Objective To compare clinical outcomes in cardiac transplant recipients treated with individualized dosing (ID) and fixed dosing (FD) of mycophenolate mofetil (MMF).Methods Fortyeight de novo cardiac transplant patients in ID group received MMF (2.0 g/day) in combination with calcineurin inhibitors and prednisone.The MMF dosages were adjusted individually based on clinical events and MPA trough levels (MPA-C0).The target range of C0 was maintained within 2.0-4.0rng/L.The FD group included 55 recipients retrospectively from the transplant database who were also treated with MMF (2.0 g/day).In this group,the MMF dose adjustment was performed empirically according to clinical events only.All of the follow-up data were collected up to 12 months post-transplantation.Results The follow-up rate was 95.8％ and the mean MPA-AUC0-12 was (54.37± 17.03) rng h-1 L-1 in the ID group.The mean MPA-C0 on the day 7 post-transplantation was significantly higher in the ID group than that at 12th month [(3.44 ± 0.58) mg/L vs.(2.79 ± 0.54)mg/L] (P＜0.05).The dose of MMF was significantly lower in the ID group at 4th week posttransplantation than in control group [(1.49± 0.48) g/day vs.(1.96 ± 0.39) g/d] (P＜0.05),while there was no significant difference at 12 th month post-transplantation [(1.61 ± 0.77) g/day vs.(1.68 ± 0.84) g/day] (P＞ 0.05).No significant difference was found in the incidence of acute rejection episode between two groups (8.7％ vs.9.1％,P＞0.05).57.6％ of overall side effects were observed within one month postoperatively,and the incidence of MPA-related side effects was significantly lower in the ID group than in the control group (47.8％ vs.67.3％,P＜0.05).Conclusion It was demonstrated that individualized use of MMF based on therapeutic drug monitoring may prevent MMF-related side effect and appears to be valuable to optimize the treatment of cardiac transplantation.

Objective Ascending aortic dissection(AAD),for which the pathogenesis remains unknown,is life-threatening.Matrix metalloproteinase-9(MMP-9)and the pathological changes of vascular smooth muscle cells(VSMCs)have been reported to have roles the pathogenesis.The study examined the expression of matrix metalloproteinase-9(MMP-9)and the pathological changes of,VSMCs in patients with AAD.Methods AAD samples were taken from 35 patients(disease group)in acute phase during aortic replacement operation for AAD and control samples were corresponding part of ascending aorta(control group,n=21)collected from the donor hearts for transplantation.Transmission electron microscepe,hematoxylin-eosin(H-E)staining.Mallory staining were used for observing the pathological changes of VSMCs and matrix in the affected aortic wall.The immunohistochemicai staining of MMP-9 was carried out in both groups and semi-quantified by staining intensity analysis.The affected patients were further grouped according to the diameter of dissected aorta as with a AAD of <55 mm or with a AAD of≥55 mm.The associations of clinical factors,such as smoking status,hypertensive disease and aneurysm diameter,with the expression of MMP-9 were analyzed.Results Increased synthetic function of VSMCs with decreased density,disrupted elastic fibers and fibrosis in the dissected aortic wall were observed in the disease group,but not in the control group.MMP-9 was scarcely expressed in the aortic wall of the patients in the control group,though it was notably expressed in the VSMCs of disease group.Both subgroups presented more MMP-9 than the control group(both P<0.001).In the disease group,sub-group with a AAD diameter of ≥55 mm presented more MMP-9 than that with a diameter of <55 mm(P<0.05).MMP-9 expression was positively correlated with a history of hypertension(P<0.01)or a great aneurysm diameter(P<0.05).MMP-9 expression was not associated with age,smoking status or other clinical factors.Conclusion Increased secretion of VSMCs and the expression of MMP-9 induced by elevated blood pressure may lead to the destruction of matrix proteins.The resulting fibrosis of the aortic wall would decrease the tensile strength of the wall.When the fibrotic aortic wall dilated further,the increased expression of MMP-9 would aggravate the damage to the wall.It can be speculated that acute AAD would occur as a result of partial tearing of the aortic intima.

Objective Mechanisms for the dissection of aorta, a devastating disease, remain unknown. Studies showed that cytokine transforming growth factor (TGF)-131, a multifunctional regulator, was highly expressed in the aneurysms or dis-section of aorta and was responsible for the onset of the diseases. We try to explore the mechanisms of thoracic aortic dissection (TAD) by comparing the expression and distribution of TGF-β1 in the aortic wall and analyzing the association of TGF-β1 with extracellular matrix (ECM) in patients with TAD and control subjects. Methods Aortic specimens taken from surgical pa-tients with TAD( n = 20 ) at Zhongshao Hospital and organ donors ( n = 20, controls) were prepared with paraffin embedded tis-sue slide. ECM was investigated with hematoxylin-eosin, Verhoeff van-Giesen (EVG) and Maason's triehrome (MT) staining.Distribution and expression of TGF-β1 within aortic wall was examined with double immunofluoreseent staining and semi-quan-tiffed by fluoreseent intensity analysis. The expression of TGF-β1 in the two groups and among various layers of the arterial wall was compared. Results TAD was morphologically characterized by decreased and disrupted elastic fibers in the tunica media of the aorta wall with hyperplasia of the collagen fibers. TGF-β1 was expressed unevenly within aortic wall, with highest in the media, followed by intima and adventitia, in both TAD patients and eantrols. Specimen from TAD patients exhibited overall in-creased TGF-β1 expression by 9.56% as compared with that from the controls ( P <0.05 ). TGF-131 expression was increased by 16.09% (P<0.05) in the media and 16.75% (P<0.05) in the adventitia in TAD group as compared with those in the control group, but no difference was detected in intima between the two groups. TGF-β1 distribution histogram analysis dis-closed that TGF-β1 expression in the tunica media was evident in the elastic fibers, and was increased by 34.83% in TAD pa-tients as compared with that in the controls (P <0. 01 ). No significant associations between TGF-β1 expression and age, gen-der, maximal aortic diameter and type of dissection in TAD patients were detected. Conclusion TGF-β1 expression is up-reg-ulated and unevenly distributed in the dissected aortic wall of TAD patients. The finding that TGF-β1 was significantly up-regulated and condensed in the elastic fibers of the tuniea media suggested the crucial role of TGF-β1 in the development of TAD.

Objective To evaluate the cardiopulmonary allograft function and to analyze key factors for long-term survival of heart-lung transplantation in a patient survived more than 5 years. Methods On December 17th, 2003 at Zhongshan Hospital of Fudan University, a homologous heart-lung transplantation was performed on a female who diagnosed with cardiopulmonary failure secondary to congenital atrial septal defect with severe pulmonary hypertension. Heart-lung allograft was preserved with 1 000 mL UW solution and 4 000 mL HTK solution.Postoperative immunosuppressive therapies were managed with Zenapax, cyclosporine A (or tacrolimus), mycophenolate mofetil and corticosteroids. Cyclosporine A maintained with serum trough levels of 100-200 μg/L and tacrolimus with serum trough levels of 8-20 μg/L. Cardiopulmonary allograft functions were evaluated by echocardiogram, pulmonary function test and thoracic CT periodically. Results The patient survived operation and experienced normal daily life with NYHA cardiac function of class Ⅰ-Ⅱ during the follow-up of 5 years and 6 months. Echocardiogram showed left ventricular ejection fraction of 65% to 86%. Pulmonary function test exhibited with nearly normal oxygen exchange, meanwhile, small airway obstruction was detected from one year after operation and keeping stable from then on. Two episodes of severe pneumonia were complicated and treated with antibiotics and fhconazob, no severe acute allograft rejection episode was experienced. Conclusions Heart-lung transplantation proves to be a reliable therapy modality for terminal cardiopulmonary failure. Excellent donor organ preservation, accurate balance of the risk between acute allograft rejection and infection, and strict preventive measures against infection are key factors for long-term survival of heart-lung transplantation.

Objective To explore the incidence and etiology of infection after heart transplantation and discuss the prophylaxis and management. Methods Retrospective study was conducted on the 140 survival heart transplant recipients (HTs) with detail follow-up information. All patients received preventive therapy against bacterial infections postoperatively, of which 87. 8% patients used antiviral drugs to prevent cytomegalovirus (CMV) infection. The immuosuppressive regiment was as follows: tacrolimus (Tac) or cyclosporine A (CsA), mycophenolate mofetil (MMF),glucocorticoid. Postoperatively all patients had throat swabs, sputum smear Gram stain, sputum culture, blood culture, urine culture and fecal culture for microbiological monitoring. Schedule tables were made to record and analyze the demography of the patients and the timetable of infections. Results The incidence of infections was 42.9 episodes per 100 HTs. Sixty-four cases (76. 2% ) of the infections occurred in the first month after transplantation and all recovered, 20 cases (23.8%) took place after 1 months, and 4 patients died. Conclusion Perioperative infections are mostly caused by bacteria and the prognosis is good. Infections 2 months after operation are commonly caused by virus or fungi with poor prognosis.

Objective Aortic dilation in bicuspid aortic valve patients usually begins at the proximal tubular ascending aorta.This study,we investigate the risk factors of aortic root dilation,in advantage of reviewing medical records of bicuspid aortic valve patients with dilated ascending aorta.Methods Include all the bicuspid aortic valve patients with dilated proximal ascending aorta who needed surgical intervention from Jan 1,2003 to May 4,2011.We exclude patients accompanied with aor tic dissection or without echocardiographic report.Divide these patients into group dilation (≥45 mm) and group non-dilation (＜ 45 mm) according to sinus diameters and proceed statistical analysis in SPSS 20.0.Results In univariate analysis,group dilation are younger and higher,and possess higher proportion of male and fusion of right-left coronary cusps,more severe aortic regurgitation,larger left ventricular diameters and higher elevation of total bilirubin,conjugated bilirubin and creatinine,but shorter duration of symptoms,less aortic stenosis and lower ejection fraction.In multivariate analysis with logistic regression model,less aortic stenosis and larger left ventricular end-diastolic diameter are the significant risks of sinus dilation.It's demonstrated in ROC curve analysis,that left ventricular systolic diameter and diastolic diameter are the two most valuable parameters indicating sinus dilation,the sensitivity and specificity is 0.93,0.83 while left ventricular diastolic diameter ＞ 60 mm and 0.79,0.89 while systolic diameter ＞ 45 mm.Conclusion Less aortic stenosis and larger left ventricular end-diastolic diameter are the significant risks of aortic root dilation in bicuspid aortic valve patients accompanied with dilated ascending aorta.The left ventricular systolic and diastolic diameters are the most valuable parameters indicating aortic root dilation.

Objective We sought to evaluate the efficacy of bipolar radiofrequency ablation of atrial fibrillation (AF) in patients undergoing cardiac surgery,and to determine independent factors affecting the recurrence.Methods From June 2007 through February 2010,81 patients with atrial fibrillation underwent a modified Cox-Maze Ⅳ procedure using a biopolar radiofrequency device( Medtronic in 32 cases,Atricure in 49 cases).There were 45 males and 36 females,aged (48.2 ± 11.0)years,including 26 cases of permanent AF,44 cases of persistent AF and 11 cases of paroxysmal AF.The mean duration time of AF was (7.56 ± 7.47 ) years.The left atrial diameter were 36 ～ 72 mm.In conjunction with cardiac surgery including:mitral valve replacement (MVR) (or add tricuspid valve plasty (TVP) in 33 cases,mitral and aortic valve replacement (DVR)( or add TVP) in 18 cases,off-pump coronary artery bypass surgery (OPCAB) in 16 cases,aortic valve replacement (AVR) in 4 cases,MVR and coronary artery bypass grafting (CABG) in 1 case,mitral valve plasty (MVP) in 1 case,and others in 8 cases.Among them,22 patients were undergoing electrophysiological mapping by high-frequency bipolar stimulation from June 2009 to February 2010.A follow-up of 12 to 44 months was completed.Recurrences were evaluated by 12-lead ECG or 24 hour Holter recording every clinic visit-1,3,6,9,and 12 months after the procedure and yearly thereafter,or if symptoms developed.Multivariate regression analysis was performed to determine independent factors affecting the recurrence.Results Hospital mortality was 1.23％.The successful ablation of AF were 100％,82.5％,and 84.8％ immediately after operation,at discharge,and at 2(6.1 ± 13.6) months after operation respectively.Multinomial regression analysis showed small left atrium ( ＜ 60 mm),and electrophysiological mapping might contribute better sinus rhythm restoration ( P ＜ 0.05 ).Conclusion Bipolar radiofrequency ablation of atrial fibrillation in patients undergoing cardiac surgery is safe and effective.Small left atrium ( ＜ 60mm) and electrophysiological mapping should be considered to improve results in selected patients.

Objective To determine,in our experience,the prevalence and presence of risk factors for metabolic syndrome (MS) in heart transplant recipients.Methods We studied 135 patients who underwent heart transplantation in our hospital from September 2000 to December 2011,According to the diagnostic criteria of MS,they were divided into two groups.All variables that could be related to the development of MS during the follow-up period were analyzed.The prevalence and presence of risk factors for MS in our experience were determined.Student t-test,Wilcoxon rank sum test and x2 test were used for univariate statistical analysis and logistic regression for multivariate analysis.Results (1) Of the 135 patients,63 developed MS (46.67％) during a mean follow-up period of 47.3 months.The multivariate analysis identified the follows as predictive factors for the development of MS:age (OR=1.09,95％ CI 1.01-1.22,P＜0.05),body mass index (BMI) (OR=1.65,95％ CI 1.16-1.87,P＜0.05),history of DM (OR =3.27,95％ CI 1.12-34.21,P＜0.05).Conclusion In our population,the prevalence of MS after heart transplant is 46.67％ during a mean follow-up period of 47.3 months.Age,pre-operative overweight especially BMI,and history of DM were significant and independent risk factors for the development of MS during the follow-up period.For these patients,dose of immunosuppressant and diet control are important.

Objective To design and synthesize compounds with protein tyrosine kinase(PTK)inhibitory activity with L029 as the lead compound. Methods L029 derivatives were designed and synthesized from L029 by reduction and/or substitution with the 3-dimethylamino-1-propyl,methyl acetate,methyl propionate in its active H and other sites. PTK activity was measured by enzyme-linked immunosorbent assay(ELISA). The inhibitory rate was calculated to screen out the compounds with PTK inhibitory activity. Re-sults Five target compounds were synthesized and their structures were confirmed by 1H NMR and MS. Three compounds T2,T3 and T5 were screened out with strong PTK inhibitory activity. Conclusion The synthetic routes of the target compounds are simple with mild reaction condition,and 3 compounds show strong inhibitory activity by ELISA. These results can provide reference for the further design and synthesis of this kind of molecules.

Objective To summarize the treatment decision-making strategy and its long-term efficacy for advanced elderly patients with severe valvular heart disease and clear indications for surgery.Methods Clinical data of 196 patients aged 75 years and older firmly diagnosed as severe valvular heart diseases were retrospectively analyzed.The patients were divided into the surgical group (a mean age of 77.4±2.0 years,n=126)and the conservative group(a mean age of 80.5±5.0 years,n =70).Factors affecting therapeutic decision-making were analyzed,and the differences in a long-term survival were compared between the two groups.Results The most common reason for choosing conservative treatment was the recommendation of the doctor giving a preliminary diagnosis and worrying about the high-risk surgery for the patients(62.9％,44/70).Only 26(37.1％)patients in the conservative group were evaluated by cardiac surgeons,among whom 12 (17.1％)patients were considered to have surgical contraindications,and 14 (20.0％) patients themselves or their family members chose conservative treatment for the fear of surgical risks.Patients in the operation group were mainly from the outpatient department of cardiac surgery,and only 8 (6.3 ％)cases were referred from department of internal medicine.Logistic regression analysis showed that female,chronic renal insufficiency,advanced age,pneumonia and emergency hospital admissions were independent predictors for the conservative option(P ＜0.01),while patients with isolated aortic valve disease tended to receive surgical treatment.Overall 5-year survival was higher in the surgical group than in the conservative group (76.4％ vs.39.9％,P ＜ 0.01).Cox regression analysis disclosed that the conservative treatment option was the single risk factor for long-term survival in all series.Conclusions Many factors affect the process of therapeutic decision-making for patients with severe valvular heart diseases,and a multidisciplinary collaboration is the best way for the optimal treatment strategy for those patients.