BACKGROUND CONTEXT: Laminoplasty is a common surgical method used to treat patients with cervical ossification of the posterior longitudinal ligament (OPLL). Although laminoplasty is preferred over traditional laminectomy, the factors affecting the complications and outcomes are unclear. Recently, sagittal balance indexes have been revealed to be predictors of clinical outcomes in patients with cervical degenerative diseases, but their relationships with laminoplasty-treated OPLL outcomes remains unknown. PURPOSE: The purpose of this study is to evaluate the relationship of preoperative cervical sagittal balance indexes and clinical outcome in laminoplasty treated OPLL patients. STUDY DESIGN: This is a retrospective case study. PATIENT POPULATION: Between January 2015 and January 2017, 181 consecutively included patients who underwent cervical laminoplasty for OPLL were enrolled (male:female ratio=126:75; mean age=60.2 years). Cervical spine lateral radiographs in neutral, flexion, and extension positions were taken before and 2 years after the surgery. OUTCOME MEASURES: The C2−C7 Cobb angle, T1 slope, C1−C7 sagittal vertical axis (SVA), C2−C7 SVA, CGH (center of gravity of the head)-C7 SVA, cervical JOA (Japanese Orthopedic Association) score, and neck VAS (visual analogue scale) score were measured preoperatively and postoperatively at the 2-year follow-up. METHODS: The patients were divided into two groups according to changes in the lordotic angle or the recovery rate of the JOA score. The relationships between the postoperative lordosis loss or the clinical outcome and the preoperative variables, including the patient's age, JOA score, C2-C7 Cobb angle, T1 slope, C1-C7 SVA, C2-C7 SVA, and CGH-C7 SVA, were investigated. RESULTS: The patients were divided into two groups according to the postoperative change in the C2-C7 Cobb angle. There were no differences in the age, preoperative C2-C7 Cobb angle, C1-C7 SVA, or C2-C7 SVA; there was only a difference in the preoperative CGH-C7 SVA and T1 slope level (p=.038, p=.042). The postoperative JOA and JOA recovery rate were related to the postoperative lordosis loss in cervical alignment (p=.048, p=.031). We again divided the patients into two groups according to the JOA recovery rate and found that only the preoperative CGH-C7 SVA and FSA device/drug status: Not applicable.

Osteosarcoma (OS), the most common malignant bone tumor, is the main cause of cancer-related deaths in children and young adults. Despite the combination of surgery and multi-agent chemotherapy, patients with OS who develop resistance to chemotherapy or experience recurrence have a dismal prognosis. MicroRNAs (miRNAs) are a class of small noncoding RNAs that repress their targets by binding to the 3′-UTR and/or coding sequences, leading to the inhibition of gene expression. miR-221 is found to be up-regulated in tumors when compared with their matched normal osteoblast tissues. We also observed significant miR-221 up-regulation in the OS cell lines, MG-63, SaoS-2, and U2OS, when compared with the normal osteoblast cell line, HOb. Overexpression of miR-221 promoted OS cell invasion, migration, proliferation, and cisplatin resistance. MG-63 and SaoS-2 cells transfected with miR-221 mimics were more resistant to cisplatin. The IC50 of MG-63 cells transfected with control mimics was 1.24 μM. However, the IC50 of MG-63 cells overexpressing miR-221 increased to 7.65 μM. Similar results were found in SaoS-2 cells, where the IC50 for cisplatin increased from 3.65 to 8.73 μM. Thus, we report that miR-221 directly targets PP2A subunit B (PPP2R2A) in OS by binding to the 3′-UTR of the PPP2R2A mRNA. Restoration of PPP2R2A in miR-221-overexpressing OS cells recovers the cisplatin sensitivity of OS cells. Therefore, the present study suggests a new therapeutic approach by inhibiting miR-221 for anti-chemoresistance in OS.

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Background Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases, and is the leading cause of pain and disability in the aged population. However, the underlying biological mechanism has not been fully understood. This study aims to reveal the causal effect of circulation metabolites on OA susceptibility. Methods A bi-directional two-sample Mendelian Randomization (MR) analysis was performed to estimate the causality of GDMs on OA. A genome-wide association study (GWAS) of 486 metabolites was used as the exposure, whereas 8 different OA phenotypes, including any-site OA (All OA), knee and/or hip OA (knee/hip OA), knee OA, hip OA, spine OA, finger and/or thumb OA (hand OA), finger OA, thumb OA, were set the outcomes. Inverse-variance weighted (IVW) was used for calculating causal estimates. Methods including weight mode, weight median, MR-egger, and MR-PRESSO were used for the sensitive analysis. Furthermore, metabolic pathway analysis was performed via the web-based Metaconflict 4.0. All statistical analyses were performed in R software. Results In this MR analysis, a total of 235 causative associations between metabolites and different OA phenotypes were observed. After false discovery rate (FDR) correction (FDR) correction and sensitive analysis, 9 robust causative associations between 7 metabolites (e.g., arginine, kynurenine, and isovalerylcarnitine) and 5 OA phenotypes were finally identified. Additionally, eleven significant metabolic pathways in 4 OA phenotypes were identified by metabolic pathway analysis. Conclusion The finding of our study suggested that identified metabolites and metabolic pathways can be considered useful circulating metabolic biomarkers for OA screening and prevention in clinical practice, and can also serve as candidate molecules for future mechanism exploration and drug target selection.

Polo-like kinase 1(PLK1) is essential for the maintenance of genomic stability during mitosis. PLK1 has been reported to be upregulated in several solid tumors, including esophageal squamous cell carcinoma (ESCC). However, the role of PLK1 in tumorigenesis of ESCC remains undetermined. We used siRNA and lentivirus-mediated PLK1 RNA interference to investigate the tumor suppressor function of PLK1 reduction in ESCC cells. Flow cytometry and Terminal deoxynuleotidyl transferase-mediated nick-end labeling assay in vitro, as well as immunohistochemitry analysis of Caspase-3 and CD31 in s.c. tumor tissue section, were performed. Knock down of PLK1 expression significantly suppressed the ability of ESCC cells to form colonies in plastic and soft agar. PLK1 reduction mediated by lentivirus caused growth suppression of ESCC in nude mice. Caspase-3 upregulation further indicated that dysregulated apoptosis might contribute to reduced tumorigenecity. In particular, downregulation of CD31 suggested that PLK1 reduction-induced angiogenesis inhibition may also contribute, at least in part, to attenuated tumorigenecity. These findings indicate that PLK1 might play roles in tumorigenesis of ESCC and that PLK1 might be a potential gene therapy target in ESCC. Apoptosis induction together with decreased angiogenesis might be involved in the mechanism of tumor suppressor function of RNA interference targeting PLK1.