Osteonecrosis of the femoral head (ONFH) is a common disabling disease. Copper has positive effects on cells that regulate bone metabolism. However, the relationship between copper metabolism (CM) and steroid-induced ONFH (SONFH) remains unclear. The GSE123568 dataset was downloaded from the Gene Expression Omnibus. The differentially expressed CM-related SONFH genes (DE-CMR-SONFHGs) were identified via differential analysis and weighted gene coexpression network analysis (WGCNA). Receiver operating characteristic (ROC) analysis was performed for the predictive accuracy of key genes. Targeting drugs and the copper death-related genes (CDRGs) relevant to key genes were investigated. The bioinformatics results were confirmed via quantitative real-time polymerase chain reaction (qRT–PCR) and Western blot (WB) analysis. Two out of 106 DE-CMR-SONFHGs were identified as key genes (PNP and SLC2A1), which had diagnostic value in distinguishing SONFH from control samples and were related to various immune cell infiltrations. Eleven PMP-targeting drugs and five SLC2A1-targeting drugs were identified. The qRT–PCR, as well as WB, results confirmed the downregulation PNP and SLC2A1 and high expression of the CDRGs DLD, PDHB, and MTF1, which are closely related to these two key genes. In conclusion, PNP and SLC2A1 were identified as key genes related to SONFH and may provide insights for SONFH treatment.

Introduction: Steroid-induced necrosis of the femoral head (SINFH) is a femoral head necrotic disease caused by prolonged use of hormones. Wen-Dan decoction is used in Chinese clinical practice for the treatment of steroid-induced necrosis of the femoral head (SINFH). However, the mechanism and active compounds of Wen-Dan decoction used to treat SINFH are not well understood. Objectives: We studied the mechanism of action of Wen-Dan decoction in treating steroidinduced necrosis of the femoral head (SINFH) via network pharmacology and in vivo experiments. Methods: The active compounds of Wen-Dan decoction and SINFH-related target genes were identified through public databases. Then, network pharmacological analysis was conducted to explore the potential key active compounds, core targets and biological processes of Wen-Dan decoction in SINFH. The potential mechanisms of Wen-Dan decoction in SINFH obtained by network pharmacology were validated through in vivo experiments. Results: We identified 608 DEGs (differentially expressed genes) (230 upregulated, 378 downregulated) in SINFH. GO analysis revealed that the SINFH-related genes were mainly involved in neutrophil activation and the immune response. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that the SINFH-related genes were mainly associated with cytokine receptor interactions, lipids, atherosclerosis, and tuberculosis. We identified 147 active ingredients of Wen-Dan decoction; the core ingredient was quercetin, and licorice was an active ingredient. Moreover, 277 target genes in the treatment of SINFH with Wen-Dan decoction were identified, and NCF1, PTGS2, and RUNX2 were selected as core target genes. QRT-PCR of peripheral blood from SINFH patients showed higher levels of PGTS2 and NCF1 and showed lower levels of RUNX2 compared to controls. QRT-PCR analysis of peripheral blood and femoral bone tissue from a mouse model of SINFH showed higher levels of PGTS2 and NCF1 and lower levels of RUNX2 in the experimental animals than the controls, which was consistent with the bioinformatics results. HE, immunohistochemistry, and TUNEL staining confirmed a significant reduction in hormone-induced femoral head necrosis in the quercetintreated mice. HE, immunohistochemistry, and TUNEL staining confirmed significant improvement in hormone-induced femoral head necrosis in the quercetin-treated mice. Conclusion: We provide new insights into the genes and related pathways involved in SINFH and report that PTGS2, RUNX2, and NCF1 are potential drug targets. Quercetin improved SINFH by promoting osteogenesis and inhibiting apoptosis.

SDRC is implicated in the pathogenesis of Staphylococcus aureus osteomyelitis. However, the precise mechanism by which SDRC contributes to the progression of this infection remains unclear. To explore SDRC’s role in osteomyelitis, experiments were conducted on mouse models infected with Staphylococcus aureus strains containing either the wild type SDRC sequence or a knockout (KO-SDRC) sequence. Levels of inflammatory factors like IL-6 and TNF-α were measured using Elisa. Furthermore, changes in osteogenic indicators such as ALP, OST, and Runx2 were detected using qPCR and Western blot analysis. Additionally, transcriptome sequencing was employed to gain deeper insights into the potential molecular mechanisms underlying SDRC’s promotion of Staphylococcus aureus-induced osteomyelitis. The study revealed that the ability of Staphylococcus aureus to form biofilms was significantly weakened in strains where the SDRC protein was knocked out. Moreover, mice infected with the KO-SDRC strain exhibited enhanced ossification processes. Transcriptome sequencing demonstrated significant overexpression of the Myh7 gene in the SDRC knockout osteomyelitis mouse. Subsequent knockout of the Myh7 gene led to notable reductions in mRNA and protein expressions of osteogenic indicators including Runx2, ALP, OSX, and Osteocalcin. Overall, these findings suggest that SDRC plays a crucial role in promoting the malignant progression of osteomyelitis caused by Staphylococcus aureus. Its main mechanism involves enhancing the formation of Staphylococcus aureus biofilms. Conversely, Myh7 may exert an inhibitory effect on the SDRC protein, reducing biofilm formation and mitigating the severity of osteomyelitis. These findings offer novel insights into potential therapeutic targets for the treatment of osteomyelitis.

Background The copper metabolism may play a role in angiogenesis and osteogenesis. However, the relationship between copper metabolism and steroid-induced osteonecrosis of the femoral head (SONFH) still remains unclear. Methods The GSE123568 dataset and 2062 copper metabolism-related genes (CMRGs) were downloaded from the Gene Expression Omnibus (GEO) and GeneCards databases, respectively. The differentially expressed copper metabolism-related SONFH genes (DE-CMR-SONFHGs) were identified by differential analysis and weighted gene coexpression network analysis (WGCNA). The Least-Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine (SVM) algorithms were employed to screen key DE-CMR-SONFHGs. Receiver operating characteristic (ROC) analysis and functional enrichment analysis were performed on the key genes. Targeting drugs were predicted with The Drug Gene Interaction Database (DGIdb). The correlation between key SONFH genes and copper death-related genes was calculated by Pearson method. The result of bioinformatics analysis were confirmed by quantitative real-time polymerase chain reaction (qRT‒PCR). Results A total of 106 DE-CMR-SONFHGs were identified. Then, 2 key genes (PNP and SLC2A1) were identified by LASSO and SVM algorithms. The ROC curves of PNP and SLC2A1 indicated that they had diagnostic value in distinguishing SONFH from control samples. Additionally, 20 immune cell populations had notably different abundances between the SONFH and control samples. PNP showed the most significant correlations with plasmacytoid dendritic cells and CD56bright natural killer cells, and SLC2A1 expression showed the most significant correlations with T follicular helper cells and T helper 17 cells. Moreover, 11 drugs that target PNP and 5 drugs that target SLC2A1 were identified. Four copper death-related genes (LIPT1, DLD, PDHB, and MTF1) were upregulated in the disease samples. The qRT‒PCR results showed that PNP and SLC2A1 expression was downregulated and that the copper death-related genes DLD, PDHB and MTF1, which are closely related to these two key genes, were notably highly expressed in the peripheral blood of SONFH patients. These findings were consistent with the bioinformatics analysis results. Conclusions Copper homeostatic imbalance may be involved in the process of SONFH. PNP and SLC2A1 were confirmed to be key genes related to SONFH, and these genes may provide insights for the treatment of SONFH.

Objectives: The present work studied the mechanism of action of Wen-Dan decoction in treating steroid-induced necrosis of the femoral head (SINFH) via network pharmacology and in vivo experiments. Methods: The active compounds of Wen-Dan decoction and SINFH-related target genes were identified through public databases. Based on the results, further network pharmacological analysis was conducted to explore the potential key active compounds, core targets and biological processes of Wen-Dan decoction in SINFH. Subsequently, the potential mechanisms of action of Wen-Dan decoction in the treatment of SINFH obtained by network pharmacology analyses were validated through in vivo experiments. Results: A total of 608 DEGs (230 upregulated and 378 downregulated) in SINFH were identified. A GO functional enrichment analysis revealed that the SINFH-related genes were mainly involved in neutrophil activation and the immune response, and a KEGG pathway analysis showed that the SINFH-related genes were mainly associated with cytokine receptor interactions, lipids and atherosclerosis, and tuberculosis. In addition, a total of 147 active ingredients of Wen-Dan decoction were identified; of these, the core ingredient was quercetin, and licorice was an active ingredient. Moreover, 277 target genes in the treatment of SINFH with Wen-Dan decoction were identified, and NCF1, PTGS2, and RUNX2 were selected as core target genes. A quantitative real-time polymerase chain reaction (qRT–PCR) assay of peripheral blood from SINFH patients and control individuals showed that the patients exhibited highest levels of PGTS2 and NCF1 in blood. The qRT–PCR analysis of peripheral blood and femoral bone tissue from a mouse model of SINFH and control mice treated with quercetin showed that the PGTS2 and NCF1 levels revealed lower levels in the experimental animals compared with the controls, which was consistent with the bioinformatics analysis results. HE staining, immunohistochemistry and TUNEL staining confirmed significant improvement in hormone-induced femoral head necrosis in the mice treated with quercetin. Conclusions: This study provides new insights into the genes and related pathways involved in SINFH and shows that PTGS2 and NCF1 could be used as potential drug targets in SINFH. Quercetin could improve SINFH by promoting osteogenesis and inhibiting apoptosis.

Purpose: Exploring the therapeutic effects of Ni-Ti shape memory alloy four-corner arthrodesis concentrator (NT-FCAC) in treating scaphoid nonunion advanced collapse (SNAC) and providing a decade-long follow-up report. Materials and methods: Twenty-six patients with SNAC underwent scaphoidectomy, along with four-corner arthrodesis fusion involving the capitate, lunate, triquetrum, and hamate, using NT-MFCAC. Grip strength was measured using a Jamar dynamometer, while wrist joint mobility was assessed using a goniometer. Preoperative and postoperative assessments were conducted using the Quick Disabilities of the Arm, Shoulder, and Hand (Quick DASH) questionnaire to monitor limb functionality restoration. Pain levels at the wrist joint were evaluated using the visual analog scale (VAS). Postoperative wrist bone fusion status was assessed through anteroposterior and lateral radiographs of the wrist joint. Results: After a 3-month postoperative period, all 26 patients exhibited osseous union at the wrist joint. Over a follow-up spanning 10–15 years, no severe postoperative complications were observed in any patient. Grip strength in the affected side of all patients recovered to 81.96% compared to the healthy side, while wrist joint mobility in the affected side reached over 60% of the healthy side’s functionality. VAS scores decreased significantly from 5.85 ± 0.73 preoperatively to 0.19 ± 0.40 at the final follow-up; Quick DASH scores reduced from 69.88 ± 5.12 preoperatively to 6.30 ± 1.25 at final follow-up. Statistically significant differences were noted in VAS and Quick DASH scores for all patients (p < 0.05). However, beyond 60 months postoperatively, subsequent follow-ups did not yield statistically significant differences in VAS and Quick DASH scores for all patients (p > 0.05). Conclusions: Utilizing NT-FCAC for SNAC treated with four-corner arthrodesis fusion results in a high rate of wrist bone fusion, preserving a significant portion of wrist joint function and exhibiting favorable long-term outcomes. This approach is suitable for treating patients with SNAC requiring four-corner arthrodesis fusion.