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Objective Hypertrophy ligamentum flavum (LFH) is a common cause of lumbar spinal stenosis, resulting in significant disability and morbidity. Although long noncoding RNAs (lncRNAs) have been associated with various biological processes and disorders, their involvement in LFH remains not fully understood. Methods Human ligamentum flavum samples were analyzed using lncRNA sequencing followed by validation through quantitative real-time polymerase chain reaction. To explore the potential biological functions of differentially expressed lncRNA-associated genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. We also studied the impact of lncRNA PARD3-AS1 on the progression of LFH in vitro. Results In the LFH tissues when compared to that in the nonhypertrophic ligamentum flavum (LFN) tissues, a total of 1,091 lncRNAs exhibited differential expression, with 645 upregulated and 446 downregulated. Based on GO analysis, the differentially expressed transcripts primarily participated in metabolic processes, organelles, nuclear lumen, cytoplasm, protein binding, nucleic acid binding, and transcription factor activity. Moreover, KEGG pathway analysis indicated that the differentially expressed lncRNAs were associated with the hippo signaling pathway, nucleotide excision repair, and nuclear factor-kappa B signaling pathway. The expression of PARD3-AS1, RP11-430G17.3, RP1-193H18.3, and H19 was confirmed to be consistent with the sequencing analysis. Inhibition of PARD3-AS1 resulted in the suppression of fibrosis in LFH cells, whereas the overexpression of PARD3-AS1 promoted fibrosis in LFH cells in vitro. Conclusion This study identified distinct expression patterns of lncRNAs that are linked to LFH, providing insights into its underlying mechanisms and potential prognostic and therapeutic interventions. Notably, PARD3-AS1 appears to play a significant role in the pathophysiology of LFH.

Background: Hypertrophy of the ligamentum flavum (HLF) is a common contributor to spinal stenosis which results in significant neurological impairments. Circular RNA (circRNA) circ_0003609 has been linked to HLF; however, the exact mechanism by which it causes this disease is unclear. Methods: Circ_0003609 expressions were regulated in HLF cells by overexpression vectors and RNA interference. Cell proliferation and fibrosis-related gene expression were checked by the Cell Counting Kit-8 (CCK-8) assay and western blotting. CircBank's prediction of the association between miR-155 and circ_0003609 was supported by a dual-luciferase reporter experiment. The function of the miR-155/sirtuin 1 (SIRT1) axis in controlling HLF fibrosis was further examined. Results: Overexpression of circ_0003609 suppressed HLF cell propagation and fibrosis compared to its silencing. It was found that circ_0003609 served as the sponge for miR-155 and that the circ_0003609/miR-155 axis controlled the fibrosis of HLF cells. It was found that circ_0003609 acted as a sponge for miR-155, regulating the fibrosis of HLF cells. Further, miR-155 targets SIRT1, and the miR-155/SIRT1 axis promotes HLF cell fibrosis. Conclusion: Circ_0003609 ameliorates hypertrophied ligamentum flavum (LF) by modulating the miR-155/SIRT1 axis, indicating a potential treatment approach for HLF. [ABSTRACT FROM AUTHOR]

Objective Conventional localization technique of V point for full‐endoscopic posterior cervical foraminotomy and discectomy (FPCD) required repeated fluoroscopies, especially in patients with short and thick necks. To address this issue, the present study aimed to introduce a new localization technique of V point, and further evaluate its efficacy. Methods A K‐wire was inserted and fixed at the pedicle eye under A/P fluoroscopy, then a working channel was established quickly along with it. Thirty‐four patients who underwent minimally invasive FPCD assisted by the new technique were included in this study. The clinical and radiological data were collected and analyzed, including radiation dose, operative time, positioning time, visual analog scale (VAS) for neck and arm pain, neck disability index (NDI) scores, Cobb angle of operative level and range of motion of the cervical spine. Results All operations were performed successfully, and no iatrogenic nerve or vascular injury occurred. None of the patients needed to be transferred to open surgery or revision surgery. The mean radiation dose was found to be1.68 ± 0.36 mSv. The mean positioning time observed was 10.68 ± 5.42 min and the average operation time was 81.18 ± 10.87 min. The operation time significantly declined as the number of patients increased. A significant difference in operation time between the first (96.22 ± 10.36 min) and last quartile (75.00 ± 3.84 min) of cases was observed (t = 4.82, P

Objective: This study was designed to investigate the relationship between the laminar slope angle (LSA) and the lumbar disc degenerative grade, the cross-section area (CSA) of multifidus muscle, the muscle-fat index, and the thickness of the ligamentum flavum. Methods: Retrospective analysis of 122 patients who were scheduled to undergo a lumbar operation for diagnoses associated with degenerative lumbar disease between January and December 2017. The L4–L5 disc grade was evaluated from preoperative sagittal T2-weighed magnetic resonance imaging of the lumber region; the CSA of the multifidus and muscle-fat index were measured at the L4 level, while the thickness of the ligamentum flavum was measured at the L4–L5 facet level from axis T2-weighed magnetic resonance imaging. The slope of the laminar was evaluated from preoperative three-dimensional computer tomography at the tip level of the facet joints and selected by the axis plane. Independent-sample T-tests were used to assess the association between age and measurement indices. Results: Our results showed that age was positively connected with the LSA of L4 and L5 in different patients, although there was no significant difference between age and the difference of the two segment LSA. Partial correlation analysis, excluding the interference of age, revealed a strong negative relationship between the LSA of L4 and the thickness of the ligamentum flavum, irrespective of whether we considered the left or right. However, there was no correlation with lumbar disc degenerative grade, the CSA of the multifidus, and the muscle-fat index. Conclusion: The thickness of the ligamentum flavum showed changes with anatomical differences in the LSA, but not the lumbar disc degenerative grade, the CSA of the multifidus, and the muscle-fat index. A small change in LSA may cause large mechanical stress; this may be one of the causative factors responsible for lumbar spinal stenosis.

Abstract Cell cycle progression in mammals is strictly controlled by a number of cyclin-dependent kinases (CDKs) and CDK inhibitors (CKIs), the expression of which is often dysregulated in cancer cells. Our previous work revealed that Cullin 4B (CUL4B), a critical component of the Cullin4B-RING E3 ligase complex (CRL4B), is overexpressed in human osteosarcoma cells through an unknown mechanism. Here, we demonstrated that CUL4B forms an E3 ligase with RBX1 (RING-box 1), DDB1 (DNA damage binding protein 1), and DCAF11 (DDB1 and CUL4 associated factor 11) in human osteosarcoma cells. In vitro and in vivo ubiquitination analyses indicated that CRL4BDCAF11 E3 ligase was able to specifically ubiquitinate a CDK inhibitor—p21Cip1 at K16, K154, K161 and K163 but not at K75 and K141. Knocking down any component of the CRL4BDCAF11 complex, including CUL4B, DDB1 or DCAF11, using short hairpin RNAs (shRNAs) attenuated the ubiquitination level of p21Cip1, inhibited osteosarcoma cell proliferation, led to cell cycle arrest at S phase, and decreased colony formation rate. Taken together, our data suggest that the CRL4BDCAF11 complex represents a unique E3 ligase that promotes the ubiquitination of p21Cip1 and regulates cell cycle progression in human osteosarcoma cells.

Targeting posttraumatic inflammation is crucial for improving locomotor function. SIRT1 has been shown to play a critical role in disease processes such as hepatic inflammation, rheumatoid arthritis, and acute lung inflammation by regulating inflammation. However, the role of SIRT1 in spinal cord injury (SCI) is unknown. We hypothesized that SIRT1 plays an important role in improving locomotor function after SCI by regulating neuroinflammation. In this study, we investigate the effect of SIRT1 in SCI using pharmacological intervention (SRT1720) and the Mx1-Cre/loxP recombination system to knock out target genes. First, we found that SIRT1 expression at the injured lesion site of wild-type (WT) mice (C57BL/6) decreased 4 h after SCI and lasted for 3 d. Moreover, administration of SRT1720, an agonist of SIRT1, to WT mice significantly improved functional recovery for up to 28 d after injury by reducing the levels of proinflammatory cytokines, the number of M1 macrophages, the number of macrophages/microglia, and the accumulation of perivascular macrophages. In contrast, administration of SRT1720 to SIRT1 knock-out (KO) mice did not improve locomotor recovery or attenuate inflammation. Furthermore, SIRT1 KO mice exhibited worse locomotor recovery, increased levels of inflammatory cytokines, and more M1 macrophages and perivascular macrophages than those of WT mice after SCI. Together, these findings indicate that SRT1720, an SIRT1 agonist, can improve functional recovery by attenuating inflammation after SCI. Therefore, SIRT1 is not only a protective factor but also an anti-inflammatory molecule that exerts beneficial effects on locomotor function after SCI. [ABSTRACT FROM AUTHOR]

Background: There is considerable controversy as to which posterior technique is best for the treatment of multi-level cervical spondylotic myelopathy. The aim of this study was to compare the clinical and radiographic results and complications of laminoplasty (LAMP) and laminectomy (LAMT) in the treatment of multi-level cervical spondylotic myelopathy. Methods: We reviewed and analyzed papers published from January 1966 and June 2013 regarding the comparison of LAMP and LAMT for multi-level cervical spondylotic myelopathy. Statistical comparisons were made when appropriate. Results: Fifteen studies were included in this systematic review. There was no significant difference in the incidence of surgical complications between LAMP and LAMT. Compared to conventional LAMT and skip LAMT, postoperative ROM was more limited in LAMP, but this was still superior to postoperative ROM following LAMT with fusion. Postoperative kyphosis occurred in 8/180 (4.44%) in LAMP and 13/205 (6.34%) in LAMT, whereas no cases of kyphosis were reported for skip LAMT. Skip LAMT appears to have better clinical outcomes than LAMP, while the outcome was similar between LAMP and LAMT with fusion. Conclusions: Based on these results, a claim of superiority for laminoplasty or laminectomy was not justified. In deciding between the two procedures, the risks of surgical and neurological complications, and radiologic and clinical outcome, must be taken into consideration if both options are available in multi-level cervical spondylotic myelopathy. [ABSTRACT FROM AUTHOR]

Background: Anterior cervical plate had developed continuously, and this study aimed to assess the biomechanics of a novel self-locking plate system for anterior cervical fixation designed by ourselves. Methods: Twelve anterior cervical plates (i.e., six novel plates and six DePuy plates) were subjected to a pull-out test and a fatigue test. In addition, 12 C1-T1 cervical spine specimens underwent anterior cervical corpectomy and C5 fusion using six novel plates and six DePuy plates. Pre- and postoperative range of motion, load–displacement, axial stiffness, torque, and twisting stiffness were compared. Results: No differences in maximum pull-out force, relative displacement, or energy absorption were observed between the DePuy plates and the novel plates (P >0.05). The novel plate system could bear an average of 5.6 × 105 times of loading, while the DePuy plate could bear 5.4 × 105 times of loading. The fatigue strengths of the new plate system and the DePuy plate were 490.75 and 485.86 MPa, respectively. No differences in fatigue life or strength were observed between the two types of plates. Cervical spine stability increased significantly after internal fixation. No differences in range of motion, load–displacement, axial stiffness, torque, or twisting stiffness were observed between the novel self-locking plate and the DePuy plate (P >0.05). Conclusions: Compared to the DePuy plate, the novel anterior cervical self-locking plate system described here has good strength and fastening ability, allowing it to provide sufficient biomechanical stability. Further clinical assessment of this system is needed. [ABSTRACT FROM AUTHOR]

Objective: To analyze perioperetive clinical features and outcomes of surgical treatment for cervical spondylotic myelopathy (CSM) in elderly patients. Methods: From 2006 to 2013, we retrospectively reviewed 136 patients with CSM who underwent surgery. The patients were divided into two groups: 70 years or older (elderly group, 58 patients) and younger than 70 years (younger group, 78 patients). The course of disease, surgical outcome, morbidities, and postoperative complications were analyzed. Results: In the elderly group, follow-up lasted 9-76 months (mean 39.6 months), the course of disease was 23.7 months (range 4-72 months). Anterior cervical decompression and fusions and posterior laminectomy and fixation were performed in 24 and 34 patients, respectively. The operative time averaged 103 min (range 48-210 min). In the younger group, follow-up lasted 10-71 months (mean 37.8 months), the course of disease was 12.6 months (range 2-58 months). Anterior cervical decompression and fusions and posterior laminectomy and fixation were performed in 75 and three patients, respectively. The prevalence of chronic diseases and postoperative complications were higher in the elderly group than the younger group. The recovery rates of JOA score were 40.82 ± 11.20% in the elderly group and 64.10 ± 22.61% in the younger group. The therapeutic effects of surgery were significantly better for the young patients than for the elderly. Conclusion: Elderly patients with CSM present long period and serious symptoms, and the degeneration of multiple organs. Surgical decompression for CSM appears to be a beneficial and safe procedure for older patients if properly handled, although the recovery rate is poorer than that of younger patients. [ABSTRACT FROM AUTHOR]

Objective: Conventional localization technique of V point for full‐endoscopic posterior cervical foraminotomy and discectomy (FPCD) required repeated fluoroscopies, especially in patients with short and thick necks. To address this issue, the present study aimed to introduce a new localization technique of V point, and further evaluate its efficacy. Methods: A K‐wire was inserted and fixed at the pedicle eye under A/P fluoroscopy, then a working channel was established quickly along with it. Thirty‐four patients who underwent minimally invasive FPCD assisted by the new technique were included in this study. The clinical and radiological data were collected and analyzed, including radiation dose, operative time, positioning time, visual analog scale (VAS) for neck and arm pain, neck disability index (NDI) scores, Cobb angle of operative level and range of motion of the cervical spine. Results: All operations were performed successfully, and no iatrogenic nerve or vascular injury occurred. None of the patients needed to be transferred to open surgery or revision surgery. The mean radiation dose was found to be1.68 ± 0.36 mSv. The mean positioning time observed was 10.68 ± 5.42 min and the average operation time was 81.18 ± 10.87 min. The operation time significantly declined as the number of patients increased. A significant difference in operation time between the first (96.22 ± 10.36 min) and last quartile (75.00 ± 3.84 min) of cases was observed (t = 4.82, P < 0.001). The VAS scores for neck and arm pain, and NDI scores were significantly improved after surgery (PVAS−Neck<0.0001, PVAS−Arm<0.0001, PNDI<0.0001). Based on MacNab criteria, the excellent plus good rate was 91.17%. The Cobb angle of operative level and range of motion of the cervical spine were significantly improved postoperatively (t = 2.846, POA = 0.015; t = 2.232, PROM−CA = 0.026). Conclusion: The new image‐assisted V point localization technique is simple and useful with little radiation exposure and short positioning time. FPCD assisted by the new technique could be a safe and effective alternative on properly selected patients. [ABSTRACT FROM AUTHOR]

Abstract: Longitudinal bone growth is governed by a complex network of endocrine signals including leptin. In mouse, leptin deficiency leads to distinct phenotypes in bones of the limb and spine, suggesting the appendicular and axial skeletons are subject to differential regulation by leptin. We established primary cultures for the chondrocytes from tibial and vertebral epiphyseal plates. Cellular proliferation and apoptosis were analyzed for the chondrocytes that had been treated with various concentrations of leptin. Crucial factors for chondrocyte proliferation and differentiation, such as BMP7 and Wnt3, were measured in the cells treated with leptin alone or in combination with pharmacological inhibitors of STAT and ERK signaling pathways. Primary culture of tibial epiphyseal plate chondrocytes has greater proliferating capability compared with that of vertebral epiphyseal plate chondrocytes. Leptin could promote the proliferation of tibial epiphyseal plate chondrocytes, while its effect on vertebral epiphyseal plate chondrocytes was inhibitory. Consistently, apoptosis is inhibited in tibial but promoted in vertebral epiphyseal plate chondrocytes by leptin. Importantly, leptin differentially modulates chondrogenic signaling pathways in tibial and vertebral epiphyseal chondrocytes through STAT and ERK pathways. Leptin differentially regulates chondrogenic proliferation and differentiation in appendicular and axial regions of the skeletons. The signaling pathways in these two regions are also distinct and subject to differential regulation by leptin through the STAT pathway in tibial epiphyseal plate chondrocytes but through the ERK pathway in vertebral epiphyseal plate chondrocytes. Therefore, the regulation of leptin is multi‐faceted in the distinct anatomical regions of the skeleton. Knowledge gained from this system will provide insights into the pathophysiological causes for the diseases related to bone development and metabolism. [ABSTRACT FROM AUTHOR]

Purpose: A retrospective radiographic study was carried out to analyze the effect of lumbar disc herniation on the kinetic motion of adjacent segments.Methods: A total of 162 patients with low back pain or radicular pain in the lower limbs without a prior history of surgery were evaluated using kinetic magnetic resonance imaging. Translational motion, angular variation, and disc height were measured at each segment from L1-L2 to L5-S1. Other factors including the degree of disc degeneration, age, gender, and vertebral segment location were analyzed to determine any predisposing risk factors for segmental instability adjacent to disc herniations.Results: Spinal levels above the disc herniation exhibited, on average, a 6.4 % increase in translational motion per mm of disc herniation (P = 0.496) and a 21.4 % increase in angular motion per mm herniation (P = 0.447). Levels below the herniation demonstrated a 5.2 % increase in translational motion per mm of disc herniation (P = 0.428) and a decrease of 10.7 % in angular motion per mm (P = 0.726). The degree of disc degeneration had no significant correlation with adjacent level motion. Similarly, disc herniation was not significantly correlated with disc height at adjacent levels, although there was a significant relationship between gender and adjacent segment disc height.Conclusions: Although disc height, translational motion, and angular variation are significantly affected at the level of a disc herniation, no significant changes are apparent in adjacent segments. Our results indicate that herniated discs have no effect on range of motion at adjacent levels regardless of the degree of disc degeneration or the size of disc herniation, suggesting that the natural progression of disc degeneration and adjacent segment disease may be separate, unrelated processes within the lumbar spine. [ABSTRACT FROM AUTHOR]

Background: Split spinal cord malformation (SSCM) is rare in scoliosis. This study evaluated the safety and effectiveness of one-stage surgical treatment of congenital scoliosis (CS) in patients with SSCM in a single Chinese center. Method: A retrospective study of 5 cases who underwent surgery for CS with SSCM (2 type I and 3 type II) from March 2004 to March 2012. Patients included 4 females and 1 male with a mean age of 13.8 years. All patients underwent one-stage posterior fusion surgery with resection of a bony spur firstly in SSCM type I, but we did nothing to the SSCM in type II. Clinical symptoms and radiological changes were evaluated preoperatively and for at least 2 years postoperatively. Results: Preoperatively, 5 patients had variant neurological and other symptoms. They had a mean preoperative Cobb angle of 63 ± 20° and T5-T12 kyphosis of 30 ± 21°. The mean postoperative Cobb angle was 30.2 ± 19.8° with a correction rate of 57.2 ± 17.0%. At the 3-month follow-up the Cobb angle loss was 3.0 ± 6.8°, and at the 2-year follow-up the Cobb angle loss was 6.5 ± 9.7°. Hyperkyphosis was significantly corrected after surgery but correction loss was indicated at the 2-year follow-up (p < 0.01). There were no neurological deficit complications or deteriorated neurological signs postoperatively or at follow-up. Conclusions: One-stage surgical treatment of CS with SSCM could be safe and effective, but we need further multicenter studies with larger samples. Intraspinal intervention of bone spur was recommended in SSCM type I before deformity correction, while in SSCM type II it was needless. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]