Novel molecular subtypes of intracranial germ cell tumours expand therapeutic opportunities.

BACKGROUND: Intracranial germ cell tumours (IGCTs) are a rare group of malignancies that are clinically classified as germinomas and nongerminomatous germ cell tumours (NGGCTs). Previous studies have found that somatic mutations involving the MAPK/mTOR signalling pathway are common early events. However, a comprehensive genomic understanding of IGCTs is still lacking. METHODS: We established a cohort including over 100 IGCTs and conducted genomic and transcriptomic sequencing. RESULTS: We identified novel recurrent driver genomic aberrations, including USP28 truncation mutations and high-level copy number amplification of KRAS and CRKL caused by replication of extrachromosomal DNA. Three distinct subtypes associated with unique genomic and clinical profiles were identified with transcriptome analysis: immune-hot, MYC/E2F and SHH. Both immune-hot and MYC/E2F were predominantly identified in germinomas and shared similar mutations involving the RAS/MAPK signalling pathway. However, the immune-hot group showed an older disease onset age and a significant immune response. MYC/E2F was characterized by a younger disease onset age and increased genomic instability, with a higher proportion of tumours showing whole-genome doubling. Additionally, the SHH subtype was mostly identified in NGGCTs. CONCLUSIONS: Novel genomic aberrations and molecular subtypes were identified in IGCTs. These findings provide molecular basis for the potential introduction of new treatment strategies in this setting.

Single-cell transcriptomic sequencing identifies subcutaneous patient-derived xenograft recapitulated medulloblastoma.

BACKGROUND: Medulloblastoma (MB) is one of the most common malignant brain tumors that mainly affect children. Various approaches have been used to model MB to facilitate investigating tumorigenesis. This study aims to compare the recapitulation of MB between subcutaneous patient-derived xenograft (sPDX), intracranial patient-derived xenograft (iPDX), and genetically engineered mouse models (GEMM) at the single-cell level. METHODS: We obtained primary human sonic hedgehog (SHH) and group 3 (G3) MB samples from six patients. For each patient specimen, we developed two sPDX and iPDX models, respectively. Three Patch+/- GEMM models were also included for sequencing. Single-cell RNA sequencing was performed to compare gene expression profiles, cellular composition, and functional pathway enrichment. Bulk RNA-seq deconvolution was performed to compare cellular composition across models and human samples. RESULTS: Our results showed that the sPDX tumor model demonstrated the highest correlation to the overall transcriptomic profiles of primary human tumors at the single-cell level within the SHH and G3 subgroups, followed by the GEMM model and iPDX. The GEMM tumor model was able to recapitulate all subpopulations of tumor microenvironment (TME) cells that can be clustered in human SHH tumors, including a higher proportion of tumor-associated astrocytes and immune cells, and an additional cluster of vascular endothelia when compared to human SHH tumors. CONCLUSIONS: This study was the first to compare experimental models for MB at the single-cell level, providing value insights into model selection for different research purposes. sPDX and iPDX are suitable for drug testing and personalized therapy screenings, whereas GEMM models are valuable for investigating the interaction between tumor and TME cells.

Gray Matter Abnormalities in Patients with Chronic Low Back Pain: A Systematic Review and Meta-Analysis of Voxel-Based Morphometry Studies.

BACKGROUND: Numerous studies utilizing voxel-based morphometry (VBM) have documented gray matter (GM) alterations in patients with chronic low back pain (CLBP) compared to healthy controls. However, the inconsistency in GM abnormalities observed across different studies has hindered their potential application as objective neuroimaging biomarkers or therapeutic targets. To address this issue, we conducted a comprehensive meta-analysis of VBM studies to identify robust GM differences between CLBP patients and healthy controls. METHODS: The databases including PubMed, Embase, and Web of Science were systematically searched from January 2000 to September 2022 to identify eligible neuroimaging studies. In this coordinate-based meta-analysis of VBM studies, the Seed-based d Mapping with Permutation of Subject Images method was used to quantitatively assess regional differences in GM between CLBP patients and healthy controls. RESULTS: Thirteen VBM studies, involving a total of 574 CLBP patients and 1239 healthy controls, were included in the meta-analysis. The findings revealed that CLBP patients exhibited increased GM in the left striatum and left postcentral gyrus and decreased GM in the left superior frontal gyrus, left cerebellum, right striatum, left insula, and right middle occipital gyrus compared to healthy controls. The jackknife sensitivity analysis confirmed the robustness of these neuroimaging findings. CONCLUSIONS: This study provides new insights into potential treatment strategies for CLBP and identifies neuroimaging biomarkers for pain chronification. These findings highlight the importance of considering regional GM abnormalities in the development of clinical interventions for CLBP.

Treatment outcomes and risk factors of patients with intracranial germ cell tumour with choriocarcinoma element or ß-HCG level higher than 500 IU/L.

BACKGROUND: In previous studies, patients with intracranial germ cell tumour (iGCT) with pure choriocarcinoma or mixed germ cell tumours with choriocarcinoma element showed similar dismal prognoses, with median overall survival (OS) of 22 months and 1-year survival rate of approximately 60%. However, these conclusions need to be updated because radiotherapy, which is the mainstay for this disease, was not applied in a number of patients. Additionally, prognostic factors need to be explored in this population. METHODS: Clinical data of patients with iGCTs with histologically confirmed choriocarcinoma element or beta-human chorionic gonadotropin (ß-HCG) > 500 IU/L were collected from the archives of our institution and retrospectively studied. RESULTS: A total of 76 patients were eligible for this study. Except for two early deaths, all patients received radiotherapy (craniospinal irradiation [CSI], n = 23; non-CSI, n = 51). The median follow-up duration for the entire series was 63 months (range, 6-188 months). The 5-year event-free survival (EFS) and OS rates were 81.5% and 84.1%, respectively. Among patients who did not have early death or progressive disease after induction chemotherapy, multivariate analysis revealed that chemotherapy cycles (> 4 vs. ≤ 4) (hazard ratio [HR] for EFS 0.144, p = 0.020; HR for OS 0.111, p = 0.028) and ß-HCG levels (> 3000 IU/L vs. ≤ 3000 IU/L) (HR for EFS 4.342, p = 0.059; HR for OS 6.614, p = 0.033) were independent factors for survival. CONCLUSIONS: Patients with iGCTs with choriocarcinoma element or ß-HCG > 500 IU/L showed improved survival with radiotherapy-based treatments. Additional chemotherapy cycles could result in additional survival benefits. Patients with ß-HCG level > 3000 IU/L had poorer prognosis.

Neural network mapping of gelastic behavior in children with hypothalamus hamartoma.

BACKGROUND: Hypothalamus hamartomas (HHs) are rare, congenital, tumor-like, and nonprogressive malformations resulting in drug-resistant epilepsy, mainly affecting children. Gelastic seizures (GS) are an early hallmark of epilepsy with HH. The aim of this study was to explore the disease progression and the underlying physiopathological mechanisms of pathological laughter in HH. METHODS: We obtained clinical information and metabolic images of 56 HH patients and utilized ictal semiology evaluation to stratify the specimens into GS-only, GS-plus, and no-GS subgroups and then applied contrasted trajectories inference (cTI) to calculate the pseudotime value and evaluate GS progression. Ordinal logistic regression was performed to identify neuroimaging-clinical predictors of GS, and then voxelwise lesion network-symptom mapping (LNSM) was applied to explore GS-associated brain regions. RESULTS: cTI inferred the specific metabolism trajectories of GS progression and revealed increased complexity from GS to other seizure types. This was further validated via actual disease duration (Pearson R = 0.532, P = 0.028). Male sex [odds ratio (OR) = 2.611, P = 0.013], low age at seizure onset (OR = 0.361, P = 0.005), high normalized HH metabolism (OR = - 1.971, P = 0.037) and severe seizure burden (OR = - 0.006, P = 0.032) were significant neuroimaging clinical predictors. LNSM revealed that the dysfunctional cortico-subcortico-cerebellar network of GS and the somatosensory cortex (S1) represented a negative correlation. CONCLUSIONS: This study sheds light on the clinical characteristics and progression of GS in children with HH. We identified distinct subtypes of GS and demonstrated the involvement of specific brain regions at the cortical-subcortical-cerebellar level. These valuable results contribute to our understanding of the neural correlates of GS.

A nomogram for predicting post-operative hydrocephalus in children with medulloblastoma.

Post-operative hydrocephalus is common among children with medulloblastoma after initial tumor resection. This study aimed to establish a novel model for predicting the development of post-operative hydrocephalus in children with medulloblastoma. Only pediatric patients who received initial medulloblastoma resection at Beijing Tiantan Hospital between January 2018 and May 2021 were included in this study. The potential risk factors associated with post-operative hydrocephalus were identified based on multivariate logistic regression and the nomogram. Receiver operating characteristic (ROC) curve were used to evaluate the performance of the nomogram model based on an independent cohort of medulloblastoma patients who underwent surgery from June 2021 to March 2022. A total of 105 patients were included in the primary cohort. Superior invasion (P = 0.007), caudal invasion (P = 0.025), and intraventricular blood ≥ 5 mm (P = 0.045) were significantly related to the development of post-operative hydrocephalus and thus were assembled into the nomogram model. The model accurately predicted post-operative hydrocephalus based on the calibration curve. The area under the ROC curves for the primary and validation cohorts was 0.849 and 0.855, respectively. In total, the nomogram we developed may aid clinicians in assessing the potential risk of pediatric patients with MB developing post-operative hydrocephalus, especially those who would otherwise not have received a diversionary procedure at presentation.

Characteristics and factors influencing hypothalamic pituitary dysfunction in patients with craniopharyngioma.

Background: Craniopharyngioma is a benign tumor originating from the sellar region. Damages in this area caused by the tumor itself, surgery, or radiotherapy may result in severe hypothalamic-pituitary dysfunction (HPD) and eventually lead to a significant impairment in the long-term quality of life of patients. This study aimed to investigate the characteristics of HPD in patients with adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) and to identify the factors affecting HPD after surgery. Methods: In this single-center retrospective study, a total of 742 patients with craniopharyngioma were included. The neuroendocrine function of these patients before and after surgery was investigated. The differences in hypothalamic-pituitary function between the ACP and PCP groups were compared. The factors influencing the aggravation of HPD after surgery were identified. Results: The median follow-up after surgery was 15 months. Before surgery, the proportion of patients with diabetes insipidus (DI) and hyperprolactinemia in the PCP group was significantly higher than that in the ACP group (P<0.01), and the proportion of patients with adrenocortical hypofunction in the PCP group was significantly lower than that in the ACP group (P=0.03). Most cases of ACP originated in the sellar region, while most cases of PCP originated in the suprasellar region (P<0.01). More patients experienced adenohypophyseal hypofunction, DI, and hypothalamic obesity at postoperative follow-up than at onset in both the ACP and PCP groups (both P<0.01), with a higher increase observed in the ACP group (P<0.01). Older age at CP onset, tumor recurrence or progression, and ACP type were risk factors for postoperative aggravation of HPD in CP patients. Conclusion: Surgical treatment significantly aggravated HPD in both the ACP and PCP groups, but the specific characteristics and risk factors leading to aggravation were different between the two groups.

Ultrasound-guided interlaminar approach for nusinersen administration in patients with spinal muscular atrophy with spinal fusion or severe scoliosis.

BACKGROUND: Intrathecal injection of medications can be challenging in spinal muscular atrophy (SMA) patients with severe scoliosis or after spine surgery. Here we report our experience with real-time ultrasound (US)-guided intrathecal administration of nusinersen in patients with SMA. METHODS: Seven patients (six children and one adult) with either spinal fusion or severe scoliosis were enrolled. We performed intrathecal injections of nusinersen under US guidance. The efficacy and safety of US-guided injection were explored. RESULTS: Five patients had undergone spinal fusion, while the other two presented severe scoliosis. Success was achieved in 19/20 lumbar punctures (95%), 15 of which were performed through the near-spinous process approach. The intervertebral space with a designated channel was selected for the five postoperative patients, while the interspaces with the smallest rotation angle were chosen for the other two patients with severe scoliosis. In 89.5% (17/19) of the punctures, the number of insertions was no more than two. No major adverse events were observed. CONCLUSION: Given its safety and efficacy, real-time US guidance is recommended for SMA patients with spine surgery or severe scoliosis, and the near-spinous process view can be used as a interlaminar puncture approach for US guidance.

Midline Lumbar Fusion Versus Posterior Lumbar Interbody Fusion Involving L5-S1 For Degenerative Lumbar Diseases: A Comparative Study.

BACKGROUND: A retrospective cohort study to evaluate the efficacy and safety of midline lumbar fusion (MIDLF) for lumbosacral fusion compared to posterior lumbar interbody fusion (PLIF). METHODS: Patients who had undergone posterior lumbosacral fusion surgery were divided into a MIDLF group (n = 37) and a PLIF group (n = 42). The follow-up time was at least 12 months. The operation data, recovery condition, complications, clinical outcomes, and status of implants and fusion were compared between the 2 groups. RESULTS: The MIDLF group experienced significantly less blood loss, lower postoperative creatine kinase levels and total drainage volume, earlier time to ambulation, and less hospital stay times after surgery compared to the PLIF group (P < 0.05). The mean postoperative back pain visual analog scale scores in the MIDLF group were significantly lower than the PLIF group (P < 0.05). The improvement in Oswestry Disability Index scores during 3-month follow-up displayed a significant difference between the 2 groups (P < 0.05). The fusion rate tended to be higher in the MIDLF group; however, the difference was not significant (P > 0.05). There was no significant difference in respect to screw loosening and cage subsidence rate. There were 2 cases of complications both occurring in the PLIF group. CONCLUSIONS: MIDLF is safe and effective for lumbosacral fusion and in line with the concept of enhanced recovery after surgery.

A Biomechanical Study on Cortical Bone Trajectory Screw Fixation Augmented With Cement in Osteoporotic Spines.

STUDY DESIGN: A biomechanical study. OBJECTIVE: To evaluate the efficacy and feasibility of cement-augmented cortical bone trajectory (CBT) screw fixation. METHODS: Forty-nine CBT screws were inserted into lumbar vertebrae guided by three-dimensionally printed templates, and then injected with 0, .5, or 1.0 mL of polymethylmethacrylate. The screw placement accuracy, cement dispersion, and cement leakage rate were evaluated radiologically. Biomechanical tests were performed to measure the axial pull-out strength and torque value. RESULTS: Overall, 83.67% of the screws were inserted without pedicle perforation. In the 1.0 mL group, cement dispersed into the pedicle zone and formed a concentrated mass more often than in the .5 mL group, but not significantly more often (P > .05). The total cement leakage rate was 18.75%. Compared with the control group, the torque value was slightly higher in the .5 mL group (P = .735) and significantly higher in the 1.0 mL group (P = .026). However, there was no significant difference between the .5 and 1.0 mL groups (P = .431). The maximal pull-out force (Fmax) was increased by 52.85% and 72.73% in the .5 and 1.0 mL groups, respectively, compared with the control group (P < .05). However, the difference was not significant between the 2 cemented groups (P = .985). CONCLUSIONS: Cement augmentation is a useful method for increasing CBT screw stability in osteoporotic spines. The cement injection volume is recommended to be 1 mL for each screw, and the cement should disperse into the vertebral body than the pedicle zones.

Spine-Related Malpractice Claims in China: A 2-year National Analysis.

STUDY DESIGN: Retrospective cross-sectional study. OBJECTIVE: To investigate the prevalence, characteristics, and risk factors of spine-related malpractice claims in China in a 2-year period. METHODS: The arbitration files of the Chinese Medical Association (CMA) were reviewed for spine-related malpractice claims. Descriptive statistics and correlation analysis were conducted on claim characteristics, clinical data, plaintiff's main allegations, and arbitration outcomes. RESULTS: A total of 288 cases of spinal claims filed in the CMA between January 2016 and December 2017 were included. Most claims were found in lumbar degenerative disorders (59.4%), lumbar trauma (13.2%), and cervical degenerative disorders (11.8%). The most common adverse events (AEs) leading to claims were new neurologic deficit (NND) (47.6%), infection (11.5%), and insufficient symptom relief (10.4%). The most common patient allegation was surgical error (66.0%), although the main arbitrated cause of AEs was disease/treatment itself (49.0%), while providers were judged as mainly responsible in only 47.3% cases. In multivariate regression analysis, cervical spine, misdiagnosis/mistreatment, and unpredictable emergency correlated with more severe damage to patients; minimally invasive surgery was predictive of judgment in plaintiff's favor, while claims in the eastern region and unpredictable emergencies were predictive of defendant's favor; only NND was associated with being arbitrated as surgical error in surgical cases where surgeons accepted major liability. CONCLUSION: The current study provided a descriptive overview and risk factor analysis of spine-related malpractice claims in China. Gaining improved understanding of the facts and causes of malpractice claims may help providers reduce the risk of claims and subsequent litigation.

Evaluation of Adjacent Segment With Pre-Existing Degeneration Using the Cerebrospinal Fluid Occlusion Sign on MRI Before Posterior Lumbar Fusion: A Multi-Center Observational Cohort Study.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: To evaluate whether pre-existing adjacent spinal canal stenosis (SCS) is associated with short-term outcomes after lumbar fusion surgery. METHODS: We included patients with lumbar spinal stenosis treated surgically between July 2015 and December 2017 at 4 centers. All patients had the same pathology, with L4-S1 as the culprit sections. Patients were divided into 2 groups based on the cerebrospinal fluid occlusion sign on MRI at the adjacent L3/4 level. Patients without SCS (grade 0) and with mild SCS (grade 1) were classified into the non-stenosis (NS) and mild stenosis (MS) groups, respectively. All patients underwent PLIF and completed at least 1-year follow-up. The incidence of adjacent segment degeneration (ASDeg) and clinical outcomes were compared between the 2 groups. RESULTS: A total of 308 patients (NS, 156; MS, 152) met the inclusion criteria. The incidence of ASDeg in the NS group (n = 40, 25.6%) was significantly lower than that in the MS group (n = 74, 48.7%; P < .001). The most frequent type of ASDeg in the 2 groups was the SCS-aggravated type. No significant difference was observed in adjacent segment disease incidence between the 2 groups (P = .243). The NS group had better outcomes according to the clinical function scores (P < .05). CONCLUSIONS: The cerebrospinal fluid occlusion sign on MRI is valuable for evaluating the adjacent segment with pre-existing degeneration. Patients with mild SCS in adjacent segments were more likely to have ASDeg, and the most frequent type of ASDeg was the SCS-aggravated type at early follow-up.

Bilateral ultrasound-guided erector spinae plane block versus wound infiltration for postoperative analgesia in lumbar spinal fusion surgery: a randomized controlled trial.

PURPOSE: Both erector spinae plane block and wound infiltration are used to improve analgesia following spinal fusion surgery. Herein, we compared the analgesic effect of bilateral erector spinae plane block with wound infiltration in this patient population. METHODS: In this randomized trial, 60 patients scheduled for elective open posterior lumbar interbody fusion surgery were randomized to receive either ultrasound-guided bilateral erector spinae plane block before incision (n = 30) or wound infiltration at the end of surgery (n = 30). Both groups received standardized general anesthesia and postoperative analgesia, including patient-controlled analgesia with sufentanil and no background infusion. Opioid consumption and pain intensity were assessed at 2, 6, 12, 24, and 48 h after surgery. The primary outcome was cumulative opioid consumption within 24 h after surgery. RESULTS: All 60 patients were included in the intention-to-treat analysis. The equivalent dose of sufentanil consumption within 24 h was significantly lower in patients given erector spinae plane block (median 11 µg, interquartile range 5-16) than in those given wound infiltration (20 µg, 10 to 43; median difference - 10 µg, 95% CI - 18 to - 3, P = 0.007). The cumulative number of demanded PCA boluses was significantly lower with erector spinae plane block at 6 h (median difference - 2, 95% CI - 3 to 0, P = 0.006), 12 h (- 3, 95% CI - 6 to - 1, P = 0.002), and 24 h (- 5, 95% CI - 8 to - 2, P = 0.005) postoperatively. The proportion given rescue analgesia was also significantly lower in patients given erector spinae plane block group within 48 h (relative risk 0.27, 95% CI 0.07 to 0.96, P = 0.037). There were no statistical differences in pain intensity at any timepoints between groups. No procedure-related adverse events occurred. CONCLUSIONS: Compared with wound infiltration, bilateral ultrasound-guided erector spinae plane block decreases short-term opioid consumption while providing similar analgesia in patients following lumbar spinal fusion surgery. Chinese Clinical Trial Registry: ChiCTR2100053008.

Radiological and clinical outcomes of midline lumbar fusion on sagittal lumbar-pelvic parameters for degenerative lumbar diseases.

BACKGROUND: Improving the sagittal lumbar-pelvic parameters after fusion surgery is important for improving clinical outcomes. The impact of midline lumbar fusion (MIDLF) on sagittal lumbar-pelvic alignment for the management of degenerative lumbar diseases is still unknown. AIM: To analyze the effects of short-segment MIDLF and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) on sagittal lumbar-pelvic parameters. METHODS: We retrospectively analyzed 63 patients with degenerative lumbar diseases who underwent single-segment MIDLF or MIS-TLIF. The imaging data of patients were collected before surgery and at the final follow-up. The radiological sagittal parameters included the lumbar lordosis (LL), lower LL, L4 slope (L4S), L5 slope (L5S), L5 incidence (L5I), L1 axis and S1 distance (LASD), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and PI-LL mismatch (PI-LL). Additionally, the clinical outcomes, including lower back and leg pain visual analog scale (VAS) and Oswestry disability index (ODI) scores, were also analyzed. RESULTS: In both groups, LL and Lower LL significantly increased, while L5I and LASD significantly decreased at the final follow-up compared to that recorded prior to operation (P < 0.05). In the MIDLF group, L4S significantly decreased compared to that recorded prior to operation (P < 0.05), while the mean SS significantly increased and the PT significantly decreased compared to that recorded prior to operation (P < 0.05). In the MIS-TLIF group, SS slightly increased and the mean PT value decreased compared to that recorded prior to operation, but without a statistically significant difference (P > 0.05). However, the PI-LL in both groups was significantly reduced compared to that recorded prior to operation (P < 0.05). There was no significant difference in the sagittal lumbar-pelvic parameters between the two groups prior to operation and at the final follow-up (P > 0.05). In addition, the change in sagittal lumbar-pelvic parameters did not differ significantly, except for ΔLASD within the two groups (P > 0.05). The mean lower back and leg pain VAS and ODI scores in both groups were significantly improved three months after surgery and at the final follow-up. Though the mean ODI score in the MIDLF group three months after surgery was slightly higher than that in the MIS-TLIF group, there was no significant difference between the two groups at the final follow-up. CONCLUSION: Short-segment MIDLF and MIS-TLIF can equally improve sagittal lumbar parameters such as LL, Lower LL, L5I, and LASD in the treatment of lumbar degenerative diseases. However, MIDLF had a larger impact on pelvic parameters than MIS-TLIF.

Anterior cervical discectomy and fusion with zero-profile versus stand-alone cages for two-level cervical spondylosis: A retrospective cohort study.

Objective: To assess the mid-long-term clinical and radiological outcomes of zero-profile (ZP) compared with stand-alone (ST) cages for two-level anterior cervical discectomy and fusion (ACDF). Methods: We included 77 patients (39 women and 38 men) who underwent two-level ACDF between May 5, 2016, and May 5, 2020, and who were followed up for at least 1 year. The subjects were divided into the ST (n = 38) and ZP (n = 39) group. For the evaluation of functional status, Japanese Orthopedic Association (JOA), Neck Disability Index (NDI), and Visual Analogue Scale (VAS) scores were used. Additionally, radiological outcomes and procedure complications were observed at final follow-up. Results: Both groups had excellent clinical outcomes at the final follow-up. There were no significant intergroup (ZP vs. ST) differences in the fusion rate (91.02% vs. 90.79%, P > 0.05) and postoperative dysphagia (15.4% vs. 2.6%, P = 0.108). However, the disc height at the final follow-up in the ZP group was higher than that in the ST group (6.86 ± 0.84 vs. 6.17 ± 1.03, P = 0.002). The ZP group accomplished a lower loss of cervical lordosis (18.46 ± 4.78 vs. 16.55 ± 4.36, P = 0.071), but without reaching statistical significance. Conclusion: ACDF with either ZP or ST cages turns out to be a dependable strategy for two-level ACDF in terms of clinical results. However, compared with the ST, the ZP cage may achieve a significantly lower loss of disc height.

Enhanced response of titanium doped iron(ii) oxalate under electric field.

Electrorheological (ER) fluid, containing polarized particles within an insulating liquid, represents a smart material, the mechanical properties of which can be altered mainly by an electric field. In this work, ER fluids based on cauliflower iron(ii) oxalate doped titanium particles show excellent rheological and wetting properties by the sample co-precipitation method. The morphology of the particles is observed by SEM and the molecular structure within the particles is obtained via XRD and FTIR. The distribution of elements within the particles is obtained by EDS. Owing to a lower current density than pure iron(ii) oxalate, the SEM and optical images show an obvious chain-like structure within the ER fluids with 2 wt% and 5 wt%, respectively, under 2 kV mm-1. Then, the rheological properties of these ER fluids are tested up to 3 kV mm-1 and the results show a gratifying property of resisting shear with different shear rates (0.1-100 s-1), which is attributed to the appearance of a stable chain-like structure. At the same time, the ER efficiency and the switching performance are obtained and the static yield stress fits the relevant electric field strength well. Ultimately, an excellent sedimentation ratio is obtained from 0 h to 600 h.

Two-stage treatment for severe spinal kyphotic deformity secondary to tuberculosis: halo-pelvic traction followed by a posterior-only approach correction.

BACKGROUND AND PURPOSE: Several surgical procedures are used to treat tuberculous kyphosis. However, the treatment of extreme spinal kyphosis is challenging, and associated with various complications. Halo traction has been used as an adjunctive method in the treatment of severe spinal deformities. However, there are few reports about the effectiveness of halo-pelvic traction (HPT) for the treatment of extreme spinal kyphosis secondary to tuberculosis. This study evaluated the effectiveness of halo-pelvic traction followed by a posterior-only approach correction in the treatment of severe spinal kyphosis secondary to tuberculosis. METHODS: The records of 19 patients with severe spinal kyphosis secondary to tuberculosis were retrospectively reviewed. All 19 patients were treated with a two-stage approach: HPT combined with posterior fusion surgery by a posterior-only approach. Radiographic parameters were measured and evaluated. America Spinal Injury Association grade (ASIA), Scoliosis Research Society outcome (SRS-22) score, and complications were also evaluated. RESULTS: There were 9 males and 10 females, with an average age of 29.7 years at the time of surgery. The average HPT duration was 10.4 weeks. The mean kyphosis angle decreased from 131.40 ± 10.7° pre-traction to 77.1 ± 7.4° post-traction (P < 0.01). The traction correction rate was 41.3%. The mean postoperative kyphosis angle was 65.7 ± 8.5°, and the surgical correction rate was 8.7%. Of the total correction, 82.6% was the result of HPT. At a mean follow-up of 26.5 months, the average kyphosis correction loss was 2.9°. The mean sagittal balance was 11.1 ± 45.2 mm before traction, - 25.0 ± 37.4 mm after traction, 7.0 ± 13 mm after surgery, and 2.8 ± 9.6 mm at the final follow-up. The mean preoperative SRS-22 score was 3.0 and postoperative was 4.2 (P < 0.01). The neurological status of most patients was improved. The total complication rate was 15.7%, including 1 neurological and 2 non-neurological complications. CONCLUSIONS: HPT is effective in the management of severe spinal kyphotic deformity secondary to tuberculosis. Preoperative HPT can greatly reduce global kyphosis, and the need for corpectomy.

METTL3 regulates m6A methylation of PTCH1 and GLI2 in Sonic hedgehog signaling to promote tumor progression in SHH-medulloblastoma.

SHH subgroup medulloblastoma (SHH-MB) is one of the most common malignant pediatric tumors that arises in the cerebellum. Previously, we showed that RNA m6A methylation participates in regulation of cerebellar development. Here we investigate whether dysregulated m6A methylation contributes to tumorigenesis of SHH-MB. We show that high expression of m6A methyltransferase METTL3 associates with worse survival in the patients with SHH-MB. A large number of hypermethylated transcripts are identified in SHH-MB tumor cells by m6A-seq. We find that METTL3 promotes tumor progression via activating Sonic hedgehog signaling. Mechanistically, METTL3 methylates PTCH1 and GLI2 RNAs and further regulates their RNA stability and translation. Importantly, targeting METTL3 by depleting METTL3 expression or treatment with its catalytic inhibitor STM2457 restrains tumor progression. Collectively, this study shows a critical function for METTL3 and m6A methylation in SHH-MB, indicative of a potential role of METTL3 as therapeutic target in SHH-MB.

Characteristics of Sciatic Scoliotic List in Lumbar Disc Herniation.

STUDY DESIGN: Retrospective radiological study. OBJECTIVES: Physical examination reveals sciatic scoliotic list (SSL) in some patients with lumbar disc herniation (LDH). We aimed to evaluate the coronal and sagittal parameters of the SSL curve, describe their characteristics, and establish a new classification system. METHODS: We retrospectively reviewed 230 patients (SSL group = 96; non-SSL group = 134) diagnosed with single-segment LDH from January 2018 to December 2020. The control group comprised 70 healthy volunteers. Radiographic parameters were compared between the groups. RESULTS: In the SSL group, the Cobb's angle was 12.5 ± 5.3° (4.2-31.2), trunk shift 26.2 ± 17.9 mm (.0-88.2 mm), and apical vertebral translation 31.7 ± 16.0 mm (1.18-8.58 mm). Further, 62.5% of patients had L4/5 disc herniation, 76.0% had disc herniation at the convex side of the lumbosacral scoliosis, and 81.3% had disc herniation at the opposite side of the trunk shift. Compared to the control group, lumbar lordosis and thoracic kyphosis decreased, pelvic tilt increased, and the sagittal vertical axis moved forward in the other patients. The sagittal imbalance in the SSL group exacerbated. Using the positional relationship between vertebrae and the central sacral vertical line (CSVL), we identified two main SSL patterns with which 95.8% of the patients were defined as Type 1. CONCLUSIONS: The SSL curve is characterized by a long thoracic or thoracolumbar curve, with a relatively straight sagittal profile and little rotation. Further, the lumbar and thoracic vertebrae shifts are on the same side as the CSVL. These features of the SSL curve differentiate it from other types of structural scoliosis.