Identification of Osteosarcoma Metastasis-Associated Gene Biomarkers and Potentially Targeted Drugs Based on Bioinformatic and Experimental Analysis.

BACKGROUND: Metastasis is the leading cause of death for patients with osteosarcoma (OS). In the present study, we explore the biomarkers for metastatic OS and provide potential therapeutic approaches. MATERIALS AND METHODS: RNA-Seq data and clinical follow-up information were downloaded from TARGET and GEO databases. A Cox regression model was used to analyze metastatic events. L1000FWD, DGIdb, and CMap databases were used to identify potential drugs related to metastasis. Invasion and migration transwell assays and an adhesion assay were used to identify biological functions of genes. RESULTS: A total of 15 metastasis-related signatures (MRSs) were associated with the prognosis based on the TARGET or GSE21257 cohorts, among which IL10RA and TLR7 genes were especially significant. In the DGIdb drug-gene interaction database, TLR7 and IFNGR1 were found to have potential interactions with drugs. After inhibiting the expression of TLR7, the migration, invasion, and adhesion ability of OS cells were significantly enhanced, which further promoted metastasis. CONCLUSION: We identified a set of MRS that may be related to OS metastases. Among them, TLR7 plays a vital role and may be a potential target for OS metastasis treatment.

A succinct technique for the extraction of the proximal femoral nail anti-rotation (PFNA) after unlocking failure: a case report.

INTRODUCTION: Proximal femoral nail anti-rotation (PFNA) is a routine method to deal with intertrochanteric fractures in the elder population. It is challenging to remove PFNA in some cases as a result of stripping of blade heads. In this case presentation, we describe a novel technique using commonly available instruments that can be used to remove stripped, even broken anti-rotation blade where conventional methods have failed. METHODS: The subject underwent a PFNA removal surgery 15 months after the previous fixation. We encountered difficulties using the regular instrument to remove the anti-rotation blade. A 5-mm tungsten carbide bur was used to drill a single cortical hole at the end of the blade. Then double-strand steel wire was threaded through the hole, and the distal part was shaped into a circle which could tie to the extraction screw. Slide Hammer was applied to gently knock out the blade along the anatomical direction of the femoral neck. RESULTS: The technique helped us successfully remove the anti-rotation blade and provided the patient with a satisfactory result. CONCLUSION: The use of a tungsten reamer and steel wire loop to remove the proximal femoral anti-rotation blade may provide a cost-effective and straightforward method of dealing with extraction failure.

Minimally invasive dual incision with mini plate internal fixation improves outcomes over 30 months in 20 patients with Sanders type III calcaneal fractures.

BACKGROUND: Calcaneal Sanders type III or higher fractures traditionally have been treated with open reduction and internal fixation (ORIF); however, ORIF has associated complications. We investigated a combination of minimally invasive dual incision and internal fixation using mini plates for treating Sanders type III calcaneal fractures. METHODS: Twenty patients with Sanders type III intra-articular calcaneal fractures with a posterior subtalar articular displacement > 2 mm were included. Surgical outcomes were assessed by visual analogue scale (VAS) pain score, American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score, and calcaneal geometry, including Böhler and Gissane angles. RESULTS: The Böhler angle, Gissane angle, and height and length of the calcaneus were increased following treatment. Based on the AOFAS score, 80% of cases had excellent or good outcomes. The mean postoperative VAS pain score was 1.6. Complications such as malunion or a screw positioning deviation occurred in 6 patients, and one patient experienced delayed wound healing. There were no wound infections. CONCLUSIONS: These results indicate that minimally invasive dual incision with mini plate internal fixation may be an effective alternative to ORIF for treating Sanders type III calcaneal fractures. Advantages include improvement of calcaneal geometry and a lower rate of wound infections.

Incidence of dysphagia of zero-profile spacer versus cage-plate after anterior cervical discectomy and fusion: A meta-analysis.

BACKGROUND: The purpose of this study is to evaluate the rate of dysphagia between zero-profile spacer versus cage-plate for the treatment of multilevel cervical spondylotic myelopathy (CSM). METHODS: The authors searched electronic databases for relevant studies that compared the clinical effectiveness of zero-profile spacer versus cage-plate for the treatment of patients with multilevel CSM. The following outcome measures were extracted: the Japanese Orthopaedic Association (JOA) scores, Neck Disability Index (NDI) score and fusion rate, dysphagia rate, adjacent segment degeneration, and cervical lordosis. Newcastle-Ottawa Quality Assessment Scale was used to evaluate the quality of each study. Data extraction and quality assessment were conducted, and RevMan 5.2 was used for data analysis. RESULTS: A total of 10 studies were included in our meta-analysis. Our pooled data revealed that zero-profile spacer was associated with decreased dysphagia rate at postoperatively 1, 3, and 6 months, and the final follow-up when compared with cage-plate group. No significant difference was observed in terms of postoperative JOA score, NDI score, and fusion rate. Compared with zero-profile spacer, the postoperative adjacent segment degeneration was significant higher in cage-plate. Pooled data from the relevant studies revealed that cervical lordosis was significantly lower in zero-profile spacer compared with cage-plate. CONCLUSIONS: Our meta-analysis reveals zero-profile spacer is better than the cage-plate in terms of dysphagia. This suggests zero-profile spacer is a superior alternative invention for the treatment of multilevel CSM to reduce the risk of dysphagia.

Long non-coding RNA reprogramming (lncRNA-ROR) regulates cell apoptosis and autophagy in chondrocytes.

Long Non-Coding RNA Reprogramming (lncRNA-ROR) plays an important role in regulating various biologic processes, whereas the effect of lncRNA-ROR in osteoarthritis (OA) is little studied. This study aimed to explore lncRNA-ROR expression in articular cartilage and identify the functional mechanism of lncRNA-ROR in OA. OA cartilage tissues were obtained from 15 OA patients, and 6 normal cartilage tissues were set as controls. Chondrocytes were isolated from the collected cartilage tissues. lncRNA-ROR was knockdown in normal cells and overexpressed in OA cells. Cell viability was determined with Cell Counting Kit-8 assay, and apoptosis was measured using flow cytometric analysis. Moreover, proteins and mRNAs involved in this study were also measured using Western blotting and quantitative real-time PCR (qPCR). Level of lncRNA-ROR was decreased in OA compared with normal chondrocytes, and overexpression of lncRNA-ROR dramatically promoted cell viability of OA chondrocytes. In addition, knockdown lncRNA-ROR inhibited apoptosis and promoted autophagy of normal chondrocytes. Moreover, lncRNA-ROR inhibited the expression of p53 in both mRNA and protein levels. Furthermore, we revealed that lncRNA-ROR regulated apoptosis and autophagy of chondrocytes via HIF1α and p53. The results indicated that lncRNA-ROR played a critical role in the pathogenesis of OA, suggesting that lncRNA-ROR could serve as a new potential therapeutic target for OA.

Down-regulation of microRNA-23b aggravates LPS-induced inflammatory injury in chondrogenic ATDC5 cells by targeting PDCD4.

OBJECTIVES: Osteoarthritis (OA), characterized by degradation of articular cartilage, is a leading cause of disability. As the only cell type present in cartilage, chondrocytes play curial roles in the progression of OA. In our study, we aimed to explore the roles of miR-23b in the lipopolysaccharide (LPS)-induced inflammatory injury. MATERIALS AND METHODS: LPS-induced cell injury of ATDC5 cells was evaluated by the loss of cell viability, enhancement of cell apoptosis, alteration of apoptosis-associated proteins, and release of inflammatory cytokines. Then, miR-23b level after LPS treatment was assessed by qRT-PCR. Next, the effects of aberrantly expressed miR-23b on the LPS-induced inflammatory injury were explored. The possible target genes of miR-23b were virtually screened by informatics and verified by luciferase assay. Subsequently, whether miR-23b functioned through regulating the target gene was validated. The involved signaling pathways were investigated finally. RESULTS: Cell viability was decreased but cell apoptosis, as well as release of inflammatory cytokines, was enhanced by LPS treatment. MiR-23b was down-regulated by LPS and its overexpression alleviated LPS-induced inflammatory injury. PDCD4, negatively regulated by miR-23b expression, was verified as a target gene of miR-23b. Following experiments showed miR-23b alleviated LPS-induced cell injury through down-regulating PDCD4 expression. Phosphorylated levels of key kinases in the NF-κB pathway, as well as expressions of key kinases in the Notch pathways, were increased by PDCD4 overexpression. CONCLUSION: MiR-23b was down-regulated after LPS treatment, and its overexpression ameliorated LPS-induced inflammatory injury in ATDC5 cells by targeting PDCD4, which could activate the NF-κB/Notch pathways.