Cryptotanshinone (CTS) has emerged as an anti-inflammatory agent in osteoarthritis (OA). However, the molecular mechanism underlying its potent therapeutic effect on OA remains largely unknown. MicroRNAs (miRNAs) act as crucial regulators in maintaining cartilage homeostasis. To investigate whether CTS protects against developing OA through regulation of miRNAs, we examined the potential CTS-mediated miRNA molecules using microarray analysis. We found that CTS significantly promoted miR-106a-5p expression in chondrocytes. Using the OA mouse model created by anterior cruciate ligament transection, we revealed that intra-articular injection of miR-106a-5p agomir attenuated OA. In addition, miR-106a-5p inhibited GLI-similar 3 (GLIS3) production by directly targeting the 3′ untranslated region. CTS promoted miR-106a-5p expression through recruitment of a member of the paired box (PAX) family of transcription factors, PAX5, to the miR-106a-5p promoter. Inhibition of PAX5 mimicked the effect of miR-106a-5p and abolished the CTS ability to regulate miR-106a-5p expression. In OA patients, miR-106-5p is downregulated which is accompanied by downregulation of PAX5 and upregulation of GLIS3. Collectively, these data highlight that the PAX5/miR-106a-5p/GLIS3 axis acts as a novel pleiotropic regulator in CTS-mediated OA cartilage protection, suggesting that miR-106a-5p and PAX5 activation and GLIS3 inhibition might be useful and attractive for therapeutic strategies to treat OA patients.

Background. Vertebral column decancellation (VCD) is a new spinal osteotomy technique to correct thoracolumbar kyphotic deformity (TLKD). Relevant biomechanical research is needed to evaluate the safety of the technique and the fixation system. We aimed to develop an accurate finite element (FE) model of the spine with TLKD following VCD and to provide a reliable model for further biomechanical analysis. Methods. A male TLKD patient who had been treated with VCD on L2 and instrumented from T10 to L4 was a volunteer for this study. The CT scanning images of the postoperative spine were used for model development. The FE model, simulating the spine from T1 to the sacrum, includes vertebrae, intervertebral discs, spinal ligaments, pedicle screws, and rods. The model consists of 509580 nodes and 445722 hexahedrons. The ranges of motion (ROM) under different loading conditions were calculated for validation. The stresses acting on rods, screws, and vertebrae were calculated. Results. The movement trend, peak stress, and ROM calculated by the current FE model are consistent with previous studies. The FE model in this study is able to simulate the mechanical response of the spine during different motions with different loading conditions. Under axial compression, the rod was the part bearing the peak stress. During flexion, the stress was concentrated on proximal pedicle screws. Under extension and lateral bending, an osteotomized L1 vertebra bore the greatest stress on the model. During tests, ligament disruption and unit deletion were not found, indicating an absence of fracture and fixation breakage. Discussion. A subject-specific FE model of the spine following VCD is developed and validated. It can provide a reliable and accurate digital platform for biomechanical analysis and surgical planning.

Bone tumors occur in bone or its accessory tissues. Benign bone tumors are easy to cure and have good prognosis, while malignant bone tumors develop rapidly and have poor and high mortality. So far, there is no satisfactory treatment method. Here, we designed a universal template vector for bone tumor therapy that simultaneously meets the needs of bone targeting, tumor killing, osteoclast suppression, and tumor imaging. The template is composed of a polydopamine (PDA) core and a multifunctional surface. PDA has excellent biosafety and photothermal performance. In this study, alendronate sodium (ALN) is grafted to enable its general bone targeting function. PDA core can carry a variety of chemotherapy drugs, and the rich ALN group can carry a variety of metal ions with an imaging function. Therefore, more personalized treatment plans can be designed for different bone tumor patients. In addition, the PDA core enables photothermal therapy and enhanced chemotherapy. Through template drug Doxorubicin (DOX) and template imaging ion Fe (Ⅱ), we systematically verified the therapeutic effect, imaging effect, and inhibition of bone dissolution of the agent on Osteosarcoma (OS), a primary malignant bone tumor, in vivo . In conclusion, our work provides a more general template carrier for the clinical treatment of bone tumors, through which personalized treatment of bone tumors can be achieved.

Objectives: To investigate whether the immediate thoracic kyphosis (TK) and acetabular anteversion (AA) postoperatively are correlated with proximal junctional failure (PJF) in adult spinal deformity (ASD) patients underwent surgical treatment.Methods: This is a retrospective study. Following institutional ethics approval, a total of 57 patients (49 Female, eight Male) with ASD underwent surgery fused to sacroiliac bone (S1, S2, or ilium) from March 2014 to January 2019 were included. All of those patients were followed up for at least 2 years. Demographic, radiographic and surgical data were recorded. The maximum range of flexion motion (F-ROM) and extension motion (E-ROM) actively of hip joints was measured and recorded at pre-and postoperation. The sum of F-ROM and E-ROM was defined as the range of hip motion (H-ROM). Receiver operating characteristic (ROC) curve analysis was used to obtain the cut off value of parameters for PJF. A Kaplan-Meier curve and log-rank test were used to analyze the differences in PJF-free survival.Results: In all, 14 patients developed PJF during follow-up. Comparisons between patients with and without PJF showed significant differences in immediate TK (P < 0.001) and AA (P = 0.027) postoperatively. ROC curve analysis determined an optimal threshold of 13 for immediate AA postoperatively (sensitivity = 74.3%, specificity = 85.7%, area under the ROC curve [AUC] = 0.806, 95% CI [0.686-0.926]). Nineteen patients with post-AA ≤13 were assigned into the observational group, and 38 patients with post-AA >13 were being as the control group. Patients in the observational group had smaller H-ROM (P = 0.016) and F-ROM (P < 0.001), but much larger E-ROM (P < 0.001). There were 10 patients showing PJF in the observational group and four in the control group (10/9 vs 4/34, P < 0.001). PJF-free survival time significantly decreased in the observational group (P = 0.001, log-rank test). Furthermore, patients in the observational group had much larger TK (post-TK, P = 0.015). The optimal threshold for post-TK (sensitivity = 85.7%, specificity = 76.7%; AUC = 0.823, 95% CI [0.672-0.974]) was 28.1 after the ROC curve was analyzed. In the observational group, those patients with post-TK ≥28.1 had significantly higher incidence of PJF (9/2 vs 1/7, P < 0.001) than those with post-TK < 28.1 . Moreover, PJF-free survival time in those patients significantly decreased (P = 0.001, log-rank test).Conclusions: ASD patients with acetabular anteversion of ≤13 at early postoperation may suffer significantly restricted hip motion and much higher incidence of PJF during follow-up, moreover, in those patients, postoperative TK ≥28.1 would be a significant risk factor for PJF developing.

Objective: To describe spinal osteotomy in lateral position, which might be a new strategy for correcting thoracolumbar kyphotic deformity combined with severe hip flexion contracture, and to present two cases in which this method was successfully performed.Methods: Spinal osteotomies in lateral position were performed in two patients with severe thoracolumbar kyphosis combined with hip flexion contracture, which was not suitable for operation in the prone position. Case 1: a 33-year-old female AS patient still had severe hip flexion contracture due to poor rehabilitation after total hip replacement (THR). The range of movement of the hip was only about 15 in right and 10 in left. Pre-operativethoracic kyphosis (TK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), and sagittal vertical axis (SVA) were 52.4 , 49.1 , 42.7 , and 315 mm, respectively. Pedicle subtraction osteotomy (PSO) at L3 was performed in the lateral position. The eggshell procedure was used during osteotomy. Case 2: a 45-year-old male AS patient presented coexisting rigid thoracolumbar kyphosis and hip flexion contracture. The range of movement of the hip was only about 20 in right and 25 in left. Pre-operativeTK, TLK, LL and SVA were 34.9 , 66.8 , 58.8 and 290.8 mm, respectively. PSO at L 2 was performed in lateral position. The eggshell procedure was also used.Results: Sagittal malalignments of both patients were greatly improved. For case 1, the total operation time was 5.5 h. The blood loss was 1500 mL and the amount of allogeneic blood transfusion was 1580 mL during the operation. SVA was reduced to 127 mm and LL decreased from preoperative 42.7 to À28.4 . The correction angle through L 3 was 34.7 and the correction angle through the osteotomy segment was 62.9 . For case 2, the duration of surgery was 6.5 h. The operative blood loss was 2000 mL and the total amount of blood transfusion was 2020 mL. SVA was reduced to 209.8 mm and LL decreased from preoperative 58.8 to 9.2 .The correction angle through L 2 was 37.1 and the correction angle through the osteotomy segment was 55 . No intra-operative or post-operative complications were observed. Six months after PSO, case 1 had good posture for standing and sitting. The case 2 underwent bilateral THRs nine months after PSO. Conclusion:PSO could be performed in the lateral position successfully. For AS patients who cannot be placed in the prone position due to coexisting severe thoracolumbar kyphosis and hip flexion contracture, performing spinal osteotomy in the lateral position as the first step is an alternative.