Integrin αVß3 antagonist-c(RGDyk) peptide attenuates the progression of ossification of the posterior longitudinal ligament by inhibiting osteogenesis and angiogenesis.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL), an emerging heterotopic ossification disease, causes spinal cord compression, resulting in motor and sensory dysfunction. The etiology of OPLL remains unclear but may involve integrin αVß3 regulating the process of osteogenesis and angiogenesis. In this study, we focused on the role of integrin αVß3 in OPLL and explored the underlying mechanism by which the c(RGDyk) peptide acts as a potent and selective integrin αVß3 inhibitor to inhibit osteogenesis and angiogenesis in OPLL. METHODS: OPLL or control ligament samples were collected in surgery. For OPLL samples, RNA-sequencing results revealed activation of the integrin family, particularly integrin αVß3. Integrin αVß3 expression was detected by qPCR, Western blotting, and immunohistochemical analysis. Fluorescence microscopy was used to observe the targeted inhibition of integrin αVß3 by the c(RGDyk) peptide on ligaments fibroblasts (LFs) derived from patients with OPLL and endothelial cells (ECs). The effect of c(RGDyk) peptide on the ossification of pathogenic LFs was detected using qPCR, Western blotting. Alkaline phosphatase staining or alizarin red staining were used to test the osteogenic capability. The effect of the c(RGDyk) peptide on angiogenesis was determined by EC migration and tube formation assays. The effects of the c(RGDyk) peptide on heterotopic bone formation were evaluated by micro-CT, histological, immunohistochemical, and immunofluorescence analysis in vivo. RESULTS: The results indicated that after being treated with c(RGDyk), the osteogenic differentiation of LFs was significantly decreased. Moreover, the c(RGDyk) peptide inhibited the migration of ECs and thus prevented the nutritional support required for osteogenesis. Furthermore, the c(RGDyk) peptide inhibited ectopic bone formation in mice. Mechanistic analysis revealed that c(RGDyk) peptide could inhibit osteogenesis and angiogenesis in OPLL by targeting integrin αVß3 and regulating the FAK/ERK pathway. CONCLUSIONS: Therefore, the integrin αVß3 appears to be an emerging therapeutic target for OPLL, and the c(RGDyk) peptide has dual inhibitory effects that may be valuable for the new therapeutic strategy of OPLL.

Exosomal miR-140-5p inhibits osteogenesis by targeting IGF1R and regulating the mTOR pathway in ossification of the posterior longitudinal ligament.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) is a disabling disease whose pathogenesis is still unclear, and there are no effective cures or prevention methods. Exosomal miRNA plays an important role in the osteogenesis of ectopic bone. Therefore, we focused on the downregulation of miR-140-5p in OPLL cell-derived exosomes to explore the mechanism by which exosomal miR-140-5p inhibits osteogenesis in OPLL. RESULTS: Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and exosomal markers. Exosomal RNA was extracted to perform miRNA sequencing and disclose the differentially expressed miRNAs, among which miR-140-5p was significantly downregulated. Confocal microscopy was used to trace the exosomal miR-140-5p delivered from OPLL cells to human mesenchymal stem cells (hMSCs). In vitro, we verified that exosomal miR-140-5p inhibited the osteoblast differentiation of hMSCs by targeting IGF1R and suppressing the phosphorylation of the IRS1/PI3K/Akt/mTOR pathway. In vivo, we verified that exosomal miR-140-5p inhibited ectopic bone formation in mice as assessed by micro-CT and immunohistochemistry. CONCLUSIONS: We found that exosomal miR-140-5p could inhibit the osteogenic differentiation of hMSCs by targeting IGF1R and regulating the mTOR pathway, prompting a further potential means of drug treatment and a possible target for molecular therapy of OPLL.

Aponeurosis discission, a low-detergent method for tissue-engineered acellular ligament scaffolds.

Detergent treatment is the most commonly used method for the decellularization of ligaments and tendon grafts. However, it is well recognized that detergent treatment can also adversely affect the extracellular matrix. This study found that discission into the aponeurosis layer of the patellar tendon (PT) before decellularization is conducive to extracting cells from the PT using a low quantity of detergent in a short time period. The acellular aponeurosis discission ligament (AADL) retains its native collagen fibril structure and mechanical properties. Moreover, the PT retained cell and tissue compatibility in vitro and in vivo. After implantation into a defective allogeneic PT, we found that the AADL healed well in the host, and its collagen structure exhibited gradual improvement 12 months after implantation with satisfactory reconstruction. IMPACT: The aponeurosis of tendons/ligaments is the main barrier to achieving complete decellularization, and it thus prevents complete recellularization for applications in tissue engineering. Aponeurosis can obstruct the removal of cell components. We found that excising the aponeurosis before decellularization allows for the removal of cellular components with a reduced amount of detergent, thus improving the biological properties of the acellular ligament. To the best of our knowledge, no similar studies have been performed. Graphical abstract.

Traumatic cervical spinal cord injury: relationship of MRI findings to initial neurological impairment.

PURPOSE: To quantify the degree of available space for the cord and cord swelling in patients following traumatic cervical spinal cord injury (TCSCI), and to assess the relationship among the available space for the cord, cord swelling, and the severity of neurological impairment. METHODS: This study included 91 patients. The following indexes were measured by two blinded observers: maximum cord available area (CAAmax) and maximum cord swelling area (CSAmax). The American Spinal Injury Association (ASIA) impairment scale (AIS) grades were used to evaluate the extent of neurological injury. Relationship among CAAmax, CSAmax, and initial AIS grades was assessed via univariate and multivariate analyses. RESULTS: Patients who were AIS grade A (complete injury) demonstrated significantly greater median CAAmax and CSAmax than AIS grade C or D (incomplete injury) (P < 0.01). Multivariate analysis identified only CAAmax (OR 20.88 [95% CI 1.50-291.21]; P = 0.024) and CSAmax (OR 17.84 [95% CI 1.15-276.56]; P = 0.039) were identified as independently influencing the likelihood of complete injury at the initial assessment. The classification accuracy was best for CAAmax and CSAmax; areas under the curve were 0.8998 (95% CI 0.7881-1.0000) and 0.9167 (95% CI 0.8293-1.0000), respectively. CONCLUSION: The present study provides a novel radiologic method for identifying the severity of TCSCI with T2-weighted MRI findings. Greater available space for the cord (CAAmax > 38%) and cord swelling (CSAmax > 29%) can be used to identify patients at risk for TCSCI and both imaging characteristics are associated with an increased likelihood of severe neurological deficits. LEVEL OF EVIDENCE: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Three-dimensional reduction method with a modified C2 isthmus screw in irreducible atlantoaxial dislocation: a technical note.

BACKGROUND: Three-dimensional reduction plays a vital role in surgical reduction of irreversible atlantoaxial dislocation (IAAD). However, the most commonly used combination of C1 pedicle screw (PS) or lateral mass screw (LMS) and C2 PS or isthmus screw often fails to achieve satisfactory reduction at one time. The difficulty is usually caused by short anteroposterior and vertical distance between heads of C1 and C2 screws, which lack enough space for reduction operation. The objective of this study is to describe a three-dimensional reduction method with a modified C2 isthmus screw and to illustrate its advantage and effectiveness for IAAD. METHODS: Twelve patients with IAAD underwent reduction and fixation with modified C2 isthmus screw combined with C1 PS or LMS, fusion with autologous bone graft. The insertion point was lateral to the intersection of caudal edge of C2 lamina and lateral mass, with a trajectory towards C2 isthmus, via lateral mass. The three-dimensional reduction was achieved through pulling and distracting. Radiographic evaluation included anteroposterior and direct distance between different insertion points, the occipitoaxial angle (O-C2A), clivus-canal angle (CCA) and cervicomedullary angle (CMA). Clinical outcomes evaluation included the Japanese Orthopaedic Association (JOA) score, Visual analog scale (VAS) and Neck Disability Index (NDI). RESULTS: All the patients maintained effective reduction during the follow-up. The anteroposterior and direct distance was significantly higher in modified C2 isthmus screw than C2 PS whether combined with C1 PS or LMS (P < 0.05). The degree of O-C2A, CCA and CMA, JOA score, NDI, and VAS were significantly improved after the surgery (P < 0.05). CONCLUSIONS: Three-dimensional reduction method with a modified C2 isthmus screw is effective and safe in managing IAAD. It can increase the anteroposterior and vertical distance between the heads of C1 and C2 screws, which is benefit for the three-dimensional reduction operation of IAAD.

Treatment for tuberculosis of the subaxial cervical spine: a systematic review.

PURPOSE: To systematically review the clinical manifestations and treatment outcomes of patients with subaxial cervical spinal tuberculosis (SCS-TB) and evaluate the current evidence for surgical or nonsurgical treatment. METHOD: A systematic review was performed using the PubMed, ScienceDirect, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Studies published in English from January 2000 to December 2018 were included in the search. A reference lists search of relevant articles was also conducted for other potential references. The risk of bias was assessed with the 13-item criteria recommended by the Cochrane Back and Neck Group and the Methodological Index for Non-Randomized Studies. RESULTS: Fifteen articles were included with a total of 456 patients, of which only 1 study was randomized and fourteen were nonrandomized. The most common symptom reported was neck pain and stiffness, and the most common segment involved was C5. Of the 456 patients, 329 (72.1%) were treated surgically. Most experienced neurologic recovery after surgery. Instrumentation resulted in maintenance of the correction of alignment throughout the follow-up period. The use of radical debridement is still in debate. CONCLUSIONS: Anti-TB therapy is necessary for all SCS-TB patients, including those underwent surgical management. For patients with neurological dysfunction, the surgical method with decompression and instrumentation could provide better cervical spinal alignment and stability. For adult, the radical debridement remains in debate, while for children, radical debridement may cause the development of progressive kyphosis during growth. Larger randomized comparative studies with longer follow-up times are needed.

The m6A methyltransferase METTL3 promotes osteosarcoma progression by regulating the m6A level of LEF1.

Osteosarcoma(OS) is the most common and aggressive malignant bone sarcoma,which occurs in rapidly growing bones in children and adolescents. However, the underlying molecular mechanisms of OS development have not been fully illustrated. N6-Methyladenosine (m6A) is the most prevalent internal chemical modification of mRNAs, which is involved in many pathological processes in cancer development. However, its role and regulatory mechanism in OS remain unknown. In this study, we aimed to investigate the roles of m6A and its methyltransferase METTL3 in OS development. The results showed that m6A level for RNA methylation and the expression level of METTL3 were up-regulated in human OS tissues and OS cell lines. Functionally, lentivirus-mediated METTL3 silence in HOS and SAOS-2 cells inhibited the cell proliferation, migration and invasion ability. Further mechanism analysis suggested that METTL3 silence decreased the m6A methylation and total mRNA level of lymphoid enhancer-binding factor 1 (LEF1), followed by inhibited the activity of Wnt/ß-catenin signaling pathway. Moreover, LEF1 over-expression abrogates the repressive effects of METTL3 silence on the proliferation, migration and invasion abilities of OS cells. Together, these results revealed that the m6A methyltransferase METTL3 promotes osteosarcoma cell progression by regulating the m6A level of LEF1 and activating Wnt/ß-catenin signaling pathway.

Long Non-coding RNA XIST May Influence Cervical Ossification of the Posterior Longitudinal Ligament Through Regulation of miR-17-5P/AHNAK/BMP2 Signaling Pathway.

Long non-coding RNAs (lncRNAs) play an important role in the development of bone-related diseases. This study was conducted to investigate the role and mechanism of lncRNA X inactive specific transcript (XIST) in the occurrence of cervical ossification of the posterior longitudinal ligament (OPLL). Here, primary human ligament fibroblasts cells (LFCs) were isolated from 30 cases of OPLL and 30 normal cervical posterior longitudinal ligament (non-OPLL) tissues to perform the qPCR and Western blot assay. We found that the mRNA level of lncRNA XIST was significantly increased in OPLL LFCs compared to non-OPLL LFCs. By bioinformatics analysis, we found that lncRNA XIST has four binding sites for miR-17-5p and found that the mRNA level of miR-17-5p was also significantly decreased in OPLL LFCs compared to non-OPLL LFCs. Since AHNAK is the target gene of miR-17-5p, we further found that the expression of AHNAK was significantly reduced in non-OPLL LFCs after being transfected with miR-17-5p mimic. The qPCR results showed that the mRNA expressions of BMP2 and Runx2 were significantly decreased. After being transfected with lncRNA XIST siRNA in the non-OPLL LFCs, the mRNA levels of lncRNA XIST, AHNAK, BMP2, and Runx2 were significantly decreased and the phosphorylated protein of Smad1/5/8 was reduced. After being cultured by mechanical vibration, the mRNA levels of lncRNA XIST, AHNAK, BMP2, Runx2, COL1, OC, OPN, and Phospho1 were significantly increased, but the mRNA expression of miR-17-5p was significantly decreased. The expression of phosphorylated Smad1/5/8 protein was also significantly increased. Together, this study was the first to determine that XIST gene inhibition plays an important role in the occurrence of cervical OPLL, through the mechanism of regulation of miR-17-5P/AHNAK/BMP2 signaling pathway. Thus, XIST may be a potential target that could be modulated for the treatment of cervical OPLL.

Anterior controllable antidisplacement and fusion surgery for the treatment of multilevel severe ossification of the posterior longitudinal ligament with myelopathy: preliminary clinical results of a novel technique.

PURPOSE: Although anterior and posterior decompression surgery are both reported to treat patients with myelopathy caused by ossification of the posterior longitudinal ligament (OPLL). The surgical strategy of the disease is still controversial when the OPLL is multilevel and severe. This present study reports the preliminary clinical results of a novel technique named anterior controllable antidisplacement and fusion (ACAF) for the treatment of multilevel-severe OPLL with myelopathy. METHODS: A series of 15 patients with cervical myelopathy caused by compression of multilevel severe OPLL were enrolled. All the patients underwent ACAF after thorough surgical designing based on preoperative imaging. The patients were followed for a mean follow-up duration of 9 months in this study. The main surgical procedures include discectomy of the involved levels, thinning of the anterior part of the involved vertebrae, intervertebral cages, anterior plate and screws installation, bilateral osteotomies of the vertebrae, and antedisplacement of the vertebrae-OPLL complex (VOC). The Japanese Orthopaedic Association (JOA) scales, Visual Analog Scale (VAS) were studied. And the pre- and postoperative radiological parameters, and surgical complications were also investigated. RESULTS: Postoperative CT and MRI showed complete decompression of the cord by antidisplacement of the VOC. Restoration of neurological defects was confirmed at the last follow-up assessment. Bone fusion was confirmed by CT at 6 months follow-up. No specific complications were identified that were associated with this technique. CONCLUSIONS: The present study demonstrates that excellent postoperative outcome can be achieved with the use of the ACAF. Though further study is required to confirm the conclusion, this novel technique has the potential to serve as an alternative surgical technique for the treatment of cervical OPLL. These slides can be retrieved under Electronic Supplementary Material.

[Early diagnosis of myelopathy hand improves efficacies of surgical treatment of cervical spondylotic myelopathy].

OBJECTIVE: To evaluate the value of early diagnosis of myelopathy hand in improving the efficacies of surgical treatment of cervical spondylotic myelopathy. METHODS: Analyses were conducted for 118 cases of cervical spondylotic myelopathy at Department of Orthopedics, Changzheng Hospital and Zhabei Campus from January 2009 to November 2012. They were diagnosed with myelopathy hand and classified by finger escape sign, 10-second grip and release test of fist along with electromyography of ill limb to evaluate the movement function of hands . They were divided into early diagnosis group with myelopathy hand (A, n = 62) and routine diagnosis group without myelopathy hand (B, n = 56) . All patients with cervical spondylotic myelopathy underwent anterior corpectomy decompression and fusion. The average follow-up period was up to 4. 1 years. Modified Japanese Orthopedic Association (JOA) score was used to evaluate neurological function preoperation and 48 months postoperation respectively. T-test of SPSS statistical software 13. 0 was used to analyze the inter-group difference of JOA scores before and after surgery. RESULTS: There were no inter-group significant differences in age, gender or smoking ratio. The JOA scores of groups A and B were 10. 1 ± 2. 3, 14. 9 ± 2. 0; 9. 8 ± 3. 1, 12. 1 ± 2. 3 before surgery and 48 months postoperation and the increase of JOA scores were 4. 8 ± 0. 9, 2. 3 ± 0. 6. The inter-group differences between JOA scores before and after surgery were statistically significant (P = 0. 00). And the inter-group differences between the increase of JOA scores at 48 months postoperation were statistically significant (P = 0. 00). CONCLUSION: Neurological function improves more for patients with cervical spondylotic myelopathy diagnosed with myelopathy hand in early stage than those diagnosed conventionally without myclopathy hand. And an early diagnosis of this sign may boost the surgical efficacies for cervical spondylotic myelopathy.

[Homogeneous spinal-shortening axial decompression procedure for tethered cord syndrome].

OBJECTIVE: Surgical detethering is a traditional treatment for symptomatic tethered cord syndrome. However, such complications as cerebrospinal fluid leakage and neurologic deterioration are common. Homogeneous spinal-shortening axial decompression (HSAD) is a modified procedure of monosegmental spinal-shortening osteotomy and it is a novel surgical alternative of reducing neural tension indirectly. The objective was to evaluate the surgical outcomes of HSAD for tethered cord syndrome. METHODS: The surgical outcomes were examined for 15 consecutive patients with tethered cord syndrome undergoing HSAD from April 2010 to July 2014. Improvements of neurological symptoms including urinary dysfunction, lower-extremity motor and sensory disturbances and/or gait abnormalities, low-back and/or lower-extremity pain, bowel incontinence and sexual dysfunction were evaluated. RESULTS: Their average follow-up period was 21.5 months. The length of spinal column shortening was 17.2 ± 2.9 mm. Urinary dysfunction (n = 9) was the most common residual deficit. All 9 patients with urological symptoms reported improvements, although deficits persisted at the last follow-up. All patients with lower-extremity motor dysfunction improved and 4 (50.0%) noted complete resolution of preoperative lower-extremity sensory symptoms. All patients reported immediate low-back or lower-extremity pain relief after HSAD. One patient reported improved sexual functioning and regained complete erectile capabilities. Two patients (11%) experienced less satisfactory symptomatic or functional benefit from HSAD. However, the main objective of surgery was to prevent further worsening of neurological status. Complete bone union at osteotomy site was noted in all cases at the last follow-up. CONCLUSION: As a novel surgical option for tethered cord syndrome, HSAD may avoid such complications as cerebrospinal fluid leakage or neurologic deterioration commonly encountered during traditional detethering surgery. All patients gain satisfactory functional outcomes without complications compared to their preoperative symptoms.

[Strengthened respiratory management for lower tracheostomy risks in patients with complete cervical spinal cord injury].

OBJECTIVE: To access the feasibility of reducing tracheostomy rates in patients with complete cervical spinal cord injury through a systemic respiratory management mode. METHODS: A retrospective review was performed for 239 patients on a systemic respiratory management mode after complete cervical spinal cord injury in Shanghai Changzheng Hospital from 2006 to 2012. Their demographic and clinical data, including age, gender, cause of injury, level of cervical spinal cord injuries, surgical approaches, tracheostomy rates and mortality rates, were collected and analyzed. Tracheostomy rates were compared with those of patients with complete cervical spinal cord injury. Tracheostomy rates were compared with those patients with complete cervical spinal cord injury from 1991 to 2005. The new respiratory management mode for patients with severe cervical spinal cord injury included maintaining adequate energy and water for patients, relieving bronchospasm, loosening phlegm, strengthening body-turning and backslapping, sputum aspiration with suction tube through nasal cavity or bronchofibroscope, strengthening deep breath and cough training, strict control of tracheostomy indications and short-term postoperative intubation reserving if necessary. RESULTS: 32 patients were implemented tracheostomy. The tracheostomy rate was 13.4%. 10 patients died, the mortality rate was 4.18%. However, the tracheostomy rate was 19.1% and mortality rate 21.4% from 1991 to 2005. The tracheostomy rate was significantly lower than before and survival rate improved significantly. CONCLUSION: The systemic respiratory management mode can effectively reduce tracheostomy rate of patients with complete cervical spinal cord injury and improve their survival rate.

C1 Transposterior Arch Lateral Mass Screws Combined With C2 Pedicle Screw and Rod Fixation for Pediatric Atlantoaxial Subluxation: A Minimal 10-Year Follow-up Outcome Analysis.

BACKGROUND AND OBJECTIVES: Although the short-term outcomes of the 1-step reduction and fixation technique using C1 transposterior arch lateral mass screws combined with C2 pedicle screw and rod fixation system for the treatment of pediatric atlantoaxial subluxation (AAS) have been satisfactory, its long-term outcomes and impact on spinal development are not well studied. This study was intended to assess the long-term reliability of this technique for pediatric AAS. METHODS: A retrospective case series study was conducted to analyze the minimum 10-year follow-up outcomes from 7 pediatric patients with AAS who underwent atlantoaxial fusion using the aforementioned technique. Quality of life and cervical range of motion were both measured thoroughly. In addition, vertical growth within the fusion construct (C1-2), overall cervical alignment, and subaxial cervical spine degeneration were evaluated radiographically. RESULTS: The mean age of the 7 patients was 8.14 ± 2.41 (6-12) years at the time of surgery. The mean follow-up period was 11.00 ± 1.15 (10-13) years. No patients presented identifiable intervertebral disk degeneration or segmental instability in the subaxial cervical spine except for 1 patient who showed mild intervertebral disk degeneration. Vertical growth did continue within the atlantoaxial complex after surgery (11.90% ± 2.37%); however, there was a decrease in the percentage of vertical growth compared with the corresponding normal populations of the same age and sex. Moreover, there was a significant decrease in the range of cervical extension and rotation motion, and the overall cervical alignment straightened at the latest follow-up. CONCLUSION: The 1-step reduction and fixation technique is a relatively reliable surgical technique for pediatric AAS, which does not adversely affect the postoperative quality of life or the subaxial cervical degeneration. Nevertheless, certain limitations, such as decreased cervical range of motion and changes in cervical alignment, should be concerned.

Increased miR-195 aggravates neuropathic pain by inhibiting autophagy following peripheral nerve injury.

UNLABELLED: Following peripheral nerve injury (PNI) microglia proliferates and adopts inflammation that contributes to development and maintenance of neuropathic pain. miRNAs and autophagy are two important factors in the regulation of inflammation. However, little is known about whether miRNAs regulate neuroinflammation and neuropathic pain by controlling autophagy. In the study, we demonstrated that miR-195 levels were markedly increased in rats subjected to L5 spinal nerve ligation (SNL). Upregulated miR-195 was also found in spinal microglia of rats with SNL. The overexpression of miR-195 contributed to lipopolysaccharide-induced expression of proinflammatory cytokines IL-1ß, TNF-α, and iNOS in cultured microglia. Upregulated miR-195 also resulted in increased mechanical and cold hypersensitivity after PNI, whereas miR-195 inhibition reduced mechanical and cold sensitivity. We further demonstrated that PNI significantly inhibited microglial autophagy activation, whereas miR-195 inhibitor treatment increased autophagy activation and suppressed neuroinflammation in vivo and in vitro. More important, autophagy inhibition impaired miR-195 inhibitor-induced downregulation of neuroinflammation and neuropathic pain. Additionally, ATG14 was identified as the functional target of miR-195. CONCLUSIONS: These data demonstrated that miR-195/autophagy signaling represents a novel pathway regulating neuroinflammation and neuropathic pain, thus offering a new target for therapy of neuropathic pain.

Surgical technique: Hemilaminectomy and unilateral lateral mass fixation for cervical ossification of the posterior longitudinal ligament.

BACKGROUND: Surgical approaches for cervical ossification of the posterior longitudinal ligament (OPLL) include anterior, posterior, or combined decompression with or without fusion. The goal of surgery is to decompress the spinal cord while maintaining the stability and sagittal alignment of the cervical spine. C5 palsy has been reported as a postoperative complication of cervical laminectomy or laminoplasty characterized as motor weakness of the muscles supplied with C5 nerve roots. Several studies have shown this phenomenon was partially attributable to posterior shift of spinal cord. DESCRIPTION OF TECHNIQUE: The rationale for choosing hemilaminectomy is to control postoperative posterior shift of the spinal cord and afford more stability by preserving ligamentous attachments and posterior bony elements as much as possible. After a fixation system of lateral mass screws and rods is installed unilaterally, laminae are removed from the underlying dura using a high-speed burr and Kerrison laminectomy rongeur on the other side. The spinous processes are preserved. PATIENTS AND METHODS: Patients with multilevel continuous/mixed cervical OPLL are good candidates for this technique. We retrospectively reviewed 146 patients who had multilevel continuous/mixed cervical OPLL and underwent surgery from January 2006 to January 2010. Neurologic condition was evaluated using the improvement ratio (IR) of the Japanese Orthopaedic Association (JOA) score for cervical myelopathy. RESULTS: The mean JOA score increased from 10 points before surgery to 14 points at last followup. The mean IR of neurologic function (JOA score) was 59%. C5 palsy was not observed in any patient after decompression, and cervical lordosis changed from 8.7° preoperatively to 9.1° at last followup. CONCLUSIONS: For patients with multilevel continuous/mixed cervical OPLL without fixed kyphosis, multilevel hemilaminectomy with unilateral lateral mass fixation is an effective alternative technique. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

[Clinical observation and evaluation of reasons for pseudarthrosis after anterior cervical fusion].

OBJECTIVE: To explore the causes of pseudarthrosis and evaluate the clinical neurological function and neck subaxial symptoms after anterior cervical fusion. METHODS: A total of 412 patients were followed up with an average of 5.4 years. The bone mineral density, bone graft trimming and placement, management of endplate, smoking and neck support fixation time were observed. Japanese Orthopedic Association (JOA) score was used to evaluate the changes of neurological functions and clinical outcomes. Visual analog scale (VAS) score was used to evaluate the neck subaxial symptoms. And pseudarthrosis was examined by flexion-extension radiography. SPSS statistical software 13.0 was used to evaluate the differences of JOA and VAS scores between pseudarthrosis and control groups. RESULTS: Among them, 37 cases of pseudarthrosis were observed. There were osteoporosis (n = 30 vs n = 119), cartilage end-plate punctuate hemorrhage (n = 18 vs n = 340), 25 and 43 cases with ineffective cervical external fixation (n = 25 vs n = 43) and smoking (n = 26 vs n = 87) in pseudarthrosis and fusion groups respectively. Significant differences existed in the above-mentioned indices between two groups. However, no significant difference existed in bone graft shape between two groups. There were significant differences in JOA and VAS scores between two groups. CONCLUSION: The causes of pseudarthrosis included decreased bone density, osteoporosis, over-curette of endplate, shortness of neck support fixation time and smoking. And pseudarthrosis may influence the long-term recovery of neurological functions or it is correlated significantly with neck symptoms.

[Clinical characteristics and early effective treatment for pulmonary infection after acute cervical spinal cord injury].

OBJECTIVE: To explore the clinical characteristics and early effective treatment for pulmonary infection after acute cervical spinal cord injury. METHODS: A total of 215 inpatients with acute cervical spinal cord injury were retrospectively analyzed. Their chest radiological films and blood profiles at discharge were analyzed. The fourth generation cephalosporin was used to treat pulmonary infection as soon as admission and the antibiotics switched according to the results of sputum culture and drug sensitive test. Incision of trachea was performed and breath supported by breath machine according to respiratory condition and blood gas analysis. All patients were turned over and slapped on the back in order to excrete phlegm in time. Sometimes bronchial lavage was used to excrete phlegm. The chest radiological examinations and sputum culture were performed twice one week. Once fungal infection was definite, specific antibiotic was used to treat infection. Three-liter bas and nasal feeding were used to improve the nutrition condition. Incision of trachea was closed as soon as possible. RESULTS: Pulmonary infection of 214 patients was finally cured. Among them, 43 suffered from pulmonary closure. One patient died from severe infection of Klebsiella pneumoniae. Pulmonary infection appeared upon admission and was mostly accompanied with hyperpyrexia. The result of sputum culture revealed baumannii and the pathogen of hemoculture was Pseudomonas aeruginosa. At 3 - 4 weeks later, mycotic infection appeared. And 17 patients suffered from Klebsiella pneumoniae and one died. CONCLUSION: Pulmonary infection after acute cervical spinal cord injury is severe and occurs early. Effective antibiotics according to the result of sputum culture, turnover & back-slapping for excreting phlegm in time, expectoration training and strengthening overall nutrition are effective therapeutic measures.

Upregulated miR-29b promotes neuronal cell death by inhibiting Bcl2L2 after ischemic brain injury.

It is increasingly clear that microRNAs (miRNAs) play an important role in controlling cell survival. However, the functional significance of miRNAs in ischemic brain injury remains poorly understood. In the present study, we assayed the expression levels of miR-29b after ischemic brain injury, and defined the target genes and biological functions of miR-29b. We found that the miR-29b levels were significantly increased in rat brain after transient middle cerebral artery occlusion and neurons after oxygen-glucose deprivation. Moreover, ectopic expression of miR-29b promoted neuronal cell death, whereas its repression decreased cell death. Furthermore, we verified that miR-29b directly targeted and inhibited Bcl2L2 gene expression, and then increased neuronal cell death. Importantly, Bcl2L2 overexpression rescued neuronal cell death induced by miR-29b. These results suggest an important role of miR-29b in regulating neuronal cell death, thus offering a new target for the development of therapeutic agents against ischemic brain injury.

Chondrosarcomas of the cervical and cervicothoracic spine: surgical management and long-term clinical outcome.

STUDY DESIGN: A retrospective review study. OBJECTIVES: To estimate the clinical outcome of various resection protocols in patients with chondrosarcoma (CHS) at the challenging region of cervical and cervicothoracic spine (CCT). SUMMARY OF BACKGROUND DATA: It is challenging to surgically manage CHS of the spine. Although total en-bloc resection has proven to be an ideal treatment, this option is not always feasible in the spine because of the constrains of critical neurovascular structures in the vicinity. Lesions at the CCT region pose even more difficulties, and few large clinical series concerning various protocols and long-term outcomes of these lesions exist at present. METHODS: Fifteen patients with CHS at the CCT region who underwent surgical management in our institute were retrospectively studied. Twelve piecemeal resections and 3 en-bloc resections were performed. Intraoperative local chemotherapy and postoperative cyberknife radiotherapy were given as adjuvant therapy. Neurologic status, local recurrence, distant metastasis, and treatment-related complications were evaluated. RESULTS: The mean follow-up time was 58.7 months (median 37 mo; ranging from 18 to 141 mo). Local recurrence was detected in 5 of 5 cases (100%) treated by intracapsular piecemeal resection, and in 1 of 7 cases (14.3%) treated by extracapsular piecemeal resection, whereas no recurrence was found in 3 cases treated by en-bloc resection. Of the 6 recurrent patients, 5 died of disease 24 to 46 months after present surgery, and the remaining patient was alive with disease in the final follow-up. There were no signs of recurrence in the remaining 9 patients. CONCLUSIONS: For CHS at the CCT region, intralesional piecemeal resection has a poor prognosis and should be avoided. Oncologically, en-bloc resection remains the best form of disease management and should be the primary treatment of choice. For cases in which an uncontaminated en-bloc resection could not be achieved, the extracapsular piecemeal resection with adjuvant therapy including local chemotherapy and cyberknife radiotherapy is an effective and achievable option.

Diagnosis of discogenic low back pain in patients with probable symptoms but negative discography.

OBJECTIVE: The purpose of the current study was to determine, whenever the patients complained of probable symptoms of discogenic low back pain and had obvious disc pathological changes on magnetic resonance imaging (MRI) but showed negative in discography, whether we could absolutely exclude the diagnosis of discogenic pain or not. METHODS: The patients we selected in our study had only one segmental disc pathology on MRI for the purpose of minimizing the interference and all patients complained of probable discogenic pain symptoms. Some special lumbar diseases were excluded by physical examination and CT or MRI scan. Finally, 45 isolated patients with negative discography were enrolled in our study from January 2006 to June 2008. Twenty-three patients were randomly distributed in experimental group, who underwent provocative discography plus intradiscal injection of dexamethasone (5 mg in each patient), while the other 22 patients in the control group received intradiscal injection of saline as a placebo. Visual analog scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate the changes of pain and function after discography. RESULTS: The mean age of the 16 male and 29 female patients was 44.9 years, whose main clinical manifestations included axial back pain (100%), pain in the region of Groin (33.3%), pain in the anterior or posterior region of thigh (42.2%), buttock pain (24.4%) and lower extremity pain (11.1%), and among them L3-L4 pathological disc was found in three patient, L4-L5 pathological disc in 28 patients and L5-S1 pathological disc in 14 patients. Discography and CT scans of the 45 patients revealed that there were grade 5 in 38 discs and grade 4 in seven discs by means of Modified Dallas classification. After about 6-month follow-up, the results showed that VAS scores and ODI scores were greatly improved during the first 3-month follow-up in the experimental group compared with pre-discography and between groups (p < 0.05), but no statistically significant difference after 24-week follow-up (p > 0.05). The probable symptoms of discogenic low back pain were significantly improved in the experimental group in the short term. CONCLUSION: The study indicated that negative discography in patients with probable symptoms of discogenic low back pain cannot absolutely exclude the diagnosis of discogenic pain. Patients of this kind may suffer from other diseases, but we cannot ignore the existence of discogenic pain.