Postoperative neck tilt in Lenke 1 and 2 AIS patients after correction surgery: a novel predictive index.

BACKGROUND: Postoperative neck tilt (PNT) is a phenomenon in adolescent idiopathic scoliosis (AIS) patients which is distinct form shoulder imbalance. There were scarce studies performed to explore the risk factors for PNT in Lenke 1 and 2 AIS patients, and whether it can be predicted after surgery remains unknown. The objective of this study is to explore the prevalence and risk factors for PNT, and introduce an index for prediction of PNT in Lenke 1 and 2 AIS patients after correction surgery. METHODS: Medical records of Lenke 1 and 2 AIS patients who received correction surgery were reviewed from February 2013 to February 2015. Posteroanterior films were evaluated before surgery and at 2 years' follow-up. Patients were divided into two groups according to whether PNT occurred at the 2 years' follow-up. Risk factors of PNT were analyzed, and PNT Index was proposed and verified. RESULTS: One hundred two Lenke 1 and 2 AIS patients were recruited in this study. The prevalence of PNT after correction was 40.2%. According to the postoperative CAT (Cervical Axis Tilt), patients were divided into two group: PNT group (CAT≧5°, n = 41) and non-PNT group (CAT< 5°, n = 61). Postoperative T1 tilt, preoperative proximal thoracic curve (PTC), postoperative PTC and postoperative coronal balance (CB) were significantly different between two groups. Logistic regression showed that postoperative PTC and postoperative CB were the primary risk factors for PNT, which could be predicted by the regression equation: PNT Index = 1.1 x postoperative PTC (degrees) - 0.9 x postoperative CB (millimeters). On the basis of ROC curve, if PNT Index was more than 10, the occurrence rate of PNT was 86%. On the contrary, the rate of no PNT phenomenon was 80%. CONCLUSION: Postoperative PTC and postoperative CB were the important factors for PNT in Lenke 1 and 2 AIS patients. Sufficient correction of PTC and moderate correction of CB should be recommended when operating on Lenke1 and 2 AIS patients.

Suppression of microglial Ccl2 reduces neuropathic pain associated with chronic spinal compression.

Introduction: Chronic spinal compression is a common complication of spinal cord injury (SCI), which can lead to spinal stenosis or herniated discs. The ensuing neuropathic pain is often associated with the activation of microglia. In this investigation, our objective was to explore whether modifying the levels of chemokine (C-C motif) ligand 2 (Ccl2) in microglia could alleviate neuropathic pain resulting from chronic spinal compression. Methods: We used a public database to look for major altered gene associated in a SCI model established in rats. We then employed adeno-associated virus (AAV) vectors, expressing siRNA for the identified significantly altered gene under a microglia-specific TMEM119 promoter. We also tested the impact of this treatment in microglia in vivo on the severity of chronic spinal compression and associated pain using a ttw mouse model for progressive spinal compression. Results: We identified chemokine (C-C motif) ligand 2 (Ccl2) as the primary gene altered in microglia within a rat SCI model, utilizing a public database. Microglial Ccl2 levels were then found to be significantly elevated in disc specimens from SCI patients diagnosed with chronic spinal compression and strongly correlated with the Thompson classification of the degeneration level and pain score. Depletion of Ccl2 in microglia-specific TMEM119 promoter were developed to transfect mouse microglia in vitro, resulting in a proinflammatory to anti-inflammatory phenotypic adaption. In vivo depletion of Ccl2 in microglia mitigated the severity of chronic spinal compression and related pain in ttw mice, likely due to significant changes in pain-associated cytokines and factors. Conclusion: Disc microglia expressing high levels of Ccl2 may contribute to chronic spinal compression and SCI-associated pain. Therapeutically targeting Ccl2 in microglia could offer a potential avenue for treating chronic spinal compression and SCI-associated pain.

The uncoupled anterior and posterior spinal ligament tension (UAPLT) - An improvement to three-dimensional spring model of adolescent idiopathic scoliosis (AIS) pathogenesis.

The pathogenesis of Adolescent Idiopathic Scoliosis (AIS) remains unclear. Previous research proposed that ligament laxity is a clinical feature that can be easily overlooked in patients with AIS. We speculated a new hypothesis which is an improvement of our three-dimensional spring model hypothesis of AIS pathogenesis. The tethered string in the spring model stimulates the spinal ligament instead of spinal cord. Spinal overgrowth in the adolescent age leads to higher tension of posterior spinal ligament. And the ligament laxity leads to lower tension of anterior spinal ligament. This uncoupled anterior and posterior spinal ligament tension maybe the key cause of AIS.

Upregulation of cGMP-dependent Protein Kinase (PRKG1) in the Development of Adolescent Idiopathic Scoliosis.

OBJECTIVE: To explore the molecular regulatory mechanisms underlying fibroblast differentiation and dysfunction in the development of adolescent idiopathic scoliosis (AIS) in an effort to identify candidate therapeutic targets for AIS. METHODS: The GSE110359 dataset, obtained from the bone marrow stromal cells of 12 AIS patients and five healthy controls, was retrieved from the GEO database. The data were preprocessed and differentially expressed genes (DEGs) were identified. KEGG pathway and Gene Ontology (GO)-Biological Process (BP) enrichment analyses were performed to identify the function of the DEGs. A protein-protein interaction (PPI) and a microRNA-transcription factor (TF)-target co-regulatory network were constructed to identify hub genes in the development of AIS. In addition, hub DEGs were evaluated by quantitative PCR (qPCR) and immunohistochemical staining. RESULTS: A total of 188 DEGs including 100 up-regulated and 88 down-regulated genes were obtained. The up-regulated DEGs were related to "p53 signaling pathway", "FoxO signaling pathway", and "cGMP-PKG signaling pathway" terms, while the down-regulated DEGs were significantly enriched in seven terms including "protein processing in endoplasmic reticulum". The key up-regulated genes, PRKG1, CCNG2, and KAT2B, and the key down-regulated genes, MAP2K1 and DUSP6, were identified by the PPI and miRNA-TF-Target regulatory network analyses. mRNA expression patterns for PRKG1, DUSP6, and KAT2B were successfully verified by qPCR. In addition, PRKG1 protein levels were found to be elevated during the immunohistochemical analysis. CONCLUSION: Increased expression of PRKG1 in AIS patients might be an attractive therapeutic target for AIS. However, further gain or loss-of-function studies should be conducted.

Gene sequence analysis and screening of feature genes in spinal cord injury.

The aim of the present study was to screen for feature genes associated with spinal cord injury (SCI), in order to identify the underlying pathogenic mechanisms. Differentially expressed genes were screened for using pre­processing data. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed to analyze and identify the genes involved in pathways associated with SCI. Subsequently, Gene Ontology enrichment analysis and Uniprot tissue analysis were used to screen out genes specifically expressed in spinal cord tissue. In addition, a protein­protein interaction network was used to demonstrate possible associations among SCI­associated feature genes. Finally, a link was identified between feature genes and SCI by analyzing protein domains in coding areas of the three feature genes. The cytochrome c oxidase subunit Va, adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F1 complex, α subunit 1 and cardiac muscle and mitochondrial ß­F1­ATPase may be downregulated in SCI, resulting in destruction of the mitochondrial electron transport chain and membrane­bound enzyme complexes/ion transporters, thus, affecting the normal function of nerves. The three screened feature genes have the potential to become candidate target molecules to monitor, diagnose and treat SCI and may be beneficial for the early diagnosis and therapeutic control of the condition.

Dysregulated COL3A1 and RPL8, RPS16, and RPS23 in Disc Degeneration Revealed by Bioinformatics Methods.

STUDY DESIGN: Bioinformatics analysis of published microarray data. OBJECTIVE: This study aimed to reveal the possible genes and pathways related to the pathogenesis of disc degeneration (DD) by analyzing the microarray data. SUMMARY OF BACKGROUND DATA: DD is one of the main causes of low back pain, which has become an enormous economic burden for society. METHODS: Gene expression data of annulus cells and nucleus pulposus cells from patients with DD and controls subjects were downloaded from Gene Expression Omnibus. T test and enrichment analysis were used to identify differentially expressed genes (DEGs) and DEGs-associated functions and pathways in DD, respectively. Protein-protein interaction network and module were constructed to analyze the key nodes associated with this disease. RESULTS: A total of 326 DEGs and 35 DEGs were obtained from the annulus cells and nucleus pulposus cells, respectively. The DEGs of DD in annulus cells were mainly involved in translation, cell adhesion, cell death regulation, and skeletal system development whereas the DEGs in nucleus pulposus cells were mainly related to the biological processes of vascular system development, skeletal system development, and enzyme-linked receptor protein signaling pathway. COL3A1 was the common DEG in both annulus cells and nucleus pulposus cells. The genes encode ribosomal proteins (RPL8, RPS16, and RPS23) in module were enriched in biological processes of translation, translation elongation, and RNA processing. CONCLUSION: The results revealed the involvement of COL3A1 in skeletal system process and RPL8, RPS16, and RPS23 in the protein synthesis processes in the progression of DD, suggesting their potential use in the diagnosis and therapy of DD. LEVEL OF EVIDENCE: N/A.

Identification of the relationships between sagittal plane and coronal plane curvature in guppy models.

OBJECTIVE: To explore the relationship between sagittal plane and coronal plane curvatures in guppies by investigating the curvature angles of sagittal and sagittal-coronal guppies. METHODS: After mating between 1000 spinal curvature guppies, 124 guppies (3-month old) were screened from progenies for the present study. Photos of all fishes were taken and the sagittal and coronal angles were calculated via angle measure tool of Photoshop 12.0 software. All data were analyzed by SPSS 11.0. RESULTS: In sagittal and sagittal-coronal curvature guppies, there was a significant linear correlation between sagittal angles and coronal angles. In 48 sagittal-coronal curvatures, their sagittal angles were above 40°, meanwhile, in 76 sagittal guppies, their sagittal angles were mostly below 40°. CONCLUSIONS: These findings indicated that the occurrence of coronal curvature might be later than sagittal curvature and could be influenced by other factors. Sagittal angles 40° might be involved in the onset of coronal curvature.

A valid cross-culturally adapted simplified Chinese version of the Quebec Back Pain Disability Scale.

OBJECTIVE: To evaluate the reliability and validity of the simplified Chinese version of the Quebec Back Pain Disability Scale (SC-QDS). STUDY DESIGN AND SETTING: The QDS was translated and cross-culturally adapted into SC following international guidelines. The SC-QDS was completed by 114 patients with low back pain (LBP) and 65 healthy controls, along with the SC Oswestry Disability Index (SC-ODI) and visual analogue scale (VAS). Psychometric evaluation included homogeneity and reproducibility by internal consistency and test-retest reliability and construct validity by calculating the Pearson's correlation coefficients among QDS, SC-ODI, and VAS. Discriminative validity was determined by student's t-test. RESULTS: SC-QDS scores were well distributed, with no floor or ceiling effects. Internal consistency was excellent (Cronbach α 0.976). The items and overall SC-QDS were correlated (r=0.640-0.898 and P<0.0001). Intraclass correlation coefficient of test-retest reliability was excellent (0.987, 95% confidence interval: 0.978-0.992). Construct validity was confirmed by high correlation of SC-QDS and SC-ODI (r=0.901 and P<0.0001) and VAS (r=0.770 and P<0.0001) scores, as was discriminative validity by significantly different SC-QDS scores for patients with LBP and controls (46.3 ± 19.9 vs. 14.6 ± 8.5 and P<0.0001). CONCLUSIONS: The SC-QDS has good internal consistency, test-retest reliability, and construct and discriminative validity. The SC-QDS is appropriate for clinical and research uses with Chinese-speaking patients with LBP in mainland China.

There may be a same mechanism of the left-right handedness and left-right convex curve pattern of adolescent idiopathic scoliosis.

The mechanism of the left-right handedness and pathogenesis of adolescent idiopathic scoliosis (AIS) is still unclear. We speculated that the pathogenesis of AIS may different from the mechanism of the laterality of convex curve pattern in AIS patients. This laterality may have correlation with the right dominance of handedness. The location and gravity of heart and aorta may determine the trend of lateral flexion and axial rotation of normal spine, which may be the reason of both left-right handedness and left-right convex curve pattern of AIS.

High selenium may be a risk factor of adolescent idiopathic scoliosis.

The pathogenesis of adolescent idiopathic scoliosis (AIS) remains little understood. Previous work has shown that guppy fish is an ideal animal model of idiopathic scoliosis which has similar epidemiological and morphological characteristic with AIS. However, some research speculated that the high-selenium environment could also induce idiopathic-type scoliosis of fish. We believe that the high-selenium related deformity of spine and guppy curveback syndrome may have the same pathogenesis. And high selenium may be a risk factor of AIS.

Three-dimensional spring model: a new hypothesis of pathogenesis of adolescent idiopathic scoliosis.

The pathogenesis of adolescent idiopathic scoliosis (AIS) has been the subject of many studies, but remains little understood. Previous work has shown that there is a correlation between the uncoupled spinal neuro-osseous growth and AIS. We believe that this uncoupled spinal neuro-osseous growth may also contribute to formation of normal curvature of the spine in the sagittal plane during the childhood. We speculate a three-dimensional spring model to better understand our hypothesis. The normal curvature of the spine, the uncoupled spinal neuro-osseous growth, and the overgrowth of the spine in the puberty may be the crucial factors in the pathogenesis of AIS.