desfechos associados a alterações da FE em pacientes com diferentes tipos de IC grave. Métodos: Foram incluídos neste estudo 626 pacientes com IC grave e classe III–IV da New York Heart Association (NYHA). Os pacientes foram classificados em três grupos de acordo com as alterações da FE, ou seja, FE aumentada (FE-A), definida como aumento da FE ≥10%, FE diminuída (FE-D), definida como diminuição da FE ≥10%, e FE estável (FE-E), definida como alteração da FE

To investigate the clinical characteristics and prognosis of patients with medium and high risk myelodysplastic syndrome (MDS).97 MDS patients above the age of 60 treated in Nanfang Hospital, Southern Medical University from February 2011 to August 2020 were enrolled. The clinical characteristics and prognosis of the MDS patients with medium risk, high risk or very high risk based on IPSS-R category were retrospectively analyzed. According to the difference of treatment regimes, the patients were divided into the transplantation group, chemotherapy group and other treatment group, and the efficacy among the patients in the 3 groups were analyzed.MDS with excess blast (MDS-EB) in the elderly patients with medium and high risk MDS were the most common, 47.4% of the patients with abnormal chromosome karyotypes, and 23.7% with complex karyotypes (≥3). 97.3% of the patients showed at least one gene mutation, and TP53 mutations were detected in nearly 20% of the patients with medium and high risk. Multivariate analysis showed that IPSS-R category and treatment regimes were the factors affecting the prognosis of elderly patients with medium and high risk MDS. The median overall survival (OS) time of the patients in the 3 groups showed significant difference (P=0.012), and the median OS of the patients in the transplantation group was significantly longer than that in the chemotherapy group and other group (P=0.003,P=0.014,respectively), while there was no significant difference in median OS between chemotherapy group and other treatment group (P=0.685).Elderly MDS patients with medium and high risk can benefit from allogeneic hematopoietic stem cell transplantation, which will prolong their OS.老年中高危骨髓增生异常综合征患者的临床特点及预后研究.探讨老年中高危骨髓增生异常综合征（MDS）患者的临床特点及预后.回顾性分析2011年2月至2020年8月在南方医科大学南方医院就诊的97例年龄≥60岁、IPSS-R危险分层为中危/高危/极高危MDS患者的临床特点及预后情况。根据采取治疗方案的不同，将患者分为移植、化疗和其他治疗3组，分析评估不同治疗组患者之间疗效的差别.老年中高危MDS患者以MDS伴原始细胞增多型（MDS-EB）为主，47.4%的患者合并染色体核型异常，其中复杂核型（≥3个）占23.7%。97.3%的患者至少存在一种基因突变，TP53突变在老年中高危MDS患者中检出率近20%。多因素分析显示，IPSS-R危险分层、治疗方案影响老年中高危MDS患者的预后。3组患者的中位生存（OS）时间统计学差异（P=0.012），移植组中位OS长于化疗组及其他治疗组（P=0.003、P=0.014），化疗组和其他治疗组的中位OS无统计学差异（P=0.685）.老年中高危MDS患者可从异基因造血干细胞移植中获益，OS延长.

Meng-Meng Han,1,* Wen-Shu Zhao,2,* Xin Wang,2,* Shan He,3 Xiao-Rong Xu,2 Cai-Jing Dang,2 Juan Zhang,2 Jia-Mei Liu,2 Mu-Lei Chen,2 Lin Xu,2 Hua Wang2 1Intensive Care Units, Beijing Longfu Hospital, Beijing, 100010, People’s Republic of China; 2Heart Center and Beijing Key Laboratory of Hypertension Research, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 3Heart Center, Beijing Chaoyang Hospital Jingxi Branch, Capital Medical University, Beijing, 100020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Xu; Hua WangHeart Center and Beijing Key Laboratory of Hypertension Research, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaTel +86-10-85231445; +86-10-85231556Email lxdrqw09_dr@163.com; huwsmndr66@yandex.comObjective: This study aimed to find echocardiographic parameters that can predict short- and long-term adverse cardiovascular events in patients with AMI.Methods: A total of 126 patients with AMI admitted to our hospital from July to December 2012 were enrolled in this study. All patients underwent echocardiographic examination within 12 hours after admission and received regular follow-ups until December 2018. The primary endpoint was a composite of the major adverse cardiovascular events (MACEs).Results: In the first year of this study, a primary endpoint occurred in 35 patients and the predictor derived from the echocardiography of 1-year primary endpointwas LVEF< 40% (OR: 9.000, 95% CI 3.242-24.987, p< 0.0001) andthe area under the curve (AUC) for the predictor was 0.676 (95% CI 0.561-0.790, p=0.002). For the total 5 years, 57 patients underwent primary endpoint. The results of the 5-year primary endpoint were: E/E’> 15 (OR: 4.094, 95% CI 1.726– 9.710, P=0.001), the wall motion score index was (WMSI)> 1.5 (OR: 12.791, 95% CI 1.511– 108.312, P=0.019), and the AUC was 0.691 (95% CI 0.595– 0.787 P< 0.0001).Conclusion: LVEF is correlated with a short-term outcome (1-year), and WMSI and E/E’ can predict a long-term outcome (5-year) in patients with acute myocardial infarction.Keywords: echocardiography, cardiovascular events, predictors, acute myocardial infarction, wall motion score index

BACKGROUND Atherosclerosis is a chronic inflammatory disease triggered by endothelial dysfunction and exaggerated by macrophage infiltration. Although endothelin-1 (ET-1) plays an important role in vascular inflammation and reactive oxygen species production, the individual effect of ET-1 in atherogenesis remains unclear. METHODS AND RESULTS ET-1 expression was increased in mouse atherosclerotic plaques and human umbilical vein endothelial cells (HUVECs) administrated by oxidized low-density lipoprotein stimulation. Moreover, the immunofluorescence co-staining showed upregulated ET-1 expression in endothelial cells. Real-time polymerase chain reaction demonstrated that ET-1 overexpression promoted adhesion molecules and chemokines secretion in HUVECs. Following this intervention, the migration of macrophages and the pro-inflammatory cytokines were increased. More importantly, the endothelial dysfunction regulated by ET-1 and subsequently the effect on macrophage activation were mediated by ETA receptor and largely reversed by protein kinase C (PKC) inhibitor. Eight-week-old male ApoE–/– mice and eET-1/ApoE–/– mice were fed with high-fat diet for 12 weeks. eET-1/ApoE–/– significantly increased atherosclerotic lesions in the whole aorta and aortic sinus, which accompanied by the induction of inflammatory cytokines and macrophages infiltration. CONCLUSIONS ET-1 accelerates atherogenesis by promoting adhesion molecules and chemokines, as well as subsequent macrophage activation. Collected, these evidence suggest that ET-1 might be a potential target for the treatment of atherogenesis.

Objectives: The pathogenesis of hypertensive heart disease (HHD) remains unclear, which might include autoimmunity. The aim of the present study was to determine whether a relationship exists between the presence of autoantibodies against β1, β2, α1 adrenoreceptors, M2-muscarinic receptors, angiotensin II type1 receptors and HHD. Methods: In the present study, 44 patients diagnosed with HHD, 36 patients with hypertension, and 40 controls were also enrolled. The measurement of these 5 autoantibodies was performed by enzyme-linked immunosorbent assay. Results: The frequencies of autoantibodies against β1, β2, α1 adrenoreceptors, autoantibodies against M2-muscarinic receptors and autoantibodies against angiotensin II type1 receptors were significantly higher in patients with HHD, when compared to patients with hypertension and normal controls (all p < 0.001). In addition, the titers of these 5 autoantibodies significantly increased in patients with HHD. Patients who were positive for all 5 autoantibodies had larger left ventricular end-diastolic diameter (60.5 ± 4.9 vs. 57.8 ± 5.0 vs. 52.5 ± 5.3 mm) and worse left ventricular ejection fraction (45.0 ± 11.0 vs. 56.6 ± 10.4 vs. 57.8 ± 5.3%), when compared to patients not positive for all the 5 autoantibodies and patients negative for all the 5 autoantibodies (χ2 = 9.524, p = 0.009 and χ2 = 7.689, p = 0.021). Furthermore, a significant positive correlation was observed between each 2 autoantibodies of these 5 autoantibodies (all p < 0.001). Conclusion: Multiple autoantibodies of cardiovascular receptors may be involved in the pathogenesis and may be predictive factors of HHD.

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To investigate the correlation between U2AF1 gene mutation and clinical manifestations and prognosis in patients with myelodysplastic syndromes (MDS).The clinical data of 203 MDS patients who accepted Next Generation Sequencing (NGS) was retrospectively analyzed in Nanfang Hospital, Southern Medical University from December 2012 to October 2019. According to whether the patients had U2AF1 gene mutation, the patients were divided into U2AF1 mutated group and non-mutated group, and the relationship between gene mutation characteristics and clinical manifestations and prognosis was analyzed. Then according to the difference of the mutation site of U2AF1, the patients in U2AF1 mutated group were divided into U2AF1The incidence of U2AF1 mutation in MDS patients was approximately 11.3% (23/203), and the mutation frequency of U2AF1 allele was 32.5%. The male ratio in U2AF1 mutated group was significantly higher than that in U2AF1 non-mutated group (P=0.001). There was no patient who had complex karyotypes or TP53 gene mutation in U2AF1 mutated group. There were no significant differences in ages, blood parameters, bone marrow blasts, WHO 2016 classification, IPSS-R category, chromosomal abnormalities like del(5q), -7/del(7q), del(20q), +8, and gene mutation like ASXL1, DNMT3A, RUNX1, SF3B1, and SRSF2 mutation between U2AF1 mutated group and the non-mutated group. Compared with the non-mutated group, there was no significant difference in the overall survival time (P=0.377), the time of acute myeloid leukemia (AML) transformation (P=0.681), and the response rate to hypome- thylating agents in U2AF1 mutated group (P=0.556). Besides, no differences were observed in sex, diagnosis age, WHO 2016 classification, IPSS-R category, blood parameters, overall survival time, and AML transformation time between U2AF1The U2AF1 gene mutation dose not affect the survival time, AML transformation time, and response rate to hypomethylating agents in MDS patients. Besides, there are no statistical differences in the clinical characteristics and prognosis of MDS patients between U2AF1骨髓增生异常综合征患者U2AF1基因突变特征与临床表现及预后的相关性.探究骨髓增生异常综合征（MDS）患者U2AF1基因突变特征与临床表现及预后的相关性.回顾性分析2012年12月至2019年10月在南方医科大学南方医院进行二代测序（NGS）检测的203例MDS患者资料。根据患者有无U2AF1基因突变，将患者分为U2AF1突变组和U2AF1非突变组，并对2组患者的基因突变特征与临床表现及预后关系进行了分析；根据U2AF1突变位点，分为U2AF111.3%（23/203）的MDS患者存在U2AF1突变，U2AF1等位基因突变频率为32.5%。U2AF1突变组男性比例明显高于U2AF1非突变组（P=0.001）。U2AF1突变组无1例患者为染色体复杂核型或TP53突变。2组患者年龄、血液学参数、骨髓原始细胞比例、WHO 2016分型、IPSS-R危险分层、5q-、 -7/7q-、20q-、+8等染色体异常及ASXL1、DNMT3A、RUNX1、SF3B1、SRSF2等基因突变差异均无统计学意义。与U2AF1非突变组相比，U2AF1突变组患者的生存时间（P=0.377）、转化为白血病时间（P=0.681）及对去甲基化药物的总反应率（P=0.556）差异均无统计学意义。此外，U2AF1本研究结果提示，U2AF1基因突变不影响MDS患者总生存时间、转化为白血病率以及对去甲基化药物的反应率。U2AF1

The hallmark of atherogenesis is characterized as endothelial dysfunction and subsequent macrophage activation. Although our previous study has demonstrated that endothelin-1 (ET-1) plays an important role in atherogenesis, the underlying mechanism remains deeply investigation. Enhanced atherosclerotic plaques were observed in endothelium-specific ET-1 overexpression ApoE-/- mice (eET-1/ApoE-/-) concomitant with increased secretion of pro-inflammatory adhesion molecules and cytokines. The conditional media used for culturing human umbilical vein endothelial cells (HUVECs) with AdET-1 infection and subjected to OX-LDL stimulation, was collected and utilized for bone marrow-derived macrophages (BMDMs) culturing. RT-PCR analysis showed increased genes expression related to classical M1 macrophages but decreased alternative activated M2 macrophages genes expression in macrophage culturing with the conditional media. Furthermore, consistent regulations of macrophage polarization were observed using isolated exosomes from the conditional media. More importantly, we noticed that miR-33 was enriched in the exosomes derived by HUVECs with AdET-1 infection, while bioinformatics analysis further indicated that miR-33 directly targeted NR4A and miR-33/NR4A axis was required for the effect of endothelial-specific ET-1 overexpression on pro-inflammatory macrophage activation. By contrast, such effects could be reversed by ET-1 knockdown. Taken together, our study indicated that the exosomes derived by HUVECs with AdET-1 infection can transfer miR-33 to macrophages and subsequently promote pro-inflammatory macrophage activation by directly targeting to NR4A. These evidences clearly revealed that miR-33/NR4A axis was the important mechanism underlying the effect of ET-1 on macrophage activation and indicated that ET-1 may act as a promising target for atherosclerosis management.

Ejection fraction (EF) has been used in phenotype analyses and to make treatment decisions regarding heart failure (HF). Thus, EF has become a fundamental part of daily clinical practice.This study aims to investigate the characteristics, predictors, and outcomes associated with EF changes in patients with different types of severe HF.A total of 626 severe HF patients with New York Heart Association (NYHA) class III-IV were enrolled in this study. The patients were classified into three groups according to EF changes, namely, increased EF (EF-I), defined as an EF increase ≥10%, decreased EF (EF-D), defined as an EF decrease ≥10%, and stable EF (EF-S), defined as an EF change10%. A p-value lower than 0.05 was considered significant.Out of 377 severe HF patients, 23.3% presented EF-I, 59.5% presented EF-S, and 17.2% presented EF-D. The results further showed 68.2% of heart failure with reduced ejection fraction (HFrEF) in the EF-I group and 64.6% of heart failure with preserved ejection fraction (HFpEF) in the EF-D group. The predictors of EF-I included younger age, absence of diabetes, and lower left ventricular ejection fraction (LVEF). The predictors of EF-D were absence of atrial fibrillation, lower uric acid level, and higher LVEF. Within a median follow-up of 40 months, 44.8% of patients suffered from all-cause death.In severe HF, HFrEF presented the highest percentage in the EF-I group, and HFpEF was most common in the EF-D group.A fração de ejeção (FE) tem sido utilizada em análises fenotípicas e na tomada de decisões sobre o tratamento de insuficiência cardíaca (IC). Assim, a FE tornou-se parte fundamental da prática clínica diária.Este estudo tem como objetivo investigar características, preditores e desfechos associados a alterações da FE em pacientes com diferentes tipos de IC grave.Foram incluídos neste estudo 626 pacientes com IC grave e classe III–IV da New York Heart Association (NYHA). Os pacientes foram classificados em três grupos de acordo com as alterações da FE, ou seja, FE aumentada (FE-A), definida como aumento da FE ≥10%, FE diminuída (FE-D), definida como diminuição da FE ≥10%, e FE estável (FE-E), definida como alteração da FE10%. Valores p inferiores a 0,05 foram considerados significativos.Dos 377 pacientes com IC grave, 23,3% apresentaram FE-A, 59,5% apresentaram FE-E e 17,2% apresentaram FE-D. Os resultados mostraram ainda 68,2% de insuficiência cardíaca com fração de ejeção reduzida (ICFEr) no grupo FE-A e 64,6% de insuficiência cardíaca com fração de ejeção preservada (ICFEp) no grupo FE-D. Os preditores de FE-A identificados foram faixa etária mais jovem, ausência de diabetes e fração de ejeção do ventrículo esquerdo (FEVE) menor. Já os preditores de FE-D encontrados foram ausência de fibrilação atrial, baixos níveis de ácido úrico e maior FEVE. Em um seguimento mediano de 40 meses, 44,8% dos pacientes foram vítimas de morte por todas as causas.Na IC grave, a ICFEr apresentou maior percentual no grupo FE-A e a ICFEp foi mais comum no grupo FE-D.

The present study describes the derivation and validation of the Chronic Heart Failure Severity Index (CHFSI).The CHFSI was derived using data obtained from a single-center prospective cohort study (2000-2014) that enrolled 756 patients. Logistic regression was used to identify independent predictors of mortality and quality of life over a 15-year follow-up period.The score was validated at the first 5-year (n = 644), second 5-year (n = 364), and third 5-year (n = 262). Independent predictors of mortality were older age (OR = 2.04, P 0.001), etiology score (OR = 2.61, P 0.001), faster heart rate (OR = 1.46, P = 0.027), higher systolic blood pressure (OR = 2.35, P 0.001), and left ventricular ejection fraction ≤45% (OR = 1.97, P = 0.018). The derived CHFSI predicted the mortality, and the AUC for the logistic model was 0.78 (95% confidence interval = 0.74-0.81, P 0.001). Based on the logistic model, an integer scoring system was derived. Patients were classified into three groups: low risk (0-7 points), intermediate risk (8-11 points) and high risk (≥12 points) groups. The cumulative mortality for 15 years was 45.5% (125/275), 84.0% (204/243), and 100% (99/99), respectively (P 0.001). The 6-min walk test revealed a significant difference in quality of life among patients in the low, medium and high risk groups (all, P 0.0001).The CHFSI is a very useful clinical predictive tool that identifies patients at risk of future mortality and their quality of life across healthcare systems.

This study aims to investigate the predictive value of pre-chemotherapy β1R-AABs by evaluating the response of newly diagnosed symptomatic multiple myeloma (MM) patients to their treatment with a bortezomib-containing regimen. Forty-five de novo MM patients and 50 normal controls (NCs) were prospectively enrolled in this study. Serum titers of β1R-AABs were detected by ELISA. These 45 MM patients were divided into two groups (positive and negative groups) according to their β1R-AABs. Follow-up examinations were performed on these patients during chemotherapy induction. The final analysis covered all 45 MM patients, including 19 patients who were positive for MM and 26 patients who were negative for MM. Multivariate analysis revealed that pre-chemotherapy β1R-AABs are possibly independent predictors for less than very good partial response (VGPR) after the bortezomib-containing regimen treatment (odds ratio: 5.967, 95% confidence interval: 1.513–23.531; p = .011). This study demonstrates for the fi...

Objective: We investigated the regulation of endothelin-1 (ET-1) expression in in vivo high-fat diet (HFD)-fed mice and in vitro cultured human aortic endothelial cells (HAECs). Methods: Male C57BL/6 mice were fed on standard chow, serum was prepared, and ET-1 levels were analyzed using an ELISA kit. Quantitative PCR was performed using iQ SYBR Green Supermix. Statistical significance was assessed using SPSS, with p < 0.05 considered significant. Results: The serum ET-1 content and endothelial expression of ET-1 mRNA were increased in the HFD-fed mice compared to the chow-fed control mice. Moreover, the mRNA expression of ET-1 was significantly increased in cultured HAECs in response to acute (< 24 h) and chronic (12–16 days) treatments with palmitic acid (PA), one of the most abundant saturated fatty acids in obesity. We found that the induction of ET-1 expression by PA was abolished by pretreating the cells with the endoplasmic reticulum (ER) stress inhibitor 4-phenylbutyric acid or the protein kinase C (PKC) inhibitor Gö 6850. Conclusion: Our findings demonstrate for the first time that PA increases ET-1 expression in endothelial cells through the induction of ER stress and the activation of PKC, providing novel mechanistic insights into the pathogenesis of obesity-associated hypertension and cardiovascular diseases.

Induced pluripotent stem cells (iPSCs) are generated by reprogramming human somatic cells through the overexpression of four transcription factors: Oct4, Sox2, Klf4 and c-Myc. iPSCs are capable of indefinite self-renewal, and they can differentiate into almost any type of cell in the body. These cells therefore offer a highly valuable therapeutic strategy for tissue repair and regeneration. Recent experimental and preclinical research has revealed their potential for cardiovascular disease diagnosis, drug screening and cellular replacement therapy. Nevertheless, significant challenges remain in terms of the development and clinical application of human iPSCs. Here, we review current progress in research related to patient-specific iPSCs for ex vivo modeling of cardiovascular disorders and drug screening, and explore the potential of human iPSCs for use in the field of cardiovascular regenerative medicine.

Background Experimental studies of acute myocardial infarction have revealed that up to half of the final infarct size may be due to reperfusion injury rather than the initial ischemic incident. Research over the past three decades has deepened our understanding of the molecular mechanisms underlying ischemic reperfusion injury and several therapeutic strategies to decrease the incidence and severity of reperfusion injury have been explored. Objective To discuss the promising therapies and future perspectives on methods to attenuate myocardial reperfusion injury. Results Existing therapies that address reperfusion can be divided into two major groups comprising nonpharmacological and pharmacological interventions. Myriad pharmacological and nonpharmacological approaches to reduce lethal reperfusion injury have been employed. Although many initial clinical studies were negative, more recent proof-of-concept clinical trials are promising. To date, the most encouraging results are with ischemic postconditioning, remote ischemic preconditioning, ANP, adenosine, cyclosporine and exenatide. Conclusion Studies demonstrate that nonpharmacological and pharmacological conditioning can be used together as part of a multifaceted approach to improve clinical outcomes in patients with ischemic heart disease.

Supplemental Digital Content is available in the text, Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation, and is associated with systolic dysfunction and increased action potential duration. Approximately 50% of DCM cases are caused by inherited gene mutations with genetic and phenotypic heterogeneity. Next generation sequencing may be useful in screening unknown mutations in such cases. A family was identified with DCM, in which the affected family members developed heart failure, arrhythmia, and sudden death. Probands and 4 affected family members underwent whole exome sequencing (WES), bioinformatics methods, and gene annotation to identify potentially causative variants. The Sanger sequencing method was used to verify the candidate mutation. WES yielded 2,238,831 variations. KCNJ12 (p.Glu334del) was identified as a candidate mutation, and the heterozygous mutation was verified by Sanger sequencing. Our study emphasizes the application of WES in identifying causative mutations in DCM. This report is the first to describe the KCNJ12 gene as a cause of DCM in patients.

This study aims to investigate the predictive value of pre-chemotherapy β1R-AABs by evaluating the response of newly diagnosed symptomatic multiple myeloma (MM) patients to their treatment with a bortezomib-containing regimen. Forty-five de novo MM patients and 50 normal controls (NCs) were prospectively enrolled in this study. Serum titers of β1R-AABs were detected by ELISA. These 45 MM patients were divided into two groups (positive and negative groups) according to their β1R-AABs. Follow-up examinations were performed on these patients during chemotherapy induction. The final analysis covered all 45 MM patients, including 19 patients who were positive for MM and 26 patients who were negative for MM. Multivariate analysis revealed that pre-chemotherapy β1R-AABs are possibly independent predictors for less than very good partial response (VGPR) after the bortezomib-containing regimen treatment (odds ratio: 5.967, 95% confidence interval: 1.513-23.531; p = .011). This study demonstrates for the first time that the presence of β1R-AABs is associated with MM. Pre-chemotherapy β1R-AABs are independent predictors for less than VGPR in de novo MM patients after the bortezomib-containing regimen was administrated. Bortezomib might not significantly give rise to cardiac impairment in MM patients.

Given both smoking and vitamin D are associated with coronary heart disease (CHD) via inflammation and smoking may interfere with the local antiinflammatory effects of vitamin D. We hypothesized that the relationship between smoking and severity of CHD may be modified by vitamin D. A cross-sectional study was conducted. 25-OH vitamin D values were determined in 348 consecutive patients (mean age 62.4 ± 10.5 years; 56.3% male) undergoing coronary angiography at the Heart Center of Chaoyang Hospital affiliated to Capital Medical University between the period of September 2014 and May 2015. We categorized the patients into 2 groups based on 25-OH vitamin D levels, that is, severe hypovitaminosis D (25-OH vitamin D = 10 ng/mL). Multivariable logistic regression models were used to estimate odds ratios (ORs) of severe coronary stenosis or higher Gensini score across three smoking status, that is, never smokers, former smokers, and current smokers in severe hypovitaminosis D and higher vitamin D groups, respectively. Of these patients, we identified 212 (60.9%) cases of severe CHD and 161 (46.3%) cases of severe hypovitaminosis D. Multivariable logistic regression model showed the ORs of severe CHD were 1.94 (95% confidence interval [CI]: 0.47, 7.98) for former smokers and 2.62 (95% CI: 0.83, 8.24) for current smokers, compared with never smokers in group with severe hypovitaminosis D (P-trend = 0.005). In contrast, smoking was not found to be significantly associated with severe CHD in group with higher 25-OH vitamin D (P-trend = 0.115). We found a significant interaction between smoking status and vitamin D on presence of severe CHD (P-interaction = 0.015). In terms of Gensini score as a dependent variable, similar results were identified. Our finding indicated the association between smoking and severity of CHD appeared to be substantially stronger among patients with severe hypovitaminosis D as compared with those with higher vitamin D levels. This suggests vitamin D sufficiency may have a protective effect against the damaging effects of smoking on coronary artery. Future cohort studies are warranted to confirm this finding.

Background There is conflicting evidence regarding two different insulin regimens for acute myocardial infarction (AMI), one focusing on delivering insulin (‘insulin focus’, glucose-insulin-potassium (GIK)) and one focusing on tight glycaemic control (‘glycaemia focus’, insulin-glucose). A longstanding controversy has focused on which strategy provides the greatest reduction in mortality. The aim of this study was to perform a meta-analysis of randomised controlled trials (RCTs) comparing GIK or insulin-glucose therapy versus standard therapy for AMI in the reperfusion era. Methods A MEDLINE/EMBASE/CENTRAL search was conducted of RCTs evaluating GIK or insulin-glucose as adjunctive therapy for AMI. The primary endpoint was all-cause mortality. The data were analysed with a random effect model. Results A total of 11 studies (including 23 864 patients) were identified, eight evaluating insulin focus with GIK and three evaluating glycaemia focus with insulin-glucose. Overall, insulin focus with GIK was not associated with a statistically significant effect on mortality (RR 1.07, 95% CI 0.89 to 1.29, p=0.487). Before the use of reperfusion, GIK also had no clear impact on mortality (RR 0.92, 95% CI 0.70 to 1.20, p=0.522). Pooled data from the three studies evaluating glycaemia focus showed that insulin-glucose did not reduce mortality in the absence of glycaemia control in patients with AMI with diabetes (RR 1.07, 95% CI 0.85 to 1.36, p=0.547). Conclusions Current evidence suggests that GIK with insulin does not reduce mortality in patients with AMI. However, studies of glycaemia are inconclusive and it remains possible that glycaemic control is beneficial.

Different postconditioning (Postcon) methods have been demonstrated to protect heart from ischemia/reperfusion injury. The relationship between Postcon by percutaneous coronary intervention (PCI) and apoptosis is not clear. Our objective was to test whether Postcon by PCI in patients with acute myocardial infarction (AMI) reduces myocardial apoptosis. Seventy-five patients were randomly assigned to one of three groups before stenting. The Routine group (n = 26) received no Postcon intervention prior to the onset of reperfusion; Postcon-30s (n = 25) and Postcon-60s groups (n = 24) underwent three cycles of 30- or 60-s balloon deflation and 30- or 60-s inflation. Additionally, 34 normal controls (NC) were enrolled in the study. Plasma concentrations of soluble Fas/APO-1 ([sFas]) and Fas ligand ([sFasL]) were determined at baseline and 7 days after PCI via ELISA. The [sFas] and [sFasL] in AMI patients were significantly elevated at baseline as compared with NC (P

To explore the in-hospital mortality and its determinants for very eldly (80+ years of age) patients with acute myocardial infarction (AMI).A retrospective cohort method was used. The 499 study subjects were very eldly patients with newly diagnosed AMI consecutively admitted into our department between January 1, 2002 and February 22, 2010.Ninety-seven out of 499 patients died during hospitalization period, with total in-hospital mortality of 19.4%. Multivariable logistic regression analysis showed the independent determinants for mortality of very elderly AMI patients were cardiac Killip grades, complete A-V block, renal dysfunction, stent implant, and the type of AMI.The independent determinants for mortality of elderly AMI patients are as following, cardiac Killip grade, complete A-V block, renal dysfunction, stent implant, and the type of MAI. Urgent PCI is safe and effective for some very elderly with AMI, which could improve their survival rate within hospitalization period.

To determine whether autoantibodies against the cardiac G-protein-coupled beta 2- and alpha 1-adrenergic and AT1 receptors are related to patients with primary hypertension.Synthetic peptides corresponding to amino acid sequences of the second extracellular loops of the beta 2- and alpha 1-adrenergic and AT1 receptors were respectively used as antigens to screen sera from patients with hypertensive heart diseases (n = 50) as well as simple hypertension (n = 40) and healthy blood donors (n = 40) using ELISA test.The positive ratio of autoantibodies against beta 2 and alpha 1 and AT1 receptors in patients with hypertensive heart diseases were significantly higher than patients with simple hypertension and healthy donors. The geometric mean titers of autoantibodies against beta 2- and alpha 1-adrenergic and AT1 receptors had no difference between the patients with hypertensive heart diseases and the patients with simple hypertension, but the geometric mean titers of two groups were higher than healthy donors. In the patients with hypertensive heart diseases, 81.0% of the patients with autoantibodies against beta 2-adrenergic receptor had autoantibodies against alpha 1-adrenergic receptor and 76.2% had autoantibodies against AT1 receptors. The percent of the autoantibodies against three receptors in patients with hypertensive heart diseases were 52.4%.Autoantibodies against beta 2- and alpha 1-adrenergic and AT1 receptors play an important role in the pathophysiological changes of primary hypertension, and may participate myocardial and vessel remodeling.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is characterized by left ventricular systolic dysfunction and heart failure. However, its pathogenesis is not clear. Our preliminary study revealed that autoantibodies against β1-adrenergic receptors (β1R-AABs) and M2-muscarinic receptors (M2R-AABs) participated in heart failure regardless of primary heart disease. Whether β1R-AABs and M2R-AABs participate in the pathogenesis of PPCM is still unknown. METHODS: Totally 37 diagnosed PPCM patients and 36 normal pregnant women were enrolled in this study. Clinical assessment and 2-dimensional echocardiographic studies as well as the measurement of β1R-AABs or M2R-AABs by enzyme linked immunosorbent assay (ELISA) were performed. RESULTS: The positive rates for β1R-AABs and M2R-AABs were 59.5% (22/37) and 45.9% (17/37) in PPCM patients, and 19.4% (7/36) (P