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Zhenjun Xu,1,* Kai Zhong,2,* Guanjun Guo,1,* Can Xu,1 Zhizhao Song,1 Dongjin Wang,1 Jun Pan1 1Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 2Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Pan; Zhenjun XuDepartment of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, People’s Republic of ChinaTel +86 25 68182222-60721Fax +86 25 83105117Email pj791028@163.com; xzj881225@163.comBackground: Aortic dissection (AD) is a threatening and catastrophic vascular disease with high mortality rate and limited therapeutic strategies. There is emerging evidence showing that circular RNAs play crucial role in regulating various cardiovascular diseases. However, the biological functions and molecular mechanisms of circRNAs in AD still remains elusive. The purpose of this study was to illustrate the potential functional roles and mechanisms of hsa_circ_TGFBR2 in vitro and in vivo.Methods: The vascular smooth muscle cells (VSMCs) and AD-VSMCs were isolated from normal aorta and AD tissues. The expression of circ_TGFBR2, miR-29a and KLF4 were detected by realtime polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). Cell proliferation was assessed by CCK-8 assay, colony formation and EDU assay. Cell migration was evaluated through transwell assay. Dual-luciferase reporter assay and RNA pulldown were performed to identify the interaction between circ_TGFBR2 and miR-29a or between miR-29a and KLF4. The wild-type sequence of circ_TGFBR2 or KLF4 were cloned into the luciferase reporter plasmid, and the activity was measured using dual-luciferase reporter assay system. And for RNA pulldown, the relative RNA enrichment of circ_TGFBR2 and miR-29a were confirmed using RT-PCR. Western Blot measured the expression of phenotype switch-related proteins. AD rat model induced by β-aminopropionitrile monofumarate (BAPN) was used to verify the role and mechanism of circ_TGFBR2.Results: Circ_TGFBR2 inhibited cell proliferation and migration of AD-VSMCs cells. Overexpression of circ_TGFBR2 promoted the expression of contractile markers (α-SMA, SM22α) and inhibited the expression of synthetic markers (MGP, OPN) in AD-VSMCs cells. Circ_TGFBR2 served as a sponge for miR-29a targeting KLF4. MiR-29a mimics rescued biological roles induced by circ_TGFBR2 overexpression. The in vivo experiments revealed that overexpression of TGFBR2 suppressed the progression of AD and increased the expression of contractile markers while inhibited the expression of synthetic markers.Conclusion: Our study revealed that circ_TGFBR2 regulated VSMCs phenotype switch and suppressed the progression of AD.Keywords: aortic dissection, circ_TGFBR2, miR-29a, KLF4, vascular smooth muscle cells

Cardiac hypertrophy can cause heart failure. However, the mechanisms underlying the progression of cardiac hypertrophy remain unclear. Emerging evidence suggests that circular RNAs (circRNAs) play a critical role in cardiac hypertrophy. However, the association between circ_nuclear factor I X (circNfix) and cardiac hypertrophy remain largely unknown. Therefore, the aim of the present study was to explore the role of circNfix in cardiac hypertrophy. In order to detect the function of circNfix in cardiac hypertrophy, cardiomyocytes were stimulated with angiotensin II (Ang II) to mimic the pathogenesis of the disease. In addition, pressure overload-induced cardiac hypertrophy in a mouse model was established using transverse aortic constriction (TAC) surgery. The mechanism via which circNfix regulated cardiac hypertrophy was investigated using RNA pull-down and luciferase reporter assays, and fluorescence in situ hybridization (FISH). circNfix was downregulated in Ang II-treated cardiomyocytes. Similarly, circNfix expression was markedly downregulated in mice following TAC surgery. In addition, circNfix overexpression significantly prevented the progression of cardiac hypertrophy in TAC-treated mice. Luciferase activity and RNA pull-down assays indicated that circNfix could indirectly target activating transcription factor 3 (ATF3) by binding with microRNA (miR)-145-5p in cardiomyocytes. miR-145-5p overexpression or ATF3 knockdown could reverse the effects of circNfix in Ang II-treated mouse cardiomyocytes. circNfix attenuated pressure overload-induced cardiac hypertrophy by regulating the miR-145-5p/ATF3 axis. Therefore, circNfix may serve as a molecular target for cardiac hypertrophy treatment., GRAPHICAL ABSTRACT

Background: To assess the effects of mitral valve (MV) replacement for functional mitral regurgitation (FMR) in patients with severe left ventricular (LV) dysfunction. Methods: 48 patients with secondary non-ischemic severe mitral regurgitation (MR) and left ventricle eject fraction (LVEF) less than 35% were underwent MV replacement. All surgeries were finished by one surgical team from January 2010 to December 2015. Twenty-three patients were females and the mean age was 60.21 ± 10.69 years (range, 29～75 years). The preoperative cardiac function classification was Ⅲ~Ⅳ (NYHA) in 40 patients. The mean follow-up time was five years. Results: Three patients (6.3%) died in hospital: 2 from low output syndrome and 1 from multi-organ failure induced by pulmonary infection. The mean postoperative intensive care unit (ICU) stay time was 4 days. The mean cardiopulmonary bypass time was 131.50 ± 3.92 min, and the mean aortic cross-clamping time was 85.39 ± 24.16 min. The left atrium diameter and the systolic pulmonary artery pressure (PAP) decreased significantly after surgery. The survival rates at 1 and 5 years were 83.3% and 54.6%, and 29 patients (60.4 %) were in NYHA class Ⅰ/Ⅱ during the follow-up time. Conclusions: Mitral valve replacement maybe offers symptomatic improvement and mid-term survival benefit for non-ischemic FMR in some patients with severe LV dysfunction.

Correctly understanding and assessing the physiological and biochemical characteristics of athletes has a very important role. Sports items, training levels, exercise load, post-exercise recovery, and athletes’ own conditions are all factors which affect athletes’ physical performance. These factors should be fully considered in the process of specific performance assessment. The salivary indicators in the current assessment of athletes’ performance are not mature, so blood and urine indicators are mainly used.

Objective Inflammation and autoimmune responses play an important role in recurrence of atrial fibrillation (AF). Serum globulin levels are a commonly used clinical index that represents inflammation and autoimmune response. This study aimed to determine the relationship between baseline serum globulin levels and the risk of recurrence after ablation in lone AF patients. Methods We enrolled 348 lone AF patients undergoing radiofrequency catheter ablation for the first time for whom complete follow-up data were available. Pre-ablation peripheral venous blood samples were obtained for measurement of serum globulin levels. Results During the follow-up period of 22 months (range, 6-62), AF recurred in 129 patients (37.1%). Recurrence was associated with a low level of pre-ablation serum globulins. Multiple Cox proportional hazard regression analysis showed that persistent AF, AF duration, left atrial diameter, no amiodarone after ablation, and the serum globulin level in particular were independent predictors of AF recurrence. According to receiver operating characteristic curve analysis, the best diagnostic cut-off serum globulin level was 25.4 g/L, which showed 74.4% sensitivity, 71.3% specificity, and 73.3% accuracy. Conclusion The baseline low serum globulin level is associated with AF recurrence after first-time ablation in lone AF patients. Therefore, it may be used as a predictor of AF recurrence in these patients.

Low carbon planning of a national sustainable development of experimentation area, chengyang area qingdao city, was researched around the technology for controlling carbon emission resource, expanding carbon sink and town low carbon construction planning. The contribution of architectural layout to low carbon emission and the contribution of afforest to carbon sequestration capacity were studied. In addition, influence of afforest imbalance ratio for town carbon emission was researched in the paper. Results show that the quantity of carbon fixation and oxygen release was 623700 tons and 459200 tons per year in chengyang area. The reasonable architectural layout contribute to reduce 13200 tons of CO2 emissions. The average fixed carbon quantity is about 0.46kg per square meter in urban area, about 4kg per square meter in outer suburb and mountainous area, accounted for about 70% of the total amount of carbon. There is serious imbalance phenomenon in the town greening. It is one of the conclusion that key point for greening should be changed from the high rate of greening to high-quality green rates, that is to increase the urban greening ratio and optimize its distribution.

The pathogenesis of aortic dissection (AD) is unclear. The aim of this study was to explore the relationship between osteopontin (OPN) and AD. Fifty AD patients were enrolled; 29 had hypertension with AD (H-AD) and 21 no hypertension with HD (NH-AD). Twenty-five healthy controls (NH-C) and 14 patients with hypertension (H-C) were also enrolled. Serum and aortic wall OPN levels were determined. Human vascular muscle cells (HVSMC) were stimulated by both low (1 μg/mL) and high (5 μg/mL) concentrations of OPN and cell proliferation as well as apoptosis was measured. Transforming growth factor-β (TGF-β), matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-9, TIMP-1, and TIMP-2 gene expressions by HVSMC were measured and Akt, IκB, Smad1/5/8 and Erk1/2 signaling pathways were detected. Our results showed that AD patients demonstrated significantly higher levels of serum and local OPN expressions compared to healthy controls. In those with hypertension, the serum concentrations of OPN were increased compared to those without hypertension. In in vitro culture, a high dose of OPN stimulation promoted the proliferation of HVSMC but did not affect cell apoptosis. Both concentrations of OPN enhanced MMP-2 gene expression and its activity in HVSMC. Moreover, Akt and IκB signaling pathways were significantly activated after OPN stimulation while the Smad1/5/8 and Erk1/2 signaling pathways were not changed. The addition of an IκB inhibitor significantly abrogated MMP-2 gene expression. Our data show that OPN may participate in the pathogenesis of AD by the enhancement of MMP-2 expression.

Stanford type A Aortic dissection (TAAD) is a deadly cardiovascular disease but the relationship between inflammatory cytokines and disease pathogenesis is still unclear. Observation of the changes of different chemokines may help to explore the etiology of TAAD much further. Clinical data was collected from TAAD patients (TAAD group) and healthy controls (HC group) in our institute between October 2013 and December 2014. Blood sample was harvested from each subject of two groups. The expression levels of eighty chemokines were examined by protein array technology. Then we tested the expressions of macrophage inflammatory protein 1β (MIP-1β), epithelial neutrophil activating peptide 78 (ENA-78), interleukin 16 (IL-16), interferon inducible protein 10 (IP-10), and FMS-like tyrosine kinase 3 (Flt-3) ligand by using luminex technology. Osteopontin (OPN) and monocyte chemotaxis protein (MCP) levels were analyzed by ELISA kits. The mean age of TAAD group is 49.9 ± 11.2 and 48.7 ± 9.9 in HC group, respectively. 76.0% of TAAD patients and 72.0% of healthy controls were male. MIP-1β and ENA-78 expression in TAAD group were significantly lower than that in HC group, while significant increasing IL-16 level was found. Plasma levels of OPN in TAAD group increased remarkably compared with HC group, but MCP-1 and MCP-2 expression significantly decreased. No correlation was shown between serum CRP levels and plasma level of these cytokines by using Spearman analysis. ROC analysis showed that OPN could be indicators for TAAD diagnosis with sensitivity of 0.92 and specificity of 0.99. Our results provide a reasonable way to focus on the chemokines in understanding the pathogenesis of human TAAD.

Objectives Our goal was to establish a prediction score and protocol for the preoperative prediction of significant coronary artery disease (CAD) in patients with rheumatic valvular heart disease. Methods Using multivariate logistic regression analysis, we validated the model based on 490 patients without a history of myocardial infarction and who underwent preoperative screening coronary angiography. Significant CAD was defined as ≥50% narrowing of the diameter of the lumen of the left main coronary artery or ≥70% narrowing of the diameter of the lumen of the left anterior descending coronary artery, left circumflex artery or right coronary artery. Results Significant CAD was present in 9.8% of patients. Age, smoking, diabetes mellitus, diastolic blood pressure, low-density lipoprotein cholesterol and ischaemia evident on an electrocardiogram were independently associated with significant CAD and were entered into the multivariate model. According to the logistic regression predictive risk score, preoperative coronary angiography is recommended in (i) postmenopausal women between 50 and 59 years of age with ≥9.1% logistic regression predictive risk score; (ii) postmenopausal women who are ≥60 years old with a logistic regression predictive risk score ≥6.6% and (iii) men ≥50 years old whose logistic regression predictive risk score was ≥2.8%. Based on this predictive model, 246 (50.2%) preoperative coronary angiograms could be safely avoided. The negative predictive value of the model was 98.8% (246 of 249). Conclusions This model was accurate for the preoperative prediction of significant CAD in patients with rheumatic valvular heart disease. This model must be validated in larger cohorts and various populations.

Early and convenient diagnosis is urgently needed for acute Stanford type A aortic dissection (AAAD) patients due to its high mortality within the first 48 hours. Circulating microRNAs (miRNAs) are promising biomarkers of cardiovascular diseases, however, little is known about circulating miRNAs involved in AAAD. Here, the blood serum was sampled from 104 AAAD+ patients and 103 age-matched donors. Initial screening was conducted using the TaqMan Low Density Array followed by RT-qPCR confirmation. According to the two-phase selection and validation process, we found that miR-25, miR-29a and miR-155 were significantly elevated, while miR-26b was markedly decreased in AAAD+ serum samples compared with AAAD− individuals. Most importantly, for individuals with hypertension, which is a major contributor to AAAD, the 4-miRNA panel also showed high accuracy in predicting those who are more likely to develop AAAD. In the blind trial set, the panel correctly classified 93.33% AAAD+ patients and 86.67% controls from the hypertension cohort. Finally, the serum miRNA-based biomarker for early AAAD detection was supported by a retrospective analysis. Taken together, we identify a distinct profile of 4-miRNA that can serve as a noninvasive biomarker for AAAD diagnosis, especially for those with hypertension.

Biogas engine-driven heat pump air conditioner is a new-style system which includes biogas engine-driven heat pump, primary heat exchanger, second heat exchanger, sprayed room and fans, pumps, etc. In summertime, the air can be reheated by the waste heat water from the biogas engine in the system, while the air can be reheated and humidified by the waste heat water in winter. Reducing or displacing electrical heating requirements can achieve the great opportunity for significant energy savings. This paper, therefore, aims to improve the energy performance of the AC system by using the waste heat from the biogas engine. The mathematic model was used to research the BHPAC. Explicitly, we investigated the influence of various factors including the outdoor air temperature and humidity in summer and winter. Results show that the biogas engine-driven heat pump air conditioner can save more energy than the electrical power heat pump. in summer, the minimum for percentage of primary energy saving for BHPAC is over 25%. With the outdoor air dry-bulb temperature and the relative humidity rises, the saving energy percentage rises. In winter, the minimum for percentage of primary energy saving for BHPAC is 37%. The more the outdoor air relative humidity of the outdoor air decreases, the more the BHPAC saves energy. It is proved that the system which is a highly actively fully utilizing energy technology has good partial load characteristic and good effects of energy saving. (C) 2010 Published by Elsevier Ltd.

Objective Many studies have shown that magnetic fields (MF) inhibit tumor growth and influence the function of immune system. However, the effect of MF on mechanism of immunological function in tumor-bearing mice is still unclear. Methods In this study, tumor-bearing mice were prepared by subcutaneously inoculating Balb/c mice with hepatocarcinoma cell line H22. The mice were then exposed to a low frequency MF (0.4 T, 7.5 Hz) for 30 days. Survival rate, tumor growth and the innate and adaptive immune parameters were measured. Results MF treatment could prolong survival time (n = 28, p

Background We previously found that the low frequency magnetic fields (LF-MF) inhibited gastric and lung cancer cell growth. We suppose that exposure to LF-MF may modulate immune function so as to inhibit tumor. We here investigated whether LF-MF can inhibit the proliferation and metastasis of melanoma and influence immune function. Methods The effect of MF on the proliferation, cell cycle and ultrastracture of B16-F10 in vitro was detected by cell counting Kit-8 assay, flow cytometry, and transmission electron microscopy. Lung metastasis mice were prepared by injection of 2 × 105 B16-F10 melanoma cells into the tail vein in C57BL/6 mice. The mice were then exposed to an LF-MF (0.4 T, 7.5 Hz) for 43 days. Survival rate, tumor markers and the innate and adaptive immune parameters were measured. Results The growth of B16-F10 cells was inhibited after exposure to the LF-MF. The inhibition was related to induction of cell cycle arrest and decomposition of chromatins. Moreover, the LF-MF prolonged the mouse survival rate and inhibited the proliferation of B16-F10 in melanoma metastasis mice model. Furthermore, the LF-MF modulated the immune response via regulation of immune cells and cytokine production. In addition, the number of Treg cells was decreased in mice with the LF-MF exposure, while the numbers of T cells as well as dendritic cells were significantly increased. Conclusion LF-MF inhibited the growth and metastasis of melanoma cancer cells and improved immune function of tumor-bearing mice. This suggests that the inhibition may be attributed to modulation of LF-MF on immune function and LF-MF may be a potential therapy for treatment of melanoma.

The biogas air conditioner is a new style air condition system which is composed of the biogas heat pump (BHP), the second heat exchanger and some auxiliary equipments such as fans, water pumps, etc. The mathematic model including the primary heat exchanger model, the second heat exchanger model, the water spraying chamber model, the mixed air model, the BHP model, was used to research the system. The seasonal energy efficiency ratio (SPER) for the air conditioner was defined to evaluate the seasonal performance of air condition. Results from the analysis show that the biogas air conditioner can save more energy than the electricity engine-driven heat pump air condition. The GEHP with the wet processing can be used in more areas than the common GEHP. Applying intelligent controller and using waste heat can improve seasonal energy efficiency ratio for biogas air conditioner.