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Background: The aim of this study was to analyze the potential therapeutic targets of anlotinib using the patient‐derived xenografts (PDX) and evaluate the efficacy of the combination of chemotherapy and anlotinib in osteosarcoma patients before surgery. Methods: Forty‐three osteosarcoma specimens were used to establish the PDX model in mice, resulting in Twenty‐one PDX successful models. Eventually, six models were randomly selected for the pharmacodynamic experiment. The tumor‐bearing mice were randomly divided into the anlotinib (3 mg/kg) and placebo groups (n = 5 each). After treatment, the tumors were harvested and analyzed by immunohistochemistry (IHC) and western blotting. Results: In PDX model establishment, the tumors from donors with relapse, metastasis or chemoresistance demonstrated higher engraftment capacity. Histology results suggested that anlotinib significantly inhibited the growth of osteosarcoma by inducing mitotic arrest, necrosis and apoptosis, and selective against tumors with high expression of VEGFR2, PDGFRβ and CD31. Based on these results, five osteosarcoma patients who had progressed during NAC were treated with the combination of anlotinib and chemotherapy before surgery, which led to tumor regression in four patients. Next‐generation sequencing showed that most patients with tumor reduction expressed medium or high levels of VEGFR2 and PDGFRβ mRNA. The toxicities were tolerable. Conclusions: In conclusion, osteosarcoma with high expression of VEGFR2, PDGFRβ and CD31 is more sensitive to anlotinib. However, the potential of synergistic effect of anlotinib and chemotherapy in osteosarcoma patients needs further investigation. [ABSTRACT FROM AUTHOR]

Purpose: A three-dimensional finite element model of the lower cervical spine was established to evaluate the biomechanical stability and stress distribution of the new lower cervical interzygapophyseal fusion device (IZFD) developed by ourselves under different construct. The aim of this study was to provide theoretical basis for further clinical application., Methods: A normal fresh cadaveric specimen (male, 35 years old) was used to establish an intact three-dimensional finite element model of C3-C6. On this basis, the comparative finite element models of the lateral mass screw rod (LMSR) system and LMSR+IZFD were established. Only C4-C5 is fixed in the lateral mass. The range of motion (ROM) and stress distribution in the flexion,extension, lateral bending and rotation of the C4-C5 segment under the three constructs were analyzed., Results: The ROM and stress distribution of the three-dimensional finite element model under load construct were within a reasonable range, which proved the validity and reliability of the model. The ROM and stress distribution of C4-C5 segment was significantly decreased in both LMSR and LMSR+IZFD constructs than those in the intact construct. The ROM and stresss distribution were even smaller in LMSR+IZFD construct than in LMSR construct., Conclusions: The IZFD combined with LMSR system can provide satisfactory stability for the lower cervical spine, and the IZFD can further improve the fixation effect of the LMSR system.

β-TCP bioceramic, as a kind of biocompatible and biodegradable artificial bone scaffolds, is increasingly used to supplement lamina autografts when performing instrumented or non-instrumented spinal fusion, clinically, although solid fusion is not always achieved. The addition of collagen to β-TCP appears to be a potential strategy to improve bone regeneration, thereby enhancing the rate of spinal fusion. This study aimed to compare the fusion in collagen/β-TCP composite, β-TCP and autologous bone in a posterior spinal fusion model. The fusion grade evaluated radiography was greater in the collagen/β-TCP group than in the β-TCP group (p < 0.05). Stiffness and yield strength of the fused segments in collagen/β-TCP group were comparable to that in autogenous bone group. Histological analysis revealed that the proportion of new bone formation in collagen/β-TCP group were significantly greater than in β-TCP group (p < 0.05). In addition, bone deposition rate in the collagen/β-TCP group was greater than in the β-TCP group (p < 0.05) and comparable to that in the autogenous bone group. We therefore concluded that collagen/β-TCP is superior to β-TCP alone in facilitating posterior spinal fusion. The addition of collagen to β-TCP represents a simple strategy that couples the osteogenic effect, providing a promising alternative to autologous bone in the clinical treatment of spinal disorders.