Ferrostatin-1 facilitated neurological functional rehabilitation of spinal cord injury mice by inhibiting ferroptosis.

BACKGROUND: To seek the potential therapy for spinal cord injury, Ferrostatin-1, the first ferroptosis inhibitor, was administrated in spinal cord injury mice to identify the therapeutic effect. METHODS: Spinal cord injury model was established by a modified Allen's method. Then, ferrostatin-1 was administrated by intraspinal injection. Cortical evoked motor potential and BMS were indicated to assess the neurological function rehabilitation. H&E, Nissl's staining, NeuN, and GFAP immunofluorescence were used to identify the histological manifestation on the mice with the injured spinal cord. Spinosin, a selective small molecule activator of the Nrf2/HO-1 signaling pathway, was administrated to verify the underlying mechanism of ferrostatin-1. RESULTS: Ferrostatin-1 promoted the rehabilitation of cortical evoked motor potential and BMS scores, synchronized with improvement in the histological manifestation of neuron survival and scar formation. Spinosin disturbed the benefits of ferrostatin-1 administration on histological and neurobehavioral manifestation by deranging the Nrf2/HO-1 signaling pathway. CONCLUSIONS: Ferrostatin-1 improved the rehabilitation of spinal cord injury mice by regulating ferroptosis through the Nrf2/HO-1 signaling pathway.

The Correlation of Global Spinal Realignment With the Quality of Life After Corrective Surgery for Delayed Thoracolumbar Osteoporotic Fracture-Related Kyphosis.

BACKGROUND AND OBJECTIVES: Few studies have been conducted to evaluate the precise impact of corrective surgery on sagittal spinal realignment and clinical outcomes in cases of delayed thoracolumbar osteoporotic fracture-related kyphosis. To assess the efficacy of corrective surgery on sagittal spinal alignment and investigate the relationship between spinal alignment and health-related quality of life (HRQoL) in patients with delayed thoracolumbar osteoporotic fracture-related kyphosis. METHODS: A total of 78 patients were enrolled. The characteristics and surgical variables were meticulously documented. The sagittal spinal parameters were measured, and the HRQoL was evaluated using Oswestry Disability Index (ODI), SF-12 Physical Component Score (SF-12 PCS), and Scoliosis Research Society-22 Patient Questionnaire (SRS-22) before and after surgery. The changes in spinal parameters and HRQoL were analyzed through the paired t -test. The Pearson correlation analysis was performed to analyze the correlation of parameters with HRQoL. Then, a multiple stepwise regression analysis was performed with HRQoL scores as the dependent variable and spinal parameters as the independent variable. RESULTS: The operative time was 185.9 ± 33.2 min, and the estimated blood loss was 782.8 ± 145.2 mL. The results of the paired t -test revealed a significant difference preoperatively and at the final follow-up in the thoracic kyphosis, thoracolumbar kyphosis (TLK), lumbar lordosis, T9 tilt, pelvic tilt, sacral slope, sagittal vertical axis, and spinosacral angle as well as the ODI, SF-12 PCS, and SRS-22 ( P < .05). Multiple stepwise regression analysis revealed that TLK and pelvic tilt, TLK and sagittal vertical axis, and TLK were the primary parameters affecting the ODI, SF-12 PCS, and SRS-22, respectively. CONCLUSION: Corrective surgery can effectively realign the global spine and improve HRQoL in patients with delayed thoracolumbar osteoporotic fracture-related kyphosis. The change of TLK is a driving factor to realign the global spine.

Bone marrow mesenchymal stem cell-derived exosomal LINC00847 inhibits the proliferation, migration, and invasion of Ewing sarcoma.

Background: Ewing sarcoma (ES) is one of the most lethal primary bone tumors with a poor survival rate. Current evidence suggests that extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) loaded with abundant biological functional lncRNAs confer therapeutic benefits against the development of various tumors. Aim: This study aimed to investigate the role of exosomal lncRNAs from BMSCs in the pathogenesis of ES. Methods: Bioinformatic analysis and quantitative real time-polymerase chain reaction (qRT-PCR) experiments were used to detect the expression level of LINC00847 in ES tissues and cells. Cell biology experiments examined the effect of in vitro proliferation, migration, and invasion abilities and the biological function of BMSCs-derived LINC00847. Finally, we constructed a LINC00847-associated competitive endogenous RNA (ceRNA) network by in silico methods. Gene Set Enrichment Analysis (GSEA) was conducted to reveal the potential molecular mechanism of LINC00847. Results: We found that LINC00847 was markedly downregulated in ES. Overexpression of LINC00847 inhibited ES cell proliferation, migration, and invasion. Furthermore, BMSCs-derived EVs inhibited the proliferation, migration, and invasion of ES cells by delivering LINC00847. We constructed a LINC00847 related-ceRNA network contains five miRNAs (miR-18a-5p, miR-18b-5p, miR-181a-5p, miR-181c-5p, and miR-485-3p) and four mRNAs (GFPT1, HIF1A, NEDD9, and NOTCH2). Conclusions: Overall, this study found that BMSCs-EVs-derived exosomal LINC00847 inhibited ES cell proliferation, migration, and invasion. The ceRNA regulatory mechanism of LINC00847 may participate in the pathogenesis of the malignant phenotype of ES. Relevance for Patients: These findings suggest that BMSCs-derived exosomal lncRNAs may be used for the personalized treatment of tumors, providing a novel theoretical framework for treating ES.

Posterior Approach With Osteotomized Debridement Versus Combined Anterior and Posterior Approach in Treating Thoracolumbar Tuberculosis: A Retrospective Cohort Study.

STUDY DESIGN: Retrospective cohort. OBJECTIVES: To compare outcomes of posterior osteotomized debridement (OD) with combined anterior and posterior approach (AP) in treating thoracolumbar tuberculosis (TB). METHODS: This study reviewed 178 patients who were diagnosed as active thoracolumbar TB and surgically treated in our center. One hundred and two patients underwent posterior OD, interbody fusion with titanium mesh cage (TMC), and instrumentation (group A). Seventy-six patients underwent one-stage posterior instrumentation, anterior debridement, and interbody fusion with TMC (group B). Patients' clinical outcomes were compared between the 2 groups. RESULTS: Erythrocyte sedimentation rate and C-reactive protein in all patients returned to normal levels within 3 months after surgery, and no recurrence occurred during the follow-up. Compared with AP approach, OD surgery was less invasive and with a lower cost (¥ 70 581 ± 17 645 vs ¥ 87 600 ± 27 328; P < .05). Patients treated by OD showed more significant improvements in Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) than those treated by AP approach 3 months postoperatively (VAS: 3.0 ± .7 vs 3.7 ± .9; ODI: 14.7 ± 4.4 vs 20.6 ± 4.6). Two groups showed similar postoperative kyphosis correction and final follow-up correction loss (P = .361 and P = .162, respectively). The OD method had a lower complication rate than AP approach (9.8% [10/102] vs 35.5% [27/76]; P < .05). CONCLUSIONS: Posterior OD is effective in treating active thoracolumbar TB. Compared with traditional AP approach, OD surgery has less surgical invasiveness, lower complication rate, and shorter fusion time.

Global Spinal Realignment After Osteotomized Debridement in Active Lumbar Spinal Tuberculosis: Correlation with Patient-Reported Outcomes.

OBJECTIVE: Osteotomized debridement (OD) has been proved to be highly effective in treating active thoracolumbar tuberculosis (TB); however, no research has investigated how OD affects spinal alignment. The goal of this study was to explore the global alignment compensatory mechanism after lumbar OD, as well as the correlation between spinopelvic parameters and patient-reported outcomes (PROs). METHODS: Sixty-two patients with active lumbar spinal TB who underwent OD surgery were included. Spinopelvic parameters (C2-7 Cobb angle [C2-7 CA], sagittal vertical axis [SVA], proximal thoracic kyphosis, thoracic kyphosis, lumbar lordosis [LL], sacral slope [SS], pelvic tilt [PT], pelvic incidence [PI], spinosacral angle, and PI minus LL [PI-LL]) and PROs (Oswestry Disability Index [ODI] and Visual Analog Scale [VAS] score) were reviewed. The correlation between spinopelvic realignment and improved PROs was evaluated. RESULTS: Compared with preoperative measurements, C2-7 CA, proximal thoracic kyphosis, thoracic kyphosis, LL, SS, and spinosacral angle significantly increased after OD, whereas SVA, PT, and PI-LL significantly decreased. ODI and VAS score significantly improved postoperatively. The improvement of VAS was observed to be correlated with variations of C2-7 CA, SVA, LL, and PI-LL. The improvement of ODI was found to be correlated with variations of SVA, LL, and PI-LL. The multiple stepwise regression analysis showed that LL was an independent predictor for ODI and VAS score. CONCLUSIONS: The whole spine and pelvis are involved in realignment after lumbar spinal OD, which is closely related to PROs. More attention should be drawn to restoring an appropriate LL in lumbar TB surgery.

Two-Level Pedicle Subtraction Osteotomy in Lateral Position for an Ankylosing Spondylitis Patient With Severe Thoracolumbar Kyphosis and Hip Flexion Contracture: A Case Report.

BACKGROUND AND IMPORTANCE: Spinal osteotomy and total hip replacement (THR) are the most common surgical interventions for ankylosing spondylitis (AS). It is recommended that patients with AS with severe thoracolumbar kyphotic deformity (TLKD) and flexed hips receive spinal osteotomy before THR to reduce the risk of hip prosthesis dislocation after THR. Standardly, spinal osteotomy is performed in the prone position; however, it is impractical to place patients with AS with kyphosis and closed hips in a prone position. In this report, we present an AS case with severe TLKD and closed hips who underwent spinal osteotomy in a lateral position first, then THR in the second stage. CLINICAL PRESENTATION: The patient with AS was a 40-year-old woamn with severe TLKD and a closed hip. Back pain, difficulty walking, and gaze loss are the chief complaints. In consideration of the infeasibility of adopting the prone position, the patient was placed in a lateral position and underwent 2-level pedicle subtraction osteotomy at L1 and L3 with a long instrumentation from T10 to S1 at the first stage. Then, THR was performed at the second stage. The patient achieved pain relief, horizontal gaze, and nearly normal ambulation after spinal deformity correction and THR. After 2-year follow-up, the spinal alignment remains good and hip function was satisfactory. DISCUSSION: The sequence of spinal osteotomy and THR performed for AS patients with TLKD and hip flexion contracture remains inconclusive. According to previous studies, patients treated with THR under a sagittal malaligned spine may require revision of the acetabular component to accommodate to the re-orientated acetabula resulting from the subsequent spinal osteotomy and realignment. Thus, we believe it is more reasonable to perform spinal osteotomy first. For osteotomy in lateral position, one of the key points is that the operation table should be tilted away from the surgeon side at a certain angle. Another point is that contralateral cancellous bone should be removed as much as possible when performing osteotomy at the side of vertebral away from the table. The satisfactory outcomes of this case revealed the feasibility of osteotomy in a lateral position for such severe AS with closed hip. CONCLUSION: Performing double-level spinal osteotomy in a lateral position first could be an alternative for patients with AS who cannot be placed in the prone position because of the severe deformity of the spine and hips.

Case Report of Angular Post-Tuberculotic Kyphosis Corrected Through Pedicle Subtraction Osteotomy Above C7.

BACKGROUND AND IMPORTANCE: Angular cervical kyphosis and its association with syringomyelia were rarely described. Correcting this kind of deformity from the front is extremely difficult or even impossible. Meanwhile, no study has made a report about correcting angular cervical kyphosis through pedicle subtraction osteotomy (PSO) above C7 because of the special anatomy of the vertebral artery. This is the first case of cervical deformity correction through PSO above C7. CLINICAL PRESENTATION: We present the case of a 52-yr-old man who previously underwent debridement, decompression, and skull traction for cervical tuberculosis at age 6 yr. The sequelae of right-hand weakness occurred after surgery, and cervical kyphosis formed gradually. The patient recently started to complain of a severe neck pain. X-rays showed a cervical sagittal malalignment due to the angular kyphosis. Computed tomography scans revealed a fused angular kyphosis at C6-7, and MRI showed a long syringomyelia distal to the kyphosis. The definite diagnosis of the patient was post-tuberculotic cervical angular kyphosis, and because of the extremely narrow surgery corridor from the front, we decided to perform the surgery in a posterior approach. Hence, the patient was treated with the PSO with a long-segment pedicle screw fixation from C3 to T5 and received satisfactory angular kyphosis correction. CONCLUSION: PSO above C7 to correct angular cervical kyphosis is feasible and reasonable when there is no other better solution, and it can achieve a satisfactory kyphotic deformity correction.

Ball Tip Technique for S2AI Screw Placement in Sacropelvic Fixation: A Comparative Study with Conventional Freehand Technique.

OBJECTIVE: To evaluate the efficiency of the ball tip technique for S2AI screw placement and introduce this technique. METHODS: Sixty-three patients who underwent pelvic fixation with S2AI screws were retrospectively reviewed. They were 29 males and 34 females with an average age of 59.6 ± 12.5 years. Among these patients, 35 patients (14 males and 21 females with an average age of 58.8 ± 11.3 years) received ball tip technique and 28 patients (15 males and 13 females with an average age of 63.7 ± 12.6 years) received conventional freehand technique. Ball tip technique was used in ball tip technique group. After a pedicle probe just penetrated the sacroiliac joint, a ball-tipped probe consisting of a ball shaped metal tip with a flexible shaft was malleted to make a guide track within ilium. This ball-tipped probe could bend automatically away from the cortex and forward through the cancellous bone when the tip met the cortical lamina of ilium, which can avoid penetration. After repeating the procedures, a guide hole was gradually formed. S2AI screw was inserted along the guide hole after tapping. In the conventional freehand group, S2AI screw was placed according to the conventional method. Postoperative computed tomography (CT) was used to assess the accuracy of screws. The time cost of screw insertion and screw-related complications were recorded. Independent t-test was used to compare the time cost between ball tip group and conventional freehand group. A chi-square test was used to compare the accuracies of the ball tip group with the conventional group. RESULTS: There were 35 patients (70 S2AI screws) in ball tip group and 28 patients (56 S2AI screws) in conventional freehand group. No screw-related complication occurred in all patients. Time costs were 9.8 ± 4.5 mins in ball tip group and 20.2.0 + 8.6 mins in conventional freehand group, respectively (P < 0.05). Four screws penetrated iliac cortex in the ball tip group vs 10 screws in conventional freehand group (5.7% vs 17.9%) (P < 0.05). CONCLUSIONS: The ball tip technique enhances the accuracy of screw placement and has less time cost compared with conventional freehand technique.

Let-7a suppresses Ewing sarcoma CSCs' malignant phenotype via forming a positive feedback circuit with STAT3 and lin28.

Cancer stem cells (CSCs) have been documented to be closely related with tumor metastasis and recurrence, and the same important role were identified in Ewing Sarcoma (ES). In our previous study, we found that let-7a expression was repressed in ES. Herein, we further identified its putative effects in the CSCs of ES (ES-CSCs). The expression of let-7a was consistently suppressed in the separated side population (SP) cells, which were identified to contain the characteristics of the stem cells. Then, we increased the expression of let-7a in ES-CSCs, and found that the ability of colony formation and invasion of ES-CSCs were suppressed in vitro. The same results were found in the tumor growth of ES-CSCs' xenograft mice in vivo. To further explore the putative mechanism involved, we also explored whether signal transducer and activator of transcription 3 (STAT3) was involved in the suppressive effects. As expected, excessive expression of let-7a could suppress the expression STAT3 in the ES-CSCs, and repressed the expression of STAT3 imitated the suppressive effects of let-7a on ES-CSCs, suppressing the ability of colony formation and invasion of ES-CSCs. Furthermore, we found lin28 was involved in the relative impacts of let-7a, as well as STAT3. Let-7a, STAT3 and lin28 might form a positive feedback circuit, which serve a pivotal role in the carcinogensis of ES-CSCs. These findings maybe provide assistance for patients with ES in the future, especially those with metastasis and recurrence, and new directions for their treatment.

LncRNA FOXP4-AS1 Promotes Progression of Ewing Sarcoma and Is Associated With Immune Infiltrates.

Ewing sarcoma (ES) is a highly malignant primary bone tumor with poor prognosis. Studies have shown that abnormal expression of lncRNA influences the prognosis of tumor patients. Herein, we established that FOXP4-AS1 was up-regulated in ES and this correlated with poor prognosis. Further analysis illustrated that FOXP4-AS1 down-regulation repression growth, migration, along with invasion of ES. On the contrary, up-regulation of FOXP4-AS1 promoted the growth, migration, as well as invasion of ES. To explore the mechanism of FOXP4-AS1, Spearman correlation analysis was carried out to determine genes that were remarkably linked to FOXP4-AS1 expression. The potential functions and pathways involving FOXP4-AS1 were identified by GO analysis, Hallmark gene set enrichment analysis, GSEA, and GSVA. The subcellular fractionation results illustrated that FOXP4-AS1 was primarily located in the cytoplasm of ES cells. Then a ceRNA network of FOXP4-AS1 was constructed. Analysis of the ceRNA network and GSEA yielded two candidate mRNAs for FOXP4-AS1. Results of the combined survival analysis led us to speculate that FOXP4-AS1 may affect the expression of TMPO by sponging miR-298, thereby regulating the malignant phenotype of ES. Finally, we found that FOXP4-AS1 may modulates the tumor immune microenvironment in an extracellular vesicle-mediated manner. In summary, FOXP4-AS1 correlates with poor prognosis of ES. It promotes the growth, migration, as well as invasion of ES cells and may modulate the tumor immune microenvironment.

The three-dimensional printed template guided technique for S2 alar iliac screw placement and a comparison with freehand technique.

PURPOSE: Sacropelvic fixation continues to present challenges when involved in the adult spinal deformity correction. The S2 alar iliac (S2AI) fixation is commonly used in sacropelvic fixation. Several techniques, including intraoperative navigation and freehand technique, were used for S2AI screws placement. The aim of this study is to analyze the anatomic parameters for S2AI screw trajectory in Asian population and introduce a novel technique described as a three-dimensional printed template guided technique (TGT). Meanwhile, the accuracy and safety of this technique were compared with the conventional freehand technique. METHODS: The S2AI trajectory parameters were measured in 100 Asian adult volunteers. Parameters were compared between different genders. Forty-eight adult patients who underwent S2AI screw placement were reviewed: 28 patients received freehand technique and 20 patients received TGT technique. Postoperative computed tomography was used to assess the accuracy of screw trajectory and cortex violation-related complications were recorded. RESULTS: The cephalocaudal angles (CAs), maximal length of screw pathway, narrowest width of pathway within the iliar teardrop, distance from the center of teardrop to sciatic notch, and distance of the start point distal to S1 dorsal foramen showed significant gender-related difference (p < 0.05). All 48 patients were placed S2AI screws bilaterally (40 screws in TGT vs. 56 screws in freehand). One screw penetrated iliac cortex in the TGT group but 10 screws penetrated iliac cortex in the freehand group (3% vs. 17.9%) (p < 0.05). CONCLUSION: Approximately 30-35° of CA and 39° mediolateral angle are appropriate for S2AI screw placement in Asian patients. Either freehand or TGT technique is safe for S2AI screw placement. TGT technique is more accurate compared with the conventional freehand technique. TRIAL REGISTRATION: This is a retrospective study.

MicroRNA-30a regulates chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells through targeting Sox9.

Cartilage injury is difficult to repair since the cartilage tissue lacks self-restoration ability. Improved formation of chondrocytes differentiated from the mesenchymal stem cells (MSC) by genetic regulation is a potentially promising therapeutic option. SOX9 is a critical transcription factor for mesenchymal condensation prior to chondrogenesis. Previous studies demonstrated that several microRNAs (miRNAs or miRs) play a critical role in the chondrogenic differentiation of MSCs. However, the interactional relations between miR-30a and SOX9 during chondrogenic differentiation of MSCs need to be further elucidated. In the present study, human bone marrow-derived mesenchymal stem cells have been isolated and induced into chondrogenic differentiation to imitate the cartilage formation in vitro. Additionally, the expression levels of several miRNAs that were reported to interact with the SOX9 3'untranslated region (UTR) were examined by using reverse transcription-quantitative PCR. The interactional relations between candidate miRNAs and SOX9 were verified with the transfection of a miRNA mimic or inhibitor and a luciferase reporter gene assay. The results indicate that miR-30a and miR-195 were consistently increased during MSC chondrogenic differentiation. Additionally, the binding of miR-30a to the SOX9 3UTR was verified. Then, the authors upregulated the expression of miR-30a and found that MSC chondrogenic differentiation was inhibited. Taken together, the results of the present study demonstrate that miR-30a has a negative regulatory effect on MSC chondrogenic differentiation by targeting SOX9. Advances in epigenetic regulating methods will likely be the future of systemic treatment of cartilage injury.

Rational construction and remarkable gas adsorption properties of a HKUST-1-like tbo-type MOF based on a tetraisophthalate linker.

To target a condensed version of the HKUST-1-like tbo-type MOF MFM-181, a new tetraisophthalate ligand, 3,6-dimethyl-1,2,4,5-tetra(5'-isophthalic acid)benzene, was rationally designed and synthesized based on ligand contraction and conformation preorganization strategy. Compared to its parent compound MFM-181, the resulting MOF ZJNU-10 features smaller cage sizes as well as higher density of open copper sites, thus endowing the material with the promising potential for C2H2/CH4 and CO2/CH4 separations associated with C2H2 purification and natural gas sweetening. At 298 K and atmospheric pressure, the uptake capacities of C2H2 and CO2 reach 151.5 and 108.3 cm3 (STP) g-1, while the IAST-predicted adsorption selectivities of C2H2 and CO2 over CH4 are up to 29.9 and 7.6, respectively.

High Ghrelin Level Predicts the Curve Progression of Adolescent Idiopathic Scoliosis Girls.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is common deformity with unknown cause. Previous studies have suggested the abnormal serum leptin and ghrelin level in AIS girls. The aim of present study was to evaluate whether the serum leptin and ghrelin level could serve as risk factor in predicting the curve progression in AIS girls. The associations between them and the physical characteristics were also investigated. MATERIALS AND METHODS: Circulating leptin and ghrelin levels from 105 AIS girls and 40 age-matched non-AIS girls were examined by enzyme-linked immunosorbent assay. The correlations between ghrelin and leptin levels and growth-related parameters (age, weight, corrected height, corrected BMI, main Cobb angle, and Risser sign) were analyzed in AIS group. Multivariate logistic regression was used to investigate factors predicting curve progression in AIS girls. RESULTS: A significantly lower leptin level (6.55 ± 2.88 vs. 8.01 ± 3.12 ng/ml, p < 0.05) and a higher ghrelin level (6.33 ± 2.46 vs. 4.46 ± 2.02 ng/ml, p < 0.05) were found in all AIS patients, as compared with normal controls. Curve progression patients had a higher ghrelin level than stable curve patients (7.61 ± 2.48 vs. 5.54 ± 2.11 ng/ml, p < 0.01); for leptin level, there was no significant difference between progression and stable group. The results of multivariate logistic stepwise regression showed that premenarche status, initial main Cobb magnitude that was more than or equal to 23°, high ghrelin level (≥7.30 ng/ml), and lower Risser grade (grades 0 to 2) were identified as risk factors in predicting curve progression. Ghrelin levels of >6.48 ng/ml were predictive for curve progression with 70.00 % sensitivity and 72.31 % specificity, and the area under the curve (AUC) was 0.741 (95 % confidence interval 0.646-0.821). CONCLUSIONS: High ghrelin level may serve as a new quantitative indicator for predicting curve progression in AIS girls.

More preoperative flexibility implies adequate neural pliability for curve correction without prophylactic untethering in scoliosis patients with asymptomatic tethered spinal cord, a retrospective study.

BACKGROUND: Tethered spinal cord is frequently associated with scoliosis. It is still controversial whether a prophylactic untethering is necessary before correction procedure in scoliosis patients with tethered spinal cord. In this study we determined the clinical outcome of a one-stage posterior scoliosis correction without a prophylactic untethering for treating scoliosis with an asymptomatic tethered spinal cord. METHODS: Seventeen (5 males and 12 females) scoliosis patients with tethered spinal cords were retrospectively reviewed. All patients underwent a one-stage posterior scoliosis correction without preventive untethering. Parameters of radiograph were used to assess correction result. The Scoliosis Research Society (SRS)-22 questionnaire was analyzed pre- and post-operatively to evaluate the clinical outcomes. The modified Japanese Orthopaedic Association (mJOA) score was used to assess the pre- and post-operative spinal cord function. RESULTS: The post-operative coronal Cobb angle was significantly decreased compared with preoperative. (23.8 ± 6.4° vs. 58.4 ± 12.6°, P < 0.01). The coronal Cobb angle was 22.4 ± 6.8° at the final follow-up evaluation. The apical vertebral translation (AVT) was also decreased significantly. (27.5 mm vs. 60.9 mm, P < 0.01). The SRS-22 total score was improved at the 1-year follow-up evaluation compared with the pre-operative SRS-22 total score (87 ± 4 vs. 70 ± 5, p < 0.05). The functional activities, pain, self-image, mental health, and surgery satisfactory scores at the final follow-up evaluation were all improved compared with the corresponding pre-operative scores, especially the self-image and mental health scores (p < 0.05). The spinal cord function was stable and there was no new neurological symptoms after scoliosis correction. No difference existed between the pre- and post-operative total mJOA score (26 ± 2 vs. 27 ± 2, p = 0.39), which including subjective symptom (p = 0.07), clinical symptom (p = 0.33), daily activities (p = 0.44) and bladder function (p = 0.67). CONCLUSION: One-stage posterior scoliosis correction is a safe and effective surgical procedure for scoliosis patients combined with asymptomatic tethered spinal cord who have adequate spinal cord function reserve.

Management of eosinophilic granuloma in pediatric patients: surgical intervention and surgery combined with postoperative radiotherapy and/or chemotherapy.

BACKGROUND: Eosinophilic granuloma (EG) of spine in pediatric patients presents kinds of clinical manifestation and a difficult management scenario. The choice of treatment, issues of surgical intervention versus conservative treatment, combination therapy or single treatment, all these factors, including neurological deficits, spinal stability, long-term complications, and continued skeletal growth, must be considered. METHODS: From 2008 to the 2015, 31 pediatric patients of spinal EG were retrospectively reviewed. They were 17 males and 14 females, with a mean age 8.89 ± 2.84 years old (range, 3.5-14 years old). All the cases were divided into two groups. Twenty-three cases (Group S) accepted surgical interventions and surgery combined with local low-dose radiotherapy and/or chemotherapy. Eight patients (Group C) accepted radiotherapy and/or chemotherapy. All the patients had imaging studies of the lesion including standard radiography, three-dimensional computed tomography (CT) scan, and magnetic resonance imaging (MRI) prior to and after treatment. Cases in group S underwent surgery-related treatment, which include six patients accepted surgery only, nine patients accepted postoperative low-dose radiotherapy, four patients accepted additional chemotherapy, and four patients accepted both. Cases in group C accepted radiotherapy and/or chemotherapy, which include five patients accepted radiotherapy, one patient accepted chemotherapy, and two patients accepted both radiotherapy and chemotherapy. Clinical symptoms, neurologic status, radiologic manifestations, treatment, outcome, and/or complications were recorded and analyzed. RESULTS: All the 31 patients had pain relief (both in group S and group C) but the patients in group S obtained more prompt pain relief. All the patients in group S obtained local kyphosis correction, reconstruction of stability of spine, and recovery of neurological deficit after treatment. They have no surgery-related complications after treatment and in follow-up. Seventeen patients who received additional postoperative radiotherapy and/or chemotherapy also had good outcomes. There were no severe radiation and chemotherapy complications in procedure. The patients (group C) who accepted non-surgical treatment also have no severe complications, and a new femur lesion was found in one patient in follow-up. CONCLUSION: Surgical intervention, including anterior and/or posterior approach with bone graft or surgery combined with postoperative low-dose radiotherapy and/or chemotherapy is a safe and effective way for treatment of the spinal EG. Compared with radiotherapy and/or chemotherapy, more prompt pain relief can be achieved via surgical intervention or surgery combined radiotherapy and/or chemotherapy.

Treatment of kyphosis in ankylosing spondylitis by osteotomy through the gap of a pathological fracture: a retrospective study.

BACKGROUND: Surgical interventions are commonly advocated for correcting kyphotic deformities and relieving severe back pain in ankylosing spondylitis (AS) patients. The aim of this study was to evaluate the clinical outcome of osteotomy performed through the gap of a pathological fracture for the treatment of kyphosis in ankylosing spondylitis and to introduce the key points of this novel surgical approach. METHODS: From January 1, 2010, to December 31, 2014, 13 consecutive AS patients who were treated with osteotomy through the fracture gap were retrospectively reviewed. Patients underwent the radiographic assessment of sagittal balance parameters. Visual analog scale (VAS) scores were used to assess improvement in back pain. RESULTS: The average follow-up time was 2 years and 1 month. The median operation time was 280 min (range, 220-460 min). The mean blood loss was 1100 mL (range, 820-1300 mL). No major acute complications such as death or complete paralysis occurred. There were no neurologic complications or cerebrospinal fluid leaks in any patient. One patient had postoperative wound infection, which subsided after a switch of antibiotics. The global kyphosis Cobb angle of patients decreased from the preoperative 55.8° ± 11.0° to 23.2° ± 6.7° (P < 0.001) after surgery. The C7 plumb line was used to assess global balance; its relationship with the posterosuperior corner of the sacrum decreased from 166 ± 37 mm to 111 ± 20 mm (P < 0.001). The thoracolumbar kyphosis Cobb angle decreased from 51.0° ± 9.9° to 21.6° ± 11.0° (P < 0.001). VAS scores for back pain decreased from 7.2 ± 1.2 to 2.1 ± 1.1 (P < 0.001). Lumbar lordosis increased from 5.7° ± 23.2° to 10.5° ± 29.2° (P = 0.001). CONCLUSIONS: Osteotomy through the pathological fracture gap is a safe and effective surgical procedure for kyphosis correction and improvement of back pain in AS patients with pathological fractures. A significant kyphosis correction and improvement of back pain can be achieved with this surgical procedure.

ZNF606 interacts with Sox9 to regulate chondrocyte differentiation.

SRY-related high-mobility-group box 9 (Sox9) gene is a transcription factor that plays an essential role in chondrocyte differentiation and cartilage formation. In this study, we identified the transcriptional factor ZNF606 as an interacting partner for Sox9 in cells. We further demonstrated that overexpression of ZNF606 inhibited the transcriptional activity of Sox9, while knockdown of ZNF606 increased Sox9-mediated transcription. Chromatin immunoprecipitation analysis revealed that ZNF606 prevents Sox9 binding to the enhancers of its target gene col2a1. Importantly, the interaction between ZNF606 and Sox9 was decreased during chondrocyte differentiation. Consistent with these findings, ZNF606 inhibited chondrocyte differentiation. Thus, our results demonstrate that ZNF606 acts as a novel Sox9 co-regulator that inhibits Sox9-mediated chondrocyte differentiation.

Leptin Receptor Metabolism Disorder in Primary Chondrocytes from Adolescent Idiopathic Scoliosis Girls.

To investigate the underlying mechanisms of low metabolic activity of primary chondrocytes obtained from girls with adolescent idiopathic scoliosis (AIS); AIS is a spine-deforming disease that often occurs in girls. AIS is associated with a lower bone mass than that of healthy individuals and osteopenia. Leptin was shown to play an important role in bone growth. It can also regulate the function of chondrocytes. Changes in leptin and Ob-R levels in AIS patients have been reported in several studies. The underlying mechanisms between the dysfunction of peripheral leptin signaling and abnormal chondrocytes remain unclear; The following parameters were evaluated in AIS patients and the control groups: total serum leptin levels; Ob-R expression in the plasma membrane of primary chondrocytes; JAK2 and STAT3 phosphorylation status. Then, we inhibited the lysosome and proteasome and knocked down clathrin heavy chain (CHC) expression in primary chondrocytes isolated from girls with AIS and evaluated Ob-R expression. We investigated the effects of leptin combined with a lysosome inhibitor or CHC knockdown in primary chondrocytes obtained from AIS patients; Compared with the controls, AIS patients showed similar total serum leptin levels, reduced JAK2 and STAT3 phosphorylation, and decreased cartilage matrix synthesis in the facet joint. Lower metabolic activity and lower membrane expression of Ob-R were observed in primary chondrocytes from the AIS group than in the controls. Lysosome inhibition increased the total Ob-R content but had no effect on the membrane expression of Ob-R or leptin's effects on AIS primary chondrocytes. CHC knockdown upregulated the membrane Ob-R levels and enhanced leptin's effects on AIS primary chondrocytes; The underlying mechanism of chondrocytes that are hyposensitive to leptin in some girls with AIS is low plasma membrane Ob-R expression that results from an imbalance between the rate of receptor endocytosis and the insertion of newly synthesized receptors into the membrane.

One-stage posterior focus debridement, fusion, and instrumentation in the surgical treatment of lumbar spinal tuberculosis with kyphosis in children.

OBJECTIVE: The purpose of this study is to investigate the clinical efficacy and feasibility of one-stage posterior focus debridement, fusion, and instrumentation in the surgical treatment of lumbar spinal tuberculosis with kyphosis in children. METHODS: From December 2007 to May 2012, 13 patients (six males and seven females) suffering from lumbar spinal tuberculosis with kyphosis were admitted. All patients were treated with one-stage posterior focus debridement, fusion, and instrumentation. Then, the clinical efficacy was estimated by statistical analysis based on the data about Frankel grade, the Cobb angle of kyphosis, and erythrocyte sedimentation rate (ESR), which were collected at certain time. RESULTS: The age of all patients ranged from 5 to 13 years (average, 8.8 years). Operation time ranged from 120 to 190 min (average, 165 min). Intraoperative blood loss ranged from 200 to 800 ml (average, 460 ml). All patients were followed up for 24 to 57 months postoperatively (average, 33.5 months). The Cobb angle was changed significantly between preoperation and postoperation (P < 0.05), and there was no significant loss at the last follow-up. The preoperation ESR (62.5 ± 15.7) returned to normal (16.6 ± 8.1) within 3 months postoperatively in all patients (P < 0.05). Bone fusion was achieved within 3-5 months (average, 3.5 months). In the 13 cases, no postoperative severe complications occurred and neurologic function improved in various degrees. CONCLUSION: The outcomes of follow-up showed that one-stage posterior focus debridement, fusion, and instrumentation can be an effective treatment method for the lumbar spinal tuberculosis with kyphosis in children.