The burden of knee osteoarthritis worldwide, regionally, and nationally from 1990 to 2019, along with an analysis of cross-national inequalities.

OBJECTIVE: To describe the disease burden of knee osteoarthritis (KOA) globally, regionally, and in 204 countries by age, sex, and sociodemographic index (SDI) from 1990 to 2019, and to explore cross-national inequalities across SDI. METHODS: The Global Burden of Disease (GBD) 2019 database collected data on KOA worldwide from 1990 to 2019, including prevalence, incidence, years lived with disability (YLDs). The average annual percentage change (AAPC) was used to measure temporal trends. In addition, the inequality slope index and the health concentration index were calculated to quantify the unequal distribution of the burden of KOA across 204 countries worldwide. RESULTS: In 2019, the global age-standardized prevalence rate increased by 7.5% compared with 1990, and the age-standardized incidence rate increased by about 6.2%; The age-standardized YLDs rate increased by about 7.8%. In addition to the Republic of Korea and the United States of America, the disease burden of KOA has increased year by year in other countries around the world. The incidence of KOA was highest at ages 50-59, while the prevalence and rates of YLDs were highest at ages 75-84. The burden of KOA was higher in women than in men. Cross-country inequality suggests that the inequality in the burden of KOA between high SDI and low SDI countries becomes greater, and that countries with high SDI bear a disproportionately high burden. CONCLUSION: The global KOA burden has risen steadily between 1990 and 2019, and cross-national inequality gaps remain large. Targeted measures must therefore be taken to address this inequality and the increasing global KOA disease burden.

Hinged External Fixation Combined with Open Debridement for Post-traumatic Elbow Stiffness: A Systematic Review and Meta-analysis.

Background: Open debridement remains the gold standard for the clinical treatment of post-traumatic elbow stiffness. However, postoperative complications, such as re-contraction and heterotopic ossification of the elbow joint, are highly prevalent. Hinged external fixation appears to offer the potential for greater improvement of joint function and reduction of complications. The purpose of this article is to provide the latest evidence on the effectiveness and safety of hinged external fixation combined with open debridement for the treatment of post-traumatic elbow stiffness. Methods: We searched for randomized controlled trials (RCTs) from the China National Knowledge Infrastructure, MEDLINE, PubMed, Web of Science, EMBASE, and Cochrane Library databases until December 31, 2022. STATA 15.1 software was used to analyze all the data for this article. The quality of the included articles was evaluated using the Cochrane Reviewer's Handbook 5.3. Results: Finally, we selected 8 high-quality RCTs for our meta-analysis, which included 555 patients. The meta-analysis demonstrated that hinged external fixation combined with open debridement for post-traumatic elbow stiffness (treatment group) showed a significant increase in elbow flexion and extension mobility (WMD = 5.16, 95% CI 4.39-5.49, Z = 13.02, P = 0.000), Mayo elbow function scores (WMD = 5.25, 95% CI 4.33-6.17, Z = 11.15, P = 0.000), and Mayo excellent rate (RR = 1.25, 95% CI 1.14-1.37, Z = 4.87, P = 0.000). Additionally, there was a significant decrease in the complication rate (RR = 1.11, 95% CI 1.02-1.20, Z = 2.54, P = 0.011) compared to open debridement alone (control group). Furthermore, the results of the publication bias test showed no significant bias. Conclusions: With the assistance of hinged external fixation, open debridement for post-traumatic elbow stiffness can lead to increased elbow mobility and a reduced complication rate. However, due to the small sample size, a multicenter randomized controlled trial with a larger sample size is still necessary to further confirm the effectiveness and safety of hinged external fixation combined with open debridement for post-traumatic elbow stiffness. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-023-01087-y.

Integrated transcriptomic analysis systematically reveals the heterogeneity and molecular characterization of cancer-associated fibroblasts in osteosarcoma.

BACKGROUND: Osteosarcoma (OS), with a peak incidence during the adolescent growth spurt, is correlated with poor prognosis for its high malignancy. The tumor microenvironment (TME) is highly complicated, with frequent interactions between tumor and stromal cells. The cancer-associated fibroblasts (CAFs) in the TME have been considered to actively involve in the progression, metastasis, and drug resistance of OS. This study aimed to characterize cellular heterogeneity and molecular characterization in CAFs subtypes and explore the potential targeting therapeutic strategies to improve the prognosis of OS patients. METHODS: The single-cell atlas of human OS tumor lesions were constructed from the GEO database. Then significant marker genes and potential biological functions for each CAFs subtype were identified and explored using the Seurat R package. Next, by performing the survival analyses and constructing the risk scores for CAFs subtypes, we aimed to identify and characterize the prognostic values of specific marker genes and different CAFs subtypes. Furthermore, we explored the therapeutic targets and innovative drugs targeting different CAFs subtypes based on the GDSC database. Finally, prognoses related CAFs subtypes were further validated through immunohistochemistry (IHC) on clinical OS specimens. RESULTS: Overall, nine main cell clusters and five subtypes of CAFs were identified. The differentially expressed marker genes for each CAFs clusters were then identified. Moreover, through Gene Ontology (GO) enrichment analysis, we defined the CAFs_2 (upregulated CXCL14 and C3), which was closely related to leukocyte migration and chemotaxis, as inflammatory CAFs (iCAFs). Likewise, we defined the CAFs_4 (upregulated CD74, HLA-DRA and HLA-DRB1), which was closely related to antigen process and presentation, as antigen-presenting CAFs (apCAFs). Furthermore, Kaplan-Meier analyses showed that CAFs_2 and CAFs_4 were correlated with poor clinical prognosis of OS patients. Meanwhile, therapeutic drugs targeting CAFs_2 and CAFs_4, such as 17-AAG/Docetaxel/Bleomycin and PHA-793887/NG-25/KIN001-102, were also explored, respectively. Finally, IHC assay confirmed the abundant CAFs_2 and CAFs_4 subtypes infiltration in the OS microenvironment compared with adjacent tissues. CONCLUSION: Our study revealed the diversity, complexity, and heterogeneity of CAFs in OS, and complemented the single-cell atlas in OS TME.

Combination of IDO inhibitors and platinum(IV) prodrugs reverses low immune responses to enhance cancer chemotherapy and immunotherapy for osteosarcoma.

In recent years, immune checkpoint blockades (ICBs) have made great progress in the treatment of cancer. However, most ICBs have not yet been observed to be satisfactory in the treatment of osteosarcoma. Herein, we designed composite nanoparticles (NP-Pt-IDOi) from a reactive oxygen species (ROS) sensitive amphiphilic polymer (PHPM) with thiol-ketal bonds in the main chain to encapsulate a Pt(IV) prodrug (Pt(IV)-C12) and an indoleamine-(2/3)-dioxygenase (IDO) inhibitor (IDOi, NLG919). Once NP-Pt-IDOi enter the cancer cells, the polymeric nanoparticles could dissociate due to the intracellular ROS, and release Pt(IV)-C12 and NLG919. Pt(IV)-C12 induces DNA damage and activates the cGAS-STING pathway, increasing infiltration of CD8+ T cells in the tumor microenvironment. In addition, NLG919 inhibits tryptophan metabolism and enhances CD8+ T cell activity, ultimately activating anti-tumor immunity and enhancing the anti-tumor effects of platinum-based drugs. NP-Pt-IDOi were shown to have superior anti-cancer activity in vitro and in vivo in mouse models of osteosarcoma, providing a new clinical paradigm for combining chemotherapy with immunotherapy for osteosarcoma.

Sulfatinib, a novel multi-targeted tyrosine kinase inhibitor of FGFR1, CSF1R, and VEGFR1-3, suppresses osteosarcoma proliferation and invasion via dual role in tumor cells and tumor microenvironment.

Introduction: Tumor progression is driven by intrinsic malignant behaviors caused by gene mutation or epigenetic modulation, as well as crosstalk with the components in the tumor microenvironment (TME). Considering the current understanding of the tumor microenvironment, targeting the immunomodulatory stromal cells such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) could provide a potential therapeutic strategy. Here, we investigated the effect of sulfatinib, a multi-targeted tyrosine kinase inhibitor (TKI) of FGFR1, CSF1R, and VEGFR1-3, on the treatment of osteosarcoma (OS). Methods: In vitro, the antitumor effect was tested by clony formation assay and apoptosis assay.The inhibition of tumor migration and invasion was detected by Transwell assay, and the de-polarization of macrophage was detected by flow cytometry.In vivo, subcutaneous and orthotopic tumor models were established to verify antitumor effect, and the underlying mechanism was verified by immunohistochemistry(IHC), immunofluorescence(IF) and flow cytometry. Results: Sulfatinib suppressed OS cell migration and invasion by inhibiting epithelial-mesenchymal transition (EMT) by blocking the secretion of basic fibroblast growth factor (bFGF) in an autocrine manner. In addition, it regulated immune TME via inhibition of the migration of skeletal stem cells (SSCs) to the TME and the differentiation from SSCs to CAFs. Moreover, sulfatinib can suppress OS by modulation of the TME by inhibiting M2 polarization of macrophages. Systemic treatment of sulfatinib can reduce immunosuppression cells M2-TAMs, Tregs, and myeloid-derived suppressor cells (MDSCs) and increase cytotoxic T-cell infiltration in tumors, the lungs, and the spleens. Discussion: Our preclinical experiments have shown that sulfatinib can inhibit the proliferation, migration, and invasion of OS by playing a dual role on tumor cells and the tumor microenvironment simultaneously and systematically reverse immunosuppression to immune activation status, which could be translated into clinical trials.

[Application of TightRope system combined with Locking-Loop biplane anatomical reconstruction technique for acute acromioclavicular joint dislocation].

Objective: To investigate the effectiveness of TightRope system combined with Locking-Loop biplane anatomical reconstruction technique in the treatment of acute acromioclavicular joint dislocation. Methods: A clinical data of 28 patients with acute acromioclavicular joint dislocation who met the selection criteria and admitted between June 2018 and December 2021 was retrospectively analyzed. There were 18 males and 10 females, with an average age of 47.7 years (range, 22-72 years). The causes of injury included falling (13 cases) and traffic accidents (15 cases). The acromioclavicular joint dislocation was rated as Rockwood type Ⅲ in 7 cases, type Ⅳ in 16 cases, and type Ⅴ in 5 cases. The time from injury to operation was 4-13 days, with an average of 9.5 days. The acromioclavicular joint dislocation was reconstructed with TightRope system and high-strength wire by Locking-Loop methods during operation. The operation time and complications were recorded. Visual analogue scale (VAS) score, Constant-Murley score, and active range of motion of shoulder (forward flexion and upward lift, abduction and upward lift, and external rotation) were recorded before operation and at 12 months after operation to evaluate the functional recovery of shoulder. The loss of acromioclavicular joint reduction was assessed by comparing the coracoclavicular distance (CCD) based on the anteroposterior X-ray films at 3 days and 12 months after operation. Results: The operation time was 58-100 minutes (median, 85 minutes). All incisions healed by first intention. All patients were followed up 12 months. During follow-up, 2 patients developed shoulder adhesion, which recovered after rehabilitation exercise. At 12 months after operation, the VAS score was significantly lower, the Constant-Murley score was significantly higher, and the range of motion of the shoulder joint (forward flexion and upward lift, abduction and upward lift, and external rotation) significantly increased when compared with preoperative ones ( P<0.05). X-ray films showed that the CCD was 8.4 (7.3, 9.4) and 9.2 (8.1, 10.1) mm at 3 days and 12 months after operation, respectively, with a significant difference ( Z=-4.665, P<0.001). During follow-up, there was no complication such as infection, titanium plate entrapment, fracture, internal fixation failure, or redislocation. Conclusion: The treatment of acute acromioclavicular joint dislocation with TightRope system combined with Locking-Loop biplane anatomical reconstruction has the advantages of small incision, joint reduction under direct vision, high fixation strength, and low incidence of postoperative complications, which can effectively relieve the pain of patients' shoulder joint and facilitate the recovery of shoulder joint function.

[Effectiveness analysis of resection and reconstruction of primary bone tumor in pelvic zone â ¡].

Objective: To investigate the effectiveness of complete resection of bone tumor in pelvic zone Ⅱ and reconstruction with allogeneic pelvis, modular prosthesis, and three-dimensional (3D) printing prosthesis. Methods: The clinical data of 13 patients with primary bone tumor in pelvic zone Ⅱ who underwent tumor resection and acetabular reconstruction between March 2011 and March 2022 were retrospectively analyzed. There were 4 males and 9 females with an average age of 39.0 years ranging from 16 to 59 years. There were 4 cases of giant cell tumor, 5 cases of chondrosarcoma, 2 cases of osteosarcoma, and 2 cases of Ewing sarcoma. The Enneking classification of pelvic tumors showed that 4 cases involved zone Ⅱ, 4 cases involved zone Ⅰ and zone Ⅱ, and 5 cases involved zone Ⅱ and zone Ⅲ. The disease duration ranged from 1 to 24 months, with an average of 9.5 months. The patients were followed up to observe the recurrence and metastasis of the tumor, and the imaging examination was performed to observe the status of implant in place, fracture, bone resorption, bone nonunion, and so on. The improvement of hip pain was evaluated by visual analogue scale (VAS) score before operation and at 1 week after operation, and the recovery of hip function was evaluated according to the Musculoskeletal Tumor Society (MSTS) scoring system after operation. Results: The operation time was 4-7 hours, with an average of 4.6 hours; the intraoperative blood loss ranged from 800 to 1 600 mL, with an average of 1 200.0 mL. There was no reoperation or death after operation. All patients were followed up 9-60 months (mean, 33.5 months). No tumor metastasis was found in 4 patients receiving chemotherapy during follow-up. Postoperative wound infection occurred in 1 case, and prosthesis dislocation occurred in 1 case at 1 month after prosthesis replacement. One case of giant cell tumor recurred at 12 months after operation, and the puncture biopsy showed malignant transformation of giant cell tumor, and hemipelvic amputation was performed. The postoperative hip pain significantly relieved, and the VAS score was 6.1±0.9 at 1 week after operation, which was significantly different from the preoperative score (8.2±1.3) ( t=9.699, P<0.001). At 12 months after operation, the MSTS score was 23.0±2.1, including 22.8±2.1 for patients with allogenic pelvis reconstruction and 23.3±2.3 for patients with prosthsis reconstruction. There was no significant difference in the MSTS score between the two reconstruction methods ( t=0.450, P=0.516). At last follow-up, 5 patients could walk with cane assistance and 7 patients could walk without cane assistance. Conclusion: The resection and reconstruction of primary bone tumor in pelvic zone Ⅱ can obtain satisfactory hip function, and the interface of allogeneic pelvis and 3D printing prosthesis have better bone ingrowth, which is more in line with the requirements of biomechanics and biological reconstruction. However, pelvis reconstruction is difficult, the patient's condition should be evaluated comprehensively before operation, and the long-term effectiveness needs further follow-up.

Neoadjuvant Chemotherapy and Expandable Prosthesis Reconstruction to Treat Osteosarcoma around the Knee in Children.

OBJECTIVE: Survival and reconstruction in osteosarcoma is quite challenging. The study aimed to investigate the prognosis in patients treated with neoadjuvant chemotherapy and determine the clinical outcomes of expandable endoprosthesis reconstruction in children. METHODS: From January 2009 to December 2014, we retrospectively analyzed 29 skeletally immature children (mean age, 10.5 years; range, 6-15 years) with osteosarcoma around the knee. Of the 29 patients who underwent neoadjuvant chemotherapy and limb salvage surgery, an expandable prosthesis was implanted for reconstruction. No patients were missed during follow-up. The evaluation index involved follow-up time, complication, functional results, and lengthening procedures. The survivorship and recurrence were assessed by GraphPad Software, and the function was evaluated by the Musculoskeletal Tumor Society (MSTS) scoring system. RESULTS: A mean follow-up time was 8.9 years (range, 6-12 years), and the overall 5-year survival was 89.1% based on Kaplan-Meier analysis. Three patients suffered a relapse and one underwent amputation. Lung metastasis developed in one patient. At 6 months after the operation, patients had a mean MSTS score of 27 points (range, 24-29). Two patients underwent revision surgery, one for implant infection and one for aseptic loosening. Prognosis is correlated with alkaline phosphatase change after treatment. CONCLUSIONS: Chemotherapy scheme and limb salvage can achieve high survival rates. This expandable prosthesis was associated with good function and low complication rates. The character of expandability could be a method to overcome discrepancies in the growth period.

[Effectiveness of arthroscopic long head of biceps tendon transposition combined with Swivelock anchor double fixation for massive and irreparable rotator cuff tears].

Objective: To investigate the effectiveness of arthroscopic long head of biceps tendon (LHBT) transposition combined with Swivelock anchor double fixation in treatment of massive and irreparable rotator cuff tears. Methods: Between June 2019 and November 2021, 25 patients with massive and irreparable rotator cuff tears were treated by arthroscopic LHBT transposition combined with Swivelock anchor double fixation. There were 12 males and 13 females. The age ranged from 47 to 74 years (mean, 62.4 years). The disease duration ranged from 1 to 62 months (median, 7 months). The rotator cuff tears were classified as Hamada grade 2 in 25 cases and Goutallier grade 1 in 2 cases, grade 2 in 22 cases, and grade 3 in 1 case. Pre- and post-operative shoulder range of motion (ROM), visual analogue scale (VAS) score, University of California Los Angeles (UCLA) score, and Constant-Murley score were recorded. Postoperative complications were observed. The reconstructed tissue integrity was confirmed by MRI. Results: All operations were successfully completed. The operation time was 120-330 minutes (mean, 189.6 minutes). All incisions healed by first intention. All patients were followed up 10-36 months (mean, 22.0 months). At last follow-up, the ROM in forward flexion, abduction, and external rotation, VAS score, UCLA score, and Constant-Murley score were superior to those before operation, and the differences were significant ( P<0.05). According to UCLA scoring standard, shoulder joint function was rated as excellent in 5 cases, good in 18 cases, and poor in 2 cases, with an excellent and good rate of 92.0%. No other complications occurred except shoulder joint adhesion in 2 cases. At last follow-up, MRI examination showed no retear of rotator cuff, and LHBT was intact. Conclusion: For massive and irreparable rotator cuff tears, arthroscopic LHBT transposition combined with Swivelock anchor double fixation can increase the force of pressing the humeral head, effectively relieve the pain, improve the ROM of joints, maximize the recovery of shoulder function, and do not increase the number of anchor nails.

Screening and Analysis of Biomarkers in the miRNA-mRNA Regulatory Network of Osteosarcoma.

Osteosarcoma is a malignant disease, and few effective strategies can completely overcome the prognosis of these patients. This study attempted to reveal the key factors and related molecular mechanisms of osteosarcoma via excavating public microarray datasets. The data were obtained from the Gene Expression Omnibus (GEO) database; the differentially expressed miRNAs and differentially expressed genes were obtained in GSE69470 and GSE12685l, respectively; the target of miRNAs were predicted with the miRDIP database; the functions of the factors were analyzed and visualized by the David database and R language, respectively. Moreover, the protein-protein interaction network and miRNA-mRNA network were performed with the STRING database and Cytoscape software to identify the hub nodes in GSE69470 and GSE12685. The results showed that 834 DEGs were found in GSE12685 and 37 miRNAs were found in GSE69470. Moreover, the target of 37 miRNAs were enriched in PI3K/AKT, P53, Wnt/ß-catenin, and TGF-ß pathways and related with skeletal system development and cell growth. Besides, the miRNAs including miR-22-3p, miR-154-5p, miR-34a-5p, miR-485-3p, miR-93-5p, and miR-9-5p and the genes including LEF1, RUNX2, CSF1R, CDKN1A, and FBN1 were identified as the hub nodes via network analysis. In conclusion, this study suggested that the miRNAs including miR-22-3p, miR-154-5p, miR-34a-5p, miR-485-3p, miR-93-5p, and miR-9-5p and the genes including LEF1, RUNX2, CSF1R, CDKN1A, and FBN1 act as key factors in the progression of osteosarcoma.

[Effectiveness analysis of computer-aided technology in the treatment of primary elbow osteoarthritis combined with stiffness under arthroscopy].

Objective: To explore the effectiveness of computer-aided technology in the treatment of primary elbow osteoarthritis combined with stiffness under arthroscopy. Methods: The clinical data of 32 patients with primary elbow osteoarthritis combined with stiffness between June 2018 and December 2020 were retrospectively analyzed. There were 22 males and 10 females with an average age of 53.4 years (range, 31-71 years). X-ray film and three-dimensional CT examinations showed osteophytes of varying degrees in the elbow joint. Loose bodies existed in 16 cases, and there were 7 cases combined with ulnar nerve entrapment syndrome. The median symptom duration was 2.5 years (range, 3 months to 22.5 years). The location of bone impingement from 0° extension to 140° flexion of the elbow joint was simulated by computer-aided technology before operation and a three-dimensional printed model was used to visualize the amount and scope of impinging osteophytes removal from the anterior and posterior elbow joint to accurately guide the operation. Meanwhile, the effect of elbow joint release and impinging osteophytes removal was examined visually under arthroscopy. The visual analogue scale (VAS) score, Mayo elbow performance score (MEPS), and elbow range of motion (extension, flexion, extension and flexion) were compared between before and after operation to evaluate elbow function. Results: The mean operation time was 108 minutes (range, 50-160 minutes). All 32 patients were followed up 9-18 months with an average of 12.5 months. There was no other complication such as infection, nervous system injury, joint cavity effusion, and heterotopic ossification, except 2 cases with postoperative joint contracture at 3 weeks after operation due to the failure to persist in regular functional exercises. Loose bodies of elbow and impinging osteophytes were removed completely for all patients, and functional recovery was satisfactory. At last follow-up, VAS score, MEPS score, extension, flexion, flexion and extension range of motion significantly improved when compared with preoperative ones ( P<0.05). Conclusion: Arthroscopic treatment of primary elbow osteoarthritis combined with stiffness using computer-aided technology can significantly reduce pain, achieve satisfactory functional recovery and reliable effectiveness.

hsa_circ_0000006 induces tumorigenesis through miR-361-3p targeting immunoglobulin-like domains protein 1 (LRIG1) in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is considered to be the most highly prevalent bone tumor. In the progression of different human cancers, the role of circular RNAs (circRNAs) has been extensively studied. Microarray analysis has indicated that hsa_circ_0000006 expression was lower in OS, but the mechanism of hsa_circ_0000006 in regulating the progression of OS remains elusive. METHODS: The expression of cancer-related genes at the transcriptional and translational levels was assessed by RT-qPCR and western blotting (WB). Colony formation and Cell Counting Kit-8 (CCK-8) assays were used to evaluate the proliferative potential of cells. The transwell assay was used to examine the invasive and migratory potential of cells. Furthermore, dual-luciferase reporter (DLR) and RNA pull-down assays were performed for the validation of the targeting sites of hsa_circ_0000006, miR-361-3p, and the 3'-untranslated region (3'-UTR) of immunoglobulin-like domains protein 1 (LRIG1) mRNA. Moreover, the protein levels of epithelial-to-mesenchymal transition (EMT) markers were analyzed by WB. RESULTS: The expression of hsa_circ_0000006 and LRIG1 were found to be down-regulated in OS tissues and cells, while miR-361-3p was up-regulated. Knockdown of hsa_circ_0000006 promoted the progression and development of OS, as well as EMT. Furthermore, hsa_circ_0000006 was revealed as a sponge of miR-361-3p, which negatively regulates miR-361-3p expression. LRIG1 was found to be an miR-361-3p target. In OS cells, the LRIG1 expression level was decreased, with elevated expression of miR-361-3p. Advanced studies demonstrated that hsa_circ_0000006 regulates LRIG1 expression through sponging miR-361-3p, then promotes the tumorigenesis of OS. CONCLUSIONS: hsa_circ_0000006 is associated with the progression and development of OS through miR-361-3p by target LRIG1, which is a significant biomarker and effective therapeutic target for patients with OS.

Apatinib inhibits cell proliferation and migration of osteosarcoma via activating LINC00261/miR-620/PTEN axis.

Apatinib has been recently identified as a potential treatment option for osteosarcoma (OS). Nonetheless, the molecular mechanism of Apatinib in regulating OS progression remains unclear. To explore the downstream molecules that mediated the tumor-suppressive effect of Apatinib on OS. Expression levels of genes were detected by RT-qPCR and western blot assays. Functional assays including Transwell assay were applied to detect the proliferation, apoptosis and migration of OS cells. Molecular interactions were detected by luciferase reporter assay and RIP assay. Apatinib inhibited the proliferation and migration of OS cells. LINC00261 was down-regulated in OS cells but then up-regulated after the treatment by Apatinib. Silencing LINC00261 abrogated the suppressive effect of Apatinib on OS cell proliferation and migration. MicroRNA-620 (miR-620) could be sponged by LINC00261. Besides, miR-620 was up-regulated in OS cells and Apatinib treatment reduced miR-620 expression. Furthermore, LINC00261 acted as a competitive endogenous RNA (ceRNA) by sequestering miR-620 to up-regulate the expression of phosphatase and tensin homolog (PTEN). Moreover, Apatinib hindered in vitro cell proliferation and migration as well as the in vivo tumorigenesis of OS through LINC00261/miR-620/PTEN axis. Apatinib-enhanced LINC00261 restrained OS via miR-620/PTEN axis, indicating LINC00261 might promote the efficacy of Apatinib on OS.

LncRNA BCRT1 facilitates osteosarcoma progression via regulating miR-1303/FGF7 axis.

Growing studies noted that lncRNA was closely related with the initiation and progression of tumors. However, the role of BCRT1 in the progression of osteosarcoma remains unknown. We noted that BCRT1 is significantly upregulated in osteosarcoma specimens and cells. Elevated expression of BCRT1 promotes cell growth and cell cycle in osteosarcoma cell. Moreover, BCRT1 induces EMT and secretion of inflammatory mediators in osteosarcoma cell. We illustrated that elevated expression of BCRT1 decreases miR-1303 expression in MG-63 cell. The expression of miR-1303 is lower in osteosarcoma specimens than in non-tumor specimens. There is an inverse interrelation between miR-1303 levels and BCRT1 levels in osteosarcoma specimens. Furthermore, we identified FGF7 is one direct target gene of miR-1303 in osteosarcoma cell. Ectopic expression of miR-1303 suppresses FGF7 expression and elevated expression of BCRT1 enhanced FGF7 expression in MG-63 cell. Finally, we illustrated that BCRT1 induces osteosarcoma cell cycle and proliferation and promotes EMT progression and inflammatory mediators secretion via modulating FGF7 expression. Our study suggested that BCRT1 acts as one oncogene in osteosarcoma progression.

[Evaluation of total scapular arthroplasty after total scapulectomy for scapular tumors].

OBJECTIVE: To evaluate the effectiveness of total scapular arthroplasty after total scapulectomy for scapular tumors. METHODS: A clinical data of 17 patients with scapular tumors treated with total scapulectomy and total scapular arthroplasty between January 2010 and December 2017 were retrospectively reviewed. There were 9 males and 8 females with an average age of 34.4 years (range, 13-64 years). Seven patients were diagnosed with chondrosarcoma, 3 with osteosarcoma, 2 with Ewing's sarcoma, 1 with high-grade sarcoma, 1 with polymorphic dedifferentiated sarcoma, 1 with fibrosarcoma, 1 with plasmacytoma, and 1 with bone giant cell tumor. According to the surgical staging system described by Enneking et al, 1 patient was rated as stage 3, 8 as stageⅠB, 8 as stageⅡB. According to the classifications of shoulder girdle resections of Malawer et al, 11 patients were type ⅢB, 5 were type ⅣB, 1 was type ⅥB. The disease duration ranged from 0.5 to 8.0 months (mean, 3.2 months) and tumor size ranged from 11.0 cm×7.5 cm×6.0 cm to 18.5 cm×18.0 cm×12.5 cm. The 1993 Musculoskeletal Tumor Society (MSTS) upper limb function scoring system and shoulder mobility were used to evaluate postoperative shoulder joint function. Tumor recurrence and metastases were monitored by radiograph. RESULTS: Poor superficial incision healing occurred in 1 patient, the rest incisions achieved healing by first intention. All patients were followed up 20-72 months (mean, 45.4 months). Two of the 17 patients died of multiple organ dysfunction syndrome caused by tumor metastases; 3 patients suffered from pulmonary metastases and were alive with disease. No local recurrence occurred in all patients. The overall survival rate was 88.2% (15/17) and the disease-free survival rate was 70.6% (12/17). Rib fracture after trauma, aseptic loosening, and atrophy of the deltoid muscle occurred in 1, 1, and 1 case, respectively. The other related complication was not observed. At last follow-up, the MSTS score was 26.1±1.4, and the flexion, extension, and abduction range of motion of shoulder joint were (70.0±7.5), (31.2±11.3), and (54.4 ±12.5) °, respectively. CONCLUSION: Reconstruction with total scapular arthroplasty after total scapulectomy can obtain a satisfactory shoulder contour and an acceptable functional outcomes in patients with scapular tumors.

Correlation of p16 and nm23-H1 expression levels with incidence and prognosis of soft tissue sarcoma.

The expression levels of p16 and nm23-H1 genes in soft tissue sarcoma (STS) were evaluated to investigate correlation of the expression levels with the incidence and prognosis of STS. Tumor tissues and para-carcinoma normal tissues were collected from 64 STS patients. The messenger ribonucleic acid (mRNA) expression levels of p16 and nm23-H1 in the tissues were detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and the protein expression levels of p16 and nm23-H1 in tissues were detected using immunohistochemistry. Spearman's correlation analysis was used for the correlation between expression levels of p16 and nm23-H1 in STS tissues and the correlation between p16 and nm23-H1 mRNA and protein expression. Moreover, the correlation of p16 and nm23-H1 expression levels in tumor tissues with pathological parameters and prognosis of STS patients were analyzed combined with clinical data. Results of RT-qPCR showed that mRNA expression levels of p16 and nm23-H1 in tumor tissues of STS patients were significantly lower than those in para-carcinoma normal tissues (P<0.01). Results of immunohistochemistry showed that the positive expression rates of p16 and nm23-H1 in tumor tissues of STS patients (43.75 and 39.06% respectively) were significantly lower than those in para-carcinoma normal tissues (85.93 and 89.06% respectively). The expression of p16 and nm23-H1 mRNA was positively correlated with protein expression levels. There was a positive correlation between the expression levels of p16 and nm23-H1 in tumor tissues of STS patients. The negative expression of p16 in tumor tissues of STS patients correlated with tumor size, tumor metastasis and clinical staging, and the negative expression of nm23-H1 correlated with tumor metastasis and clinical staging. The overall 5-year survival rate of patients was 54.68%, and the prognosis of patients with positive expression levels of p16 and nm23-H1 was better. Univariate survival analyses revealed that p16 and nm23-H1 were influencing factors of the overall survival rate of STS patients. p16 and nm23-H1 expression in STS is low, and their expression levels are closely related to the pathological parameters and prognosis of STS patients, so they can serve as reference indexes for prognosis estimation of STS.

Bone transport using the Ilizarov method for osteosarcoma patients with tumor resection and neoadjuvant chemotherapy.

BACKGROUND: Studies on the applications of bone transport using the Ilizarov method for osteosarcoma (OS) patients with surgical resection and neoadjuvant chemotherapy are rare. METHODS: A retrospective analysis was conducted in 10 patients with limb OS receiving limb-salvage treatment by Ilizarov method from 2007 to 2012 in our hospital. The general information, treatment outcomes and follow-up data of the patients were collected. RESULTS: The mean length of the transported fragment and the mean transport distance of the affected limb were both 14 cm. The mean time in the external fixator was 34.2 ±â€¯11.2 months (16-47 months) and the mean external fixation index (EFI) was 75 days/cm. The mean follow-up time was 68.6 ±â€¯26.6 months (37-103 months). Seven patients underwent additional operations to treat the postoperative complications, and the mean number of operation was 1.7 times. Only one patient underwent amputation due to tumor relapse and all patients survived without tumor. The limb-salvage rate was 90%. At the time of external fixator removal, the ASAMI-bone score was good in 66.7% of patients and the ASAMI-function score was fair in 66.7% of cases. The mean MSTS score was 18.6 ±â€¯3.2 (n = 9). At 10 months after fixator removal, both the ASAMI-bone score and ASAMI-function score were both excellent in 80% and good in 20% cases, and the mean MSTS score was further improved to 27.2 ±â€¯1.11 (n = 5). CONCLUSION: Bone transport using the Ilizarov method can achieve good therapeutic effectiveness in the limb-salvage treatment for OS patients with neoadjuvant chemotherapy as long as the complications can be timely recognized and well managed.

The multidisciplinary treatment of osteosarcoma of the proximal tibia: a retrospective study.

BACKGROUND: Survival and reconstruction constitute important challenges in multimodal treatment of osteosarcoma of the proximal tibia. The purpose of this study was to assess the efficacy and prognosis of neoadjuvant chemotherapy and custom-designed endoprosthetic arthroplasty. METHODS: A total of 69 patients with osteosarcoma of the proximal tibia were evaluated, including 43 males and 26 females, treated with multidisciplinary limb-salvage remedy from October 2003 to December 2013. They were at least 12 years old (mean, 20 years; range, 12-57 years). The gap between tumor and main artery/nerve was showed in MRI. Mean follow up was 69.5 months (range, 9-144 months). Kaplan-Meier survival curves were generated to assess prognosis and relapse rate. The initial symptoms and disease duration for each patient were recorded. Correlation analyses were performed for the association of various parameters with prognosis. Functional outcomes were evaluated using the Musculoskeletal Tumor Society (MSTS) guidelines after 6 months postoperatively, to analyze the relation between bone excision size and function recovery. RESULTS: The resection lengths measured intraoperatively ranged from 80 to 230 mm, and contained 3 cm of normal bone around the tumor. A total of 3 courses of preoperative chemotherapy were administered to all cases. At final follow-up, 1 case showed recurrence. Meanwhile, 8 patients (11.6%) died from lung metastasis. Post-operative infection occurred in 3 patients; 1 case was maintained with revision surgery. Two cases underwent amputation. The mean MSTS system score was 21.6. CONCLUSIONS: The multidisciplinary treatment result in an overall positive outcome, with improved function.

miR-223-3p Inhibits Human Osteosarcoma Metastasis and Progression by Directly Targeting CDH6.

Cadherin-6 (CDH6) is aberrantly expressed in cancer and closely associated with tumor progression. However, the functions of CDH6 in human osteosarcoma and the molecular mechanisms underlying CDH6 in osteosarcoma oncogenesis remain poorly understood. In this work, we assessed the role of CDH6 in human osteosarcoma and identified that the expression of CDH6 was closely related with the overall survival and poor prognosis of osteosarcoma patients. MicroRNAs (miRNAs) have been implicated as important epigenetic regulators during the progression of osteosarcoma. Using dual-luciferase reporter assays, we showed that miR-223-3p suppresses CDH6 expression by directly binding to the 3' UTR of CDH6. miR-223-3p overexpression significantly inhibited cell invasion, migration, growth, and proliferation by suppressing the CDH6 expression in vivo and in vitro. Besides, CDH6 overexpression in the miR-223-3p-transfected osteosarcoma cells effectively rescued the inhibition of cell invasion, migration, growth, and proliferation mediated by miR-223-3p. Additionally, Kaplan-Meier analysis suggests that the expression of miR-223-3p predicts favorable clinical outcomes for osteosarcoma patients. Moreover, the expression of miR-223-3p was downregulated in osteosarcoma patients and was negatively associated with the expression of CDH6. Collectively, these data highlight that miR-223-3p/CDH6 axis is an important novel pleiotropic regulator and could early predict the metastatic potential in human osteosarcoma treatments.

miR-216a inhibits osteosarcoma cell proliferation, invasion and metastasis by targeting CDK14.

Osteosarcoma (OS) has emerged as the most common primary musculoskeletal malignant tumour affecting children and young adults. Cyclin-dependent kinases (CDKs) are closely associated with gene regulation in tumour biology. Accumulating evidence indicates that the aberrant function of CDK14 is involved in a broad spectrum of diseases and is associated with clinical outcomes. MicroRNAs (miRNAs) are crucial epigenetic regulators in the development of OS. However, the essential role of CDK14 and the molecular mechanisms by which miRNAs regulate CDK14 in the oncogenesis and progression of OS have not been fully elucidated. Here we found that CDK14 expression was closely associated with poor prognosis and overall survival of OS patients. Using dual-luciferase reporter assays, we also found that miR-216a inhibits CDK14 expression by binding to the 3'-untranslated region of CDK14. Overexpression of miR-216a significantly suppressed cell proliferation, migration and invasion in vivo and in vitro by inhibiting CDK14 production. Overexpression of CDK14 in the miR-216a-transfected OS cells effectively rescued the suppression of cell proliferation, migration and invasion caused by miR-216a. In addition, Kaplan-Meier analysis indicated that miR-216a expression predicted favourable clinical outcomes for OS patients. Moreover, miR-216a expression was downregulated in OS patients and was negatively associated with CDK14 expression. Overall, these data highlight the role of the miR-216a/CDK14 axis as a novel pleiotropic modulator and demonstrate the associated molecular mechanisms, thus suggesting the intriguing possibility that miR-216a activation and CDK14 inhibition may be novel and attractive therapeutic strategies for treating OS patients.