Pharmacological inhibition of neddylation impairs long interspersed element 1 retrotransposition.

Aberrant long interspersed element 1 (LINE-1 or L1) activity can cause insertional mutagenesis and chromosomal rearrangements and has been detected in several types of cancers. Here, we show that neddylation, a post-translational modification process, is essential for L1 transposition. The antineoplastic drug MLN4924 is an L1 inhibitor that suppresses NEDD8-activating enzyme activity. Neddylation inhibition by MLN4924 selectively impairs ORF2p-mediated L1 reverse transcription and blocks the generation of L1 cDNA. Consistent with these results, MLN4924 treatment suppresses the retrotransposition activity of the non-autonomous retrotransposons short interspersed nuclear element R/variable number of tandem repeat/Alu and Alu, which rely on the reverse transcription activity of L1 ORF2p. The E2 enzyme UBE2M in the neddylation pathway, rather than UBE2F, is required for L1 ORF2p and retrotransposition. Interference with the functions of certain neddylation-dependent Cullin-really interesting new gene E3 ligases disrupts L1 reverse transcription and transposition activity. Our findings provide insights into the regulation of L1 retrotransposition and the identification of therapeutic targets for L1 dysfunctions.

High expression of integrin-binding sialoprotein (IBSP) is associated with poor prognosis of osteosarcoma.

INTRODUCTION: Osteosarcoma is a malignant tumor, accounting for 20% of primary malignant bone tumors worldwide. However, the role of IBSP as a biomarker in osteosarcoma progression has not been studied yet. METHODS: 85 cases of IBSP expression and clinical characteristics were obtained from TARGET database. Through the Kaplan-Meier curve, subgroup analysis, and univariate and multivariate Cox analysis, we further assessed the independent predictive capacity of IBSP expression for overall survival (OS) and relapse-free survival (RFS). RESULTS: The mRNA expression of IBSP was higher in osteosarcoma than normal tissue (P < 0.0001). IBSP expression grouped by vital status showed statistical differences (P = 0.042). The race (P = 0.0183), vital status (P = 0.0034), and sample type (P = 0.0020) showed significant differences. IBSP expression exhibited satisfied diagnostic ability for osteosarcoma. The univariate and multivariate analysis confirmed that IBSP expression was an independent risk factor for OS (HR = 3.425, 95% CI: 1.604-7.313, P = 0.002) and RFS (HR = 3.377, 95% CI: 1.775-6.424, P < 0.001) in osteosarcoma patients. High IBSP expression was significantly associated with poor OS and RFS (P < 0.0001). The higher IBSP expression was observed in osteosarcoma (P < 0.001), confirmed by the IHC staining. The CCK-8 and colony formation assay showed that IBSP knockdown inhibits cell proliferation while overexpression promotes cell proliferation (P < 0.05). CONCLUSION: High expression of IBSP was associated with poor OS and RFS. IBSP could serve as a potential biomarker for osteosarcoma, which could aid in early detection and disease monitoring.

Analysis of Potential Risk Factors for Cement Leakage into Paraspinal Veins after Vertebroplasty for Acute Osteoporotic Vertebral Fractures Based on a 3D Reconstruction Technique: A Retrospective Matched Case-Control Study.

OBJECTIVE: Pulmonary embolism, cardiac embolism, and even cerebral embolism due to paraspinal vein leakage (PVL) are increasingly reported, and their risk factors need to be adequately investigated for prevention. To this end, this study investigated the correlation of the distribution and morphological characteristics of fracture lines with the occurrence of PVL after percutaneous vertebroplasty (PVP), which has not been previously reported. METHODS: Patients with acute single-segment thoracolumbar osteoporotic vertebral compression fractures (OVCFs) treated with PVP at our institution from January 2019 to July 2022 were selected for a matched case-control study. The case and control groups included those with and without PVL, respectively, matched at a 1:1 ratio based on general clinical characteristics. Additionally, fracture map and heatmap analysis was performed in both groups. In addition to the general clinical characteristics, the vertebral height ratio, puncture angle, delivery rate, and indexes were assessed via the three-dimensional CT reconstruction fracture line mapping technique, namely, the distribution of fracture lines, fracture line length, main fracture line shape, location of fracture line involvement, and number of fracture line branches, were compared between the two groups. The Wilcoxon rank-sum test, t tests, analysis of variance, and conditional logistic regression were used for statistical analysis. RESULTS: Among 658 patients with OVCFs, 54 who did and 54 who did not develop PVL were included in this study. Significant differences in the puncture angle, fracture line distribution (MR-1, ML-2, MM-2, MR-2, ML-3, MM-3, LL-1, LM-1, LL-2, LM-2), fracture line involvement of the posterior wall, total fracture line length, and main fracture line length were found between the two groups (p < 0.05). Logistic univariate analysis showed significant differences in the puncture angle, fracture line distribution (MR-1, ML-2, MM-2, MR-2, ML-3, MM-3, LL-1, LL-2, LM-2, LL-3), total fracture line length, main fracture line length, and fracture line involvement of the posterior wall between the two groups (p < 0.05). Logistic multifactorial analysis showed that the fracture line distribution (UR-3, ML-3, LM-2, LR-2) and main fracture line length were independent risk factors for the development of PVL in both groups. In addition, the fracture maps and heatmaps showed a greater degree of fracture line encapsulation and more extensive involvement in the middle and lower regions of the vertebral body in the PVL group than in the control group. CONCLUSIONS: Through a three-dimensional computed tomography reconstruction-based fracture line mapping technique, this study revealed for the first time that the distribution of fracture lines (UR-3, ML-3, LM-2, LR-2) and main fracture line length were independent risk factors for PVL after PVP in patients with acute single-segment thoracolumbar OVCFs. In addition, we hypothesized that the fracture line-vein traffic branch that may appear within 2 weeks after injury in acute OVCF patients may be one of the mechanisms influencing the above potential independent risk factors associated with PVL.

The Dual Effect of 3D-Printed Biological Scaffolds Composed of Diverse Biomaterials in the Treatment of Bone Tumors.

Bone tumors, including primary bone tumors, invasive bone tumors, metastatic bone tumors, and others, are one of the most clinical difficulties in orthopedics. Once these tumors have grown and developed in the bone system, they will interact with osteocytes and other environmental cells in the bone system's microenvironment, leading to the eventual damage of the bone's physical structure. Surgical procedures for bone tumors may result in permanent defects. The dual-efficacy of tissue regeneration and tumor treatment has made biomaterial scaffolds frequently used in treating bone tumors. 3D printing technology, also known as additive manufacturing or rapid printing prototype, is the transformation of 3D computer models into physical models through deposition, curing, and material fusion of successive layers. Adjustable shape, porosity/pore size, and other mechanical properties are an advantage of 3D-printed objects, unlike natural and synthetic material with fixed qualities. Researchers have demonstrated the significant role of diverse 3D-printed biological scaffolds in the treatment for bone tumors and the regeneration of bone tissue, and that they enhanced various performance of the products. Based on the characteristics of bone tumors, this review synthesized the findings of current researchers on the application of various 3D-printed biological scaffolds including bioceramic scaffold, metal alloy scaffold and nano-scaffold, in bone tumors and discussed the advantages, disadvantages, and future application prospects of various types of 3D-printed biological scaffolds. Finally, the future development trend of 3D-printed biological scaffolds in bone tumor is summarized, providing a theoretical foundation and a larger outlook for the use of biological scaffolds in the treatment of patients with bone tumors.

Is Tranexamic Acid Beneficial in Open Spine Surgery? and its Effects Vary by Dosage, Age, Sites, and Locations: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The role of tranexamic acid (TXA) in controlling blood loss during spine surgery remains unclear. With the publication of new randomized controlled trials (RCTs), we conducted a meta-analysis to determine the safety and efficacy of TXA in spine surgery. METHODS: PubMed, Embase, Web of Science, and Cochrane databases were searched for relevant studies through 2022. Only RCTs were eligible for this study. The extracted data were analyzed using RevMan 5.3 software for meta-analysis. RESULTS: Twenty RCTs including 1497 patients undergoing spine surgery were included in this systematic evaluation. Compared with the control group, TXA significantly reduced total blood loss (mean difference [MD] = - 218.96, 95% confidence interval [CI] = - 309.77 to - 128.14, P < 0.00001), perioperative blood loss (MD = - 90.54, 95% CI = - 139.33 to - 41.75, P = 0.0003), postoperative drainage (MD = - 102.60, 95% CI = - 139.51 to - 65.70, P < 0.00001)，reduced hospital stay (MD = - 1.42, 95% CI = - 2.71 to - 0.14, P = 0.03), reduced total blood transfusion volume (MD = - 551.06, 95% CI = - 755.90 to - 346.22, P < 0.00001), and international normalized ratio (MD = -0.03, 95% CI = -0.04 to -0.02, P < 0.00001). CONCLUSIONS: Based on the meta-analysis of 20 RCTs, we demonstrated that TXA reduces blood loss in open spine surgery, decreases transfusion rates, and shortens hospital stays. The TXA administration during the perioperative period does not increase the incidence of postoperative complications.

Construction and validation of a novel prognostic model for lung squamous cell cancer based on N6-methyladenosine-related genes.

BACKGROUND: N6-methyladenosine (m6A) is the most prevalent modification in mRNA in biological processes and associated with various malignant tumor initiation and progression. The present study aimed to construct a prognostic risk model based on m6A-related genes (the downstream genes influenced by m6A modulators) for LUSC. METHODS: Based on TCGA, we stratified LUSC patients with and without genetic alteration of m6A modulators into altered and unaltered groups. Using univariate Cox and Lasso regression analyses, we identified prognostic m6A-related genes to construct a prognostic risk model. We then applied a multivariate Cox proportional regression model and the survival analysis to evaluate the risk model. Moreover, we performed the Receiver operating characteristic curve to assess the efficiency of the prognostic model based on TCGA and GSE43131. We analyzed the characteristics of tumor-associated immune cell infiltration in LUSC through the CIBERSORT method. RESULTS: Three m6A-related genes (FAM71F1, MT1E, and MYEOV) were identified as prognostic genes for LUSC. A novel prognostic risk model based on the three m6A-related genes was constructed. The multivariate Cox analysis showed that the prognostic risk model was an independent risk factor (HR = 2.44, 95% CI = 1.21~3.56, p = 0.029). Patients with a high-risk group had worse overall survival both in TCGA (p = 0.018) and GSE43131 (p = 0.00017). The 1, 2, and 3-year AUC value in TCGA was 0.662, 0.662, and 0.655, respectively; The 1, 2, and 3-year AUC value in GSE43131 was 0.724, 0.724, and 0.722, respectively. The proportion of infiltrated neutrophils in the high-risk group was higher than that in the low-risk group (p = 0.028), whereas that of resting NK cells (p = 0.002) was lower. CONCLUSION: A novel prognostic risk model based on three m6A-related genes for LUSC was generated in this study.

Imaging of muscle and adipose tissue in the spine: A narrative review.

Interpretation of the morphology and characteristics of soft tissues, such as paravertebral muscles and fat, has always been a "relative blind spot" in the spine. The imaging features of the non-bony structures of the spine have been studied and reinterpreted, and changes in the non-bony structure are associated with spinal disease. Soft tissue parameters such as, the "paraspinal muscle cross-sectional area," "subcutaneous fat thickness," and the "paraspinal muscle fat infiltration rate" on computed tomography, magnetic resonance imaging and other imaging techniques are reproducible in the diagnosis, treatment and prognosis of spinal disorders and have the potential for clinical application. In addition, focus on the association between sarcopenia and spinal epidural lipomatosis with spinal disorders is increasing. Currently, there is no summary of studies on fat and muscle in the spinal region. Given this, within the context of recent research trends, this article provides a synthesis of research on adipose and muscle tissue in the spine, discusses advances in the study of the imaging manifestations of these structures in spinal disorders, and expands the perspectives.

Case report: Clinical highlights and radiological classification of IgG4-related spinal pachymeningitis: A rare case series and updated review of the literature.

Purpose: Hypertrophic pachymeningitis associated with immunoglobulin G4-related disease (IgG4-RD) has been rarely reported, and there is little information and no clear consensus on the management of IgG4-related spinal pachymeningitis (IgG4-RSP). The present study described its possible clinical features, including the symptoms, imaging, treatment and prognosis of patients with IgG4-RSP. Methods: We report three patients who presented with progressive neurological dysfunction due to spinal cord compression. Relevant articles were searched from the PubMed, Web of Science, and Embase databases, and the resulting literature was reviewed. Results: The literature review provided a summary of 45 available cases, which included three cases from our center. Progressive worsening of neurological impairment was observed in 22 patients (48.9%). The lesions involved the thoracic spine (n=28, 62.2%), cervical spine (n=26, 57.8%), lumbar spine (n=9, 20.0%), and sacral spine (n=1, 2.2%). Furthermore, the lesions were located in the dura mater (n=18, 40.0%), epidural space (n=17, 37.8%), intradural-extramedullary space (n=9, 20.0%), and intramedullary space (n=1, 2.2%). On magnetic resonance imaging (MRI), the lesions generally appeared as striated, fusiform, or less often lobulated oval changes, with homogeneous (n=17,44.7%) and dorsal (n=15,39.5%) patterns being the most common. Thirty-five patients had homogeneous T1 gadolinium enhancement. Early surgical decompression, corticosteroid treatment, and steroid-sparing agents offered significant therapeutic advantages. A good therapeutic response to disease recurrence was observed with the medication. Conclusion: The number of reported cases of IgG4-RSP remains limited, and patients often have progressive worsening of their neurological symptoms. The features of masses identified on the MRI should be considered. The prognosis was better with decompression surgery combined with immunosuppressive therapy. Long-term corticosteroid treatment and steroid-sparing agent maintenance therapy should be ensured. A systemic examination is recommended to identify the presence of other pathologies.

An Experimental and Numerical Study of Polyelectrolyte Hydrogel Ionic Diodes: Towards Electrical Detection of Charged Biomolecules.

Polyelectrolyte hydrogel ionic diodes (PHIDs) have recently emerged as a unique set of iontronic devices. Such diodes are built on microfluidic chips that feature polyelectrolyte hydrogel junctions and rectify ionic currents owing to the heterogeneous distribution and transport of ions across the junctions. In this paper, we provide the first account of a study on the ion transport behavior of PHIDs through an experimental investigation and numerical simulation. The effects of bulk ionic strength and hydrogel pore confinement are experimentally investigated. The ionic current rectification (ICR) exhibits saturation in a micromolar regime and responds to hydrogel pore size, which is subsequently verified in a simulation. Furthermore, we experimentally show that the rectification is sensitive to the dose of immobilized DNA with an exhibited sensitivity of 1 ng/µL. We anticipate our findings would be beneficial to the design of PHID-based biosensors for electrical detection of charged biomolecules.

Predictive risk factors for recollapse of cemented vertebrae after percutaneous vertebroplasty: A meta-analysis.

BACKGROUND: As one of the most common complications of osteoporosis, osteoporotic vertebral compression fracture (OVCF) increases the risk of disability and mortality in elderly patients. Percutaneous vertebroplasty (PVP) is considered to be an effective, safe, and minimally invasive treatment for OVCFs. The recollapse of cemented vertebrae is one of the serious complications of PVP. However, the risk factors associated with recollapse after PVP remain controversial. AIM: To identify risk factors for the recollapse of cemented vertebrae after PVP in patients with OVCFs. METHODS: A systematic search in EMBASE, MEDLINE, the Cochrane Library, and PubMed was conducted for relevant studies from inception until March 2020. Studies investigating risk factors for the recollapse of cemented vertebrae after PVP without additional trauma were selected for analysis. Odds ratios (ORs) or standardized mean differences with 95% confidence interval (CI) were calculated and heterogeneity was assessed by both the chi-squared test and the I-squared test. The methodological quality of the included studies was assessed according to the Newcastle-Ottawa Scale. RESULTS: A total of nine case-control studies were included in our meta-analysis comprising 300 cases and 2674 controls. The significant risk factors for the recollapse of cemented vertebrae after PVP in OVCF patients were fractures located at the thoracolumbar junction (OR = 2.09; 95%CI: 1.30 to 3.38; P = 0.002), preoperative intravertebral cleft (OR = 2.97; 95%CI: 1.93 to 4.57; P < 0.00001), and solid lump distribution pattern of the cement (OR = 3.11; 95%CI: 1.91 to 5.07; P < 0.00001). The analysis did not support that age, gender, lumbar bone mineral density, preoperative visual analogue scale score, injected cement volume, intradiscal cement leakage, or vertebral height restoration could increase the risk for cemented vertebra recollapse after PVP in OVCFs. CONCLUSION: This meta-analysis suggests that thoracolumbar junction fractures, preoperative intravertebral cleft, and solid lump cement distribution pattern are associated with the recollapse of cemented vertebrae after PVP in OVCF patients.

Morphologic analysis of Chinese lumbar endplate by three-dimensional computed tomography reconstructions for helping design lumbar disc prosthesis.

ABSTRACT: Lumbar disc prostheses have been used increasingly in recent years. The successful design of lumbar disc prostheses depends on accurate morphometric parameters. However, the morphologic dimensions of lumbar endplate area have not been investigated in Chinese population.A total of 1800 lumbar endplates were retrospectively accessed in 150 Chinese adults. Eighteen parameters of each lumbar segment were measured by three-dimensional computed tomography reconstructions from T12/L1 to L5/S1. These obtained parameters were compared between genders, bilateral sides, vertebral segments, and different populations.Endplate length and width increased in general, and there was a significant decrease for length/width ratio from T12 to S1 (P = .03). The average concavity depth of the lower lumbar endplate (2.09 ±â€Š0.93 mm) was usually larger than that of the upper lumbar endplate (1.61 ±â€Š0.74 mm) (P = .02). The percentage of the most concave point of the upper and lower lumbar endplate was 50.01 ±â€Š10.76% and 56.41 ±â€Š9.93%, respectively. Anterior, medium, or posterior intervertebral endplate height was severally 10.01 ±â€Š1.98 mm, 10.46 ±â€Š2.03 mm, and 6.41 ±â€Š1.74 mm, and increased among vertebral segments (P = .01).The intervertebral endplate angle significantly increased from T12-L1 to L5-S1 (P = .01). Parameters displayed significant difference between genders. The morphometric parameters of different populations also showed differences.In conclusion, there is a morphologic discrepancy in dimensions of lumbar endplate regarding genders, vertebral segments, and different populations. It is essential to design the lumbar disc prosthesis suited for Chinese patients specially, for which the morphometric parameters in our study can be utilized.

The intrinsic axon regenerative properties of mature neurons after injury.

Thousands of nerve injuries occur in the world each year. Axon regeneration is a very critical process for the restoration of the injured nervous system's function. However, the precise molecular mechanism or signaling cascades that control axon regeneration are not clearly understood, especially in mammals. Therefore, there is almost no ideal treatment method to repair the nervous system's injury until now. Mammalian axonal regeneration requires multiple signaling pathways to coordinately regulate gene expression in soma and assembly of the cytoskeleton protein in the growth cone. A better understanding of their molecular mechanisms, such as axon regeneration regulatory signaling cascades, will be helpful in developing new treatment strategies for promoting axon regeneration. In this review, we mainly focus on describing these regeneration-associated signaling cascades, which regulate axon regeneration.

Bacterial dysbiosis incites Th17 cell revolt in irradiated gut.

Th17 cells are critical members in mediating immune responses of adaptive immunity. In humans and mice, gut is a main site where Th17 cells are resided, and Th17 cell polarization also occurs in the gut. This process can be mediated by many factors, such as commensal bacteria, dendritic cells and cytokines, such as TGF-ß and IL-6. Physiologically, polarized Th17 cells function in anti-infection and maintaining the integrity of intestinal epithelium. However, Th17 cells are plastic. For example, they will become pro-inflammatory cells if being exposed to IL-23. The pathogenic roles of Th17 cells have been well documented in inflammatory bowel disease. Besides, Th17 cells can accumulate in irradiated gut as well. Critically, radiation enteritis and inflammatory bowel disease present several similarities in disease pathology and pathophysiology. Herein, bacterial dysbiosis highly correlates with the pathogenicity of Th17 cells in inflammatory bowel disease. To our knowledge, radiation serves as a factor in inducing bacterial dysbiosis. Using this action, can Th17 cells be incited to promote inflammation in irradiated gut? In this review, we will sequentially introduce polarization of Th17 cells at steady state, radiation-induced Th17 accumulation in the gut, and advances in the management of radiation enteritis by using pharmacological therapy for bacterial dysbiosis.

The Impact of Urgent (<8 Hours) Decompression on Neurologic Recovery in Traumatic Spinal Cord Injury: A Meta-Analysis.

OBJECTIVE: The relationship between urgent decompression and neurologic recovery for traumatic spinal cord injury (TSCI) remains controversial. This meta-analysis was conducted to determine the beneficial effects of surgery within 8 hours for patients with TSCI. METHODS: A systematic search in EMBASE, MEDLINE, Cochrane Library, and PubMed for relevant studies was conducted from the earliest records until December 2019. Studies that compared outcomes of early (<8 hours) surgery versus late (≥8 hours) surgery for patients with TSCI were selected for analysis. RESULTS: Nine cohort studies involving 716 participants met the eligibility criteria. Early (<8 hours) surgery for patients showed a more significant improvement in American Spinal Injury Association scores (standardized mean difference, 0.75, 95% confidence interval [CI], 0.51-0.99; P < 0.05). Especially for patients with initial complete TSCI, neurologic improvement rate significantly increased in the early surgery group (relative ratio [RR], 3.96; 95% CI, 2.02-7.76; P < 0.05), whereas in patients with initial incomplete TSCI, no significant differences were found between the 2 groups in neurologic improvement rate (RR, 1.41; 95% CI, 0.95-2.10; P > 0.05). There were no significant differences between the 2 groups in length of hospital stay (standardized mean difference, 0.34; 95% CI, -0.24 to 0.92; P > 0.05) and complications (RR, 0.92; 95% CI, 0.70-1.22; P > 0.05). CONCLUSIONS: This meta-analysis provides evidence of benefits from urgent (<8 hours) decompression for patients with TSCI in terms of neurologic recovery. The improvement effect is more definite in patients with initial complete TSCI.

Decoding epigenetic codes: new frontiers in exploring recovery from spinal cord injury.

Spinal cord injury that results in severe neurological disability is often incurable. The poor clinical outcome of spinal cord injury is mainly caused by the failure to reconstruct the injured neural circuits. Several intrinsic and extrinsic determinants contribute to this inability to reconnect. Epigenetic regulation acts as the driving force for multiple pathological and physiological processes in the central nervous system by modulating the expression of certain critical genes. Recent studies have demonstrated that post-SCI alteration of epigenetic landmarks is strongly associated with axon regeneration, glial activation and neurogenesis. These findings not only establish a theoretical foundation for further exploration of spinal cord injury, but also provide new avenues for the clinical treatment of spinal cord injury. This review focuses on the epigenetic regulation in axon regeneration and secondary spinal cord injury. Together, these discoveries are a selection of epigenetic-based prognosis biomarkers and attractive therapeutic targets in the treatment of spinal cord injury.

Catastrophic thoracolumbar spinal massive hematoma triggered by intraspinal anesthesia puncture: A CARE-compliant case report.

RATIONALE: Intraspinal anesthesia, the most common anesthesia type of orthopedic operation, is regarded as safe and simple. Despite of the rare incidence, puncture related complication of intraspinal anesthesia is catastrophic for spinal cord. Here we present an intradural hematoma case triggered by improper anesthesia puncture. The principal reason of this tragedy was rooted in the neglect of spine deformities diagnosis before anesthesia. To the best of our knowledge, there is no specific case report focusing on the intradural hematoma triggered by improper anesthesia puncture. PATIENT CONCERNS: Hereby a case of thoracolumbar spinal massive hematoma triggered by intraspinal anesthesia puncture was reported. The presenting complaint of the patient was little neurologic function improvement after surgery at 6-month follow-up. DIAGNOSES: Emergency MRI demonstrated that massive spindle-like intradural T2-weighted image hypointense signal masses from T12 to S2 badly compressed the dural sac ventrally, and his conus medullaris was at L3/4 intervertebral level with absence of L5 vertebral lamina. Hereby, the diagnoses were congenital spinal bifida, tethered cord syndrome, spine intradural hematoma, and paraplegia. INTERVENTIONS: Urgent surgical interventions including laminectomy, spinal canal exploration hematoma removal, and pedicle fixation were performed. The patient received both medication (mannitol, mecobalamin, and steroids) and rehabilitation (neuromuscular electric stimulation, hyperbaric oxygen). OUTCOMES: Postoperation, he had regained only hip and knee flexion at II grade strength. His neurologic function was unchanged until 3 weeks postoperation. Six-month follow-up showed just little neurologic function improvement, and the American Spinal Injury Association grade was C. LESSONS: By presenting an intradural hematoma case triggered by improper anesthesia puncture, we shared the treatment experience and discussed the potential mechanism of neurologic compromise. The principal reason for this tragedy is preanesthesia examination deficiency. Necessary radiology examinations must be performed to prevent misdiagnosis for spinal malformation.

Matrine induces apoptosis and autophagy of glioma cell line U251 by regulation of circRNA-104075/BCL-9.

BACKGROUND: Matrine, a traditional Chinese medicine, has been reported to exert anti-tumor effects in several types of cancers. Here, we explored the anti-tumor effects of matrine on the glioma cells. METHODS: Glioma cell line U251 cells were treated with matrine to assess viability and proliferation using CCK8 and EdU assays. PI/FITC staining was performed for apoptosis assay. Transfections were performed for circRNA-104075 or Bcl-9 overexpression. Western blot analysis was performed to evaluate changes of protein levels and changes of gene level were detected by qRT-PCR in U251 cells. RESULTS: Matrine suppressed cell viability while induced apoptosis and autophagy in U251 cells. Matrine also decreased circRNA-104075 expression significantly. Overexpression of circRNA-104075 was found to counteract the inhibitory effects of matrine on cell proliferation and promoting effects on apoptosis and autophagy in U251 cells. Moreover, the suppressed Wnt/ß-catenin and PI3K/AKT signaling pathways by matrine were activated by circRNA-104075 overexpression. Furthermore, Bcl-9 expression was also down-regulated by matrine treatment. Bcl-9 overexpression elevated the decreased cell proliferation while suppressed the increased apoptosis and autophagy induced by matrine in U251 cells. CONCLUSION: Taken together, the present findings suggested that matrine induced apoptosis and autophagy through down-regulating circ-104075 and Bcl-9 expression via inhibition of PI3K/AKT and Wnt-ß-catenin pathways in glioma cells. The present study provides a foundation for further preclinical and clinical evaluations of matrine as a glioma therapy.

Gouty spondylodiscitis with lumbar vertebral body retrolisthesis: A case report.

RATIONALE: Gout occurs mainly in joints, but rarely in the spine. In the spine, urate crystals can cause intervertebral space instability but rarely lead to retrolisthesis. Here, we present an extremely rare disease with gout invaded the intervertebral disc with lumbar retrolisthesis. PATIENT CONCERNS: A 61-years male patient with gout history has suffered from severe low back pain and intermittent claudication. Physical examination showed the level of muscle strength of his left first toe was 3/5. Images illustrated a destruction of the intervertebral space, and a retrolisthesis at L4/5 interspace and the dural sac obviously compressed. DIAGNOSES: Combining with lab examinations, imaging examinations, and histopathological results, the patient was diagnosed with gouty arthritis associated with lumbar spinal stenosis, L4-5 spondylodiscitis and L4 vertebral body retrolisthesis. INTERVENTION: The patient underwent posterior decompression, reduction, and interbody fusion, and then received an aggressive postoperative rehabilitation program. OUTCOMES: The patient's low back pain was significantly alleviated after the operation. Postoperative X-ray shows the internal fixation was well placed and the sequence of spine was reconstructed. 12 weeks later, the lower limb symptoms of the patients were obviously improved, his muscle strength of the left first toe was 4/5, Japanese Orthopaedic Association (JOA) score was 19 and the improvement rate was 61.5%. LESSONS: Gouty spondylodiscitis can cause intervertebral space instability. Sagittal imbalance and degeneration of disc with decreasing of segmental disc height are considered as the main factors of retrolisthesis. The appearance may lead to misdiagnose a patient with gout history with a destruction of the intervertebral space. Surgery is a compromise method for gouty spondylodiscitis patients with urgent neurological symptoms.

Hydrogel Microparticles Functionalized with Engineered Escherichia coli as Living Lactam Biosensors.

Recently there has been an increasing need for synthesizing valued chemicals through biorefineries. Lactams are an essential family of commodity chemicals widely used in the nylon industry with annual production of millions of tons. The bio-production of lactams can substantially benefit from high-throughput lactam sensing strategies for lactam producer screening. We present here a robust and living lactam biosensor that is directly compatible with high-throughput analytical means. The biosensor is a hydrogel microparticle encapsulating living microcolonies of engineered lactam-responsive Escherichia coli. The microparticles feature facile and ultra-high throughput manufacturing of up to 10,000,000 per hour through droplet microfluidics. We show that the biosensors can specifically detect major lactam species in a dose-dependent manner, which can be quantified using flow cytometry. The biosensor could potentially be used for high-throughput metabolic engineering of lactam biosynthesis.

Ginsenoside Rb1 protects against spinal cord ischemia-reperfusion injury in rats by downregulating the Bax/Bcl-2 ratio and caspase-3 and p-Ask-1 levels.

The aim of this study was to confirm the effects of ginsenoside Rb1 on neural cell apoptosis in the spinal cord of rats with spinal cord ischemia-reperfusion injury (SCII) and to explore its potential mechanisms. A total of 100 healthy adult Sprague-Dawley (SD) rats were randomly divided into four groups: normal control (n = 10), sham-operated (n = 10), SCII model (n = 40), and ginsenoside Rb1-treated groups (n = 40). Basso, Beattie, Bresnahan (BBB) scale was used to examine rat hindlimb locomotor function. Nissl and Tunnel staining were used to observe neural cell injury and apoptosis, respectively, in the spinal cord of rats with SCII. Immunofluorescence staining was performed to detect the expression of Bax and Bcl-2. The levels of caspase-3 and phosphorylated Ask-1 (p-Ask-1) were detected by western blotting. Ginsenoside Rb1 prevented neural cell apoptosis in the spinal cord and improved hindlimb locomotor dysfunction of rats (P < .05). Moreover, SCII-induced upregulation of caspase-3 and p-Ask-1 levels and the Bax/Bcl-2 ratio were significantly decreased by ginsenoside Rb1 (P < .05). The protective effects of ginsenoside Rb1 on neural cells in the spinal cord of rats with SCII were mediated by the ginsenoside Rb1-induced downregulation of caspase-3 and p-Ask-1 levels and the Bax/Bcl-2 ratio.