Regulatory mechanism of FCGR2A in macrophage polarization and its effects on intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) poses a significant health burden, necessitating a deeper understanding of its molecular underpinnings. Transcriptomic analysis reveals 485 differentially expressed genes (DEGs) associated with IDD, underscoring the importance of immune regulation. Weighted gene co-expression network analysis (WGCNA) identifies a yellow module strongly correlated with IDD, intersecting with 197 DEGs. Protein-protein interaction (PPI) analysis identifies ITGAX, MMP9 and FCGR2A as hub genes, predominantly expressed in macrophages. Functional validation through in vitro and in vivo experiments demonstrates the pivotal role of FCGR2A in macrophage polarization and IDD progression. Mechanistically, FCGR2A knockdown suppresses M1 macrophage polarization and NF-κB phosphorylation while enhancing M2 polarization and STAT3 activation, leading to ameliorated IDD in animal models. This study sheds light on the regulatory function of FCGR2A in macrophage polarization, offering novel insights for IDD intervention strategies. KEY POINTS: This study unveils the role of FCGR2A in intervertebral disc (IVD) degeneration (IDD). FCGR2A knockdown mitigates IDD in cellular and animal models. Single-cell RNA-sequencing uncovers diverse macrophage subpopulations in degenerated IVDs. This study reveals the molecular mechanism of FCGR2A in regulating macrophage polarization. This study confirms the role of the NF-κB/STAT3 pathway in regulating macrophage polarization in IDD.

Hybrid transformer convolutional neural network-based radiomics models for osteoporosis screening in routine CT.

OBJECTIVE: Early diagnosis of osteoporosis is crucial to prevent osteoporotic vertebral fracture and complications of spine surgery. We aimed to conduct a hybrid transformer convolutional neural network (HTCNN)-based radiomics model for osteoporosis screening in routine CT. METHODS: To investigate the HTCNN algorithm for vertebrae and trabecular segmentation, 92 training subjects and 45 test subjects were employed. Furthermore, we included 283 vertebral bodies and randomly divided them into the training cohort (n = 204) and test cohort (n = 79) for radiomics analysis. Area receiver operating characteristic curves (AUCs) and decision curve analysis (DCA) were applied to compare the performance and clinical value between radiomics models and Hounsfield Unit (HU) values to detect dual-energy X-ray absorptiometry (DXA) based osteoporosis. RESULTS: HTCNN algorithm revealed high precision for the segmentation of the vertebral body and trabecular compartment. In test sets, the mean dice scores reach 0.968 and 0.961. 12 features from the trabecular compartment and 15 features from the entire vertebral body were used to calculate the radiomics score (rad score). Compared with HU values and trabecular rad-score, the vertebrae rad-score suggested the best efficacy for osteoporosis and non-osteoporosis discrimination (training group: AUC = 0.95, 95%CI 0.91-0.99; test group: AUC = 0.97, 95%CI 0.93-1.00) and the differences were significant in test group according to the DeLong test (p < 0.05). CONCLUSIONS: This retrospective study demonstrated the superiority of the HTCNN-based vertebrae radiomics model for osteoporosis discrimination in routine CT.

LumVertCancNet: A novel 3D lumbar vertebral body cancellous bone location and segmentation method based on hybrid Swin-transformer.

Lumbar vertebral body cancellous bone location and segmentation is crucial in an automated lumbar spine processing pipeline. Accurate and reliable analysis of lumbar spine image is expected to advantage practical medical diagnosis and population-based analysis of bone strength. However, the design of automated algorithms for lumbar spine processing is demanding due to significant anatomical variations and scarcity of publicly available data. In recent years, convolutional neural network (CNN) and vision transformers (Vits) have been the de facto standard in medical image segmentation. Although adept at capturing global features, the inherent bias of locality and weight sharing of CNN constrains its capacity to model long-range dependency. In contrast, Vits excel at long-range dependency modeling, but they may not generalize well with limited datasets due to the lack of inductive biases inherent to CNN. In this paper, we propose a deep learning-based two-stage coarse-to-fine solution to address the problem of automatic location and segmentation of lumbar vertebral body cancellous bone. Specifically, in the first stage, a Swin-transformer based model is applied to predict the heatmap of lumbar vertebral body centroids. Considering the characteristic anatomical structure of lumbar spine, we propose a novel loss function called LumAnatomy loss, which enforces the order and bend of the predicted vertebral body centroids. To inherit the excellence of CNN and Vits while preventing their respective limitations, in the second stage, we propose an encoder-decoder network to segment the identified lumbar vertebral body cancellous bone, which consists of two parallel encoders, i.e., a Swin-transformer encoder and a CNN encoder. To enhance the combination of CNNs and Vits, we propose a novel multi-scale attention feature fusion module (MSA-FFM), which address issues that arise when fusing features given at different encoders. To tackle the issue of lack of data, we raise the first large-scale lumbar vertebral body cancellous bone segmentation dataset called LumVBCanSeg containing a total of 185 CT scans annotated at voxel level by 3 physicians. Extensive experimental results on the LumVBCanSeg dataset demonstrate the proposed algorithm outperform other state-of-the-art medical image segmentation methods. The data is publicly available at: https://zenodo.org/record/8181250. The implementation of the proposed method is available at: https://github.com/sia405yd/LumVertCancNet.

Retraction Notice to: circ_001653 Silencing Promotes the Proliferation and ECM Synthesis of NPCs in IDD by Downregulating miR-486-3p-Mediated CEMIP.

[This retracts the article DOI: 10.1016/j.omtn.2020.01.026.].

microRNA-129-5p shuttled by mesenchymal stem cell-derived extracellular vesicles alleviates intervertebral disc degeneration via blockade of LRG1-mediated p38 MAPK activation.

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been reported to deliver exogenous microRNAs (miRNAs or miRs) to reduce the progression of intervertebral disc degeneration (IDD). The purpose of the current study was to investigate the therapeutic potential of MSC-derived EVs delivering miR-129-5p in IDD. First, miR-129-5p expression levels were quantified in nucleus pulposus (NP) tissues of IDD patients. An IL-1ß-induced NP cell model with IDD was then established, and co-cultured with EVs derived from MSCs that had been transfected with miR-129-5p mimic or inhibitor to elucidate the effects of miR-129-5p on cell viability, apoptosis, and ECM degradation. In addition, RAW264.7 cells were treated with the conditioned medium (CM) of NP cells. Next, the expression patterns of polarization markers and those of inflammatory factors in macrophages were detected using flow cytometry and ELISA, respectively. Lastly, rat models of IDD were established to validate the in vitro findings. It was found that miR-129-5p was poorly-expressed in NP tissues following IDD. Delivery of miR-129-5p to NP cells by MSC-derived EVs brought about a decrease in NP cell apoptosis, ECM degradation and M1 polarization of macrophages. Moreover, miR-129-5p directly-targeted LRG1, which subsequently promoted the activation of p38 MAPK signaling pathway, thus polarizing macrophages toward the M1 phenotype. Furthermore, MSC-derived EVs transferring miR-129-5p relieved IDD via inhibition of the LRG1/p38 MAPK signaling in vivo. Altogether, our findings indicated that MSC-derived EVs carrying miR-129-5p confer protection against IDD by targeting LRG1 and suppressing the p38 MAPK signaling pathway, offering a novel theranostic marker in IDD.

circ_001653 Silencing Promotes the Proliferation and ECM Synthesis of NPCs in IDD by Downregulating miR-486-3p-Mediated CEMIP.

Functional changes of nucleus pulposus cells (NPCs) are considered to be the initiating factors of intervertebral disc degeneration (IDD). In this study, we investigated whether circular RNA homo sapiens (hsa)_circ_001653 (circ_001653) could bind to microRNA-486-3p (miR-486-3p) to regulate the biological properties of NPCs and the synthesis of extracellular matrix (ECM) in IDD. Initially, circ_001653 was highly expressed in isolated NPCs and degenerative NP tissues in close relation to the severity of IDD. To evaluate the effects of circ_001653 on cellular processes, we performed experiments in vitro and in vivo with altered expression of circ_001653 and miR-486-3p. An increased expression of circ_001653 in the NPCs and the degenerative NP tissues was directly associated with elevated apoptosis and an imbalance between anabolic and catabolic factors of the ECM. miR-486-3p regulated NPC proliferation and inhibited the expression of CEMIP, the cell migration-inducing hyaluronan binding protein. circ_001653 regulated miR-486-3p expression, functioning in NPCs to upregulate CEMIP, whereas circ_001653 silencing alleviated IDD in the mouse model. Altogether, circ_001653 downregulation could potentially alleviate NPC apoptosis and the metabolic imbalance of the ECM through the miR-486-3p/CEMIP axis. These mechanistic insights may present new therapeutic targets for the treatment of IDD.

SPAG9 is overexpressed in osteosarcoma, and regulates cell proliferation and invasion through regulation of JunD.

Sperm-associated antigen 9 (SPAG9) is a recently characterized oncoprotein that is considered to be involved in several forms of malignant tumor. However, its biological function and expression pattern in human osteosarcoma have not yet been elucidated. In the present study, SPAG9 expression was analyzed in 58 cases of human osteosarcoma by immunohistochemistry. The results demonstrated that SPAG9 was overexpressed in 63.8% (37/58) of osteosarcoma tissues, while normal bone tissues exhibited negative SPAG9 expression. SPAG9 small interfering RNA was employed in the U2OS cell line, which has high endogenous expression, and SPAG9 transfection was performed in the MG63 cell line, which has low endogenous expression. MTT and Matrigel invasion assays demonstrated that SPAG-9-knockdown significantly reduced U2OS cell invasion and proliferation, while SPAG9 transfection enhanced MG63 cell proliferation and invasion. Furthermore, it was observed that SPAG9 positively regulated cyclin D1, phosphorylated-c-Jun NH2-terminal kinase (JNK) and JunD expression. Treatment with the JNK inhibitor, SP600125, abolished the upregulatory effect of SPAG9 on JunD. Taken together, the present study identified SPAG9 as a critical oncoprotein involved in osteosarcoma proliferation and invasion, possibly functioning through JNK-JunD signaling.

Downregulation of microRNA-586 Inhibits Proliferation, Invasion and Metastasis and Promotes Apoptosis in Human Osteosarcoma U2-OS Cell Line.

In this study, we aim to examine the association of microRNA-586 (miR-586) with osteosarcoma (OS) cell proliferation, apoptosis, invasion, and metastasis. U2-OS cell lines were divided into 4 groups: an miR-586 group, anti-miR-586 group, control group (empty plasmid) and blank group (no plasmid). qRT-PCR was used to detect miR-586 expression, cell counting kit-8 and EdU assays to detect cell proliferation, flow cytometry to detect cell cycle distribution, Annexin V/PI double staining to detect cell apoptosis, and the Transwell assay to detect cell invasion and metastasis. miR-586 expression was significantly higher in the miR-586 group but significantly lower in the anti-miR-586 group compared with the control and blank groups. Cell proliferation at 2-5 days after cell transfection and the EdU-positive cell number increased obviously in the miR-586 group but decreased clearly in the anti-miR-586 group. In the miR-586 group, cells at G0/G1 stage and apoptosis cells significantly decreased, while cells at G2/M and S stages and invasive and metastatic cells significantly increased compared to the control and blank groups; however, opposite trends were found in the anti-miR-586 group. Downregulation of miR-586 expression in OS may inhibit cell proliferation, invasion and metastasis, and promote cell apoptosis.

MicroRNA-144 inhibits the proliferation, apoptosis, invasion, and migration of osteosarcoma cell line F5M2.

This study is aimed to investigate the role of microRNA-144 (miR-144) in osteosarcoma cell line F5M2 proliferation, apoptosis, invasion, and metastasis. Between 2007 and 2014, 66 cases of osteosarcoma samples in the corresponding adjacent normal tissue samples were selected from surgical resection or biopsy in the Department of Orthopedics, Shengjing Hospital, China Medical University. MiR-144 levels and Ezrin messenger RNA (mRNA) levels in osteosarcoma and the adjacent bone tissues were detected, and clinical and pathological features were analyzed. Exogenous miR-144 was transfected into human osteosarcoma cell lines at two different concentrations (low and high), and the expression levels of miR-144 and Ezrin protein between highly metastatic osteosarcoma cells and lowly metastatic osteosarcoma cells were compared. Real-time polymerase chain reaction (RT-PCR) and Western blot were used for detecting the expression levels of miR-144 or Ezrin protein, respectively. Cell proliferation was measured by methylthiazol tetrazolium (MTT) assay. Cell invasion and migration was evaluated by Transwell assays. Finally, flow cytometry was employed to determine the cell apoptosis. MiR-144 expression in osteosarcoma tissue was significantly lower than that in the surrounding normal bone tissue (P < 0.001), while Ezrin mRNA expression in osteosarcoma tissue was significantly higher than that in the surrounding normal bone tissue (P < 0.001); correlation analysis showed a significant negative correlation between miR-144 and Ezrin mRNA levels (r = 0.982, P < 0.001). MiR-144 and Ezrin mRNA expressions were significantly related with cell metastasis (P < 0.05) but were not related with other clinical factors such as gender, age, tumor location, tumor size, Enneking staging, and Dahlin's histological classification. The results of RT-PCR showed that the expression level of miR-144 in osteosarcoma cells increased after transfected with exogenous miR-144 mimics, and this increase positively correlated with the transfection concentration of miR-144 mimics. Furthermore, Western blotting revealed a significant and dose-dependent decrease in Ezrin protein levels in F5M2 cells transfected with miR-144. MTT and Transwell assays showed that the invasion and metastasis of F5M2 cells was significantly decreased following exogenous overexpression of miR-144. Our study supports the view that the miR-144 may regulate Ezrin protein expression by inhibiting the invasion and metastasis of osteosarcoma cells.

Persistent hypoalbuminemia is a predictor of outcome in cervical spinal cord injury.

BACKGROUND CONTEXT: Hypoalbuminemia is associated with increased morbidity and mortality in various clinical settings and several major diseases. Albumin has multiple physiologic properties that could be beneficial in central nervous system injury. PURPOSE: We sought to determine if albumin is associated with patient outcome after cervical spinal cord injury by conducting a retrospective analysis. STUDY DESIGN/SETTING: A retrospective study of cervical spinal cord injury (CSCI) patients was conducted to investigate if serum albumin levels and other characteristics influence outcome (mechanical ventilation and death). PATIENT SAMPLE: A total of 178 consecutive patients were included in the present study. OUTCOME MEASURES: Demographic data were recorded, including age, gender, smoking history, time from injury to admission, severity of neurologic injury, neurologic level of lesion, mechanism of neurologic injury, Glasgow Coma Score, vitals in the Orthopedic Department, the occurrence of early surgical intervention (48 hours after injury), and daily serum albumin levels. METHODS: No funds were received in support of this work. No specific conflicts of interest were involved in this article. Serum albumin levels and other characteristics known to influence outcome were included in univariate statistical analyses and the multiple logistic regression model to analyze the relationship with mechanical ventilation and death after cervical injury. RESULTS: Approximately 41.0% (73/178) of patients had complete spinal cord injury (ASIA A), 36.5% (65/178) of patients required mechanical ventilation, and 8.4% (15/178) of patients died within the first month after injury. Albumin remained lower than 30 g/L for a period of time (≥5 days) in patients with an unfavorable outcome (patients requiring mechanical ventilation or who had died). Multiple logistic regression analysis identified age (>50 years), persistent hypoalbuminemia (<30 g/L and ≥5 days), C5 and above neurologic injury, and ASIA A as predictors for mechanical ventilation. In addition, persistent hypoalbuminemia, ASIA A, and C4 and above neurologic injury were significantly associated with death. CONCLUSION: Similar to the ASIA scale and neurologic level, persistent hypoalbuminemia seems to be an independent predictor of outcome in patients with CSCI. Thus, a randomized trial assessing albumin in the treatment of cervical spinal cord injury is warranted.

Tyrosine phosphorylation is essential for DSCAML1 to promote dendrite arborization of mouse cortical neurons.

Dendritic self-avoidance is critical for appropriate dendrite arborization. We herein examined the role of Down syndrome cell adhesion molecule like-1 (DSCAML1) in regulating dendritic self-avoidance and that of tyrosine phosphorylation in mediating the effects of DSCAML1. Knocking down DSCAML1 in newborn mouse cortical neurons compromised dendritic self-avoidance as evidenced by dendritic fasciculation and increased dendritic self-crossing. Introduction of a DSCAML1(Y1808F) mutant into the DSCAML1-knocked down neurons failed to reverse the abnormal dendritic arborization. These results suggest that DSCAML1 promotes dendritic self-avoidance in cortical neurons, and that phosphorylation at Y1808 is essential in mediating the effects of DSCAML1.

C1 posterior arch crossing screw fixation for atlantoaxial joint instability.

STUDY DESIGN: Anatomical measurements and in vitro biomechanical testing were performed to evaluate a new method for posterior C1 fixation. OBJECTIVE: This study sought to assess C1 posterior arch crossing screw fixation for posterior C1-C2 fixation, using anatomical measurements and biomechanical testing with traditional C1 pedicle screws (PS) in a cadaveric model. SUMMARY OF BACKGROUND DATA: Atlantoaxial instability often requires surgery, and the current methods for atlas fixation incur some risk to the vascular and neurological tissues. Thus, new, effective, and safe methods are needed for salvage operations. METHODS: Morphometric analysis of the C1 posterior arch was performed using 3-dimensional computed tomography. Six fresh ligamentous human cervical spines (C0-C4) were evaluated for their biomechanics. The specimens were tested in their intact condition and after stabilization (C1-C2 PS, C1 posterior arch screws [PAS] with C2 PS) and injury due to 1.5 N·m of pure moment in flexion, extension, lateral bending, and axial rotation. During testing, 3-dimensional angular motion was measured with a motion capture platform (Vicon Nexus). Data for all scenarios were recorded, and statistical analysis was performed. RESULTS: Anatomical assessment indicated that 91.51% of C1 posterior tubercles exceeded 7 mm in thickness, 93.40% had a width of the posterior arch of greater than 3.5 mm, and 65.57% had a unilateral screw length of greater than 15 mm, indicating that the posterior arch fixation could be achieved by two 3.5 × 15-mm screws placed in a crossed manner. Twenty-two cases (11%) were not suitable for crossing screw placement because the posterior arch was flat and the entry point was present on the same side. Biomechanical testing showed that the PS and PAS rod-screw systems significantly reduced flexibility in flexion, extension, and rotation compared with the intact position. For lateral bending, there was a trend for the C1 PS and PAS systems toward decreased flexibility in comparison with the intact position. At the same time, C1 PAS decreased C1-C2 movement by 33.0% in left bending (P = 0.171) and 24.4% in right bending (P = 0.095); however, no significant difference was observed for left bending with C1 PAS compared with C1 PS, and the C1 PS and PAS systems significantly reduced the flexibility more than destabilization. CONCLUSION: Crossing screw fixation of the C1 posterior arch is straightforward and imposes little risk of injury to the neural and vascular structures as long as the implants remain intraosseous. According to the results of our anatomical and biomechanical study, C1 posterior arch crossing screw fixation may constitute an alternative method for posterior atlantoaxial fixation. LEVEL OF EVIDENCE: 3.

Developmental expression patterns of kainate receptors in the mouse spinal cord.

Kainate receptors, a subtype of ionotropic glutamate receptors, perform important functions in the spinal cord. This study aimed to examine the expression pattern of various kainate receptor subunits in the spinal cord over different stages of development. The regional distribution and levels of Grik1-5 mRNAs, which encode kainate receptor subunits, were examined in the spinal cord of embryonic, perinatal, and adult mice using in-situ hybridization and real-time PCR. At different developmental stages, the expression of Grik1-5 genes showed different regional distributions in the spinal cord. At E16.5, Grik2 and Grik3 were mainly expressed in the dorsal horns whereas Grik5 was expressed in the entire spinal cord. At P0 and P7, Grik2 expression accumulated at laminae II-IV, whereas Grik1 accumulated at the superficial laminae of the dorsal horns. At P30 and P60, the expression of Grik1-5 was concentrated in the superficial laminae of the dorsal horns. Development-related changes were observed in the expression pattern of Grik1-5. Grik5 was expressed in the entire spinal cord up to the perinatal period, whereas from P7 to adult stages, Grik5 expression was almost exclusively restricted to the dorsal horns. Similar observations were present with Grik1, Grik2, and Grik3. Consistently, quantitative determination of the expression levels of Grik1-5 was in accordance with the in-situ hybridization results. This age-related dynamic expression of kainate receptors may act as one driving force for the development of the anatomofunctional pattern and the maturation of the somatosensory circuitry in the spinal cord.

[Second measurement of three-dimensional CT reconstruction data for scoliosis orthopaedic surgery].

OBJECTIVE: To explore the clinical application and outcomes of preoperative second measurement of three-dimensional (3-D) CT reconstruction data for scoliosis orthopedic surgery. METHODS: Between August 2006 and March 2008, 11 patients with severe rigid scoliosis received surgery treatment, including 4 males and 7 females with an average age of 17.2 years (range, 15-19 years). Preoperative second measurement of 3-D CT reconstruction data was conducted to guide the surgery, including the angle and width of pedicle, the entry point, and the choice of screws whose lengths and diameters were suitable. A total of 197 pedicle screws were implanted. The operation time, blood loss, postoperative nerve function, and Cobb's angles at sagittal and coronal view were all recorded, and the postoperative CT scan was performed to assess the accuracy of pedicle screw insertion according to Andrew classification. RESULTS: Pedicle screws were implanted within 1-11 minutes (mean, 5.8 minutes), and the blood loss was 450-2 300 mL (mean, 1 520 mL). The postoperative X-ray films showed the correction rates of Cobb's angle were 68.5% in coronal view and 55.5% in sagittal view. The accuracy of pedicle screw insertion was rated as grade I in 77 screws (39.1%), grade II in 116 screws (58.9%), and grade III in 4 screws (2.0%) according to postoperative CT scan. All 11 cases were followed up 14 months to 2 years without any complications. CONCLUSION: Preoperative second measurement of 3-D CT reconstruction data can make the surgery process easy and accurate in treatment of severe scoliosis.

[The "wake-up correction" for preventing spinal cord injury in scoliosis surgery].

OBJECTIVE: To observe the effects of "wake-up correction" technique for preventing iatrogenic spinal cord injury in scoliosis surgery. METHODS: Twenty-one patients who had scoliosis with Cobb's angle 92 degrees - 145 degrees received operation of pedicle screw insertion in all or important vertebral bodies, release of stiff segments, decompression and osteotomy. All the patients were trained how to wake up before anesthesia. Maintenance of anesthesia was achieved with infusion of propofol at target-controlled concentration 3-4 mg/L and remifentanil at 0.15 microg/(kg.min). Fresh gas 2 L/min of N(2)O:O(2) 1:1 was inhaled during mechanical ventilation. Wake-up methods:the muscle relaxant was stopped injection 30 min before wake-up, decreasing propofol's target-controlled concentration to 1-2 mg/L and remifentanil to 0.05 - 0.10 microg/(kg x min). Once the spontaneous respiration returned, woke up the patients and asked them move both toes following our orders (the first wake-up). Then patients inhaled 6% sevoflurane in fresh gas 6 L/min (N(2)O:O(2) 1:1). When the end-tidal anesthetic gas concentration was arrived 1.3 - 1.5 MAC, all of the anesthetics were stopped. The correction operation was completed and the patient was woke up again (the second wake-up). Recorded data included time used to wake up, directive action returning time, whether the patient had memory of wake-up during operation when following up. RESULTS: All patients woke up with satisfaction. The time taken the first wake-up was (10.3 + or - 4.5) min, and for the second was (4.3 + or - 2.3) min. There were two patients who had slightly agitation during correction. There was no one who had neurological injury. There was no memory of wake-up and no pain in all patients during operation. Cobb' angle was corrected to 22 degrees - 38 degrees (average 29 degrees ), and the correction rate was 74%. CONCLUSION: The "wake-up correction" is effective and satisfactory by detecting the cord function in time.

Posterior fixation and fusion with atlas pedicle screw system for upper cervical diseases.

OBJECTIVE: To evaluate the feasibility, safety and efficacy of atlas pedicle screws system fixation and fusion for the treatment of upper cervical diseases. METHODS: Twenty-three consecutive patients with upper cervical disorders requiring stabilization, including 19 cases of atlantoaxial dislocation (4 congenital odontoid disconnections, 6 old odontoid fractures, 4 fresh odontoid fractures of Aderson II C, 3 ruptures of the C(1) transverse ligament, and 2 fractures of C(1)), 2 cases of C2 tumor (instability after the resection of the tumors), and 2 giant neurilemomas of C(2)-C(3)(instability after resection of the tumors), were treated by posterior fixation and fusion with the atlas pedicle screw system, in which the screws were inserted through the posterior arch of C1. The operative time, bleeding volume and complications were reported. All patients were immobilized without external fixation or with rigid cervical collars for 1-3 months. All patients were followed up and evaluated with radiographs and CT. RESULTS: In the 23 patients, 46 C(1) pedicle screws, 42 C(2) pedicle screws and 6 lower cervical lateral mass screws and 2 lower cervical pedicle screws were placed. The mean operative time and bleeding volume was 2.7 hours and 490 ml respectively. No intraoperative complications were directly related to surgical technique. No neurological, vascular or infective complications were encountered. All patients were followed up for 3-36 months (average 15 months). Firm bony fusion was documented in all patients after 3-6 months. One patient with atlas fracture showed anterior occipitocervical fusion. There was no implant failure. CONCLUSIONS: Posterior fixation and fusion of the atlas pedicle screw system is feasible and safe for the treatment of upper cervical diseases, and may be applicable to a larger number of patients.

[Comparison between gene therapy and gradual release carrier for bone morphogenetic protein-2 in repairing bone defects].

To compare the effects between gene therapy and gradual release carrier for bone morphogenetic protein-2 (BMP-2) in repairing bone defects, bone defects for 15 mm were created.on the bilateral radius in rabbits and treated with four kinds of implantations, ie, composite of transgeneic MSCs and PLA/PCL (Group A), composite of MSCs and gradual release carrier for BMP-2 (Group B), composite of MSCs and PLA/PCL (Group C), and PLA/PCL alone (Group D). After 4, 8, and 12 weeks of the operations, X-ray, histological examination, biomechanics analysis, and bone density measurement were conducted. Results showed that both osteoblasts and mesenchymal cells displayed strongly positive expression of BMP-2 in Group A after 4 weeks of the operation, the speed and quality of bone formation in Group A were much better than those in Group B. After 12 weeks of the operations, bone defects were completely repaired in Group A. BMP-2 gene therapy is really a good method to repair segmental bone defects.

[Effect of modified unilaterally-open expansive laminoplasty using bridge grafting and restructing posterior ligamentous complex methods on axial symptoms and cervical curvature change].

OBJECTIVE: To explore if the modified unilaterally-open expansive laminoplasty using bridge grafting and reconstructing posterior ligamentous complex methods is effective in preventing persisting axial symptoms, restriction of neck motion, and loss of cervical curvature. METHODS: From June 2000 to October 2005, 138 patients with cervical spondylotic myelopathy underwent this procedure. Of them, 78 who were followed for more than 2 years (group A) were included in this study. Another 69 patients who underwent conventional unilaterally open-door laminoplasty served as controls (group B). The JOA scores and the incidence of newly developed or deteriorated axial symptoms were recorded. Preoperative and postoperative ranges of neck motion were measured on lateral flexion and extension radiographs. Preoperative and postoperative cervical curvature indices were calculated according to Ishihara's method. RESULTS: The patients of group A were followed 24-44 months (mean 33 months), and the patients of group B were followed 24-53 months(mean 35 months). The operative time was 114+/-20 min in group A and 70+/-25 min in group B, showing statistically significant difference (P<0.05). The operative blood loss was 280+/-72 ml in group A and 210+/-80 ml in group B (P>0.05). According to JOA scoring, the average recovery rates were 67.0%+/-17.3% in group A and 65.0%+/-21.4% in group B (P>0.05). Postoperative development or deterioration of axial symptoms occurred in 12% of patients in group A and 51% of patients in group B, showing statistically significant difference (P<0. 05). Postoperative range of neck motion was 88.0%+/-10.1% of the preoperative one in group A and 64.0%+/-16.3% in group B (P< 0.05). There was no significant difference between preoperative (15.3+/-8.2) and postoperative (13.5+/-9.3) cervical curvature index in group A, whereas the mean value of postoperative index (11.1+/-5.7) was significantly smaller than that of preoperative one (17.2+/-13.5) in group B (P<0.05). CONCLUSION: This new procedure was less invasive to the posterior extensor mechanism than the conventional unilaterally-open laminoplasty and was effective in preventing postoperative morbidities.

[Application of atlas pedicle screw system fixation and fusion for treatment of upper cervical disease].

OBJECTIVE: To explore the feasibilities, methods, outcomes and indications of atlas pedicle screw system fixation and fusion for the treatment of upper cervical diseases. METHODS: From October 2004 to January 2006, 17 patients with upper cervical diseases were treated with atlas pedicle screw system fixation and fusion. There were 13 males and 4 females, ageing 19 to 52 years. Of 17 cases, there were 14 cases of atlantoaxial dislocation (including 3 cases of congenital odontoid disconnection,4 cases of old odontoid fracture, 2 cases of new odontoid fracture (type II C), 3 cases of rupture of the transverse ligament, and 2 cases of atlas fracture; 2 cases of tumor of C2; 1 case of giant neurilemoma of C2.3 with instability after the resection of tumors. JOA score before operation was 8.3+/-3.0. RESULTS: The mean operative time and bleeding amount were 2.7 hours (2.1-3.4 hours) and 490 ml (300-750 ml) respectively. No injuries to the vertebral artery and spinal cord were observed. The medial-superior cortex of lateral mass was penetrated by 1 C1 screw approximately 3 mm without affecting occipito-atlantal motions. All patients were followed up 3-18 months. The clinical symptoms were improved in some extents and the screws were verified to be in a proper position, no breakage or loosening of screw and rob occurred. All patients achieved a solid bone fusion after 3-6 months. JOA score 3 months after operation was 14.6+/-2.2. JOA improvement rates were 73%-91% (mean 82%). CONCLUSION: The atlas pedicle screw system fixation and fusion is feasible for the treatment of upper cervical diseases and has better outcomes, wider indications if conducted properly.

[Reconstruction of segmental bone defect by gene modified tissue engineering bone combined with vascularized periosteum].

OBJECTIVE: To evaluate the therapeutic effect of bone morphogenetic protein 2 (BMP-2) gene modified tissue engineering bone (GMB) combined with vascularized periosteum in the reconstruction of segmental bone defect. METHODS: Adenovirus carrying BMP-2 gene (Ad-BMP-2) was transfected into the isolated and cultured rabbit bone marrow stromal cells (MSCs). The transfected MSCs were seeded on bovine cancellous bone scaffolds (BCB) to construct gene modified tissue engineering bone (GMB). The bilateral rabbits radial defects (2.5 cm long) were created as animal model. The rabbits were divided into five groups to reconstruct the defects with CMB combined with vascularized periosteum (group A); or GMB combined with vascular bundle implantation (group B); or GMB combined with free periosteum (group C); or GMB only (group D); or BCB scaffolds only (group E). Angiogenesis and osteogenesis were observed by X-ray, histological examination, biomechanical analysis and capillary ink infusion. RESULTS: In group A, the grafted GMB was revascularized rapidly. The defect was completely reconstructed at 8 weeks. The mechanism included both intramemerbrane and endochondral ossification. In group B, the vascular bundle generated new blood vessels into the grafted GMB, but the osteogenesis process was slow in the central zone, which healed completely at 12 weeks. In group C, the free graft of periosteum took at 4 weeks with angiogenesis. The thin extremal callus was formed at 8 weeks and the repairing process almost finished at 12 weeks. Better osteogenesis was found in group D than in group E, due to the present of BMP2 gene-transfected MSCs. The defects in group D were partial repaired at 12 weeks with remaining central malunion zone. The defects in group E should nonunion at 12 weeks with only fibre tissue. CONCLUSIONS: BMP-2 gene modified tissue engineering bone combined with vascularized periosteum which provides periosteum osteoblasts as well as blood supply, has favorable ability of osteogenesis, osteoinduction and osteoconduction. It is an ideal method for the treatment of segmental bone defect.