The protective effects of simvastatin in Cadmium-Induced preosteoblast injury through Nox4.

Cadmium (Cd) has a direct toxic effect on bones. Statins such as simvastatin have protective effects on various diseases, including on tissue injury. The current study revealed the efficacy of simvastatin on Cd-induced preosteoblast injury. Preosteoblast MC3T3-E1 cells were incubated with various doses of CdCl2 for 12 h, 24 h and 48 h, and then the cell cytotoxicity was assessed using MTT assay and flow cytometry, respectively. The expression level of Nox4 was assessed by Western blot and qRT-PCR. The morphological appearance of MC3T3-E1 cells was observed under a microscope. Cells exposed to CdCl2 (5 µM) were further treated by simvastatin at various doses, subsequently cell viability, apoptosis and the expression of Nox4 were measured. Furthermore, to confirm the protective effects of simvastatin on Cd-induced pre-osteoblast injury, functional rescue assays were performed after corresponding cell treatment by simvastatin (10-8 M), CdCl2 (5 µM), and overexpression of Nox4. Expressions of cell apoptosis-related markers were measured by Western blot and qRT-PCR. The results revealed that CdCl2 caused MC3T3-E1 cell injury because the cell viability was decreased and the apoptosis was increased. Nox4 expression was up-regulated with the increase of CdCl2 concentrations. Simvastatin increased the cell viability, relieved the cell apoptosis and Nox4 expression previously increased by CdCl2. The effects of CdCl2 on MC3T3-E1 cells and Nox4 expression could be attenuated by simvastatin, and promoted by Nox4 overexpression. The current study found that simvastatin protects Cd-induced preosteoblast injury via Nox4, thus, it can be used as a potential drug for treating cadmium-induced bone injury.

Expert consensus on protocol of rehabilitation for COVID-19 patients using framework and approaches of WHO International Family Classifications.

Coronavirus disease 2019 (COVID-19) has widely spread all over the world and the numbers of patients and deaths are increasing. According to the epidemiology, virology, and clinical practice, there are varying degrees of changes in patients, involving the human body structure and function and the activity and participation. Based on the World Health Organization (WHO) International Classification of Functioning, Disability and Health (ICF) and its biopsychosocial model of functioning, we use the WHO Family of International Classifications (WHO-FICs) framework to form an expert consensus on the COVID-19 rehabilitation program, focusing on the diagnosis and evaluation of disease and functioning, and service delivery of rehabilitation, and to establish a standard rehabilitation framework, terminology system, and evaluation and intervention systems based the WHO-FICs.

The Effect of Timing on the Treatment and Outcome of Combined Fourth and Fifth Carpometacarpal Fracture Dislocations.

PURPOSE: In this study, we designed a prospective project to test the hypothesis that acute fourth and fifth carpometacarpal (CMC) fracture dislocations can be treated conservatively with good restoration of strength, range of motion (ROM), and function, whereas patients with delayed treatment of fourth and fifth CMC fracture dislocations should be treated with open reduction and internal fixation (ORIF). METHODS: We evaluated the results of 20 patients with acute and 6 patients with subacute fourth and fifth CMC fracture dislocations. All 20 acute CMC fracture dislocations were treated conservatively, whereas 3 of the 6 patients with subacute injuries underwent operative intervention. The sensibility, ROM, and grip strength of the hands were tested during 1-year follow-up. The Michigan Hand Outcomes Questionnaire and control radiographs were also taken. RESULTS: All 20 patients with acute CMC fracture dislocations showed good restoration of grip strength, ROM, and function, with an average Michigan Hand Outcomes Questionnaire score of 98 ± 2 at 1-year follow-up. Patients with delayed diagnosis who underwent conservative treatment had noticeable deformity of their injured hands, pain complaints, limited ROM at the fourth and fifth CMC joints, and decreased grip strength. The 3 patients with delayed diagnosis treated with ORIF showed good restoration of grip strength, ROM, and function. CONCLUSIONS: Patients with acute CMC fracture dislocations can be treated by closed reduction with good restoration of grip strength, ROM, and function. In patients with delayed presentation of CMC fracture dislocations, we recommend ORIF. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.