Wen Zhang, Xuan Zhang, Xiao-li Wu, Liu-sheng He, Xiao-feng Zeng, Amrie C. Grammer and Peter E. Lipsky
2010, 25(1): 1-12.
Abstract:Objective To investigate the role of TNF receptor-associated factor 2 (TRAF-2) and TRAF6 in CD40-induced nuclear factor-κB (NF-κB) signaling pathway and whether CD40 signaling requires TRAF2. Methods Human B cell lines were transfected with plasmids expressing wild type TRAF2 or dominant negative TRAF2,TRAF2-shRNA,or TRAF6-shRNA. The activation of NF-κB was detected by Western blot,kinase assay,transfactor enzyme-linked immunosorbent assay (ELISA),and fluorescence resonance energy transfer (FRET). Analysis of the role of TRAF-2 and TRAF-6 in CD40-mediated NF-κB activity was examined following stimulation with recombinant CD154. Results TRAF2 induced activity of IκB-kinases (IKKα,IKKi/ε),phosphorylation of IκBα,as well as nuclear translocation and phosphorylation of p65/RelA. In contrast,TRAF6 strongly induced NF-κB activation and nuclear translocation of p65 as well as p50 and c-Rel. Engagement of CD154-induced nuclear translocation of p65 was inhibited by a TRAF6-shRNA,but conversely was enhanced by a TRAF2-shRNA. Examination of direct interactions between CD40 and TRAFs by FRET documented that both TRAF2 and TRAF6 directly interacted with CD40. However,the two TRAFs competed for CD40 binding. Conclusions These results indicate that TRAF2 can signal in human B cells,but it is not essential for CD40-mediated NF-κB activation. Moreover,TRAF2 can compete with TRAF6 for CD40 binding,and thereby limit the capacity of CD40 engagement to induce NF-κB activation.
Supported by Key Projects of the National Science & Technology Pillar Program in the Eleventh Five-year Plan Period (2008-BAI59B02)
Keywords:human B lymphocytes;TNF receptor-associated factor 2;TNF receptor-associated factor 6;IκB kinase;IκBα;p65
Abstract:Objective To study the pharmacokinetics of a novel recombinant human granulocyte colonystimulating factor (rhG-CSFa) in rats and to determine the proteolytic rates of rhG-CSFa in the whole blood and serum of rats in vitro. Methods The pharmacokinetics of rhG-CSFa and conventional (wild type,WT) granulocyte colonystimulating factor (G-CSF) were investigated in Sprague-Dawley rats which received either intravenous or subcutaneous injection of rhG-CSFa or WT G-CSF at three different doses (20,50,or 100 μg/kg). The blood samples of rats were collected at multiple time points (from 0.08 to 12 h) and the concentrations of rhG-CSFa and WT G-CSF in serum were determined with a sandwich enzyme-linked immunosorbent assay (ELISA). For the study of proteolytic rates in vitro,the concentrations of rhG-CSFa or WT G-CSF were determined at 3-minute intervals after addition of the respective drug to rat’s whole blood or serum. Results Pharmacokinetic analysis of serum rhG-CSFa or WT G-CSF levels indicated that,at each dose tested,for either route of drug administration,the area under concentration-time curve values and the maximum serum concentration of rhG-CSFa were higher than those of WT G-CSF,and the serum half life of rhG-CSFa was longer than that of WT G-CSF. Subsequent in vitro whole blood and serum stability study showed that the rates of drug degradation in WT G-CSF were 1.8 folds and 1.5 folds higher than those in rhG-CSFa,respectively. Conclusion rhG-CSFa has better serum and whole blood stability in vitro and higher bioavailability in vivo as compared to WT G-CSF.
Keywords:recombinant human granulocyte colony-stimulating factor;pharmacokinetics;half life;bioavailability;proteolytic rate
Abstract:Objective To examine the expression of FLICE-inhibitory protein (FLIP) in juvenile idiopathic arthritis (JIA) and analyze its correlation with synovial inflammation. Methods The expression of FLIP was assessed in 11 JIA and 3 normal synovial tissue samples by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The cell types expressing FLIP were further characterized,and the correlation of FLIP expression with the degree of synovial inflammation,as well as the activity of caspase 8 was then analyzed. Results RT-PCR revealed the expression of FLIP mRNA in all 11 JIA samples,but not in 3 normal synovial tissues. In JIA,FLIP expression could be found in both the lining and sublining layers,mainly in the macrophage-like cells. Moreover,the expression of FLIP in JIA synovial tissues was positively correlated with the degree of synovial inflammation (r=0.563,P<0.05). Conclusion The expression of antiapoptotic FLIP in JIA synovial tissue and its correlation to accumulation of inflammatory cells in synovial tissue suggests that FLIP potentially extends the lifespan of synovial cells and thus contributes to the progression of joint destruction.
Meng-tao Li, Jun Ai, Zhuang Tian, Quan Fang, Wen-jie Zheng and Xue-jun Zeng
2010(1): 27-31.
Abstract:Objective To investigate the prevalence of anti-endothelial cell antibodies (AECAs) in the sera of connective tissue diseases (CTD) patients with pulmonary arterial hypertension (PAH) and its correlation with clinical manifestations. Methods AECAs in sera of 39 CTD patients with PAH,22 CTD patients without PAH,and 10 healthy donors as controls were detected with Western blotting. The prevalence of different AECAs in different groups was compared and its correlation with clinical manifestations was also investigated. Results The prevalence of AECAs was 82.1% in CTD patients with PAH,72.7% in CTD patients without PAH,and 20.0% in healthy donors. Anti-22 kD AECA was only detected in CTD patients with PAH (15.4%). Anti-75 kD AECA was more frequently detected in CTD patients with PAH than in those without PAH (51.3% vs. 22.7%,P<0.05). In CTD patients with PAH,anti-75 kD AECA was more frequently detected in those with Raynaud’s phenomenon or with positive anti-RNP antibody. Conclusion AEC As could be frequently detected in CTD patients with or without PAH,while anti-22 kD and anti-75 kD AECA might be specific in CTD patients with PAH.
Guang-wen Li, Guan-yi Zheng, Jin-guo Li and Xu-dong Sun
2010(1): 32-37.
Abstract:Objective To study the relationship between carotid atherosclerosis and cerebral infarction (CI). Methods Between November 2008 and March 2009,147 CI patients (CI group) and 48 patients with non-cerebrovascular diseases (control group) were enrolled from inpatients of Neurology Department of our hospital. The diagnostic criterion of thickened carotid intima was set as 1.0 mm≤intima-media thickness (IMT) 0.05). Conclusions Carotid atherosclerosis is to some extent able to reveal the atherosclerotic condition of cerebral arteries and act as an important predictor for the risk of CI. The color Doppler ultrasonography of carotid arteries can provide a convenient way for the prevention and treatment of CI.
Abstract:Objective To investigate the association between preoperative,operative,and postoperative factors and persistent pleural effusion after the extracardiac Fontan procedure. Methods Ninety-five consecutive patients diagnosed with univentricular heart underwent extracardiac connection using Gore-Tax conduits at the Department of Children’s Heart Centre,Justus-Liebig-University Giessen in Germany from June 1996 to July 2007. The outcome measures were duration and volume of chest tube drainage after surgical intervention. The investigated factors included age and weight at the time of operation,anatomical diagnosis,preoperative oxygen saturation,mean pulmonary artery pressure,ventricular end-diastolic pressure,fenestration,cardiopulmonary bypass time,conduit size,postoperative pulmonary artery pressure,administration of angiotensin-converting enzyme inhibitors,and postoperative infection. Associations between these factors and persistent pleural effusion after the extracardiac Fontan procedure were analyzed. Results Every patient suffered postoperative effusion. The median duration of postoperative chest tube drainage was 9 days (range,3-69 days),and the median volume was 12 mL·kg-1·d-1 (range,2.0-37.5 mL·kg-1·d-1). Thirty-seven (38.9%) patients had pleural drainage for more than 15 days,and the volume in 35 (36.8%) patients exceeded 25 mL·kg-1·d-1. Nineteen (20%) patients required placement of additional chest tubes for re-accumulation of pleural effusion after removal of previous chest tubes. Fifteen (17.8%) patients were hospitalized again due to pleural effusion after discharge. The median length of hospital stay after the operation was 14 days (range,4-78 days). Multivariate analysis results showed that non-fenestration,low preoperative oxygen saturation,and postoperative infections were independent risk factors for prolonged duration of pleural drainage (P<0.05). Long cardiopulmonary bypass time,non-fenestration,small conduit size,and low preoperative oxygen saturation were independent risk factors for excessive volume of pleural drainage (P<0.05).Conclusions For reduing postoperative duration and volume of pleural drainage following Fontan procedure,it seems to be important to improve the preoperative oxygen saturation,use large size of conduit,shorten cardiopulmonary bypass time,and make fenestration during the operation,as well as avoid postoperative infections.
Jian Cao, Hui Zou, Bing-po Zhu, Hao Wang, Jian Li, Yu Ding and Xiao-ying Li
2010(1): 44-49.
Abstract:Objective To investigate the variation of sex hormone and its receptor level in elderly male patients with coronary heart disease (CHD) and to evaluate the correlations between CHD and sex hormone as well as sex hormone receptor. Methods Altogether 139 male CHD patients (CHD group) aged 60-92 years and 400 healthy men (control group) aged 60-90 years were included in this cross sectional study. The plasma concentrations of dehydroepiandrosterone sulfate (DHEAS),total testosterone (TT),free testosterone (FT),estradiol (E2),sex hormone binding globulin (SHBG),luteinizing hormone (LH),and follicle-stimulating hormone (FSH) were measured. The androgen receptor (AR) was tested by flow cytometry. Correlations between CHD and levels of sex hormones and AR were analyzed. Results Compared with the control group,the levels of DHEAS,TT,FT,SHBG,and the fluorescence intensity of AR in the CHD group significantly reduced (P<0.05),while the levels of FSH and E2 significantly increased (P<0.01) Age was negatively correlated with TT (r=-0.28,P=0.00) and FT (r=-0.17,P=0.01),while it was positively correlated with SHBG (r=0.14,P=0.04) and E2 (r=0.33,P=0.00). AR fluorescence intensity was negatively correlated with systolic blood pressure (r=-0.12,P=0.01). Binary logistic regression analysis showed that TT,SHBG,and AR were all negatively correlated with CHD (P<0.05). Conclusions Elderly male patients with CHD are found to have low levels of DHEAS,TT,FT,SHBG,and AR,while high concentrations of E2 and FSH. Low levels of TT and SHBG may be the potential risk factors of CHD in elderly men.
Yusoh Nuriyah, Xue-tao Ren, Li Jiang, Xi-pu Liu and Yan-hong Zou
2010(1): 50-52.
Abstract:Objective To study the agreement between ophthalmologists and community health workers in detecting shallow anterior chamber with oblique flashlight test. Methods Totally 425 subjects were given an eye examination in a community health center. The anterior chamber depth of each subject was examined by one ophthalmologist and two trained community health workers (one nurse and one non-professional health worker) using oblique flashlight test. Inter-observer agreement was determined using the weighted kappa statistic. Results Among the enrolled subjects,148 (35%) were male and 277 (65%) were female. Good agreement was noted in all the three observers. The comparison between the ophthalmologist and the nurse showed a kappa statistic of 0.42 for both eyes (P<0.001). The kappa statistic was 0.54 and 0.52 for right and left eyes respectively between the ophthalmologist and the non-professional health worker (P<0.001). As for agreement between the nurse and the non-professional health worker,the kappa statistic was 0.49 and 0.38 for right and left eyes,respectively (P<0.001). Conclusion The oblique flashlight test may be used as an applicable tool by trained community health workers for screening of shallow anterior chamber and play a role in blindness prevention in community.
Keywords:glaucoma;shallow anterior chamber;oblique flashlight test
Abstract:Objective To evaluate the clinical features,diagnosis,treatment,and outcome of intralobar pulmonary sequestration (ILS). Methods Patients who were diagnosed with ILS in our hospital between January 1988 and January 2009 were retrospectively reviewed. We recorded the clinical symptoms,imaging findings,operative technique,complications,and outcome of these patients. Results Forty-seven patients (25 men and 22 women) with an average age of 32.3 years were enrolled. Forty-two patients had symptoms including cough and hemoptysis. Chest X-ray,computed tomography (CT),magnetic resonance imaging (MRI),and angiography were performed. Thoracotomy was performed in 45 patients,while thoracoscopy was performed in 2 patients. Lobectomy was the most common treatment procedure. Massive bleeding developed in 2 patients due to injury of aberrant supplying artery intraoperatively,1 patient had atrial fibrillation,1 patient had thrombosis of upper extremity postoperatively. All patients were confirmed the diagnosis pathologically,4 accompanied with bronchogenic cyst,15 with bronchiectasis,8 with infection,2 with aspergilloma,and 1 with carcinoid. No late complications occurred. Conclusions ILS is rare,surgery is recommended because some patients may have potential severe complications. Contrast enhanced CT and three-dimensional reconstruction is the best diagnostic method. Both thoracotomy and thoracoscopy are appropriate for the selected candidates.
Ji-dong Wu, Yue-hong Zheng, Nim Choi and Furtado Rui
2010(1): 57-60.
Abstract:Objective To investigate the role of revascularization procedures with autologous greater saphenous vein in surgical management of iliac-femoral artery pseudoaneurysm in parenteral drug abusers. Methods Twenty-one patients with iliac-femoral artery pseudoaneurysm caused by parenteral drug abuse from 2004 to 2007 were enrolled. Among them,15 patients were male and 6 were female; their average age was 31.3 years. The size of pseudoaneurysms ranged from 3.0 cm to 7.5 cm. Common femoral artery and distal external iliac artery were often involved. We performed arterial reconstruction on these patients with autologous greater saphenous vein as a graft after excising iliac-femoral artery pseudoaneurysm through a single curved inguinal incision. All patients were followed up,and the complications were recorded. Results The surgical procedures were finished without intraoperative mortality or perioperative complications. All patients were free of claudication symptoms after the surgery except one case with preoperative popliteal artery stenosis. One case of infection and wound tissue fistula was found later. One case had inguinal incisional hematoma and another complained of numbness in thigh skin. Conclusions The use of autologous greater saphenous venous grafts for arterial reconstruction after pseudoaneurysm excision in drug abusers is safe and effective. This technique offers more advantages than arterial ligation alone without revascularization. An optimal greater saphenous venous graft is a prerequisite for revascularization.
Jin Wen, Han-Zhong Li, Zhi-gang Ji, Quan-zhong Mao, Bing-bing Shi and Wei-gang Yan
2010(1): 61-64.
Abstract:SILENT extra-adrenal retroperitoneal paragangliomas (PGLs) arise from dispersed paraganglias which tend to be symmetrically distributed in close relation to the aorta and sympatheticnervous system. They are rarely encountered in everyday surgical practice.
Abstract:Chinese Medical Sciences Journal (Chin Med Sci J) is a peer-reviewed, general medical journal published by the Chinese Academy of Medical Sciences. Chin Med Sci J reports on all aspects of basic and clinical medicine and pharmacology in China, while contributions from abroad are welcomed as well.