Hematopoietic cell kinase enhances osteosarcoma development via the MEK/ERK pathway.

Osteosarcoma (OS) is a sarcoma with high rates of pulmonary metastases and mortality. The mechanisms underlying tumour generation and development in OS are not well-understood. Haematopoietic cell kinase (HCK), a vital member of the Src family of kinase proteins, plays crucial roles in cancer progression and may act as an anticancer target; however, the mechanism by which HCK enhances OS development remains unexplored. Therefore, we investigated the role of HCK in OS development in vitro and in vivo. Downregulation of HCK attenuated OS cell proliferation, migration and invasion and increased OS cell apoptosis, whereas overexpression of HCK enhanced these processes. Mechanistically, HCK expression enhanced OS tumorigenesis via the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; HCK upregulation increased the phosphorylation of MEK and ERK and promoted epithelial-mesenchymal transition, with a reduction in E-cadherin in vitro. Furthermore, HCK downregulation decreased the tumour volume and weight in mice transplanted with OS cells. In conclusion, HCK plays a crucial role in OS tumorigenesis, progression and metastasis via the MEK/ERK pathway, suggesting that HCK is a potential target for developing treatments for OS.

BMP2 variants in the risk of ankylosing spondylitis.

The purpose of the study was to explore the genetic effects of bone morphogenetic protein (BMP2) polymorphisms on the susceptibility to ankylosing spondylitis (AS) in Chinese Han population. The case-control study included 120 AS cases and 110 healthy controls. Hardy-Weinberg equilibrium test was performed in control group. BMP2 rs235768 and rs3178250 polymorphisms were analyzed by polymerase chain reaction and direct sequencing. Additionally, the χ2  test was used to estimate association strength between BMP2 genetic polymorphisms and AS susceptibility, and the results were assessed via odds ratio (OR) with the corresponding 95% confidence interval (95%CI). Results adjustment was performed using logistic regression analysis. AA, AT, TT genotype and A, T allele frequencies of BMP2 rs235768 polymorphism presented no significant differences between case and control groups (P > .05 for all). TC genotype of rs3178250 polymorphism showed significantly higher in case group than that in control group (P = .048). After adjusting, TC genotype was a risk factor for AS (OR = 2.095; 95%CI = 1.086-4.038; P = .027). BMP2 rs3178250 polymorphism may increase individual susceptibility to AS in Chinese Han population.

Increasing pelvic incidence is associated with more global sagittal imbalance in ankylosing spondylitis with thoracolumbar kyphosis: an observational retrospective study of 94 cases.

BACKGROUND: Ankylosing spondylitis (AS) patients with kyphosis have an abnormal spinopelvic alignment and pelvic morphology. Most studies focus on the relationship of pelvic tilt (PT) or sacral slope (SS) and deformity, and relatively few studies have addressed the relationship between pelvic incidence (PI) and kyphosis in AS patients. The purpose of this study is to analyze the correlation between pelvic incidence (PI) and the spinopelvic parameters describing local deformity or global sagittal balance in AS patients with thoracolumbar kyphosis. METHODS: A total of 94 patients with AS (91 males and 3 females) and 30 controls (27 males and 3 females) were reviewed. The mean age was 36.8 years in AS patients and 34.4 years in controls. Gender ratios and mean age were similar in both group. Sagittal spinopelvic parameters, including PI, PT, SS, thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), sagittal vertical axis (SVA), the first thoracic vertebra pelvic angle (TPA), spinosacral angle (SSA) and spinopelvic angle (SPA) were measured. The same spine surgeons measured all the parameters of the AS and control group. All the sagittal spinopelvic parameters were compared between the groups. The relationship between PI and other spinopelvic parameters was analyzed with Pearson correlation (r) and unary linear regression model. RESULTS: All the sagittal parameters were found to be significantly different between AS patients and controls. Compared with the control group, the AS patients had significantly higher PI(47.4° vs. 43.2°, P < 0.001). Correlation analysis revealed that PI in AS patients was significantly positively correlated with TPA(r = 0.533, R2 = 0.284, P < 0.001), and negatively correlated with SPA(r = - 0.504, R2 = 0.254, P < 0.001). However, no correlations were found between PI and SVA, SSA, TK, TLK or LL in AS patients. CONCLUSION: This study revealed that increasing PI was significantly correlated with more global sagittal imbalance, not with the local deformity in AS patients with thoracolumbar kyphosis.

Correlation between Disc Imaging Observations and Clinical Efficacy after Percutaneous Endoscopic Lumbar Discectomy: A 1-Year Follow-up Study.

OBJECTIVE: The connection between alterations in the disc structure following percutaneous endoscopic lumbar discectomy (PELD) and symptoms in patients postsurgery has not been reported yet. The purpose of the present study was to discuss the potential correlation between the changes in the morphological characteristics of various reference surfaces of the intervertebral disc after percutaneous endoscopic lumbar discectomy (PELD) and clinical outcomes, to identify the morphological parameters that affect efficacy and provide an evidence-based foundation for assessing postoperative efficacy. METHODS: From October 2019 to October 2021, after percutaneous endoscopic lumbar discectomy (PELD), 98 individuals were enrolled. MRI DICOM data of the lumbar spine were obtained before and after surgery, specifically around 3 months. The morphological parameters of the operated and adjacent segments of the discs were measured using T2-weighted images from three reference planes. Outcomes were assessed using the Oswestry disability index (ODI), visual analogue pain scores for the back and leg (VAS-back/VAS-leg), Japanese Orthopaedic Association (JOA) scores, and recovery rates. Postoperative changes in disc parameters and outcomes were compared between patients with different severity and types of LDH based on the MSU staging. Patients completed the questionnaire during outpatient follow-up appointments 3, 6, and 12 months after the surgery. The follow-up period was 14.69 ± 4.21 months, ranging from 12 to 24 months. RESULTS: Parameters such as area and circumference of intervertebral discs in the cross-section were not associated with the change in the efficacy index. Postoperatively, a negative correlation between the variation of the disc height, disc height index, and protrusion distance and the difference in VAS scores for low back pain at 3 and 6 months was observed among the two sagittal change parameters. Differences between changes in disc imaging parameters and postoperative efficacy were not statistically significant between various types of lumbar disc herniation. CONCLUSION: For the patients after percutaneous endoscopic lumbar discectomy, the changes in parameters such as disc area and circumference in the cross-sectional plane are not associated with efficacy, and the changes in disc height and herniation distance in the sagittal plane provide a morphologic basis for the assessment of short-term postoperative efficacy. In addition, the changes in disc morphologic parameters and postoperative efficacy do not differ between various types of lumbar disc herniation.

MiR-99b regulates cerebral ischemia neuronal injury through targeting IGF1R.

BACKGROUND: Recently, microRNA-99b (miR-99b) shows diverse functions in different human disease. However, further studies about the potential effect of miR-99b in cerebral ischemia injury still need to be done. METHODS: The expressions of miR-99b and IGF1R were detected via RT-qPCR assay. Western blot assay was applied to measure the protein expression of Caspase-3, Bax and Bcl-2. MTT assay was used to observe cell viability of SH-SY5Y cells. The association of miR-99b and IGF1R was testified by dual luciferase assay. And human SH-SY5Y cells were treated with the oxygen-glucose deprivation/reperfusion (OGD/R) to mimic CIR injury. RESULTS: The expression of miR-99b was increased in the OGD/R model. And upregulation of miR-99b promoted cell viability and inhibited apoptosis induced by OGD/R. Moreover, IGF1R was confirmed as a direct target gene of miR-99b. The expression of IGF1R was obviously decreased under OGD/R conditions. CONCLUSIONS: MiR-99b promoted the viability and suppressed apoptosis of SH-SY5Y cells under OGD/R conditions through targeting IGF1R.

Trans-intervertebral osteotomy classification of posterior spinal corrective osteotomy procedures via the intervertebral space.

•This is a diagnostic study for a classification for posterior spinal osteotomy procedures via the intervertebral space.•Proposed â€‹a novel classification â€‹with â€‹excellent reliability â€‹and â€‹validity, differ from the SRS-Schwab osteotomy classification.•Give a novel definition of "trans-intervertebral osteotomy" (TIO) for posterior spinal osteotomy procedures.•Thoroughly discussed about the histories of posterior spinal osteotomy procedures via the intervertebral space.•Systematically introduced the TIO technique with fine original schematics.

A simple, universal and multifunctional template agent for personalized treatment of bone tumors.

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.

Spine-Pelvis-Hip Alignments in Degenerative Spinal Deformity Patients and Associated Procedure of One-Stage Long-Fusion with Multiple-Level PLIF or Apical-Vertebra Three Column Osteotomy-a Clinical and Radiographic Analysis Study.

OBJECTIVE: To explore the spine-pelvis-hip alignments in degenerative spinal deformity (DSD) patients, and compare the outcomes in the procedure of long-fusion with posterior lumbar inter-body fusion (PLIF) or single-level three-column osteotomy (STO) at lower lumbar level (LLL, L3 -S1 ) and thoracolumbar levels (TLL, T10 -L2 ) for those patients. METHODS: This is a retrospective study. Following institutional ethics approval, a total of 83 patients (Female, 67; Male, 16) with DSD underwent long-fusion with PLIF or STO surgery between March 2015 and December 2017 were reviewed. All of those patients were assigned into LLL and TLL groups. The average age at surgery was 65.2 years (SD, 8.1). Demographic (age, gender, BMI, and comorbidities), radiographs (both coronal and sagittal parameters) and health-related quality of life (HRQOL) assessments were documented. The radiographic parameters and HRQOL-related measurements at pre- and post-operation were compared with paired-samples t test, and those variables in the two groups were analyzed using an independent-sample t test. The relationships between pelvic incidence (PI) and other sagittal parameters were investigated with Pearson correlation analysis. The Pearson χ2 or Fisher's exact was carried out for comparison of gender, incidence of comorbidities and post-operative complications. RESULTS: There were 53 and 30 patients in the LLL and TLL groups respectively. Those spino-pelvic radiographic parameters had significant improvements after surgeries (P < 0.001). The patients in the two group with different pre-operative thoracolumbar kyphosis (TLK, P = 0.003), PI (P = 0.02), and mismatch of PI minus lumbar lordosis (PI-LL, P = 0.01) had comparable post-operative radiographic parameters except PI (P = 0.04) and pelvic-femur angle (PFA, P = 0.02). Comparing the changes of those spine-pelvic-hip data during surgeries, the corrections of TLK in TLL group were significant larger (P = 0.004). Pearson correlation analysis showed that there were negative relationship between PI and TLK (r = -0.302, P = 0.005), positive relationship between PI and LL (r = 0.261, P = 0.016) at pre-operation. Those patients underwent the surgical procedure that long-segment instrumentation and fusion with STO would have higher incidence of complications involving longer operative timing (P = 0.018), more blood loss (P < 0.001), revision surgery (P = 0.008), and cerebrospinal fluid leakage (P = 0.001). All the HRQOL scores significantly improved at final follow-up (P < 0.001), with no difference of intra-group. CONCLUSION: Patients suffered de-novo scoliosis or hyper-kyphosis with low PI would be vulnerable to significant thoracolumbar degeneration, and have more changes of spine-pelvis-hip data after long-fusion surgery, however, those with high PI would be closed to significant lumbar degeneration. Although spine-pelvis-hip alignments in DSD patients can be restored effectively after long-fusion with PLIF or STO, the incidence of complications in patients underwent STO was significant higher than that in patients performed multi-level PLIF.

Correlation of Acetabular Anteversion and Thoracic Kyphosis Postoperatively with Proximal Junctional Failure in Adult Spinal Deformity Fused to Pelvis.

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.

Association of Sagittal Spinopelvic Realignment with Correction in Lower Lumbar Lordosis after Surgical Treatment in Degenerative Lumbar Scoliosis.

OBJECTIVE: To assess the effect that correction of lower lumbar lordosis (3L) has on global spine realignment due to the key role of 3L for scoliosis surgery in patients with degenerative lumbar scoliosis (DLS). METHODS: This study is a retrospective review performed between June 2018 and January 2020, including consecutive patients with DLS. Only patients age ≥ 45 years who had already undergone a selective root block operation and had the procedure of long-fusion extending to pelvis and posterior lumbar interbody fusion (PLIF) at lower lumbar spine (L4 -S1 ) were retained for analysis. Spinopelvic parameters measured included thoracic kyphosis (TK), lumbar lordosis (LL), 3L, pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), T1 pelvic angle (TPA), and sagittal vertical axis (SVA) at pre-operation and the third month follow-up. The mismatch (PI-LL) was calculated subsequently. Pearson correlation and linear regression analysis were performed to explore the association of the changes in global spinopelvic parameters with 3L correction. RESULTS: Thirty-nine patients (five males, 34 females) with the average age of 63.84 years (SD 7.53; range, 45-75 years) at the time of surgery were identified. All patients had the surgical procedure of long-fusion (≥4 vertebras) with PLIF at lower lumbar spine between L4 and S1 spine. Lower instrumented vertebras (LIV) fused to pelvis (S1 , 14; S2 , 18; ilium, 7) were operated in all patients. Seventeen patients were with upper instrumented vertebras (UIV) at thoracolumbar spine (L2 -T11 ), and 22 patients at thoracic spine (T10 and above). The median of instrumented segments was 10 (5-14). 3L significantly increased (P = 0.02) after surgical treatment by mean change of 4.21° (range, -19.7° to +22.2°). Perioperatively, all spinopelvic parameters regarding to TK, LL, SS, PT, TPA, SVA, and mismatch (PI-LL) had significant changes (P < 0.001). The change in 3L correlated significantly with the changes in spinopelvic parameters (r = 0.772 for LL, -0.589 for SVA, -0.439 for TPA, and -0.428 for PI-LL). After linear regression analysis, the formulas were obtained: d-LL = 14.977 + 0.636 × d-3L, (R2 = 0.596); d-(PI-LL) = 16.575 + 0.62 × d-3L, (R2 = 0.183); d-TPA = -7.284 to 0.358 × d-3L, (R2 = 0.193); d-SVA = -30.556-2.639 × d-3L (R2 = 0.347). CONCLUSIONS: Correction in lower lumbar lordosis, following the surgical procedure of long-fusion with PLIF at lower lumbar spine, could result in significant changes in full-spine parameters. The significant association of changes in each of global spine parameter with the correction of 3L perioperatively could provide important information for surgeons to make a surgical plan for spinal correction.

Pedicle Subtraction Osteotomy in Lateral Position: A New Strategy for Correcting Severe Thoracolumbar Kyphosis Combined with Hip Flexion Contracture in Ankylosing Spondylitis.

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 L2 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 -28.4°. The correction angle through L3 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 L2 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.

Low pelvic incidence is associated with Andersson lesions in ankylosing spondylitis patients with kyphosis.

INTRODUCTION/OBJECTIVES: This study was to investigate the role of pelvic incidence (PI) in the development of Andersson lesions (ALs) in ankylosing spondylitis (AS) patients with kyphosis and to evaluate the difference in sagittal spinopelvic parameters between inflammatory ALs and mechanical ALs. METHOD: A total of 135 AS patients with kyphosis were reviewed. The patients were classified into AL group and non-AL group based on the presence or absence of ALs. Additionally, AS patients with ALs were also classified as either inflammatory or mechanical lesions depending on the radiological features of the lesions. The sagittal spinopelvic parameters of all these AS patients were measured and compared. Logistic regression analysis was performed to determine the powerful variables for predicting ALs in AS patients. RESULTS: ALs were detected in 34 patients (25.2%) of the total 135 AS patients. The mean PI of the AL group was 40.0°, which was significantly lower than that (48.3°) of the non-AL group (P < 0.001). No statistically significant difference was observed in PI (P = 0.350) between the inflammatory lesion group and the mechanical lesion group. Logistic regression analysis showed that only PI was a statistically significant risk factor for ALs (P < 0.001) and was negatively correlated with ALs (odds ratio = 0.76). CONCLUSIONS: These data suggest that low PI is closely associated with ALs in AS patients with kyphosis and that it might be a possible risk factor for the development of ALs. Moreover, both inflammatory and mechanical ALs patients had similarly low PI.Key Points• Low PI was closely associated with ALs in AS patients with kyphosis and might be a possible risk factor for development of ALs.• Either inflammatory or mechanical ALs patients had similar low PI.

Development of a Three-Dimensional Finite Element Model of Thoracolumbar Kyphotic Deformity following Vertebral Column Decancellation.

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.

Cryptotanshinone Protects Cartilage against Developing Osteoarthritis through the miR-106a-5p/GLIS3 Axis.

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.

Positioning thoracic pedicle screw entry point using a new landmark: a study based on 3-dimensional computed tomographic scan.

STUDY DESIGN: A novel method to identify the entry point. OBJECTIVE: To quantify the position of thoracic pedicle screw entry points on the lamina at various segments of the thoracic vertebrae in normal subjects and patients with adolescent idiopathic scoliosis and propose a new technique to select entry points using a new landmark. SUMMARY OF BACKGROUND DATA: Thoracic pedicle screws have been widely used in thoracic surgery, and the placement of pedicle screws has been studied extensively. However, there are only qualitative studies on selecting the entry point, and no study has quantified the position of entry points. METHODS: A retrospective study using 3-dimensional computed tomographic reconstruction techniques were used to study the morphology of thoracic vertebrae in 110 adolescents (56 cases of adolescent idiopathic scoliosis and 54 normal subjects). A quantitative area was used to select the entry point. Thoracic pedicle screw entry point was determined using the new landmark as reference and thoracic pedicle screws were placed in 21 patients. Postoperative computed tomographic scanning was performed to assess the safety and effectiveness of this entry point selection technique. RESULTS: We determined that the accuracy of pedicle screw placing after positioning entry point using the quantitative area was significantly superior to that after positioning entry point using the traditional method (P < 0.05). CONCLUSION: The new technique quantifies the position of each thoracic pedicle screw entry point and it is convenient, easy to operate, and has relatively high accuracy of screw placement. This positioning technique can provide safe and accurate clinical guidance for selecting thoracic pedicle screw entry point.