[Three-dimensional printing combined with distal humeral osteotomy for cubital varus deformity in children].

OBJECTIVE: To explore clinical effect of three-dimensional(3D) printing combined with distal humerus osteotomy for children with cubital varus deformity. METHODS: From January 2017 to January 2020, 17 cubital varus deformity children treated with distal humerus osteotomy were retrospective analysis, included 11 boys and 6 girls, aged from 5 to 11 years old with an average of (7.8±1.7) years old. A model of affected side elbow joint was made by 3D printing technique before operation, pre-operation was performed on the model. Three-dimensional model was successfully used for distal humeral osteotomy during operation. Carrying angle, flexion and extension angle of elbow joint were compared before and six months after operation, and Flynn scoring criteria was used to evaluate clinical effect. RESULTS: All children were followed up for 6 to 12 months with an avergae of (9.6±1.7) months. One child occurred wound infection and healed completely after dressing change. No complications such as nonunion, internal fixation and nerve injury occurred. Carrying angle of affected limb was improved from (-20.8±2.4)°before operation to (7.2±2.3)°at 6 months after operation (P<0.01). Angle of affected elbow joint extension improved from (-5.6±3.9)° before opeation to(-2.6±2.1)°at 6 months after operation (P<0.01). There was no significant difference in extension angle of elbow joint between preopertaion and postopertaion at 6 months (P>0.05). While there was no difference in elbow joint function on the healthy side and affected side at 6 months after opertaion (P>0.05). According to Flynn scoring criteria, 13 patients got excllent results and 4 moderate. CONCLUSION: Three-dimensional printing combined with distal humerus osteotomy in treating elbow varus deformity could receive satisfactory clinical effect, which could accurately assist correction of cubital varus deformity, restore physiological structure and function of elbow joint.

Effect of 3D Printing Technology in Proximal Femoral Osteotomy in Children with Developmental Dysplasia of the Hip.

OBJECTIVE: To investigate the effect and safety of 3D printing technology in proximal femoral osteotomy in children with developmental dysplasia of the hip. METHODS: 40 cases of children with developmental dysplasia of the hip treated by pelvic osteotomy combined with proximal femoral osteotomy at Ningbo No. 6 Hospital from January 2017 to December 2019 were retrieved and retrospectively analyzed. Among them, 20 cases received preoperative measurement and design assisted by 3D printing technology (the 3D printing group), and 20 cases received conventional preoperative measurement and design (the conventional group). RESULTS: All patients were followed up for an average of 25 (12~36) months. During the follow-up, there were no complications such as infection, fracture of internal fixation, or malunion of osteotomy. Compared with the conventional group, the 3D printing group had a shorter operation time, less intraoperative blood loss, and fewer intraoperative X-ray fluoroscopies (all p < 0.05). In the last follow-up, the clinical efficacy was evaluated by the McKay standard: in the 3D printing group, 14 cases were excellent, 5 cases were good, and 1 case was fair. In the conventional group, 10 cases were excellent, 9 cases were good, and 1 case was fair (Z = -0.382, p > 0.05). CONCLUSION: Preoperative 3D printing of bilateral femur and other large physical models is accurate, which is ideal for the development of individual preoperative planning. Proximal femoral osteotomy using preoperative measurements and simulated surgical data improves the safety of the operation.

Case Report: Unusual Presentation of Myositis Ossificans of the Elbow in a Child Who Underwent Excessive Postoperative Rehabilitation Exercise.

Traumatic myositis ossificans (MO) is an unusual complication after muscle injury and is predominantly seen in young adults and adolescents. Pediatric MO cases are even rarer. We report an 8-year-old girl who was diagnosed with a lateral humeral condyle fracture. She was treated surgically, and her elbow joint was fixed with plaster. Rehabilitation exercise was administered 1 month after the operation. Due to the wrong exercise method, a palpable bony mass appeared around the elbow 1 month later. The clinical radiological diagnosis showed MO, and conservative treatment was administered. After 3 years of follow-up, the affected limb functioned well, with no sign of recurrence. Here, we report this long-term follow-up case of MO resulting from excessive rehabilitation exercise.

lncRNAPVT1 targets miR-152 to enhance chemoresistance of osteosarcoma to gemcitabine through activating c-MET/PI3K/AKT pathway.

BACKGROUND: LncRNA PVT1 has been reported to be involved in a variety of biological processes, including cell proliferation, cell differentiation and cancer progression. However, the mechanism by which LncRNA PVT1 contributes to chemoresistance of osteosarcoma cell, has not been fully elucidated. METHODS: We first generatedLncRNA PVT1-overexpressed MG63 cells and LncRNA PVT1 knockdown MG63/DOX cells. Then, we examined the effect of LncRNA PVT1 on cell viability and colony formation ability by MTT assay and soft agar assay, respectively. In addition, we performed flow cytometry analysis to detect apoptosis induced by GEM. Dual luciferase reporter assay and RIP were used to confirmed the interaction between LncRNA PVT1 and miR-152. Finally, we determined protein level of c-MET, p-PI3K, and p-AKT by westernblot. RESULTS: LncRNA PVT1 overexpression promoted cell proliferation and exhibited the anti-apoptotic property in LncRNA PVT1-overexpressing MG63 cells treated with gemcitabine. While, LncRNA PVT1-depleted MG63/DOX cells treated with gemcitabine exhibited significant lower survival rate and high percentage of apoptosis. Next, we found that LncRNA PVT1 could target and downregulated the level of miR-152. Interestingly, miR-152 greatly rescued the biological outcomes of LncRNA PVT1 not only in MG63 but also in MG63/DOX cells. We observed that LncRNA PVT1 markedly induced PI3K/AKT pathway activation, which was abolished by miR-152 mimics overexpression. Finally, c-MET inhibitor was used to confirm the essential role of c-MET in LncRNA PVT1 and miR-152-regulated PI3K/AKT signaling. CONCLUSION: We showed thatlncRNA PVT1 played a contributory role in chemoresistance of osteosarcoma cells through c-MET/PI3K/AKT pathway activation, which was largely dependent on miR-152. Our findings advance our understanding of how lncRNA PVT1 promotes chemoresistance of osteosarcoma cells and facilitate development of novel strategies for treating osteosarcoma.

Thrombospondin 1 Triggers Osteosarcoma Cell Metastasis and Tumor Angiogenesis.

Osteosarcomas, especially those with metastatic or unresectable disease, have limited treatment options. The antitumor effects of pharmacologic inhibitors of angiogenesis in osteosarcomas are hampered in patients by the rapid development of tumor resistance, notably through increased invasiveness and accelerated metastasis. Here we demonstrated that thrombospondin 1 (TSP-1) is a potent inhibitor of the growth and metastasis of the osteosarcoma cell line MG-63. Moreover, we demonstrate that upregulation of TSP-1 facilitated expression of vasculostatin in MG-63 cells. In angiogenesis assays, overexpression of TSP-1 inhibited MG-63 cells and induced tube formation of human umbilical vein endothelial cells (HUVECs) in a CD36-dependent fashion. Finally, in xenografted tumors, we observed that TSP-1 overexpression inhibited angiogenesis and tumor growth. These results provided strong evidence for an important role of the TSP-1/CD36/vasculostatin signaling axis in mediating the antiangiogenic activity of osteosarcoma.

miRNA-133b targets FGFR1 and presents multiple tumor suppressor activities in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common bone malignancy prevalent in children and young adults. MicroRNA-133b (miR-133b), through directly targeting the fibroblast growth factor receptor 1 (FGFR1), is increasingly recognized as a tumor suppressor in different types of cancers. However, little is known on the biological and functional significance of miR-133b/FGFR1 regulation in osteosarcoma. METHODS: The expressions of miR-133b and FGFR1 were examined by RT-qPCR and compared between 30 paired normal bone tissues and OS tissues, and also between normal osteoblasts and three OS cells lines, MG-63, U2OS, and SAOS-2. Using U2OS and MG-63 as the model system, the functional significance of miR-133b and FGFR1 was assessed on cell viability, proliferation, apoptosis, migration/invasion, and epithelial-mesenchymal transition (EMT) by overexpressing miR-133b and down-regulating FGFR1 expression, respectively. Furthermore, the signaling cascades controlled by miR-133b/FGFR1 were examined. RESULTS: miR-133b was significantly down-regulated while FGFR1 robustly up-regulated in OS tissues and OS cell lines, when compared to normal bone tissues and normal osteoblasts, respectively. Low miR-133b expression and high FGFR1 expression were associated with location of the malignant lesion, advanced clinical stage, and distant metastasis. FGFR1 was a direct target of miR-133b. Overexpressing miRNA-133b or knocking down FGFR1 significantly reduced the viability, proliferation, migration/invasion, and EMT, but promoted apoptosis of both MG-63 and U2OS cells. Both the Ras/MAPK and PI3K/Akt intracellular signaling cascades were inhibited in response to overexpressing miRNA-133b or knocking down FGFR1 in OS cells. CONCLUSION: miR-133b, by targeting FGFR1, presents a plethora of tumor suppressor activities in OS cells. Boosting miR-133b expression or reducing FGFR1 expression may benefit OS therapy.