Background/Aims: Congenital scoliosis (CS) is a result of anomalous development of vertebrae and is frequently associated with somitogenesis malformation. Although noncoding RNAs (ncRNAs) have been recently determined to be involved in the pathogenesis of CS, the competing endogenous RNA (ceRNA) regulatory networks in CS remain largely unknown. Methods: Sequencing was conducted to explore the ncRNA expression profiles in rat embryos (gestation day 9) following vitamin A deficiency (VAD) (n = 9 for the vitamin A deficiency-induced congenital scoliosis (VAD-CS) group and n = 4 for the control group). Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was conducted to verify the expression levels of selected mRNAs, long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs). Bioinformatics analysis was used to discover the possible relationships and functions of the ceRNAs. Results: A total of 749 mRNAs, 56 miRNAs, 685 lncRNAs, and 70 circRNAs were identified to have significantly different expression levels in the two groups. Wnt, PI3K-ATK, FoxO, EGFR, and mTOR were found to be the most significant pathways involved in VAD-CS pathogenesis. The circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks of CS were built, and the gene expression mechanisms regulated by ncRNAs were unveiled via the ceRNA regulatory networks. Conclusion: We comprehensively identified ceRNA regulatory networks of embryonic somite development in VAD-CS as well as revealed the contribution of different ncRNA expression profiles. Our data demonstrate the association between mRNAs and ncRNAs in the pathogenic mechanism of CS.

Study Design. Retrospective radiographic study. Objective. To investigate the growth of the vertebrae around distal instrumented vertebra (DIV) in patients with early-onset scoliosis (EOS) who underwent dual growing rod (DGR) treatment. Summary of Background Data. Previous studies indicated that DGR was likely to preserve or even stimulate the spinal growth. However, report pertaining to the effect of growing rod on the growth of individual vertebral body is rare. Methods. The EOS patients treated with DGR who had at least four lengthenings and 5-year follow-up were enrolled. Spine radiographs at index surgery and final follow-up were reviewed. The height, width, and depth of vertebral body from DIV–2 to DIV+2, and the height of the adjacent intervertebral space (IVS) were measured. The percentage of growth was calculated. Results. Thirty-one patients (mean age, 6.2 ± 2.5 years old) met the inclusion criteria, 74.2% (23/31) of whom were female. The average follow-up was 6.2 years (range, 5.0–10.4 yr). The measured vertebrae were divided into DIV group (n = 65), DIV- group (DIV-1 and DIV-2, n = 60), and DIV+ group (DIV+1 and DIV+2, n = 47). There were 33, 90, and 78 measured IVSs in DIV, DIV–, and DIV+ group, respectively. The total percentage growth of vertebral height was significantly higher in DIV– group than that in DIV and DIV+ groups (56.6 ± 20.3% vs. 45.6 ± 18.0% and 42.7 ± 16.2%, respectively, P ≤ 0.001). The vertebrae in DIV– group also had the highest annual height growth rate (8.7 ± 2.6% vs. 7.0 ± 2.4% and 6.6 ± 2.0%, respectively, P ≤ 0.001). A significant decrease of IVS height was observed in DIV– and DIV groups (P ≤ 0.001). Conclusion. Traditional DGR with periodical distraction stimulated the longitudinal growth of the two segments immediately above DIV in patients with EOS. DGR technique had a negative effect on the development of intervertebral discs within distracted levels. Level of Evidence: 3

Congenital scoliosis (CS) is the result of anomalous vertebrae development, but the pathogenesis of CS remains unclear. Long non‐coding RNAs (lncRNAs) have been implicated in embryo development, but their role in CS remains unknown. In this study, we investigated the role and mechanisms of a specific lncRNA, SULT1C2A, in somitogenesis in a rat model of vitamin A deficiency (VAD)‐induced CS. Bioinformatics analysis and quantitative real‐time PCR (qRT‐PCR) indicated that SULT1C2A expression was down‐regulated in VAD group, accompanied by increased expression of rno‐miR‐466c‐5p but decreased expression of Foxo4 and somitogenesis‐related genes such as Pax1 , Nkx3‐2 and Sox9 on gestational day (GD) 9. Luciferase reporter and small interfering RNA (siRNA) assays showed that SULT1C2A functioned as a competing endogenous RNA to inhibit rno‐miR‐466c‐5p expression by direct binding, and rno‐miR‐466c‐5p inhibited Foxo4 expression by binding to its 3′ untranslated region (UTR). The spatiotemporal expression of SULT1C2A, rno‐miR‐466c‐5p and Foxo4 axis was dynamically altered on GDs 3, 8, 11, 15 and 21 as detected by qRT‐PCR and northern blot analyses, with parallel changes in Protein kinase B (AKT) phosphorylation and PI3K expression. Taken together, our findings indicate that SULT1C2A enhanced Foxo4 expression by negatively modulating rno‐miR‐466c‐5p expression via the PI3K‐ATK signalling pathway in the rat model of VAD‐CS. Thus, SULT1C2A may be a potential target for treating CS.

No abstract

Objective The aim of the present study was to investigate whether an innovative way of administering tranexamic acid (TXA), that is, injecting it retrogradely through the drain and clamping it for 1 h, can reduce postoperative bleeding after degenerative lumbar scoliosis surgery. Methods Sixty degenerative lumbar scoliosis patients who underwent posterior lumbar decompression with fusion of three or more levels were retrospectively enrolled and categorized into three groups (TXA, Gelfoam, and control groups). The demographic distribution, operative parameters, length and amount of Hemovac drainage, blood transfusion rate, length of stay, laboratory results (complete blood count and coagulogram), and the postoperative complications were collected and analyzed. Results The age of patients in the Gelfoam group was significantly younger than in the TXA and control groups (59.75 ± 6.95 vs 66.10 ± 8.80, P = 0.016 and 59.75 ± 6.95 vs 67.90 ± 5.33, P = 0.000, respectively). There were no significant differences in sex, body mass index, comorbid medical status, and operation level between each of the two groups. The three groups did not differ significantly in estimated blood loss during surgery, the mean red blood cell transfusion requirement during hospitalization, and the entire perioperative allogenic blood transfusion rate. The postoperative total blood loss and total drainage were lower in the TXA group than in the control group (1027.14 ± 466.56 vs 1390.07 ± 314.85 mL, P = 0.006; 322.20 ± 187.32 vs 605.50 ± 184.70 mL, P = 0.000, respectively). The length of drainage retention in the TXA group was significantly shorter than in the Gelfoam and control groups (46.10 ± 9.00 vs 68.00 ± 12.31 h, P = 0.000 and 46.10 ± 9.00 vs 76.40 ± 10.97 h, P = 0.000, respectively). The TXA and Gelfoam groups also had significantly shorter hospital stays than the control group (7.50 ± 0.95 vs 9.80 ± 2.44 days, P = 0.000, and 7.90 ± 1.16 vs 9.80 ± 2.44 days, P = 0.003, respectively). At discharge, the mean hemoglobin and hematocrit level were significantly higher in the TXA group compared with the control group (11.77 ± 1.78 g/dL vs 10.67 ± 0.94 g/dL, P = 0.002; 34.82 ± 3.57% vs 31.79 ± 3.85%, P = 0.014). No significant difference was identified with respect to prothrombin time, activated partial thromboplastin time, and D‐dimmer among groups (P > 0.05). The three groups were comparable in wound problem incidences. Symptomatic deep vein thrombosis and pulmonary embolism were not observed in this study. Conclusion Topical injection of TXA retrogradely via a drain at the end of a degenerative lumbar scoliosis operation and clamping the drain for an hour can effectively decrease the postoperative blood loss and the length of hospitalization without increasing the complication rate.

Study Design. A prospective study of cardiopulmonary function in patients with congenital scoliosis (CS). Objective. To investigate the relationship of thoracic cage deformity and exercise tolerance in CS patients. Summary of Background Data. Congenital thoracic scoliosis and chest deformity lead to restrictive pulmonary dysfunction and in some severe cases cause cardiopulmonary failure. However, it is still unknown the relationship between thoracic deformity and exercise performance. Methods. Patients with congenital thoracic spinal deformity were included and had radiological assessment of thoracic cage, pulmonary function testing, and cardiopulmonary exercise testing. Thoracic dimension including height, width, and depth were measured and geometry parameters were calculated. Two-tailed Pearson and Spearman correlation test and linear regression analysis were performed to investigate correlation of radiographic parameters, pulmonary function, and physical capacity. Results. Sixty patients (41 females and 19 males) were included, with an average age of 18.9 years. Patients with smaller thoracic height (P < 0.001) and width (P < 0.01) and larger depth (P < 0.05) had significantly worse static pulmonary function. In exercise testing, these patients showed significant tendency of ventilation insufficiency, including lower minute ventilation (P < 0.05), faster breathing frequency (P < 0.05), and smaller tidal volume (P < 0.01). Thoracic depth was negatively correlated to exercise capacity, reflected by work rate (P < 0.001), peak oxygen intake (P < 0.001), and heart rate (P = 0.043). Patients with abnormal thoracic geometry, especially a lower ratio of height to depth and a lower ratio of width to depth, have significantly worse static pulmonary function and exercise capacity (all P < 0.05). Conclusion. Decreasing thoracic height and width results in restrictive pulmonary dysfunction. Distortion and asymmetry of the thoracic cage are associated with abnormal breathing pattern and reduction of exercise capacity. Level of Evidence: 3

The pathogenesis of ankylosing spondylitis (AS) remains undetermined. Ferroptosis is a newly discovered form of regulated cell death involved in multiple autoimmune diseases. Currently, there are no reports on the connection between ferroptosis and AS. Methods: AS samples from the Gene Expression Omnibus were divided into two subgroups using consensus clustering of ferroptosis-related genes (FRGs). Weighted gene co-expression network analysis (WGCNA) of the intergroup differentially expressed genes (DEGs) and protein–protein interaction (PPI) analysis of the key module were used to screen out hub genes. A multifactor regulatory network was then constructed based on hub genes. Results: The 52 AS patients in dataset GSE73754 were divided into cluster 1 (n = 24) and cluster 2 (n = 28). DEGs were mainly enriched in pathways related to mitochondria, ubiquitin, and neurodegeneration. Candidate hub genes, screened by PPI and WGCNA, were intersected. Subsequently, 12 overlapping genes were identified as definitive hub genes. A multifactor interaction network with 45 nodes and 150 edges was generated, comprising the 12 hub genes and 32 non-coding RNAs. Conclusions: AS can be divided into two subtypes according to FRG expression. Ferroptosis might play a regulatory role in AS. Tailoring treatment according to the ferroptosis status of AS patients can be a promising direction.

No abstract