OBJECTIVETo investigate the impact of in utero exposure to di-n-butyl phthalate (DBP) on the apoptosis of testicular cells in the pubertal male rat offspring.

METHODSTen pregnant SD rats were randomly divided into a control and an experimental group to be treated intragastrically with olive oil (1 ml per day) and DBP (500 mg per kg of body weight per day) respectively between gestation days 12 and 19. At the pubertal age (postnatal day 45, PND 45), the testes of the male rat offspring were removed for observation of the cell structure under the transmission electron microscope and the development of different spermatogenetic cells by HE staining. The apoptosis of testicular cells was detected by the TUNEL method, the expressions of the apoptosis-regulating proteins Bcl-2, Bcl-XL, Bax and p53 were determined by immunohistochemistry and Western blot, and the data obtained were compared between the two groups by t-test.

RESULTSTransmission electron microscopy revealed increased apoptosis and vacuolization of testicular cells in the PND-45 rat offspring, HE staining showed markedly decreased numbers of different spermatogenetic cells, TUNEL manifested significantly increased apoptosis of testicular cells in the experimental group as compared with the control (12.00 ± 5. 22 vs 3.17 ± 1.47, P < 0.01), and immunohistochemistry and Western blot exhibited remarkably higher expressions of Bax and p53 in the former than in the latter group (P < 0.05).

CONCLUSIONIn utero exposure to DBP can increase the apoptosis of germ cells and Sertoli cells, induce the vacuolization of testicular cells, and significantly elevate the expressions of the apoptosis-promoting proteins Bax and p53 in the pubertal male rat offspring.

Animals ; Apoptosis ; Body Weight ; Dibutyl Phthalate ; adverse effects ; Female ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley ; Sertoli Cells ; cytology ; pathology ; Spermatogenesis ; Testis ; cytology ; pathology ; Tumor Suppressor Protein p53 ; metabolism ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo observe the effect of sirolimus-based immunosuppression administered on heart transplant recipients with chronic renal dysfunction.

METHODSFrom June 2004 to December 2008, standard calcineurin inhibitors (CNI)-based immunosuppressive regimen was changed to reduced-dose CNI plus sirolimus due to CNI-related chronic renal dysfunction in 20 out of 138 cardiac transplant recipients at Fuwai Hospital. The standard immunosuppressive regimen included steroid, CNI (cyclosporine or tacrolimus), and mycophenolate mofetil or azathioprine. Sirolimus was started at 0.75 - 1.50 mg/d with titration to achieve levels of 5 - 15 µg/L, and CNI dose was reduced gradually to 1/2-2/3 of the baseline level. Patients were followed for changes in renal function, lipid level and clinical side effects related to immunosuppressive therapy. Endomyocardial biopsy (EMB) was performed routinely at 3 weeks, 3, 6 and 12 months after transplantation. EMB was also performed at 3 months after regimen change within 1 year post-transplantation or when rejections were suspected in patients beyond 1 year post-transplantation. Echocardiography was performed for monitoring purpose.

RESULTSThe mean follow-up after regimen change was (7.9 ± 6.3) months. Final sirolimus dose was (0.89 ± 0.22) mg/d and blood drug level was (7.6 ± 3.8)µg/L. Cyclosporine dose was reduced from (191.7 ± 60.0) mg/d to (123.6 ± 34.8) mg/d, with blood drug concentration reduced from (175.5 ± 58.0) µg/L to (111.9 ± 56.0) µg/L in 18 patients (P < 0.01). Tacrolimus average dose was reduced from 4.25 mg/d to 3.00 mg/d, with blood drug concentration reduced from 13.5 µg/L to 10.5 µg/L in 2 patients. Serum creatinine level fell from (160.4 ± 25.5) µmol/L to (134.4 ± 26.8) µmol/L (P < 0.01) and urea nitrogen fell from (13.8 ± 4.7) µmol/L to (10.4 ± 3.0) µmol/L (P < 0.01) at one month after regimen change. Twenty two EMBs were performed in 11 patients within 1 year post-transplant, there were 4 episodes of acute rejected (ISHLT grade 2). Twenty patients are all alive and cardiac function was normal. The most common side effect was hyperlipidemia, and triglycerides, total cholesterol and low density lipoprotein levels were significantly increased at 1 month post regimen change (P < 0.05 or P < 0.01). Leukocyte, hemoglobin and platelet as well as liver function remained unchanged at 1 month post regimen change (all P > 0.05).

CONCLUSIONOur results show that change from CNI-based immunosuppressive regimen to reduced-dose CNI plus sirolimus is an effective and safe approach for the management of patients with CNI-related chronic renal dysfunction, leading to an improvement in renal function without compromise in anti-rejection efficacy and with tolerable side effects.

Calcineurin Inhibitors ; Female ; Heart Transplantation ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Kidney Failure, Chronic ; drug therapy ; Male ; Middle Aged ; Retrospective Studies ; Sirolimus ; therapeutic use

ObjectiveTo detect the concentration and distribution of fluoride ions in osteoblasts exposed to fluoride in vitro culture,and to provide basic information for studying the effect of fluoride on osteoblast injury.MethodsIn vitro cultured osteoblasts were exposed to 0,5,10,20,40 mg/L fluoride for 3,10,30 d (n =6),respectively.Concentration and distribution of fluoride ions in the cytoplasm and the nucleus of these osteoblasts were determined by nuclear magnetic resonance spectroscopy.Results(①) After cultured for 3 d,fluoride ion content of the bone cytoplasm exposed to different concentrations of fluoride 0,5,10,20,40 mg/L were (0.83 ±0.65),(0.54 ± 0.23),(0.65 ± 0.77),(0.59 ± 0.87),(3.64 ± 1.21 )mg/L,respectively,and the values of exposed to 40 mg/L fluoride group was significantly higher than that of exposed to 0,5 mg/L groups (all P ＜ 0.05).(②)after cultured for 10 d,the composition of the fluoride ion in cytoplasm of exposed to fluoride 10,20,40 mg/L groups were (4.03 ± 1.23),(3.66 ± 0.98),(6.26 ± 2.10)mg/L,respectively,which were higher than that of exposed to 0,5 mg/L groups [(0.78 ± 0.75),(2.69 ± 0.89)mg/L,respectively,all P ＜ 0.05].Of fluoride 20,40 mg/L groups,the composition of the fluoride ion in nucleus were (1.63 ± 1.19),(2.17 ± 1.21 )mg/L,respectively,which were higher than that of 0,5 mg/L groups[(0.65 ± 0.46),(1.57 ± 0.33) mg/L,all P ＜ 0.05].(③)After cultured for 30 d,of the exposed to fluoride 10,20,40 mg/L groups,the composition of the fluoride ion in cytoplasm were (3.99 ± 0.84),(4.33 ± 1.67),(5.80 ± 1.38)mg/L,respectively,which were higher than that of 0,5 mg/L groups[(0.88 ± 0.44),(2.84 ± 0.43)mg/L,all P ＜ 0.05].The composition of the fluoride ion in nucleus of the fluoride 20,40 mg/Lgroups were (3.33 ± 1.46),(3.53 ± 1.22)mg/L,respectively,which were significantly higher than that of 0,5mg/L groups [(0.70 ± 0.66),(1.99 ± 0.76)mg/L,all P ＜ 0.05].ConclusionsWhen osteoblasts are exposed to fluoride environment,fluoride ions enter into the osteoblasts quickly,and quickly accumulate in the nucleus,showing a special affinity between fluoride and bone tissue.Intracellular fluoride ions increase with the increase of contact time and exposure dose.

OBJECTIVETo assess the safety and feasibility of laparoscopic and open repair of perforated peptic ulcer.

METHODSStudies on comparison between laparoscopic repair(LR) and open repair(OR) of perforated peptic ulcer were collected. Data of operating time, blood loss, time to first flatus, postoperative hospital stay, postoperative complications and mortality between LR group and OR group were meta-analyzed using fixed effect model and random effect model.

RESULTSNineteen studies including 1507 patients were selected for this study,including laparoscopic surgery(n=673) and open surgery(n=834). There were significant differences in blood loss, time to first flatus, postoperative hospital stay, wound infection rate and mortality between LR group and OR group. However, no significant differences existed in operative time, postoperative sepsis, pulmonary infection, abdominal abscess, and suture leakage between the two groups.

CONCLUSIONSLaparoscopic repair of perforated peptic ulcer is associated with improved outcomes in terms of less blood loss, quicker recovery, and lower rates of wound infection and mortality. Laparoscopic repair of perforated peptic ulcer is safe and feasible.

Humans ; Laparoscopy ; Laparotomy ; Peptic Ulcer Perforation ; surgery ; Treatment Outcome

OBJECTIVEPrimary indications for endomyocardial biopsy (EMB) include heart transplant rejection surveillance and identifying cardiomyopathy or myocarditis. EMB procedures have not yet gained widespread acceptance because of concerns about possible complications associated with EMB procedures. In this single-center retrospective study, we analyzed the incidence of major and minor EMB procedure-related complications of 439 EMBs during the past 4.5 years.

METHODSFrom May 2004 to November 2008, 15 patients with cardiomyopathy and 1 patient with suspected cardiac tumor underwent 16 EMB procedures and 131 heart transplant recipients underwent 423 EMB procedures with the use of a modified Cordis bioptome. All EMB procedures were made via the right internal jugular vein approach and RV septum EMBs were performed under fluoroscopic guidance without additional echocardiographic monitoring. Operators were allowed to perform EMB procedure alone if a minimum of 50 EMB procedures had been previously supervised by a senior operator and all EMBs were performed by 4 operators. All patients underwent a 12-lead electrocardiogram (ECG), 12-hour continuous ambulatory ECG monitoring, chest X-ray and transthoracic echocardiography before and after EMB procedures to obtain a detailed evaluation of the incidence of conduction abnormalities, arrhythmias, pericardial effusions and worsening valve insufficiency.

RESULTSThere was no major complications like cardiac tamponade, hemothorax and pneumothorax. Minor complications such as conduction abnormalities including temporary RBBB (lasting < 24 h after EMB procedures) were found in 2 cases (0.47%) and sustained RBBB (> 24 h) was evidenced in 1 case (0.23%). There were no A-V block, complex ventricular arrhythmias or episodes of atrial fibrillation during and post procedure. In addition, 4 cases (0.91%)of EMB induced mild-moderate tricuspid regurgitation during the procedure were diagnosed by echocardiography.

CONCLUSIONThe EMB procedure via the right internal jugular vein approach under fluoroscopic guidance is safe and associated with a very low complication rate when performed by experienced operators.

Adolescent ; Adult ; Aged ; Biopsy ; adverse effects ; methods ; Endocardium ; pathology ; Humans ; Middle Aged ; Myocarditis ; pathology ; Retrospective Studies ; Safety ; Young Adult

OBJECTIVETo summarize and analyze clinical outcomes and experience about using extracorporeal membrane oxygenation (ECMO) in supporting heart transplant patients in the peri-operative period of in Fuwai Hospital retrospectively.

METHODSWe performed 131 orthotopic heart transplantations from June 2004 to December 2008. Fourteen cases used veno-artery ECMO (Medtronic Ltd) for mechanical circulatory support in the peri-operative period of heart transplantation. Active clotting time(ACT) was maintained between 160 - 200 seconds, mean blood flow was 1.8 - 3.3 L/min during ECMO assistant period.

RESULTSTwelve survivals discharged with NYHAI, two patients died of multiple orgen failure with severe infection and complication of central nervous system. The ECMO time was 75 - 824 h and mean time 149 h. 12 survivals with ECMO assistance decreases the dose of vasoactive drugs, after bedside UCG evaluating heart function recovery with stable circulation, ECMO could be weaned off uneventfully after 100 h. Five patients with seven times bleeding complication and one patient with catheter-associated arterial thrombosis of distal limb, all ECMO patients with low-albuminemia and hyperbilirubinemia at some degree, eleven patients with increasing blood creatine and five patients were treated with continous renal replacement therapy, one patient with pertinacious hyperbilirubinemia was treated with plasma exchange and molecular absorbent recirculating system. Seven patients were extension incision healing and six patients were tracheotomy.

CONCLUSIONSECMO can bridge patients with end-stage heart failure to heart transplant, and extend the use of marginal donors, grasp the ECMO indication and timing of application, avoiding irreversible dysfunction of the vital organs and preventing complication during ECMO, ECMO may decrease mortality of severe patients in the peri-operative period of heart transplantation.

Extracorporeal Membrane Oxygenation ; adverse effects ; methods ; Heart Failure ; therapy ; Heart Transplantation ; mortality ; Hospital Mortality ; Humans ; Perioperative Care ; methods ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo access the prevalence and risk factors for hypertension after heart transplantation (HT), and the impact of post-transplant hypertension on medium-term survival among HT patients.

METHODSData from 265 consecutive patients underwent HT between June 2004 and May 2012 in Fuwai hospital and survived for at least 6 months were retrospectively analyzed. Hypertension was defined as systolic pressure ≥ 140 mm Hg (1 mm Hg = 0.133 kPa) and/or diastolic pressure ≥ 90 mm Hg or current treatment with antihypertensive drugs. Patients were divided into post-HT hypertension group and non-hypertension group. Logistic regression analysis was used to determine preoperative and postoperative risk factors for hypertension after HT. Kaplan-Meier method and log rank test were used for survival analysis.

RESULTSHypertension was present in 17.4% (46/265) patients before HT and in 57.4% (152/265) patients post HT. The median follow-up time was 37 months (20 - 57 months). Logistic regression analysis showed that male gender (OR: 2.27, 95%CI: 1.16 - 4.42, P < 0.05), history of pre-HT hypertension (OR: 2.22, 95%CI: 1.05 - 4.71, P < 0.05), and cyclosporine A based immunosuppressive therapy (OR: 2.54, 95%CI: 1.51 - 4.29, P < 0.01) were independent risk factors for the development of post-HT hypertension. At the end of 1, 3, 5 years, the survival rate of heart transplant patients by Kaplan-Meier method estimation were 100%, 97.2%, 86.7% in post-HT hypertension group; 98.1%, 93.8%, 93.8% in non-hypertension group. Log rank test displayed that there was no significant difference between the two survival curves (P > 0.05).

CONCLUSIONSHypertension is a frequent comorbidity after HT. Male gender, pre-HT hypertension together with cyclosporine A based immunosuppressive therapy are independent predictors for the development of post-HT hypertension. By adjusting the controllable risk factors and active control of blood pressure, the medium-term survival is similar between patients with or without postoperative hypertension in this cohort.

Adult ; Female ; Heart Transplantation ; Humans ; Hypertension ; etiology ; Logistic Models ; Male ; Middle Aged ; Postoperative Complications ; etiology ; Prognosis ; Retrospective Studies ; Risk Factors

ObjectiveTo observe the morphological changes of bone in the progress of chronic fluorosis.MethodsWistar rats were randomly divided into three groups,30 rats in each group:normal control group,experimental group Ⅰ and experimental group Ⅱ according to body weight.Rats in normal control group drank distilled water freely.Experimental group Ⅰ and group Ⅱ drunk distilled water with sodium fluoride preparation of fluorine containing ion 100,150 mg/L solution for six months,respectively.Bone mineral density was detected by X-ray,bone morphological changes were observed under light microscope and bone histomorphometric parameters were calculated using image analysis software.ResultsThe bone mineral density values were different statistically between the three groups after feeding for 2 and 4 months(F =19.79,3.28,all P ＜ 0.05).However no significant difference was found after feeding for 6 months(F =1.80,P ＞ 0.05).The bone mineral density of experimental group Ⅰ (0.20 ± 0.03,0.21 ± 0.03) was significantly higher than that of the normal control group(0.17 ± 0.03,0.20 ± 0.04) after feeding for 2 and 4 months.The bone mineral density of experimental group Ⅱ (0.21 ± 0.02) was lower than that of normal control group(0.22 ± 0.03) after feeding for 6 months.The bone lamella in experimental group Ⅰ was arranged disorderly,the number of osteocytes increased with their nucleus atrophy and the osteoblasts were more than that of control grouo which arranged in layers observed under light microscooy.In exoerimental group Ⅱ,the bone lamella was bent deformation,the number of osteocytes had decreased with their nucleus shrinking or even disappeared and the number of osteoclasts had increased significantly observed under light microscopy.In experimental group Ⅰ,the mean trabecular density [(0.33 ± 0.03)％] increased and the mean trabecular separation,thickness [( 163.57 ± 1.99),(59.26 ± 7.18 ) μm] decreased compared with that of normal control group [(0.31 ± 0.02)％,(186.60 ± 2.90)μm,(86.42 ± 1.48)μm,all P ＜ 0.05].In experimental group Ⅱ,the mean trabecular density[(0.26 ± 0.02)％] decreased,the mean trabecular thickness[(71.42 ± 10.77)μm] reduced compared with that of normal control group[(0.31 ± 0.02)％,(86.42 ± 1.48)μm].ConclusionsExcess fluoride can damage bone tissue.Low doses of fluoride can stimulate osteoblast activity and enhance osteogenesis.The activity of osteoblasts is great than that of osteoclasts.High doses of fluoride can stimulate both osteoblasts and osteoclasts activity,but mainly the activity of osteoclasts,and bone resorption increases.

Carcinoma, Non-Small-Cell Lung ; classification ; therapy ; China ; Humans ; Lung Neoplasms ; classification ; therapy ; Practice Guidelines as Topic ; Receptor Protein-Tyrosine Kinases ; metabolism

Objective To demonstrate the efficiency and safety of the modified reverse controlled antegrade and retrograde subintimal tracking(CART)technique for chronic total occlusion(CTO)recanalization.Methods Thirteen patients with CTO underwent this modified reverse CART technique.Based on the traditional reverse CART,the technology advocated the use of antegrade guidewire Knuckle technology to promote access to the subintimal space.With the use of a strong penetrating and well controllable retrograde guidewire,balloon was inflated in the CTO lesion in favor of advancing the retrograde guidewire through the lesion to reach the proximal true lumen.Results The occlusion site was located in the RCA in 10 patients and in the LAD in 3 patients.Among the 13 lesions,2 had J-CTO score = 1,4 had J-CTO score = 2,6 had J-CTO score = 3,and 1 had J-CTO score=4.Nine cases were considered as the Werner`s Collateral Connection grade 1 and other 4 cases were grade 2.All 13 cases had achieved technical success.1 case needed pericardiocentesis due to collateral branch perforation.Conclusions CTO lesions can be efficiently and safely recanalized using this modified reverse CART technique.