[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.

Expert consensus on the bone repair strategy for osteoporotic fractures in China.

Osteoporotic fractures, also known as fragility fractures, are prevalent in the elderly and bring tremendous social burdens. Poor bone quality, weak repair capacity, instability, and high failure rate of internal fixation are main characteristics of osteoporotic fractures. Osteoporotic bone defects are common and need to be repaired by appropriate materials. Proximal humerus, distal radius, tibia plateau, calcaneus, and spine are common osteoporotic fractures with bone defect. Here, the consensus from the Osteoporosis Group of Chinese Orthopaedic Association concentrates on the epidemiology, characters, and management strategies of common osteoporotic fractures with bone defect to standardize clinical practice in bone repair of osteoporotic fractures.

Targeting Bone Tumor and Subcellular Endoplasmic Reticulum via Near Infrared II Fluorescent Polymer for Photodynamic-Immunotherapy to Break the Step-Reduction Delivery Dilemma.

Specific localization of photosensitizers (PSs) to a certain organelle could result in targeted attack to cause greater trauma to cancer cells, eventually maximizing photodynamic therapy (PDT). However, currently, efficient and precise transportation of PSs via drug delivery to tumor cells and subcellular organelles is still challenging, due to a so-called step-reduction delivery dilemma (SRDD) which also threatens anticancer drug delivery to exert their efficacy. Herein, a cascade targeting near infrared II (NIR II) fluorescent nanoparticles (NPER/BO-PDT ) is designed that can target bone tumor first and then target the subcellular organelle of endoplasmic reticulum (ER). It is found that NPER/BO-PDT achieves the targeted accumulation of the bone tumor and then ER. NPER/BO-PDT generates reactive oxygen species (ROS) in the subcellular organelles of ER under near infrared light irradiation. The continuous ER stress by ROS promotes the release of more damage-associated molecular patterns, induces immunogenic cell death, stimulates the adaptive immune response, and further synergistically inhibits tumor growth, achieving the so-called photodynamic-immunotherapy. Overall, this study exemplifies a safe and efficient nano-drug delivery system for a bone and ER cascade targeting via delivery of PSs to break the SRDD and highlights potential clinical translation.

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.

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.

Long Noncoding RNA ADAMTS9-AS2 Inhibits the Proliferation, Migration, and Invasion in Bladder Tumor Cells.

BACKGROUND: Bladder tumor is the fifth most prevalent tumor in men, yet its pathogenesis remains to be fully identified. Albeit a host of long noncoding RNAs (lncRNA) are emerging as new players involved in bladder tumor, the functions of many lncRNAs are still enigmatic. Reports on the deluge of studies on lncRNA ADAMTS9-AS2 have been convincingly associated with various tumors, but without mention of its roles in bladder tumor. Therefore, the roles of ADAMTS9-AS2 in bladder tumor cells were explored in our study. MATERIALS AND METHODS: Quantitative real-time PCR assays and bioinformatic tools were applied in bladder tumor cells to identify the ADAMTS9-AS2 and ADAMTS9 expression. Western blot assays were performed to obtain the protein levels of bladder tumor related key molecules. CCK8, clonogenic assay, scratch wound healing, and transwell assays were separately applied to identify the functional roles of ADAMTS9-AS2 on proliferation, migration, and invasion in bladder tumor cells. RESULTS: First, ADAMTS9-AS2 downregulation in bladder tumor cells was identified. Overexpression and knockdown experiments showed that ADAMTS9-AS2 expression was positively related to ADAMTS9, which is in accordance with the results from GEO database. Second, ADAMTS9-AS2 contributed to the inhibition of proliferation, migration, and invasion in bladder tumor cells. Third, ADAMTS9-AS2 was linked with PI3K/AKT/mTOR pathway related-molecules, several key autophagy, and apoptotic proteins. CONCLUSION: Conjointly, our findings suggested that ADAMTS9-AS2 might function as a tumor suppressor to restrain the proliferation, migration, and invasion in bladder tumor cells. The potential mechanism of ADAMTS9-AS2 related to PI3K/AKT/mTOR signal pathway was further identified. Of note, we found that ADAMTS9-AS2 has a significant effect on several key autophagy and apoptotic proteins. Therefore, these observations will provide supportive evidence to ADAMTS9-AS2 as a potential biomarker in patients with bladder tumor.

A Highly Sensitive Electrochemiluminescence Biosensor for Pyrophosphatase Detection Based on Click Chemistry-Triggered Hybridization Chain Reaction in Homogeneous Solution.

The abnormal expression of pyrophosphatase (PPase) is closely related to many diseases and malignant tumors, so the detection for PPase is of great significance in clinical diagnosis, disease monitoring, and other biomedical aspects. In this study, a sensitive and specific electrochemiluminescence (ECL) biosensor combined highly specific Cu+-catalyzed azide-alkyne cycloaddition (CuAAC) with high efficiency of hybridization chain reaction (HCR) for the purpose of detecting pyrophosphatase has been designed. Highly efficient hybridization chain reaction amplification processed in homogeneous solution and the amplification products were connected to the electrode surface in one step, which solved the problem of low DNA amplification efficiency on the electrode surface because of the steric hindrance. Ru(phen)32+ was embedded into the dsDNA and functioned as ECL probes; the enhanced ECL intensity of the system had a linear relationship with the logarithm of PPase concentration in the range of 0.025-50 mU with a detection limit of 8 µU. The method was proved to be of good specificity, repeatability, and stability that could be used for screening and quantitatively determining pyrophosphatase inhibitor sodium fluoride. The practicability of this method in clinical application has been proved through the detection of serum from the clinical arthritis patients. Moreover, the method can be used to monitor PPase activity of arthritis patients before and after administration to provide reference for the effect of drug treatment.

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.

Ratiometric Immunosensor for GP73 Detection Based on the Ratios of Electrochemiluminescence and Electrochemical Signal Using DNA Tetrahedral Nanostructure as the Carrier of Stable Reference Signal.

DNA tetrahedron nanostructure (DTNs) has the merits of simple synthesis, high yield, structural stability, and mechanical rigidity, and its three-dimensional structure provides a satisfactory biosensing interface to the improvement of the binding efficiency of antigenic proteins and antibodies. Electrochemiluminescence (ECL) reagent, tris(4,4'-dicarboxylicacid-2,2'-bipyridyl)ruthenium(II) dichloride (Ru(dcbpy)3Cl2), was modified on the electrode through the formation of classical sandwich complex of antibody-antigen-antibody. ECL response of the system increased with the increment of the target (golgi protein 73 (GP73) in this study) with high selectivity. Besides, the composed double-stranded DNA (dsDNA) in each side of DTNs could act as an excellent carrier of methylene blue (MB), thus producing a stable electrochemical internal reference signal on the electrode surface to correct the potential interferences. Therefore, a highly selective and reproductive ratiometric immunosensor was developed on the basis of the ratio of ECL of Ru(dcbpy)3Cl2 and electrochemistry of MB. The ratio value of the ECL/electrochemistry had a linear relationship with GP73 concentration in the range of 15 pg/mL-0.7 ng/mL, and the limit of detection was 15 pg/mL. The proposed ratiometric ECL immunoassay has been applied to detect GP73 in real serum samples with satisfactory results.

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.

Construction of versatile multilayered composite nanoparticles from a customized nanogel template.

We present a highly adaptable design platform for multi-responsive, multilayered composite nanoparticles (MC-NPs) with fine-tunable functional layers. A flexible disulfide-linked nanogel template is obtained by a controlled in-situ gelation method, enabling a high degree of control over each successive layer. From this template, we optimize "smart" biomaterials with biofunctional surfaces, tunable drug release kinetics, and magnetic or pH-responsive functionality, fabricated into MC-NPs for targeted drug release and periosteum-mimetic structures for controlled rhBMP-2 release towards bone tissue formation in-vivo. Such a versatile platform for the design of MC-NPs is a powerful tool that shows considerable therapeutic potential in clinical fields such as oncology and orthopedics.

MicroRNA-300 decreases cell viability, inhibits migration and promotes apoptosis of osteosarcoma cells via downregulation of Twist1.

Osteosarcoma (OS) is the most frequently occurring pediatric bone malignancy in the world. Numerous miRNAs have previously been demonstrated to participate in the initiation and development of OS. The present study aimed to reveal the role of microRNA­300 (miR­300) in OS cells and elucidate the underlying mechanism involved. The expression of miR­300 in the MG63 human OS cell line was monitored via quantitative polymerase chain reaction (qPCR). Following transfection with miR­300 mimic, miR­300 inhibitor or scramble control, MG63 cell viability, migration and apoptosis were respectively measured by 3­(4,5­dimethyl­2­thiazolyl)­2,5­diphenyltetrazolium bromide (MTT), modified two­chamber migration assay and flow cytometry. Dual­Luciferase reporter assays, qPCR and western blot analysis were subsequently performed to verify whether Twist1 was a direct target of miR­300. Furthermore, the expression levels of nuclear factor (NF)­κB pathway proteins were detected via western blot analysis. In MG63 cells, miR­300 was effectively overexpressed or suppressed by transfection with miR­300 mimic or inhibitor, respectively (P<0.001). Overexpression of miR­300 significantly suppressed cell viability and migration, whereas it enhanced apoptotic rate (P<0.001). miR­300 suppression exhibited contrary results (P<0.05, P<0.01 or P<0.001). Twist1 was demonstrated to act as a direct target of miR­300, and was negatively regulated by miR­300. In addition, miR­300 overexpression downregulated the expression of the primary factors involved in the NF­κB signaling pathway. These effects on OS cell proliferation and apoptosis may be due to the miR­300 targeting of Twist1 and the suppressive effect on the NF­κB signaling pathway.

Influence of neoadjuvant chemotherapy on prognosis of patients with synovial sarcoma.

BACKGROUND: This study aimed to explore the clinical efficacy of neoadjuvant chemotherapy combined with surgery in primary synovial sarcoma of the limbs and trunk through retrospective analysis of patients with primary synovial sarcoma of the limbs and trunk treated by this treatment in our hospital. METHODS: A total of 89 patients diagnosed with synovial sarcoma were enrolled in this study between January 2005 and December 2011 in PLA General Hospital. Most of the patients received neoadjuvant chemotherapy combined with operative treatment (84.3%), 10.1% of them received adjuvant chemotherapy combined with operative treatment, and only 5.6% received merely operative treatment. The influence on the prognosis of patients with synovial sarcoma was analyzed by the statistics overall survival (OS), progression-free survival (PFS), local control (LC), and freedom from distant metastasis (FFDM). RESULTS: The median follow-up time was 68.6 months. The 5-year OS, 5-year PFS, 5-year LC, and 5-year FFDM of the patients were 80.2, 60.5, 78.8, and 80.8%, respectively. The OS of the patients with a tumor size >5 cm was lower (91.4 vs 73.1%, P < 0.05). Besides, the OS and FFDM of neoadjuvant chemotherapy were better than those of adjuvant chemotherapy (84.5 vs 55.6%, P = 0.015, and 83.8 vs 55.6%, P = 0.028, respectively). However, there was no significant difference in the LC and PFS. CONCLUSIONS: Neoadjuvant chemotherapy was beneficial for patients with synovial sarcoma, and it could improve survival time and control distant metastasis. Tumor size was an important factor influencing patients' prognosis.

Ionic Colloidal Molding as a Biomimetic Scaffolding Strategy for Uniform Bone Tissue Regeneration.

Inspired by the highly ordered nanostructure of bone, nanodopant composite biomaterials are gaining special attention for their ability to guide bone tissue regeneration through structural and biological cues. However, bone malformation in orthopedic surgery is a lingering issue, partly due to the high surface energy of traditional nanoparticles contributing to aggregation and inhomogeneity. Recently, carboxyl-functionalized synthetic polymers have been shown to mimic the carboxyl-rich surface motifs of non-collagenous proteins in stabilizing hydroxyapatite and directing intrafibrillar mineralization in-vitro. Based on this biomimetic approach, it is herein demonstrated that carboxyl functionalization of poly(lactic-co-glycolic acid) can achieve great material homogeneity in nanocomposites. This ionic colloidal molding method stabilizes hydroxyapatite precursors to confer even nanodopant packing, improving therapeutic outcomes in bone repair by remarkably improving mechanical properties of nanocomposites and optimizing controlled drug release, resulting in better cell in-growth and osteogenic differentiation. Lastly, better controlled biomaterial degradation significantly improved osteointegration, translating to highly regular bone formation with minimal fibrous tissue and increased bone density in rabbit radial defect models. Ionic colloidal molding is a simple yet effective approach of achieving materials homogeneity and modulating crystal nucleation, serving as an excellent biomimetic scaffolding strategy to rebuild natural bone integrity.

Survival and prognostic factors in Chinese patients with osteosarcoma: 13-year experience in 365 patients treated at a single institution.

This study was designed to retrospectively analyze the survival and prognostic factors in Chinese osteosarcoma patients received neoadjuvant chemotherapy or/and surgery in a single institution. A total of 365 patients with pathological proved osteosarcoma undergoing neoadjuvant chemotherapy or/and surgery in a single institution between December 1999 and December 2012 were retrospectively analyzed for the demographic, tumor-related, and treatment-related variables, prognostic factors for survival rate and chemotherapy response. There were 231 males and 134 females (ratio, 1.72:1). The average age was 21±10years, with peak age between 10 and 20 years old (62%, 226/365). Of 365 patients, 319 (87.4%) suffered from primary tumor only, and 46 (12.6%) had metastases upon initial presentation. The overall 5-year survival rate was 65%. Upon univariate analysis, tumor site (femur 60.3%; other long bone 70.2%; trunk 33.6%; P=0.012), primary metastases (yes 36.7%; no 68.9%; P=0.000), tumor response to preoperative chemotherapy (good 89.8%; poor 47.5%; P=0.001) and recurrence/metastases after treatment (yes 36.2%; no 63.8%; P=0.000) were associated with higher 5-year survival rate. All factors except tumor site maintained their significance in multivariate testing. Male sex and nonconventional subtype of tumor were related to a higher likelihood of poor chemotherapy response.The absence of metastases at initial presentation, negative local recurrence or metastases after treatment, and tumor response to chemotherapy are of independent prognostic value in osteosarcoma. The overall prognostic factors and survival in Chinese patients are similar to those patients reported in western countries.

[Effectiveness of unicompartment allografts replacement for bone tumor around the knee].

Objective: To analyze the effectiveness of unicompartment allografts replacement for reconstructing bone defect after bone tumor resection around knee. Methods: Between January 2007 and January 2014, a total of 9 patients received unicompartment allografts replacement to treat bone tumor around the knee, including 6 males and 3 females, with an average age of 25.8 years (range, 17-38 years). There were 7 patients with bone giant cell tumor (postoperative recurrence of bone giant cell tumor in 1 case) and 2 patients with chondromyxoid fibroma. The tumors were located at the distal femur in 7 cases and proximal tibia in 2 cases, and the tumors were almost at the lateral limbs. The symptom duration was 2-5 months (mean, 3.2 months). The size of lesion ranged from 6 cm×2 cm to 9 cm×4 cm by X-ray film and MRI; and the metastasis was excluded by CT. The length of the allograft was 8.0-9.2 cm (mean, 8.6 cm). Results: The intraoperative blood loss volume was 400-550 mL (mean, 480 mL); and 0-3 U of erythrocyte was transfused after operation. The continuous exudate of incision occurred in 1 patient, and cured after 3 months; the other incisions healed primarily at 2 weeks after operation. All patients were followed up 3-10 years (mean, 6 years). No operation area infection, allograft bone poor healing or rupture was found. At 1 year after operation, the knee range of motion was 90-110° (mean, 100°); the Musculoskeletal Tumor Society score was 24-29 (mean, 26). Low density area (osteolysis) was found in 6 allografts; no articular surface collapse, hairline fracture, or fracture was found in patients; callus formation was observed in the contact surface between the allograft and the host bone, and the cortical bone showed good continuity. Conclusion: Unicompartment allografts replacement can provide good support and function in terms of bone tumor resection, and achieve good effectiveness by biological reconstruction.