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Abstract Inflammatory reactions are involved in the development of steroid-induced osteonecrosis of the femoral head(ONFH). Studies have explored the therapeutic efficacy of inhibiting inflammatory reactions in steroid-induced ONFH and revealed that inhibiting inflammation may be a new strategy for preventing the development of steroid-induced ONFH. Exosomes derived from M2 macrophages(M2-Exos) display anti-inflammatory properties. This study aimed to examine the preventive effect of M2-Exos on early-stage steroid-induced ONFH and explore the underlying mechanisms involved. In vitro, we explored the effect of M2-Exos on the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells(BMMSCs). In vivo, we investigated the role of M2-Exos on inflammation, osteoclastogenesis, osteogenesis and angiogenesis in an early-stage rat model of steroid-induced ONFH. We found that M2-Exos promoted the proliferation and osteogenic differentiation of BMMSCs. Additionally, M2-Exos effectively attenuated the osteonecrotic changes, inhibited the expression of proinflammatory mediators, promoted osteogenesis and angiogenesis, reduced osteoclastogenesis, and regulated the polarization of M1/M2 macrophages in steroid-induced ONFH. Taken together, our data suggest that M2-Exos are effective at preventing steroid-induced ONFH. These findings may be helpful for providing a potential strategy to prevent the development of steroid-induced ONFH.

Abstract Background Spondyloarthritis (SpA) is a group of multifactorial bone diseases influenced by genetic factors, the environment and lifestyle. However, current studies have found a limited number of SpA-related genes, and the genetic and pathogenic mechanisms of SpA are still unclear. Methods A tissue-specific transcriptome-wide association study (TWAS) of SpA was performed using GWAS (including 3966 SpA patients and 448,298 controls) summary data and gene expression weights of whole blood and skeletal muscle. The SpA-associated genes identified by TWAS were further compared with the differentially expressed genes (DEGs) identified in the SpA gene expression profile acquired from the Gene Expression Omnibus database (GEO, GSE58667). Finally, functional enrichment and annotation analyses of the identified genes were performed. Results The TWAS detected 499 suggestive genes associated with SpA in whole blood and skeletal muscle, such as CTNNAL1 (P SM = 3.04 × 10−2, P WB = 9.58 × 10−3). The gene expression profile of SpA identified 20 candidate genes that overlapped in the TWAS data, such as MCM4 (P TWAS = 1.32 × 10−2, P DEG = 2.75 × 10−2) and KIAA1109 (P TWAS = 3.71 × 10−2, P DEG = 4.67 × 10−2). Enrichment analysis of the genes identified by TWAS identified 93 significant GO terms and 33 KEGG pathways, such as mitochondrion organization (GO: 0007005) and axon guidance (hsa04360). Conclusion We identified multiple candidate genes that were genetically related to SpA. Our study may provide novel clues regarding the genetic mechanism, diagnosis, and treatment of SpA.

Abstract There are various internal fixation methods in treating lumbosacral spinal tuberculosis. The study compared the stability and stress distribution in surrounding tissues/implants, such as discs, endplates and screw-rod internal fixation system, etc. when applying three different lumbar internal fixation methods to treat lumbosacral spinal tuberculosis. A finite element model was constructed and validated. The spinal stability was restored using three methods: a titanium cage with lateral double screw-rod fixation (group 1), autologous bone with posterior double screw-rod fixation (group 2), and a titanium cage with posterior double screw-rod fixation (group 3). For comparison, group 4 represented the intact L3-S1 spine. Finally, a load was applied, and the ranges of motion and Von Mises stresses in the cortical endplates, screw-rod internal fixation system and cortical bone around the screws in the different groups were recorded and analyzed. All six ranges of motion (flexion, extension, left/right lateral bending, left/right rotation) of the surgical segment were substantially lower in groups 1 (0.53° ~ 1.41°), 2 (0.68° ~ 1.54°) and 3 (0.55° ~ 0.64°) than in group 4 (4.48° ~ 10.12°). The maximum stress in the screw-rod internal fixation system was clearly higher in group 2 than in groups 1 and 3 under flexion, left/right lateral bending, and left/right rotation. However, in extension, group 1 had the highest maximum stress in the screw-rod internal fixation system. Group 2 had the lowest peak stresses in the cortical endplates in all directions. The peak stresses in the cortical bone around the screws were higher in group 1 and group 2 than in group 3 in all directions. Thus, titanium cage with posterior double screw-rod fixation has more advantages in immediate reconstruction of lumbosacral spinal stability and prevention of screw loosening.

Abstract Background SF-6Dv2, the latest version of SF-6D, has been developed recently, and its measurement properties remain to be evaluated and compared with the EQ-5D-5L. The aim of this study was to assess and compare the measurement properties of the SF-6Dv2 and the EQ-5D-5L in a large-sample health survey among the Chinese population. Methods Data were obtained from the 2020 Health Service Survey in Tianjin, China. Respondents were randomly selected and invited to complete both the EQ-5D-5L and SF-6Dv2 through face-to-face interviews or self-administration. Health utility values were calculated by the Chinese value sets for the two measures. Ceiling and floor effects were firstly evaluated. Convergent validity and discriminate validity were examined using Spearman’s rank correlation and effect sizes, respectively. The agreement was assessed using intraclass correlation coefficients (ICC). Sensitivity was compared using relative efficiency and receiver operating characteristic. Results Among 19,177 respondents (49.3% male, mean age 55.2 years, ranged 18–102 years) included in this study, the mean utility was 0.939 (0.168) for EQ-5D-5L and 0.872 (0.184) for SF-6Dv2. A higher ceiling effect was observed in EQ-5D-5L than in SF-6Dv2 (72.8% vs. 36.1%). The Spearman’s rank correlation (range: 0.30–0.69) indicated an acceptable convergent validity between the dimensions of EQ-5D-5L and SF-6Dv2. The SF-6Dv2 showed slightly better discriminative capacities than the EQ-5D-5L (ES: 0.126–2.675 vs. 0.061–2.256). The ICC between the EQ-5D-5L and SF-6Dv2 utility values of the total sample was 0.780 (p

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