Cathepsin K (CatK) is one of the most potent proteases in lysosomal cysteine proteases family, of which main function is to mediate bone resorption. Currently, CatK is among the most attractive targets for anti-osteoporosis drug development. Although many pharmaceutical companies are working on the development of selective inhibitors for CatK, there is no FDA approved drug till now. Odanacatib (ODN) developed by Merck & Co. is the only CatK inhibitor candidate which demonstrated high therapeutic efficacy in patients with postmenopausal osteoporosis in Phase III clinical trials. Unfortunately, the development of ODN was finally terminated due to the cardio-cerebrovascular adverse effects. Therefore, it arouses concerns on the undesirable CatK inhibition in non-bone sites. It is known that CatK has far-reaching actions throughout various organs besides bone. Many studies have also demonstrated the involvement of CatK in various diseases beyond the musculoskeletal system. This review not only summarized the functional roles of CatK in bone and beyond bone, but also discussed the potential relevance of the CatK action beyond bone to the adverse effects of inhibiting CatK in non-bone sites.

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Objective. To systematically evaluate the efficacy of acupuncture associated with physical and mental intervention when treating idiopathic tinnitus and the improvement of tinnitus symptoms, so as to supply evidence-based medicine for its popularization and adoption. Methods. PubMed, EMBASE, ScienceDirect, Cochrane Library, China knowledge Network Database (CNKI), China VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM) online database were searched for the controlled trial of acupuncture associated with physical and mental intervention when treating idiopathic tinnitus. The retrieval time limit is from January 2010 to March 2022. Separately, two researchers extracted the data, and according to the Cochrane Handbook 5.3, the bias risk of each piece of literature was assessed. The collected data were measured using RevMan5.3 statistical software. Results. Finally, 5 CT articles were included in this study, with a total sample size of 282. Meta-analysis showed that the effective rate of the study group was significantly higher than that of the control group ( P < 0.05 ). The scores of tinnitus disorder scale (THI) after treatment were analyzed by Meta. The THI scores of the study group after treatment were significantly lower than those before treatment. Meta-analysis of the severity of tinnitus after treatment showed that the severity of tinnitus in the observation group after treatment was significantly lower than that before treatment. There is a certain publication deviation in the literature, which may be related to the heterogeneity of the research and the small number of literatures. Conclusion. On the basis of acupuncture treatment, associated with physical and mental intervention is helpful to the recovery of patients with idiopathic tinnitus, can effectively improve their clinical symptoms, and is suitable for clinical application. A popularization of this concept in clinical practice is worth considering, but further research and follow-up with a higher methodological quality and longer intervention time are needed to confirm its efficacy.

Introduction Bone delay union is mostly caused by lack of blood supply. Although autografts, allografts and artificial bone have been widely used to treat bone delay union, the bone regeneration fails in the ischemic site accompanied by the bone donor site complications and disease transmission. Recently, there is a growing recognition of the importance of hydrogel scaffolds which are regarded as an eligible engineer tissue for bone repair. However, hydrogel is still limited in improving neovascularization. Methods In this work, black phosphorus nanosheet and deferoxamine (BPN-DFO) were loaded in the gelatin hydrogel to overcome the high risk of bone delay union and systemically investigated the regeneration capability of BPN-DFO hydrogel in vitro and vivo. Results The resulting BPN-DFO hydrogel scaffold showed superior swollen, degradation and release rate, as well as satisfied biocompatibility. BPN-DFO hydrogel shown the significant up-expression of mRNA related to bone regeneration and cell proliferation. In vivo, the proposed BPN-DFO hydrogel significantly improved osteogenesis and neovascularization in the ischemic tibial bone site of SD rats with acute femoral artery occlusion. Both macroscopic and histological evaluation of new regenerated bone showed newly formed blood vessel and collagen using BPN-DFO hydrogel. The immunohistochemistry and RT-PCR revealed that the bone regeneration could be improved via BMP/Runx2 pathway. Conclusion The BPN-DFO hydrogel possesses potential tissue engineer material for ischemic bone defect treatment. However, furthermore studies are needed to testify the safety and efficacy of BPN-DFO hydrogel.

Purpose The aim of this study is to investigate the effectiveness of using a new distraction support in intramedullary nailing treatment for tibial shaft fracture.Methods: Patients at the trauma center who underwent the treatment for tibial shaft fractures from July 2013 to December 2018 were enrolled. The patients were randomized in control group(n=43) and distraction support(SD) group(n=42). All operations were performed by the same senior surgeon. The hospital day, blood loss, operative time, infect rate, delayed union rate and malalignment rate(p=0.68) were obtained for the evaluation.Results: 85 participants were recruited and all cases were achieved the acceptable reduction. The operative time was significantly shorter for DS group than control group (75.3 vs.90.4 p<0.001). Blood loss was significantly lower in the DS group compared to the control group(60.1vs.85.4 p=0.003) . There were no obvious difference about infect rate(p=0.98), delay union(p=0.45), hospital days(p=0.37) and malalignment rate(p=0.68) between the two groups.Conclusion: Distraction support was effective in intramedullary nailing surgery. The application of distraction support may be a useful method in our future work.