ABSTRACT
BACKGROUND@#Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.@*METHODS@#The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.@*RESULTS@#Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.@*CONCLUSIONS@#The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.
Subject(s)
Animals , Mice , Humans , Proto-Oncogene Proteins c-akt/metabolism , Actins/metabolism , Neoplasm Recurrence, Local , TOR Serine-Threonine Kinases/metabolism , Urinary Bladder Neoplasms , Glycolysis , Cell Line, Tumor , Cell Proliferation , Mammals/metabolism , Tripartite Motif Proteins/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Integrin beta ChainsABSTRACT
Objective:To evaluate the incidence and its impact fortors of sleep disorders among patients with gout.Methods:A total of 414 patients with gout were included in the study. A series of questionnaires including socio-economical and disease related scale, the Pittsburgh Sleep Quality Index (PSQI), Fatigue Scale-14, the Patient Health Questionnaire, the Generalized Anxiety Disorder questionnaire, the 10 cm Visual Analog Scale for total pain, patient self-reported confidence in gout treatment and the Health Assessment Questionnaire-Disability Index were carried out in the patients. The statistical methods used in the study included t test, rank sum test, chi-square test and regression analysis. Results:The median age of gout patients in this study was 54 years and 96.4% were men, the mean serum uric acid level was (474.98±120.14) μmol/L. Among them, 201 (48.6%) patients showed sleep disorders, and the worse sleep quality was reflected in subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency and each dimension of PSQI. It was found that sleep disorders in gout patients were associated with living in rural areas, unemployment, long disease duration, disease stage, depression, anxiety, lack of confidence in regular blood examination and some other factors. In addition, patients with severe pain ( OR=1.087, P=0.029), fatigue ( OR=1.125, P=0.002), tophi ( OR=1.843, P=0.014) and functional disability ( OR=2.916, P<0.001) were more likely to get sleep disorders. Conclusions:The incidence of sleep disorders in patients with gout is high, and it′s associated with disease duration, psychological status, pain, tophi, disease stage, functional disability.
ABSTRACT
Objective:To investigate the current situation in construction and operation status of official WeChat public platform of community hospitals in Shanghai Downtown and provide the reference for effective application of WeChat public platform in community hospitals.Methods:The current situation of health service provided with WeChat public platform of community hospitals was investigated by website survey.We focused on the opening rate,menu services,information push and off-line operations of WeChat public platform from the perspective of ethics.Results:Of the investigated 98 hospitals,a total of 48 WeChat public platforms were established,accounting for 49.0％.Among which 28 public platforms provided menu bar service,accounting for 58.3％.The public platforms still needed to be improved in terms of article push quantity,reading quantity and daily management.Conclusion:The development level of WeChat public platform of community hospital in shanghai downtown is uneven and WeChat public platform of community hospital exists low service level,imperfect management,lack of publicity and other problems generally.It is recommended that hospitals strengthen the construction of WeChat platform from three aspects,including strengthening team management,keeping the "Six in One" and seeking for commercial assistance.