ObjectiveTo evaluate the effect and safety d sorafenib in treatment of patients with metastatic renal cell carcinoma.Methods40 patients with metastatic renal cell carcinoma,were given sorafenib tablets methanesulfonate treatment,the initial dose of 800mg/d,bid,continuous administration of 21d,stopping 7d,The adverse reactions,efficacy and immunohistochemistry results were observed.Results40 cases with metastatic renal cell carcinoma were not found complete remission (CR) and partial remission (PR) ; The 32 cases in stable disease (SD)(80.0％ ) and 8 cases ( 20.0％ ) in PD; The incidence of 28 cases ( 70.0％ ) in digestive system; The expression of positive rate 30.5％ of local in connexin 32,Cx32 was significantly lower than that 1.2％ in metastatic renal cell carcinoma( x2 =8.123,P ＜0.01 ),The expression of Cx32 was negatively correlated with the clinical stage( r =-0.419,P ＜0.05 ) ;The expression positive rate of vascular endothelial growth factor(VEGF) in renal cell carcinoma was significantly higher than 18.5％ in normal renal tissue( x2 =8.723,P ＜ 0.01 ) ; The expression positive rate 72.0％ in the limitations of renal cell carcinoma and metastatic renal cell carcinoma 89.1％ was not statistically significant( x2 =1.978,P ＞ 0.05 ).ConclusionSorafenibin for advanced kidney cancer had better disease control effect,and was new choice for treatment of metastatic renal cell carcinoma.

Objective To further investigate the effect of sinomenine (SIN) on TNF-α-induced VCAM-1 expression in human umbilical vein endothelial cells (HUVECs). Methods HUVECs were isolated from freshly collected umbilical cords. Positive control samples were stimulated with TNF-α, but free of SIN. Negative control samples were treated in the same way, but without TNF-α and SIN. Experimental samples were co-cultured with TNF-α and SIN at various concentrations (0.25, 0.5, and 1.0 mol/L), or TNF-α and dexamethasone (Dex) at concentration of 1.0×10-6 mol/L, or TNF-α with Dex (at concentration of 1.0×10-6mol/L) and SIN at different concentrations (0,25, 0.5, and 1.0 mmol/L) (co-treated groups). VCAM-1 expression was detected by flow cytometry (FCM). Results SIN inhibited expression of VCAM-1 in TNF-α-induced HUVECs, the best effect was shown in the 1.0 mmol/L SIN treated group. VCAM-1 decreased more markedly in the co-treated groups. Conclusion SIN inhibits TNF-α-induced VCAM-1 expression on HUVECs in vitro, and SIN maybe synergistic with Dex in inhibiting TNF-α-induced VCAM-1 expression on HUVECs in vitro.

BACKGROUND: Rheumatoid factor (RF) is a kind of autoantibody which is routinely used as a factor in patients with rheumatoid arthritis (RA) to evaluate disease activity and severity.But in clinical practice, it occurs frequently that RF values do not decrease according to clinical improvement in RA patients. OBJECTIVE: To investigate the association between rheumatoid factor (RF) and activity or disease severity of RA.DESIGN, TIME AND SETTING: A randomized cross-sectional study was performed in the Department of Rheumatology and Immunology, the Third Affiliated Hospital of Sun Yat-sen University during September 2006 and September 2007.PARTICIPANTS: Seventy-six patients,65 females and 11 males,mean age of (44±13) years,with RA diagnosed according to the American College of Rheumatology (ACR) criteria for RA were included in this study. METHODS: Seventy-six patients with active RA were randomly recruited and assessed for functional status,radiographic change,joint pain,morning stiffness, tender joint count (TJC), tender joint score (TJS), swollen joint count (SJC), swollen joint score (SJS), Health Assessment Questionnaire (HAQ), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),RF,and hemoglobin. The method of Pearson correlation or Spearman rank correlation was performed for assessing the association between RF and these indices separately, normally distributed data for Pearson correlation, nonnormally distributed data for Spearman rank correlation. MAIN OUTCOME MEASURES: Correlation of RF with above mentioned factors. RESULTS: None of the correlation coefficients between RF and indices including age,disease duration, functional status,radiographic change,joint pain, morning stiffness, TJC,TJS,SJC,SJS,HAQ,ESR,CRP,hemoglobin were significant (P＞0.05). CONCLUSION: No associations between RF and activity or severity of RA are studied.

BACKGROUND: Enthesitis is the most important pathologic change and one of the characteristic manifestations of spondyloarthropathy(SpA). However, its clinical manifestations lack specificity, and medical imaging techniques become an important auxiliary means in its diagnosis. Currently, ultrasound has been applied to examine the entheses of patients with SpA abroad, but so far there is no investigation about the ultrasonic manifestations of entheses in healthy volunteers.OBJECTIVE: To comprehend the acoustic imaging manifestations of entheses in healthy volunteers, and primarily investigate the feasibility of ultrasound in detecting entheses and the possible impact factors of acoustic imaging manifestations.DESIGN: A nonrandomized inter-controlled trail.SETTING and PARTICIPANTS: A total of 30 young healthy workers and medical students who worked or studied in the Third Affiliated Hospital of Sun Yat-sen University were included in our study, including 22 male and 8 female. None of them suffered from any arthropathies or chronic low back pain.INTERVENTION: High frequency and Color Doppler ultrasound were adopted to detect 540 entheses of 30 healthy volunteers, the entheseal thicknesses were compared respectively according to left and right sides, as well as the gender. X-ray was used to inspect if there were any abnormal findings at the attaching bones.MAIN OUTCOME MEASURES: The thickness, the echo inside entheses, the entourage, the attaching bone and the entheseal blood flow were detected.RESULTS: In normal entheses, there was a little lower but equal resonance, in which there was clear funicular fibrin resonance but without blood signal. Most entheses had a little higher membrane resonance, which was clearly divided from entourage. The surface of attaching bone was smooth and continuous. The mean thickness of the lower insertion of rectus femoris tendon, the upper insertion of patellar ligament, the lower insertion of patellar ligament, the lower insertion of tibial collateral ligament, the lower insertion of fibular collateral ligament, the insertion of Achilles tendon and plantar aponeurosis in male volunteers were(0.50 ±0.06), (0. 50 ±0. 07),(0.42±0.04), (0.20±0.03), (0.38±0.04), (0.52±0.07)and (0. 32 ±0.03) cm respectively, while the mean thickness of the corresponding insertions in female volunteers were (0.44 ± 0. 04), (0. 46 ± 0. 03 ),(0.39±0.03), (0.19±0.02), (0.32±0.02), (0.41±0.06)and (0. 28 ± 0.03) cm respectively. All entheses except for the lower insertion of tibial collateral ligament were thicker in male than in female( P ＜ 0. 05 ),but there were no significant differences in the thickness between left and right insertions ( P ＞ 0. 05 ). Calcification, erosion and hyperplasia of the attaching bone or increasing blood flow were found in 11 entheses of 8 volunteers(2.0% of all the 540 entheses detected) . There were 15 items of abnormal signs all together. Some of the abnormal sites had traumatic histories.CONCLUSION: The thicknesses are almost the same in the corresponding insertions between left and right sides, but the thicknesses of most insertions in male are thicker than those in female. Stature, body mass and exercise might impact on entheseal thickness. Trauma can cause abnormal acoustic imaging manifestations of entheses. Ultrasound is an available approach to detecting etheses.

Objective Previous study had shown that signal transduction was changed when Hela cells were transfected with HLA-B27gene.An increase of monocyte chemotactic protein-1(MCP-1)of Hela cells was observed.To determine the role of MCP in the pathogenesis of ankylosing spondylitis(AS),expression of MCP-1,2,3and4in peripheral blood mononuclear cells(PBMC),synovial fluid mononuclear cells(SFMC)and synovial tis-sues of AS patients were tested.Methods Gene expression profiles of PBMC from AS patients and healthy volun-teers were determined by cDNA microarray with1176target gene filter.The differentiated expressed gene MCP-1in PBMC,SFMC and synovial tissue of AS patients were confirmed by semi-quantitative RT-PCR.Results The gene expression profile of SFMC of AS patients was significantly different from those of PBMC from AS and PBMC from healthy volunteers.The MCP-1level was positively correlated with MCP-3(r=0.76,P=0.03).The expressions of MCP-1were higher in synovial tissues of AS than those of healthy volunteers(P=0.0035).MCP-1levels in monocytes of AS patients and control subjects were increased after LPS stimulation for4hours.Conclusions There is increased expression of MCP-1in SFMC and synovial tissue of AS patients.The results indicate that MCP-1may play a potential key role in the homing of cells migrating from blood to joint and in the pathogenesis of joint inflammation in AS patients.

Objective To evaluate the effect of deferoxamine on ventilator-associated lung injury in rats.Methods Twenty-four healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 250-300 g,were divided into 3 groups (n =8 each) using a random number table method:control group (group C),ventilator-associated lung injury group (group VALI),and ventilator-associated lung injury plus deferoxamine group (VALI+DFO group).Normal saline 2 ml was intraperitoneally injected in C and VALI groups,and deferoxamine 200 mg/kg (dissolved in 2 ml normal saline) was intraperitoneally injected in group VALI+DFO.The animals were connected to a small animal ventilator 15 min later and mechanically ventilated in volume-controlled mode,with tidal volume 40 ml/kg,respiratory rate 40-60 breaths/min,inspiratory/expiratory ratio 1 ∶ 1,and inspired oxygen fraction ratio 1.0.The rats were sacrificed after the end of mechanical ventilation,and the left lung tissues were removed for examination of the pathological changes (with a light microscope) which were scored and for determination of wet/dry weight ratio (W/D ratio).The right lung was lavaged,and lavage fluid was collected to prepare macrophage suspension,and the alveolar macrophage and mitochondrial reactive oxygen species (ROS) levels were determined using flow cytometry.Results Compared with group C,the pathological score,W/D ratio of lung tissues,and alveolar macrophage and mitochondrial ROS levels were significantly increased in group VALI,and the pathological score was significantly increased in group VALI (P＜0.05).Compared with group VALI,the pathological score,W/D ratio of lung tissues,and alveolar macrophage and mitochondrial ROS levels were significantly decreased in group VALI and DFO (P＜0.05).Conclusion Deferoxamine can reduce ventilator-associated lung injury,and the mechanism may be related to inhibiting oxidative stress in rats.

The self-renewal and multipotent potentials in neural stem cells (NSCs) maintain the normal physiological functions of central nervous system (CNS). The abnormal differentiation of NSCs would lead to CNS disorders. However, the mechanisms of how NSCs differentiate into astrocytes, oligodendrocytes (OLs) and neurons are still unclear, which is mainly due to the complexity of differentiation processes and the limitation of the cell separation method. In this study, we modeled the dynamics of neural cell interactions in a systemic approach by mining the high-throughput genomic and proteomic data, and identified 8615 genes that are involved in various biological processes and functions with significant changes during the differentiation processes. A total of 1559 genes are specifically expressed in neural cells, in which 242 genes are NSC specific, 215 are astrocyte specific, 551 are OL specific, and 563 are neuron specific. In addition, we proposed 57 transcriptional regulators specifically expressed in NSCs may play essential roles in the development courses. These findings provide more comprehensive analysis for better understanding the endogenous mechanisms of NSC fate determination.
Animals ; Astrocytes ; cytology ; metabolism ; Cell Differentiation ; genetics ; Gene Expression Profiling ; Gene Regulatory Networks ; Mice ; Neural Stem Cells ; cytology ; metabolism ; Oligodendroglia ; cytology ; metabolism ; Protein Interaction Mapping

Objective: To evaluate the role of 2B-containing NMDA receptors (NR2B) in sevoflurane anesthesia-induced cognitive dysfunction in aged rats. Methods: Thirty-two healthy male Sprague-Dawley rats, aged 18 months, weighing 570-630 g, were divided into 4 groups (n=8 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S), sevoflurane anesthesia plus NR2B specific inhibitor Ro 25-6981 group (group S+ RO) and Ro 25-6981 group (group RO). S and S+ RO groups inhaled 3% sevoflurane for 4 h. Ro 25-6981 1 mg/kg was intraperitoneally injected at 15 min before inhaling sevoflurane in group S+ RO.Morris water maze test was performed at 2 days after the end of anesthesia to assess cognitive function.The rats were then sacrificed, and hippocampal tissues were obtained for determination of the expression and phosphorylation of ERK1/2 by Western blot. Results: Compared with group C, the escape latency was significantly prolonged, the frequency of crossing the original platform was reduced, the time of staying at the original platform quadrant was shortened, and the phosphorylation of ERK1/2 was decreased in group S (P<0.05), and no significant change was found in the escape latency in S+ RO and RO groups (P>0.05). Compared with group S, the escape latency was significantly shortened, the frequency of crossing the original platform was increased, the time of staying at the original platform quadrant was prolonged, and the phosphorylation of ERK1/2 was increased in group S+ RO(P<0.05). There was no significant difference in ERK1/2 expression among the four groups (P>0.05). Conclusion The mechanism by which sevoflurane anesthesia induces cognitive dysfunction is related to up-regulating the expression of NR2B and inhibiting the activity of ERK1/2 in aged rats.

Objective: To understand the mortality and influencing factors on injecting drug users (IDUs) with HIV/AIDS, in Guizhou province, 1996-2015. Methods: A retrospective cohort study was conducted on IDUs with HIV/AIDS that were reported through national comprehensive HIV/AIDS information system, in Guizhou province during 1996-2015. Cox proportional hazard regression model was used to analyze the influencing factors on the mortality of HIV/AIDS. Results: A total of 3 958 cases of IDUs with HIV/AIDS were recruited in this study, with all-cause mortality rate of 44.01% (1 742/3 958) and total mortality rate of 7.80/100 person-years, respectively. The median survival time between diagnosis and death was 8.08 years. Mortality rate was 3.57/100 person-years in the group receiving antiretroviral therapy (ART). The mortality appeared to be 4.08/100 person-years in the group who were on methadone maintenance treatment (MMT). Data from the multiple regression analysis indicated that factors of gender, ethnicity, age when HIV/AIDS diagnosis was made, CD₄⁺T lymphocyte (CD₄) count at the first testing, ART and MMT were significantly associated with deaths among these people. The risk of death in females was 0.82 times (95%CI: 0.69-0.98) higher than that in males. The risk of deaths among the ethnic minority subjects was 1.39 times (95%CI: 1.21-1.60) higher than that of the Hans. The risk of death appeared to be 2.44 times higher (95%CI: 1.07-5.56) in the over-50-year of age group than in the <20 year-old group, when HIV/AIDS was diagnosed for the first time. The risk of death in CD₄ ≥500/μl group in the first time was 0.27 times (95%CI: 0.22-0.32) more than CD₄ <200/μl group in the firs time. The risk of death in cases who were treated with ART or MMT was 2.83 times (95%CI: 2.45-3.26) and 1.35 times (95%CI: 1.15-1.59) higher than those who did not receive any treatment, respectively. Conclusion Higher risks on death seemed to be related to the following factors: being male, older age at the time of diagnosis, lower CD₄ at diagnosis, not on ART or MMT among the IDUs with HIV/AIDS in Guizhou province, between 1996-2015.

Objective To evaluate the role of 2B-containing NMDA receptors(NR2B)in sevoflu-rane anesthesia-induced cognitive dysfunction in aged rats.Methods Thirty-two healthy male Sprague-Dawley rats,aged 18 months,weighing 570-630 g,were divided into 4 groups(n＝8 each)using a ran-dom number table method: control group(group C),sevoflurane anesthesia group(group S),sevoflurane anesthesia plus NR2B specific inhibitor Ro 25-6981 group(group S+RO)and Ro 25-6981 group(group RO).S and S+RO groups inhaled 3％sevoflurane for 4 h.Ro 25-6981 1 mg/kg was intraperitoneally injec-ted at 15 min before inhaling sevoflurane in group S+RO.Morris water maze test was performed at 2 days af-ter the end of anesthesia to assess cognitive function.The rats were then sacrificed,and hippocampal tis-sues were obtained for determination of the expression and phosphorylation of ERK1/2 by Western blot.Results Compared with group C,the escape latency was significantly prolonged,the frequency of crossing the original platform was reduced,the time of staying at the original platform quadrant was shortened,and the phosphorylation of ERK1/2 was decreased in group S(P＜0.05),and no significant change was found in the escape latency in S+RO and RO groups(P>0.05).Compared with group S,the escape latency was significantly shortened,the frequency of crossing the original platform was increased,the time of staying at the original platform quadrant was prolonged,and the phosphorylation of ERK1/2 was increased in group S+RO(P＜0.05).There was no significant difference in ERK1/2 expression among the four groups(P>0.05).Conclusion The mechanism by which sevoflurane anesthesia induces cognitive dysfunction is re-lated to up-regulating the expression of NR2B and inhibiting the activity of ERK1/2 in aged rats.