These results suggest that the recommended dose and halved maintenance dose may be inappropriate in patients with Child-Pugh class B and C cirrhosis due to the high C, and that voriconazole C should be monitored earlier to avoid AEs.

Brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor TrkB have been reported to be associated with poor prognosis in neuroblastoma (NB) patients. Our previous studies indicated that BDNF activation of TrkB induces chemo-resistance through activation of phosphoinositide-3-kinase (PI3K)/Akt pathway. In this study, we investigated the role of BDNF/TrkB on metastasis in NB. A tetracycline-regulated TrkB-expressing NB cell line (TB3) was used. Scratch wound healing assay, Boyden chamber migration, and invasion assays were performed to study the migration and invasion of TB3 cells. A tumor xenograft model using SCID-Beige mice was utilized to detect the metastasis of NB tumors in vivo. Inhibitors of PI3K, MAPK, Akt, and mTOR were used. Western blotting was performed to study the expressions of P-Akt, P-Erk, and P-mTOR. Our results showed that in TrkB-expressing NB cells, BDNF treatment significantly increased gap closing (P < 0.01) in scratch wound healing assay, also significantly enhanced the numbers of migrating cells (P < 0.01) and invading cells (P < 0.01) in the Boyden chamber migration and invasion assays. In vivo, NB distant metastases were significantly increased in mice with TrkB-expressing xenograft tumors compared to those with non-TrkB-expressing tumors (P < 0.05). Pre-treatment with any of the inhibitors for PI3K (LY294002), MAPK (PD98059), Akt (perifosine), or mTOR (rapamycin) blocked the BDNF/TrkB-induced increases of cell migration and invasion in TB3 cells, and also blocked the BDNF/TrkB-induced expressions of P-Akt, P-Erk, and P-mTOR. These data indicated that BDNF/TrkB increased metastasis in NB via PI3K/Akt/mTOR and MAPK pathways, and BDNF/TrkB and the downstream targets may be potential targets for the treatment of NB metastasis.Electronic supplementary materialThe online version of this article (doi:10.1007/s13277-016-5433-z) contains supplementary material, which is available to authorized users.

No abstract

Background/Aims: Systemic lupus erythematosus (SLE) is a heterogeneous chronic inflammatory autoimmune disorder, in the pathogenesis of which miRNAs play a versatile function. The purpose of this study was to investigate the effect of miRNA-410 on the pathogenesis of SLE in T cells of SLE patients. Methods: Real-time PCR was used to test the mRNA levels of miRNA-410 in SLE patients and healthy controls. ELISA analysis was performed to examine the production levels of IL-10. Luciferase Assay was used to confirm the targeting effect of miRNA-410 on 3'UTR of STAT3 mRNA. Results: We found that the expression level of miR-410 in T cells of SLE patients was decreased comparing to that in healthy controls, whereas overexpression of miR-410 significantly reduced the expression levels of IL-10. Furthermore, miR-410 suppresses the transcription activity of STAT3 by binding directly to the 3 'UTR of STAT3 mRNA. Moreover, silence of STAT3 down regulated IL-10 expression in CD3+ T cells. Conclusion: Our results demonstrate that miR-410 is the key regulatory factor in the pathogenesis of SLE by regulating the expression of IL-10 through targeting STAT3. These data suggest a novel function of miR-410 and bring new insight into understanding the complex mechanisms involved in SLE.

BackgroundThe prevalence, characteristics, and trends in obesity, overweight, and malnutrition among children and adolescents in 2010 and 2014 in Shenyang, China was described.MethodsThis was a multiple cross-sectional study using data from the 2010 and 2014 National Survey on Students’ Constitution and Health. A total of 31,031 children and adolescents were included in this survey. Differences in the percentages of obesity, overweight, and malnutrition by age, gender, and living region in 2010 and 2014 were compared using the χ2 test. Stepwise logistic regression was performed to select potential covariates for the dependent variable (overweight, obesity, or malnutrition).ResultsThe prevalence of obesity and overweight in 2010 was 8.99% and 13.72%, respectively, and 12.64% and 14.06% in 2014, respectively. The prevalence of malnutrition was 10.68% and 10.69% in 2010, and 2014, respectively. In 2010 and 2014, boys and girls 7–11 years of age had higher rates of obesity than other age groups (P < 0.01). The prevalence of obesity and overweight was significantly higher in the urban residents compared to the rural residents, and was also significantly higher in boys than girls (P < 0.01); however, the prevalence of malnutrition was significantly lower in boys than girls (P < 0.01). Compared to 2010, the prevalence of obesity in 2014 increased significantly in boys and girls, and urban and rural residents (P < 0.05), but the prevalence of malnutrition did not change. The prevalence of obesity, overweight, and malnutrition was associated with gender, age, and living region by univariate logistic regressions.ConclusionThe prevalence of obesity and overweight has continuously risen since 2010, and there is a low-age trend of obesity and overweight among children and adolescents in Shenyang, China. The increasing rate of obesity and overweight was faster in rural than urban areas. Malnutrition did not significantly decrease during the 4-year period from 2010–2014.