Feasibility and anteversion accuracy of a patient-specific instrument for femoral prosthesis implantation in total hip arthroplasty.

BACKGROUND: The aim of this study was to evaluate the precision and feasibility of patient-specific instruments (PSI) in total hip arthroplasty (THA) as compared to the traditional free-hand (FRH) approach. METHODS: During the period of January 1, 2021 to December 31, 2022, a randomized allocation was used for patients receiving unilateral primary THA to either the PSI or conventional operation group. The placement and size of the PSI were specifically chosen to guide femoral neck resection and prosthesis implantation. The study analyzed component positions and evaluated radiographic and clinical outcomes in 30 patients who received PSI-assisted THAs and 30 patients who received FRH THAs. This study was registered at China Clinical Trial Registry (number: ChiCTR2300072325) on June 9th, 2023. RESULTS: The use of PSI in THA resulted in significantly higher precision in achieving the desired component position as compared to the FRH approach. The PSI group showed significantly smaller absolute errors of femoral anteversion (p < 0.001). No significant differences were found in operation time, intra-operative blood loss, hospitalization duration, or time to walk after surgery. CONCLUSION: In conclusion, the application of patient-specific instruments in THA provides a simple and reliable solution to enhance the precision of femoral prosthesis placement with high accuracy and feasibility. This study highlights the potential benefits of using the PSI in THA.

Screening and identification of potential key biomarkers for glucocorticoid-induced osteonecrosis of the femoral head.

BACKGROUND: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common disease in osteoarticular surgery, with a high disability rate, which brings great physical and mental pain and economic burden to patients. Its specific pathogenesis has not been fully demonstrated, and there is a lack of recognized effective biomarkers for earlier detection and prompt treatment. This has become an urgent clinical problem for orthopedic scholars. MATERIALS AND METHODS: We downloaded the gene expression profile dataset GSE123568 from the Gene Expression Omnibus database, used STRING and Cytoscape to carry out module analysis and built a gene interaction network. The four core genes most related to GIONFH in this network were ultimately found out by precise analysis and animal experiment were then conducted for verification. In this verification process, thirty-six New Zealand white rabbits were randomly divided into blank control group, model group and drug group. Except for the blank control group, the animal model of GIONFH was established by lipopolysaccharide and methylprednisolone, while the drug group was given the lipid-lowering drugs for intervention as planned. The rabbits were taken for magnetic resonance imaging at different stages, and their femoral head specimens were taken for pathological examination, then the expression of target genes in the femoral head specimens of corresponding groups was detected. Validation methods included RT-PCR and pathological examination. RESULTS: A total of 679 differential genes were selected at first, including 276 up-regulated genes and 403 down-regulated genes. Finally, four genes with the highest degree of correlation were screened. Animal experiment results showed that ASXL1 and BNIP3L were in low expression, while FCGR2A and TYROBP were highly expressed. CONCLUSION: Through animal experiments, it was confirmed that ASXL1, BNIP3L, FCGR2A and TYROBP screened from the comparative analysis of multiple genes in the database were closely related to GIONFH, which is important for early diagnosis of Glucocorticoid-induced osteonecrosis of the femoral head.

Metabolic Profiling Analysis of the Effect and Mechanism of Gushiling Capsule in Rabbits With Glucocorticoid-Induced Osteonecrosis of the Femoral Head.

Gushiling capsule (GSLC) is an effective traditional Chinese medicine for the treatment of glucocorticoid-induced osteonecrosis of the femoral head (GIONFH). This study established the serum metabolite profiles of GSLC in rabbits and explored the metabolic mechanism and effect of GSLC on GIONFH. Seventy-five Japanese white rabbits were randomly divided into the control, model, and GSLC groups. The rabbits in the model group and the GSLC group received injection of prednisolone acetate. Meanwhile, rabbits in the GSLC group were treated by gavage at a therapeutic dose of GSLC once a day. The control group and the model group received the same volume of normal saline gavage. Three groups of serum samples were collected at different time points, and the changes in the metabolic spectrum were analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The resulting data set was analyzed using multivariate statistical analysis to identify potential biomarkers related to GSLC treatment. The metabolic pathway was analyzed by MetaboAnalyst 4.0 and a heatmap was constructed using the HEML1.0.3.7 software package. In addition, histopathological and radiography studies were carried out to verify the anti-GIONFH effects of GSLC. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) score plots revealed a significant separation trend between the control group and the model group and the GSLC group (1-3 weeks), but there were no significant differences in the GSLC group (4-6 weeks). Orthogonal PLS-DA (OPLS-DA) score plots also revealed an obvious difference between the model and the GSLC groups (4-6 weeks). Ten potential metabolite biomarkers, mainly phospholipids, were identified in rabbit serum samples and demonstrated to be associated with GIONFH. Hematoxylin and eosin staining and magnetic resonance imaging indicated that the pathological changes in femoral head necrosis in the GSLC group were less than in the model group, which was consistent with the improved serum metabolite spectrum. GSLC regulated the metabolic disorder of endogenous lipid components in GIONFH rabbits. GSLC may prevent and treat GIONFH mainly by regulating phospholipid metabolism in vivo.

Screening of Potential Key Biomarkers for Ewing Sarcoma: Evidence from Gene Array Analysis.

Background: Ewing's sarcoma (ES) is a common bone cancer in children and adolescents. There are ethnic differences in the incidence and treatment effects. People have made great efforts to clarify the cause; however, the molecular mechanism of ES is still poorly understood. Methods: We download the microarray datasets GSE68776, GSE45544 and GSE17674 from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) of the three datasets were screened and enrichment analysis was performed. STRING and Cytoscape were used to carry out module analysis, building a protein-protein interaction (PPI) network. Finally, a series of analyses such as survival analysis and immune infiltration analysis were performed on the selected genes. Results: A total of 629 differentially expressed genes were screened, including 206 up-regulated genes and 423 down-regulated genes. The pathways and rich-functions of DEGs include protein activation cascade, carbohydrate binding, cell-cell adhesion junctions, mitotic cell cycle, p53 pathway, and cancer pathways. Then, a total of 10 hub genes were screened out. Biological process analysis showed that these genes were mainly enriched in mitotic nuclear division, protein kinase activity, cell division, cell cycle, and protein phosphorylation. Conclusion: Survival analysis and multiple gene comparison analysis showed that CDCA8, MAD2L1 and FANCI may be involved in the occurrence and prognosis of ES. The purpose of our study is to clarify the DEG and key genes, which will help us know more about the molecular mechanisms of ES, provide potential pathway or targets for the diagnosis and treatment.

Up-regulation of SIRT1 induced by 17beta-estradiol promotes autophagy and inhibits apoptosis in osteoblasts.

Osteoporosis is a common systemic skeletal metabolism disorder resulting in bone fragility and increased fracture risk. Silent information regulator factor 2 homolog 1 (SIRT1) is crucial in the regulation of several biological processes, including bone metabolism, autophagy, apoptosis, and aging. This study aimed to assess whether the up-regulation of SIRT1 induced by 17beta-estradiol (17ß-E2) could promote autophagy and inhibit apoptosis in osteoblasts via the AMPK-mTOR and FOXO3a pathways, respectively. The study found that 17ß-E2 (10-6 M) administration induced the up-regulation of SIRT1 in osteoblasts. Up-regulation of SIRT1 induced by 17ß-E2 increased the expression level of LC3, Beclin-1, Bcl-2, p-AMPK, FOXO3a but decreased caspase-3 and p-mTOR expression, and then promoted autophagy and inhibited apoptosis. More autophagosomes were observed under a transmission electron microscope (TEM) in 17ß-E2 and SRT1720 (a selective SIRT1 activator) co-treated group. When Ex527 (a SIRT1-specific inhibitor) was pretreated, the reversed changes were observed. Taken together, our findings demonstrated that the up-regulation of SIRT1 induced by 17ß-E2 could promote autophagy via the AMPK-mTOR pathway and inhibit apoptosis via the FOXO3a activation in osteoblasts, and SIRT1 might become a more significant target in osteoporosis treatment.

Factors Affecting the Aluminum, Arsenic, Cadmium and Lead Concentrations in the Knee Joint Structures.

Background: Toxic elements, such as aluminum (Al), arsenic (As), cadmium (Cd), and lead (Pb), are persistent environmental pollutants that can cause adverse effects on the health of exposed individuals. Bone is one of the primary target organs of accumulation and potential damage from toxic elements. Objectives: This study was performed to determine the Al, As, Cd, and Pb concentrations in the femoral cancellous bone, femoral cartilage, anterior cruciate ligament, meniscus, tibial cartilage, tibial cancellous bone and infrapatellar fat pad. Furthermore, the aim of this study was to explore the relationships between toxic element concentrations and related factors such as gender, age, place of residence, hypertension and diabetes, and to determine the correlations among these toxic elements in knee joint structures. Methods: The samples used this study were collected from 51 patients following total knee arthroplasty. The Al, As, Cd, and Pb concentrations were determined using inductively coupled plasma optic emission spectrometry. Results: Significant differences were found in the Al, As, Cd, and Pb concentrations among the knee joint structures. Cd concentration in the tibial cancellous bone in women was significantly higher than in men. Pb concentration in the infrapatellar fat pad of urban patients was significantly higher as compared to rural patients. Al concentrations in the femoral cancellous bone, femoral cartilage, anterior cruciate ligament, meniscus and tibial cartilage were significantly higher in patients living in urban areas than in rural areas. As concentration in the tibial cancellous bone of diabetic patients was significantly higher compared to non-diabetic patients. In addition, significant Spearman's positive correlations were found between Al and Pb in the knee joint structures. Conclusion: The obtained results of the investigated toxic elements may serve as a basis for establishing the reference values of Al, As, Cd, and Pb in the knee joint structures. The results reported in the study provides novel data regarding the relationships between the toxic element concentrations and gender, age, place of residence, hypertension and diabetes in the studied structures of knee joint. Furthermore, new interactions among these toxic elements were noted.

17ß-Estradiol Induces Mitophagy Upregulation to Protect Chondrocytes via the SIRT1-Mediated AMPK/mTOR Signaling Pathway.

Increasing evidence reveals that estrogen, especially 17ß-estradiol (17ß-E2), is associated with articular cartilage metabolism disorder and postmenopausal osteoarthritis (OA). SIRT1, AMPK, and mTOR are regarded as critical mitophagy regulators. Recent studies have shown that mitophagy displays a protective effect against OA, but the molecular mechanism is not well known. This study aimed to investigate the effect of 17ß-E2 on Sirtuin-1 (SIRT1) expression and the induction of mitophagy upregulation by 17ß-E2 via the SIRT1-mediated AMP-activated protein kinase (AMPK)/mammalian target of the rapamycin (mTOR) signaling pathway to protect chondrocytes. ATDC5 chondrocytes were treated with different concentrations of 17ß-E2 (0 M, 1 × 10-9 M, 1 × 10-8 M, and 1 × 10-7 M) for 24 h or pretreatment with or without NAM (SIRT1 inhibitor), Compound C (AMPK inhibitor) and S1842 (mTOR inhibitor) for 30 min prior to treatment with 17ß-E2 (1 × 10-7 M) for 24 in each groups. Expression of SIRT1 was evaluated by real-time PCR, Western blotting and confocal immunofluorescence staining. Then, the mitophagosomes in cells were observed under a transmission electron microscopy (TEM), and the AMPK/mTOR signaling pathway was detected by Western blotting. The mitophagy-related proteins, p-AMPK, p-mTOR, p-JNK, and p-p38 were also identified by Western blot analysis. The chondrocytes viability and proliferation were determined by MTT and 5-Bromo-2'-deoxyuridine (BrdU) assay. These experiments were independently repeated 3 times The study found that 17ß-E2 increased the expression level of SIRT1, p-AMPK, and mitophagy-related proteins but decreased p-mTOR expression, and then induced mitophagy upregulation in chondrocytes. More mitochondrial autophagosomes were observed in 17ß-E2-treated chondrocytes under a transmission electron microscope. Also, 17ß-E2 improved cell viability and proliferation with the higher expression of SIRT1 and activation of the AMPK/mTOR signaling pathway. However, SIRT1 inhibitor nicotinamide (NAM) and AMPK inhibitor Compound C blocked the beneficial effect of 17ß-E2. In summary, this study was novel in demonstrating that 17ß-E2 induced mitophagy upregulation to protect chondrocytes via the SIRT1-mediated AMPK/mTOR signaling pathway.