Background: There is a paucity of literature about prognostic evaluation for patients with breast cancer (BC) and bone metastasis at presentation. To date, little is known about how to accurately predict the prognosis of BC patients with bone metastasis at presentation. Thus, an accurate prediction tool of prognosis in this population is urgently needed. Our goal is to construct novel and prognostic nomograms for BC patients with bone metastasis at presentation. Methods:We searched Surveillance, Epidemiology, and End Results (SEER) database for BC patients with bone metastasis at presentation between 2010 and 2016. Multivariate analysis was performed to obtain significantly independent variables. Then, novel prognostic nomograms were constructed based on those independent predictors.Results: Tumor grade, histological type, primary tumor size, tumor subtype, surgery, chemotherapy and number of metastatic organs except bone were recognized as significantly independent variables of both overall survival (OS) and cancer-specific survival (CSS). Then those significant variables were integrated to construct nomograms for 3-and 5-year survival. Calibration plots for the 3-and 5-year survival in training and validation sets showed that the prediction curve was close to a 45 degree slash. The C-indices of OS in training and validation cohorts were 0.705 and 0.678, respectively. Similar results were observed for CSS in training and validation cohorts.Conclusions: Our proposed nomograms can effectively and accurately predict the prognosis of BC patients with bone metastasis at presentation, which provide a basis for individual treatments for metastatic lesions.

Many miRNAs play critical roles in modulating various biological processes of osteoclast differentiation and function. Microphthalmia-associated transcription factor (MITF), a target of miR-340, served as pivotal transcription factor involved in osteoclast differentiation. However, the role of miR-340 and MITF during osteoclast differentiation has not yet been clearly established. Tartrate-resistant acid phosphatase (TRAP) staining assay was performed to identify osteoclasts differentiated from bone marrow-derived macrophages (BMMs). Quantitative reverse transcription PCR (qRT-PCR) or Western blotting was undertaken to examine the mRNA or protein expression respectively. Luciferase reporter assay was performed to investigate the interaction between miR-340 and MITF. MITF was knocked down and miR-340 was overexpressed and transfected into BMMs to detect their effects on osteoclast differentiation. Firstly, qRT-PCR analysis showed that miR-340 was down-regulated during osteoclast differentiation stimulated by macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-κB (RANK) ligand (RANKL). Besides, we found that overexpression of miRNA-340 inhibited osteoclast differentiation and suppressed both the mRNA and protein level of MITF. Finally, Western blot and qRT-PCR analysis revealed that silencing MITF inhibited TRAP, calcitonin receptor, V-ATPase d2, and cathepsin K. miR-340 suppresses osteoclast differentiation by inhibiting MITF. Our findings may provide promising therapeutic targets for osteoclast-associated diseases.

Aim: To compare the clinical and radiographic outcomes of percutaneous endoscopic-assisted lumbar interbody fusion (PELIF) versus oblique lumbar interbody fusion (OLIF) for the treatment of symptomatic low-grade lumbar spondylolisthesis. Material & methods: The clinical and radiographic records of 48 patients underwent single-level minimally invasive lumbar fusion with a PELIF (n = 16) or OLIF (n = 32) were reviewed. Results: The clinical and radiographic outcomes were similar in both groups. PELIF procedure exhibited superior capability of the enlargement of foraminal width, but inferior capability of the restoration of foraminal height than OLIF procedure. Conclusion: PELIF minimizes the iatrogenic damages and perioperative risks to a great extent, and seems to be a promising option for the treatment of symptomatic low-grade lumbar spondylolisthesis.

BackgroundZero-profile implant has become more and more popular in anterior cervical discectomy and fusion (ACDF) for the treatment of degenerative cervical spondylosis. However, there was no enough evidence judging its efficiency and safety. The aim of this analysis was to evaluate the efficacy and safety of Zero-profile implant compared with conventional cage-plate (CCP) in ACDF.MethodsAll studies directly comparing the outcomes between the Zero-profile implant and CCP implant in ACDF were included, and the search strategy followed the requirements of the Cochrane Library Handbook. Two of the authors extracted relevant data and checked the accuracy independently using standardized data collection form.ResultsSeven studies involving 560 patients were included, 262 in the Zero-profile group and 298 in the CCP group. Zero-profile implant had a lower rate of postoperative dysphagia at 2 weeks, 6 months, and 1 year (p = 0.0002, p = 0.008, and p = 0.001, respectively) than CCP implant. Zero-profile also reduced blood loss (p = 0.0001), while operation time and incidence of postoperative transient dysphagia had no statistical significance (p = 0.92, p = 0.42, respectively) between two groups.ConclusionBased on the results of our analysis, the application of Zero-profile implant in ACDF had a lower rate of postoperative dysphagia at 2 weeks, 6 months, and 1 year than CCP implant. Zero-profile implant also had fewer blood loss during operation. More rigorous and adequately powered prospective randomized controlled trials with larger sample size are required to elucidate a more objective outcome.

Transforming growth factor β1 (TGFβ1)/Smad4 signaling plays a pivotal role in maintenance of the dynamic balance between bone formation and resorption. The microRNA miR-155 has been reported to exert a significant role in the differentiation of macrophage and dendritic cells. The goal of this study was to determine whether miR-155 regulates osteoclast differentiation through TGFβ1/Smad4 signaling. Here, we present that TGFβ1 elevated miR-155 levels during osteoclast differentiation through the stimulation of M-CSF and RANKL. Additionally, we found that silencing Smad4 attenuated the upregulation of miR-155 induced by TGFβ1. The results of luciferase reporter experiments and ChIP assays demonstrated that TGFβ1 promoted the binding of Smad4 to the miR-155 promoter at a site located in 454 bp from the transcription start site in vivo, further verifying that miR-155 is a transcriptional target of the TGFβ1/Smad4 pathway. Subsequently, TRAP staining and qRT-PCR analysis revealed that silencing Smad4 impaired the TGFβ1-mediated inhibition on osteoclast differentiation. Finally, we found that miR-155 may target SOCS1 and MITF to suppress osteoclast differentiation. Taken together, we provide the first evidence that TGFβ1/Smad4 signaling affects osteoclast differentiation by regulation of miR-155 expression and the use of miR-155 as a potential therapeutic target for osteoclast-related diseases shows great promise.

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MicroRNAs (miRNAs) are small noncoding RNAs of 19-25 nt that can regulate gene expression at a posttranscriptional level. Increasing evidence indicates that miRNAs participate in almost every step of cellular processes and are often aberrantly expressed in human cancer. The aim of this study was to investigate the functional significance of miR-191 and to identify its possible target genes in osteosarcoma cells. Here, we found that the expression level of miR-191 was increased in osteosarcoma tissues in comparison with the adjacent normal tissues. The enforced expression of miR-191 was able to promote cell proliferation in Saos-2 and MG62 cells, while miR-191 antisense oligonucleotides blocked cell proliferation. At the molecular level, our results further revealed that expression of tumor suppressor gene, checkpoint kinase 2, was negatively regulated by miR-191. Therefore, we consider that miR-191 act as an onco-MicroRNA for osteosarcoma and it would offer a new way in molecular targeting cancer treatment.

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