LINC00641 regulates autophagy and intervertebral disc degeneration by acting as a competitive endogenous RNA of miR-153-3p under nutrition deprivation stress.

Emerging evidence supports the involvement of autophagy in the pathogenesis of intervertebral disc degeneration (IDD). MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) play fundamental roles in various cellular processes, including autophagy. However, it remains largely unknown as to how autophagy is regulated by miRNAs and lncRNAs in IDD. Biological functions of miR-153-3p and long intergenic nonprotein coding RNA 641 (LINC00641) were investigated. Luciferase reporter assays was done to validate miR-153-3p targets. To induce nutritional stress, nucleus pulposus (NP) cells were cultured in the normal nutritional condition and the low nutritional condition. Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) was used to analyze miR-153-3p and LINC00641 in response to nutrient deprivation. Autophagic activity was assessed by transmission electron microscopy, western blot analysis and green fluorescent protein-light chain 3 puncta. Pull-down assay and RNA fluorescent in situ hybridization were performed to validate LINC00641 target and the location. MiR-153-3p is downregulated in NP tissues from IDD patients. Further, LINC00641 can affect collagen II and matrix metalloproteinase-3 expressions. Upregulation of LINC00641 and downregulation of miR-153-3p are detected in NP cells under nutritional stress. LINC00641 can regulate autophagic cell death by targeting miR-153-3p and autophagy-related gene 5 (ATG5). MiR-153-3p inhibits autophagy and IDD by targeting ATG5. More important, LINC00641 targets miR-153-3p, and thus affects ATG5 expression, autophagic cell death and IDD. These findings uncover a novel regulatory pathway that is composed of LINC00641, miR-153-3p, and ATG5 in IDD. This mechanism may stimulate to a more understanding of IDD pathogenesis and provide new sights for the treatment of this disorder.

Ideal T1 laminar screw fixation based on computed tomography morphometry.

BACKGROUND: The application of laminar screws is an alternative fixation for the first thoracic vertebra (T1). This paper is to determine the anatomical characteristics for adequate laminar screw fixation, and present a modified method of sagittal reconstruction of T1 to provide more accurate measurements. METHODS: Computed tomography (CT) images of 62 patients (32 males, 30 females) were used for the analysis. The following parameters of the T-1 lamina were measured using Mimics software: lamina length, axis angle, minimal outer cortical width, cancellous width, minimal outer cortical height, cancellous height, and spinous process height. Right or left modified sagittal reconstructions (parallel to right or left screws) were innovatively used for measurement. RESULTS: There were no significant differences between the left and right sides for each measurement performed (P > 0.05), but significant differences were detected between males and females (P < 0.05). The mean length of the T1 lamina was 32.8 mm of the T1 minimal outer cortical width was 7.4 mm, and 3.8% of males had a minimal outer cortical width < 5 mm, while 8.6% of females had a minimal outer cortical width < 5 mm. The mean minimal outer cortical height was 10.8 mm, and 1.9% of males had a minimal outer cortical height < 9 mm, while 7.7% of females had a minimal outer cortical height < 9 mm. CONCLUSION: This study suggests there are no anatomical limitations for T1 laminar screw placement in most people. The modified sagittal reconstruction method described allows for easy and precise measurement to aid in the insertion of laminar screws in T1, and gives good visualization of laminar screw insertion direction.

Comparison of unilateral versus bilateral percutaneous kyphoplasty for the treatment of patients with osteoporosis vertebral compression fracture (OVCF): a systematic review and meta-analysis.

PURPOSE: To compare the short- and long-term clinical outcomes, operation times, restoration rate, dosage of polymethylmeth-acrylate (PMMA) injected, complications and X-rays exposure frequency between unilateral and bilateral kyphoplasty approaches for the treatment of OVCF. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Randomized or non-randomized controlled trials published up to April 2015 that compared the unilateral and bilateral PKP for the treatment of OVCF were acquired by a comprehensive search in the Cochrane Controlled Trial Register, PubMed, MEDLINE, EMBASE, Web of Science, OVID. Exclusion criteria were patients with neoplastic etiology (metastasis or myeloma), infection, neural compression syndrome, invasive and degenerative disease, traumatic fracture, re-operation, neurological deficits, significant scoliosis and spinal stenosis. The main end points included: operation times, the short- and long-term postoperative Visual Analogue Scale (VAS) scores, the short-term postoperative Oswestry Disability Index (ODI), restoration rate, dosage of PMMA injected, cement leakage, X-ray exposure frequency and postoperative adjacent-level fractures. RESULTS: A total of 8 studies involving 428 patients were included in the meta-analysis. The mean operative time was shorter in the unilateral groups compared with the bilateral groups [P < 0.05, weighted mean difference (WMD) -19.74 (-30.56, -8.92)]. There was no significant difference in the short-term postoperative VAS scores [P > 0.05, WMD 0.03 (-0.34, 0.40)], the long-term postoperative VAS scores between them [P > 0.05, WMD 0.01 (-0.42, 0.45)] and the short-term postoperative ODI [P > 0.05, WMD -0.33 (-2.36, 1.69)] between the two groups. The unilateral approaches required significantly less dosage of PMMA than the bipedicular approaches did [P < 0.05, WMD -1.56 (-1.59, -1.16)]. The restoration rate in the bilateral groups was higher than the unilateral groups [P < 0.05, WMD -7.82 (-12.23, -3.41)]. There was no significant difference in the risk ratio of cement leakage [P > 0.05, RR 0.86 (0.36, 2.06)] and postoperative adjacent-level fractures [P > 0.05, RR 0.91 (0.25, 3.26)] between the two methods. The mean X-ray exposure frequency in the unilateral groups was greater than the bilateral groups [P < 0.05, WMD -5.69 (-10.67, -0.70)]. CONCLUSIONS: A definitive verdict could not be reached regarding which approach is better for the treatment of OVCF. Although unilateral PKP was associated with shorter operative time, less X- ray exposure frequency and dosage of PMMA than bilateral PKP. There was no apparent difference in the short- and long-term clinical outcomes and complications between them. However, bilateral PKP approaches were higher than unilateral PKP in term of the restoration rate. But on account of lack of some high-quality evidence, we hold that amounts of high-quality randomized controlled trials should be required and more complications should be analysed to resolve which surgical approach is better for the treatment of OVCF in the future.

Role of hypoxia-induced VEGF in blood-spinal cord barrier disruption in chronic spinal cord injury.

Chronic spinal cord lesions (CSCL) which result in irreversible neurologic deficits remain one of the most devastating clinical problems. Its pathophysiological mechanism has not been fully clarified. As a crucial factor in the outcomes following traumatic spinal cord injury (SCI), the blood-spinal cord barrier (BSCB) disruption is considered as an important pathogenic factor contributing to the neurologic impairment in SCI. Vascular endothelial growth factor (VEGF) is a multirole element in the spinal cord vascular event. On one hand, VEGF administrations can result in rise of BSCB permeability in acute or sub-acute periods and even last for chronic process. On the other hand, VEGF is regarded to be correlated with angiogenesis, neurogenesis and improvement of locomotor ability. Hypoxia inducible factor-1 (HIF-1) is a primary regulator of VEGF during hypoxic conditions. Therefore, hypoxia-mediated up-regulation of VEGF may play multiple roles in the BSCB disruption and react on functional restoration of CSCL. The purpose of this article is to further explore the relationship among HIF-1, hypoxia-mediated VEGF and BSCB dysfunction, and investigate the roles of these elements on CSCL.

Value of micro-CT for monitoring spinal microvascular changes after chronic spinal cord compression.

Neurological degeneration can occur after compression of the spinal cord. It is widely accepted that spinal cord compression leads to ischemic lesions and ultimately neurological dysfunction due to a narrowed spinal canal. Therefore, an in-depth understanding of the pathogenesis of spinal cord compression injury is required to help develop effective clinical interventions. In the present study, we propose a new method of quantitative 3D micro-CT to observe microvascular events in a chronic spinal cord compression rat model. A total of 36 rats were divided into two groups: sham control group (n = 12) and compressive spinal cord injury group (n = 24). Rats were scarified at four weeks after surgery. In each group, CD34 micro-vessel immunohistochemical staining was performed in half of the animals, while micro-CT scanning was performed in the other half. Microvessel density (MVD) was measured after immunohistochemical staining, while the vascular index (VI) was measured in 3D micro-CT. In comparison with sham control, abnormal somatosensory evoked potentials (SEP) can be seen in all 24 cases of the compression group, and VI shows the amount of microvessels reduced consistently and significantly (p < 0.01). A significant correlation is also found between MVD and VI (r = 0.95, p < 0.01). These data suggest that quantitative 3D micro-CT is a sensitive and promising tool for investigating microvascular changes during chronic compressive spinal cord injury.

[Comparative study of Kurokawa's double door laminoplasty and modified Kurokawa's double door laminoplasty for the treatment of cervical disorders].

OBJECTIVE: To observe and compare the medium-long-term efficacy of Kurokawa's and modified Kurokawa's double door laminoplasty for the treatment of cervical disorders. METHODS: A retrospective analysis was performed to compare the outcomes and complications between two kinds of operations on 172 cases from January 2002 to December 2010, including 106 cases of cervical spondylotic myelopathy, 52 cases of cervical stenosis, 21 cases of cervical ossification of the posterior longitudinal ligament. Patients were divided into two groups according to two surgical methods: traditional group, including 51 male and 18 female patients, with mean age of (56 ± 18) years (35-76 years); modified group, including 75 male and 28 female patients, with mean age of (58 ± 20)years (35-80 years). The two groups were comparable and compared according to different data using t test, χ(2) test and rank sum test. RESULTS: All patients were followed up continuously for (52 ± 33)months, 123 patients were followed up ≥ 2 years, 71 patients ≥ 5 years. All patients' Japanese Orthopaedic Association (JOA) score improved significantly at the latest follow-up(t = 3.420, P < 0.01); no significant difference between the patients' JOA score improvement rate of two groups. The postoperative incidence rate of axial symptoms in patients of modified group (3.9%) was significantly lower than the traditional group (14.5%) (χ(2) = 7.548, P < 0.05), and cervical intervertebral activity decreased in the modified group was better than the traditional group in the first 3 months postoperatively (27% ± 6% vs. 19% ± 4%,Z = 6.34, P < 0.05), but during the medium-long-term follow-up, no significant difference in the cervical intervertebral activity decreased between two groups. CONCLUSIONS: Medium-long-term efficacy of Kurokawa's and modified Kurokawa's double door laminoplasty is satisfied and reliable. Avoiding damaging of semispinalis cervicis insertion in spinous process of C2, the modified operation method can protect the extensor group of the neck muscle and reduce the incidence of postoperative axial symptoms better.

Pathophysiological mechanisms of chronic compressive spinal cord injury due to vascular events.

Cervical spondylotic myelopathy is the main cause of non-traumatic spinal cord injury, with chronic static and/or dynamic compressive spinal cord injury as the unique pathogenesis. In the progression of this condition, the microvascular network is compressed and destroyed, resulting in ischemia and hypoxia. The main pathological changes are inflammation, damage to the blood spinal cord barriers, and cell apoptosis at the site of compression. Studies have confirmed that vascular regeneration and remodeling contribute to neural repair by promoting blood flow and the reconstruction of effective circulation to meet the nutrient and oxygen requirements for nerve repair. Surgical decompression is the most effective clinical treatment for this condition; however, in some patients, residual neurological dysfunction remains after decompression. Facilitating revascularization during compression and after decompression is therefore complementary to surgical treatment. In this review, we summarize the progress in research on chronic compressive spinal cord injury, covering both physiological and pathological changes after compression and decompression, and the regulatory mechanisms of vascular injury and repair.

Two kinds of posterior approach for Kvmmell's disease after osteoporotic thoracolumbar fracture.

OBJECTIVE: To compare the surgical results of two kinds of posterior approach for osteoporotic thoracolumbar Kvmmell's disease. METHODS: Clinical and radiographic results of 1-segmental pedicle screw fixation combined with vertebroplasty (Group A, n equal to 12) or posterior shortening osteotomy (Group B, n equal to 16) for osteoporotic thoracolumbar Kvmmell's disease were analyzed retrospectively. Japanese orthopedic association (JOA) and visual analogue scale (VAS) scores were used for clinical evaluation. Neurological status was judged by Frankel grades. X-ray was used to evaluate the radiographic results. Complications related to operation and devices were also considered. RESULTS: The follow-up period was 12-54 months (average 29 months). Pre-and post-operative VAS were 9.3 and 3.2 in Group A, 8.9 and 2.5 in Group B, respectively. The mean JOA score at the final follow-up was significantly higher than that of pre-operation (t equal to 5.306, P less than 0.001). There was no significant difference between Groups A and B (t equal to 0.618, P larger than 0.05). The kyphosis were corrected from preoperative 33.9 degree A)/37.3 degree B) to postoperative 10.3 degree A)/6.5 degree B), and 15.3 degree (A)/13.7 degree B) at the final follow-up. There was a significant difference between the two groups at the final follow-up. Frankel grade was improved from grade C preoperatively to postoperatively grade D or E in 7 cases of Group A and 5 cases of Group B, from grade D to E in 5 cases of Group A and 11 cases of Group B. The mean improvement was 1.6 and 1.7 grades for Groups A and B, respectively. There were no serious complications related to internal fixation. CONCLUSIONS: The similar clinical results can be obtained by the two kinds of posterior surgical methods for osteoporotic Kvmmell's disease. Posterior spinal shortening is a better choice for patients with serious kyphosis combined with neurological deficit than the other.

Is the speed of chronic compression an important factor for chronic spinal cord injury rat model?

OBJECTIVE: To evaluate the effect of expansion speed on chronic compressive spinal cord injury in the rat. METHODS: Thirty-six Sprague-Dawley rats were divided into four groups: a control group, a group receiving compressor in the C5-C6 epidural space with instant compression (group 1), and two other groups receiving water-absorbing polyurethane polymer sheets with two expansion speeds, which reached maximum volume in 2 h (group 2: fast expansion) or 24 h (group 3: slow expansion). A C6 laminectomy was performed in the control group. Neurological function, MRI, large motoneuron number in the ventral horn, and myelin staining intensity in the posterior funiculus were evaluated. RESULTS: In the instant compression group, compression was confirmed on T2-weighted images by a hypointense signal change in the intramedulla. In the gradual compressive injury groups, large motoneuron number (p<0.001), but not myelin staining intensity, was significantly decreased in both the fast and slow expansion groups compared with the instant compression group. However, there was no difference in Basso Beattie Bresnahan score, cord distortion in T2-weighted image, large motoneuron numbers, or myelin staining between the fast and slow expansion groups. CONCLUSION: Instant spinal cord compression caused acute injury. Gradual expansion compression induced reliable pathology and MRI characteristics consistent with chronic compressive spinal cord injury. The speed of expansion is not a significant problem for establishing a reliable model if the chronic compression is induced by gradual expansion.

HIF-1α/VEGF signaling pathway may play a dual role in secondary pathogenesis of cervical myelopathy.

Cervical spondylotic myelopathy (CSM) is one of the most common spinal cord disorders affecting the elderly. Yet the exact pathophysiology of CSM remains unclear. Vascular response to initial mechanical compression and associated ischemia may involve in secondary pathophysiology. Chronic compressive lesions to cervical cord resulting in lack of perfusion have established considerable evidences to support ischemia as an important pathogenesis both in patients and animal models, a similarity as that of acute spinal cord injury (SCI). In hypoxic condition following SCI, the up-regulation of vascular endothelial growth factor (VEGF), is consistent with increasing hypoxia induced factor-1α (HIF-1α) in acute periods. HIF-1α/VEGF signaling pathway is thought to play a dual role following SCI. In one hand, VEGF was demonstrated to be correlated with angiogenesis (protecting vascular endothelial cells, increasing blood vessel density and improving regional blood flow), neurogenesis (antiapoptotic, neurotrophic, attenuate axonal degradation), and locomotor ability improvement. In other hand, some studies revealed that VEGF have limited therapeutic effect, even exacerbate the secondary damage following SCI. VEGF administrations in acute or subacute periods result in elevation of blood-spinal cord barrier (BSCB) permeability even last for chronic course. BSCB permeability elevation initiates a secondary cascade of events involving excitotoxicity, infiltration of leukocytes and tissue edema. With comprehensive understanding of temporal and spatial of HIF-1α/VEGF signaling pathway, development of therapeutic strategies to promote new vessel growth while minimize the deleterious effects of VEGF-induced microvascular permeability, and thereby improve neurologic function, seems to be feasible and promising.

Transpedicular fixation in management of thoracolumbar burst fractures: monosegmental fixation versus short-segment instrumentation.

STUDY DESIGN: A prospective clinical trial was conducted. OBJECTIVE: To compare the clinical and radiologic late results of monosegmental transpedicular fixation versus short-segment pedicle instrumentation (SSPI) in management of thoracolumbar burst fractures and evaluate the efficacy of monosegmental transpedicular fixation. SUMMARY OF BACKGROUND DATA: SSPI (1 level above and 1 below the fracture level) are accepted by many surgeons as an accepted technique for the treatment of thoracolumbar burst fractures. To preserve more motion segments, some authors have advocated monosegmental pedicle instrumentation (MSPI). The recent developments showed that MSPI yielded good clinical results; however, there were no report about comparison of clinical outcome between monosegmental and biosegmental transpedicular fixation in management of thoracolumbar burst fractures. METHODS: Eighty-five patients with thoracolumbar burst fractures fulfilling the inclusion criteria were included in the study. The patients were randomized by a simple method into 2 groups. Group 1 were treated with monosegmental transpedicular fixation (n = 47), and group 2 were treated with biosegmental transpedicular fixation (n = 38). Clinical (Low Back Outcome Score and Oswestry Disability Index) and radiologic (load-sharing classification index, sagittal index, and percentage of anterior body height compression) outcomes were analyzed. RESULTS: The 2 groups were similar in age, follow-up period, and severity of the deformity and fracture. The postoperative and follow-up sagittal index, local kyphosis, percentage of anterior body height compression, and average correction loss in local kyphosis in both groups were not significantly different. The failure rate between the 2 surgical approaches was also not significantly different (group 1 = 6.38% and group 2 = 5.26%). Oswestry Disability Index improved in both groups by >25 points in a similar amount (P = 0.23). The average follow-up Low Back Outcome Score was 74.9 and 60.2 for group 1 and group 2, respectively (P = 0.033). CONCLUSION: In conclusion, radiologic parameters demonstrated that both MSPI and SSPI are the effective and reliable operative techniques for selected thoracolumbar burst fractures. MSPI shortened the operative time and decreased the amount of blood loss significantly and, thus, offered better clinical results. Nevertheless, long-term studies are supposed to be performed to support the outcomes.

[Osteogenic potential of three kinds of calcium phosphate ceramics as carriers for recombinant human morphogenetic protein-2 in vivo].

OBJECTIVE: To investigate and compare the osteogenic potential of three kinds of calcium phosphate ceramic as carriers for recombinant human bone morphogenetic protein-2(rhBMP-2) in vivo. METHODS: BCP ceramics (HA, TCP, HA/TCP) impregnated with rhBMP-2 (experimental groups) and without rhBMP-2(control groups) were implanted into 6 muscles pockets on the dorsum of 3-month-old Wistar rabbits. The rabbits were sacrificed 2, 4 and 8 weeks after implantation and bone induction was estimated by alkaline phosphatase (ALP) activity measurement. The implants were also examined histologically and histomorphometrically by HE staining and computerized graphical analysis. RESULTS: The ALP activity of implants with rhBMP-2 was higher than that of control groups (P < 0.05), but there was no difference between 2 and 4 weeks in experimental groups. In all experimental groups, the implants exhibited that new bone formation increased with the lapse of time. The amount of new bone formation is more in HA/rhBMP-2 group than in the other two group in the 2nd and 4th weeks, but there was no difference between them (P > 0.05). In the 8th week, the amount of bone formation was most in HA/TCP with rhBMP-2, and was more than that in the 2nd and 4th weeks. Whereas in control groups, there was only fibrous connective tissue. CONCLUSION: HA/TCP is a good carriers of rhBMP-2 and can be used as bone substitutes clinically.