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 contribution of preoperative balanced halo-pelvic traction to severe rigid spinal deformity correction.

PURPOSE: The aim of this study was to assess the clinical efficacy of balanced halo-pelvic traction (HPT) and evaluate its contribution to the correction surgery in treating adult severe rigid spinal deformity. METHODS: One hundred and eight adult patients with severe rigid spinal deformity who underwent preoperative HPT and correction surgery were reviewed. The main coronal curve, segmental kyphotic angle, coronal balance (CB), sagittal balance (SVA), and the length of spine were measured before HPT, after HPT, post-operatively, and at final follow-up. The HPT contribution rates to deformity correction were calculated. RESULTS: The pre-HPT main coronal curve was 103.4 ± 10.6°, improved to 61.0 ± 13.4° after traction and further improved to 44.2 ± 10.2° after surgical correction, and maintained at 50.3 ± 9.9° at final follow-up. CB started at 4.2 ± 4.8 cm, improved to 2.1 ± 2.5 cm after HPT, 0.8 ± 1.2 cm after operation, and 0.7 ± 0.9 cm at final follow-up. The pre-HPT sagittal segmental kyphotic angle was 67.3 ± 17.7°, was then improved to 42.2 ± 27.5° after traction and further improved to 34.9 ± 10.2° after surgery, and maintained at 35.4 ± 10.4° at final follow-up. The length of spine improved from 35.9 ± 5.9 to 42.6 ± 6.0 cm via HPT, reached up to 45.0 ± 6.0 cm after operation, and maintained at 44.3 ± 5.2 cm at final follow-up. CONCLUSION: HPT is effective for the treatment of severe rigid spinal deformity. Balanced HPT can dramatically improve coronal and sagittal deformity as well as spinal length before corrective surgery.

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.

Improvement of pulmonary function and reconstructed 3D lung volume after deformity correction for thoracic spinal posttubercular kyphosis: a multicenter study.

OBJECTIVE: The aim of this study was to investigate the influence of corrective surgery on thoracic spinal posttubercular kyphosis (PTK) with respect to lung volume and pulmonary function. METHODS: This was a retrospective study of 126 patients (72 males and 54 females) who underwent posterior vertebral column resection (PVCR) for severe thoracic spinal PTK between September 2013 and June 2020. The patients' spinal parameters, results of their pulmonary function test (PFT), and CT-based 3D lung volume were recorded and analyzed preoperatively and at final follow-up. The correlation of kyphosis correction with the PFT and lung volume was evaluated. RESULTS: The mean local kyphosis decreased from 112.5° to 37.2°, and the mean local scoliosis decreased from 20.9° to 5.2°; C2-7 lordosis, thoracic kyphosis, and lumbar lordosis also significantly improved after surgery. The mean CT-based lung volume significantly increased from 2.9 L preoperatively to 3.6 L at the final follow-up. The indices of PFT, including forced vital capacity (FVC), percent predicted FVC, total lung capacity, and forced expiratory volume in 1 second, were also significantly improved, and 60 patients with pulmonary dysfunction recovered to normal at the final follow-up. The correlation analysis revealed that the correction of local kyphosis was closely correlated with the improvement in PFT and the increase in lung volume. CONCLUSIONS: PVCR cannot only effectively realign the spine in patients with severe thoracic spinal PTK deformity but also significantly improve pulmonary function. Adequate local kyphosis correction should be highly valued, as it is a key factor in increasing lung volume.

A novel classification of osteotomized debridement based on the range of focus in treating active thoracolumbar tuberculosis: a multicenter study.

INTRODUCTION: Osteotomized debridement (OD) is increasingly used in the treatment of active thoracolumbar tuberculosis (TB). So far, no nomenclature has been established to describe the patterns of OD, and thus the surgical outcomes cannot be directly analyzed and compared among the patients treated with different extents of OD. The purpose of this study was to establish a reliable classification of OD for further study of spinal TB. MATERIALS AND METHODS: This was a multicenter retrospective study. The proposed classification included 6 grades of OD based on sagittal range of vertebral body destruction: grade 0 involves single-level intervertebral disc and adjacent superficial endplates; grade 1 involves adjacent endplates and vertebral bodies, but no pedicle is involved; grade 2 involves adjacent endplates, vertebral bodies, and a lower or upper pedicle; grade 3 involves adjacent endplates, vertebral bodies, and both of lower and upper pedicles; grade 4 involves an entire vertebral body and an adjacent lower or upper pedicle; grade 5 involves two continuous entire vertebral bodies. Two hundred and five patients with active thoracolumbar TB who underwent OD surgery were included, and all ODs were classified. The reliability of this classification was evaluated twice by 10 readers, and Fleiss kappa coefficients were calculated. RESULTS: In the 205 patients, 208 ODs were performed. Grade 2 OD was the commonest type (98/208, 47.1%), followed by grade 1 (50/208, 24.0%), grade 3 (26/208, 12.5%), grade 0 (20/208, 9.6%), grade 4 (8/208, 3.8%), and grade 5 (6/208, 2.9%). The average accuracy of the two readings was 86.2% and 90.1%, respectively. The intra-rater reliability for the classification was "almost perfect agreement" with a Fleiss kappa coefficient average of 0.92. The inter-rater reliability was "almost perfect agreement" with a coefficient average of 0.89 for two readings. CONCLUSIONS: This classification proved to be intuitive and reliable. The graded OD provides a platform for preoperative evaluation and allows comparative analysis of clinical outcomes in different extents of OD.

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease.

BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025). CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach. CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158. IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

Patients with Asian-type DEL can safely be transfused with RhD-positive blood.

Red blood cells (RBCs) of Asian-type DEL phenotype express few RhD proteins and are typed as serologic RhD-negative (D-) phenotype in routine testing. RhD-positive (D+) RBC transfusion for patients with Asian-type DEL has been proposed but has not been generally adopted because of a lack of direct evidence regarding its safety and the underlying mechanism. We performed a single-arm multicenter clinical trial to document the outcome of D+ RBC transfusion in patients with Asian-type DEL; none of the recipients (0/42; 95% confidence interval, 0-8.40) developed alloanti-D after a median follow-up of 226 days. We conducted a large retrospective study to detect alloanti-D immunization in 4045 serologic D- pregnant women throughout China; alloanti-D was found only in individuals with true D- (2.63%, 79/3009), but not in those with Asian-type DEL (0/1032). We further retrospectively examined 127 serologic D- pregnant women who had developed alloanti-D and found none with Asian-type DEL (0/127). Finally, we analyzed RHD transcripts from Asian-type DEL erythroblasts and examined antigen epitopes expressed by various RHD transcripts in vitro, finding a low abundance of full-length RHD transcripts (0.18% of the total) expressing RhD antigens carrying the entire repertoire of epitopes, which could explain the immune tolerance against D+ RBCs. Our results provide multiple lines of evidence that individuals with Asian-type DEL cannot produce alloanti-D when exposed to D+ RBCs after transfusion or pregnancy. Therefore, we recommend considering D+ RBC transfusion and discontinuing anti-D prophylaxis in patients with Asian-type DEL, including pregnant women. This clinical trial is registered at www.clinicaltrials.gov as #NCT03727230.

Global realignment after posterior vertebral column resection in severe thoracolumbar post-tubercular kyphosis: correlation with patient-reported outcomes.

PURPOSE: To investigate spinal realignment in patients with severe post-tubercular kyphosis (PTK) who underwent posterior vertebral column resection (PVCR) and its correlation with patient-reported outcomes (PROs). METHODS: Eighty-two patients were included in this study. Spinopelvic parameters (focal scoliosis (FS), coronal balance (CB), sagittal vertical axis (SVA), focal kyphosis (FK), C2-7 lordosis (CL), thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), and pelvic incidence minus lumbar lordosis (PI-LL)) and PROs (Visual Analog Scale (VAS) and Oswestry Disability Index (ODI)) were analyzed. The correlation between spinopelvic parameters and PROs was evaluated. RESULTS: FK, FS, CL, TK, LL, and PI-LL significantly changed after surgery. FK decreased from pre-operative 108.5 ± 16.4° to 31.8 ± 4.5° at three months after surgery and increased to 38.7 ± 6.6° at final follow-up (P < 0.001). FS decreased from pre-operative 20.9 ± 2.2° to 5.1 ± 2.2° at final follow-up (P < 0.001). CL decreased from pre-operative 7.2 ± 7.3° to 3.3 ± 8.3° at final follow-up (P = 0.002). TK improved from pre-operative - 5.6 ± 7.1° to 12.9 ± 8.2° at final follow-up (P < 0.001). LL decreased from pre-operative 75.5 ± 12.6° to 45.5 ± 7.9° at final follow-up (P < 0.001). PI-LL improved from pre-operative - 24.8 ± 13.4° to 4.8 ± 9.9° at final follow-up (P < 0.001). The improvement of PROs was found to be significantly correlated with the variations of FK, CL, TK, LL, and PI-LL. The multiple regression analysis revealed that FK was an independent predictor for the improvement of VAS and ODI. CONCLUSIONS: PVCR is effective in treating severe PTK, which can significantly improve patients' clinical and radiographic outcomes. Spine surgeons should pay more attention to reducing the residual kyphosis.

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.

Halo traction combined with posterior-only approach correction for cervical kyphosis with Neurofibromatosis-1: minimum 2 years follow-up.

BACKGROUND: Surgical management of cervical kyphosis in patients with NF-1 is a challenging task. Presently, anterior-only (AO), posterior-only (PO) and combined anterior-posterior (AP) spinal fusion are common surgical strategies. However, the choice of surgical strategy and application of Halo traction remain controversial. Few studies have shown and recommended posterior-only approach for cervical kyphosis correction in patients with NF-1. The aim of this study is to evaluate the safety and the effectiveness of halo Traction combined with posterior-only approach correction for treatment of cervical kyphosis with NF-1. METHODS: Twenty-six patients with severe cervical kyphosis due to NF-1 were reviewed retrospectively between January 2010 and April 2018. All the cases underwent halo traction combined with posterior instrumentation and fusion surgery. Correction result, neurologic status and complications were analyzed. RESULTS: In this study, cervical kyphosis Cobb angle decreased from initial 61.3 ± 19.7 degrees to postoperative 10.6 ± 3.7 degrees (P<0.01), with total correction rate of 82.7%, which consist of 45.8% from halo traction and 36.9% from surgical correction. JOA scores were improved from preoperative 13.3 ± 1.6 to postoperative 16.2 ± 0.7 (P<0.01). Neurological status was also improved. There was no correction loss and the neurological status was stable in mean 43 months follow-up. Three patients experienced minor complications and one patient underwent a second surgery. CONCLUSION: Halo traction combined with PO approach surgery is safe and effective method for cervical kyphosis correction in patients with NF-1. A satisfied correction result, and successful bone fusion can be achieved via this procedure, even improvement of neurological deficits can also be obtained. Our study suggested that halo traction combined with PO approach surgery is another consideration for cervical kyphosis correction in patients with NF-1.

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.

The clinical characteristics of patients with acute leukemia or stem cell transplantation exhibiting immune based platelet refractoriness.

BACKGROUND: To investigate the related factors influencing immune platelet transfusion refractoriness (PTR) in acute leukemia (AL) from induction to consolidation and compare management for immune PTR, so as to improve the Platelet increment in AL. METHODS: The primary analysis included 890 patients with AL, 225 of whom were the immune PTR (25 %).They are patients in our center from induction to consolidation or transplantation in the past 10 years. Flow cytometry, karyotype characteristics and other basic information were compared between the immune PTR vs control (no-PTR) groups. We analyzed the treatment outcomes of immune PTR including matched platelets, intravenous immunoglobulin (IVIG), increasing apheresis platelet does. RESULTS: Immune PTR is more likely to occur in patients with poor prognosis in acute lymphoblastic leukemia (ALL) (P = 0.01).There is a relation between NPM1 mutation and occurrence of immune PTR (P = 0.029).The incidence of PTR at 35-59Y was higher than that at <35Y(OR = 0.68, 95 % CI = 0.48-0.96) and ≥60Y(OR = 0.49,95 % CI = 0.28-0.83), and the difference was statistically significant(P = 0.03, P = 0.01).The Platelet increment with 1 unit (u) was 47.12 %, 2 u increased to 71.14 %, and the matched 2 u (75.11 %) had the best effect. IVIG improved the Platelet increment, but there was no difference between 0.4 g/kg IVIG and 1 g/kg IVIG. Immune PTR is more likely to occur in the ages of 35-60 years. CONCLUSION: There are specific AL patient characteristics which predispose to the phenomenon of immune based PTR. Meanwhile, increasing the IVIG dose could not improve Platelet increment obviously.

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.