Objective To evaluatethe effect of mTORC1 inhibitor on the proliferation in human pancreatic neuroendocrine tumors(pNET)cell line BON,to explore the function of glutamine metabolism in it.Methods In vitro cultured human pancreatic neuroendocrine tumors(pNET)cell line BON,BON cells were treated with different concentrations of rapamycin(1,5,10,25,50, 100 nM)for 12,24 h.Then CCK-8 assay are used to calculate the growth inhibitory rate.Rapamycin treated with BON 12 h,test the glutamine uptake level compared with control.Then deprive of glucose and/or glutamine,CCK-8 assay were used in observation of cell proliferation,cell cycle distribution was analyzed by flow cytomety.Results Rapamycin significantly inhibited the growth of BON cells in a time-and dose-dependent manner(P <0.05).Meanwhile,rapamycin can reduce the glutamine uptake level compared with control.BON obviously depends on glutamine for growth,without glucose and glutamine group have obvious difference in growth rate(P <0.05).Conclusion mTORC1 inhibitor can inhibit BON cells proliferation and influence the glutamine uptake lev-el.suggesting that mTORC1 inhibitor might inhibit BON cells proliferation by influenced the glutamine metabolic pathway.

Objective: To investigate factors affecting X-ray structure of the spine in patients with ankylosing spondylitis (AS). Methods: A total of 206 AS patients were recruited. Clinical and laboratory parameters in AS patients were recorded in detail. Disease activity index [Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAScrp)], X-ray structural damage index-modified stoke ankylosing spondylitis spine score (mSASSS) and grading results of radiographic examination of sacroiliac joint were calculated. Statistical analysis using Statistical Package form Soci-science(SPSS) 17.0 Chi-square test, rank test, Logistics regression analysis and other statistical methods were used. Differences of mSASSS levels, spine involvement (mSASSS>0) and rates of bone bridge formation were compared between different groups. Results: Incidences of spine involvement (100%) and bone bridge formation(65.2%) in AS patients ≥40 years old were significantly higher than those in AS patients <40 years old (90.6%、31.9%)(χ²=4.651, P=0.031; χ²=16.647, P<0.01), and the level of mSASSS was also higher (Z=5.575, P<0.01). In AS patients with BMI ≥24 kg/m², disease duration ≥5 years (49.2%, 50.4%), rates of bone bridge formation was significantly higher than those in AS with BMI <24 kg/m², but the disease duration (34.5%, 19.7%)(χ²=4.014, P=0.045; χ²=18.173, P=0.03), and mSASSS values were significantly higher (Z=2.281, P=0.023, Z=4.828, P<0.01). Bone bridge formation rate in smoking patients (50.6%) was significantly higher than that in non-smoking patients (31.0%) (χ²=7.346, P=0.007) and mSASSS value was significantly higher (Z=2.045, P=0.041). Bone bridge formation rates in AS with high-ESR and high-CRP(48.6%, 49.0%) were significantly higher than those in patients with normal-ESR and normal-CRP(25.6%, 28.9%)(χ²=10.784, P=0.001; χ²=8.102, P=0.004) and mSASSS value was clearly higher(Z=2.379, P<0.01; Z=3.112, P<0.01). Bone bridge formation rate in AS with BASDAI≥4 or ASDAScrp≥2.1 groups (52.8%, 46.4%) were significantly higher than that in AS with BASDAI<4 or ASDAScrp<2.1 groups (34.2%, 30.7%) (χ²=5.681, P=0.017; χ²=4.646, P=0.031) and mSASSS values were significantly higher (Z=3.887, P<0.01; Z=3.895, P=0.004). Rates of bone bridge formation among different X-ray grading of sacroiliac joint (10.8%, 35.6%, 60.3%) and MRI findings (33.3%, 50.0%, 15.4%) differed with each other (χ²=25.714, P<0.01; χ²=6.855, P=0.032). Logistics regression analysis showed that BMI [OR(95%CI)=1.145(1.037, 1.265), P<0.01], disease duration [OR(95%CI)=1.144(1.055, 1.239), P<0.01], smoking [OR(95%CI)=2.832(1.343, 5.969), P<0.01] and sacroiliac joint X-ray staging [OR(95%CI)=2.584(1.337, 4.997), P<0.01] were risk factors for the bone bridge formation in spine of AS. Conclusion Spinal involvement in AS is related to disease activity. Bone bridge formation correlateswith disease duration, BMI and disease-status, especially with smoking.

Objective To explore the serum levels of fibroblast growth factor 23 (FGF23) in patients with rheumatoid arthritis (RA) and to investigate the relationship between FGF23 and RA disease activity and the occurrence of osteoporosis (OP).Methods Serum levels of FGF23 from 174 cases of patients with RA and 88 normal subjects were detected by enzyme linked immunosorbent assay (ELISA).Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry.All the clinical and laboratory indexes of RA patients were recorded in details,disease activity score (DAS28) and health assess questionnaire (HAQ) were also calculated in the meantime.Radiographic changes in both hands of RA patients were assessed by Sharp's method.T test,nonparametric test,x2 test,correlation analysis and Logistic regressive analysis were used for statistical analysis.Results Serum levels of FGF3 [145.46(67.67,245.93) pg/ml] in RA patients were higher than the control group [32.64(12.34,44.70) pg/ml,Z=11.416,P＜0.01].The positive rate of serum levels of FGF23 (≥71.95 pg/ml) in RA was 74.7％(130/174),while the positive rate in control was 4.5％(4/88,x2=115.16,P＜0.01).The threshold of FGF23 serum levels for diagnosing RA was 48.56 pg/ml (AUC=0.932,Youden index=0.743,P＜0.01,sensitivity 89.1％,specificity 85.2％).In RA patients with serum FGF23 ≥48.56 pg/ml,compared with negative FGF23 group,VAS,HAQ,number of joint swelling and BMD at femoral neck,Ward,GT,Total hip,L4 and L1-4 were significantly higher in FGF23 positive group (P＜0.05).Linear correlation analysis found that in RA patients with serum FGF23 ≥48.56 pg/ml,anti-CCP was negatively correlated with serum FGF23 levels (r=-0.171,P=0.035).And DAS28 was positively correlated with serum FGF23 (r=0.163,P=0.045).BMD at femoral neck,Ward,GT,Total hip,L4 and L1-4 were negatively correlated with serum FGF23 (P＜0.05).Results of logistic regression analysis showed that sex (OR=8.518,95％CI (2.636,27.522),P＜0.01,age [OR=1.129,95％CI (1.079,1.180),P＜0.01] and Sharp score [OR=1.008,95％CI(1.003,1.013),P=0.001]were risk factors for OP in RA patients.BMI[OR=0.801,95％CI(0.707,0.909),P=0.001] was a protective factor for OP in RA patients.Conclusion Serum FGF23 level is significantly higher in RA patients.Meanwhile,the serum FGF23 level correlates with RA disease activity and BMD.

Zinc oxide quantum dots (ZnO QDs) were synthesized by gel-sol method and employed as the transdermal aloesin (Alo) carriers. ZnO QDs were surface-functionalized with amino using aminopropyltriethoxysilane (APTES). Alo was covalently bonded on the surface of ZnO QDs via N,N'-carbonyldiimidazole to obtain Alo NPs, which were characterized by transmission electron microscope (TEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analyzer (TGA). TEM images showed that ZnO QDs were analogously sphere and monodisperse with a reasonably narrow size distribution, of which was around 4 nm. The size of Alo NPs increased to around 8 nm due to the surface modification. The intense bands at around 3 400 cm and 1 200 cm in the FTIR spectrum of Alo NPs from the vibration of -OH indicated the linkage of Alo on the surface of ZnO QDs. The results of TGA analysis showed that the mass ratio of ZnO QDs and Alo were 39.27% and 35.14%, respectively. The penetration of Alo NPs was much higher than raw Alo according to the passive penetration experiments with Franz-type diffusion cells instrument using full-thickness cavy skin, which manifested the improvement of the penetration for Alo delivered by ZnO QDs. The pH-controlled drug release behavior was investigated. At pH 7.4, only a small amount of Alo (1.45% ± 0.21%) had been released after 2 h. In contrast, as incubation at pH 5.0 of which pH was similar to endosomal environment, Alo was released very fast (87.63% ± 0.46% in 2 h) from Alo NPs, confirming that Alo NPs could response to the pH and realize the intracellular drug release. The inhibitory effect of Alo NPs on tyrosinase was in a dose dependent manner. When the concentration of Alo NPs was 12.5 μg/mL, the inhibition rate was up to 40.32% ± 1.57%. All the results show that the Alo NPs hold a great potential in transdermal tyrosinase inhibition.
Administration, Cutaneous ; Animals ; Chromones ; administration & dosage ; Drug Delivery Systems ; Glucosides ; administration & dosage ; Guinea Pigs ; Monophenol Monooxygenase ; metabolism ; Nanoparticles ; Quantum Dots ; Zinc Oxide