Abstract Background To investigate the effect and underlying mechanism of umbilical cord blood-mononuclear cells (UCB-MNCs) in treating knee osteoarthritis (KOA) in rabbits. Methods A rabbit KOA model was prepared by anterior cruciate ligament transection (ACLT). Fifty New Zealand white rabbits were randomly divided into the control group, model group, sodium hyaluronate (SH) group, platelet-rich plasma (PRP) group and UCB-MNC group. Knee injections were performed once a week for five consecutive weeks. The gross view of the knee joint, morphology of knee cartilage and structural changes in the knee joint were observed on CT scans, and graded by the Lequesne MG behavioral score and the Mankin score. TNF-α and IL-1β levels in the synovial fluid of the knee were measured by the enzyme-linked immunosorbent assay (ELISA). Expression levels of MMP-13 and COL-II in the knee cartilage were detected by Western blotting and qRT-PCR. Results The Lequesne MG behavioral score and the Mankin score were significantly higher in the model group than those in the control group (P < 0.05). Rabbits in the SH, PRP and UCB-MNC groups had sequentially lower scores than those in the model group. Imaging features of KOA were more pronounced in the model group than in the remaining groups. CB-MNC significantly relieved KOA, compared to SH and PRP. Significantly higher levels of TNF-α and IL-1β in the synovial fluid of the knee, and up-regulated MMP-13 and down-regulated COL-II in the knee cartilage were detected in the model group than in the control group. These changes were significantly reversed by the treatment with SH, PRP and UCB-MNCs, especially UCB-MNCs. Conclusion Injections of UCB-MNCs into knees protect the articular cartilage and hinder the progression of KOA in rabbits by improving the local microenvironment at knee joints.
INTRODUCTION:Serum response factor (SRF) is important in muscle development, tissue repair, and neuronal regulation. OBJECTIVES:This research aims to thoroughly examine the effects of SRF on spinal cord injury (SCI) and its ability to significantly impact the recovery and regeneration of neuronal axons. METHODS:The researchers created rat models of SCI and scratch injury to primary spinal cord neurons to observe the expression of relevant factors after neuronal injury. RESULTS:We found that the SRF, Ras, Raf, and cofilin levels increased after injury and gradually returned to normal levels. Afterward, researchers gave rats with SCI an SRF inhibitor (CCG1423) and studied the effects with nuclear magnetic resonance and transmission electron microscopy. The SRF inhibitor rodents had worse spinal cord recovery and axon regrowth than the control group. And the apoptosis of primary neurons after scratch injury was significantly higher in the SRF inhibitor group. Additionally, the researchers utilized lentiviral transfection to modify the SRF expression in neurons. SRF overexpression increased neuron migration while silencing SRF decreased it. Finally, Western blotting and RT-PCR were conducted to examine the expression changes of related factors upon altering SRF expression. The results revealed SRF overexpression increased Ras, Raf, and cofilin expression. Silencing SRF decreased Ras, Raf, and Cofilin expression. CONCLUSION:Based on our research, the SRF promotes axonal regeneration by activating the "Ras-Raf-Cofilin" signaling pathway.
Circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) mechanism have emerged as critical mechanism in cancer initiation and progression. However, the roles of the circRNA-microRNA (miRNA)-messenger RNA ceRNA network in osteosarcoma are still not fully characterized. In this study, therefore, circ_0078767-related ceRNA mechanism in osteosarcoma was studied. Bioinformatics tools primarily identified differentially expressed circRNAs and their downstream miRNAs in osteosarcoma, implying the potential interaction between circ_0078767, miR-330-3p, and cyclin-dependent kinase 14 (CDK14) in this malignancy, which were further verified by means of RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter gene assays. Aberrant abundance of circ_0078767 was found in both osteosarcoma tissues and cells, relating to dismal prognosis in patients with osteosarcoma. Functionally, circ0078767 strengthened the proliferation, invasiveness, and migration of osteosarcoma cells, which could be neutralized by miR-330-3p. Additionally, miR-330-3p targeted and decreased CDK14 expression whereby motivating the malignant phenotypes of osteosarcoma cells. Through in vivo experiments, we further confirmed that circ_0078767 targeted miR-330-3p to upregulate CDK14, whereby strengthening the in vivo tumorigenic and metastatic ability of osteosarcoma cells. Circ_0078767 promotes the occurrence and development of osteosarcoma by upregulating CDK14 in a miR-330-3p-dependent manner.
全膝关节置换术(total knee arthroplasty,TKA)是一种治疗膝关节晚期严重病变有效率较高的骨科康复手术,虽然TKA对各种类型膝关节晚期严重病变均具有较好的治疗康复效果,但TKA往往因为技术较复杂、手术造成的创伤范围比较广而造成出血量过多的情况.氨甲环酸(tranexamic acid,TXA)是一种人工合成的赖氨酸类似物,是一种纤溶酶和纤溶酶原的竞争性抑制剂,它已被临床研究证明能够通过有效地阻断纤维蛋白的溶解而使其具有止血作用,从而可以有效减少TKA患者在手术期的失血量.但是目前对于TKA的给药方式、剂量、给药频率和安全性缺乏统一意见.所以本文就TXA在TKA中最新应用研究进展做了综述.
目的 评估静脉应用氨甲环酸减少膝关节镜下前交叉韧带重建术后关节失血量的临床效果.方法 选择自2019年至2020年期间在滨州医学院烟台附院接受膝关节镜下前交叉韧带重建手术治疗的80例患者作为研究对象,其中男55例,女25例;年龄19~49岁,平均(31.4±10.7)岁.患者被随机分成氨甲环酸组和对照组,氨甲环酸组的患者于止血带充气前按体重15 mg/kg静滴应用氨甲环酸,术后按体重每小时10 mg/kg持续应用氨甲环酸3h,对照组不使用氨甲环酸.术后24 h评估膝关节引流血量,术后1d、7d、14 d评估膝关节膝关节髌骨周径、膝关节活动度及疼痛视觉模拟评分(visual analogue scale,VAS).结果 与对照组相比,术后24 h氨甲环酸组的膝关节引流血量明显减少(P<0.05);术后7d,氨甲环酸组的VAS、膝关节活动度和髌骨周径更优势(P<0.05);术后14 d,氨甲环酸组的VAS和髌骨周径更优势(P<0.05),膝关节活动度无明显差异(P>0.05).结论 关节镜下前交叉韧带重建术后静脉应用氨甲环酸可以有效减少失血量,减轻术后早期膝关节肿胀及疼痛.
Aims: Sulforaphene (SFE), a naturally occurring isothiocyanate found in cruciferous vegetables, has attracted increasing attention for its anti-cancer effect in many cancers. Main methods: We explored the therapeutic effects of SFE in modulating the progression of osteosarcoma. CCK8 assay, colony formation assay, western blot, wounding healing assay and transwell assay were conducted to detect the proliferation, apoptosis, migration and invasion of osteosarcoma cells (U2OS and Saos2) treated with different concentrations of SFE. In addition, tumor xenograft in nude mice is performed to test the effects of SFE in tumorigenesis in vivo. Moreover, the levels of FSTL1 and NF-kappa B were determined by western blot, and loss of functions of FATL1 and NF-kappa B were further conducted to evaluate the underlying mechanisms of SFE on osteosarcoma development. Key findings: The results revealed that SFE inhibited the growth while promoted apoptosis of U2OS and Saos2 cells in a dose-dependent manner. Mechanistically, SFE significantly inhibited the expression of NF-cB and FSTL1. However, the genetic intervention of FSTL1 or pharmacologically inhibiting NF-kappa B weakened the antitumor role of SFE. Significance: This study suggested that SFE alleviates the progression of osteosarcoma through modulating the FSTL1/NF-kappa B pathway.
Background: Osteosarcoma (OS) is a complex cancer and depends on multiple biological processes and pathways. Therefore, there is an urgent need to identify reliable prognostic biomarkers for predicting clinical outcomes and helping personalize treatment of OS. Results: An expression Quantitative Trait Methylations (eQTMs)-based risk score model was developed to infer the prognostic efficacy for OS based on gene expression and methylation level. Some OS-specific eQTMs were identified and divided to positive and negative eQTMs. We found that some OS-specific eQTMs were significantly associated with survival in OS according to the eQTM-based risk score. The global characteristics for these prognosis-associated eQTMS were depicted and analyzed. These prognosis-associated eQTMS are stable in multiple experiments and showed better performance in predicting survival than single gene expression, age and gender of OS. Functional analysis indicated that the genes in prognosis-associated eQTMS were associated with essential biology processes of cancer development. In addition, these genes were also drug targets for many kinds of drugs and may provide assistance for studying drug repurposing of OS. Conclusion: These results highlight the potential of eQTMs as novel diagnostic, prognostic and therapeutic targets for OS.
Background: Osteosarcoma (OS) patients with surgical resection still relapse with poor prognosis due to the inability to detect distant metastasis. It’s essential to identify metastasis-related biomarkers for OS. Methods: Here, a computational pipeline follow relative expression orderings (REOs) using gene expression was constructed in metastases and non-metastases OS patients. Results: 138 metastasis-associated gene pair signatures (MGPSs) were identified follow two independent datasets. A metastases-specific co-expressed MGPS network was constructed for extracting biomarker for clinical application. MGPS such as MYL5 and RPL27A showed strong positive correlation (Cor =0.75, P <0.001). There were thirteen prognostic MGPSs in above network. These prognostic MGPSs could become as a specific classifier to distinguish metastases and non-metastases OS patients. MGPSs were associated with cancer metastasis-related functions. Drug and MGPS network could provide some drug candidates for treatment of OS. Conclusions: Collectively, the roles of the MGPSs in OS were elucidated, which could be beneficial for understanding OS pathogenesis and treatment.
目的 探讨加长柄人工关节置换术治疗复杂性转子间骨折的临床疗效.方法 选取本院2016年5月~2017年9月行加长柄人工关节置换术治疗的复杂性转子间骨折病例38例进行回顾性分析,观察、记录术后首次下床时间、完全负重时间、术后并发症及住院时间,术前及术后Harris评分评价髋关节功能.结果 所有患者手术顺利,首次下床时间平均为1.5d(1d-2d),平均完全负重时间为3d(2d-5d),平均住院时间10d(7d-14d),髋关节功能Harris术后1年平均(91.43±3.7).结论 加长柄人工关节置换术是治疗复杂性转子间骨折的有效方法,手术效果显著,术后髋关节功能恢复良好.
Wogonoside possesses anti-oxidative, anti-inflammatory, anti-allergy and anti-tumor properties. The aim of the present study was to evaluate whether wogonoside alleviates spinal cord injury (SCI)-induced inflammation via nuclear factor (NF)-κB and nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation. Sprague-Dawley rats were positioned in the jaws of a calibrated aneurysm clip with a closing pressure of 55 g. The jaws were placed on the dorsal and ventral surfaces of the spinal cord and left in place for 1 min. SCI rats were treated with 12, 25 and 50 mg/kg wogonoside. Following this, the locomotor function was assessed using the Basso Beattie Bresnahan scale. The water content of the spinal cord was measured, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 levels were assessed and western blot analysis was performed to evaluate the expressions of NF-κB and NLRP3. Wogonoside was demonstrated to significantly ameliorate the SCI-induced reduction in Basso Beattie Bresnahan score (P<0.01) and significantly reduce the water content of the spinal cord in rats with SCI-induced inflammation (P<0.01). Results also indicated that treatment with wogonoside significantly reduced the levels of IL-1β, TNF-α and IL-6 in rats with SCI-induced inflammation (P<0.01), potentially via the phosphorylation of NF-κB inhibitor α. Furthermore, treatment with wogonoside inhibited the expressions of toll-like receptor 4, NLRP3 and caspase-1 protein in SCI model rats (P<0.01). In conclusion, the results of the present study suggest that wogonoside alleviates SCI-induced inflammation by suppressing NF-κB and NLRP3 inflammasome activation.
Objective To investigate the incidence of osteodystrophy induced by diving decompression in Yantai.Methods One hundred and seventy-one dive fishing personnel,who were hospitalized in our hospital,were selected as our research subjects.Paranasal sinuses,both shoulders,hips and knees had routine X-ray detection for study.Results Of all the patients,166 had a history of different degrees of joint pain and muscle pain.X-rays detection revealed that most divers were suffering from decompressed osteodystrophy.Conclusions With the extension of diving service,the incidence of decompressed osteodystrophy was increased gradually year by year.
Metastasis is the primary cause of mortality in osteosarcoma. Targeting metastasis is a major strategy in osteosarcoma treatment. As a traditional Chinese medicine, Trillium tschonoskii Maxim has been widely used in the therapy of various diseases, including cancer. However, currently there is no evidence regarding the anti-metastasic effect of Paris saponin VII (PS VII), which is extracted from Trillium tschonoskii Maxim, on osteosarcoma cells and its underling mechanisms. The present study aimed to examine the effect of PS VII on the migration and invasion of osteosarcoma cells. Viability and proliferation of osteosarcoma cells were examined by MTT assay. Migration and invasion of osteosarcoma cells was then detected using scratch wound healing assays and Transwell assays, respectively. Additionally, the expression of matrix metalloproteinase (MMP)-2 and -9 was determined at the mRNA and protein level following treatment with PS VII. Mitogen-activated protein kinase (MAPK) expression was also detected by western blot analysis. Finally, an inhibitor of p38 MAPK was used to verify the effect of PS VII on the expression of MMP-2 and -9, as well as the migration and invasion osteosarcoma cells. This demonstrated that the proliferation, migration and invasion of the osteosarcoma cells were suppressed following treatment with PS VII. PS VII downregulated the expression of MMP-2 and -9 in a dose- and time-dependent manner. PS VII also exerted its ability to downregulate the phosphorylation of p38 MAPKs. Furthermore, by using a p38 inhibitor, SB203580, the role of PS VII in MMP-2 and -9 expression and osteosarcoma cell invasion was revealed. Taken together, these results demonstrated that PS VII suppresses the migration and invasion of osteosarcoma cells via the p38 MAPK signaling pathway.
Objective To systematically compare the outcomes of cervical disc arthroplasty with anterior cervical discecto-my and fusion in the treatment of single-level degenerative cervical disc disease. Methods The references concerning cervical disc arthroplasty and anterior cervical discectomy and fusion for the singel-level degenerative cervical disc disease were re-trieved through PubMed,Cochrane Library,Ovid,SpringerLink,the China Biological Medicine Database,Wafang Database and Weipu Database,as well as by manually searching the related journals and literature. The eligible trials were extracted accord-ing to the inclusion and exclusion criteria. The methodological quality of the included trials were evaluated. RevMan5. 1 soft-ware was used for data analysis. Results Eight randomized controlled trials were included in the final Meta-analysis. The re-sults of Meta-analysis showed that statistically difference between these procedures in the SF-36(MD = 0. 98,95% CI:- 0. 33~ - 2. 29,Z = 1. 46,P = 0. 14),complications(OR = 0. 60,95% CI:0. 34 ~ 1. 04,P = 0. 07),reoperation rate(OR = 0. 52, 95% CI:0. 26 ~ 1. 05,Z = 1. 83,P = 0. 07). There were no statistically difference in the neck disability index(MD = - 2. 74, 95% CI:- 4. 57 ~ - 0. 91,Z = 2. 93,P = 0. 003),neck VAS(MD = - 2. 84,95% CI:- 4. 85 ~ - 0. 84,Z = 2. 78,P = 0. 005) and arm pain VAS(MD = - 1. 84,95% CI:- 3. 07 ~ - 0. 61,Z = 2. 92,P = 0. 003). Conclusion In treatment of single-level degenerative cervical disc disease,cervical disc arthroplasty has better outcomes in the improvement of pain symptom and neck function,but no superiority in complications,reoperation rate and SF-36 scores.