BACKGROUND:Simvastatin enhanced the expression of bone morphogenetic protein-2(BMP-2),which plays an anabolic role in bone metabolism and osteoblastic lineage differentiation.However,little is known about the molecular mechanism of simvastatin on regulation of bone marrow stromal cells differentiation.OBJECTIVE:To investigated the effect of simvastatin on osteoblastic differentiation of bone marrow stromal cells based on genetics level.METHODS:Bone marrow stromal cells derived from femur and tibia were cultured in different mediums with simvastatin or Vehicle for 7 days Following extraction and purification,mRNA was reverse-transcripted into cDNA.Fluorescence labelina was employed and the samples were then hybridized with oligonucleotide chip to screen the different genes,which were utillzed to analyze osteogenesis-related factors.Alkaline phosphatase and Von Kossa staining were performed at days 14 and 21,respectively.RESULTS AND CONCLUSIONS:At day 14,alkaline phosphatase-positive cells were more in the experimental group than control group.Von Kossa staining demonstrated that simvastatin could promote BMSCs osteoblastic differentiation and mineralization.Comparative analysis showed that 103 genes out of 22 575 rat genes had differential expression (≥2 fold or≤ 0.5 fold),and some genes were related to cell proliferation and ostoeblastic differentiation,including C/EBP δ,Cited,Ascl2,Ptpnl6,Wisp2,Tieg,etc.Simvastatin could induce osteoblastic differentiation of bone marrow stromal cells,involving in many osteogenetic-related genes.

BACKGROUND: Recently simvastatin has been shown to stimulate osteogenic differentiation and bone formation, but there is no report about the effect of simvastatin on the bone development of young rats.OBJECTIVE: To evaluate the effects of simvastatin on osteogenic relative genes of proximal tibia trabecular bone and osteogenic differentiation of bone marrow stromal cells (BMSCs).METHODS: Twenty 1-week-old Spragua-Dawley young rats were randomly and equally divided into simvastatin and control groups. Rats in the simvastatin group were treated with a subcutaneous injection of simvastatin[5 mg/(kg·d)] for 2 weeks, while rats in the control group were treated with placebo for 2 weeks. The expressions of bone morphogenetic protein-2 (BMP-2), matrix metalloproteinase-13 (MMP-13), and vascular endothelial growth factor (VEGF) of trabecular bone in the tibia were analyzed by mmunohistochemicel staining. BMSCs harvested from the rat femur were osteogenic-differentiation cultured. Alkaline phosphatase (ALP) staining was performed on day 14, real-time PCR analysis was applied to investigate the BMP2, RUNX2,Osterix, MSX2, DLX3, DLX5 mRNA expressions during osteogenic differentiation in vitro on day 21, and von Kossa staining was detected on day 28.RESULTS AND CONCLUSION: ① There was no significant difference in the expressions of BMP-2, MMP-13, and VEGF between simvastatin and control groups. ② The percentages of ALP positive-stained cells were about 30% and there was no significant difference between the two groups (P ＞ 0.05). ③There was no significant difference in the expressions of BMP-2,RUNX2, Osterix, MSX2, DLX3, DLX5 mRNA in osteoganic differentiation-induced BMSCs. ④ von Kossa staining demonstrated that dark brown calcified spots in various sizes were observed, but there was no significant difference in size and density between simvastatin and control groups. A subcutaneous injection of simvastatin[5 mg/(kg·d)] for 2 weeks could not remarkably affect osteogenic relative genes of bone trabecula and osteogenic differentiation of BMSCs.

Prostate cancer （PCa） is one of the most common malignant tumors in the male genitourinary system. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is a carcinogenic pathway responsible for the migration， proliferation， and drug resistance of various cancers. In recent years， as the research on the pathogenesis of PCa is deepening， the role of the PI3K/Akt signaling pathway in the development of PCa has attracted much attention. Traditional Chinese medicine， comprehensively regulating multiple components， targets， and pathways， has shown great potential in the treatment of PCa. This article reviews the research progress of traditional Chinese medicine targeting the PI3K/Akt signaling pathway in the treatment of PCa and discusses the expression of the PI3K/Akt signaling pathway in PCa， which involves inhibiting apoptosis of PCa cells， promoting the cell cycle， invasion， and migration of PCa cells， promoting tumor tissue angiogenesis， and mediating the androgen receptor. Additionally， it summarizes the single Chinese medicines that target and regulate this pathway， including Hedyotis diffusa， Taxus chinensis， Bovisc Alculus， and Atractylodis Macrocephalae Rhizoma. The active ingredients of these Chinese medicines mainly include flavonoids， alkaloids， terpenes， polyphenols， lignans， and other compounds. The Chinese medicine compound prescriptions targeting the PI3K/Akt pathway mainly include Wenshen Sanjie prescription， Jianspi Lishi Huayu prescription， Yishen Tonglongtang， Qilan prescription， Xihuangwan， and modified Shenqi Dihuangtang. This review is expected to provide a scientific basis for deeply understanding the pathogenesis of PCa and identifying potential therapeutic targets， as well as to provide new ideas for clinical research and drug development for PCa.

OBJECTIVE： To systematically evaluate the efficacy and safety of cyclosporin combined with glucocorticoid versus cyclophosphamide combined with glucocorticoid in the treatment of membranous nephropathy （MN）. METHODS： Retrieved from Embase， Medline， CNKI， VIP and Wanfang database， RCTs about cyclosporin combined with glucocorticoid （trial group） versus cyclophosphamide combined with glucocorticoid （control group） in the treatment of MN were collected. Meta-analysis was conducted by using Rev Man 5.3 statistical software after literature screening， data extraction and quality evaluation with Jadad scale. RESULTS： Totally 6 RCTs were included， involving 312 patients in total. Results of Meta-analysis showed that remission rate 3 months after treatment [OR＝3.42，95％CI（2.05，5.71），P＜0.000 01] and relapse rate [OR＝3.12，95％CI（1.45，6.70），P＝0.004]， leukocyte count 12 months after treatment [MD＝1.77，95％CI（0.96，2.58），P＜0.000 1] in trial group were significantly higher than control group. There was no statistical significance in remission rate 6 months after treatment [OR＝2.06，95％CI（0.80，5.30），P＝0.13] and remission rate 12 months after treatment [OR＝1.30，95％CI（0.68，2.48），P＝0.42]， blood creatinine level 3 months after treatment [MD＝－1.55，95％CI（－6.72，3.62），P＝0.56] and blood creatinine level 6 months after treatment [MD＝－1.21，95％CI（－5.96，3.54），P＝0.62]， cholesterol level 12 months after treatment [MD＝－0.77，   95％CI（－1.81，0.28），P＝0.15] or ALT level[MD＝－0.40，95％CI（－4.38，3.58），P＝0.98] between 2 groups. ADR were reported in 5 RCTs， but their results were different. CONCLUSIONS： Long-term efficacy of cyclosporine combined with corticosteroid is similar to that of cyclophosphamide combined with corticosteroid in the treatment of MN. Cyclosporin combined with glucocorticoid has a faster effect， but a higher relapse rate.