RESUMO
OBJECTIVE To systematically evaluate the efficacy and safety of denosumab versus bisphosphonates in the treatment of osteoporosis， and to provide evidence-based reference for clinical treatment. METHODS Randomized controlled trials （RCTs） about denosumab （trial group） versus bisphosphonates （control group） in the treatment of osteoporosis were retrieved from PubMed， Embase， Medline， the Cochrane Library， Chinese Journal Fulltext Database， Chinese Science and Technology Journal Database， Wanfang database from January 2012 to December 2022. After the data extraction of included clinical studies， the quality of included studies was evaluated with Cochrane Handbook for Systematic Review 5.1.0， and meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 6 RCTs were included， involving 3 145 patients. Meta-analysis showed that the improvement rate of lumbar bone mineral density （BMD） [MD＝1.78， 95%CI（1.13， 2.43）， P＜0.000 01]， femoral neck BMD [MD＝1.26， 95%CI （1.08， 1.45）， P＜0.000 01] and total hip BMD [MD＝1.16，95%CI（0.93，1.39），P＜0.000 01] in trial group were significantly better than control group. C-terminal telopeptide of type Ⅰ collagen after 6 months [MD＝－0.09， 95%CI （－0.16， －0.02）， P＝0.01] and N-terminal propeptide of type Ⅰ collagen after 12 months [MD＝－9.07， 95%CI （－11.22， －6.92）， P＜ 0.001] in trial group were significantly higher than control group. There was no statistical difference in the fracture incidence rate after 12 months [OR＝1.02， 95%CI （0.67，1.54）， P＝0.92] and the incidence of adverse reaction [OR＝0.99， 95%CI （0.67，1.46）， P＝0.97] between 2 groups. CONCLUSIONS Denosumab has more advantages in improving BMD and bone metabolism， compared with bisphosphonates.
RESUMO
OBJECTIVE：To systematically e valuate the efficacy and safety of duloxetine in the improvement of pain symptoms of knee osteoarthritis （KOA），and to provide evidence-based reference for clinical treatment of KOA. METHODS ：Retrieved from PubMed，Embase，Medline，Cochrane Library ，CNKI，VIP and Wanfang database ，during the establishment of the database to Sept. 2019，RCTs about duloxetine （trial group ）vs. placebo （control group ）in the improvement of pain symptoms of KOA were collected. After data extraction and quality evaluation using Cochrane system evaluator ’s manual 5.1.0，Meta-analysis was performed by using Stata 14.0 software for WOMAC total score ，WOMAC pain score ，WOMAC stiffness score ，WOMAC function score and BPI-S score ，as well as the incidence of adverse reaction such as dry mouth ，somnolence and nausea. RESULTS：A total of 6 RCTs were included ，involving 2 059 patients. Meta-analysis results showed that WOMAC total score [MD＝－0.34，95％CI（－0.48，－0.20），P＜0.05]，WOMAC pain score [MD ＝－0.41，95％CI（－0.54，－0.29），P＜0.05]， WOMAC stiffness score [MD ＝－0.24，95％ CI（－0.37，－0.12），P＜0.05]，WOMAC function score [MD ＝－0.43，95％CI （－0.55，－0.31），P＜0.05]，BPI-S score [MD ＝－0.38，95％CI（－0.48，－0.28），P＜0.05] of trial group were significantly lower than those of control group ；the incidence of dry mouth [RR ＝3.55，95％CI（2.00，6.29），P＜0.05]，somnolence [RR ＝3.23， 95％CI（1.88，5.54），P＜0.05] and nausea [RR ＝6.95，95％CI（2.99，16.15），P＜0.05] in trial group were significantly higher than control group ，with significant difference. CONCLUSIONS ：Duloxetine can relieve the pain and improve knee function in patients with KOA ，but it is necessary to pay attention to its adverse reactions.
RESUMO
AIM: To explore whether tumor necrosis factor-α (TNF-α) induces necroptosis in murine long bone osteocyte-like cell line MLO-Y4 and the possible mechanism.METHODS: The MLO-Y4 cells were divided into control group, TNF-α group, TNF-α+necrostatin-1 (Nec-1) group, TNF-α+Z-VAD group and TNF-α+receptor-interacting protein 3 (RIP3)-siRNA group.The death rate of MLO-Y4 cells was assessed by flow cytometry with Annexin V-FITC/PI staining.The morphological features of the cells were observed under transmission electron microscope (TEM).The protein levels of RIP1, RIP3 and cleaved caspase-3 were determined by Western blot.Finally, the numbers of total cells and RIP1-RIP3-positive cells were observed under laser scanning confocal microscope.The production of reactive oxygen species (ROS) in the cells was measured by DCFH-DA staining.RESULTS: Compared with control group, the apoptotic or necroptotic rate of the cells induced by TNF-α was increased significantly (P<0.01).The increased apoptotic or necroptotic rate was dramatically reduced by treating with Nec-1, Z-VAD or RIP3-siRNA transfection (P<0.01).In TNF-α group and TNF-α+Z-VAD group, a lot of MLO-Y4 cells with typical necroptotic morphological features were observed under TEM.However, obvious necroptotic cells were not found in Nec-1 or RIP3-siRNA treatment group.The protein level of RIP1 in the cells treated with Nec-1 was sharply lower than that in TNF-α group (P<0.01).However, Z-VAD did not reduce the elevated levels of RIP1 and RIP3.RIP3-siRNA effectively down-regulated the protein level of RIP3 compared with TNF-α group (P<0.01).Nec-1 effectively down-regulated the protein levels of RIP1 colocalized with RIP3 compared with TNF-α group (P<0.01).However, Z-VAD did not reduce the levels of RIP1 colocalized with RIP3.Nec-1, Z-VAD and RIP3 siRNA significantly decreased the ROS levels (P<0.01).CONCLUSION: TNF-α induces the necroptosis of MLO-Y4 cells.RIP3 play vital roles in the cell necroptotic signal pathway.ROS may be the executor of necroptosis of MLO-Y4 cells.