ACACA reduces lipid accumulation through dual regulation of lipid metabolism and mitochondrial function via AMPK- PPARα- CPT1A axis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a multifaceted metabolic disorder, whose global prevalence is rapidly increasing. Acetyl CoA carboxylases 1 (ACACA) is the key enzyme that controls the rate of fatty acid synthesis. Hence, it is crucial to investigate the function of ACACA in regulating lipid metabolism during the progress of NAFLD. METHODS: Firstly, a fatty liver mouse model was established by high-fat diet at 2nd, 12th, and 20th week, respectively. Then, transcriptome analysis was performed on liver samples to investigate the underlying mechanisms and identify the target gene of the occurrence and development of NAFLD. Afterwards, lipid accumulation cell model was induced by palmitic acid and oleic acid (PA ∶ OA molar ratio = 1∶2). Next, we silenced the target gene ACACA using small interfering RNAs (siRNAs) or the CMS-121 inhibitor. Subsequently, experiments were performed comprehensively the effects of inhibiting ACACA on mitochondrial function and lipid metabolism, as well as on AMPK- PPARα- CPT1A pathway. RESULTS: This data indicated that the pathways significantly affected by high-fat diet include lipid metabolism and mitochondrial function. Then, we focus on the target gene ACACA. In addition, the in vitro results suggested that inhibiting of ACACA in vitro reduces intracellular lipid accumulation, specifically the content of TG and TC. Furthermore, ACACA ameliorated mitochondrial dysfunction and alleviate oxidative stress, including MMP complete, ATP and ROS production, as well as the expression of mitochondria respiratory chain complex (MRC) and AMPK proteins. Meanwhile, ACACA inhibition enhances lipid metabolism through activation of PPARα/CPT1A, leading to a decrease in intracellular lipid accumulation. CONCLUSION: Targeting ACACA can reduce lipid accumulation by mediating the AMPK- PPARα- CPT1A pathway, which regulates lipid metabolism and alleviates mitochondrial dysfunction.

del Nido cardioplegia in surgery for aortic root disease: a historically controlled study.

BACKGROUND: To determine the safely and effectively of del Nido cardioplegia (DNC) in surgery for aortic root disease, with mild hypothermic cardiopulmonary bypass (CPB). METHODS: From July to December 2017, all patients undergoing the surgery for aortic root disease (total aortic root replacement, valve-sparing aortic root replacement and replacement of aortic valve plus ascending aorta), with mild hypothermic CPB, were retrospectively reviewed at our institution. Patients were divided into two groups based on the type of cardioplegia: the classical blood cardioplegia (CBC group) and del Nido cardioplegia (DNC group). Demographics, operative details, perioperative data and postoperative complications were recorded and compared. A propensity score matching was performed in this study. RESULTS: The preoperative data in DNC group were similar to CBC group. The volume of ultrafiltration was lower in DNC than CBC group (2,053.49±806.62 DNC vs. 2,666.00±967.14 CBC, P=0.001), when matched. The use of temporary pacemaker was more in DNC group (n=20, 46.5%, P=0.023), and the rate of automatic heart resuscitating was higher in the CBC group (92.0% vs. 72.1% DNC group, P=0.024, unmatched).There were no differences in in-hospital mortality, troponin T (mean 0.66 ng/mL for CBC group vs. 0.49 ng/mL for DNC group, P=0.152), left ventricular ejection fraction (mean 58.37% for CBC group vs. 60.07% for DNC group, P=0.395) or other postoperative complications between two groups, after matching. In subgroup analysis, the ultrafiltration volume was lower in DNC than CBC group (1,932.26±749.39 DNC vs. 2,640.00±996.24 CBC, P=0.004), when ACC time less than or equal to 90 minutes. The apache score was better in DNC group (4.75±3.41, P=0.041), when ACC time greater than 90 min. There were no statistical significances in other characteristics between groups. CONCLUSIONS: DNC is safe and effective for surgery for aortic root disease, not inferior to the CBC.

Single-dose del Nido cardioplegia used in adult minimally invasive valve surgery.

BACKGROUND: To analyze the protective effect of single-dose del Nido cardioplegia (DNC) in adult minimally invasive valve surgery. METHODS: From January to December 2017, 165 consecutive adult patients who underwent minimally invasive valve surgery by the same team of surgeons were divided into two cohorts based on the type of cardioplegia administered during surgery: (I) single-dose DNC (DNC group (n=76, male 41, female 35) used in patients from May to December, 2017 and (II) intermittent standard 4:1 blood cardioplegia based on St.Thomas solution (SBC group, n=89, male 45, female 44) used in patients from January to April, 2017. Preoperative baseline demographics, preoperative comorbidities, operative variables, postoperative complications, and patient outcomes were collected and compared between the two groups. RESULTS: Preoperative characteristics were shown to be similar between the two groups before and after propensity matching. Patients in the DNC group required a significantly lower volume of cardioplegia. The volume of ultrafiltration in the DNC group was substantially higher than that in the SBC group. The spontaneous return of heartbeat rate in the DNC group was considerably higher than that in the SBC group (97.0% vs. 78.8%, P=0.006). The Euroscore II in the DNC group was markedly lower than that in the SBC group (2.00 vs. 3.00, P<0.05). The level of blood urea nitrogen (BUN) in the DNC group was significantly lower than that in the SBC group (6.20 vs. 6.95, P<0.05). There were no differences in surgery procedure, cross-clamp time, bypass time, Apache score, troponin T (cTnT), brain natriuretic peptide (BNP), liver and renal function, postoperative complications or patient outcomes between two groups. Regression analysis showed that cTnT increased with the prolongation of myocardial ischemia time, and was closely related to the type of operation, but had no significant correlation with the type of cardioplegia. CONCLUSIONS: In our initial experience, single-dose DNC in adult minimally invasive valve surgery in which the cross-clamp time was mostly less than 90 min, achieved equivalent myocardial protection and clinical outcomes when compared with standard whole blood cardioplegia. In addition, single-dose DNC made the minimally invasive valve surgery procedure progress in a smoother and more convenient fashion.

Single Femoral Venous Drainage Versus Both Vena Cava Drainage in Isolated Repeat Tricuspid Valve Surgery.

To assess the potential advantages of minimally invasive surgery using a single femoral venous drainage method versus femoral venous and superior vena cava or jugular venous drainage method during repeat tricuspid valve surgery.From January 2010 to December 2016, 50 repeat tricuspid valve procedures were performed using a minimally invasive approach without aortic cross-clamping at our institution. The arterial cannula was inserted into the femoral artery, and at the same time, the venous cannula was placed in the femoral vein in 28 patients (FV group) during cardiopulmonary bypass (CPB). The venous cannula was inserted into the femoral vein and the superior vena cava or jugular vein in 22 patients (FSV group).Overall, 36 patients underwent tricuspid valve replacement (TVR) and 14 patients underwent tricuspid valvuloplasty (TVP). The CPB time and operation time, respectively, were 72.96 ± 25.90 minutes versus 78.59 ± 31.95 minutes (P = 0.495) and 170.75 ± 73.31 minutes versus 228.87 ± 61.45 minutes (P = 0.004) in the FV group versus the FVS group. There were no significant differences in the ventilator-assisted time, the first-day LVEF, and the intensive care unit (ICU) stay between the FV group and the FSV group.Both types of drainage were effective and could ensure safety during the operative procedure. The vacuum-assisted single femoral venous drainage method simplified the minimally invasive isolated repeat tricuspid valve surgical process more significantly and is the more appropriate choice.

Superior vena cava reconstruction under the left internal jugular vein to left femoral vein bypass support.

The complete surgical resection of malignant thymoma is recommended. We present a rare case of tumor resection and superior vena cava (SVC) reconstruction under veno-venous bypass support from the left internal jugular vein to the left femoral vein. The full amount of systemic heparinization (3 mg/kg) was avoided. The surgical pathology revealed thymic squamous cell carcinoma. No complications such as fatal extensive bleeding, coagulopathy, thromboembolism or transfusion reaction were found postoperatively. The patient was discharged home uneventfully. The support of this veno-venous bypass allows a safe and feasible thymic tumor resection and SVC reconstruction.

A New Venous Drainage Technique in Minimally Invasive Redo Tricuspid Surgery: Vacuum-Assist Venous Drainage via a Single Femoral Venous Cannula.

OBJECTIVE: To summarise the experiences of applying vacuum-assist with a single femoral venous cannula drainage technique in minimally invasive isolated redo tricuspid surgery. METHODS: Eight consecutive patients underwent minimally invasive redo tricuspid surgery through a right thoracotomy at our institute. All of the patients had isolated significant tricuspid regurgitation after previous cardiac surgeries, and received minimally invasive redo tricuspid surgery. The arterial cannula was inserted into the femoral artery, and at the same time, the venous cannula was placed into the femoral vein. The venous cannula was guided by transoesophageal echocardiography and reached the superior vena cava (SVC). The caval veins did not need to be snared with the heart beating during the operation, but applying the vacuum-assisted venous drainage (VAVD) controller was necessary. RESULTS: This cannulation makes it possible to achieve adequate drainage (3.48±0.44L/min) and accomplishes complete arterial perfusion. Most importantly, it guarantees a good visual field without blood and allows safe surgery. The average time of cardiopulmonary bypass (CPB) was 68.25±13.84min. The length of ICU and hospital stays were 4.13 ±3.52 days and 8.14±4.98 days, respectively. In eight patients, there was no early death in the hospital. One patient experienced acute renal dysfunction. CONCLUSION: Vacuum-assist venous drainage via a single femoral venous cannula in isolated redo tricuspid surgery is safe, effective, reliable, and significantly simplifies the procedure.

Intravitreal anti-VEGF injections for treating wet age-related macular degeneration: a systematic review and meta-analysis.

AIMS: Age-related macular degeneration (AMD) is the main cause of blindness. Anti-vascular endothelial growth factor is used to prevent further neovascularization due to wet AMD. The purpose of this systematic review was to investigate the effect and protocol of anti-vascular endothelial growth factor treatment on wet AMD. METHODS: A comprehensive literature search was performed in PubMed, Embase, the Cochrane Library, CNKI, and reference lists. Meta-analysis was performed using Stata12.0 software, best corrected visual acuity (BCVA), retinal thickness, and lesion size were evaluated. RESULTS: Twelve randomized controlled trials spanning from 2010 to 2014 and involving 5,225 patients were included. A significant difference was observed between the intravitreal ranibizumab (IVR) group and the intravitreal bevacizumab group (standard mean difference = -0.14, 95% confidence interval [CI] = -0.23 to -0.05). No significant differences were observed in best corrected VA, retinal thickness, or lesion size between IVR and the intravitreal aflibercept group. Compared to monthly injection, IVR as-needed injections (PRN) can raise VA by 1.97 letters (weighted mean difference = 1.97, 95% CI = 0.14-3.794). Combination therapy of IVR and photodynamic therapy can significantly raise VA by 2.74 letters when combined with IVR monotherapy (weighted mean difference = 2.74, 95% CI = 0.26-5.21). CONCLUSION: The superiority remains unclear between IVR and intravitreal bevacizumab in the treatment of neovascular AMD. Intravitreal aflibercept dosed every 2 months required fewer injection times, but produced similar efficacy as monthly IVR. IVR PRN could significantly increase VA. Combined with photodynamic therapy, IVR therapy could also increase VA effectively.

Kininogen 1 and insulin-like growth factor binding protein 6: candidate serum biomarkers of proliferative vitreoretinopathy.

BACKGROUND: The aim was to validate whether kininogen 1 (KNG1) or insulin-like growth factor binding protein 6 (IGFBP-6) are serum biomarkers of proliferative vitreoretinopathy (PVR). METHODS: Samples from vitreous and corresponding serum samples were collected from patients with PVR. The donor vitreous samples and serum samples from healthy volunteers and volunteers who had undergone vitrectomies for other conditions were used as controls. The samples were subsequently analysed using Western blotting (WB) and enzyme-linked immunosorbent assay. RESULTS: The Western blotting outcomes indicated both IGFBP-6 and KNG1 could be specifically detected in the vitreous and serum samples of patients with PVR. The concentrations of KNG1 and IGFBP-6 were significantly higher in both vitreous and serum samples from patients with severe PVR than in the samples from patients with moderate PVR. The serum concentrations of KNG1 or IGFBP-6 had decreased by the post-vitrectomy examinations. The receiver operating characteristic (ROC) analyses when the concentrations of IGFBP-6 or KNG1 were greater than 181.4 pg/ml or 441.75 ng/ml, respectively, predicted severe PVR with both a sensitivity and specificity of over 70 per cent. When the concentrations of IGFBP-6 or KNG1 were greater than 98.5 pg/ml or 88.5 ng/ml, respectively, they predicted the PVR prognosis with both a sensitivity and specificity of 80 per cent. CONCLUSIONS: KNG1 and IGFBP-6 may be candidate serum biomarkers of PVR.

Elucidation of the pathogenic mechanism of rhegmatogenous retinal detachment with proliferative vitreoretinopathy by proteomic analysis.

PURPOSE: To understand the molecular mechanisms of rhegmatogenous retinal detachment (RRD) with proliferative vitreoretinopathy (PVR), the vitreous proteome in RRD patients with severe PVR (grade C or D) was investigated. METHODS: The analysis of the vitreous proteome in RRD patients with PVR (n = 24) and donor samples (n = 8) was analyzed by one-dimensional (1D) SDS-PAGE and reverse-phase liquid chromatography tandem mass spectrometry (RP-LC-MS/MS). The data were analyzed using GeneGO MetaCore software. The research followed the tenets of the Declaration of Helsinki for the use of human subjects. RESULTS: In total, 516 and 364 proteins were identified in the vitreous of RRD patients with PVR and donor samples, including 48 overlapping proteins. In the PVR vitreous samples, the levels of extracellular (EC) proteins were increased and the levels of cytoskeleton proteins were decreased. In the pathologic process of PVR, inflammation was identified as an important GeneGo network. Furthermore, the complement and coagulation cascade was the essential pathway. Among the interaction network, the key node proteins in this network were p53 and transcription factor E2F1, respectively. CONCLUSIONS: 1D-SDS-PAGE coupled with RP-LC-MS/MS is a valuable resource to aid in the characterization of the proteome of RRD patients with PVR. Inflammation is the important pathologic process of PVR, while complement and coagulation cascade was the crucial pathway. p53 and E2F1 may be the new targets for successful treatment of RRD with PVR.