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Aim: This study aimed to analyze the clinical characteristics and outcomes of patients with primary dumbbell chordoma of the cervical spine and to summarize the causes of misdiagnosis. Methods: The clinical data of patients were retrospectively collected. The diagnostic process, surgical procedures, and outcomes were analyzed, then the difference was compared between dumbbell and non‐dumbbell chordomas of the cervical spine. Results: This study included six patients with primary dumbbell chordoma (one male and five females) with a mean age of 32.2 ± 24.5 years (range: 5–61 years). Five cases with no computed tomography (CT) examination before the first operation were misdiagnosed, and on magnetic resonance imaging (MRI), primary dumbbell chordoma showed the following specific features: extensive invasion of the surrounding soft tissues with an obscure boundary (≥5 cm), intervertebral disc sparing, and hemorrhagic necrosis, furthermore, the CT features included atypical destructive vertebral lesions, minimal intralesional calcification, and neural foraminal enlargement. After comparison with non‐dumbbell chordomas, it show statistical difference (p < 0.05) in terms of calcification, foramen enlargement, FNA, misdiagnosis rate but with different recurrent rate. Conclusion: Primary dumbbell chordomas of the cervical spine can easily be misdiagnosed as neurogenic tumors. Preoperative CT‐guided fine‐needle aspiration puncture biopsy helps make an accurate diagnosis. Gross total excision with postoperative radiotherapy has been proven effective in reducing the recurrence rate. [ABSTRACT FROM AUTHOR]

Objective: Degenerative thoracolumbar hyperkyphosis (DTH) is a disease that negatively affects individual health and requires surgical intervention, yet the ideal surgical approach and complications, especially distal junctional failures (DJF), remain poorly understood. This study aims to investigate DJF in DTH and to identify the risk factors for DJF so that we can improve surgical decision‐making, and advance our knowledge in the field of spinal surgery to enhance patient outcomes. Methods: This study retrospectively reviewed 78 cases (late osteoporotic vertebral compression fracture [OVCF], 51; Scheuermann's kyphosis [SK], 17; and degenerative disc diseases [DDD], 10) who underwent corrective surgery in our institute from 2008 to 2019. Clinical outcomes were assessed using health‐related quality of life (HRQOL) measures, including the visual analogue scale (VAS) scores for back and leg pain, the Oswestry disability index (ODI), and the Japanese Orthopaedic Association (JOA) scoring system. Multiple radiographic parameters, such as global kyphosis (GK) and thoracolumbar kyphosis (TLK), were assessed to determine radiographic outcomes. Multivariate logistic regression analysis was employed to identify the risk factors associated with DJF. Results: HRQOL improved, and GK, TLK decreased at the final follow‐up, with a correction rate of 67.7% and 68.5%, respectively. DJF was found in 13 of 78 cases (16.7%), two cases had wedging in the disc (L3‐4) below the instrumentation, one case had a fracture of the lowest instrumented vertebrae (LIV), one case had osteoporotic fracture below the fixation, nine cases had pull‐out or loosening of the screws at the LIV and three cases (23.1%) required revision surgery. The DJF group had older age, lower computed tomography Hounsfield unit (CT HU), longer follow‐up, more blood loss, greater preoperative sagittal vertical axis (SVA), and poorer postoperative JOA and VAS scores (back). The change in TLK level was larger in the non‐DJF group. Post‐sagittal stable vertebrae (SSV) moved cranially compared with pre‐SSV. Conclusion: Age, CT HU, length of follow‐up, estimated blood loss, and preoperative SVA were independent risk factors for DJF. We recommend fixation of the two vertebrae below the apex vertebrae for DTH to minimize surgical trauma. [ABSTRACT FROM AUTHOR]

Objective: Re‐resection of spinal giant cell tumors is an exceedingly difficult procedure. Moreover, the prognosis of patients with en bloc resection or intralesional excision for re‐resection has rarely been reported. This study aimed to compare the prognostic value of en bloc resection with that of intralesional excision in patients undergoing re‐resection for giant cell tumors of the spine. Methods: This retrospective analysis evaluated patients who underwent revision surgeries for relapse of giant cell tumors of the spine at our center between January 2005 and January 2021. Local progression‐free survival represents the duration between en bloc resection or intralesional excision and tumor recurrence. Neurological recovery, survival rates, local control, and complications were evaluated. The Kaplan–Meier estimator was used for survival analysis. Results: A total of 22 patients (nine men and 13 women) with a mean age of 34.1 (range 19–63) years were included. Significant statistical differences were found in the local tumor recurrence rate between patients treated with en bloc resection and those treated with intralesional excision (p < 0.05). The 5‐ and 10‐year local progression‐free survival rates were both 90% in the en bloc resection group, while in the intralesional excision group, the 5‐year local progression‐free survival rate was 80% with a 10‐year rate of 45.7%. The en bloc resection group had a lower local tumor recurrence rate than that of the intralesional excision group (p < 0.05), but the former had a higher rate of complications (p = 0.015). Conclusions: This study revealed a low local recurrence rate in patients who underwent en bloc resection for giant cell tumors, while the perioperative complication rate was high. [ABSTRACT FROM AUTHOR]

The spine is the most common site of bone metastases. Many cancer patients will ultimately develop spinal metastatic disease with symptomatic epidural spinal cord compression. At present, the main treatment for cervical spine tumors is surgical resection combined with postoperative radiotherapy. Implant materials for cervical spine anterior column reconstruction need to meet amounts of different properties, such as biocompatibility, bioactivity and the ability to maintain long‐term mechanical strength. The selection of different materials determines the surgical efficacy and prognosis of patients to a certain extent. This article provides an overview of a variety of implant materials used for anterior column reconstruction after cervical spine tumor resection, introduces and analyzes their properties, advantages, disadvantages, derivatives, and applications in clinical practice, and looks forward to the future development of implant materials. [ABSTRACT FROM AUTHOR]

Purpose: Spinal metastases of lung cancer (SMLC) usually have high degree of malignancy and require surgical treatment. However, there are several controversies about the efficacy of surgery. This study aimed to investigate factors predicting prognosis of SMLC after surgery‐based comprehensive treatment. Methods: A cohort of 112 cases of SMLC who underwent surgical treatment between 2009 and 2020 were retrospectively reviewed and analyzed. The surgical strategies included total en‐bloc spondylectomy, debulking surgery, palliative decompression, and vertebral augmentation procedures. The patients were regularly followed‐up. Survival analysis was performed, as well as analysis of the patients' neurological recovery, pain relief, and improvement of Karnosky performance score (KPS). Cox regression was used to analyze influencing factors of survival time, and Kaplan–Meier method was performed in survival analysis. Results: The cohort included 63 males and 49 females, with an average age of 60.6 ± 10.6 years. Median survival time was 16 months. A total of 86.7% of paralysis patients' neurological function recovered and 83.9% of patients with low KPS score (10–40) improved. Surgical method was significantly correlated with improvement of neurological function (p < 0.001) and KPS (p < 0.001). The mean bleeding volume was 502 ml and operative time was 170 min. The survival rates at 3, 6, 12, 24, and 36 months were 92.0%, 80.4%, 63.4%, 63.4%, and 22.6%, respectively. Postoperative Frankel grade (p < 0.001), postoperative KPS score (p = 0.001), and application of molecular targeted drugs (p < 0.001) were significantly correlated with survival time in univariate analysis, while application of molecular targeted drugs was an independent predictor for a longer survival by a multivariate analysis. Conclusion: Surgery‐based comprehensive treatment brought a fair outcome, with elongated survival time. Surgery can significantly improve patients' neurological function and physical performance status. Adjuvant targeted therapy is an independent positive factor for patients' survival. [ABSTRACT FROM AUTHOR]

Dental pulp stem cells (DPSCs) must undergo odontoblastic differentiation in order to facilitate the process of dentin-pulp complex repair. Herein, we sought to explore the ability of Neu5Ac (one form of sialic acid) to influence DPSC osteo-/odontoblastic differentiation via modulating mitogen-activated protein kinase (MAPK) signaling. Methodology. DPSCs were isolated from human third permanent teeth and were grown in vitro. Fluorescent microscopy was used to detect the existence of sialic acid on the DPSC membrane. Following the treatment of different concentrations of Neu5Ac and removing sialic acid from the cell surface by neuraminidase, the osteo-/odontoblastic differentiation of these cells was evaluated via mineralization, alkaline phosphatase, and in vivo assays. In addition, the expression of genes related to osteo-/odontoblastic differentiation and MAPK signaling at different stages of this differentiation process was analyzed in the presence or absence of Neu5Ac. Results. The existence of sialic acid on the DPSC membrane was confirmed by fluorescent microscopy, and the ability of osteo-/odontoblastic differentiation was decreased after removing sialic acid by neuraminidase. Treatment of DPSCs with Neu5Ac (0.1 mM or 1 mM) significantly enhanced their mineralization ability and alkaline phosphatase activity. The expression levels of DMP1, DSPP, BSP, and RUNX2 were also increased. Treatment of nude mice with ManNAc (the prerequisite form of Neu5Ac) also enhanced DPSC mineralization activity in vivo. Furthermore, Neu5Ac treatment enhanced p-ERK expression in DPSCs, while ERK pathway inhibition disrupted the ability of Neu5Ac to enhance the osteo-/odontoblastic differentiation of these cells. Conclusions. Neu5Ac can promote DPSC osteo-/odontoblastic differentiation through a process associated with the modulation of the ERK signaling pathway activity. [ABSTRACT FROM AUTHOR]

Aftiphilin (AFTPH) plays an important role in regulating intracellular trafficking, exocytosis, and the pro‐inflammatory response. However, the potential prognostic role of AFTPH in cancers remains unclear. Here, we examined the expression profiles and prognostic significance of AFTPH in breast invasive carcinoma (BRCA), diffuse large B‐cell lymphoma (DLBC), lung squamous cell carcinoma (LUSC), and pancreatic adenocarcinoma (PADD) using the GEPIA and UALCAN databases. AFTPH expression was observed to be higher in cancer tissues than in normal tissues, but expression did not differ significantly between tumor stages for the four cancer types. AFTPH expression in cancer cell lines was investigated using the CCLE database; AFTPH was found to be highly expressed in four cancer cell lines. The relationship between AFTPH expression and patient prognosis was analyzed using GEPIA, LinkedOmics, and Kaplan–Meier plotter databases. Low expression of AFTPH was associated with improved prognosis for BRCA, DLBC, LUSC, and PAAD. Genetic alterations of AFTPH in cancers were explored using the cBioPortal website, revealing that gene copy number gains and amplification are common in BRCA, DLBC, LUSC, and PAAD. Related genes and markers associated with AFTPH were discovered using the LinkedOmics database. Furthermore, transfection of cells with AFTPH siRNA demonstrated that AFTPH exerts positive effects on cell proliferation in BRCA, LUSC, and PAAD cells. In conclusion, AFTPH may be a potential therapeutic target and prognostic biomarker for BRCA, DLBC, LUSC, and/or PAAD. [ABSTRACT FROM AUTHOR]

Dentin‐pulp regeneration requires dental pulp stem cells (DPSCs), but the role of long noncoding RNAs (lncRNAs) during this process remains unclear. Here, we cultured human DPSCs in osteogenic/odontogenic medium for 14 days and analyzed cells via RNA‐sequencing. The data were validated by quantitative reverse transcription‐polymerase chain reaction and lncRNA–microRNA (miRNA)–messenger RNA (mRNA) networks were constructed to reveal the potential competing endogenous RNA regulatory role of lncRNAs. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis were performed. One lncRNA, SNHG7, was identified and validated by genetic shRNA silencing. A total of 89 lncRNAs, 1,636 mRNAs, and 113 miRNAs were differentially expressed after differentiation. Bioinformatics identified an array of affected signaling pathways including phosphoinositide‐3‐kinase–protein kinase B, transforming growth factor‐β, and Wnt. mRNAs were enriched in cell migration, cell differentiation, stem cell development, ossification, and skeletal development. One lncRNA, SNHG7, was indentified to inhibit the odonto/osteogenic differentiation of DPSCs when silenced. In summary, we reveal several lncRNAs that significantly change during DPSC differentiation, including SNHG7. This reveals new targets for dentin‐pulp complex regeneration and tissue engineering. [ABSTRACT FROM AUTHOR]

Osteosarcoma, one of the most common malignant bone tumors, is characterized by a high rate of metastasis, and the survival rate of patients with metastatic osteosarcoma is poor. Previous studies have reported that miRNAs often regulate the occurrence and development of various tumors. In this work, we identified miRNA‐542‐5p as a critical miRNA in osteosarcoma by overlapping three Gene Expression Omnibus datasets, and then evaluated miRNA‐542‐5p expression profiles using Gene Expression Omnibus and Sarcoma‐microRNA Expression Database. We used MISIM to investigate miRNAs correlated with miR‐542 and identified potential target genes of miRNA‐542‐5p using miRWalk. Functional and pathway enrichment analyses were performed using The Database for Annotation, Visualization and Integrated Discovery. Protein–protein interaction was performed using Search Tool for the Retrieval of Interacting Genes and Cytoscape. We report that the relative level of miRNA‐542‐5p was significantly higher in osteosarcoma than in healthy bone. Expressions of hsa‐miR‐330 and hsa‐miR‐1202 were found to be strongly correlated with that of miR‐542‐5p. Furthermore, we identified a total of 514 down‐regulated genes as possible targets of miR‐542‐5p. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that the putative target genes of miR‐542‐5p were most enriched in the cell‐cycle process. The differentially expressed genes CDCA5, PARP12 and HSPD1 were found to be hub genes in protein–protein interaction networks. Finally, transfection of the osteosarcoma cell line U2OS with miR‐542‐5p mimics or inhibitor revealed that miR‐542‐5p can promote cell proliferation. In conclusion, our results suggest that miR‐542‐5p may promote osteosarcoma proliferation; thus, this miRNA may have potential as a biomarker for diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Background: In the treatment of spinal metastases, stereotactic body radiotherapy (SBRT) delivers precise, high‐dose radiation to the target region while sparing the spinal cord. A range of doses and fractions had been reported; however, the optimal prescribed scheme remains unclear. Methods: Two reviewers performed independent literature searches of the PubMed, EMBASE, Cochrane Database, and Web of Science databases. Articles were divided into one to five fractions groups. The Methodological Index for Non‐randomized Studies (MINORS) was used to assess the quality of studies. Local control (LC) and overall survival (OS) were presented for the included studies and a pooled value was calculated by the weighted average. Results: The 38 included studies comprised 3,754 patients with 4,731 lesions. The average 1‐year LCs for the one to five fractions were 92.7%, 84.6%, 86.8%, 82.6%, and 80.6%, respectively. The average 1‐year OS for the one to five fractions were 53.0%, 70.4%, 60.1%, 48%, and 80%, respectively. The 24 Gy/single fraction scheme had a higher 1‐year LC (98.1%) than those of 24 Gy/two fractions (85.4%), 27 Gy/three fractions (84.9%), and 24 Gy/three fractions (89.0%). The incidence of vertebral compression fracture was 10.3%, with 10.7% in the single‐fraction group and 10.1% in the multi‐fraction group. The incidence of radiation‐induced myelopathy was 0.19%; three and two patients were treated with single‐fraction and multi‐fraction SBRT, respectively. The incidence of radiculopathy was 0.30% and all but one patient were treated with multi‐fraction SBRT. Conclusions: SBRT provided satisfactory efficacy and acceptable safety for spinal metastases. Single‐fraction SBRT demonstrated a higher local control rate than those of the other factions, especially the 24 Gy dose. The risk of vertebral compression fracture (VCF) was slightly higher in single‐fraction SBRT and more patients developed radiculopathy after multi‐fraction SBRT. [ABSTRACT FROM AUTHOR]

A major problem in osteosarcoma treatment is cisplatin resistance. We have reported the anti-osteosarcoma effect of oleandrin; however, whether oleandrin sensitizes osteosarcoma to cisplatin is unknown. We investigated the chemosensitization of oleandrin and potential mechanisms in osteosarcoma cells U-2OS, SaOS-2, and MG-63. The median-effect analysis demonstrated that cisplatin + oleandrin exerted synergistic (U-2OS and MG-63) or additive effects (SaOS-2), which were consistent with the changes of the intracellular accumulation of platinum (Pt) and Pt-DNA adducts. Immunohistochemistry staining showed that the expression level of the mature form CTR1, the major influx transporter of cisplatin, was low in osteosarcoma tissue. However, oleandrin with or without cisplatin significantly increased the expression and membrane localization of the mature CTR1. Furthermore, CTR1 knockdown reversed the synergistic effect and decreased cisplatin uptake. The mRNA microarray analysis suggested that oleandrin downregulated the expression of proteasome-related genes, which was verified by the proteasome activity assay. Besides, the proteasome inhibitor MG132 upregulated the expression of the mature CTR1 in U-2OS and MG-63 cells. Overall, we conclude that oleandrin sensitizes osteosarcoma cells to cisplatin in synergistic or additive manners. The synergy results from the enhanced cisplatin uptake via oleandrin-mediated inhibition of proteasome activity and subsequent blockage of the mature CTR1 degradation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Medicinal mushrooms contain biologically active substances that can be used as an immune‐modulating agent in poultry. The present study aimed to investigate the effects of Flammulina velutipes mushroom waste (FVW) on performance, immune response and serum immunity in growing layer hens. RESULTS: No significant differences (P > 0.05) were observed with respect to average daily feed intake, body weight gain and feed conversion ratio among the experimental groups during the entire study period (1–70 days). Antibody titers against Newcastle disease and infectious bronchitis were higher (P < 0.05) in the FVW fed groups than in the control and antibiotic groups. On day 28, serum immunoglobulin (Ig)A and IgG were higher (P < 0.05) in the 6% FVW group than in the control and antibiotic fed groups. On day 70, serum IgA was higher (P < 0.05) in FVW fed groups than in the control group; IgG was higher (P < 0.05) in the FVW groups than in the control and antibiotic groups. However, IgM was higher (P < 0.05) in both the 4% and 6% FVW groups than in the control and antibiotic groups for both experimental periods. Serum cytokine interleukin (IL)‐2 and tumor necrosis factor‐α concentrations were significantly higher (P < 0.05) in both the 4% and 6% FVW grousp than in the control and antibiotic groups; IL‐4 was significantly higher (P < 0.05) in the FVW groups than in the control group; and IL‐6 was significantly higher (P < 0.05) in the 6% FVW group than in the control and antibiotic groups. CONCLUSION: FVW at the 6% level can be used as a potential phytogenic feed stuff in growing layer hen rations with respect to improving the immune response without affecting normal weight gain. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Chordomas are rare bone tumors with a poor prognosis and no approved targeted therapy. Y‐box binding protein‐1 (YBX1) promotes tumor growth, invasion and drug resistance. However, the role of YBX1 in chordoma is unclear. In this study, we examined the expression of YBX1 using immunohistochemistry and found that YBX1 was significantly upregulated in 32 chordoma tissues compared to distant normal tissues. In addition, YBX1 upregulation was associated with surrounding tissue invasion, recurrence and poor prognosis. Biological function studies demonstrated that YBX1 promoted cell proliferation and invasion, accelerated G1/S phase transition, and inhibited apoptosis. Further investigation revealed that YBX1 enhanced epidermal growth factor receptor (EGFR) transcription by directly binding to its promoter in chordoma cells. YBX1 regulated protein expression of p‐EGFR, p‐AKT and its downstream target genes that influenced cell apoptosis, cell cycle transition and cell invasion. YBX1 activated the EGFR/AKT pathway in chordoma and YBX1‐induced elevated expression of key molecules in the EGFR/AKT pathway were downregulated by EGFR and AKT pathway inhibitors. These in vitro results were further confirmed by in vivo data. These data showed that YBX1 promoted tumorigenesis and progression in spinal chordoma via the EGFR/AKT pathway. YBX1 might serve as a prognostic and predictive biomarker, as well as a rational therapeutic target, for chordoma. YBX1 promoted tumorigenesis and progression in spinal chordoma via the EGFR/AKT pathway. YBX1 might serve as a prognostic and predictive biomarker, as well as a rational therapeutic target, for chordoma. [ABSTRACT FROM AUTHOR]

Titanium-based implants possessing adequately low elasticity modulus and custom­designed structures are urgently demanded in recent years for orthopedic applications. Electron beam melting (EBM) provides an opportunity to fabricated porous titanium scaffolds that meet the as-mentioned requirements, and it further allows for improved bone regeneration and increased contact area at implant-tissue interface. As a novel additive manufacturing (AM) technique, EBM could conveniently produce scaffolds with tunable porosity and shapes and complex structures based on the popular 'bottom-up' concept. In the present work, EBM-produced Ti6Al4V cylinders designed with either a small pore size (EBMS, 640 μm) or a large one (EBML, 1200 μm) were characterized in respect of microstructure, permeability and specific surface area, and their cytocompatibility and osteogenic ability were evaluated subsequently in vitro. Both samples EBMS and EBML could support the attachment and proliferation of hMSCs with minimal inflammatory cytokines secretion. The EBMS scaffolds were relatively more compatible with hMSCs than the EBML and they better sustained osteogenesis probably for their larger specific surface area. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor (HIF)-1α is a key nuclear transcription factor that regulates the cellular response to hypoxia, and is important for solid tumor growth and survival. However, the underlying role of HIF-1α in human chondrosarcoma has not been well characterized. This study aims to investigate the expression patterns of HIF-1α in chondrosarcoma, and its association with clinicopathologic features, Bcl-xL expression, apoptosis index (AI), and overall survival of patients with chondrosarcoma. Our results shown that the protein levels of HIF-1α were increased, and the mRNA and protein levels of Bcl-xL were also increased in SW1353 cells under hypoxic conditions. In eight patients with chondrosarcoma, increased expression of HIF-1α and Bcl-xL was detected in chondrosarcoma tissues compared with the paired adjacent normal tissues. Of 34 archival specimens of chondrosarcomas, 20 (58.8%) showed high HIF-1α protein expression as compared to benign cartilage tumors. Increased HIF-1α expression was correlated with a higher pathological grade and MSTS stage of chondrosarcoma. Moreover, HIF-1α expression was significantly associated with Bcl-xL expression and AI. More significantly, the survival rate of patients with HIF-1α high tumors was significantly lower than that of patients with HIF-1α low tumors. These findings suggest that increased HIF-1α levels mediated up-regulation of Bcl-xL play a prominent role in evasion of apoptosis and tumor progression, and can be predictive for the prognosis in human chondrosarcoma. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:143-151, 2011 [ABSTRACT FROM AUTHOR]