ABSTRACT
To explore the role of forkhead box protein O1 (FOXO1) in the progression of glioblastoma multiforme (GBM) and related drug resistance, we deciphered the roles of FOXO1 and miR-506 in proliferation, apoptosis, migration, invasion, autophagy, and temozolomide (TMZ) sensitivity in the U251 cell line using in vitro and in vivo experiments. Cell viability was tested by a cell counting kit-8 (CCK8) kit; migration and invasion were checked by the scratching assay; apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and flow cytometry. The construction of plasmids and dual-luciferase reporter experiment were carried out to find the interaction site between FOXO1 and miR-506. Immunohistochemistry was done to check the protein level in tumors after the in vivo experiment. We found that the FOXO1-miR-506 axis suppresses GBM cell invasion and migration and promotes GBM chemosensitivity to TMZ, which was mediated by autophagy. FOXO1 upregulates miR-506 by binding to its promoter to enhance transcriptional activation. MiR-506 could downregulate E26 transformation-specific 1 (ETS1) expression by targeting its 3'-untranslated region (UTR). Interestingly, ETS1 promoted FOXO1 translocation from the nucleus to the cytosol and further suppressed the FOXO1-miR-506 axis in GBM cells. Consistently, both miR-506 inhibition and ETS1 overexpression could rescue FOXO1 overactivation-mediated TMZ chemosensitivity in mouse models. Our study demonstrated a negative feedback loop of FOXO1/miR-506/ETS1/FOXO1 in GBM in regulating invasiveness and chemosensitivity. Thus, the above axis might be a promising therapeutic target for GBM.
Subject(s)
Animals , Mice , Humans , Brain Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Drug Resistance, Neoplasm , Feedback , Gene Expression Regulation, Neoplastic , Glioblastoma/metabolism , MicroRNAs/metabolism , Temozolomide/therapeutic use , Forkhead Box Protein O1/metabolismABSTRACT
Objective To develop Chinese version of the Manchester patient safety framework, and evaluate the feasibility of its clinical application. Methods The Manchester patient safety framework (MaPSaF) was transformed into Chinese version by translation and back-translation together with inquiries from experts. The trial study was done firstly among 136 nurses in five pilot wards and followed by five times of focus-oriented group interviews. A semi-structured, in-depth interview was then performed in 12 randomly selected participants and acquired data were analyzed by category analysis. Result Two themes were abstracted: Chinese version of MaPSaF showed a good practicability, effectiveness and operability and it was effective for deepened understanding of patient′s safety culture. Conclusion The Chinese version of MaPSaF can be used for safety culture evaluation during nursing process in China.
ABSTRACT
Objective To evaluate whether the size,number or location of fibroids affect therapeutic efficacy of uterine artery embolization (UAE).Methods 84 patients with symptomatic uterine fibroids who had received uterine fibroid embolization with the use of polyvinyl alcohol(PVA)or gelfoam sponge particles(GSP).According to the lesion's size,number or location,all patients were divided into different groups and following -up as outpatients. Patient's symptomatic improvement and imaging following -up was assessed after UAE.Results A technically suc-cessful embolization was done in all patients.Postoperative 12 -month following -up was performed in 77 cases.No major life -threatening complications were found and the clinical symptoms were improved after UAE.In the different groups,the uterine size and the leiomyoma size after UAE were markedly decreased(t =5.842,P <0.05).Further comparison showed that the mean reduction in fibroids volume after UAE was not significant between the two groups, so was the mean reduction in uterine volume.Solitary leiomyoma group showed no significant difference in volume reduction rate of fibroids and uterine after UAE as compared with multiple leiomyoma group.Changes were not signifi-cantly in Submucosal uterine fibroids,Subserosal uterine fibroids,Intramural uterine fibroids.Conclusion UAE is an effective treatment for uterine fibroids.In this study,the size,number,and location of fibroids did not affect therapeutic efficacy or the complication rate of UAE.
ABSTRACT
Objective To evaluate the effect of the two methods of delivery,hands-on vs.handspoised,on maternal and neonatal outcomes and health service utility during vaginal delivery.Methods 218 primiparous pregnant women admitted from January to May 2013 were randomly assigned to the control group,who adopted two hands-on or traditional method (108 cases) and the intervention group who chose hand-poised method (110 cases).The delivery outcomes and medical resource utilization were compared between two groups.Results The rate of perineal trauma,postpartum hemorrhage and edema was significantly lower in the intervention group compared with that of the control group.No significant difference in neonatal outcome was observed between the two groups.The second stage duration of the intervention group was longer but the whole hospital duration and costs was significantly lower than those of the control group.Conclusions Our data suggest that a policy of hands-poised care is a safe and effective birthing alternative and could improve delivery outcome and reduce hospitalization days and costs.