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As a pre-clinical assessment, the present study aimed to investigate the safety and effectiveness of a novel valved pulmonary arterial conduit constructed entirely from biomaterials by transplanting it in the outflow tract of the right ventricle in sheep. Under extracorporeal circulation, the valved pulmonary arterial conduit was used to replace the pulmonary artery of sheep with a beating heart. The performance was assessed at 30, 90 and 180 days post-surgery. Hemodynamic and structural changes were evaluated, and safety was assessed after 180 postoperative days. The hemodynamic effect and biosafety of the implant were further evaluated by observing the changes in various pressure indicators of the heart, echocardiographic results, anatomical and pathological examination results, liver and kidney functions, routine blood tests, a blood coagulation test, and other test results following implantation of the purely biotic valved conduit. The conduit was successfully implanted in 12 sheep and no mortality occurred postoperatively. During the 180-day follow-up, there was no obvious stenosis or regurgitation of the right ventricular outflow tract and pulmonary valve after valved conduit implantation. The findings of autopsy, pathology and laboratory examinations were unremarkable. The implantation of this biosynthetic vascular graft into animals meets the safety and effectiveness requirements for clinical application. This pulmonary arterial conduit has potential clinical application for children with complex congenital heart disease who require pulmonary artery reconstruction to achieve a radical cure.

Aims Estrogen plays an important role in cardioprotection. Animal experiments showed that the G-protein coupled estrogen receptor 30 (GPR30) specific agonist G1 could reduce post-ischemic dysfunction and inhibit cardiac fibroblast proliferation. However, the underlying mechanism of action is not clear. The current study tests the hypothesis that GPR30 reduces myocardial infarct area and fibrosis in female ovariectomized (OVX) mice by activating the PI3K/AKT pathway. Main methods In this study, we established a myocardial infarction (MI) animal model derived from OVX C57BL/6 female mice, and investigated the effect of G1 on cardiac function by echocardiography and Hemodynamics, morphology and expression of fibrosis-related and apoptosis-related proteins by Masson's trichrome and H&E, Immunofluorescence, Western blotting and TUNEL. Key findings Combination with OVX significantly increased myocardial fibrosis and MI area compared to MI treatment alone, as determined by echocardiography and hemodynamics. Further addition of G1 changed the expression of apoptosis-related proteins, decreased the levels of tumor necrosis factor-α and interleukin-10, and reduced the degree of myocardial fibrosis and myocardial infarct area. Primary cultured cardiac fibroblasts (CFs) were subjected to hypoxia/serum deprivation (H/SD) simulating the in vivo ischemia model. When the PI3K/AKT pathway was inhibited by wortmanin in H/SD CFs, G1 failed to induce significant changes in the expression of apoptosis-related proteins. Significance It suggested that GPR30 may improve cardiac function in female OVX mice by activating the PI3K/AKT pathway and reducing myocardial infarct size and fibrosis.

AIMS The aim of the study was to evaluate the midterm safety and efficacy of a self-expanding valve (Venus P-valve) in the treatment of patients with pulmonary regurgitation and a native right ventricular outflow tract (RVOT) in China. METHODS AND RESULTS Patients who had moderate or severe pulmonary regurgitation after surgical repair of the RVOT with a transannular or RVOT patch were included in the study. Fifty-five patients (67% female; average age 28.7±12.4 years) from six different hospitals in China were enrolled. The procedure success rate was 98.2%. In the one failure, the patient experienced valve dislodgement two days after the procedure. During the 12-month follow-up, two patients died, one due to infective endocarditis. Three other patients developed infective endocarditis. Two patients developed atrial flutter, and one patient had a pulmonary embolism. Echocardiography examinations at 12 months showed that two patients had mild pulmonary regurgitation, and 19 patients had trace pulmonary regurgitation. No paravalvular regurgitation occurred. The mean peak pulmonary gradient was 16.3±7.4 (range 4-38) mmHg. Compared with the baseline data, the right ventricular end-diastolic volume index (RVEDVI) was reduced from 137.6±15.8 mL/m2 to 83.9±16.0 mL/m2 (p

Background Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction and cardiomyocyte injury, which induced by metabolic disorder. Nowadays, there is still a lack of drugs for the treatment of DCM. Growth differentiation factor 11 (GDF11) is a novel member of the transforming growth factor β superfamily that alleviates cardiac hypertrophy, myocardial infarction, and vascular injury by regulating oxidative stress, inflammation, and cell survival. However, the roles and underlying mechanisms of GDF11 in DCM remain largely unknown. Methods In this study, we sought to determine whether GDF11 could prevent DCM. The mouse model of diabetes was established by administering a high-fat diet and intraperitoneal injecting streptozotocin. After that, intramyocardial injection of an adeno-associated virus carrying GDF11 gene was used to achieve myocardium-specific overexpression. Results Our data showed that GDF11 overexpression remarkably improved cardiac dysfunction and interstitial fibrosis by reducing the levels of reactive oxygen species and protecting against cardiomyocyte loss. Mechanistically, decreased sirtuin 1 (SIRT1) expression was observed in diabetic mice, which was significantly increased after GDF11 overexpression. To further explore how SIRT1 mediates the role of GDF11, the selective inhibitor EX527 was used to block SIRT1 signaling pathway, which abolished the protective effects of GDF11 against DCM. In vitro studies confirmed that GDF11 protected against H9c2 cell injury in high glucose and palmitate by attenuating oxidative injury and apoptosis, and these effects were also eliminated by SIRT1 depletion. Conclusion Our results demonstrated for the first time that GDF11 protected against DCM by regulating SIRT1 signaling pathway, and GDF11 had the potential to become a novel target for reversing cardiac dysfunction in diabetic patients.

SARS‐CoV‐2, the virus responsible for the global coronavirus disease (COVID‐19) pandemic, attacks multiple organs of the human body by binding to angiotensin‐converting enzyme 2 (ACE2) to enter cells. More than 20 million people have already been infected by the virus. ACE2 is not only a functional receptor of COVID‐19 but also an important endogenous antagonist of the renin‐angiotensin system (RAS). A large number of studies have shown that ACE2 can reverse myocardial injury in various cardiovascular diseases (CVDs) as well as is exert anti‐inflammatory, antioxidant, anti‐apoptotic and anticardiomyocyte fibrosis effects by regulating transforming growth factor beta, mitogen‐activated protein kinases, calcium ions in cells and other major pathways. The ACE2/angiotensin‐(1‐7)/Mas receptor axis plays a decisive role in the cardiovascular system to combat the negative effects of the ACE/angiotensin II/angiotensin II type 1 receptor axis. However, the underlying mechanism of ACE2 in cardiac protection remains unclear. Some approaches for enhancing ACE2 expression in CVDs have been suggested, which may provide targets for the development of novel clinical therapies. In this review, we aimed to identify and summarize the role of ACE2 in CVDs.

Using imaging data of human anatomy, 3D printing technology can be used for computer reconstruction. The data are the input for a 3D printer, and a structural model is constructed, which is convenient for direct visual inspection and operation [1]. Through more than twenty years of development, outstanding progress has been made in oral, maxillofacial, orthopedic, and plastic surgery and other disciplines. Moreover, 3D printing technology has been widely used in implant and tissue design, surgical planning, medical research, and medical education and as a training tool [2, 3]. Because it has broad development prospects, 3D printing has become an important new technology in the manufacturing industry of “Strategic Emerging Industries Classification (2018)” issued by the National Bureau of Statistics.

Melatonin functions as an endogenous protective molecule in multiple vascular diseases, whereas its effects on thoracic aortic aneurysm and dissection (TAAD) and underlying mechanisms have not been reported. In this study, TAAD mouse model was successfully induced by β-aminopropionitrile fumarate (BAPN). We found that melatonin treatment remarkably prevented the deterioration of TAAD, evidenced by decreased incidence, ameliorated aneurysmal dilation and vascular stiffness, improved aortic morphology, and inhibited elastin degradation, macrophage infiltration, and matrix metalloproteinase expression. Moreover, melatonin blunted oxidative stress damage and vascular smooth muscle cell (VSMC) loss. Notably, BAPN induced a decrease in SIRT1 expression and activity of mouse aorta, whereas melatonin treatment reversed it. Further mechanistic study demonstrated that blocking SIRT1 signaling partially inhibited these beneficial effects of melatonin on TAAD. Additionally, the melatonin receptor was involved in this phenomenon. Our study is the first to report that melatonin exerts therapeutic effects against TAAD by reducing oxidative stress and VSMC loss via activation of SIRT1 signaling in a receptor-dependent manner, thus suggesting a novel therapeutic strategy for TAAD.

Background Laboratory studies demonstrate glucose‐insulin‐potassium ( GIK ) as a potent cardioprotective intervention, but clinical trials have yielded mixed results, likely because of varying formulas and timing of GIK treatment and different clinical settings. This study sought to evaluate the effects of modified GIK regimen given perioperatively with an insulin‐glucose ratio of 1:3 in patients undergoing cardiopulmonary bypass surgery. Methods and Results In this prospective, randomized, double‐blinded trial with 930 patients referred for cardiac surgery with cardiopulmonary bypass , GIK (200 g/L glucose, 66.7 U/L insulin, and 80 mmol/L KC l) or placebo treatment was administered intravenously at 1 mL /kg per hour 10 minutes before anesthesia and continuously for 12.5 hours. The primary outcome was the incidence of in‐hospital major adverse cardiac events including all‐cause death, low cardiac output syndrome, acute myocardial infarction, cardiac arrest with successful resuscitation, congestive heart failure, and arrhythmia. GIK therapy reduced the incidence of major adverse cardiac events and enhanced cardiac function recovery without increasing perioperative blood glucose compared with the control group. Mechanistically, this treatment resulted in increased glucose uptake and less lactate excretion calculated by the differences between arterial and coronary sinus, and increased phosphorylation of insulin receptor substrate‐1 and protein kinase B in the hearts of GIK ‐treated patients. Systemic blood lactate was also reduced in GIK ‐treated patients during cardiopulmonary bypass surgery. Conclusions A modified GIK regimen administered perioperatively reduces the incidence of in‐hospital major adverse cardiac events in patients undergoing cardiopulmonary bypass surgery. These benefits are likely a result of enhanced systemic tissue perfusion and improved myocardial metabolism via activation of insulin signaling by GIK . Clinical Trial Registration URL: clinicaltrials.gov. Identifier: NCT 01516138.

Mitochondrial unfolding protein response (UPRmt) effectively resists the pathological cardiac hypertrophy and improves the mitochondrial function. However, the specific activation mechanism and drugs that can effectively activate UPRmt in the cardiac muscle are yet to be elucidated. The aim of this study was to determine the regulation role of UPRmt on preventing pathological cardiac hypertrophy by tetrahydrocurcumin (THC) and explore its underlying molecular mechanism. Male C57BL/6J wild-type (WT) mice were divided into a control group and subjected to sham treatment for 4 weeks, and a test group which was subjected to transverse aortic constriction (TAC) surgery. Animals in the control and test group were orally administered THC (50 mg/kg) for 4 weeks after TAC procedure; an equivalent amount of saline was orally administered in the control sham-treated group and the TAC group. Subsequently, oxidative stress and UPRmt markers were assessed in these mice, and cardiac hypertrophy, fibrosis, and cardiac function were tested. Small interfering RNA (siRNA) targeting proliferator-activated receptor-gamma coactivator (PGC)-1α and activating transcription factor 5 (ATF5) were used to determine the UPRmt activation mechanism. THC supplement partly upregulated UPRmt effectors and inhibited TAC-induced oxidative stress compared with TAC-operated WT mice, thereby substantially attenuating contractile dysfunction, cardiac hypertrophy, and fibrosis. Furthermore, PGC-1α knockdown blunted the UPRmt activation and the cardioprotective role of THC. The interaction between PGC-1α and ATF5 was tested in neonatal rat cardiac myocytes under normal conditions. The results showed that PGC-1α was an upstream effector of ATF5 and partly activated UPRmt. In vitro, phenylephrine- (PE-) induced cardiomyocyte hypertrophy caused ATF5 upregulating rather than downregulating corresponding to the downregulation of PGC-1α. The PGC-1α/ATF5 axis mediated the UPRmt activation and stress-resistance role of THC in vitro. Collectively, the present study provides the first evidence that PGC-1 and ATF5 can form a signaling axis to partly activate UPRmt that mediates the cardioprotective role of THC in pathological cardiac hypertrophy.

Xiaowu Wang,1,* Bo Xu,1,* Hongliang Liang,1 Shuyun Jiang,1 Hongmei Tan,1 Xinrong Wang,1 Xia Wang,2 Shiqiang Yu,1 Jincheng Liu1 1Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, People’s Republic of China; 2Department of Health Statistics, Faculty of Preventive Medicine, Fourth Military Medical University, Xi’an 710032, Shaanxi, People’s Republic of China *These authors contributed equally to this work Purpose: Oral warfarin anticoagulation is a long-term treatment that is required after heart valve replacement. This treatment can prevent serious complications, such as embolism, thereby increasing patients’ postoperative survival rates and quality of life. Patients treated with artificial mechanical heart valve replacement were followed up over the phone at different times after the procedure, which is an effective method for preventing accidents related to postoperative oral warfarin anticoagulation. Our goal was to determine a method for providing theoretical guidance to patients on oral warfarin anticoagulation following heart valve replacement. Patients and methods: The participants of this study were patients who received artificial mechanical heart valve replacements and were followed up for 2 years after the procedure. Patient adherence to medical advice was calculated, and the distribution characteristics of adherence to prescribed timing, prescribed dose, and regular clinical follow-up among patients of both sexes and of different ages, regions, and educational levels attained were compared. Results: Univariate and multifactorial logistic regression analyses were used to evaluate the factors influencing adherence. Our analyses showed that adherence to oral warfarin anticoagulation in patients after heart valve replacement is influenced by sex, age, residential location, and educational attainment. The medication habits of patients can be evaluated accordingly via phone follow-up. As such, dose adjustment recommendations can be provided, significantly increasing the adherence to oral warfarin anticoagulation in patients after heart valve replacement. Conclusion: Adherence to oral warfarin anticoagulation among patients after heart valve replacement is affected by sex, age, type of residence, and educational level, as well as adherence to clinical follow-up over the phone. The follow-up sessions help establish good doctor–patient communication, which is critical for timely medication guidance, thus shortening medication administration delays and decreasing the overall length of therapy. Keywords: warfarin, artificial mechanical heart valve replacement, AMHVR, telephone follow-up, adherence, distribution characteristics

Objectives The aim of this study was to evaluate the safety and feasibility of total arch repair with open placement of a novel double-branched stent graft for acute Type A aortic dissection (TAAD). Methods We retrospectively analysed the effect of the double-branched stent graft for total aortic arch placement with acute TAAD from December 2013 to February 2015. The effectiveness of the open placement of the double-branched stent graft was estimated by complete thrombus obliteration of the false lumen surrounding it on computed tomography angiography. Follow-up was performed at 6 months postoperatively and annually thereafter. Results The double-branched stent graft was successfully placed into the true lumen of the descending aorta, aortic arch, left subclavian artery and left common carotid artery through the delivery system in 21 patients with acute TAAD. The mean cardiopulmonary bypass time was 210.2 ± 32.4 min, the mean aortic cross-clamp time was 94.9 ± 18.0 min, and the selective cerebral perfusion and deep hypothermia cardiopulmonary arrest time was 27.0 ± 10.4 min. The in-hospital mortality rate was 4.8%. The mean follow-up duration was 38.2 ± 12.5 months. No severe complications related to the surgery or residual dissection occurred during the follow-up. All survivors resumed normal activities. Conclusions The novel double-branched stent graft is proved to be safe and effective for total arch repair with acute TAAD in this study. It would be a new selective method for total arch repair in patients with acute TAAD. Clinical registration number Research on pathogenic risk factors or characteristic features and clinical treatment of aortic dissection in Chinese Population (20120216-4).

Information and communication technology is undergoing rapid development, and many disruptive technologies, such as cloud computing, Internet of Things, big data, and artificial intelligence, have emerged. These technologies are permeating the manufacturing industry and enable the fusion of physical and virtual worlds through cyber-physical systems (CPS), which mark the advent of the fourth stage of industrial production (i.e., Industry 4.0). The widespread application of CPS in manufacturing environments renders manufacturing systems increasingly smart. To advance research on the implementation of Industry 4.0, this study examines smart manufacturing systems for Industry 4.0. First, a conceptual framework of smart manufacturing systems for Industry 4.0 is presented. Second, demonstrative scenarios that pertain to smart design, smart machining, smart control, smart monitoring, and smart scheduling, are presented. Key technologies and their possible applications to Industry 4.0 smart manufacturing systems are reviewed based on these demonstrative scenarios. Finally, challenges and future perspectives are identified and discussed.

A 70-year-old woman presented with severe hypertrophic obstructive cardiomyopathy (HOCM) (maximum ventricular septum thickness of 28 mm, peak pressure gradient (PG) in the left ventricular outflow tract (LVOT) of 153 mmHg). We performed percutaneous trans-apex intra-septal radiofrequency ablation (PTAISRA) of the interventricular septum under guidance of transthoracic echocardiography. At six-months follow up, the symptoms were significantly relieved; the septal thickness was reduced to 18 mm and the peak LVOT PG reduced to 44 mmHg. This case highlights a novel use of radiofrequency ablation for the treatment of HOCM. Long-term safety and efficacy merit evaluation.

Product configuration system, as an effective tool to bridge the gap between customer requirements and product offerings, enables customer-centric product development in a cost-efficient way. Despite its advantages, however, most existing product configurators are centralized, i.e. the configuration process is conducted in a single company within its own product family. It cannot fulfill the ever increasing tendency towards personalization. This is because customers no longer have to choose from the limited options within the company’s solution space in a “configure-to-order” (CTO) model, they also propose or even create their individualized design in an “engineer-to-order” (ETO) model. Moreover, companies, especially large ones, are not willing to invest much into the niche market to produce the highly personalized components. To solve this problem, an open architecture product platform with adaptable interface can be adopted to integrate the original equipment manufacturer (OEM) with various vendors into a co-creation process. This paper proposes a conceptual framework of a personalized product configuration system based on the adaptable open architecture product platform. The technical configurator is enabled by a two-stage process (i.e. modular design and scalable design) to ensure the adaptability and scalability of product variety, while the sales configurator is established by considering each customer’s preferences and conducting the configuration process in an ETO manner. The technical details of the prototype system implementation are described and an illustrative example of a personalized bicycle configuration process is given to validate the overall framework.

Nowadays, with the rapid development of information technologies (e.g. web 2.0, cloud computing and virtual reality) and manufacturing technologies (e.g. additive manufacturing), users become more actively involved in the product development stage to create personalized products with higher efficiency. This emerging manufacturing paradigm is known as mass personalization, of which user experience (e.g. emotional factors and product utility), co-creation (e.g. user participation), and product change (e.g. modular design) are regarded as three key characteristics. In previous studies, researchers often treat each characteristic separately with an illustrative example to demonstrate its significant effect respectively. They, however, cannot fully reflect the product development process for mass personalization, and may cause inconsistency in implementing the existing methods into real cases. To fill the gap, this work proposes a three-model based (i.e. physical model, cyber model and user experience model) generic framework for conducting user experience based product development for mass personalization. A case study of a personalized smart wearable product development is described, of which the three key characteristics are considered collectively. It can also be seen as a typical case integrating the frontier techniques to enable mass personalization. The authors hope this work can provide some useful guidance to product designers and engineer-to-order companies.

Through the synergies of advanced IT technologies in sensor network and hardware infrastructure, both industrial and consumer products are evolving rapidly to carry more smart features. To sharpen competitive edge in global market, manufacturers today ought to enable their customers to personalize their products to meet diversifying customer needs (CNs). However, the increasing complexity of smart product is dramatically expanding the design space due to over-loaded smart features, which results in significant challenges in the personalization of smart products. Typically, manufacturers operating in a configure-to-order (CTO) manner would adopt a mass customization strategy and implement it with a product configuration system (also known as product configurator). The user experience (UX) of personalizing products by conducting product configuration is crucial for encouraging customer retention and loyalty. This project studied the product personalization process for smart products by observing a group of customers conducting a series of product configuration tasks in several types of product configurators we developed for different platforms (web-based and Virtual Reality (VR) based version). By analyzing mental and physical reaction of the customer, a more systematic understanding of user preference has been attained. The proposed VR-based approach for realizing customer-centric product personalization has been proved to be valid and should be a valuable reference in the future development of the product configuration system.

Total aortic-arch replacement (TAR) is one of the major cardiovascular surgeries, which is by far the most effective emergency treatment of Acute Aortic Dissection type-A (AADA). In TAR, cardiopulmonary bypass is established and the aortic arch is replaced and reconstructed. Though hypothermic circulatory arrest (HCA) and unilateral antegrade cerebral perfusion (uACP) are often used for brain protection, parts of the brain may still encounter insufficient blood supply. With prolonged HCA time, this insufficiency causes brain injuries. Currently, there lacks an effective, real-time cerebral imaging technique that can be used in cardiac surgeries. Electrical impedance tomography (EIT) is a low-cost, non-invasive imaging method, which is sensitive to the bio-electrical impedance of tissues. In this study, we are the first using electrical impedance tomography (EIT) intraoperatively to image and monitor the relative changes in cerebral blood volume (rc-CBV). A subject with AADA is monitored using EIT in TAR surgeries and EIT images during the HCA + uACP period are reconstructed and analyzed. A blood factorization model was proposed to estimate the relative changes in blood proportion using EIT images. We found that (1) EIT images are sensitive to the changes in the rate of cerebral perfusion. (2) During uACP, the right hemisphere is perfused directly via cannulation into the right subclavian artery and the circulation to the left cerebral is mainly compensated through the circle of Willis. EIT and rc-CBV images show relatively high impedance and low blood ratios in the left hemisphere, which indicates that the patient may have insufficient collateral circulation. (3) EIT has moderate spatial resolutions, which provides additional information regarding the pathological changes in different regions deep in the brain. We conclude that cerebral EIT is a promising imaging method and it may provide early warning signs regarding insufficient cerebral blood supply in TAR surgeries.

C1q-tumor necrosis factor-related protein-3 (CTRP3) is an adipokine, which exerts protective function in ischemic or diabetic heart injury. However, the role of CTRP3 in cardiac hypertrophy remains unclear. The aim of this study was to investigate the pharmacological effects of CTRP3 on pathological cardiac hypertrophy induced by hypertension. Male C57BL/6 J wild-type (WT) mice, Ctrp3 knockout mice, and mice infected with lentivirus overexpressing mouse Ctrp3 underwent sham surgery or transverse aortic constriction (TAC) surgery. After 4 weeks, cardiac hypertrophy, fibrosis, and cardiac function were examined. Compared with WT mice, Ctrp3 deficiency substantially impaired contractile dysfunction, exacerbated the enlargement of cardiomyocytes and myocardial fibrosis, and reprogramed the expression of pathological genes after TAC. Conversely, CTRP3 overexpression played a role in restoring the left ventricular cardiac contractile function, alleviating cardiac hypertrophy and fibrosis, and inhibiting the expression of hypertrophic and fibrotic signaling in mice after TAC. Furthermore, CTRP3 regulated the expression of the p38/CREB pathway and of the primary modulating factors of the endoplasmic reticulum stress, i.e., GRP78 and the downstream molecules eukaryotic translation inhibition factor 2 submit α, C/EBP homologous protein, and inositol-requiring enzyme-1. Further, inhibition of p38 MAPK by SB203580 blunted the ER stress intensified by Ctrp3 deficiency. In vitro, CTRP3 protected neonatal rat cardiac myocytes against phenylephrine-induced cardiomyocyte hypertrophy. We conclude that CTRP3 protects the host against pathological cardiac remodeling and left ventricular dysfunction induced by pressure overload largely by inhibiting the p38/CREB pathway and alleviating p38-induced ER stress.

Detecting concurrency bugs, such as data race, atomicity violation and order violation, is a cumbersome task for programmers. This situation is further being exacerbated due to the increasing number of cores in a single machine and the prevalence of threaded programming models. Unfortunately, many existing software-based approaches usually incur high runtime overhead or accuracy loss, while most hardware-based proposals usually focus on a specific type of bugs and thus are inflexible to detect a variety of concurrency bugs. In this paper, we propose Hydra, an approach that leverages massive parallelism and programmability of fused CPU-GPU architectures to simultaneously detect multiple concurrency bugs in threaded software, including data race, atomicity violation and order violation. Hydra extends contemporary fused CPU and GPU by introducing two modules: 1) a trace collecting module (TCM) that instruments and collects program behavior on CPU; 2) a trace preprocessing module (TPM) that processes and then transfers the traces to GPU for bug detection. Furthermore, Hydra exploits three optimizations to improve speed and accuracy, which includes: 1). using the bloom filter to filter out unnecessary traces; 2). avoiding eviction of shared traces; 3). comparing only last-write traces for shared data with the happens-before relation. Hydra incurs small hardware complexity and requires no changes to internal critical-path processor components such as cache and its coherence protocol, and is with about 1.1 percent hardware overhead under a 32-core configuration. Experimental results show that Hydra only introduces about 0.18 percent overhead on average for detecting one type of bugs and 0.46 percent overhead for simultaneously detecting multiple bugs, yet with the similar detectability of a heavyweight software bug detector (e.g., Helgrind).

Recently, we demonstrated that melatonin reduced protein kinase RNA (PKR)-like ER kinase (PERK)-eukaryotic initiation factor 2 alpha (eIF2α)-activating transcription factor-4 (ATF4)-mediated myocardial endoplasmic reticulum (ER) stress and apoptosis during myocardial ischemia-reperfusion (MI/R) injury. However, the underlying mechanisms are still not clear. Myocardial reperfusion injury salvage kinase (RISK) pathway as well as survivor activating factor enhancement (SAFE) pathway are two pivotal intrinsic pro-survival signaling cascades. In this study, we performed in vivo and in vitro experiment to investigate the ameliorative effect of melatonin on ER stress with a focus on RISK and SAFE pathways interaction. Male C57Bl/6 mice received melatonin (300 μg/25 g/day, 3 days before MI/R surgery; 300 μg/25 g, 25 min before the onset of ischemia) pre-treatment with or without the administration of LY294002 (a PI3K/Akt inhibitor), U0126 (an ERK1/2 inhibitor) or AG490 (a STAT3 pathway inhibitor). H9c2 cells were pre-treated with melatonin (100 μM, 8 h) in the presence or absence of LY294002, U0126 or AG490. Compared with the I/R-injured group, melatonin effectively reduced myocardial apoptosis, oxidative stress and improved cardiac function. In addition, melatonin pre-treatment also increased the phosphorylation of Akt, GSK-3β, ERK1/2 and STAT3 and reduced PERK-eIF2α-ATF4-mediated ER stress. However, these effects were blocked by LY294002, U0126 or AG490. Additionally, either LY294002 or U0126 treatment could inhibit STAT3 phosphorylation, whereas AG490 administration also reduced both Akt and ERK1/2 phosphorylation, indicating an interplay exists between RISK and SAFE pathways in melatonin's cardioprotective effect. In summary, our study demonstrates that RISK and SAFE pathways mediate the cardioprotective effect of melatonin against MI/R injury. Melatonin pre-treatment attenuates PERK-eIF2α-ATF4-mediated ER stress and apoptosis during MI/R injury via RISK and SAFE pathways interaction.

Objective This study aimed to evaluate the safety and feasibility of total endovascular repair of the aortic arch using a novel designed stent-graft system (Yanger stent-graft system; Lifetech Scientific, Shenzhen, China) in vitro and in a canine model. Methods The Yanger stent-graft system is composed of a main stent-graft, branched stent-graft, and a delivery system. In an in vitro aortic arch simulation test bench, the system was tested, and the success rate of stent-graft releasing, anchoring, and positioning was recorded and analyzed. Meanwhile, in vivo implantation of the Yanger stent-graft system was carried out in 16 healthy adult crossbreed dogs. The feasibility of using these stent-grafts was evaluated with aortography, multislice computed tomography, and autopsy 6 months after the procedure. Results All stent-graft releasing and positioning were successful for in vitro test. In the canine model, the Yanger stent-graft system was placed successfully in the aortic arch in all 14 dogs with the exception of 2 mortalities. All dogs survived for at least 3 months with normal physiologic signs. Aortography, multislice computed tomography, and animal necropsy revealed good fixation in all cases. The ascending aorta, descending aorta, brachiocephalic trunk, and left subclavian artery were all covered without endoleak. There was no significant obstruction or stenosis in brachiocephalic branches at the 6-month follow-up. Conclusions Total endovascular repair of aortic arch with the novel designed Yanger stent-graft system is safe and feasible in preclinical studies. With a better understanding of preclinical knowledge, patient selection criteria and first-in-human studies will be addressed.

This study was designed to determine the long-term safety and efficacy of using modified double-disk occluders for perimembranous ventricular septal defect (pmVSD) closure in adults. From January 2004 to December 2014, 337 adults with pmVSDs were treated through transcatheter intervention using 2 types of double-disk occluders; 302 patients received a symmetrical concentric pmVSD occluder, and 35 patients received an asymmetrical concentric pmVSD occluder. All patients were followed up through electrocardiography and transthoracic echocardiography until June 2015. The success rate was 100% for both procedures. During the median 71-month follow-up period, no cases of infective endocarditis, cerebrovascular accidents, heart failure, or death occurred. Two major adverse events (0.6%) were recorded: complete atrioventricular block requiring surgical treatment in one patient and severe tricuspid valvular regurgitation requiring surgical repair in another patient. Cardiac conduction block was the most common minor adverse event. The mean left ventricular (LV) end-diastolic volume decreased from 96.6 ± 23.2 ml before intervention to 86.0 ± 22.0 ml (p

Cloud manufacturing (CMfg) promotes a dynamic distributed manufacturing environment by connecting the service providers and manages them in a centralized way. Due to the distinct production capabilities, the service providers tend to be delegated services of different granularities. Meanwhile, users of different types may be after services of different granularities. A traditional aggregate production planning method is often incapable of dealing with type of problems. For this reason, a multi-level aggregate service planning (MASP) methodology is proposed. The MASP service hierarchy is presented, which integrates the services of different granularities into a layered structure. Based on this structure, one of data mining technologies named time series is introduced to provide dynamic forecast for each layer. In this way, MASP can not only deal with the services of multi-granularity, but also meet the requirements of all related service providers irrespective of their manufacturing capabilities. A case study has been carried out, showing how MASP can be applied in a CMfg environment. The results of the prediction are considered reliable as the order of magnitude of the production for each service layer is much greater than that of the corresponding mean forecast error.

Rationale: No medical intervention has been identified that decreases acute kidney injury and improves renal outcome at 1 year after cardiac surgery. Objectives: To determine whether administration of nitric oxide reduces the incidence of postoperative acute kidney injury and improves long-term kidney outcomes after multiple cardiac valve replacement requiring prolonged cardiopulmonary bypass. Methods: Two hundred and forty-four patients undergoing elective, multiple valve replacement surgery, mostly due to rheumatic fever, were randomized to receive either nitric oxide (treatment) or nitrogen (control). Nitric oxide and nitrogen were administered via the gas exchanger during cardiopulmonary bypass and by inhalation for 24 hours postoperatively. Measurements and Main Results: The primary outcome was as follows: oxidation of ferrous plasma oxyhemoglobin to ferric methemoglobin was associated with reduced postoperative acute kidney injury from 64% (control group) to 50% (nitric oxide group) (relative risk [RR], 0.78; 95% confidence interval [CI], 0.62-0.97; P = 0.014). Secondary outcomes were as follows: at 90 days, transition to stage 3 chronic kidney disease was reduced from 33% in the control group to 21% in the treatment group (RR, 0.64; 95% CI, 0.41-0.99; P = 0.024) and at 1 year, from 31% to 18% (RR, 0.59; 95% CI, 0.36-0.96; P = 0.017). Nitric oxide treatment reduced the overall major adverse kidney events at 30 days (RR, 0.40; 95% CI, 0.18-0.92; P = 0.016), 90 days (RR, 0.40; 95% CI, 0.17-0.92; P = 0.015), and 1 year (RR, 0.47; 95% CI, 0.20-1.10; P = 0.041). Conclusions: In patients undergoing multiple valve replacement and prolonged cardiopulmonary bypass, administration of nitric oxide decreased the incidence of acute kidney injury, transition to stage 3 chronic kidney disease, and major adverse kidney events at 30 days, 90 days, and 1 year.

Objective Paravalvular leak (PVL) after valve replacement remains clinically challenging. Percutaneous closure is an effective therapy for patients with PVLs because reoperation is associated with high rates of morbidity and mortality. The purpose of this study was to retrospectively compare the clinical outcome of transcatheter closure and surgical repair in patients with a PVL. Methods From January 2000 to May 2016, 131 patients with PVL were treated at three major medical centers in China. Perioperative characteristics and outcomes of the procedure were reviewed. Results Sixty-eight (51.9%) patients with PVLs were treated with percutaneous transcatheter closure (group I). The procedure was successful in 67 (98%) with no hospital deaths. Sixty-three (48.1%) patients with PVLs had a reoperation (group II). Five of the surgical patients had a third open-heart operation for residual regurgitation, and one underwent successful percutaneous closure. Six patients died in the hospital postoperatively. All patients in group II but only 11 in group I needed perioperative blood transfusions. The procedural time and hospital stay after the procedure were significantly shorter in group I than in group II. At the 1-year follow-up, cardiac function improved by ≥ 1 New York Heart Association functional class in 55 (82%) patients in group I and in 39 (68%) patients in group II. Conclusions Transcatheter closure was shown to be a safe, effective therapeutic option in patients with PVL. It was associated with a lower hospital mortality rate, shorter procedural time, and fewer blood transfusions than surgical treatment in selected patients.

Objective To explore the feasibility of using electrical impedance tomography (EIT) to provide noninvasive cerebral imaging and monitoring in total aortic arch replacement (TAAR). Design A prospective, observational study. Setting Department of cardiovascular surgery in a university hospital. Participants Forty-two patients undergoing TAAR using hypothermic circulatory arrest and unilateral antegrade cerebral perfusion. Interventions None. Measurements and Main Results Cerebral impedances of the patients were monitored intraoperatively by an EIT system. The prognostic information of the patients, including postoperative neurological dysfunction, was collected during their hospitalizations. Eight (19.0%) subjects had at least 1 postoperative neurological dysfunction complication. The results show that cerebral impedance was related negatively to perfusion flow, and the gradual increase in cerebral resistivity might reflect the evolving process of brain tissue caused by hypoxia. Maximum resistivity asymmetry index was extracted from the reconstructed images to quantify the pathological changes of the brain. The area under the receiver operating characteristic curve of maximum resistivity asymmetry index for postoperative neurological dysfunction was 0.864. In multivariate logistic regression, maximum resistivity asymmetry index was the strongest independent predictor of neurological dysfunction with an odds ratio of 24.3. Conclusion EIT is a promising technique to provide noninvasive cerebral imaging and monitoring in TAAR.

The advancement of information communication technologies(ICT) has begun to change both industrial and consumer products towards ones with attributes of smartness and servitization. Nevertheless, smart features and deep integration with smart environment tend to complicate the effort for the provision of personalized products. To solve this problem, this paper puts forward a Smart Service Products (SSP) model comprising smart environment-enabled features and services-enabled smartness, apart from its own physical capability and functionality. A cloud-based framework for SSP personalization is proposed to enable the supply of personalized SSP with short lead-time and mass efficiency. Hence, a real case is implemented to validate the approach. NRF (Natl Research Foundation, S’pore) Published version

Berberine (BBR) confers cardioprotective effect against myocardial ischemia reperfusion injury (MI/RI). Activation of Notch1/Hairy and enhancer of split 1 (Hes1) signaling also reduces MI/RI. We hypothesize that BBR may protect against MI/RI by modulating Notch1/Hes1-Phosphatase and tensin homolog deleted on chromosome ten (PTEN)/Akt signaling. In this study, male Sprague-Dawley rats were exposed to BBR treatment (200 mg/kg/d) for 2 weeks and then subjected to MI/RI. BBR significantly improved cardiac function recovery and decreased myocardial apoptosis, infarct size, serum creatine kinase and lactate dehydrogenase levels. Furthermore, in cultured H9c2 cardiomyocytes, BBR (50 μmol/L) attenuated simulated ischemia/reperfusion-induced myocardial apoptosis. Both in vivo and in vitro study showed that BBR treatment up-regulates Notch1 intracellular domain, Hes1, Bcl-2 expression and p-Akt/Akt ratio, down-regulates Bax Caspase-3 and cleaved Caspase-3 expression. However, the anti-apoptotic effect conferred by BBR was blocked by Notch1 siRNA, Hes1 siRNA or LY294002 (the specific inhibitor of Akt signaling) in the cultured cardiomyocytes. In summary, our results demonstrate that BBR treatment attenuates MI/RI by modulating Notch1/Hes1-PTEN/Akt signaling.

Objective To establish a systematic registry of aortic dissection in China, assess the clinical features of Chinese patients with acute aortic dissection (AAD), and compare our results with the data published by the International Registry of Acute Aortic Dissection (IRAD). Methods We established the first Registry of Aortic Dissection in China (Sino-RAD) in 2011. Then we evaluated 1003 patients with AAD in Sino-RAD and compared our results with those reported by IRAD. Results Compared with IRAD, the patients with AAD in Sino-RAD were significantly younger. Also, the ratio of male patients in Sino-RAD was significantly greater for the total cohort and the type A and B cohorts. The overall in-hospital mortality was 10.3% in Sino-RAD. For type A dissection, more patients in Sino-RAD received medical treatment and fewer received surgical treatment. The overall mortality, mortality of medical treatment, and mortality of surgical treatment was lower in Sino-RAD. In type B dissection, fewer patients in Sino-RAD received medical and surgical treatment and more received endovascular treatment. Conclusions The first Sino-RAD, including 15 large cardiovascular centers throughout China, was established. Our data were compared with those reported by IRAD. We found that, compared with Western populations, Chinese patients with AAD showed 6 differences, including earlier onset, more male patients, a low incidence of hypertension, a low incidence of chest pain, a high incidence of back pain, great differences in the choice of therapeutic strategies, and relatively low in-hospital mortality.

Objective To review the experiences in repairing the anomalous origin of one pulmonary artery in infants. Methods From March 2005 to May 2010, 11 infants diagnosed with anomalous origin of one pulmonary artery underwent surgical treatment. Their mean age was 12.7 months (two months to three years), and their mean body weight was 7.1 kg (4 to 13 kg). Seven patients had anomalous origin of the right pulmonary artery, and four patients had anomalous origin of the left pulmonary artery. All 11 patients had an intracardiac anomaly or vascular malformations as well as pulmonary hypertension. A median sternotomy and cardiopulmonary bypass (CPB) were used in all 11 patients. The mean follow-up was 20.5 months (6 to 60 months). Results The operation time was 169 to 293 min (231 ± 55 min), the CPB time was 87 to 210 min (138 ± 47 min), and the aortic cross-clamp time was 45 to 133 min (86 ± 28 min). There was one hospital death (mortality 9%) in a patient with tetralogy of Fallot who had low cardiac output after the operation. In all cases, there was no application of artificial or homologous grafts. All surviving patients had satisfactory early to midterm results except for one patient with mild pulmonary stenosis. Conclusion The surgical correction of anomalous origin of one pulmonary artery without artificial or homologous grafts has satisfactory early to midterm results in infants. doi: 10.1111/jocs.12456 (J Card Surg 2015;30:85–91)

Melatonin confers cardioprotective effect against myocardial ischemia/reperfusion (MI/R) injury by reducing oxidative stress. Activation of silent information regulator 1 (SIRT1) signaling also reduces MI/R injury. We hypothesize that melatonin may protect against MI/R injury by activating SIRT1 signaling. This study investigated the protective effect of melatonin treatment on MI/R heart and elucidated its potential mechanisms. Rats were exposed to melatonin treatment in the presence or the absence of the melatonin receptor antagonist luzindole or SIRT1 inhibitor EX527 and then subjected to MI/R operation. Melatonin conferred a cardioprotective effect by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase release, upregulating SIRT1, Bcl-2 expression and downregulating Bax, caspase-3 and cleaved caspase-3 expression. Melatonin treatment also resulted in reduced myocardium superoxide generation, gp91(phox) expression, malondialdehyde level, and increased myocardium superoxide dismutase (SOD) level, which indicate that the MI/R-induced oxidative stress was significantly attenuated. However, these protective effects were blocked by EX527 or luzindole, indicating that SIRT1 signaling and melatonin receptor may be specifically involved in these effects. In summary, our results demonstrate that melatonin treatment attenuates MI/R injury by reducing oxidative stress damage via activation of SIRT1 signaling in a receptor-dependent manner.

Objectives The objective of this study was to evaluate the safety and efficacy of the surgical versus transcatheter approach to correct perimembranous ventricular septal defects (pmVSDs) in a prospective, randomized, controlled clinical trial. Background pmVSD is a common congenital heart disease in children. Surgical closure of pmVSD is a well-established therapy but requires open-heart surgery with cardiopulmonary bypass. Although the transcatheter approach is associated with significant incidence of complete atrioventricular block, it may provide a less invasive alternative. Critical comparison of the safety and efficacy of the 2 interventions necessitates a prospective, randomized, controlled trial. Methods Between January 2009 and July 2010, 229 children with pmVSD were randomly assigned to surgical or transcatheter intervention. Clinical, laboratory, procedural, and follow-up data over a 2-year period were compared. Results Neither group had mortality or major complications. However, statistical analysis of the 2 groups demonstrated significant differences (p Conclusions Transcatheter device closure and surgical repair are effective interventions with excellent midterm results for treating pmVSD in children. Transcatheter device closure has a lower incidence of myocardial injury, less blood transfused, faster recovery, shorter hospital stay, and lower medical expenses. (Transcatheter Closure Versus Surgery of Perimembranous Ventricular Septal Defects; NCT00890799 )

The pentalogy of Cantrell is a rare and fatal malformation. A left ventricular diverticulum is a common finding of this pentalogy. The present report summarizes our experience with three patients who suffered from pentalogy of Cantrell. All three cases had a left ventricular diverticulum. The intracardiac malformations and the left ventricular diverticulum were corrected simultaneously. All patients recovered uneventfully. One-stage surgical correction could improve short-term outcomes in selected patients with pentalogy of Cantrell.

Micro-RNA (miR)-155 is a novel gene regulator with important roles in inflammation. Herein, our study aimed to explore the role of miR-155 in LPS-induced acute lung injury(ALI). ALI in mice was induced by intratracheally delivered LPS. Loss-of-function experiments performed on miR-155 knockout mice showed that miR-155 gene inactivation protected mice from LPS-induced ALI, as manifested by preserved lung permeability and reduced lung inflammation compared with wild-type controls. Bone marrow transplantation experiments identified leukocytes, but not lung parenchymal-derived miR-155-promoted acute lung inflammation. Real-time PCR analysis showed that the expression of miR-155 in lung tissue was greatly elevated in wild-type mice after LPS stimulation. In situ hybridization showed that miR-155 was mainly expressed in alveolar macrophages. In vitro experiments performed in isolated alveolar macrophages and polarized bone marrow-derived macrophages confirmed that miR-155 expression in macrophages was increased in response to LPS stimulation. Conversely, miR-155 gain-of-function in alveolar macrophages remarkably exaggerated LPS-induced acute lung injury. Molecular studies identified the inflammation repressor suppressor of cytokine signaling (SOCS-1) as the downstream target of miR-155. By binding to the 3′-UTR of the SOCS-1 mRNA, miR-155 downregulated SOCS-1 expression, thus, permitting the inflammatory response during lung injury. Finally, we generated a novel miR-155 knockout rat strain and showed that the proinflammatory role of miR-155 was conserved in rats. Our study identified miR-155 as a proinflammatory factor after LPS stimulation, and alveolar macrophages-derived miR-155 has an important role in LPS-induced ALI.

We investigated the myocardial protective effect of a moderate-potassium cold blood cardioplegic solution (K+, 10 mmol/L) in pediatric cardiac surgery.Sixty-eight pediatric patients with congenital heart disease and undergoing open heart surgery with cardiopulmonary bypass were randomly allocated to the high potassium (HP [K+, 20 mmol/L, n=31]) cold blood cardioplegia group or the moderate potassium (MP [K+, 10 mmol/L, n=37]) cold blood cardioplegia group. Heart arresting time, rhythm recovery time, mechanical ventilation time, inotropic drug use in the intensive care unit, perioperative serum cardiac troponin I concentrations, morbidities, and mortalities were compared between the two groups.There were no differences in cardiopulmonary bypass time, aorta cross-clamping time, cardioplegia volume, lowest body temperature during cardiopulmonary bypass, total volume of cardioplegia delivered, hematocrit value, and fluid output during the operation between the two groups. However, there was a longer arresting time and a shorter rhythm recovery time in the MP group (35.6±2.4 s, and 30.8±3.1 s) when compared with that in the HP group (24.7±2.7 s, and 42.0±4.0 s, both p0.05). The total mediastinal drainage volume, the length of stay in the intensive care unit, the postoperative inotropic drug use, and the postoperative hospital time were similar between the two groups, but the number of patients with a long postoperative mechanical ventilation time (24 hours) in the MP group (6 of 36) was less than that in HP group (13 of 30; p0.05). At 1 hour, 3 hours, and 6 hours after myocardium reperfusion, the serum concentration of cardiac troponin I significantly decreased in the MP group (in ng/mL: 15.18±3.57, 24.83±4.91, and 19.62±3.93, respectively) when compared with that in the HP group (in ng/mL: 32.67±5.31, 39.26±7.43, and 30.52±5.17, respectively, p0.05).The present study demonstrated that the M (10 mmol/L) cold blood cardioplegia formula is associated with better myocardial protective effects when compared with conventional HP cardioplegia in pediatric patients.

The clinical profiles and outcomes of acute aortic dissection (AAD) have not been evaluated in China. We retrospectively analyzed, from January 1, 2008 to December 31, 2011, the data from 1,812 patients (mean age 51.1 ± 10.9 years; 77.5% men) with AAD (726 with type A and 1,086 with type B) from 19 large hospitals. Most patients had hypertension and presented with an abrupt onset of chest and/or back pain. Patients with type A AAD were more likely to present with typical symptoms and signs. Computed tomography was the most common initial imaging modality, used in 76.3% of patients with an AAD. The overall in-hospital mortality rate was 17.7%, with most of the deaths occurring within the first week. Surgery was used in 75.3% of patients with type A AAD. The mortality in this cohort was 33.8%. Endovascular treatment was performed in 76.1% of patients with type B AAD. The mortality rate was 2.2%. Multivariate analysis showed that hypertension (odds ratio 2.80, p

Background and Aims Patients with diabetes show enhanced susceptibility to myocardial ischemia/reperfusion (MI/R) injury. Epidemiological studies indicated that consumption of α-linolenic acid (ALA) significantly reduces the risk of cardiac events in post-acute myocardial infarction patients. The present study attempted to investigate the effects of ALA intake on MI/R injury in normal and diabetic rats and its mechanisms. Methods The high-fat diet-fed streptozotocin (HFD-STZ) rat model was developed. Age-matched normal and HFD-STZ rats were randomly assigned to receive normal diet or ALA (oral gavage, 500 μg/kg per day). After 4 weeks of feeding, animals were subjected to 30 min of myocardial ischemia and 4 or 6 h of reperfusion. Results Compared with the normal control, HFD-STZ rats showed more severe myocardial functional impairment and injury. Although ALA intake for 4 weeks did not change myocardial function and injury in normal rats, it significantly improved the instantaneous first derivation of left ventricle pressure, reduced infarct size, plasma creatine kinase and lactate dehydrogenase activities, and apotosis at the end of reperfusion in HFD-STZ diabetic rats. Moreover, ALA intake not only significantly reduced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentrations but reduced the increase in superoxide production and malonaldialdehyde formation and simultaneously enhanced the antioxidant capacity in the diabetic hearts. Myocardial PI3K expression and Akt phosphorylation were increased by ALA intake in diabetic but not normal rats. Conclusions Chronic ALA intake confers cardioprotection in MI/R by exerting anti-inflammatory and anti-oxidative stress effects in diabetic but not normal rats, which is possibly through PI3K-Akt-dependent mechanism.

Quantum dots (QD) can be fabricated by nanosecond laser irradiation on silicon samples in the oxygen, nitrogen or air atmospheres. The enhanced photoluminescence (PL) emerges at about 700 nm and the shape of PL peaks is similar almost. Random stimulated emission can be observed on QD treated with annealing. Calculation of primary principle shows that the kind and the density of bonds on QD surface play an important role in enhancement of PL emission. We propose a physical model to explain the mechanism of the PL enhancement.

Aims The aim of this study was to evaluate the safety and efficacy of transcatheter closure for perimembranous ventricular septal defect (pmVSD) and its long-term results. The most common congenital heart condition is pmVSD. Transcatheter closure of pmVSD is a recently described technique with limited results for mid- to long-term follow-up. Methods and results Between June 2002 and June 2008, 848 patients with pmVSD were enrolled in our study and treated percutaneously with pmVSD occluders. All patients were followed up until December 2008, an average of 37 months. According to colour Doppler transthoracic echocardiography before the intervention and ventriculography, the average end-diastolic pmVSD size was 5.1 and 5.4 mm, respectively. Placement of the device was successful in 832 patients (98.1%) and the median device size was 8.6 mm. During follow-up, 103 adverse events (12.4%) were reported. Most adverse events were categorized as minor and there were nine major adverse events (8.7%), including two complete atrioventricular block requiring pacemaker implantation. Kaplan–Meier estimates showed >85% freedom from major or minor adverse events during a maximal follow-up of 79 months. Conclusions In experienced hands, transcatheter pmVSD closure can be performed safely and successfully with low morbidity and mortality. Long-term prognostic results are favourable, and the transcatheter approach provides a less-invasive alternative that may become the first choice in selected pmVSD patients. This trial is registered with ClinicalTrials.gov, number [NCT00890799][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00890799&atom=%2Fehj%2F31%2F18%2F2238.atom

Background: The permeability of pulmonary microvessel endothelial cells increases markedly after acute lung injury via paracellular gap. Connexin40 is a primary component of pulmonary microvessel endothelial cells gap junction channel and mediates intercellular communication. However, the relationship between connexin40 and the permeability of pulmonary microvessel endothelial cells is still unknown. Therefore, we determined whether connexin40 affected rabbits' pulmonary microvessel endothelial cells permeability after acute lung injury induced by gunshot trauma. Methods: We used an acute lung injury model in New Zealand rabbits following gunshot chest trauma and correlated connexin40 inmunohistochemistry in gunshot lung tissue with Evans blue leak rate. Cultured pulmonary microvessel endothelial cells were divided into three groups, control (G control ), injured serum (G serum ), and blocker agent (G blocker ). Gap junction channel function was assessed by scrape-loading and dye transfer techniques. Pulmonary microvessel endothelial cells permeability was measured by Evans blue-labeled albumin transfer. Results: Connexin40 expression decreased time dependently, whereas Evans blue leak rate increased. Connexin40 expression and Evans blue leak rate exhibited a strong inverse correlation (y = -0.934, p < 0.05). Injured serum decreased gap junction channel function, and the gap junction channel blocker aggravated this effect. Similarly, pulmonary microvessel endothelial cells permeability increased significantly in G serum and G blocker . Conclusions: Connexin 40 expression in pulmonary microvasculature endothelial cells is downregulated after acute lung injury induced by gunshot trauma. This is associated with impaired gap junction channel function and increased pulmonary microvessel endothelial cells permeability.

BACKGROUND Cerebral damage is a major problem after reconstructive surgery of the aortic arch and the descending aorta. Current protective strategies, including deep hypothermia and antegrade cerebral perfusion (ACP), are used to prolong the tolerated duration of circulatory arrest. The aim of the study was to observe the influence of deep hypothermic circulatory arrest (DHCA) and ACP on neuronal apoptosis in the hippocampus. To further elucidate the mechanisms of neurologic injury and protection, we assessed the expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax. METHODS We randomly divided 18 pigs into 3 groups: The control group (n = 6) received normal-temperature cardiopulmonary bypass (CPB), the DHCA group (core temperature, 18 degrees C; n = 6) received DHCA for 90 minutes, and the third group (DHCA + ACP) (core temperature, 18 degrees C; ACP, flow rate of 30 mL/kg per minute at a pressure of 15-25 mm Hg; n = 6) received DHCA for 90 minutes. Hippocampal tissue was sampled 2 hours after CPB was finished. Bcl-2 and Bax expression was examined by immunohistochemistry. Morphologic changes in hippocampal tissue were measured with transmission electron microscopy. RESULTS Bax protein levels were significantly higher in the DHCA group than in the other 2 groups (P < .05), whereas Bcl-2 protein levels were significantly higher in the DHCA + ACP group than in the other 2 groups (P < .05). Obvious neuronal apoptosis was observed in the DHCA group but not in the controls, and few apoptotic neurons were seen in the DHCA + ACP group. CONCLUSIONS DHCA can induce neuronal apoptosis in the hippocampus. ACP during the DHCA period protects cerebral tissue by suppressing apoptosis through decreasing Bax expression and increasing Bcl-2 expression.

Objective: Given the increasing popularity of percutaneous closure of ventricular septal defects (VSDs), a comparative analysis of the different treatments (surgical vs. percutaneous closure) for VSDs is needed. Methods: This is a single center, retrospective clinical study. A total of 2,178 patients with VSDs were enrolled, including 852 patients treated with percutaneous closure (device group) and 1,326 patients underwent traditional surgical repair (surgical group). Several characteristics (e.g. procedure success rate, complications, blood transfusions) were compared between the 2 groups. Results: There were no differences (p > 0.05) between the device and surgical groups according to the success rates (99.8 vs. 100%) and occurrences of main complications (1.9 vs. 2.5%). The incidence of minor complications was significantly lower in the device group (0.6%, 5/852) than the surgical group (6.4%, 85/1,326) (p < 0.01). No blood transfusions were needed in the device group, while 136 patients (10.3%) required blood transfusions in the surgical group. The duration of hospital stay was shorter in the device group than in the surgical group (3.2 vs. 12.9 days, p < 0.01). Conclusion: Percutaneous VSD closure is an effective method with fewer complications, shorter hospital stay and good cosmetic effect. It can serve as a reasonable alternative treatment for traditional open heart surgery.

Background Granulocyte colony-stimulating factor (G-CSF), an important hematopoietic growth factor of the myeloid lineage, exerts profound immunoregulatory effects in T-cell tolerance. The study objective was to investigate the potential mechanism of G-CSF's antirejection effects in a fully mismatched rat cardiac allograft model. Methods The allograft recipients were treated with subcutaneous injection of recombinant human G-CSF (rh-G-CSF) at a dose of 250 μg/kg/d for 6 days starting from the day of cardiac transplantation. The alloreactive T-cell response and rejection level of G-CSF–treated rats were compared with those of control rats using mixed lymphocyte reactions (MLR) and histological examinations. Cytokine and cellular profiles were determined using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The presence and suppressive functions of regulatory T cells were determined by adoptive cell transfer experiments. Results Posttransplantation treatment of recipients with rh-G-CSF alone prolonged allograft survival, improved allograft biopsy grading scores, and induced alloreactive T-cell hyporesponsiveness accompanied by high levels of interleukin-10 (IL-10) and transforming growth factor–β1 (TGF-β1) production in MLR. It also enhanced CD4 + CD25 + T cells in peripheral blood. The splenocytes from rh-G-CSF–treated recipients transferred antirejection effects to secondary recipients. Conclusions Posttransplantation treatment of cardiac allograft recipients with rh-G-CSF leads to alloreactive T-cell hyporesponsiveness in vivo and in vitro associated with recruitment of CD4 + CD25 + T cells in the peripheral blood. This study may provide insight into the application of G-CSF to control acute rejection of solid organ transplantations.

Surgical repair and endovascular stent-graft placement are both therapies for thoracic aortic dissection. A combination of these two approaches may be effective in patients with type A dissection. In this study, we evaluated the prognosis of this combined technique. From December 2003 to December 2006, 15 patients with type A dissection were admitted to our institute; clinical data were retrospectively reviewed. Follow-up was performed at discharge and approximately 12 months after operation. Endovascular stent-graft placement by interventional radiology and surgical repair for reconstruction of aortic arch was performed in all patients. Total arch replacement for distal arch aneurysm was carried out under deep hypothermia with circulatory arrest; antegrade-selected cerebral perfusion was used for brain protection. Four patients concomitantly received a coronary artery bypass graft. Hospital mortality rate was 6.7%; the patient died of cerebral infarction. Neurological complications developed in two patients. Multi-detector-row computed tomography scans performed before discharge revealed complete thrombosis of the false lumen in six patients and partial thrombosis in eight patients. At the follow-up examination, complete thrombosis was found in another three patients, aortic rupture, endoleaks, or migration of the stent-graft was not observed and injuries of peripheral organs or anastomotic endoleaks did not occur. For patients with aortic type A dissection, combining intervention and surgical procedures is feasible, and complete or at least partial thrombosis of the false lumen in the descending aorta can be achieved. This combined approach simplified the surgical procedures and shortened the circulatory arrest time, minimizing the necessity for further aortic operation.

Optimal management of muscular ventricular septal defects (MVSDs) remains controversial. Left ventriculotomy is the cornerstone of surgical repair but is frequently complicated by residual shunts, left ventricular dysfunction, apical aneurysm, or arrhythmias. In this study, we evaluated the long-term outcomes of surgical repairs in infants with isolated MVSDs. We retrospectively analyzed clinical data from 56 children with MVSDs (31 males, 25 females). Follow-up by questionnaire and Doppler echocardiography was performed at discharge and between 2 and 124 months after surgery. Patient age was 2 to 40 months (median, 21 months) and weight was 3.0 to 15.3 kg (median, 5.3 kg). Two patients died after surgery (hospital mortality, 3.57%). One patient with MVSDs died of low cardiac output caused by the long duration of cardiopulmonary bypass. Another patient with Swiss cheese MVSD received a single patch closure but died of low cardiac output immediately after cardiopulmonary bypass. Immediate complications such as a third-degree atrial-ventriclar block occurred in 2 patients, but they recovered before discharge and showed no residual shunt. No deaths occurred during follow-up, but a residual shunt was found in 1 patient. Delayed complete heart block requiring a pacemaker occurred in 1 patient. One patient showed paroxysmal supraventricular tachycardia that was treated with amiodarone. The left ventricular ejection fraction was 0.45-0.55 in 8 patients and 0.55-0.73 in 46 patients. No apical aneurysm was found. All the surviving patients returned to normal school life. Our results indicate that surgery is a suitable treatment option in infants and children with isolated MVSDs and that preoperative diagnosis is crucial to a successful outcome. Infants can tolerate a left ventriculotomy incision for MVSDs in the lower or apical ventricular septum.

The pathogenesis of myocardial stunning caused by brief ischemia and reperfusion remains unclear. The aim of the present study was to investigate the underlying mechanism of myocardial stunning. An isolated cell model of myocardial stunning was firstly established in isolated rat ventricular myocytes exposed to 8 min of simulated ischemia and 30 min of reperfusion, the cardiomyocyte contractile function was used to evaluate myocardial stunning. A diastolic Ca(2+) overload without significant changes in systolic Ca(2+) and the amplitude of Ca(2+) transient during the first 10 min of reperfusion played an important role in the occurrence of myocardial stunning. Decreasing Ca(2+) entry into myocardial cells with low Ca(2+) reperfusion was a very efficient way to prevent myocardial stunning. Diastolic Ca(2+) overload was closely related to the reverse mode of Na(+)/Ca(2+) exchanger (NCX) rather than L-type Ca(2+) channel. The activity of the reverse mode of NCX was found significantly higher at the initial time of reperfusion, and KB-R7943, a selective inhibitor of the reverse mode of NCX, administered at first 10 min of reperfusion rather than at the time of ischemia significantly attenuated myocardial stunning. In addition, NCX inhibition also attenuated the Ca(2+) oscillation and cardiac dysfunction when field stimulus was stopped at first 10 min of reperfusion. These data suggest that one of the important mechanisms of triggering myocardial stunning is diastolic Ca(2+) overload caused by activation of the reverse mode of NCX of cardiomyocytes during the initial period of reperfusion following brief ischemia.

Several deficiencies in currently available right ventricular valved conduits make them problematic for use in infants and children. A solution would be to develop a tissue-engineered valved conduit containing autologous cells. A method was devised to produce a decellularized bovine matrix scaffold for developing a tissue-engineered right ventricular valved conduit. Fresh bovine jugular veins were treated with sodium deoxycholate and Triton X-100. The major structural proteins of the fresh and decellularized jugular venous valves and vessel walls were detected by histological methods. Thickness, water absorption rate, water maintenance rate, disruption strength, and extensibility were determined. Circumferential and radial specimens of valves and vessel walls were subjected to tensile testing. Histological analysis showed that no cell fragments were retained within the decellularized matrix scaffold and the major structural proteins had been retained intact. There were no significant differences in thickness, rates of absorption and maintenance of water, disruption strength, and extensibility between the decellularized and fresh veins. It was concluded that this treatment can successfully remove cellular components while maintaining the major structural components and the histological and biological properties of bovine jugular veins.

The effects of sevoflurane inhalation during cardiopulmonary bypass (CPB) on postoperative courses and serum cardiac troponin I (cTnI) concentrations in pediatric patients undergoing cardiac surgery have not been extensively investigated. In this single-center, prospective, randomized trial, an anesthetic regimen containing 2% sevoflurane used throughout the CPB process was compared with a total intravenous anesthesia (TIVA) regimen. One hundred and three patients undergoing congenital heart defect repair with CPB were included in this prospective randomized controlled study. They were randomized into two groups: the sevoflurane group, who received 2% sevoflurane during CPB via an oxygenator, and the control group, who received only an oxygen-air mixture. The pre- and intra-operative parameters were comparable between the two groups. There was a slight but significant increase of arterial diastolic pressure in the sevoflurane group immediately after CPB compared with control patients (46.9 ± 9.3 mm Hg vs. 43.6 ± 8.9 mm Hg; p = 0.033). There was no death in either group. The postoperative ventilation time (in mean [95% confidence interval]) was shorter in the sevoflurane group than that in the control group (26.1 [19.2, 33.0] h vs. 37.7 [24.4, 50.9] h; p = 0.014). The postoperative ICU time, hospital days, and serial serum cTnI concentrations were not significantly different between the two groups. Inhalation of 2% sevoflurane during CPB is beneficial to the recovery of pediatric patients undergoing cardiac surgery but has no significant effect on postoperative cTnI release.