Emerging evidence has indicated that BRCC 36-mediated K63-linked ubiquitination modification was involved in diverse cellular functions , including endocytosis , apoptosis and DNA damage repair .We previously showed that activation of cGMP/PKG pathway con-tributed to the binding of BRCC36 and the pro-fibrotic factor Smad3.The current study tested the hypothesis that BRCC 36 functions as a negative regulator of transforming growth factor-beta ( TGF-β)/Smad3 pathway and participates in cardiac remodeling .In isolated adult mouse cardiac fibroblasts , we have demonstrated that TGF-β1 treatment significantly increased the expression of BRCC 36.Over-expression BRCC36 suppressed TGF-β1-induced Smad3 phosphorylation, nuclear translocation, extracellular matrix molecular expres-sion and cell proliferation .On the contrary, silencing BRCC36 by transfection of adenovirus-carrying BRCC36 shRNA potentiated to
enhance the pro-fibrotic effect of TGF-β.In vivo, under chronic pressure overload condition-induced by transverse aortic constriction , myocardial pro-survival protein Bcl-2 and Mcl-1 expression were significantly decreased and the pro-apoptosis protein Puma was in-creased.However, the cardiac-specific over-expression of BRCC36 significantly increased myocardial Bcl-2 and Mcl-1 and inhibited Puma expression .Interestingly , we also found that sustained pressure overload resulted in a significant myocardial DNA injury in wild type mice, which was characterized by the increase of γH2AX level.However, cardiac-specific BRCC36 over-expression significantly decreased the level of γH2AX in the pressure overloaded heart in the transgenic mice , while effectively enhanced myocardial RAD 51 expression, a marker of DNA damage repair.Furthermore, BRCC36 over-expression effectively attenuated TAC-induced cardiac fibro-sis and remodeling in the transgenic mice , compared with the wild type mice .Collectively , the results have suggested that BRCC 36 ef-fectively protected heart against chronic pressure overload-induced cardiac remodeling though antagonizing TGF-β/Smad3 pathway and enhancing myocardial DNA injury repair response .

Humans have been struggling for two centuries to reduce the health and economic burden caused by pneumococcal infection. Invasive pneumococcal disease （IPD）， meningitis， and acute otitis media caused by pneumococcus occur worldwide， especially in infants， children and elderly. Pneumococcus is resistant to most antibiotics and vaccines remain the most effective measure against the pneumococcal epidemic. The development of the pneumococcal vaccine was initiated at the beginning of 21 century. In 2014， incidence and mortality of pneumococcal pneumonia and IPD induced by vaccine serotypes decreased accordingly after the introduction of 13-valent pneumococcal conjugate vaccine （PCV）. Subsequently， the new challenge is to further improve the low response of some existing vaccine serotypes， include more serotypes in the PCV， and research on the application of PCV in specific populations. This review briefly describes the development of PCV.

Objective To evaluate the application of TeamSTEPPS in training of community osteoporosis management team .Methods The TeamSTEPPS was applied for training of osteoporosis management team, and 1 513 residents aged ≥45 year were screened for osteoporosis in Kangjian community from January 2014 to March 2017.The identified patients with osteopenia and osteoporosis were intervened for one year.Cognitive level of the risk factors and symptoms associated with osteoporosis were assessed by questionnaires before and after the intervention .The bone density was examined at baseline and 6 months, 12 months after intervention.The effect of intervention was evaluated .Results A total of 467 patients (30.87%) with osteopenia and 476 patients (31.46%) with osteoporosis were detected .The cognitive levels of osteoporosis risk factors , including low calcium, vitamin D deficiency, lack of exercise, low weight, women menopause, matrilineal family history, smoking, excessive alcohol drinking and coffee drinking, were higher than those before intervention ( χ2＝62.909,78.742,59.974,50.478,29.512, 34.699,6.500,15.779,6.089,all P＜0.05).The awareness rates of symptoms , including lower back pain or body bone pain, shorter height and hunchback , low energy or nonviolent fracture , were also increased (χ2＝59.942,76.220,16.856,all P＜0.01).After intervention, the bone mineral density levels were increased compared to those before intervention (F＝530.28, P＜0.01 for osteopenia group; F＝339.51, P＜0.01 for osteoporosis group ); meanwhile, the differences were also significant between 6 months, 12 months after intervention and before intervention , between 12 months and 6 months after intervention (t＝-0.452,-0.968,-0.516,all P＜0.01 for osteopenia group; t＝-0.530,-1.045,-0.518, all P＜0.01 for osteoporosis group ).Conclusion The community osteoporosis management team trained by TeamSTEPPS can effectively improve the management levels of osteoporosis among residents in the community.