Clinical Observation of Coronary Artery Bypass Grafting with Heart Valve Replacement for Coronary Heart Disease with Heart Valvular Disease

Objective: To analyze and explore the clinical observation of coronary artery disease with coronary heart disease and coronary heart disease (CHD) undergoing coronary artery bypass grafting. Methods: From December 2015 to December 2016, 80 patients with coronary heart disease and heart valve were randomly divided into two groups: observation group and control group (40 cases). The observation group was treated with coronary artery bypass grafting combined with simultaneous heart valve replacement. The control group was treated with coronary stent implantation and non-synchronous valve replacement. The improvement of postoperative cardiac function, postoperative hospitalization, adverse events and bridge patency were compared between the two groups. Results: The improvement of cardiac function and the incidence of adverse events were significantly better in the observation group than in the control group (P <0.05). The time of hospitalization and the time of ventilator were significantly shorter than those of the control group (P <0.05). The patency rate of the bridge was significantly higher than that of the control group (P <0.05). Conclusion: Coronary artery bypass grafting combined with heart valve replacement in patients with coronary heart disease complicated with valvular heart disease can achieve significant curative effect, which is more ideal and safer than coronary artery bypass surgery combined with non-synchronous valve replacement

MicroRNA-323a-3p Promotes Pressure Overload-Induced Cardiac Fibrosis by Targeting TIMP3

Background/Aims: Cardiac fibrosis is a major cause of diverse cardiovascular diseases. MicroRNAs have recently been proven a novel class of regulators of cardiac fibrosis. In this study, we sought to investigate the role of miR-323a-3p and its mechanisms in regulating cardiac fibrosis. Methods: The transverse aortic constriction (TAC) mice model was induced and neonatal cardiac fibroblasts (CFs) were cultured. MTT (3- [4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay was used to detect the cell viability. Echocardiography was used to evaluate cardiac function. Masson’s Trichrome stain was used to evaluate the development of fibrosis. Luciferase activity assay was performed to confirm the miRNA’s binding site. Real-time PCR and Western blot were used to evaluate the level of mRNA and protein. Results: MiR-323a-3p was found up-regulated in myocardial tissues subjected to TAC and in CFs cultured with Angiotensin Ⅱ (Ang Ⅱ). Overexpression of miR-323a-3p significantly increased the mRNA levels of collagen Ⅰ, collagen Ⅲ, MMP2 and MMP9, while inhibition of miR-323a-3p prevented the proliferation, collagen production and the protein level of transforming growth factor (TGF-β) in rat neonatal CFs. Strikingly, injection of antagomiR-323a-3p elevated cardiac function and inhibited the expression of TGF-β in the TAC mice. TIMP3 was a direct target of miR-323a-3p, as the overexpression of miR-323a-3p decreased the protein and mRNA levels of TIMP3. In the CFs with pre-treatment of Ang Ⅱ, siRNA-TIMP abolished the effects of AMO-323a-3p on the inhibition of the proliferation of CFs, the down-regulation of collagen Ⅰ and collagen Ⅲ, and the expression of TGF-β. Conclusion: Our findings provide evidence that miR-323a-3p promotes cardiac fibrosis via miR-323a-3p-TIMP3-TGF-β pathway. miR-323a-3p may be a new marker for cardiac fibrosis progression and that inhibition of miR-323a-3p may be a promising therapeutic target for the treatment of cardiac fibrosis

Effect of melt conditioning on heat treatment and mechanical properties of AZ31 alloy strips produced by twin roll casting

In the present investigation, magnesium strips were produced by twin roll casting (TRC) and melt conditioned twin roll casting (MC-TRC) processes. Detailed optical microscopy studies were carried out on as-cast and homogenized TRC and MC-TRC strips. The results showed uniform, fine and equiaxed grain structure was observed for MC-TRC samples in as-cast condition. Whereas, coarse columnar grains with centreline segregation were observed in the case of as-cast TRC samples. The solidification mechanisms for TRC and MC-TRC have been found completely divergent. The homogenized TRC and MC-TRC samples were subjected to tensile test at elevated temperature (250-400 °C). At 250 °C, MC-TRC sample showed significant improvement in strength and ductility. However, at higher temperatures the tensile properties were almost comparable, despite of TRC samples having larger grains compared to MC-TRC samples. The mechanism of deformation has been explained by detailed fractures surface and sub-surface analysis carried out by scanning electron and optical microscopy. Homogenized MC-TRC samples were formed (hot stamping) into engineering component without any trace of crack on its surface. Whereas, TRC samples cracked in several places during hot stamping process.EPSRC – LiME, UK and Towards Affordable, Closed-Loop Recyclable Future Low Carbon Vehicle Structures – TARF-LCV(EP/I038616/1), Department of Mechanical Engineering, Imperial College London, UK, Mr. Steve Cook, Mr. Peter Lloyd, Mr. Graham Mitchell and Mr. Carmelo and BCAST, Brunel University London

3D bioactive composite scaffolds for bone tissue engineering

Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. Developing bioactive three-dimensional (3D) scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering (BTE). A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts. However, individual groups of materials including polymers, ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone. Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds. This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers, hydrogels, metals, ceramics and bio-glasses in BTE. Scaffold fabrication methodology, mechanical performance, biocompatibility, bioactivity, and potential clinical translations will be discussed

Troxerutin Protects Against Myocardial Ischemia/Reperfusion Injury Via Pi3k/Akt Pathway in Rats

Background/Aims: Troxerutin, also known as vitamin P4, has been commonly used in the treatment of chronic venous insufficiency (CVI) disease. However, its effect on in vivo myocardial ischemia/reperfusion (I/R) injury, a model that closely mimics acute myocardial infarction in humans, is still unknown. Methods: The myocardial I/R injury rat model was created with troxerutin preconditioning. Myocardial infarct size was evaluated by the Evans blue-TTC method. Hemodynamic parameters, including the heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximal rate of rise in blood pressure in the ventricular chamber (+dp/dt max), and maximal rate of decline in blood pressure in the ventricular chamber (-dp/dt max) were monitored. Serum TNF-α and IL-10 were determined by ELISA kit. Cell apoptosis was detected by MTT method. Results: Troxerutin preconditioning significantly reduced myocardial infarct size, improved cardiac function, and decreased the levels of creatine kinase (CK), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the I/R injury rat model. The serum and mRNA levels of TNF-α and IL-10 as well as some apoptosis markers (Bax, Caspase 3) also decreased. Moreover, troxerutin pretreatment markedly increased the phosphorylation of Akt, and blocking PI3K activity by LY294002 abolished the protective effect of troxerutin on I/R injury. Conclusion: Troxerutin preconditioning protected against myocardial I/R injury via the PI3K/Akt pathway

Modulation of HERG K+ Channels by Chronic Exposure to Activators and Inhibitors of PKA and PKC: Actions Independent of PKA and PKC Phosphorylation

Background: Human ether-a-go-go-related gene (HERG) channel is the major molecular component of the native rapid delayed rectifier K+ current (IKr) that is a crucial determinant of cardiac repolarization. Impairment of IKr/HERG function is commonly believed to be a mechanism causing long QT syndromes (LQTS), a lethal ventricular tachyarrhythmia. The cAMP-dependent protein kinase A (PKA) and PKC activities are markedly increased in some pathological conditions of the heart such as heart failure. This study was designed to investigate the effects of acute and chronic exposure to PKA or PKC activators and inhibitors on HERG channel activities and to provide insight into the mechanisms for the modulations. Methods: Channel activity was measured in HEK293 cells stably expressing HERG using whole-cell patch-clamp techniques. Intracellular reactive oxygen species (ROS) were measured by CM-H2DFDA. Mitochondrial membrane potential (ΔΨm) was measured using JC-1 dye. HERG channel phosphorylation was assayed by [32P]orthophosphate methods. Results: Acute exposure of cells to PKA or PKC activators by bath superfusion minimally affected IHERG, and so did the PKA or PKC inhibitor. By comparison, prolonged exposure (chronic incubation) of cells to PKA or PKC activators significantly impaired HERG K+ channel function as reflected by reduced IHERG density and positive shift of the steady-state activation curve. Antioxidants vitamin E and MnTBAP both abolished the depressive effects of PKA or PKC activators on HERG function. Further, both PKA and PKC activators stimulated production of intracellular reactive oxygen species (ROS), an effect efficiently prevented by antioxidants or by PKA and PKC inhibitors. Conclusions: HERG function is insensitive to PKA or PKC phosphorylation modulation per se, but can be impaired by the activators of PKA or PKC with long exposure likely via generation of ROS. In view of the critical role of HERG K+ channel in regulating cardiac repolarization and the sustained activation of both PKA and PKC in many pathological conditions of the heart such as heart failure, it is conceivable that HERG impairment by ROS accumulation induced by PKA and PKC contributes to the impaired cardiac repolarization

Prokineticin 2 relieves hypoxia/reoxygenation-induced injury through activation of Akt/mTOR pathway in H9c2 cardiomyocytes

AbstractProkineticin 2 (PK2) was reported to be decreased in the hearts of end-state heart failure patients. Our study aimed to explore the effects of PK2 on hypoxia/reoxygenation (H/R) injury and the underlying mechanism. H9c2 cardiomyocytes were treated with 5 nM PK2 in the presence or absence of 5 mM dual phosphatidylinositol 3-kinase (PI3K)/the mammalian target of rapamycin (mTOR) inhibitor (BEZ235) for 24 h and then subjected to H/R treatment. Cell viability and lactate dehydrogenase (LDH) release were evaluated by CCK-8 and LDH release assays, respectively. Apoptosis was determined by flow cytometry analysis. Oxidative stress was assessed by measuring superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) content. Results showed that H/R treatment decreased PK2 expression and inactivated the Akt/mTOR pathway in H9c2 cardiomyocytes. PK2 treatment activated the Akt/mTOR pathway in H/R-exposed H9c2 cardiomyocytes. H/R stimulation suppressed cell viability, increased LDH release, induced apoptosis and oxidative stress in H9c2 cardiomyocytes, while these effects were neutralised by treatment with PK2. However, the inhibitory effects of PK2 on H/R-induced injury in H9c2 cardiomyocytes were abolished by the addition of BEZ235. In conclusion, PK2 relieved H/R-induced injury in H9c2 cardiomyocytes by activation of the Akt/mTOR pathway

Identification and evaluation of shale oil micro-migration and its petroleum geological significance

Taking the Lower Permian Fengcheng Formation shale in Mahu Sag of Junggar Basin, NW China, as an example, core observation, test analysis, geological analysis and numerical simulation were applied to identify the shale oil micro-migration phenomenon. The hydrocarbon micro-migration in shale oil was quantitatively evaluated and verified by a self-created hydrocarbon expulsion potential method, and the petroleum geological significance of shale oil micro-migration evaluation was determined. Results show that significant micro-migration can be recognized between the organic-rich lamina and organic-poor lamina. The organic-rich lamina has strong hydrocarbon generation ability. The heavy components of hydrocarbon preferentially retained by kerogen swelling or adsorption, while the light components of hydrocarbon were migrated and accumulated to the interbedded felsic or carbonate organic-poor laminae as free oil. About 69% of the Fengcheng Formation shale samples in Well MY1 exhibit hydrocarbon charging phenomenon, while 31% of those exhibit hydrocarbon expulsion phenomenon. The reliability of the micro-migration evaluation results was verified by combining the group components based on the geochromatography effect, two-dimension nuclear magnetic resonance analysis, and the geochemical behavior of inorganic manganese elements in the process of hydrocarbon migration. Micro-migration is a bridge connecting the hydrocarbon accumulation elements in shale formations, which reflects the whole process of shale oil generation, expulsion and accumulation, and controls the content and composition of shale oil. The identification and evaluation of shale oil micro-migration will provide new perspectives for dynamically differential enrichment mechanism of shale oil and establishing a “multi-peak model in oil generation” of shale