Mesenchymal Stem Cells and Extracellular Vesicles: Therapeutic Potential in Organ Transplantation.

At present, organ transplantation remains the most appropriate therapy for patients with end-stage organ failure. However, the field of organ transplantation is still facing many challenges, including the shortage of organ donors, graft function damage caused by organ metastasis, and antibody-mediated immune rejection. It is therefore urgently necessary to find new and effective treatment. Stem cell therapy has been regarded as a "regenerative medicine technology." Mesenchymal stem cells (MSCs), as the most common source of cells for stem cell therapy, play an important role in regulating innate and adaptive immune responses and have been widely used in clinical trials for the treatment of autoimmune and inflammatory diseases. Increasing evidence has shown that MSCs mainly rely on paracrine pathways to exert immunomodulatory functions. In addition, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are the main components of paracrine substances of MSCs. Herein, an overview of the application of the function of MSCs and MSC-EVs in organ transplantation will focus on the progress reported in recent experimental and clinical findings and explore their uses for graft preconditioning and recipient immune tolerance regulation. Additionally, the limitations on the use of MSC and MSC-EVs are also discussed, covering the isolation of exosomes and preservation techniques. Finally, the opportunities and challenges for translating MSCs and MSC-EVs into clinical practice of organ transplantation are also evaluated.

Unilateral cerebral arterial tortuosity: Associated with aneurysm occurrence, but potentially inversely associated with aneurysm rupture.

PURPOSE: To investigate the association of tortuosity of the main cerebral arteries with intracranial aneurysm (IA) occurrence and rupture. To investigate the relationship between arterial tortuosity and aneurysm morphology as well as conventional risk factors of vascular diseases. METHODS: Three subject groups were analyzed in this study: Patients with ruptured IAs, patients with unruptured IAs, and healthy subjects. The groups were matched by sex and age using tendency score matching. Their intracranial magnetic resonance angiography (MRA) images were collected retrospectively. The intracranial arterial structures were segmented from the MRA images. Arterial tortuosity was measured and statistically compared between the different subject groups and different vessels. Correlation analysis was conducted between arterial tortuosity and clinical risk factors as well as aneurysm morphology. RESULTS: 120 patients were included in the study (average age: 67.5 years; 60% female), 40 for each group after matching. The tortuosity of the aneurysm-bearing artery was significantly greater than that of the contralateral artery in both the ruptured and unruptured IA groups (p < 0.001). There was no significant association between clinical risk factors (history of hypertension, hyperlipidemia, diabetes, smoking, and alcohol use) and arterial tortuosity. There were significant negative correlations between aneurysm-bearing artery tortuosity and aneurysm morphological features such as maximal diameter (p = 0.0011), neck diameter (p < 0.0001), maximum height (p = 0.0024), and size ratio (p = 0.0269). CONCLUSION: The occurrence of cerebral aneurysms correlates to increased unilateral arterial tortuosity, but the risk of aneurysm enlargement/rupturing decreases with greater arterial tortuosity. Abnormal tortuosity may be congenital as tortuosity has no clear connection with acquired common risk factors of vascular diseases.

Macrophage polarization states in atherosclerosis.

Atherosclerosis, a chronic inflammatory condition primarily affecting large and medium arteries, is the main cause of cardiovascular diseases. Macrophages are key mediators of inflammatory responses. They are involved in all stages of atherosclerosis development and progression, from plaque formation to transition into vulnerable plaques, and are considered important therapeutic targets. Increasing evidence suggests that the modulation of macrophage polarization can effectively control the progression of atherosclerosis. Herein, we explore the role of macrophage polarization in the progression of atherosclerosis and summarize emerging therapies for the regulation of macrophage polarization. Thus, the aim is to inspire new avenues of research in disease mechanisms and clinical prevention and treatment of atherosclerosis.

Follow-Up Infarct Volume Prediction by CTP-Based Hypoperfusion Index, and the Discrepancy between Small Follow-Up Infarct Volume and Poor Functional Outcome-A Multicenter Study.

(1) Background: Follow-up infarct volume (FIV) may have implications for prognostication in acute ischemic stroke patients. Factors predicting the discrepancy between FIV and 90-day outcomes are poorly understood. We aimed to develop a comprehensive predictive model of FIV and explore factors associated with the discrepancy. (2) Methods: Patients with acute anterior circulation large vessel occlusion were included. Baseline clinical and CT features were extracted and analyzed, including the CTP-based hypoperfusion index (HI) and the NCCT-based e-ASPECT, measured by automated software. FIV was assessed on follow-up NCCT at 3−7 days. Multiple linear regression was used to construct the predictive model. Subgroup analysis was performed to explore factors associated with poor outcomes (90-mRS scores 3−6) in small FIV (<70 mL). (3) Results: There were 170 patients included. Baseline e-ASPECT, infarct core volume, hypoperfusion volume, HI, baseline international normalized ratio, and successful recanalization were associated with FIV and included in constructing the predictive model. Baseline NIHSS, baseline hypertension, stroke history, and current tobacco use were associated with poor outcomes in small FIV. (4) Conclusions: A comprehensive predictive model (including HI) of FIV was constructed. We also emphasized the importance of hypertension and smoking status at baseline for the functional outcomes in patients with a small FIV.

MicroRNA-29b reduces myocardial ischemia-reperfusion injury in rats via down-regulating PTEN and activating the Akt/eNOS signaling pathway.

Reperfusion may cause injuries to the myocardium in ischemia situation, which is called ischemia/reperfusion (I/R) injury. The study aimed to explore the roles of microRNA-29b (miR-29b) in myocardial I/R injury. Myocardial I/R injury rat model was established. Differentially expressed miRNAs between the model rats and the sham-operated rats were analyzed. miR-29b expression in myocardial tissues was measured. Gain-of-function of miR-29b was performed, and then the morphological changes, infarct size, myocardial function, oxidative stress, and the cell apoptosis in myocardial tissues were detected. The target relation between miR-29b and PTEN was detected through bio-information prediction and dual luciferase reporter gene assay. Activation of Akt/eNOS signaling was detected. H9C2 cells were subjected to hypoxia/reoxygenation treatment to perform in vitro experiments. I/R rats presented severe inflammatory infiltration, increased infarct size and cell apoptosis, increased oxidative stress and decreased myocardial function. miR-29b was downregulated in I/R rats, and up-regulation of miR-29b reversed the above changes. miR-29b directly bound to PTEN, and overexpression of miR-29b reduced PTEN expression level and increased the protein levels of p-Akt/Akt and p-eNOS/eNOS. In vivo results were confirmed in in vitro experiments. This study provided evidence that miR-29b could alleviate the myocardial I/R injury in vivo and in vitro by inhibiting PTEN expression and activating the Akt/eNOS signaling pathway.

Non-Coding RNAs: Emerging Therapeutic Targets in Spinal Cord Ischemia-Reperfusion Injury.

Paralysis or paraplegia caused by transient or permanent spinal cord ischemia-reperfusion injury (SCIRI) remains one of the most devastating post-operative complications after thoracoabdominal aortic surgery, even though perioperative strategies and surgical techniques continue to improve. Uncovering the molecular and cellular pathophysiological processes in SCIRI has become a top priority. Recently, the expression, function, and mechanism of non-coding RNAs (ncRNAs) in various diseases have drawn wide attention. Non-coding RNAs contain a variety of biological functions but do not code for proteins. Previous studies have shown that ncRNAs play a critical role in SCIRI. However, the character of ncRNAs in attenuating SCIRI has not been systematically summarized. This review article will be the first time to assemble the knowledge of ncRNAs regulating apoptosis, inflammation, autophagy, and oxidative stress to attenuate SCIRI. A better understanding of the functional significance of ncRNAs following SCIRI could help us to identify novel therapeutic targets and develop potential therapeutic strategies. All the current research about the function of nRNAs in SCIRI will be summarized one by one in this review.

Normothermic ex vivo Heart Perfusion Combined With Melatonin Enhances Myocardial Protection in Rat Donation After Circulatory Death Hearts via Inhibiting NLRP3 Inflammasome-Mediated Pyroptosis.

OBJECTIVE: The adoption of hearts from donation after circulatory death (DCD) is a promising approach for the shortage of suitable organs in heart transplantation. However, DCD hearts suffer from serious ischemia/reperfusion injury (IRI). Recent studies demonstrate that nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis is a novel target to ameliorate myocardial IRI. Melatonin is shown to inhibit NLRP3 inflammasome-mediated pyroptosis. Therefore, this study is designed to verify the hypothesis that melatonin can protect the heart graft preserved with ex vivo heart perfusion (EVHP) against myocardial IRI via inhibiting NLRP3 inflammasome-mediated pyroptosis in a rat model of DCD. METHODS: Donor-heart rats were randomly divided into three groups: (1) Control group: non-DCD hearts were harvested from heart-beating rats and immediately preserved with allogenic blood-based perfusate at constant flow for 105 min in the normothermic EVHP system; (2) DCD-vehicle group; and (3) DCD-melatonin group: rats were subjected to the DCD procedure with 25 min of warm ischemia injury and preserved by the normothermic EVHP system for 105 min. Melatonin (200 µmol/L) or vehicle was perfused in the cardioplegia and throughout the whole EVHP period. Cardiac functional assessment was performed every 30 min during EVHP. The level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis of heart grafts submitted to EVHP were evaluated. RESULTS: Twenty five-minute warm ischemia injury resulted in a significant decrease in the developed pressure (DP), dP/dt max , and dP/dt min of left ventricular of the DCD hearts, while the treatment with melatonin significantly increased the DP, dP/dt max of the left ventricular of DCD hearts compared with DCD-vehicle group. Furthermore, warm ischemia injury led to a significant increase in the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis in the hearts preserved with EVHP. However, melatonin added in the cardioplegia and throughout the EVHP period significantly attenuated the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis compared with DCD-vehicle group. CONCLUSION: EVHP combined with melatonin post-conditioning attenuates myocardial IRI in DCD hearts by inhibiting NLRP3 inflammasome-mediated pyroptosis, which might expand the donor pool by the adoption of transplantable DCD hearts.

Mesenchymal stem cell-derived conditioned medium protects vascular grafts of brain-dead rats against in vitro ischemia/reperfusion injury.

BACKGROUND: Brain death (BD) has been suggested to induce coronary endothelial dysfunction. Ischemia/reperfusion (IR) injury during heart transplantation may lead to further damage of the endothelium. Previous studies have shown protective effects of conditioned medium (CM) from bone marrow-derived mesenchymal stem cells (MSCs) against IR injury. We hypothesized that physiological saline-supplemented CM protects BD rats' vascular grafts from IR injury. METHODS: The CM from rat MSCs, used for conservation purposes, indicates the presence of 23 factors involved in apoptosis, inflammation, and oxidative stress. BD was induced by an intracranial-balloon. Controls were subjected to a sham operation. After 5.5 h, arterial pressures were measured in vivo. Aortic rings from BD rats were harvested and immediately mounted in organ bath chambers (BD group, n = 7) or preserved for 24 h in 4 °C saline-supplemented either with a vehicle (BD-IR group, n = 8) or CM (BD-IR+CM group, n = 8), prior to mounting. Vascular function was measured in vitro. Furthermore, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) have been performed. RESULTS: BD in donors was associated with significantly impaired hemodynamic parameters and higher immunoreactivity of aortic myeloperoxidase (MPO), nitrotyrosine, caspase-3, caspase-8, caspase-9, and caspase-12 compared to sham-operated rats. In organ bath experiments, impaired endothelium-dependent vasorelaxation to acetylcholine in the BD-IR group compared to BD rats was significantly improved by CM (maximum relaxation to acetylcholine: BD 81 ± 2% vs. BD-IR 50 ± 3% vs. BD-IR + CM 72 ± 2%, p < 0.05). Additionally, the preservation of BD-IR aortic rings with CM significantly lowered MPO, caspase-3, caspase-8, and caspase-9 immunoreactivity compared with the BD-IR group. Furthermore, increased mRNA expression of vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 in the aortas from the BD-IR rats compared to BD group were significantly decreased by CM. CONCLUSIONS: The preservation of BD rats' vascular grafts with CM alleviates endothelial dysfunction following IR injury, in part, by reducing levels of inflammatory response and caspase-mediated apoptosis.

Donor heart preservation with hypoxic-conditioned medium-derived from bone marrow mesenchymal stem cells improves cardiac function in a heart transplantation model.

BACKGROUND: In heart transplantation, donor hearts inevitably suffer from ischemia/reperfusion (I/R) injury, which leads to primary graft dysfunction and affects patients' survival rate. Bone marrow mesenchymal stem cells (BMSCs) have been reported to attenuate myocardial I/R injury via their paracrine effects, which can be enhanced by hypoxic preconditioning. We hypothesized that the donor heart preservation with hypoxic conditioned medium (CdM) derived from BMSCs would improve post-transplant graft function. METHODS: Normoxic or hypoxic CdM were isolated from rat BMSCs cultured under normoxic (20% O2) or hypoxic (1% O2) condition. Donor hearts were explanted; stored in cardioplegic solution supplemented with either a medium (vehicle), normoxic CdM (N-CdM), or hypoxic CdM (H-CdM); and then heterotopically transplanted. Antibody arrays were performed to compare the differences between hypoxic and normoxic CdM. RESULTS: After heart transplantation, the donor heart preservation with normoxic CdM was associated with a shorter time to return of spontaneous contraction and left ventricular systolic diameter, lower histopathological scores, higher ejection fraction, and fractional shortening of the transplanted hearts. The cardioprotective effects may be associated with the inhibition of apoptosis and inflammation, as reflected by less TUNEL-positive cells and lower levels of plasma proinflammatory cytokines (interleukin-1ß, interleukin-6, tumor necrosis factor-α) and cardiac troponin I in the N-CdM group compared with the vehicle group. These therapeutic effects can be further enhanced by hypoxic preconditioning. Antibody arrays revealed that nine proteins were significantly increased in hypoxic CdM compared with normoxic CdM. Furthermore, compared with vehicle and N-CdM groups, the protein levels of PI3K and p-Akt/Akt ratio in the transplanted hearts significantly increased in the H-CdM group. However, no significant difference was found in the phosphorylation of Smad2 and Smad3 for the donor hearts among the three groups. CONCLUSIONS: Our results indicate that the cardioplegic solution-enriched with hypoxic CdM can be a novel and promising preservation solution for donor hearts.

Application of Mesenchymal Stem Cells During Machine Perfusion: An Emerging Novel Strategy for Organ Preservation.

Although solid organ transplantation remains the definitive management for patients with end-stage organ failure, this ultimate treatment has been limited by the number of acceptable donor organs. Therefore, efforts have been made to expand the donor pool by utilizing marginal organs from donation after circulatory death or extended criteria donors. However, marginal organs are susceptible to ischemia-reperfusion injury (IRI) and entail higher requirements for organ preservation. Recently, machine perfusion has emerged as a novel preservation strategy for marginal grafts. This technique continually perfuses the organs to mimic the physiologic condition, allows the evaluation of pretransplant graft function, and more excitingly facilitates organ reconditioning during perfusion with pharmacological, gene, and stem cell therapy. As mesenchymal stem cells (MSCs) have anti-oxidative, immunomodulatory, and regenerative properties, mounting studies have demonstrated the therapeutic effects of MSCs on organ IRI and solid organ transplantation. Therefore, MSCs are promising candidates for organ reconditioning during machine perfusion. This review provides an overview of the application of MSCs combined with machine perfusion for lung, kidney, liver, and heart preservation and reconditioning. Promising preclinical results highlight the potential clinical translation of this innovative strategy to improve the quality of marginal grafts.

Surgical treatment of mild to moderately dilated ascending aorta in bicuspid aortic valve aortopathy: the art of safety and simplicity.

BACKGROUND: Evaluate the safety and efficacy of our modified technique of the extravascular procedure for treating mild to moderately dilated ascending aorta in patients with bicuspid aortic valve (BAV) aortopathy. METHODS: From January 2015 to December 2018,119 consecutive patients with BAV and ascending aorta dilatation (dimension 40 mm~ 45 mm) were diagnosed in our institution. Among these,49 patients received aggressive aortic valve replace (AVR) + ascending aorta wrapped (wrapped group) while the other 70 patients received AVR + ascending aorta replacement (wheat group). All patients clinical and follow up data were collected for 12 months. RESULTS: Aortic clamping and cardio-pulmonary bypass times were significantly longer in wheat group than wrap group (P < 0.001and 0.021,respectively). The first 24 h drainage in wheat group were much more than wrap group(P = 0.04). Ascending aorta diameter、left ventricular end diameter and ejection fraction were statistically different between pre- and post-operation (p < 0.001) in both groups, but the heart function and complication were no difference during follow up. CONCLUSIONS: External wrapping of the ascending aorta and wheat procedure have good short-term and long-term results in BAV patients with a mild to moderately dilated ascending aorta. The perioperative period results of external wrapping of the ascending aorta for BAV patients were encouraging.

Diabetes Mellitus Is Not a Risk Factor for Patients Supported With Left Ventricular Assist Device.

BACKGROUND: Diabetes mellitus has been proved to be a potent, independent risk factor for mortality in patients with heart failure. However, the influence of diabetes on outcomes after continuous-flow left ventricular assist device (CF-LVAD) implantation is still under debate. This study sought to investigate the effect of preoperative diabetes on all-cause mortality and major postoperative complications among patients with contemporary CF-LVAD support. METHODS: A systematic literature search (PubMed, Embase, and ISI Web of Knowledge, and Cochrane Central Register of Controlled Trials) was performed. The primary endpoint was hazard ratio for all-cause mortality. Secondary endpoints were postoperative complications, including infection, transient ischemia attack, intracranial hemorrhage, and pump thrombosis. A meta-analysis was conducted to generate pooled hazard ratio and 95% confidence interval (CI) for all-cause mortality and pooled odds ratio (OR) and 95% CI for postoperative complications. RESULTS: A total of 1120 patients (478 diabetic patients, 642 nondiabetic patients) from four studies were included in this study. Diabetes did not increase the risk for all-cause mortality among patients with CF-LVAD support (hazard ratio 1.33; 95% CI, 0.88 to 2.02; P = .18). Moreover, pooled analysis demonstrated no significant difference was found in the diabetes and nondiabetes groups in terms of infection (OR 1.18; 95% CI, 0.89 to 1.56; P = .24), transient ischemia attack (OR 1.30; 95% CI, 0.86 to 1.97; P = .21), intracranial hemorrhage (OR 1.86; 95% CI, 0.93 to 3.71; P = .08), and pump thrombosis (OR 1.01; 95% CI, 0.68 to 1.48; P = .97). CONCLUSIONS: The results of this meta-analysis demonstrate that diabetes does not increase all-cause mortality or rates of major adverse events during contemporary CF-LVAD support.

A Spray-on, Nanocomposite-Based Sensor Network for in-Situ Active Structural Health Monitoring.

A new breed of nanocomposite-based spray-on sensor is developed for in-situ active structural health monitoring (SHM). The novel nanocomposite sensor is rigorously designed with graphene as the nanofiller and polyvinylpyrrolidone (PVP) as the matrix, fabricated using a simple spray deposition process. Electrical analysis, as well as morphological characterization of the spray-on sensor, was conducted to investigate percolation characteristic, in which the optimal threshold (~0.91%) of the graphene/PVP sensor was determined. Owing to the uniform and stable conductive network formed by well-dispersed graphene nanosheets in the PVP matrix, the tailor-made spray-on sensor exhibited excellent piezoresistive performance. By virtue of the tunneling effect of the conductive network, the sensor was proven to be capable of perceiving signals of guided ultrasonic waves (GUWs) with ultrahigh frequency up to 500 kHz. Lightweight and flexible, the spray-on nanocomposite sensor demonstrated superior sensitivity, high fidelity, and high signal-to-noise ratio under dynamic strain with ultralow magnitude (of the order of micro-strain) that is comparable with commercial lead zirconate titanate (PZT) wafers. The sensors were further networked to perform damage characterization, and the results indicate significant application potential of the spray-on nanocomposite-based sensor for in-situ active GUW-based SHM.

Is the era of bilateral internal thoracic artery grafting coming for diabetic patients? An updated meta-analysis.

OBJECTIVE: Because of an increased risk of sternal wound complications, the use of bilateral internal thoracic artery grafting in diabetic patients remains controversial. The objective of the present meta-analysis is to compare the safety and efficacy of single internal thoracic artery and bilateral internal thoracic artery grafting in the diabetic population. METHODS: Four electronic databases, including PubMed, the Cochrane Library, Embase, and ISI Web of Knowledge, were comprehensively searched. Prospective randomized trials or observational studies comparing single internal thoracic artery and bilateral internal thoracic artery were considered eligible for the current study. RESULTS: A literature search yielded 1 randomized controlled trial and 17 observational studies (129,871 diabetic patients: 124,233 single internal thoracic arteries and 5638 bilateral internal thoracic arteries). Pooled analysis demonstrated overall incidence of deep sternal wound infection in the bilateral internal thoracic artery grafting group was significantly higher than in the single internal thoracic artery grafting group (3.26% for bilateral internal thoracic artery vs 1.70% for single internal thoracic artery). No significant difference was found between both groups in terms of risk of deep sternal wound infection when the skeletonized harvesting technique was adopted. Furthermore, in-hospital mortality was comparable between both groups (2.80% for bilateral internal thoracic artery vs 2.36% for single internal thoracic artery). However, compared with single internal thoracic artery grafting, bilateral internal thoracic artery grafting could confer a lower risk for long-term overall mortality (hazard ratio, 1.41; 95% confidence interval, 1.18-1.67; P < .001; I2 = 63%) and cardiac mortality (hazard ratio, 3.15; 95% confidence interval, 2.23-4.46; P < .001; I2 = 0%). CONCLUSIONS: Compared with single internal thoracic artery grafting, bilateral internal thoracic artery grafting is associated with enhanced long-term survival among diabetic patients. Skeletonization of bilateral internal thoracic artery is not associated with an increased risk of deep sternal wound infection. Therefore, surgeons should be encouraged to adopt bilateral internal thoracic artery grafting in a skeletonized manner more routinely in diabetic patients.

Tumor Microenvironment Regulation by the Endoplasmic Reticulum Stress Transmission Mediator Golgi Protein 73 in Mice.

The unfolded protein response (UPR) signal in tumor cells activates UPR signaling in neighboring macrophages, which leads to tumor-promoting inflammation by up-regulating UPR target genes and proinflammatory cytokines. However, the molecular basis of this endoplasmic reticulum (ER) stress transmission remains largely unclear. Here, we identified the secreted form of Golgi protein 73 (GP73), a Golgi-associated protein functional critical for hepatocellular carcinoma (HCC) growth and metastasis, is indispensable for ER stress transmission. Notably, ER stressors increased the cellular secretion of GP73. Through GRP78, the secreted GP73 stimulated ER stress activation in neighboring macrophages, which then released cytokines and chemokines involved in the tumor-associated macrophage (TAM) phenotype. Analysis of HCC patients revealed a positive correlation of GP73 with glucose-regulated protein 78 (GRP78) expression and TAM density. High GP73 and CD206 expression was associated with poor prognosis. Blockade of GP73 decreased the density of TAMs, inhibited tumor growth, and prolonged survival in two mouse HCC models. Conclusion: Our findings provide insight into the molecular mechanisms of extracellular GP73 in the amplification and transmission of ER stress signals.

Meta-Analysis of Repeat Revascularization of Off-Pump and On-Pump Coronary Artery Bypass Surgery.

BACKGROUND: There is an ongoing debate focusing on clinical outcomes after off-pump coronary artery bypass graft surgery (OPCABG) and on-pump coronary artery bypass graft surgery (ONCABG). The objective of the present meta-analysis is to update and compare repeat revascularization rates between OPCABG and ONCABG procedures. METHODS: Data sources including PubMed, EMBASE, Cochrane Library, and ISI Web of Knowledge were searched between 1966 and October 2017. Studies considered for inclusion should conform to the following criteria: prospective randomized clinical trials comparing OPCABG and ONCABG. Outcome should include repeat revascularization rate at the time of 1-month, 1-year, or 5-year follow-up. RESULTS: A literature search yielded 11 randomized controlled trials, and a total of 11,246 patients were randomly allocated to OPCABG or ONCABG procedures. Pooled analysis demonstrated a statistically significant 53% increase in repeat revascularization rate at 1-year follow-up with OPCABG relative to ONCABG in the fixed effects model (odds ratio 1.53, 95% confidence interval: 1.17 to 2.00, p = 0.002), whereas there was no significant difference in repeat revascularization rate at 5-year follow-up between OPCABG and ONCABG in the fixed effects model (OR 1.16, 95% confidence interval: 0.95 to 1.41, p = 0.14). In general, exclusion of any single trial did not affect repeat revascularization rate at 1-year and 5-year follow-up. There was no evidence of significant publication bias. CONCLUSIONS: The result of our meta-analysis suggests that compared with ONCABG, OPCABG increases repeat revascularization rate at 1-year follow-up, but does not affect that of 5-year follow-up.

GP73 regulates Hepatic Steatosis by enhancing SCAP-SREBPs interaction.

Elevated Golgi phosphoprotein 2 (GP73, also known as GOLPH2 or GOLM1) expression in serum and liver, which can be induced by viral infection and cytokine treatments, is intimately connected with liver disease, including acute hepatitis, cirrhosis and hepatocellular carcinoma (HCC). However, its pathogenic roles in hepatic diseases have never been clarified in detail. Here, we showed that the upregulated GP73 is indispensable for SREBPs activation and lipogenesis. Notably, GP73 overexpression enhanced SCAP-SREBPs binding and its Golgi trafficking even under cholesterol sufficiency. Consistent with these functional findings, GP73 blockage could alleviate tunicamycin-induced liver steatosis by reducing SREBPs activation. A significant positive correlation of GP73 with genes in lipid metabolism pathway was also identified in liver cancer based on data from The Cancer Genome Atlas (TCGA) dataset. Our findings revealed previously unrecognized role of GP73 in lipid metabolism.

Intra-operative device closure of perimembranous ventricular septal defect without cardiopulmonary bypass under guidance of trans-epicardial echocardiography: a single center experience.

BACKGROUND: Intraoperative device closure of perimembranous ventricular septal defect(VSD) through a lower mini-sternotomy is safe, less invasive, and has excellent surgical and cosmetic outcomes. Our study is to evaluate the feasibility of closing VSD under guidance of trans-epicardial echocardiography. METHODS: We reviewed the clinical course of 41 patients referred to our institution for minimally invasive closure of perimembranous VSD. The trans-epicardial echocardiography(TEE) was used to monitor the whole procedure to guide the positioning of device and evaluate the operative effect instantly after operation. RESULT: The procedure was successfully done in 38 patients(92.6 %) with mean age of 1.2 ± 1.5 years(range 0.5-6.1 years),mean weight of 10.78 ± 6.87 kg(range 5.2 ~ 26 kg) and VSD size of 5.1 ± 1.13 mm(range 5 ~ 10 mm). Three cases failed, including two cases whose guide-wires could not pass through VSDs and one case whose occluder could not repair VSD well. Three patients had tiny residual shunts because of the shifting of occluders. There were no major complications such as arrhythmia, valve regurgitation and the failure of occluder during follow-up(Mean 2.3 ± 1.2 years). TEE provided superior imaging of shapes and surrounding structures of the VSDs, and guide-wires passing through VSDs. CONCLUSIONS: Intraoperative device closure of perimembranous VSD through a lower mini-sternotomy without cardiopulmonary bypass appears to be a safe and effective procedure. The use of trans-epicardial echocardiography provides useful information for intraoperative device closure of VSD.

Hybrid coronary revascularization versus coronary artery bypass grafting for multivessel coronary artery disease: systematic review and meta-analysis.

BACKGROUND: The concept of hybrid coronary revascularization (HCR) combines the left internal mammary artery (LIMA)-left anterior descending (LAD) graft and percutaneous coronary intervention (PCI) to non-LAD vessels. Multiple comparative studies have evaluated the safety and feasibility of HCR and coronary artery bypass grafting (CABG) for multivessel coronary artery disease (MCAD). However, the sample size of each study was small, and evidences based on single-institutional experience. The purpose of this meta-analysis was to compare the short-term outcomes of HCR with those of CABG for MCAD. METHOD: PubMed, EMBASE and Cochrane Library databases, as well as conference proceedings, were searched for eligible studies published up to March 2014. We calculated summary odds ratios (OR) for primary endpoints (death, stroke; myocardial infarction (MI); target vessel revascularization (TVR); major adverse cardiac or cerebrovascular events (MACCEs)) and secondary endpoints (atrial fibrillation (AF); renal failure; length of stay in the intensive care unit (LoS in ICU); length of stay in hospital (LoS in hospital); red blood cell (RBC) transfusion). Data from 6176 participants were derived from ten cohort studies. RESULTS: HCR was non-inferior to CABG in terms of MACCEs during hospitalization (odds ratio (OR), 0.68, 95% confidence interval (CI), 0.34-1.33)and at one-year follow-up(0.32, 0.05-1.89) , and no significant difference was found between HCR and CABG groups in in-hospital and one-year follow-up outcomes of death, MI, stroke, the prevalence of AF and renal failure, whereas HCR was associated with a lower requirement of RBC transfusion and shorter LoS in ICU and LoS in hospital than CABG (weighted mean difference (WMD) -1.25, 95% CI, -1.62 to -0.88; -17.47, -31.01 to -3.93; -1.77, -3.07 to -0.46; respectively). CONCLUSION: Our meta-analysis indicates that HCR is feasible, safe and effective for the treatment of MCAD, with similar in-hospital and one-year follow-up outcome, significantly lower requirement of RBC transfusion, and faster recovery compared with CABG.