Osteosarcoma (OS) is a primary bone tumor with high malignancy and the mechanism of hematogenous metastasis in OS is still not clear. The plasma exosomes derived from osteosarcoma play a key role in the process of tumor metastasis. Here, we established RNA-seq dataset for lncRNAs, circRNAs and mRNAs in plasma exosomes from 10 OS patients and 5 healthy donors. A total of 329.52 Gb of clean data was obtained. Besides, 1754 lincRNAs, 7096 known and 1935 new circRNA was identified. Finally, gene expression profiles and differentially expressed genes (DEGs) were analyzed among these 15 samples. There were 331 DEGs of mRNA, 132 of lincRNA and 489 of circRNA was obtained, respectively. This data set provides a significant resource for relevant researchers to excavate potential dysregulated lncRNAs, circRNAs and mRNAs of plasma exosomes in OS versus normal conditions.
Function of survivin protein (encoded by BIRC5) in circulating tumor cells (CTCs) of osteosarcoma (OS) has not been investigated. The goal of this study is to determine whether the expression of survivin protein of CTCs is associated with circulating immune cell infiltration and disease prognosis of OS. Blood samples of 20 patients with OS were collected. CanPatrol™ CTC enrichment technology combined with in situ hybridization (ISH) was applied to enrich and test CTCs and survivin protein. Bioinformation analysis combined with data of routine blood test was used to verify the association between survivin and immune cell infiltration in circulatory system. To screen independent prognostic factors, Kaplan–Meier survival curve, univariate and multivariable Cox regression analyses were performed. Bioinformatics analysis showed that BIRC5 was strongly negatively related to lymphocyte, including T cell, NK cell and B cell, which released that BIRC5 played a key role in immune escape via reducing immune cell infiltration in circulatory system. Meanwhile, the number of survivin+ CTCs was significantly negatively connection with lymphocyte count (R = −0.56, p = 0.011), which was consistent with bioinformatics analysis. Kaplan–Meier curve showed that the overall survival rate in high survivin+ CTCs group was significantly lower than low group (88.9
患者,男,38 岁,2 d前交通事故伤致全身多处肿痛,于 2020 年6 月19 日送至我院就诊.患者8岁时曾被诊断为甲型血友病.X线片显示:左侧股骨上段粉碎性骨折;双侧股骨头缺血坏死(Ⅲ ~ Ⅳ期)并双侧髋关节继发性骨关节炎;双侧膝关节重度骨关节炎.凝血因子全套提示凝血因子Ⅷ为1%.考虑患者为甲型血友病合并左侧股骨转子下骨折及股骨上段粉碎性骨折,双侧膝、髋关节为血友病性关节炎,双侧股骨头缺血坏死.入院后补充足量新鲜冰冻血浆,第8 天凝血因子Ⅷ为50%,凝血时间正常.于2020年6月28日输注足量血浆源性因子Ⅷ浓缩物,并备足凝血因子制剂后,在全身麻醉下行左侧股骨上段粉碎性骨折切开复位锁定钢板内固定术.
The bystin-like ( BYSL ) gene is expressed in a wide range of eukaryotes and is closely associated with tumor progression. However, its function and mechanism in osteosarcoma remain unclear. Herein, the protein expression and clinical role of BYSL in human osteosarcoma tissues were assessed. High expression of BYSL was positively related to the metastasis status and poor patient prognosis. Mechanistically, upregulation of BYSL enhanced Nrf2 expression under hypoxia in osteosarcoma cells. MicroRNAs are important epigenetic regulators of osteosarcoma development. Noteworthy, bioinformatics analysis, dual-luciferase reporter and rescue assays showed that miR-378a-3p inhibited BYSL expression by binding to its 3′-untranslated region. Analysis of miR-378a-3p function under hypoxia and normoxia showed that its upregulation suppressed osteosarcoma cells invasion and inhibited epithelial-to-mesenchymal transition by suppressing BYSL . Collectively, the results show that the miR-378a-3p/BYSL may associate with metastasis risk in osteosarcoma.
Osteoporosis is a systemic and metabolic bone disease that usually occurs in postmenopausal women, which mainly manifests as bone loss and increased bone fragility that both facilitate fracture. However, few drugs for osteoporosis have shown good efficacy and limited side effects. Vaccarin has demonstrated its antiosteoporosis effects by inhibiting the formation and osteolytic activities of osteoclasts in our previous investigation. In this study, multivariate statistical analysis and ultrahigh-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry were used to analyze the serum metabolites of ovariectomized mice treated with or without vaccarin. As a result, 9 serum metabolites were identified as biomarkers. The metabolic levels of 3 crucial biomarkers, namely, lysophosphatidylcholine [22 : 6, (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)], 1-linoleoylglycerophosphocholine and 1-palmitoyl-Sn-glycero-3-phosphocholine, that were correlated with glycerophospholipid metabolism increased and then decreased significantly after vaccarin treatment. Molecular docking analysis and osteoclasts differentiation experiment further revealed that vaccarin may bind with phospholipase A2 and downregulated its activity to reduce the osteoclastogenesis. Therefore, the occurrence of osteoporosis is closely related with glycerophospholipid metabolism disorders, and vaccarin exerts antiosteoporosis effects by reducing the levels of glycerophospholipid metabolites.
Osteosarcoma (OS) is the most common primary malignant bone tumour with a peak in incidence during adolescence. Delayed patient presentation and diagnosis is common with approximately 15% of OS patients presenting with metastatic disease at initial diagnosis. With the introduction of neoadjuvant chemotherapy in the 1970s, disease prognosis improved from 17% to 60%-70% 5-year survival, but outcomes have not significantly improved since then. Novel and innovative therapeutic strategies are urgently needed as an adjunct to conventional treatment modalities to improve outcomes for OS patients. Angiogenesis is crucial for tumour growth, metastasis and invasion, and its prevention will ultimately inhibit tumour growth and metastasis. Dysregulation of angiogenesis in bone microenvironment involving osteoblasts and osteoclasts might contribute to OS development. This review summarizes existing knowledge regarding pre-clinical and developmental research of targeted anti-angiogenic therapy for OS with the aim of highlighting the limitations associated with this application. Targeted anti-angiogenic therapies include monoclonal antibody to VEGF (bevacizumab), tyrosine kinase inhibitors (Sorafenib, Apatinib, Pazopanib and Regorafenib) and human recombinant endostatin (Endostar). However, considering the safety and efficacy of these targeted anti-angiogenesis therapies in clinical trials cannot be guaranteed at this point, further research is needed to completely understand and characterize targeted anti-angiogenesis therapy in OS.
目前,骨质疏松症作为全球性的公共卫生健康问题已严重影响人类健康,虽然近年来对骨质疏松症的研究不断深入,但仍不能完整及正确地诠释其相关的发病机制.由于炎症因子在炎症性骨病中发挥重要作用,不但可以作为监测疾病进展的生物标志物,也可作为临床诊疗的诊断指标.大量研究表明,炎症因子可通过激活或抑制相关的信号通路及影响相关酶蛋白的表达量等来影响成骨细胞与破骨细胞的活性和功能,进而在影响骨质疏松症的发生发展中起着至关重要的作用.本文根据炎症因子对骨质疏松症的不同作用分为促进、抑制、双作用炎症因子三大类型,并就它们影响骨质疏松症发病机制中的作用作一简要综述,从而为骨质疏松症的相关研究提供理论依据.
Osteosarcoma, the most common primary bone tumor in children and adolescents, is characterized by high malignancy, rapid progression and high metastatic potential. However, no significant progress has been made in treating osteosarcoma recently. The prognosis of osteosarcoma is usually unsatisfied. One of the main reasons is that we cannot be able to identify the Achilles heel of osteosarcoma. A growing number of evidence suggests that different types of RNA play various roles in the development of osteosarcoma. The competing endogenous RNA (ceRNA) is a newly emerging theory, which can propose messenger RNA (mRNA), long non-coding RNA (lncRNA), pseudogene and other different transcripts. Therefore, it can play a role in the regulation of microRNA (miRNA) through competition. In the latest researches, it is shown that the interaction of these transcripts play an important role in the occurrence and development of osteosarcoma by mediating biological processes such as proliferation, apoptosis, metastasis and chemotherapy resistance of osteosarcoma cells. In addition, these different types of transcripts may provide new biomarkers and potential therapeutic targets for osteosarcoma. The present studies review the development of ceRNA hypothesis, summarizes existing knowledge system of ceRNA, and develop a systematic review of the role of different types of ceRNA in the pathogenesis and biological function of osteosarcoma. This review could lay the foundation for the basic and clinical study of osteosarcoma and promote the early diagnosis and treatment effects of osteosarcoma.
Osteoarthritis (OA) is a common degenerative disease. Its most significant pathological change is destruction of articular cartilage and the main clinical symptoms are pain and dysfunction of joints. Recent studies have shown that the expression of non-coding RNA (ncRNA) in chondrocytes can abnormally up-regulate or down-regulate and alter the activities of chondrocytes like their proliferation, migration and apoptosis, thus leading to the occurrence and development of osteoarthritis. Exosomes are extracellular vesicles with a diameter of 40-100 nm, which are secreted in intercellular fluid, act as medium of intercellular communication. They protect ncRNA, protein, lipid and other bioactive materials from enzymatic degradation by encapsulating them and transferring to sibling chondrocytes, due to their good tissue permeability. They can also improve communication between cells and regulate the activities of chondrocytes. Thus, exosomes behave like gene carriers. The ncRNA carried by exosomes can supplement or adsorb the abnormal ncRNA in chondrocytes, so as to regulate the activity of chondrocytes, and is therefore considered as a possible candidate with capabilities to repair cartilages. In this study we reviewed existing literatures related to the roles and effects of exosome miRNA, lncRNA and circRNA on osteoarthritis. We also reviewed the pathogenesis of exosome ncRNA in osteoarthritis.
Some primary bone tumors are prone to hematogenous metastasis and after that, the therapeutic effect is not that good and prognosis is poor. Circulating tumor cells (CTC) shed from the tumor cells of primary or metastatic focus and then enter into blood circulation. CTC may appear in the early stage of the tumor, which can implant in distant organs to form metastatic sites and self-implant in the primary sites leading to the tumor recurrence; CTC are closely related with the prognosis of patients with tumors. In most primary bone tumors, CTC are heterogeneous compared with primary tumor cells. Studying CTC from various aspects can provide a basis for the early diagnosis and treatment of primary bone tumors. This review summarizes the current researches of CTC in common primary bone tumors, and expects the future of research direction and application practice in clinic.
为了探讨"金课"建设理念下的新型教学模式在脊柱骨科临床见习教学中的应用效果,文章以100名在脊柱骨病科进行临床见习的2016级本科实习生为研究对象,将其随机分为实验组和对照组,其中实验组采用"金课"理念下的新型教学模式,对照组采用传统授课模式,并在教学结束后对两组学生进行理论及技能考核,对教学效果进行匿名问卷调查,结果显示,实验组学生的理论、技能成绩高于对照组,且教学效果反馈满意度更高.
Malignant bone tumors, one of the most common bone tumors includes osteosarcoma, Ewing's sarcoma, multiple myeloma, and metastatic bone tumors etc. These tumors are often accompanied by distant metastatic lesions at time of diagnosis, leading to low 5-year survival rates. At present, the use of biomarkers for early detection in order to facilitate early treatment are very limited. Therefore, most medical researchers are exploring the roles of exosomes in detecting malignant bone tumors. Exosomes are extracellular microvesicles secreted by different types of cells, which exist in a variety of body fluids. They are new intercellular information carriers that play important physiological roles. Current literature have reported that the RNA contained in exosomes (such as mRNA, miRNAs, lncRNAs and circRNAs) play important roles in the incidence as well as development of malignant bone tumors. However, the previous studies mostly focused on the roles of exosomal RNA in malignant bone tumor diseases, in tumor cell proliferation or apoptosis, transfers, evasion of immune surveillance and chemotherapy drug resistance etc. However, exosomal RNAs may function in the whole process of the disease progression via regulation networks. Our review of existing literature revealed that exosomal RNAs affacted the proliferation, metastasis, immune evasion and drug resistance of five common malignant bone tumors; Osteosarcoma, Ewing sarcoma, Chondrosarcoma, multiple myeloma, and metastatic bone tumors. Therefore, by elucidating on the mechanism of exosomal RNAs in the occurrence and development of malignant bone tumors, this study, could provide new ideas for early diagnosis, concomitant diagnosis, efficacy estimation (chemotherapy, radiotherapy and immunotherapy, etc.) as well as assessing the prognosis of malignant bone tumors.