[Trametenolic acid inhibits migration and invasion of hepatocellular carcinoma HepG2.2.15 cells via RhoC/ROCK1 pathway].

This study investigated the effect of trametenolic acid(TA) on the migration and invasion of human hepatocellular carcinoma HepG2.2.15 cells by using Ras homolog gene family member C(RhoC) as the target and probed into the mechanism, aiming to provide a basis for the utilization of TA. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of HepG2.2.15 cells exposed to TA, and scratch and Transwell assays to examine the cell migration and invasion. The pull down assay was employed to determine the impact of TA on RhoC GTPase activity. Western blot was employed to measure the effect of TA on the transport of RhoC from cytoplasm to cell membrane and the expression of RhoC/Rho-associated kinase 1(ROCK1)/myosin light chain(MLC)/matrix metalloprotease 2(MMP2)/MMP9 pathway-related proteins. RhoC was over-expressed by transient transfection of pcDNA3.1-RhoC. The changes of F-actin in the cytoskeleton were detected by Laser confocal microscopy. In addition, the changes of cell migration and invasion, expression of proteins in the RhoC/ROCK1/MLC/MMP2/MMP9 pathway, and RhoC GTPase activity were detected. The subcutaneously transplanted tumor model of BALB/c nude mice and the low-, medium-, and high-dose(40, 80, and 120 mg·kg~(-1), respectively) TA groups were established and sorafenib(20 mg·kg~(-1)) was used as the positive control. The tumor volume and weight in each group were measured, and the expression of related proteins in the tumor tissue was determined by Western blot. The results showed that TA inhibited the proliferation of HepG2.2.15 cells in a concentration-dependent manner, with the IC_(50) of 66.65 and 23.09 µmol·L~(-1) at the time points of 24 and 48 h, respectively. The drug administration groups had small tumors with low mass. The tumor inhibition rates of sorafenib and low-, medium-and high-dose TA were 62.23%, 26.48%, 55.45%, and 62.36%, respectively. TA reduced migrating and invading cells and inhibited RhoC protein expression and RhoC GTPase activity in a concentration-dependent manner, dramatically reducing RhoC and membrane-bound RhoC GTPase. The expression of ROCK1, MLC, p-MLC, MMP2, and MMP9 downstream of RhoC can be significantly inhibited by TA, as confirmed in both in vitro and in vivo experiments. After HepG2.2.15 cells were transfected with pcDNA3.1-RhoC to overexpress RhoC, TA down-regulated the protein levels of RhoC, ROCK1, MLC, p-MLC, MMP2, and MMP9 and decreased the activity of RhoC GTPase, with the inhibition level comparable to that before overexpression. In summary, TA can inhibit the migration and invasion of HepG2.2.15 cells. It can inhibit the RhoC/ROCK1/MLC/MMP2/MMP9 signaling pathway by suppressing RhoC GTPase activity and down-regulating RhoC expression. This study provides a new idea for the development of autophagy modulators targeting HSP90α to block the proliferation and inhibit the invasion and migration of hepatocellular carcinoma cells via multiple targets of active components in traditional Chinese medicines.

Research progress on the regulation of bone marrow stem cells by noncoding RNAs in adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity in young women, but its pathogenesis remains unclear. The primary pathogenic factors contributing to its development include genetics, abnormal bone metabolism, and endocrine factors. Bone marrow stem cells (BMSCs) play a crucial role in the pathogenesis of AIS by regulating its occurrence and progression. Noncoding RNAs (ncRNAs) are also involved in the pathogenesis of AIS, and their role in regulating BMSCs in patients with AIS requires further evaluation. In this review, we discuss the relevant literature regarding the osteogenic, chondrogenic, and lipogenic differentiation of BMSCs. The corresponding mechanisms of ncRNA-mediated BMSC regulation in patients with AIS, recent advancements in AIS and ncRNA research, and the importance of ncRNA translation profiling and multiomics are highlighted.

BMP6 participates in the pathogenesis of adolescent idiopathic scoliosis by regulating osteopenia.

Adolescent idiopathic scoliosis (AIS) is a complex disease characterized by three-dimensional structural deformities of the spine. Its pathogenesis is associated with osteopenia. Bone-marrow-derived mesenchymal stem cells (BMSCs) play an important role in bone metabolism. We detected 1919 differentially expressed mRNAs and 744 differentially expressed lncRNAs in BMSCs from seven patients with AIS and five patients without AIS via high-throughput sequencing. Multiple analyses identified bone morphogenetic protein-6 (BMP6) as a hub gene that regulates the abnormal osteogenic differentiation of BMSCs in AIS. BMP6 expression was found to be decreased in AIS and its knockdown in human BMSCs significantly altered the degree of osteogenic differentiation. Additionally, CAP1-217 has been shown to be a potential upstream regulatory molecule of BMP6. We showed that CAP1-217 knockdown downregulated the expression of BMP6 and the osteogenic differentiation of BMSCs. Simultaneously, knockout of BMP6 in zebrafish embryos significantly increased the deformity rate. The findings of this study suggest that BMP6 is a key gene that regulates the abnormal osteogenic differentiation of BMSCs in AIS via the CAP1-217/BMP6/RUNX2 axis.

Isolated neural arch tuberculosis with tuberculomas: case report.

We reported a case of atypical spinal tuberculosis on the posterior elements of lumbar spine in a 52-year-old female. It was easy to be misdiagnosed as spinal tumor due to its imaging characteristics. We performed puncture biopsy to initially consider tuberculosis, and then the patient was accepted surgical treatment. The intraoperative removed specimen was sent to pathological examination, microbial culture, Xpert MTB/RIF and metagenomic next-generation sequencing (mNGS) and then the diagnosis of neural arch tuberculosis was confirmed. After operation, the patient obtained stable effect by anti-tuberculosis drug treatment. In a word, the uncommon case had an important reference significance for the diagnosis of atypical spine tuberculosis and differentiation from spinal tumors. It is critical to make right preliminary diagnosis by appropriate examination as it determined the next diagnosis and treatment in special and rare clinical cases.

Filum terminale arteriovenous shunt with nidus structure: a report of rare condition and treatment consideration.

BACKGROUND:  In the literature, filum terminale arteriovenous shunts (FTAVSs) always feature a single shunt point. Nidus-type FTAVSs have rarely been reported, and the best treatment strategy is unclear. This is a report of one exceptional case of a nidus-type FTAVS and surgical treatment of the lesion. CASE DESCRIPTION: The patient suffered from cauda equina syndrome for 9 months. Magnetic resonance imaging and spinal angiography revealed a nidus-type FTAVF at the L2 level. Surgical resection was performed in the hybrid operating room, and the nidus was completely resected with the assistance of intraoperative methylene blue angiography and neurophysiological monitoring. The postoperative neurological function was stable. CONCLUSIONS: A nidus-type arteriovenous shunt could originate from the FT, and in such cases, complete surgical resection with intraoperative neurophysiological monitoring in a hybrid operating room should be suggested.

The role of endocrine hormones in the pathogenesis of adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity characterized by changes in the three-dimensional structure of the spine. It usually initiates during puberty, the peak period of human growth when the secretion of numerous hormones is changing, and it is more common in females than in males. Accumulating evidence shows that the abnormal levels of many hormones including estrogen, melatonin, growth hormone, leptin, adiponectin and ghrelin, may be related to the occurrence and development of AIS. The purpose of this review is to provide a summary and critique of the research published on each hormone over the past 20 years, and to highlight areas for future study. It is hoped that the presentation will help provide a better understanding of the role of endocrine hormones in the pathogenesis of AIS.

The efficacy and deficiency of contemporary treatment for spinal cord arteriovenous shunts.

Contemporary treatments for spinal cord arteriovenous shunts are only based on clinicians' treatment experiences and expertise due to its rarity. We reviewed the clinical course of the largest multicentred cohort to evaluate the efficacy and deficiency of contemporary interventional treatments for spinal cord arteriovenous shunts. The clinical features, treatment results and clinical outcomes of 463 patients with spinal cord arteriovenous shunts were retrospectively assessed. The main outcome was the neurological deterioration that was evaluated based on the modified Aminoff and Logue scale. According to post-treatment digital subtraction angiography, complete obliteration was defined as disappearance of the intradural lesion, whereas partial obliteration was defined as any residual intradural lesion remaining visible and was further categorized as shunt-reduction obliteration (the nidus or shunt points were reduced) or palliative obliteration (only obliterated aneurysms or feeders). Cure rate was 40.6% for the whole cohort, 58.5% after microsurgery, and 26.4% after embolization. The curative resection was associated with non-metameric lesions, lesions with a maximum diameter <3 cm and lesions without anterior sulcal artery supply. The curative embolization was associated with fistula-type lesions, non-metameric lesions, and main drainage diameter <1.5 mm. The permanent treatment-related neurological deficits rate was 11.2% for the whole cohort, 16.1% after microsurgery, and 5.6% after embolization. The pretreatment clinical deterioration rate was 32.5%/year, which decreased to 9.3%/year after clinical interventions. Following partial treatment, the long-term acute and gradual deterioration rates were 5.3%/year and 3.6%/year, respectively. The acute deteriorations were associated with metameric lesions, craniocervical lesions, lesions with a maximum diameter ≥2 cm and residual aneurysm. Residual aneurysm was the only predictor of acute deterioration for non-metameric spinal cord arteriovenous shunts. The gradual deteriorations were associated with palliative obliteration, absence of pretreatment acute deterioration and intact main drainage. Although clinical risks of spinal cord arteriovenous shunts were reduced following clinical interventions, contemporary treatments for spinal cord arteriovenous shunt remains associated with considerable risks and incomplete efficacy. Individualized treatment plans should be adopted according to the angio-architectural features and major clinical risks of specific lesions. There is a higher opportunity for complete obliteration for lesions with simple angio-architecture. However, for most of spinal cord arteriovenous shunts with complex vascular anatomy, partial treatment is the only choice. For these patients, palliative obliteration targeting the aneurysms is recommended for reducing haemorrhagic risk, whereas shunt-reduction obliteration is necessary for non-haemorrhagic myelopathy. Contemporary treatment is ineffective in reducing haemorrhagic risk of incurable metameric spinal cord arteriovenous shunts.

Retrospective analysis of deformed complex vertebral osteotomy in children with severe thoracic post-tubercular angular kyphosis.

BACKGROUND: Many surgical options have been described to manage post-tubercular kyphosis, but the standard approach for treating severe post-tubercular angular kyphosis in children has not been established yet. The present study was performed to evaluate the safety and efficacy of deformed complex vertebral osteotomy (DCVO) for the treatment of severe thoracic post-tubercular angular kyphosis (> 70°) in children. METHODS: Deformed complex vertebrae indicated that multiple deformed and fused vertebrae were usually involved with two or more vertebral bodies and the partial or total fusion of many segments' facet joints and intervertebral discs. Thus, DCVO indicated that a wider posterior wedge-shaped and three-column osteotomy was performed within deformed complex vertebrae to correct a more extensive range of angles. From 2010 to 2017, 15 children who suffered from severe thoracic post-tubercular angular kyphosis underwent DCVO. Deformed complex vertebrae involved two vertebral bodies in 9 patients and three vertebral bodies in 6 patients. The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were assessed preoperatively and at the final follow up. This was a retrospective study analysing the outcome after grade 4/5 spinal osteotomies in deformed complex vertebrae. RESULTS: The mean duration of surgery was 239 ± 37.81 min. The average period of follow-up was 31.6 ± 6.98 months. The preoperative mean kyphosis of deformed complex vertebrae was 83.39° ± 9.04°; the mean thoracic kyphosis (TK) and lumbar lordosis (LL) were 81.09° ± 8.51° and 80.51° ± 7.64°, respectively; the mean sagittal vertical axis (SVA) was 3.83 cm ± 1.43 cm. The postoperative mean kyphosis of deformed complex vertebrae was reduced to 19.98° ± 2.47° (P < 0.001) with a mean kyphosis correction of 63.41°; at the final follow up, it was 18.4° ± 2.29° (P < 0.001) without obvious loss of correction. The postoperative mean TK, LL, and SVA were reduced to 24.05° ± 3.84°, 46.9° ± 3.53°, and 0.6 cm ± 0.34 cm, respectively (P < 0.001 for all); and there was no obvious loss of sagittal alignment and balance at the final follow up (p = 0.982, p = 0.604, p = 0.754). Complicated with neural dysfunction preoperatively, 5 Frankel's grade D cases showed complete neurological recovery at final follow up. VAS score reduced from 3.6 ± 1.18 to 0.87 ± 0.64 (P < 0.001); and ODI score reduced from 22.21 ± 6.93 to 5.02 ± 2.6 (P < 0.001) at the final follow up. CONCLUSIONS: DCVO was an individualized osteotomy for treating severe thoracic post-tubercular angular kyphosis in children and could be safe and effective in reducing the incidence of complications and significantly improving kyphosis correction.

Abnormal TNS3 gene methylation in patients with congenital scoliosis.

BACKGROUND: Congenital scoliosis (CS) is a congenital deformity of the spine resulting from abnormal and asymmetrical development of vertebral bodies during pregnancy. However, the etiology and mechanism of CS remain unclear. Epigenetics is the study of heritable variations in gene expression outside of changes in nucleotide sequence. Among these, DNA methylation was described first and is the most characteristic and most stable epigenetic mechanism. Therefore, in this study, we aim to explore the association between genome methylation and CS which are not been studied before. METHODS: Two pairs of monozygotic twins were included, with each pair involving one individual with and one without CS. Agilent SureSelect XT Human Methyl-Sequencing was used for genome methylation sequencing. MethylTarget was used to detect methylation levels in target regions. Immunohistochemistry was performed to visualize expression of associated genes in candidate regions. RESULTS: A total of 75 differentially methylated regions were identified, including 24 with an increased methylation level and 51 with a decreased methylation level in the CS group. Nine of the differentially methylated regions were selected (TNS3, SEMAC3, GPR124, MEST, DLK1, SNTG1, PPIB, DEF8, and GRHL2). The results showed that the methylation level of the promoter region of TNS3 was 0.72 ± 0.08 in the CS group and 0.43 ± 0.06 in the control group (p = 0.00070 < 0.01). There was no significant difference in the degree of methylation of SEMAC3, GPR124, MEST, DLK1, SNTG1, PPIB, DEF8, or GRHL2 between the two groups. Immunohistochemistry showed significantly decreased TNS3 expression in the cartilage of the articular process in CS (CS: 0.011 ± 0.002; control: 0.018 ± 0.006, P = 0.003 < 0.01). CONCLUSION: Compared with the control group, high-level methylation of the TNS3 promoter region and low TNS3 expression in the cartilage layer of the articular process characterize CS. Thus, DNA methylation and TNS3 may play important roles in the pathogenesis of CS.

Posterior-only surgical correction with heavy halo-femoral traction for the treatment of extremely severe and rigid adolescent idiopathic scoliosis (> 130°).

INTRODUCTION: The treatment of extremely severe and rigid spinal deformities was a great surgical challenge. Pulmonary impairment often occurred, which increased the challenges to already daunting surgical approaches. The present study was performed to evaluate the safety and efficacy of posterior-only surgical correction with heavy halo-femoral traction (HFT) for the treatment of extremely severe and rigid adolescent idiopathic scoliosis (AIS) of more than 130°. MATERIALS AND METHODS: From 2010 to 2017, 11 patients suffered from extremely severe and rigid AIS of more than 130° underwent posterior-only surgical correction with HFT. The preoperative mean coronal Cobb angle of major curve was 139.01° ± 5.83°, and the mean flexibility was 17.21% ± 3.33%; the mean angle of thoracic kyphosis (TK) and lumbar lordosis (LL) were 65.02° ± 7.21° and 39.05° ± 4.08°, respectively; the mean trunk shift (TS) and sagittal vertical axis (SVA) were 3.3 ± 0.97 cm and 3.97 ± 1.16 cm, respectively; moreover, the percent forced vital capacity (FVC%) and percent forced expiratory volume in 1 s (FEV1%) were 50.08% ± 6.07% and 53.46% ± 5.96%, respectively; the mean body height and weight were 140.09 ± 4.95 cm and 37 ± 4.34 kg, respectively. RESULTS: The mean duration of surgery was 335.91 ± 48.31 min and blood loss was 1590 ± 520.1 ml. The average period of follow-up was 32.18 ± 8.17 months. After heavy HFT, the mean coronal Cobb angle of major curve was reduced to 82.98° ± 6.91° with correction rate of 40.39%. After posterior-only surgical correction, the mean coronal Cobb angle was further reduced to 51.17° ± 5.4° with correction rate of 63.27%. The postoperative mean TK, LL, TS and SVA were improved to 23.85° ± 5.14°, 44.95° ± 2.26°, 1.32 ± 0.72 cm and 1.42 ± 0.83 cm, respectively. At the final follow-up, the corrective loss rate of Cobb angle was only 0.72%; moreover, the mean FVC% and FEV1% were increased to 65.45% ± 5.29% and 69.08% ± 5.32% with improvement of 15.36% and 15.62%, respectively; the mean body height and weight were increased to 154.45 ± 5.32 cm and 45 ± 4.02 kg with improvement of 14.36 cm and 8 kg, respectively. The spinal cord function was stable, and there were no new neurological symptoms after correction. CONCLUSIONS: Posterior-only surgical correction with heavy HFT could be safe and effective for the treatment of extremely severe and rigid AIS of more than 130° in reducing the incidence of complications and greatly improving curve correction.

Minimum 5-year follow-up outcomes for one-stage posterior instrumentation without neurosurgery intervention for correction of scoliosis associated with Chiari I malformation and syringomyelia.

INTRODUCTION: Traditionally, the common belief has been that, all patients with Chiari I malformation (CM-1) and syringomyelia (SM) undergoing a neurosurgical procedure even if they are neurologically asymptomatic. As the pathology of CM-1 and SM has become better understood, the traditional concepts have been challenged. The objective of this study was to investigate the minimum 5-year follow-up clinical outcomes of surgical treatment of patients with scoliosis associated with CM-1 and SM and to evaluate the necessity of neurosurgical intervention before corrective surgery. METHODS: This retrospective study was performed from May 2009 to September 2014. We enrolled 35 patients with scoliosis associated with CM-1 and SM who were undergoing spinal correction surgery without neurosurgical intervention. During the surgery, spinal cord monitor and wake-up test were used. Preoperative, postoperative, and final follow-up major curve coronary Cobb angle, correction rate, apical vertebral rotation (AVR), apical vertebral translation (AVT), thoracic kyphosis angle (T5-T12), lumbar lordosis angle (L1-S1) were analyzed on radiographs. RESULTS: The mean follow-up period was 82.5 months. The preoperative and postoperative mean curve coronary Cobb angle was from 55.7 ± 7.5° to 20.1 ± 5.8°, correction rate was 63.9%, AVR from 2.8 ± 0.6° to 1.3 ± 0.5°, AVT from 5.1 ± 1.4 to 1.7 ± 0.7 cm, thoracic kyphosis angle from 18.7 ± 4.0° to 32.2 ± 2.7°, lumbar lordosis angle from 36.3 ± 4.1° to 43.8 ± 3.2°. No neurological deficits occurred during the operation and follow-up. CONCLUSIONS: Our minimum 5-year follow-up outcomes showed that in a distinct patient population of neurologically asymptomatic individuals with CM-1, SM and progressive scoliosis, posterior instrumented spinal deformity surgery can be safely done without neurosurgical interverventions with the help of preoperative flexibility evaluation and intraoperative neuromonitoring.

Health-related quality of life outcomes and influencing factors in patients with unruptured intracranial aneurysms after endovascular treatment.

BACKGROUND: Health-related quality of life (HRQoL) is an important indicator when evaluating prognosis and disease-related treatments. Our current knowledge of the HRQoL outcomes of unruptured intracranial aneurysm (UIA) patients treated by the endovascular intervention appeared to be very limited. To fill this gap, the present study investigated the HRQoL outcomes and identified the influencing factors in UIA patients treated by endovascular intervention. METHODS: We conducted a single-center cross-sectional study on patients who underwent endovascular treatment for UIAs. HRQoL outcomes were assessed by the 36-item Short Form Health Survey (SF-36). The SF-36 results of the Chinese reference population were used as the reference data. The independent variables with a univariate analysis result of P < 0.05 were included in the multivariate analysis. Finally, multivariable linear regression analysis was performed to identify the factors influencing HRQoL. Bonferroni correction was utilized for multiple testing correction. RESULTS: A total of 200 patients (83 males and 117 females, mean age of 55.2 ± 9.48 years) with UIAs treated by endovascular intervention were enrolled. The scores of SF-36 in 8 domains for UIA patients treated by endovascular intervention did not all reach the average level of the Chinese reference population after an average recovery period of 30.67 ± 8.6 months. Ischemic cerebrovascular disease history, advanced age, and mRS progression at discharge were independent risk factors of HRQoL for UIA patients treated by endovascular intervention, but physical exercise at least once a week and daily sleep time no < 6 h were independent protective factors. CONCLUSION: The HRQoL of UIA patients treated by the endovascular intervention was decreased to varying degrees compared with those of the Chinese reference population. The influencing factors of HRQoL explored by this study provide insights for improving the clinical management and daily lives of these patients. HRQoL assessment should be included in future aneurysm prognostic studies to provide better evidence.

Current Knowledge of and Perspectives about the Pathogenesis of Blood Blister-like Aneurysms of the Internal Carotid Artery: A Review of the Literature.

Blood blister-like aneurysms (BBAs) are rare and usually appear at nonbranching sites in the supraclinoid portion of the internal carotid artery (ICA). Because it is difficult to obtain histological specimens of the aneurysm wall and because experimental models are challenging to establish, the pathogenesis of BBAs remains uncertain. In this paper, we reviewed the diagnostic, radiological, and pathophysiological characteristics of patients with BBAs. We also summarized the existing evidence and potential mechanisms related to the causes of BBAs. Current evidence indicates that atherosclerosis and dissection are the main prerequisites for the formation of BBAs. Hemodynamics may play a role in the process of BBA formation due to the unique vascular anatomy of the supraclinoid ICA. Further research on histopathology and hemodynamics is warranted in this field.

Comprehensive Treatment and Vascular Architecture Characteristic of High-Flow Vascular Malformations in Periorbital Regions.

OBJECTIVE: This study analyzed the vascular architecture characteristics of high-flow vascular malformations (VMs) in periorbital regions, as well as the treatment and imaging prognosis of occlusion degree of the outflow veins. METHOD: The clinical data of 24 patients with high-flow VMs in periorbital regions treated in our center from 2012 to 2019 were analyzed retrospectively, and the vascular architecture characteristics, treatment methods, and follow-up results were recorded. RESULTS: The vascular architecture of high-flow VMs in periorbital regions which usually contained the intracranial feeding arteries (24/24,100.0%) and intracranial outflow veins (18/24, 75.0%). The average age of first diagnosis was 23 ±â€Š16 years; the average age of treatment was 37 ±â€Š10 years; the median follow-up time was 42.5 months. Twenty-four patients with high-flow VMs in periorbital regions had 58 treatments in all. The imaging cure was achieved in 6 patients by complete occlusion of outflow veins, and no recurrence was found by DSA. Eighteen patients who get incomplete occlusion of outflow veins were given 49 treatments, and 8 patients had imaging recurrence. Seven patients (7/24, 29.2%) had treatment-related complications in all. CONCLUSIONS: Patients with high-flow VMs in periorbital regions are the most complex cases. The prognosis of patients whose outflow veins can be completely occluded is relatively good. The stepwise embolization while preserving organ function is advisable. Nevertheless, the incidence of treatment complications is still high.

Natural history of spinal cord arteriovenous shunts: an observational study.

The natural history of intradural spinal cord arteriovenous shunts is unknown. We performed an observational study in a consecutive patient cohort with symptomatic intradural spinal cord arteriovenous shunts who were admitted to three institutes to investigate the clinical course of this complex disease, which would provide valuable evidence to inform clinical decision-making. The clinical course of patients with symptomatic intradural spinal cord arteriovenous shunts from initial presentation to occurrence of clinical deterioration, initiation of treatment, or last follow-up was analysed. Patients with at least 1 month of observation were included in this study. Clinical onset and deterioration patterns were divided into acute and gradual. Annual and cumulative rates of clinical deterioration as well as their risk factors were analysed using Kaplan-Meier life table analysis and Cox proportional hazards model. To assess risks and benefits of treatment, post-treatment clinical courses were further assessed. Four hundred and sixty-six patients with a mean observational period of 36.9 ± 58.8 months were included; 56.7% of patients presented with acute onset, of whom 77.3% experienced spontaneous recovery. Age of onset older than 28 years, initial modified Aminoff and Logue scale of >3, mid-thoracic lesions and non-ventral lesions were independent predictors of failure for spontaneous recovery. The annual risk of general, acute and gradual clinical deterioration after onset was 30.7%, 9.9% and 17.7%, respectively. Risk of deterioration was highest in the early period after initial onset. Acute onset was the only independent risk factor [hazard ratio 1.957 (95% confidence interval, CI 1.324-2.894); P = 0.0008] of acute deterioration and gradual onset was the strongest predictor [hazard ratio 2.350 (95% CI 1.711-3.229); P < 0.0001] of the gradual deterioration among all the stratifying factors. After invasive treatment, complete obliteration was achieved in 37.9% of patients (138 of 364) and improved or stable clinical status was noted in 80.8% of patients. Forty-two patients (11.5%) experienced permanent complications. Overall post-treatment deterioration rate was 8.4%/year, and 5.3%/year if permanent complications were excluded. The natural history of symptomatic spinal cord arteriovenous shunts is poor, especially in the early period after onset, and early intervention is thus recommended. Initial onset pattern significantly affects the natural history of the lesion, which prompts a differentiated treatment strategy.

Prevalence of and risk factors for anxiety and depression in Chinese patients with unruptured intracranial aneurysms treated by endovascular intervention.

BACKGROUND: Studies on anxiety and depression in unruptured intracranial aneurysm (UIA) patients after treatment via endovascular intervention are rare and controversial. We aimed to explore the prevalence of anxiety and depression among Chinese patients with UIAs treated by endovascular intervention and to identify which factors contribute to the development of these symptoms. METHODS: We performed a cross-sectional study on anxiety and depression in patients who underwent endovascular treatment for UIAs using the Hospital Anxiety and Depression Scale (HADS). The demographic, clinical and radiological data for all patients were retrospectively collected from the aneurysm database and medical records. Moreover, we utilized data from a large sample of 200 UIA patients and multivariate logistic regression analysis to investigate the risk factors for anxiety and depression in these patients. Candidate variables with P values less than 0.20 in univariate analysis were included in the multivariate logistic regression analysis. RESULTS: Two hundred patients returned completed questionnaires in this study. Of these 200 patients, 34 (17.0%) suffered from anxiety and 31 (15.5%) suffered from depression 30.67 ± 8.6 months after being discharged. The multivariate analysis results indicated that shorter sleep times were statistically significantly associated with depression (OR = 1.62, 95% CI: 1.14 ~ 2.29, P = 0.007, Adjusted P = 0.02). . CONCLUSION: The prevalences of anxiety and depression in UIA patients treated by endovascular intervention were 17.0 and 15.5%, respectively. Shorter sleep times were significantly associated with depression. Our findings provide evidence for the clinical and psychological management of these patients.

Posterior-only surgical correction with heavy halo-femoral traction for the treatment of rigid congenital scoliosis associated with split cord malformation.

BACKGROUND: Whether or not, prophylactic neurosurgical interventions of split cord malformation (SCM) before undertaking corrective surgery was the focus of debate. The present study was performed to evaluate the safety and efficacy of posterior-only surgical correction with heavy halo-femoral traction for the treatment of rigid congenital scoliosis (RCS) associated with SCM. METHODS: From 2011 to 2017, 24 patients suffered from RCS associated with SCM underwent posterior-only surgical correction with heavy halo-femoral traction. The apex of the deformity was lumbar (n = 9), thoracic (n = 11), and thoracolumbar (n = 4). There were 13 cases of failure of segmentation; 4 cases of failure of formation and 7 cases of mixed defects. Based on SCM classification, there were 14 patients with SCM type 1 and 10 patients with SCM type 2. The Scoliosis Research Society (SRS)-22 and modified Japanese Orthopaedic Association (mJOA) scores were assessed preoperatively and at the final follow up. RESULTS: The mean duration of surgery was 327.08 ± 43.99 min and the mean blood loss was 1303.33 ± 526.86 ml. The mean follow-up period was 20.75 ± 8.29 months. The preoperative mean coronal Cobb angle was 80.38° ± 13.55°; on the bending radiograph of the convex side, the mean Cobb angle was 68.91° ± 15.48°; the mean flexibility was 15.04% ± 7.11%. After heavy halo-femoral traction, the mean coronal Cobb angle was reduced to 56.89° ± 13.39°. After posterior-only surgical correction, postoperative mean coronal Cobb angle was further reduced to 32.54° ±11.33°. The postoperative mean correction rate was 60.51% ± 7.79%. At the final follow up, the corrective loss rate of Cobb angle was only 3.17%. The SRS-22 total score improved at the final follow-up evaluation compared with the preoperative SRS-22 total score. The spinal cord function was stable and there were no new neurological symptoms after correction. There were no significant differences between final follow-up and preoperative mJOA total scores. CONCLUSIONS: Without prophylactic neurosurgical intervention and spine-shortening osteotomy, posterior-only surgical correction with heavy halo-femoral traction could be safe and effective for the treatment of RCS associated with SCM.

Suboccipital transtentorial approach to remove a cerebellar cavernous malformation adjacent to cerebellomesencephalic fissure.

BACKGROUND: Microsurgical removal of cerebral cavernous malformations (CCMs) at the region of cerebellomesencephalic fissure is technical challenging. METHODS: A 51-year-old gentleman complained severe vertigo and vomiting for 10 days before admission. The symptoms did not improve after medicine treatment. Neuroimaging studies in other hospital revealed a CCM and hematoma at the region of cerebellomesencephalic fissure invading both the left cerebellum and its peduncles. The CCM was successfully removed through a suboccipital transtentorial approach. The detailed surgical techniques were reported. CONCLUSION: A suboccipital transtentorial approach could be used to remove CCMs at the region of cerebellomesencephalic fissure.

Ghrelin up-regulates cartilage-specific genes via the ERK/STAT3 pathway in chondrocytes of patients with adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a severe spinal deformity that often occurs during puberty. The occurrence of AIS is suggested to be related to abnormal development of cartilage. Our previous study found increased serum ghrelin levels in AIS patients that may linked to the development of AIS. However, whether ghrelin affects cartilage in AIS patients is unclear. We used quantitative real-time PCR (qRT-PCR) and immunohistochemistry to detect the expression of cartilage-specific genes and the ghrelin receptor, growth hormone secretagogue receptor (GHSR). The mRNA and protein levels of collagen II (COLII), SOX9, AGGRECAN (ACAN) and GHSR were higher in AIS patients than in controls. In addition, the protein levels of GHSR downstream signaling pathway members p-STAT3 (Ser727), and p-ERK1/2 were increased. Furthermore, we treated chondrocytes from AIS patients with 100 nM ghrelin, the cell proliferation assay and Western blotting showed that ghrelin promotes chondrocyte proliferation and enhances COLII, SOX9, ACAN, p-ERK1/2 and p-STAT3 expression, respectively. Interestingly, all these observed alterations were abolished by ghrelin + [D-Lys3]-GHRP-6 (a ghrelin receptor inhibitor) treatment. And after U0126 (an inhibitor of ERK1/2 phosphorylation) treatment, ERK1/2 and STAT3 (Ser727) phosphorylation was simultaneously suppressed indicating that ERK1/2 is an upstream pathway protein of STAT3 (Ser727). In conclusion, ghrelin plays an important role in upregulating cartilage-specific genes on AIS primary chondrocytes by activating ERK/STAT3 signaling pathway.

Adiponectin regulates bone mass in AIS osteopenia via RANKL/OPG and IL6 pathway.

BACKGROUND: Osteopenia have been well documented in adolescent idiopathic scoliosis (AIS). Adiponectin has been shown to be inversely proportional to body mass index and to affect bone metabolism. However, the circulating levels of adiponectin and the relationship between adiponectin and low bone mass in AIS remain unclear. METHODS: A total of 563 AIS and 281 age-matched controls were recruited for this study. Anthropometry and bone mass were measured in all participants. Plasma adiponectin levels were determined by enzyme-linked immunosorbent assay (ELISA) in the AIS and control groups. An improved multiplex ligation detection reaction was performed to study on single nucleotide polymorphism. Facet joints were collected and used to measure the microstructure, the expression of RANKL, OPG, osteoblast-related genes, inflammatory factors, adiponectin and its receptors by qPCR, western blotting and immunohistochemistry. Furthermore, primary cells were extracted from facet joints to observe the reaction after adiponectin stimulation. RESULTS: Compared with the controls, lower body mass index and a marked increase in circulating adiponectin were observed in AIS osteopenia (17.09 ± 1.09 kg/m2 and 21.63 ± 10.30 mg/L). A significant difference in the presence of rs7639352was detected in the AIS osteopenia, AIS normal bone mass and control groups. The T allele showed a significant higher proportion in AIS osteopenia than AIS normal bone mass and control groups (41.75% vs 31.3% vs 25.7%, p < 0.05). micro-CT demonstrated that the AIS convex side had a significant lower bone volume than concave side. RNA and protein analyses showed that in cancellous bone, higher RANKL/OPG and adipoR1 levels and lower runx2 levels were observed, and in cartilage, higher adipoR1 and IL6 levels were observed in AIS. Furthermore, convex side had higher RANKL/OPG, IL6 and adipoR1 than concave side. Compared with normal primary cells, convex side primary cells showed the most acute action, and concave side primary cells showed the second-most acute action when exposed under same adiponectin concentration gradient. CONCLUSION: Our results indicated that high circulating adiponectin levels may result from gene variations in AIS osteopenia. Adiponectin has a negative effect on bone metabolism, and this negative effect might be mediated by the ADR1-RANKL/OPG and ADR1-IL6 pathways.