Osteoarthritis (OA) is a degenerative illness that greatly impacts the life quality of patients. Currently, the therapeutic approaches for OA are very limited in clinical. The extracellular vesicles (EVs) derived from different mesenchymal stem cells displayed a prominent therapeutic effect on OA. But most EVs have limited resources and the risks of host rejection, immunological response, and etc. Human umbilical cord mesenchymal stem cells (hUCMSCs) hold the advantages of easy availability, minimal immune rejection, and excellent immunomodulatory effects, although hUCMSCs-EVs have seldom been applied in OA. Herein, we investigated the potential immunomodulatory and anti-inflammatory effects of hUCMSCs-EVs on the treatment of OA. In our results, the treatment of hUCMSCs-EVs promoted the polarization of M2-type macrophages and the expression of anti-inflammation-related cytokines (IL-10). Notably, the supernate of M2 macrophages induced by hUCMSCs-EVs inhibited the level of inflammation-associated factors in OA chondrocytes caused by IL-1β. Further, injection of hUCMSCs-EVs in the articular lumen ameliorated progression of OA and exerted chondroprotective potential based on the OA joint model created by the surgical transection of the anterior cruciate ligament (ACLT). In addition, we found five highly enriched miRNAs in hUCMSCs-EVs, including has-miR-122-5p, has-miR-148a-3p, has-miR-486-5p, has-miR-let-7a-5p, and has-miR-100-5p by High-throughput sequencing of miRNAs, with targeted genes mainly enriched in the PI3K-Akt signaling pathway. Furthermore, we also detected the protein abundance of hUCMSCs-EVs using liquidation chromatography with tandem quadrupole mass spectrometry (LC–MS/MS) analysis. Thus, our study indicates that hUCMSCs-EVs can alleviate cartilage degradation during the OA progression, mechanically may through delivering key proteins and modulating the PI3K-Akt signaling pathway mediated by miRNAs to promote polarization of M2 macrophage, exhibiting potent immunomodulatory potential. The current findings suggest that hUCMSCs-EVs might serve as a new reagent for the therapy of OA. Graphical Abstract

Background: Telomere length shortening can cause senescence and apoptosis in various immune cells, resulting in immune destabilization and ageing of the organism. In this study, we aimed to systematically assess the causal relationship of leukocyte telomere length (LTL) with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) using a Mendelian randomization study.Methods: LTL (n=472174) was obtained from the UK Biobank genome-wide association study pooled data. AS (n=229640), RA (n=212472) were obtained from FinnGen database. MR-Egger, inverse variance weighting, and weighted median methods were used to estimate the effects of causes. Cochran’s Q test, MR Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots were used to look at sensitivity, heterogeneity, and multiple effects. Forward MR analysis considered LTL as the exposure and AS, RA as the outcome. Reverse MR analysis considered AS, RA as the exposure and LTL as the outcome.Results: In the forward MR analysis, inverse variance-weighted and weighted median analysis results indicated that longer LTL might be associated with increased risk of AS (IVW: OR = 1.55, 95% CI: 1.14-2.11, p = 0.006). MR Egger regression analysis showed no pleiotropy between instrumental variables (IVs) (Egger intercept= 0.008, p = 0.294). The leave-one-out analysis showed that each single nucleotide polymorphism (SNP) of AS was robust to each outcome. No significant causal effects were found between AS, RA and LTL in the reverse MR analysis.Conclusion: Longer LTL may be related with an increased risk of developing AS, and these findings provide a foundation for future clinical research on the causal association between LTL and AS.

Background: Amputation is a serious complication of acute compartment syndrome (ACS), and predicting the risk factors associated with amputation remains a challenge for surgeons. The aim of this study was to analyze the risk factors for amputation in patients with ACS and develop a nomogram to predict amputation risk more accurately. Methods: The study population consisted of 143 patients (32 in the amputation group and 111 in the limb preservation group) diagnosed with ACS. LASSO and multivariate logistic regression were used to screen predictors and create a nomogram. The model’s accuracy was assessed by receiver operating characteristic (ROC) curves, C-index, calibration curves, and decision curve analysis (DCA). Results: The predictors included cause of injury, vascular damage, shock, and fibrinogen in the nomogram. The C-index of the model was 0.872 (95% confidence interval: 0.854–0.962), and the C-index calculated by internal validation was 0.838. The nomogram’s area under the curve (AUC) was 0.849, and the calibration curve demonstrated a high degree of agreement between the nomogram’s predictions and actual observations. Additionally, the DCA indicated good clinical utility for the nomogram. Conclusion: The risk of amputation in ACS patients is associated with the cause of injury, vascular damage, shock, and fibrinogen. Our nomogram integrating clinical factors and biochemical blood markers enables doctors to more conveniently predict the risk of amputation in patients with ACS.

Although observational studies have explored factors that may be associated with osteoporosis, it is not clear whether they are causal. Osteoporosis in men is often underestimated. This study aimed to identify the causal risk factors associated with bone mineral density(BMD) in men. Single nucleotide polymorphisms (SNPs) associated with the exposures at the genome-wide significance (p < 5x10^-8) level were obtained from corresponding genome-wide association studies (GWASs) and were utilized as instrumental variables. Summary-level statistical data for BMD were obtained from two large-scale UK Biobank GWASs. A Mendelian randomization (MR) analysis was performed to identify causal risk factors for BMD. Regarding the BMD of the heel bone, the odds of BMD increased per 1-SD increase of free testosterone (FT) (OR = 1.13, P = 9.4 × 10⁻¹⁷), together with estradiol (E2) (OR = 2.51, P = 2.3 × 10⁻⁴). The odds of BMD also increased with the lowering of sex-hormone binding globulin (SHBG) (OR = 0.87, P = 7.4 × 10⁻⁸) and total testosterone (TT) (OR = 0.96, P = 3.2 × 10⁻²) levels. Regarding the BMD of the lumbar spine, the odds of BMD increased per 1-SD increase in FT (OR = 1.18, P = 4.0 × 10⁻³). Regarding the BMD of the forearm bone, the odds of BMD increased with lowering SHBG (OR = 0.75, P = 3.0 × 10⁻³) and TT (OR = 0.85, P = 3.0 × 10⁻³) levels. Our MR study corroborated certain causal relationships and provided genetic evidence among sex hormone traits, lifestyle factors and BMD. Furthermore, it is a novel insight that TT was defined as a disadvantage for osteoporosis in male European populations.

Background: Unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) are widely used for the treatment of medial unicompartmental knee osteoarthritis (OA). However, the best approach remains controversial. This study aimed to present a systematic review and a meta-analysis to directly compare the clinical outcomes between HTO and UKA. We hypothesized that the clinical outcomes after UKA and HTO would be similar. Methods: Electronic databases (Web of Science, PubMed, Embase, CENTRAL, and Biosis Preview) were searched for related studies published before November 30, 2021. Retrospective and prospective studies that directly compared the postoperative outcomes between UKA and HTO were included. Odds ratio (ORs) and 95% confidence interval (CIs) for complications, revision to total knee arthroplasty (TKA), and weighted mean difference (MD) and 95% CIs in range of motion (ROM), pain, walking speed and function score were evaluated. Two reviewers independently assessed the quality of the studies. Subgroup and sensitivity analyses were performed to explore the heterogeneity. Results: Twenty-three retrospective and 6 prospective studies were included. A total of 3004 patients (3084 knees) were evaluated for comparison. Complications (OR, 4.88, 95% CI: 2.92–6.86) were significantly greater in the HTO group than in the UKA group. Postoperative function scores including Lysholm score (MD, −2.78, 95% CI: −5.37 to −0.18) and Hospital for Special Surgery (HSS) score (MD, −2.80, 95% CI: −5.39 to −0.20) were significantly lower in the HTO group than the UKA group. The postoperative ROM was similar between HTO and mobile-bearing UKA (MD, −3.78, 95% CI: −15.78 to 8.22). However, no significant differences were observed between the HTO and UKA group in terms of postoperative pain, walking speed, and revision to TKA. Conclusions: UKA is superior to HTO in minimizing complications and enhancing postoperative function scores. Mobile-bearing UKA has a similar ROM compared with HTO. Both HTO and UKA provide satisfactory clinical outcomes in terms of walking speed, relieving pain, and revision to TKA. UKA appears to be more suitable for the elderly, and both mobile-bearing UKA and HTO are viable surgical options for younger active individuals.

Three-dimensional computed tomography mapping of 136 tongue-type calcaneal fractures from a single centre Xiaobo Guo, Xiaonan Liang, Jiangtao Jin, Jinwei Chen, Junyang Liu, Yu Qiao, Jianwen Cheng, Jinmin Zhao