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Mechanical stimulus is critical to cardiovascular development during embryogenesis period.The mechanoreceptors of endocardial cells and cardiac myocytes may sense mechanical signals and initiate signal transduction that induce gene expression at a cellular level,and then translate molecular-level events into tissue-level deformations,thus guiding embryo development.This review summarizes the regulatory roles of mechanical signals in the early cardiac development including the formation of heart tube,looping,valve and septal morphogenesis,ventricular development and maturation.Further,we discuss the potential mechanical transduction mechanisms of platelet endothelial cell adhesion molecule 1-vascular endothelial-cadherin-vascular endothelial growth factor receptor 2 complex,primary cilia,ion channels,and other mechanical sensors that affect some cardiac malformations.
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Animals , Humans , Heart/embryology , Mechanotransduction, Cellular , Myocytes, Cardiac/physiology , Vascular Endothelial Growth Factor A/metabolismABSTRACT
OBJECTIVE@#To introduce the design of customized pelvic prosthesis, to evaluate the biomechanical property under three load conditions of customized pelvic prosthesis under three load cinditions.@*METHODS@#A titanium alloy prosthesis for reconstruction of pelvic tumors was designed by CAD software. The strength and stiffness of the custom prosthesis under static and slow gait conditions were analyzed and evaluated by finite element method.@*RESULTS@#The results of the finite element analysis suggested that the maximum von Mises stress in the pelvic under three load conditions were 39.0, 202.8 and 42.4 MPa; the maximum displacement were 0.199, 0.766 and 0.847 mm. The maximum von Mises stress in the prosthesis under three load conditions were 62.3, 318 and 468 MPa. The maximum Von Mises stress in the Ti-alloy prosthesis and pelvic was far smaller than the yield strength of Ti-alloy.@*CONCLUSIONS@#The study can design the size and shape of prosthesis accurately according to patient's condition. The finite element method can reduce the bone stress level and fracture risk, prolong the service life of prostheses, and ensure the safety and stability of the postoperative patients under normal gait.
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Humans , Biomechanical Phenomena , Finite Element Analysis , Fractures, Bone , Gait , Prostheses and Implants , Prosthesis Design , Stress, MechanicalABSTRACT
This study aims to evaluate the clinical outcomes of endoscopic vein harvesting (EVH) for coronary artery bypass grafting (CABG) in obese patients.Totally,153 obese patients who underwent EVH (n=81) or standard bridging technique (SBT,n=72) in CABG surgery from May 2012 to October 2014 in our hospital were enrolled in this retrospective non-randomized controlled study.The general situation of operation,postoperative complications and short medium-term outcomes were analyzed.The baseline characteristics were similar between these two groups (P＞0.05).There were no statistical differences in total operation time (226±28 min vs.224±30 min,P＞0.05),number of damaged vessels (0.12±0.05 vs.0.16±0.06,P＞0.05) and short medium-term outcomes including revascularization rate (1.25％ vs.2.78％,P＞0.05),vessel dysfunction rate (11.25％ vs.11.11％,P＞0.05) and mortality (0.00％ vs.0.00％,P＞0.05).Use of EVH was associated with significant reduction of total harvesting time (41±6 min vs.63±11min,P＜0.05),incision length (4.4±1.1 cm vs.18.2±4.5 cm,P＜0.05) and postoperative lower extremity complications (P＜0.05).EVH can reduce the risk of wound complications,whereas does not influence short-and medium-term outcomes in obese patients.It can be considered a reliable procedure of harvesting vessel conduits for obese patients undergoing CABG.
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This study aims to evaluate the clinical outcomes of endoscopic vein harvesting (EVH) for coronary artery bypass grafting (CABG) in obese patients.Totally,153 obese patients who underwent EVH (n=81) or standard bridging technique (SBT,n=72) in CABG surgery from May 2012 to October 2014 in our hospital were enrolled in this retrospective non-randomized controlled study.The general situation of operation,postoperative complications and short medium-term outcomes were analyzed.The baseline characteristics were similar between these two groups (P＞0.05).There were no statistical differences in total operation time (226±28 min vs.224±30 min,P＞0.05),number of damaged vessels (0.12±0.05 vs.0.16±0.06,P＞0.05) and short medium-term outcomes including revascularization rate (1.25％ vs.2.78％,P＞0.05),vessel dysfunction rate (11.25％ vs.11.11％,P＞0.05) and mortality (0.00％ vs.0.00％,P＞0.05).Use of EVH was associated with significant reduction of total harvesting time (41±6 min vs.63±11min,P＜0.05),incision length (4.4±1.1 cm vs.18.2±4.5 cm,P＜0.05) and postoperative lower extremity complications (P＜0.05).EVH can reduce the risk of wound complications,whereas does not influence short-and medium-term outcomes in obese patients.It can be considered a reliable procedure of harvesting vessel conduits for obese patients undergoing CABG.
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Objective To study the mechanism of right ventricular pulmonary artery coupling by fitting the pressure volume loop of pulmonary arterial hypertension patients and calculating the related parameters.Methods During January of 2015 to December of 2015,34 patients with pulmonary hypertension and 5 patients with patent oval foramen(PFO)were admitted in Wuhan Asian Heart Hospital,. Inclusion criteria for the pulmonary hypertension group were in accordance with the newest European guidelines for pulmonary hypertension . All of the patients were conducted invasive pressure catheter intervention and MRI. All the pressure data were digitized by GetData software and the CMR tools3D was used to derive right ventricular volume data, fitting the pressure volume loop and calculate the Pmax, Ees, Ea and other related parameters. 5 patients with PFO and 34 patients with pulmonary hypertension were divided into three groupswhich included:the control group (i.e. the patients with PFO), patients with pulmonary artery mean pressure less than 50 mmHg as group A and pulmonary artery mean pressure greater than or equal to 50 mmHg as group B. The pressure volume loop of the three groups were compared and the related parameters were calculated.Results The right ventricular Pmax were(53.05±12.87) mmHg, (134.73±26.38) mmHg, (207.88±65.67) mmHg, in the control group, group A and B respectively. There were significant differences when compared among the 3 groups. There was no statistical difference in Ees between the control group and group A(P>0.05). The Ees of group B was significantly higher than the control group[(1.53±0.97)vs.(0.60±0.28),P<0.05]. The Ea of group B was higher than the control[(1.34±0.74) vs.(0.39±0.15),P<0.05]. The overall ratio of Ees/Ea was lower in group B as compared to the control group [(1.12±0.47)vs.(1.62±0.51),P<0.05].Conclusions In the early stage of pulmonary hypertension, right ventricular contractility preserves and can overcome the slightly elevated afterload .The right ventricle and pulmonary artery coupled with good work. With the increasing mean pulmonary artery,the afterload of right ventricular increases and right ventricular contractility needs further increase to fight against the elevated afterload. The elevation of contractility cannot overcome the change of afterload, resulting in the off paired of mechanical efflciency, causing the right ventricle- pulmonary artery coupling decreases.
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BACKGROUND: Hallux valgus is a common orthopedic disease, and its causes are complex and treatment is varied. The mechanical analysis of hallux valgus is an issue of concern. The finite element analysis makes it predictable to treat hallux valgus. OBJECTIVE: To explore the clinical application of finite element analysis in biomechanical study of hallux valgus.METHODS: The first author searched CNKI and PubMed databases from January 1980 to March 2017 using the key words of "finite element, hallux valgus" in English and Chinese, respectively. The repetitive, irrelevant and low-quality articles were excluded. Finally 33 eligible articles were included in accordance with the inclusion criteria, and the critical issues of finite element analysis applied in hallux valgus were reviewed. RESULTS AND CONCLUSION: (1) There are many researches concerning finite element of hallux valgus, which mostly require physicians to work with engineers. These methods are already very mature, but most of the model and material properties of the data come from foreign researches. (2) The finite element analysis is important and reliable for the etiology of hallux valgus, preoperative planning and prognosis. (3) The finite element model of the hallux valgus is only used on static analysis and gait cycle analysis, the modeling details and definition of material properties still need to be improved.
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Objective The aim of our study was to investigate the influence of hexavalent chromium exposure on mRNA expression of cell cycle related genes in electroplating workers, and to provide population data for investigating the toxic mechanisms of hexavalent chromium. Methods A total of 155 cases of workers occupationally exposed to hexavalent chromium were selected, including 89 males and 66 females, and the average age of workers was 39.65±8.856 years old. Questionnaire was used to collect essential information of workers. Peripheral blood was collected from electroplating workers. The inductively couple plasma mass spectrometry (ICP-MAS) was used to measure total blood chromium content. The workers were divided into four groups according to the blood chromium content. After extracting total RNA from whole blood and reverse transcription, the mRNA expression levels of p16 and CDK6 genes were detected by real-time quantitative PCR. Meanwhile, the levels of blood chromium (BCr) and the mRNA expression of p16 and CDK6 genes were compared among four groups. The impact of BCr, smoking habits, drinking habits, gender on the mRNA expression of CDK6 gene was analyzed. Results The levels of BCr in group 1 to 4 were 0.04ppb, 0.47±0.29 ppb, 2.76±1.16 ppb, 9.36 ±4.38 ppb, respectively, and the difference between every two groups was significant (P<0.05) . The median of p16 gene expression in four groups was 4.22, 7.19, 7.47, and 14.60, respectively, and the difference between every two groups was not significant (P>0.05) . The mRNA expression levels of CDK6 gene in groups 2 to 4 were 15.05, 8.03 and 24.81, respectively, which were significantly higher than that in group 1 (P<0.05) . The results of logistic regression showed that the level of Bcr was the main influence factor, while smoking habits, drinking habits and gender had no obvious impact on the mRNA expression of CDK6 gene. Conclusions Long-term exposure of hexavalent chromium led to higher mRNA expression of CDK6 gene, and it may serve as a biomarker for workers occupationally exposed to hexavalent chromium.
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Objective To investigate the employers' and employees' satisfaction of Zhejiang Province on occupation health examination and diagnosis of occupational diseases, and to guide and to standardize the occupation health examination and occupational disease diagnosis. Methods A random sample of 953 employers, 1791 workers with health examination and 135 workers with diagnosis of occupational diseases were selected in the survey, and the questionnaire about the Satisfuction on occupation health examination and occupation disease diagnosis were used in this survey. Results A total of 2879 questionnaires were sent out, in which 2841 valid questionnaires were returned, and the effective recovery rate was 98.68%. The recognition rates on comfortable environment, clear instructions process, workflow notification, and attention notification were all above 98%. The satisfaction rates for all items were above 86%, and the total satisfaction rate was 89.27% . The total satisfaction rates of workers with health examination, workers with diagnosis of occupational diseases and employers were 89.28%, 82.03%, and 90.22%, respectively. The recognition rates on clear instructions process and attention notification, and the satisfaction rates on service attitude, result information and overall satisfaction were significantly different between different types of respondents (P<0.05) . The results of pair wise comparison showed that the satisfaction rates of workers with diseases diagnosis on service attitude, results information and overall satisfaction were significantly lower than those of employers (P<0.05) . The overall satisfaction rate of workers with diagnosis of occupational diseases was lower than that of workers with health examination (P=0.011) . The recognition rates of workers with health examination on clear instructions process and attentions notification were lower than those of employers (P<0.016) . There was a significant difference in the overall satisfaction between respondents in different regions (P<0.01) . Conclusion The service of occupational health examination and occupational disease diagnosis services should be further improved. We should better learn the demands of employees and employers, improve service attitude, optimize service processes, shorten service time, and improve service quality and satisfaction.
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Heart transplantation is considered the best treatment modality for advanced heart disease.While old age has conventionally been considered a contraindication for heart transplantation due to the reported adverse effect of advanced age,however donor hearts' shortage continues to stimulate the discussion about the recipient's upper age limit.Our study was based on a retrospective analysis for the results of 52 (18％) patients aged 60 years and older undergoing heart transplantation between May 2008 and December 2015,and these patients were compared with 236 (82％) adult recipients who were younger than 60 years at the time of transplantation and during the same period.In older group,71％ were males with the mean age of 63.38+3.55 years,and in younger group,83.4％ were males with a mean age of43.72±11.41 years (P=0.27).Dilated cardiomyopathy was the most common indication for transplantation among patients in both groups (P=0.147).In older group,the 3-month survival rate was higher than that in younger group (P=0.587),however the 6-month survival rate showed no significant difference (P=0.225).Although the 1-year survival rate was higher in older group (P=0.56),yet the 3-year survival rate between the two groups showed no statistically significant difference (P=0.48).According to our experience among older heart transplant candidates who were 60 years and older,we believe that advanced age should not be an excluding criterion to cardiac transplantation.
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Fontan surgery is a widely used palliative procedure that significantly improves the survival period of patients with complex congenital heart disease (CHD). However, it does not decrease postoperative complication rate. Previous studies suggested that elevated mean pulmonary artery pressure (mPAP) and vascular resistance lead to decreased exercise tolerance and myocardial dysfunction. Therapy with endothelial receptor antagonists (Bosentan) has been demonstrated to improve the patients' prognosis. A double-blind, randomized controlled trial was performed to explore the efficacy of Bosentan in treating patients who underwent the Fontan procedure. Eligible participants were randomly divided into Bosentan group and control group. Liver function was tested at a local hospital and the results were reported to the phone inspector every month. If the results suggested abnormal liver function, treatment would be adjusted or terminated. All the participants finished the follow-up study, with no patients lost to follow-up. Unblinding after 2-year follow-up, no mortality was observed in either group. However, secondary end-points were found to be significantly different in the comparable groups. The cardiac function and 6-min walking distance in the Bosentan group were significantly superior to those in the control group (P=0.018 and P=0.027). Bosentan could improve New York Heart Association (NYHA) functional status and improve the results of the 6-min walking test (6MWT) in Fontan patients post-surgery, and no other benefits were observed. Furthermore, a primary meta-analysis study systematically reviewed all the similar clinical trails worldwide and concluded an overall NYHA class improvement in Fontan patients who received Bosentan treatments.
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Adolescent , Child , Female , Humans , Male , Double-Blind Method , Follow-Up Studies , Fontan Procedure , Heart Defects, Congenital , Drug Therapy , Pathology , General Surgery , Liver , Pathology , Palliative Care , Prognosis , Sulfonamides , Treatment OutcomeABSTRACT
OBJECTIVE:To compare the efficacy,safety,vascular endothelial growth factor(VEGF)and matrix metallopro-teinase-2 (MMP-2) of docetaxel combined with carboplatin and paclitaxel combined with cisplatin (DDP) in the treatment of ad-vanced ovarian cancer. METHODS:120 patients with advanced ovarian cancer were randomly divided into docetaxel combined with carboplatin group(60 cases)and paclitaxel combined with DDP group(60 cases). Docetaxel combined with carboplatin group received 70 mg/m2 Docetaxel injection,intravenous infusion of 1 h,d1;50 mg/m2 carboplatin injection,intravenous infusion of 1 h,d2. Paclitaxel combined with DDP group received 135 mg/m2 Paclitaxel injection,intravenous infusion of 24 h,d1;30 mg/m2 DDP for injection,intravenous infusion,d3;60 mg/m2 Paclitaxel injection (a maximum of 2.0 m2) by intraperitoneal infusion,d8. 3-week was regarded as 1 treatment course,and it lasted 6 courses. Clinical efficacy,VEGF,MMP-2,progression-free survival, overall survival before and after treatment,mortality rate within 2 years of treatment and the incidence of adverse reactions in 2 groups were compared. RESULTS:There were no significant differences in the objective response rate,disease control rate,mortal-ity rate,incidence of adverse reactions between 2 groups(P>0.05). The progression-free survival in docetaxel combined with car-boplatin group was significantly longer than paclitaxel combined with DDP group,the difference was statistically significant (P0.05). After treat-ment,VEGF and MMP-2 level in 2 groups were significantly lower than before,and VEGF at different time points and MMP-2 level after 4 weeks,8 weeks and 12 weeks of treatment in docetaxel combined with carboplatin group were lower than paclitaxel combined with DDP group,the differences were statistically significant(P<0.05). CONCLUSIONS:Docetaxel combined with car-boplatin and paclitaxel combined with DDP shows similar efficacy and safety in the treatment of advanced ovarian cancer,but docetaxel carboplatin combined with is superior to paclitaxel combined with DDP in reducing VEGF and MMP-2 and improving pro-gression-free survival.
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Aims: This study aims to evaluate benefit and safety compared dual antiplatelet therapy with single aspirin therapy after coronary artery bypass grafting. Study Design: A systematic review and Meta-analysis. Place and Duration of Study: Medline, Embase, ScienceDirect and Cochrane Library databases were searched for randomized controlled trials or observational studies focusing on anticoagulant therapy after coronary artery bypass grafting until December 2014. Methodology: Endpoints included postoperative mortality, bleeding events, myocardial infraction, stroke, repeat revascularization and graft occlusion. All these endpoints were compared between dual antiplatelet therapy and single aspirin therapy. Newcastle-Ottawa and Jadal scale were used to assess the quality of observational studies and randomized controlled trials respectively. Software R2.15.2 was utilized for Meta-analysis. Results: 15 studies composed of 31,365 patients were included. Compared with single aspirin therapy, dual antiplatelet therapy resulted in reducing risk of vein graft occlusion (OR=0.53, 95%CI 0.36-0.81, P=0.001), but no significant difference for artery graft occlusion (OR=0.91, 95%CI 0.39-2.12, P=0.882), Risk of postoperative mortality (OR=0.57, 95%CI 0.38-0.85, P=0.006) and repeat revascularization (OR=0.15, 95%CI 0.05-0.45, P=0.001) was also reduced. There were no significant difference for MI (OR=0.77, 95%CI 0.55-1.09, P=0.137), Stroke (OR=0.85, 95%CI 0.60-1.19, P=0.330) and bleeding (OR=0.95, 95%CI 0.82-1.09, P=0.465). In subgroup analysis of off-pump CABG, dual antiplatelet therapy reduced risk of graft occlusion (OR=0.49, 95%CI 0.30-0.82, P=0.006), MI (OR=0.28, 95%CI 0.11-0.72, P=0.009), mortality (OR=0.39, 95%CI 0.25-0.60, P<0.001), and did not increase risk of bleeding (OR=0.75, 95%CI 0.55-1.02, P=0.066). Conclusions: Dual antiplatelet therapy reduced risk of postoperative graft occlusion and mortality in the early and late postoperative phase after CABG. It appeared to be more beneficial for off-pump CABG.
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<p><b>BACKGROUND</b>Although heart transplantation (HTx) has become a standard therapy for end-stage heart diseases, experience with pediatric HTx is limited in China. In this article, we will try to provide the experience with indications, complications, perioperative management, immunosuppressive therapy, and survival for pediatric HTx based on our clinical work.</p><p><b>METHODS</b>This is a retrospective chart review of the pediatric patients undergoing HTx at Department of Cardiovascular Surgery of Union Hospital from September 2008 to December 2014. We summarized the indications, surgical variables, postoperative complications, and survival for these patients.</p><p><b>RESULTS</b>Nineteen pediatric patients presented for HTx at Union Hospital of Tongji Medical College, of whom 10 were male. The age at the time of transplantation ranged from 3 months to 18 years (median 15 years). Patient weight ranged from 5.2 kg to 57.0 kg (median 38.0 kg). Pretransplant diagnosis included cardiomyopathy (14 cases), complex congenital heart disease (3 cases), and tumor (2 cases). All recipients received ABO-compatible donor hearts. Postoperative complications occurred in 12 patients, including cardiac dysfunction, arrhythmia, pulmonary infection, renal dysfunction, and rejection. Two of them experienced cardiac failure and required extracorporeal membrane oxygenation. The immunosuppression regimen was comprised of prednisone, a calcineurin inhibitor, and mycophenolate. All patients recovered with New York Heart Association (NYHA) Class I-II cardiac function and were discharged. Only one patient suffered sudden death 19 months after transplantation.</p><p><b>CONCLUSION</b>Orthotopic HTx is a promising therapeutic option with satisfying survival for the pediatric population in China with end-stage heart disease.</p>
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Adolescent , Child , Female , Humans , Infant , Male , China , Heart Transplantation , Immunosuppressive Agents , Therapeutic Uses , Retrospective Studies , Treatment OutcomeABSTRACT
<p><b>BACKGROUND</b>Compared to the Western countries, Chinese patients present a special primary disease spectrum, diverse valvular pathogenesis, and different postoperational anticoagulation strategy. This research aimed to evaluate the mid- to long-term clinical performance of Hancock II bioprosthesis in the Chinese population.</p><p><b>METHODS</b>This study retrospectively reviewed all patients who received surgical treatments with at least one Hancock II bioprosthesis implantation from January 2004 to December 2013 at a single center in China. Totally 647 patients were included in the clinical evaluation, and 629 patients were successfully discharge, among whom 605 patients were completely followed-up. The follow-up rate was 96.2%. The mean and median follow-up time was 62.0 ± 59.0 and 56.0 months, respectively. Postoperative outcomes of survival rates, reoperations and valve related morbidities were assessed. Continuous and categorical variables were compared using the t -test and Chi-square test, respectively. Survival and freedom from adverse events were calculated by using a Kaplan-Meier method.</p><p><b>RESULTS</b>The overall in-hospital mortality was 2.8% (18/647) while there were 34 deaths (5.6%, 34/605) in the follow-up stage after discharge. The overall survival rate was 94.6% and 82.7% at 5 years and 10 years, respectively. The cumulative survival rate of 10 years was 82.8% in AVR group, 84.4% in MVR group, and 78.4% in DVR group. The overall rate of freedom from reoperations was 95.5% at 5 years and 86.8% at 10 years. The freedom from reoperation at 10 years was 87.0%, 88.1%, and 84.0% in AVR, MVR, and DVR group, respectively. The freedom from morbidities at 10 years was: 90.3% for thromboembolism, 95.2% for hemorrhage, 97.5% for prosthesis endocarditis, 95.9% for paravalvular leak, and 94.6% for structural valve deterioration, respectively.</p><p><b>CONCLUSIONS</b>Hancock II bioprosthesis exhibited a satisfactory mid- to long-term durability and promising clinical performance in the Chinese population. The occurrence rates of death and other adverse events in this single-center study were overall coincident and quite acceptable when compared with existing data.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Aortic Valve , General Surgery , Bioprosthesis , China , Heart Valve Diseases , General Surgery , Heart Valve Prosthesis , Retrospective Studies , Survival RateABSTRACT
Objective To explore the genetic defects in patients with pulmonary atresia (PA).Methods Twenty-three patients with PA were studied from recent 1 year.There were 15 boys and 8 girls,aged 2 days to 10 years.Among them,there were 3 cases with complete ventricle septum,20 cases with VSD,3 cases without main pulmonary trunk,20 cases with PDA,6 cases with integrated major aorto-pulmonary collateral arteries(MAPCAs),3 cases with integrated right aortic arch,2 cases with integrated extra-cardiac abnormality with the manifestation of facial abnormality,1 case with integrated aberrant right subclavian artery,and 1 case with integrated tracheal bronchus.The chromosomes of the children were routinely analyzed.Negative chromosomes were examined to identify the 22ql 1.2 microdeletion by fluorescence in situ hybridization (FISH) test.Results One case of trisomy syndrome was found.22ql 1.2 microdeletion was found in 3 cases.Among 22q1 1 microdeletion cases,1 case was intact ventricular septum,2 cases were integrated VSD.22q1 1.2 microdeletion was not found in the rest 19 cases.Conclusions Twenty-one trisomy syndrome and Del 22q1 1.2 syndrome may play an important role in the pathogenesis of PA.TBX1 probe can be used to examine 22q1 1.2 microdeletion.Del 22q1 1.2 syndrome was suspected in cases of incorporating aberrant subclavian artery,MAPCAs and severe poor development of pulmonary artery.
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The main pathogenesis of saphenous vein graft neointimal hyperplasia after coronary artery bypass grafting (CABG) is inflammation-caused migration and proliferation of vascular smooth muscle cells (VSMCs). Janus kinase 2/signal transducer and activators of transcription 3 (JAK2/STAT3) pathway is an important signaling pathway through which VSMCs phenotype conversion occurs. Suppressor of cytokine signaling 3 (SOCS3) is the classic negative feedback inhibitor of JAK2/STAT3 pathway. Growing studies show that SOCS3 plays an important anti-inflammatory role in numerous autoimmune diseases, inflammatory diseases and inflammation-related tumors. However, the effect and mechanism of SOCS3 on vein graft disease is unclear. The purpose of this study was to investigate the effects of SOCS3 on the inflammation, migration and proliferation of VSMCs in vitro and the mechanism. The small interference RNA plasmid targeting rat SOCS3 (SiRNA-rSOCS3) and the recombinant adenovirus vector carrying rat SOCS3 gene (pYrAd-rSOCS3) were constructed, and the empty plamid (SiRNA-control) and vector (pYrAd-GFP) only carrying GFP reported gene were constructed as control. The rat VSMCs were cultured. There were two large groups of A (SOCS3 up-regulated): control group, IL-6/IFN-γ group, IL-6/IFN-γ+pYrAd-rSOCS3 group, IL-6/IFN-γ(+)pYrAd-GFP group; and B (SOCS3 down-regulated): control group, IL-6/IFN-γ group, IL-6/IFN-γ+SiRNA-rSOCS3 group and IL-6/ IFN -γ+SiRNA-control group. The pYrAd-rSOCS3 and SiRNA-rSOCS3 were transfected into VSMCs induced by IL-6/IFN-γ. After 24 h, real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expression of SOCS3, STAT3 (only by Western blotting), P-STAT3 (only by Western blotting), IL-1β, IL-6, TNF-α, MCP-1 and ICAM-1. The MTT, Transwell assay and flow cytometry were used to examine VSMCs proliferation, migration and cell cycle progression, respectively. As compared with control group, the mRNA and protein expression of SOCS3, STAT3, P-STAT3, IL-1β, IL-6, TNF-α, MCP-1 and ICAM-1 was significantly up-regulated in VSMCs stimulated by IL-6/IFN-γ. However, in VSMCs transfected with pYrAd-rSOCS3 before stimulation with IL-6/IFN-γ, the expression of SOCS3 mRNA and protein was further up-regulated, and that of STAT3, P-STAT3, IL-1β, IL-6, TNF-α, MCP-1 and ICAM-1 was significantly down-regulated as compared with IL-6/IFN-γ group and IL-6/IFN-γ+pYrAd-GFP group. The expression of those related-cytokines in IL-6/IFN-γ+SiRNA-rSOCS3 group was markedly increased as compared with IL-6/IFN-γ group and IL-6/IFN-γ+SiRNA-control group. The absorbance (A) values, the number of cells migrating to the lower chamber, and percentage of cells in the G2/M+S phase were increased in VSMCs stimulated by IL-6/IFN-γ. In VSMCs incubated with pYrAd-rSOCS3 or SiRNA-rSOCS3 before IL-6/IFN-γ stimulation, the A values, the number of cells migrating to the lower chamber, and the percentage of cells in the G2/M+S phase were significantly decreased, and increased respectively. These results imply that IL-6/IFN-γ, strong inflammatory stimulators, can promote transformation of VSMCs phenotype form a quiescent contractile state to a synthetic state by activating JAK2/STAT3 pathway. Over-expresssed SOCS3 might inhibit pro-inflammatory effect, migration and growth of VSMCs by blocking STAT3 activation and phosphorylation. These data in vitro confirm that SOCS3 may play a negatively regulatory role in development and progression of vein graft failure. These conclusions can provide a novel strategy for clinical treatment of vein graft diseases and a new theoretic clue for related drug development.
Subject(s)
Animals , Male , Rats , Blotting, Western , Cell Cycle , Cell Movement , Cell Proliferation , Cells, Cultured , Cytokines , Genetics , Metabolism , Flow Cytometry , Gene Expression , Inflammation Mediators , Metabolism , Interferon-gamma , Genetics , Metabolism , Pharmacology , Interleukin-6 , Genetics , Metabolism , Pharmacology , Janus Kinase 2 , Metabolism , Muscle, Smooth, Vascular , Cell Biology , Myocytes, Smooth Muscle , Metabolism , Phosphorylation , RNA Interference , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , STAT3 Transcription Factor , Genetics , Metabolism , Signal Transduction , Suppressor of Cytokine Signaling 3 Protein , Suppressor of Cytokine Signaling Proteins , Genetics , MetabolismABSTRACT
The main pathogenesis of saphenous vein graft neointimal hyperplasia after coronary artery bypass grafting (CABG) is inflammation-caused migration and proliferation of vascular smooth muscle cells (VSMCs). Janus kinase 2/signal transducer and activators of transcription 3 (JAK2/STAT3) pathway is an important signaling pathway through which VSMCs phenotype conversion occurs. Suppressor of cytokine signaling 3 (SOCS3) is the classic negative feedback inhibitor of JAK2/STAT3 pathway. Growing studies show that SOCS3 plays an important anti-inflammatory role in numerous autoimmune diseases, inflammatory diseases and inflammation-related tumors. However, the effect and mechanism of SOCS3 on vein graft disease is unclear. The purpose of this study was to investigate the effects of SOCS3 on the inflammation, migration and proliferation of VSMCs in vitro and the mechanism. The small interference RNA plasmid targeting rat SOCS3 (SiRNA-rSOCS3) and the recombinant adenovirus vector carrying rat SOCS3 gene (pYrAd-rSOCS3) were constructed, and the empty plamid (SiRNA-control) and vector (pYrAd-GFP) only carrying GFP reported gene were constructed as control. The rat VSMCs were cultured. There were two large groups of A (SOCS3 up-regulated): control group, IL-6/IFN-γ group, IL-6/IFN-γ+pYrAd-rSOCS3 group, IL-6/IFN-γ(+)pYrAd-GFP group; and B (SOCS3 down-regulated): control group, IL-6/IFN-γ group, IL-6/IFN-γ+SiRNA-rSOCS3 group and IL-6/ IFN -γ+SiRNA-control group. The pYrAd-rSOCS3 and SiRNA-rSOCS3 were transfected into VSMCs induced by IL-6/IFN-γ. After 24 h, real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expression of SOCS3, STAT3 (only by Western blotting), P-STAT3 (only by Western blotting), IL-1β, IL-6, TNF-α, MCP-1 and ICAM-1. The MTT, Transwell assay and flow cytometry were used to examine VSMCs proliferation, migration and cell cycle progression, respectively. As compared with control group, the mRNA and protein expression of SOCS3, STAT3, P-STAT3, IL-1β, IL-6, TNF-α, MCP-1 and ICAM-1 was significantly up-regulated in VSMCs stimulated by IL-6/IFN-γ. However, in VSMCs transfected with pYrAd-rSOCS3 before stimulation with IL-6/IFN-γ, the expression of SOCS3 mRNA and protein was further up-regulated, and that of STAT3, P-STAT3, IL-1β, IL-6, TNF-α, MCP-1 and ICAM-1 was significantly down-regulated as compared with IL-6/IFN-γ group and IL-6/IFN-γ+pYrAd-GFP group. The expression of those related-cytokines in IL-6/IFN-γ+SiRNA-rSOCS3 group was markedly increased as compared with IL-6/IFN-γ group and IL-6/IFN-γ+SiRNA-control group. The absorbance (A) values, the number of cells migrating to the lower chamber, and percentage of cells in the G2/M+S phase were increased in VSMCs stimulated by IL-6/IFN-γ. In VSMCs incubated with pYrAd-rSOCS3 or SiRNA-rSOCS3 before IL-6/IFN-γ stimulation, the A values, the number of cells migrating to the lower chamber, and the percentage of cells in the G2/M+S phase were significantly decreased, and increased respectively. These results imply that IL-6/IFN-γ, strong inflammatory stimulators, can promote transformation of VSMCs phenotype form a quiescent contractile state to a synthetic state by activating JAK2/STAT3 pathway. Over-expresssed SOCS3 might inhibit pro-inflammatory effect, migration and growth of VSMCs by blocking STAT3 activation and phosphorylation. These data in vitro confirm that SOCS3 may play a negatively regulatory role in development and progression of vein graft failure. These conclusions can provide a novel strategy for clinical treatment of vein graft diseases and a new theoretic clue for related drug development.
ABSTRACT
<p><b>OBJECTIVE</b>To improve the biological properties of decellularized aortic valves by polyethylene glycol (PEG)-mediated covalent incorporation of vascular endothelial growth factor (VEGF).</p><p><b>METHODS</b>PEG crosslinking of decellularized aortic valves were completed via a Michael-type addition reaction, followed by covalent incorporation of VEGF through another Michael-type addition reaction between the unsaturated propylene acyl of PEG and the thiol groups on cysteine residues of VEGF. The effect of VEGF incorporation was evaluated by enzyme-linked immunosorbent assay (ELISA) and immune fluorescence assay. The endothelial progenitor cells (EPCs) were seeded on decellularized aortic valves with or without these modifications, and after 10 days of culture, the valves were examined for DNA content and by hematoxylin-eosin staining and scanning electron microscopy.</p><p><b>RESULTS</b>Immune fluorescence and ELISA showed that the maximal VEGF incorporation on the decellularized aortic valve reached 908.94∓0.27 pg. Compared with the unmodified valves and the valves with PEG crosslinking, decellularized aortic valves with covalent incorporation of VEGF significantly promoted the adhesion and proliferation of EPCs, which formed a confluent cell monolayer on the valve surface.</p><p><b>CONCLUSIONS</b>PEG-mediated covalent incorporation of VEGF in the decellularized aortic valves improves the adhesion and proliferation of the seeded EPCs to facilitate the construction of tissue-engineered heart valves.</p>
Subject(s)
Animals , Aortic Valve , Cell Adhesion , Cell Proliferation , Cells, Cultured , Endothelial Cells , Cell Biology , Heart Valve Prosthesis , Polyethylene Glycols , Pharmacology , Stem Cells , Cell Biology , Swine , Tissue Engineering , Vascular Endothelial Growth Factor A , PharmacologyABSTRACT
<p><b>BACKGROUND</b>Although heart transplantation has become a standard therapy for end-stage heart disease, there are few published studies regarding the use of transplant organs from marginal donors. Here we describe the clinical outcome we have obtained using marginal donor hearts.</p><p><b>METHODS</b>We analyzed 21 cases of orthotopic heart transplantation for end-stage heart disease performed in our department between September 2008 and July 2010. Of these patients, six received hearts from marginal donors and the remainder received standard-donor hearts. The two groups were compared in terms of both mortality and the incidence of perioperative complications such as infection, acute rejection, and right heart insufficiency.</p><p><b>RESULTS</b>The 1-year survival rate of both groups was 100%. Only one death was recorded in standard-donor group during follow-up. Patients who received marginal donor hearts (83%) experienced more early complications than did the standard-donor-heart group (13%), but the mortality of the two groups was the same. The duration of post-ICU stay was greater in the marginal donor group than in the standard-donor group, (35.5 ± 17.4) days and (21.7 ± 2.6) days, respectively (P < 0.05).</p><p><b>CONCLUSIONS</b>The use of marginal donor hearts increases the number of patients who can receive and benefit from transplants. However, it may introduce an increased risk of early complications, thus care should be taken both in the choice of patients who will receive marginal donor hearts and in the perioperative treatment of those for whom the procedure is performed.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Antibodies, Monoclonal , Therapeutic Uses , Heart Transplantation , Methods , Immunosuppressive Agents , Therapeutic Uses , Methylprednisolone , Therapeutic Uses , Recombinant Fusion Proteins , Therapeutic Uses , Tissue DonorsABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy of using small interfering RNA targeting TF as a therapy for vein graft failure.</p><p><b>METHODS</b>External jugular vein to carotid artery interposition vein grafts, which were applied to a low flow condition, were made in 120 Sprague-Dawley rats weighing 260 to 300 g. These rats were randomly divided into 4 groups, 30 rats each group. Group A was atelocollagen-TF Stealth Select RNAi group. Group B was atelocollagen-TF Stealth RNAi group. Group C was atelocollagen group. Group D was control group. Small interfering RNA mixed with atelocollagen was administrated to the external wall of grafted veins. The TF protein expression of vein grafts was analyzed by Western blot at 1, 3, 7, 14, and 28 d postoperatively, and by immunochemistry at 3 d postoperatively. The proliferation index was determined at 14 d postoperatively. Neointimal hyperplasia was evaluated at 28 d postoperatively. BLOCK-iT fluorescent oligo was used to confirm its stability and successful transfer into the vein graft wall at 3 and 7 d postoperatively for another group (n=12).</p><p><b>RESULTS</b>Fluorescence of BLOCK-iT fluorescent oligo could be detected in the graft wall even at 7 d postoperatively. Knockdown of the TF expression was achieved by perivascular application of siRNA using atelocollagen. Compared with control group, the intima thickness at 28 d after grafting was significantly reduced (P < 0.05). This phenomenon was preceded by significant reduction of cell proliferation in siRNA-treated grafts at 14 d postoperatively (P < 0.05).</p><p><b>CONCLUSION</b>The expression of TF in vein grafts can be effectively inhibited by specific siRNAs using a atelocollagen-based nonviral delivery approach in vivo, so that the neointimal thickening can be prevented. Transplants;</p>