Selection of lncRNAs That Influence the Prognosis of Osteosarcoma Based on Copy Number Variation Data.

Osteosarcoma is the most common primary malignancy in the musculoskeletal system. It is reported that copy number variation- (CNV-) derived lncRNAs contribute to the progression of osteosarcoma. However, whether CNV-derived lncRNAs affect the prognosis of osteosarcoma remains unclear. Here, we obtained osteosarcoma-related CNV data and gene expression profiles from The Cancer Genome Atlas (TCGA) database. CNV landscape analysis indicated that copy number amplification of lncRNAs was more frequent than deletion in osteosarcoma samples. Thirty-four CNV-lncRNAs with DNA-CNV frequencies greater than 30% and their corresponding 294 mRNAs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses revealed that these mRNAs were mainly enriched in olfaction, olfactory receptor activity, and olfactory transduction processes. Furthermore, we predicted that a total of 23 genes were cis-regulated by 16 CNV-lncRNAs, while 30 transcription factors (TFs) were trans-regulated by 5 CNV-lncRNAs. Through t-tests, univariate Cox regression analysis, and the least absolute shrinkage and selection operator (LASSO), we constructed a CNV-related risk model including 3 lncRNAs (AC129492.1, PSMB1, and AC037459.4). The Kaplan-Meier (K-M) curves indicated that patients with high-risk scores showed poor prognoses. The areas under the receiver operating characteristic (ROC) curves (AUC) for predicting 3-, 5-, and 7-year overall survival (OS) were greater than 0.7, showing a satisfactory predictive efficiency. Gene set enrichment analysis (GSEA) revealed that the prognostic signature was intimately linked to skeletal system development, immune regulation, and inflammatory response. Collectively, our study developed a novel 3-CNV-lncRNA prognostic signature that would provide theoretical guidance for the clinical prognostic management of osteosarcoma.

Screening of Potential Biomarkers in the Peripheral Serum for Steroid-Induced Osteonecrosis of the Femoral Head Based on WGCNA and Machine Learning Algorithms.

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (SONFH) has produced a substantial burden of medical and social experience. However, the current diagnosis is still limited. Thus, this study is aimed at identifying potential biomarkers in the peripheral serum of patients with SONFH. METHODS: The expression profile data of SONFH (number: GSE123568) was acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in SONFH were identified and used for weighted gene coexpression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the biological functions. The protein-protein interaction (PPI) network and machine learning algorithms were employed to screen for potential biomarkers. Gene set enrichment analysis (GSEA), transcription factor (TF) enrichment analysis, and competing endogenous RNA (ceRNA) network were used to determine the biological functions and regulatory mechanisms of the potential biomarkers. RESULTS: A total of 562 DEGs, including 318 upregulated and 244 downregulated genes, were identified between SONFH and control samples, and 94 target genes were screened based on WGCNA. Moreover, biological function analysis suggested that target genes were mainly involved in erythrocyte differentiation, homeostasis and development, and myeloid cell homeostasis and development. Furthermore, GYPA, TMCC2, and BPGM were identified as potential biomarkers in the peripheral serum of patients with SONFH based on machine learning algorithms and showed good diagnostic values. GSEA revealed that GYPA, TMCC2, and BPGM were mainly involved in immune-related biological processes (BPs) and signaling pathways. Finally, we found that GYPA might be regulated by hsa-miR-3137 and that BPGM might be regulated by hsa-miR-340-3p. CONCLUSION: GYPA, TMCC2, and BPGM are potential biomarkers in the peripheral serum of patients with SONFH and might affect SONFH by regulating erythrocytes and immunity.

Three dimensional patient-specific printed cutting guides for closing-wedge distal femoral osteotomy.

PURPOSE: Medial closing-wedge distal femoral osteotomy (MCWDFO) was used to treat valgus knee malalignment combined with lateral compartment disease. The clinical outcome of the osteotomy depends on the accurate correction of valgus malalignment. The aim of this study was to evaluate the accuracy of a MCWDFO assisted by three-dimensional (3D)-printed cutting guides and locking guides. PATIENTS AND METHODS: Thirty-three consecutive patients (33 knees) were operated on using the same MCWDFO. 3D-printed cutting guides and locking guides were used to locate the osteotomy cut plane and to facilitate closing the wedge in 12 patients (3D-guide group). Another 21 patients (conventional group) underwent MCWDFO following the conventional technique. The desired correction was defined as a weight-bearing line (WBL) coordinate 50% of the width of the tibial plateau from the medial tibial margin. The deviation between the planned and executed WBL coordinate, surgical time and fluoroscopic time were compared. RESULTS: The mean deviation between the planned and executed WBL coordinate was 4.9% in the 3D-guide group and 7.6% in the conventional group (P = 0.024). Shorter surgical time was found in the 3D-guide group (mean, 77.7 minutes vs. mean, 96.5 minutes; P < 0.001), while the mean number of intra-operative fluoroscopic images was 6.1, compared with 34.7 in the conventional group (P < 0.001). CONCLUSION: The use of 3D-printed cutting guides and locking guides can increase the precision of the MCWDFO in patients with lateral compartment disease and valgus deformity, making our surgery more efficiency and occupying less fluoroscopic time.

Head Transplantation in Mouse Model.

AIMS: The mouse model of allo-head and body reconstruction (AHBR) has recently been established to further the clinical development of this strategy for patients who are suffering from mortal bodily trauma or disease, yet whose mind remains healthy. Animal model studies are indispensable for developing such novel surgical practices. The goal of this work was to establish head transplant mouse model, then the next step through the feasible biological model to investigate immune rejection and brain function in next step, thereby promoting the goal of translation of AHBR to the clinic in the future. METHODS AND RESULTS: Our approach involves retaining adequate blood perfusion in the transplanted head throughout the surgical procedure by establishing donor-to-recipient cross-circulation by cannulating and anastomosing the carotid artery on one side of the body and the jugular vein on the other side. Neurological function was preserved by this strategy as indicated by electroencephalogram and intact cranial nerve reflexes. CONCLUSIONS: The results of this study support the feasibility of this method for avoiding brain ischemia during transplantation, thereby allowing for the possibility of long-term studies of head transplantation.

Allogeneic head and body reconstruction: mouse model.

AIMS: There is still no effective way to save a surviving healthy mind when there is critical organ failure in the body. The next frontier in CTA is allo-head and body reconstruction (AHBR), and just as animal models were key in the development of CTA, they will be crucial in establishing the procedures of AHBR for clinical translation. METHODS AND RESULTS: Our approach, pioneered in mice, involves retaining the donor brain stem and transplanting the recipient head. Our preliminary data in mice support that this allows for retention of breathing and circulatory function. Critical aspects of the current protocol include avoiding cerebral ischemia through cross-circulation (donor to recipient) and retaining the donor brain stem. Successful clinical translation of AHBR will become a milestone of medical history and potentially could save millions of people. CONCLUSIONS: This experimental study has confirmed a method to avoid cerebral ischemia during the surgery and solved an important part of the problem of how to accomplish long-term survival after transplantation and preservation of the donor brain stem.