BACKGROUND:The effects and molecular mechanism of simvastatin on the proliferation and differentiation of osteoblasts remain unclear. Especial y, we do not know much about the effects of connexin 43.
OBJECTIVE:To evaluate the effects of simvastatin on the proliferation and differentiation of osteoblasts and the regulatory effect of simvastatin on the expression of osteogenic genes and connexin 43.
METHODS:Newborn Sprague-Dawley rats were chosen and the cranium digestion method was used to culture osteoblasts. The different concentrations of simvastatin (0.062 5, 0.125, 0.25, 0.5 and 1.0μmol/L) were used to deal with osteoblasts. The proliferative effect of simvastatin on osteoblasts was measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The effect of simvastatin on osteoblast differentiation was measured with alkaline phosphatase activities. The mRNA and protein expression of osteogenic genes and connexin 43 were measured by real time quantitative RT-PCR and western blot assay.
RESULTS AND CONCLUSION:There were no significant differences in absorbance values of simvastatin groups at 3 days (P>0.05). However, at 4 and 5 days, absorbance values were lower in the simvastatin groups than those in the control group (P<0.05). Compared with the control group, alkaline phosphatase activities of osteoblasts were greater in the simvastatin groups (P<0.05). Moreover, the effects of 0.25μmol/L simvastatin on alkaline phosphatase activities of osteoblasts were most significant. Osteocalcin, alkaline phosphatase activities, type I col agen and connexin 43 mRNA and protein expressions were increased after treatment with 0.25μmol/L simvastatin (P<0.05). These results indicated that simvastatin may inhibit the proliferation and improve the differentiation of osteoblasts by upregulating the mRNA and protein expression of osteogenic genes and connexin 43. These data may provide the new intervention target for osteoporosis treated with statins.

Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients.Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region,were analyzed retrospectively.The first part,data of 106 patients with moderate,high-risk NMIBC were collected.A total of 83 patients were male,while the other 23 patients were female.The average age was 66.7 years old.The clinical staging were T1 in 86(81.1％) cases,Ta in 20(18.9％) cases and carcinoma in situ in 6 (5.7％) patients.Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor.The incidence rate of recurrence and progression during more than 6 months' follow-up time were observed.Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method.The second part,treatment compliance of 276 patients with bladder cancer,including moderate/high-risk NMIBC in 263 cases,moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries,were observed.Patients consisted of 211 males and 65 females with average age of 68.3 years.Results With a median follow-up of 12 months,9 (8.5％) patients experienced tumor recurrence and 2 (1.9％) patients were found progression in the first part.The one-year cancer free recurrence rate of the patients was 91.5％.Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR =3.214,95％CI0.804-12.845,P =0.099).In the second port,an incidence rate of adverse effects was 64.1％ (177/276).The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment.A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 ％),9 cases (3.3 ％) with economic reasons and 11 cases (4.0％) with serious complications.Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects.Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy.