Objective: Osteoarthritis (OA) is a common joint disorder characterized by degenerative articular cartilage, subchondral bone remodeling, and inflammation. Increasing evidence suggests that the substantial crosstalk between cartilage and synovium is closely related to Osteoarthritis development, but the events that cause this degeneration remain unknown. This study aimed to explore the alterations in intercellular communication involved in the pathogenesis of Osteoarthritis using bioinformatics analysis.Methods: Single-cell transcriptome sequencing (scRNA-seq) profiles derived from articular cartilage tissue of patients with Osteoarthritis were downloaded from a public database. Chondrocyte heterogeneity was assessed using computational analysis, and cell type identification and clustering analysis were performed using the “FindClusters” function in the Seurat package. Intercellular communication networks, including major signaling inputs and outputs for cells, were predicted, and analyzed using CellChat.Results: Seven molecularly defined chondrocytes clusters (homeostatic chondrocytes, hypertrophic chondrocyte (HTC), pre-HTC, regulatory chondrocytes, fibro-chondrocytes (FC), pre-FC, and reparative chondrocyte) with different compositions were identified in the damaged cartilage. Compared to those in the intact cartilage, the overall cell–cell communication frequency and communication strength were remarkably increased in the damaged cartilage. The cellular communication among chondrocyte subtypes mediated by signaling pathways, such as PTN, VISFATIN, SPP1, and TGF-β, was selectively altered in Osteoarthritis. Moreover, we verified that SPP1 pathway enrichment scores increased, but VISFATIN pathway enrichment scores decreased based on the bulk rna-seq datasets in Osteoarthritis.Conclusion: Our results revealed alterations in cell–cell communication among OA-related chondrocyte subtypes that were mediated by specific signaling pathways, which might be a crucial underlying mechanism associated with Osteoarthritis progression.

Background: The treatment for distal tibial fractures remains controversial to date. Minimally invasive percutaneous plate osteosynthesis (MIPPO) and intramedullary nailing (IMN) are well-accepted and effective methods for distal tibial fractures, but these methods were associated with complications. This study aimed to assess and compare the clinical and functional outcomes in patients with distal tibial fractures treated with MIPPO or IMN.Methods: We systematically reviewed randomized controlled trials (RCTs) that compared MIPPO with IMN in patients with distal tibial fractures from inception till 15 August 2019. Also, quantitative summaries of time to reunion, rate of complications, and functional outcomes were evaluated.Results: The pooled results suggested that patients in the MIPPO group had a longer time to reunion with a mean difference of 1.21 weeks [P= 0.02; 95% confidence interval (CI) 0.16–2.26)] than those in the IMN group. The overall union complications and deep infection between IMN and MIPPO were similar (P> 0.05). IMN had a significantly low risk of wound complications [risk ratio (RR) = 0.51,P= 0.00, 95% CI 0.34–0.77)]. The pooled functional outcomes of the two groups remained controversial by different evaluating scores.Conclusions: Compared to MIPPO, IMN had a significantly low risk of wound complications and associated with limited time for reunion. Although the pooled functional outcomes of the two groups were controversial due to different evaluating scores, IMN was the preferred surgical technique than MIPPO for treating distal tibial fractures.

Purpose: The existing implants for fixation of femoral neck fractures have poor biomechanical stability, so the failure rate is high. We designed two modified intramedullary implants for treating unstable femoral neck fractures (UFNFs). We tried to improve the biomechanical stability of fixation by shortening the moment and reducing stress concentration. Each modified intramedullary implant was compared with cannulated screws (CSs) through finite element analysis (FEA).Methods: Five different models were included: three cannulated screws (CSs, Model 1) in an inverted triangle configuration, the dynamic hip screw with an anti-rotation screw (DHS + AS, Model 2), the femoral neck system (FNS, Model 3), the modified intramedullary femoral neck system (IFNS, Model 4), and the modified intramedullary interlocking system (IIS, Model 5). Three-dimensional (3D) models of femur and implants were constructed by using 3D modelling software. Three load cases were simulated to assess the maximal displacement of models and fracture surface. The maximal stress at the bone and implants was also evaluated.Results: FEA data showed that Model 5 had the best performance in terms of maximum displacement while Model 1 had the worst performance for this index under axial load of 2100 N. With respect to Maximum stress, Model 4 had the best performance while Model 2 had the worst performance under axial load. The general trends under bending and torsion load were consistent with that under axial load. Our data demonstrated that the two modified intramedullary implants exhibited the best biomechanical stability, followed by FNS and DHS + AS, and then three cannulated screws in axial, bending, and torsion load cases.Conclusion: The two modified intramedullary designs showed the best biomechanical performance among the five implants included in this study. Therefore, this might provide some new options for trauma surgeons to deal with unstable femoral neck fractures.

Background: Necrosis of the Femoral Head (NFH) represents a challenging orthopedic condition, characterized by elusive early detection and rapid progression, predominantly in the middle-aged demographic. Current research on the pathophysiological and immunoregulatory mechanisms underpinning immune cell infiltration in NFH is sparse. This study employs bioinformatics analysis of publicly available RNA sequencing databases to elucidate the pivotal molecules and pathways implicated in NFH progression.Methods: The NFH-related dataset GSE123568 was obtained from the Gene Expression Omnibus (GEO). Subsequently, CIBERSORT was utilized to assess the proportion and distribution of immune cell types, followed by the identification of critical Hub immune cells using LASSO and RFE algorithms. The dataset GSE123568 was then explored to identify significantly differentially expressed genes (DEGs). These genes were further refined by intersecting with death-associated genes reported in existing literature. GO and KEGG pathway enrichment analyses were conducted to elucidate their underlying molecular mechanism. A protein-protein interaction (PPI) network was constructed using the STRING database and visualized via Cytoscape. Hub genes were identified using the CytoHubba plugin, followed by enrichment analysis, and their expression levels were evaluated using the ROC curve. In addition, we performed expression data visualization and ROC curve analysis on the external dataset GSE74089 to further evaluate the discriminative power of the hub genes. Moreover, the study analyzed the correlation between the identified hub genes and Hub immune cells. Finally, we verified the hub genes utilizing real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry.Results: Four types of immune cells (Neutrophil, Mast cell resting, Myeloid dendritic cell activated, Macrophage M0) were identified. Fourteen pivotal genes (BCL2L1, BIRC2, NFKBIA, XIAP, CFLAR, AKT1, BIRC3, IKBKB, RIPK1, CASP8, TNFRSF1A, IL1B, CASP1, STAT3) were identified, and the findings were validated using the external dataset GSE74089. Among these, STAT3 exhibited the most pronounced positive correlation with neutrophils (r = 0.6804, p = 3.525e-05). Conversely, XIAP displayed the most significant negative correlation with Myeloid dendritic cell activated (r = −0.3610, p = 0.04003). In experiments, the experimental outcomes for five hub genes (CASP8, TNFRSF1A, AKT1, XIAP and STAT3) were congruent with the results obtained from bioinformatics analysis.Conclusion: Our study identified CASP8, TNFRSF1A, AKT1, XIAP, STAT3 and BCL2L1 as potential biomarkers for NFH patients and elucidated the immune cell types with the strongest association to these markers. These insights may be crucial for the early diagnosis, understanding of the pathophysiological mechanisms, and the development of treatment strategies for NFH.

Autophagy occurs throughout the development and maturation of bone tissues and various types of bone cells and plays a vital role in osteoporosis progression. This study aimed to explore the role of runt-related transcription factor 2 (RUNX2) in osteoblast autophagy and its related molecular mechanisms. MC3T3-E1 cells were treated with different concentrations of rapamycin, and their viability was determined using a cell counting Kit-8 (CCK-8). The cells were then transfected with si-RUNX2 and RUNX2 overexpression plasmids, and the viability of these rapamycin-treated cells was measured using CCK-8, while the expression of autophagy-related genes/proteins and osteoblast differentiation-related genes was determined using Western blotting and RT-qPCR. Finally, Alizarin red staining was used to observe osteoblast mineralization, and transmission electron microscopy was employed to detect autophagosomes in cells administered different treatments. Rapamycin significantly inhibited cell viability and promoted cell autophagy compared with the control (P < 0.05). Cells with RUNX2 knockdown and overexpression were successfully established. Further, RUNX2 overexpression was found to significantly enhance the viability and osteoblast mineralization of rapamycin-treated cells and suppress cell autophagy. RUNX2 overexpression also increased p-p38MAPK/p38MAPK levels and ALP, OCN, and OSX expression, and markedly downregulated Beclin-1, LC3-II/LC3-I, p62, ATG1, p-Beclin-1, and ATG5 levels (P < 0.05). However, the trends after RUNX2 knockdown opposed those observed after RUNX2 overexpression. RUNX2 may regulate osteoblast differentiation and autophagy by mediating autophagy-related and osteoblast differentiation-related genes/proteins, as well as the p38MAPK signaling pathway. Graphical abstract

Objective To develop a new approach to intraoperatively identify the presence of coronal plane deformities (both valgus and varus) when treating tibial fractures with closed reduction and intramedullary nail fixation. Methods A retrospective analysis was conducted by enrolling 33 consecutive patients with tibial fractures who received closed reduction and intramedullary nail fixation from January 2018 to January 2019 at our trauma center. Out of the 33 patients, 23 were males and 10 were females and the average age was 41 years (ranging 22 to 69 years of age). Standard anteroposterior and lateral preoperative radiographs were routinely performed. After intraoperatively inserting the tibial intramedullary nail through the standard entry point, the parallel relationship between the distal horizontal interlocking screw and the tibiotalar joint surface on the anteroposterior fluoroscopy was used to determine the occurrence of valgus or varus deformities of the distal tibial fragment. Radiographic and clinical outcomes were analyzed using the average interval from injury to surgery, the lateral distal tibial angle (LDTA) of the unaffected and affected sides, complications and the Olerud–Molander ankle score. Results All 33 patients were postoperatively followed for 13 to 25 months (mean 18.7 months). The fractures achieved bone union at an average of 4.3 months (ranging from 3 to 6 months). The total complication rate was 60.6% (20 cases), including four cases that showed deep vein thrombosis, one case showing an infection and delayed union and 15 cases showing slight to moderate anterior knee pain. The postoperative LDTA of the unaffected side measured 87.3° to 89.6 ° (average 88.7° ± 0.8°), and the LDTA of the affected side was 87.5° to 90.4° (average 88.9° ± 1.1°). There was no significant difference between the unaffected and affected sides (t = −1.865, P = 0.068). The intraoperative measurement indicated six cases of valgus angulation and three cases of varus angulation deformities, and all deformities were corrected during surgery. According to the Olerud–Molander ankle score, clinical outcomes demonstrated 22 excellent cases, eight good cases, two fair cases, and one poor case 12 months after surgery. Conclusion The parallel relationship between the distal horizontal interlocking screw and tibiotalar joint surface on intraoperative anteroposterior films were able to determine the onset of valgus or varus angulations of the distal tibial fragment in the fracture zone after the tibial intramedullary nail was inserted through the standard entry point.