BackgroundStrontium is a widely used anti-osteoporotic agent due to its dual effects on inhibiting bone resorption and stimulating bone formation. Thus, we studied the dose response of strontium on osteo-inductive efficiency in human adipose-derived stem cells (hASCs).MethodQualitative alkaline phosphatase (ALP) staining, quantitative ALP activity, Alizarin Red staining, real-time polymerase chain reaction and Western blot were used to investigate the in vitro effects of a range of strontium concentrations on hASC osteogenesis and associated signaling pathways.ResultsIn vitro work revealed that strontium (25–500 μM) promoted osteogenic differentiation of hASCs according to ALP activity, extracellular calcium deposition, and expression of osteogenic genes such as runt-related transcription factor 2, ALP, collagen-1, and osteocalcin. However, osteogenic differentiation of hASCs was significantly inhibited with higher doses of strontium (1000–3000 μM). These latter doses of strontium promoted apoptosis, and phosphorylation of ERK1/2 signaling was increased and accompanied by the downregulation of Bcl-2 and increased phosphorylation of BAX. The inhibition of ERK1/2 decreased apoptosis in hASCs.ConclusionLower concentrations of strontium facilitate osteogenic differentiation of hASCs up to a point; higher doses cause apoptosis of hASCs, with activation of the ERK1/2 signaling pathway contributing to this process.

Background Identifying risk factors and early intervention are critical for improving the satisfaction rate of total knee arthroplasty (TKA). Our study aimed to identify patient-specific variables and establish a nomogram model to predict dissatisfaction at 1 year after TKA. Methods This prospective cohort study involved 208 consecutive primary TKA patients with end-stage arthritis who completed self-reported measures preoperatively and at 1 year postoperatively. All participants were randomized into a training cohort (n = 154) and validation cohort (n = 54). Multiple regression models with preoperative and postoperative factors were used to establish the nomogram model for dissatisfaction at 1 year postoperatively. The least absolute shrinkage and selection operator method was used to screen the suitable and effective risk factors (demographic variables, preoperative variables, surgical variable, and postoperative variables) collected. These variables were compared between the satisfied and dissatisfied groups in the training cohort. The receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis were used to validate the discrimination, calibration, and clinical usefulness of the model. Results were evaluated by internal validation of the validation cohort. Results The overall satisfaction rate 1 year after TKA was 77.8%. The nomogram prediction model included the following risk factors: gender; primary diagnosis; postoperative residual pain; poor postoperative range of motion; wound healing; and the rate of change in the degree of coronal lower limb alignment (hip–knee–ankle angle, HKA).The ROC curves of the training and validation cohorts were 0.9206 (95% confidence interval [CI], 0.8785–0.9627) and 0.9662 (0.9231, 1.0000) (95% CI, 0.9231, 1.0000), respectively. The Hosmer–Lemeshow test showed good calibration of the nomogram (training cohort, p = 0.218; validation cohort, p = 0.103). Conclusion This study developed a prediction nomogram model based on partially modifiable risk factors for predicting dissatisfaction 1 year after TKA. This model demonstrated good discriminative capacity for identifying those at greatest risk for dissatisfaction and may help surgeons and patients identify and evaluate the risk factors for dissatisfaction and optimize TKA outcomes.

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Background: Sonication is very efficacious for the microbiological diagnosis of periprosthetic joint infection (PJI), but it involves many steps and multiple workplaces and personnel and therefore carries a potential contamination risk. We present an innovative version of the sonication culture method that involves direct sonication of the retrieved implant and soft tissue, without a sonication tube, intraoperatively and incubation using a BACT/ALERT 3D blood culture system to enhance the efficacy of microbiological diagnosis of PJI. Methods:We performed a prospective study of consecutive patients requiring implant removal and classified them as having PJI or aseptic failure according to standard criteria. The removed prosthetic components and adjacent soft tissue were directly sonicated in a small metal container, without a sonication tube, during the operation. The sonication fluid was immediately incubated in blood culture bottles in the operating room and cultured in the BACT/ALERT 3D blood culture system. The synovial fluid was also cultured in the BACT/ALERT 3D system to serve as a comparison.Results: Of the 64 included patients, 36 had PJI and 28 had aseptic failure. Fluid from direct sonication and conventional synovial fluid showed sensitivities of 91.7% and 55.6% (p < 0.001) and specificities of 82.1% and 92.9%, respectively. Fourteen cases of PJI were detected by culture of fluid from direct sonication but not by culture of synovial fluid. Higher sensitivity was obtained by direct sonication of only tissue than by direct sonication of only the implant (88.9% versus 75.0%). No significant difference in detection time was found between Staphylococcus aureus and coagulase-negative Staphylococcus.Conclusions: When combined with incubation in BACT/ALERT bottles, direct intraoperative sonication of implants and soft tissues without a sonication tube was more sensitive than conventional synovial fluid culture and could reliably and rapidly detect the bacteria commonly found in PJI.

Background Many observational studies focus on the relationship between Nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD). However, the conclusions are controversial and the causal relationship between NAFLD and BMD remains unclear. Method A bi-directional two-sample Mendelian randomization (MR) analysis was performed to investigate the potential causal links between NAFLD and BMDs. We applied genetic variants as instrumental variables obtained from the Genetic Factors for Osteoporosis (GEFOS) dataset and several published genome-wide association studies (GWASs). We obtained summary statistics for heel (H) BMD (n = 426,824), femoral neck (FN) BMD (n = 32,735), lumbar spine (LS) BMD (n = 28,498), ultra-distal forearm (UF) BMD (n = 21,907), and total body (TB) BMD (n = 56,284) from some GWAS meta-analyses. Additionally, the NAFLD GWAS included 377,988 individuals of European ancestry which consist of 4,761 NAFLD cases and 373,227 control cases. We used inverse variance weighted (IVW), four supplemental methods, and several sensitivity analyses to estimated and cross-validate the potential causal relationship in the present MR analysis. Results The sensitivity analyses do not find any violation of the MR assumptions. We found that NAFLD has no causal association with H-BMD (beta − 0.017; 95%CI -0.0458,0.0117; p = 0.2461), FN-BMD (beta − 0.0166; 95%CI -0.1592,0.1259; p = 0.8191), LS-BMD (beta − 0.021; 95%CI -0.1475,0.1055; p = 0.7446), UF-BMD (beta − 0.0524; 95%CI -0.1726,0.0679; p = 0.3935), TB-BMD (beta − 0.0596, 95%CI -0.1236,0.0044; p = 0.0678). Similarly, reverse MR analysis provided little support for a causal effect of BMDs on NAFLD. Conclusion This MR study found no evidence to support a bi-directional causality between NAFLD and BMD.

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