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1.
Cell ; 159(1): 134-147, 2014 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-25242744

RESUMO

Exon circularization has been identified from many loci in mammals, but the detailed mechanism of its biogenesis has remained elusive. By using genome-wide approaches and circular RNA recapitulation, we demonstrate that exon circularization is dependent on flanking intronic complementary sequences. Such sequences and their distribution exhibit rapid evolutionary changes, showing that exon circularization is evolutionarily dynamic. Strikingly, exon circularization efficiency can be regulated by competition between RNA pairing across flanking introns or within individual introns. Importantly, alternative formation of inverted repeated Alu pairs and the competition between them can lead to alternative circularization, resulting in multiple circular RNA transcripts produced from a single gene. Collectively, exon circularization mediated by complementary sequences in human introns and the potential to generate alternative circularization products extend the complexity of mammalian posttranscriptional regulation.


Assuntos
Processamento Alternativo , Éxons , Genoma Humano , Elementos Alu , Animais , Sequência de Bases , Células-Tronco Embrionárias/metabolismo , Evolução Molecular , Humanos , Íntrons , Mamíferos/genética , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Alinhamento de Sequência
2.
Mediators Inflamm ; 2024: 3188216, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38385005

RESUMO

Background: Rheumatoid arthritis (RA) remains one of the most prevalent chronic joint diseases. However, due to the heterogeneity among RA patients, there are still no robust diagnostic and therapeutic biomarkers for the diagnosis and treatment of RA. Methods: We retrieved RA-related and pan-cancer information datasets from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. Six gene expression profiles and corresponding clinical information of GSE12021, GSE29746, GSE55235, GSE55457, GSE77298, and GSE89408 were adopted to perform differential expression gene analysis, enrichment, and immune component difference analyses of RA. Four machine learning algorithms, including LASSO, RF, XGBoost, and SVM, were used to identify RA-related biomarkers. Unsupervised cluster analysis was also used to decipher the heterogeneity of RA. A four-signature-based nomogram was constructed and verified to specifically diagnose RA and osteoarthritis (OA) from normal tissues. Consequently, RA-HFLS cell was utilized to investigate the biological role of CRTAM in RA. In addition, comparisons of diagnostic efficacy and biological roles among CRTAM and other classic biomarkers of RA were also performed. Results: Immune and stromal components were highly enriched in RA. Chemokine- and Th cell-related signatures were significantly activated in RA tissues. Four promising and novel biomarkers, including CRTAM, PTTG1IP, ITGB2, and MMP13, were identified and verified, which could be treated as novel treatment and diagnostic targets for RA. Nomograms based on the four signatures might aid in distinguishing and diagnosing RA, which reached a satisfactory performance in both training (AUC = 0.894) and testing (AUC = 0.843) cohorts. Two distinct subtypes of RA patients were identified, which further verified that these four signatures might be involved in the immune infiltration process. Furthermore, knockdown of CRTAM could significantly suppress the proliferation and invasion ability of RA cell line and thus could be treated as a novel therapeutic target. CRTAM owned a great diagnostic performance for RA than previous biomarkers including MMP3, S100A8, S100A9, IL6, COMP, LAG3, and ENTPD1. Mechanically, CRTAM could also be involved in the progression through immune dysfunction, fatty acid metabolism, and genomic instability across several cancer subtypes. Conclusion: CRTAM, PTTG1IP, ITGB2, and MMP13 were highly expressed in RA tissues and might function as pivotal diagnostic and treatment targets by deteriorating the immune dysfunction state. In addition, CRTAM might fuel cancer progression through immune signals, especially among RA patients.


Assuntos
Artrite Reumatoide , Neoplasias , Humanos , Silício , Metaloproteinase 13 da Matriz , Biomarcadores , Algoritmos
3.
BMC Musculoskelet Disord ; 24(1): 304, 2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37072780

RESUMO

BACKGROUND: Restoration of sagittal balance is a crucial consideration in posterior lumbar interbody fusion (PLIF) surgery and adverse postoperative outcomes are associated with inadequate restoration of sagittal alignment. However, there remains a shortage of substantial evidence regarding the effect of rod curvature on both sagittal spinopelvic radiographic parameters and clinical outcomes. METHOD: A retrospective case-control study was conducted in this study. Patient demographics (age, gender, height, weight and BMI), surgical characteristics (number of fused levels, surgical time, blood loss and hospital stay) and radiographic parameters (lumbar lordosis [LL], sacral slope [SS], pelvic incidence [PI], pelvic tilt [PT], PI-LL, Cobb angle of fused segments [Cobb], rod curvature [RC], Posterior tangent angle of fused segments [PTA] and RC-PTA) were analyzed. RESULTS: Patients in the abnormal group had older mean age and suffered more blood loss than those in the normal group. In addition, RC and RC-PTA were significantly lower in the abnormal group compared to the normal group. Multivariate regression analysis revealed that lower age (OR = 0.94; 95% CI: 0.89-0.99; P = 0.0187), lower PTA (OR = 0.91; 95% CI: 0.85-0.96; P = 0.0015) and higher RC (OR = 1.35; 95% CI: 1.20-1.51; P < 0.0001) were related to higher odds of better surgical outcomes. The receiver operating characteristic curve analysis showed that the ROC curve (AUC) for predicting outcomes of surgery by RC classifier was 0.851 (0.769-0.932). CONCLUSIONS: In patients who underwent PLIF surgery for lumbar spinal stenosis, those who had a satisfactory postoperative outcome tended to be younger, had lower blood loss, and higher values of RC and RC-PTA compared to those who had poor recovery and required revision surgery. Additionally, RC was found to be a reliable predictor of postoperative outcomes.


Assuntos
Lordose , Fusão Vertebral , Estenose Espinal , Animais , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Estenose Espinal/complicações , Resultado do Tratamento , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Fusão Vertebral/efeitos adversos , Lordose/cirurgia
4.
BMC Musculoskelet Disord ; 20(1): 580, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31787080

RESUMO

BACKGROUND: Surgery is usually recommended for thoracolumbar fracture with neurologic deficit. However, traditional open posterior approach requires massive paraspinal muscles stripping, and the canal decompression may be limited and incomplete. We aimed to investigate a new approach via the Wiltse approach and the Kambin's Triangle. METHODS: Twenty-one consecutive patients with traumatic upper lumbar fracture who received this new approach surgery between January 2015 and January 2016 constituted the new approach group. Twenty-nine patients received the traditional open posterior surgery between January 2014 and January 2015 were classified as the traditional posterior surgery group. Surgical informations including operative time, blood loss, drainage volume, hospitalization days were collected and compared among the two groups. The American Spinal Injury Association (ASIA) impairment scale and Visual Analog Score (VAS) were evaluated preoperatively, postoperatively and at 12 months follow-up. RESULTS: Patients in the new approach group had fewer operation time (128.3 ± 25.1 vs 151 ± 32.2 min, P = 0.01), less blood loss (243.8 ± 135.5 vs 437.8 ± 224.9 ml, P = 0.001) and drainage volume (70.7 ± 57.2 vs 271.7 ± 95.5 ml, P < 0.001), as well as shorter hospitalization stay than the traditional posterior surgery group (6.6 ± 1.8 vs 8.5 ± 2.4 d, P = 0.004). Similar neurologic recovery according to ASIA grade was achieved in both groups (Recovery index: 0.90 ± 0.53 vs 0.86 ± 0.51, P = 0.778). While the pain level was significantly lower in the new approach group postoperatively (2.6 ± 0.7 vs 3.5 ± 0.9, P < 0.001) and at 12 months follow-up (1.4 ± 0.9 vs 2.4 ± 0.8, P < 0.001). CONCLUSION: The present new approach was successfully applied in the treatment of upper lumbar fracture with neurologic deficit. It can reduce iatrogenic trauma and achieve similar or better outcomes compared to the traditional posterior surgery.


Assuntos
Descompressão Cirúrgica/métodos , Vértebras Lombares/cirurgia , Doenças do Sistema Nervoso/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Adulto , Descompressão Cirúrgica/tendências , Feminino , Seguimentos , Hospitalização/tendências , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico por imagem , Doenças do Sistema Nervoso/epidemiologia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Resultado do Tratamento
6.
Eur Spine J ; 24(8): 1631-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25840783

RESUMO

PURPOSE: To make a preliminary classification of double-layer sign according to the morphological characteristics of the ossified and central hypodense mass and clarify implications of different patterns of "double-layer sign". METHODS: The 268 patients of cervical ossification of the posterior longitudinal ligament (OPLL) who underwent anterior corpectomy were retrospectively analyzed from January 2009 to January 2014. All these patients were performed cervical plain X-rays, CT and MRI. The double-layer sign was observed on axial bone window of CT images. According to the morphological characteristics of the ossified and central hypodense mass, this sign was classified into three types: type A was crescent shape, type B was short-straight shape and type C was long-straight shape. Type A was named when the central hypodense mass traced an arc and the OPLL is much more extensive than the dural ossification (DO). It belonged to type B when the central hypodense mass traced a short-straight line, less than or equal to half of the base width of the vertebrae. The OPLL may be extensive or equal to the DO. Type C was defined when it was more than half of the base width, presenting with a long-straight line and DO is much more extensive than OPLL. Intraoperative findings including dural mater ossification and adhesion, postoperative CSF leakage and outcome were all studied. Two spinal surgeons with rich experiences read the CT images according to this classification method and verified its consistency. RESULTS: Ninety-two patients were found in association with DO during the anterior decompression procedure, meanwhile the double-layer sign could be seen on axial bone window of CT imaging. In these 92 patients, there were 51 patients presenting with type A, and the ossified mass was completely resected with ossified dura mater reserved. Only two patients presented with dural defect and postoperative CSF leakage. Thirty-five patients was classified as type B, of which six accompanied by CSF leakage. All the other six patients of type C presented with CSF leakage after operation. There was a significant correlation between the occurence of CSF leakage and pattern of double-layer sign, but not gender, age, duration of symptoms, extent of OPLL and occupying rate. The Kappa value between the two surgeons was 0.82, showing a good consistency of the method. CONCLUSIONS: OPLL patients with double-layer sign of type C is almost inevitably followed by CSF leakage after anterior decompression. For type A and B, occurrence of CSF leakage is not as high as we thought before. Pattern of double-layer sign should be a considered factor when anterior or posterior approach is chosen.


Assuntos
Vazamento de Líquido Cefalorraquidiano/diagnóstico por imagem , Vértebras Cervicais/diagnóstico por imagem , Descompressão Cirúrgica , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Adulto , Idoso , Vazamento de Líquido Cefalorraquidiano/etiologia , Vértebras Cervicais/patologia , Vértebras Cervicais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Ossificação do Ligamento Longitudinal Posterior/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
7.
Eur Spine J ; 24(8): 1673-80, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25192727

RESUMO

PURPOSE: To introduce the new method of spinal canal "Rule of Nine" on axial computed tomography (CT) to determine whether ossified posterior longitudinal ligament (OPLL) can be resected completely and safely. METHODS: From January 2008 to January 2013, we retrospectively analyzed 308 patients with cervical OPLL who underwent anterior corpectomy. Patients were examined by cervical plain X-ray, CT, and magnetic resonance imaging. The characteristics of OPLL on axial CT, dural mater adhesion and ossification, complete resection of the ossified mass, cerebrospinal fluid (CSF) leakage, spinal cord injury (SCI), and postoperative outcome were all studied. OPLL was characterized at the maximum ossified level using spinal canal "Rule of Nine" on axial CT. RESULTS: OPLL was completely and safely resected in 129 patients, whose ossified mass was within the safety zone. No CSF leakage or SCI occurred. The most ossified material was resected when OPLL was within the danger zone in 21 patients. There were two cases of SCI and seven of CSF leakage. In the other 158 patients, the ossified mass was within the intermediate zone. In 96 patients the width of the ossified mass was <2 resection units. It was completely resected and one case had CSF leakage. In the other 62 cases, the ossified mass was >2 resection units and there were nine cases of CSF leakage. CSF leakage and SCI increased significantly when the ossified mass was ≥6 units. The inter- and intraobserver κ values were 0.76 and 0.84, respectively, showing a good reliability. CONCLUSIONS: Our new method can be used to determine whether OPLL can be resected completely and safely, and identify potential risks and complications.


Assuntos
Técnicas de Apoio para a Decisão , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Canal Medular/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Vazamento de Líquido Cefalorraquidiano/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Complicações Pós-Operatórias , Reprodutibilidade dos Testes , Estudos Retrospectivos
8.
BMC Genomics ; 15: 287, 2014 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-24734784

RESUMO

BACKGROUND: Intron-derived long noncoding RNAs with snoRNA ends (sno-lncRNAs) are highly expressed from the imprinted Prader-Willi syndrome (PWS) region on human chromosome 15. However, sno-lncRNAs from other regions of the human genome or from other genomes have not yet been documented. RESULTS: By exploring non-polyadenylated transcriptomes from human, rhesus and mouse, we have systematically annotated sno-lncRNAs expressed in all three species. In total, using available data from a limited set of cell lines, 19 sno-lncRNAs have been identified with tissue- and species-specific expression patterns. Although primary sequence analysis revealed that snoRNAs themselves are conserved from human to mouse, sno-lncRNAs are not. PWS region sno-lncRNAs are highly expressed in human and rhesus monkey, but are undetectable in mouse. Importantly, the absence of PWS region sno-lncRNAs in mouse suggested a possible reason why current mouse models fail to fully recapitulate pathological features of human PWS. In addition, a RPL13A region sno-lncRNA was specifically revealed in mouse embryonic stem cells, and its snoRNA ends were reported to influence lipid metabolism. Interestingly, the RPL13A region sno-lncRNA is barely detectable in human. We further demonstrated that the formation of sno-lncRNAs is often associated with alternative splicing of exons within their parent genes, and species-specific alternative splicing leads to unique expression pattern of sno-lncRNAs in different animals. CONCLUSIONS: Comparative transcriptomes of non-polyadenylated RNAs among human, rhesus and mouse revealed that the expression of sno-lncRNAs is species-specific and that their processing is closely linked to alternative splicing of their parent genes. This study thus further demonstrates a complex regulatory network of coding and noncoding parts of the mammalian genome.


Assuntos
Processamento Alternativo , RNA Longo não Codificante/genética , Animais , Cromossomos Humanos Par 15 , Humanos , Camundongos , Especificidade da Espécie
9.
Artigo em Inglês | MEDLINE | ID: mdl-38702912

RESUMO

The shapes of micro- and nano-products have profound influences on their functional performances, which has not received sufficient attention during the past several decades. Electrohydrodynamic atomization (EHDA) techniques, mainly include electrospinning and electrospraying, are facile in manipulate their products' shapes. In this review, the shapes generated using EHDA for modifying drug release profiles are reviewed. These shapes include linear nanofibers, round micro-/nano-particles, and beads-on-a-string hybrids. They can be further divided into different kinds of sub-shapes, and can be explored for providing the desired pulsatile release, sustained release, biphasic release, delayed release, and pH-sensitive release. Additionally, the shapes resulted from the organizations of electrospun nanofibers are discussed for drug delivery, and the shapes and inner structures can be considered together for developing novel drug delivery systems. In future, the shapes and the related shape-performance relationships at nanoscale, besides the size, inner structure and the related structure-performance relationships, would further play their important roles in promoting the further developments of drug delivery field. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.


Assuntos
Sistemas de Liberação de Medicamentos , Humanos , Nanofibras/química , Animais , Nanopartículas/química , Hidrodinâmica
10.
Int J Gen Med ; 17: 725-738, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481615

RESUMO

Background and Aim: Cervical hyperextension injury is very frequent with anterior longitudinal ligament (ALL) injury, and the ligament damage has a remarkable effect on whether and what type of operation should be performed. This study aims to establish a new scoring system for the accurate diagnosis of ALL damage. Methods: The imaging data of the consecutive patients was measured and scored by four radiologists. Intraoperative exploration was performed by three surgeons. The crude and adjusted odds ratios (cOR and aOR) and receiver operating characteristic curve (ROC) were constructed to assess the diagnostic accuracy of the scoring system. Results: A total of 255 patients with cervical spine trauma were included in this study. There was no statistical difference in the relationship between demographics and ALL injuries (P > 0.05). Thickness of prevertebral soft tissue (aOR = 11.922, P = 0.004), intervertebral disk angle (aOR = 13.21, P = 0.002), avulsion fracture of the anterior edge of the vertebral body (aOR = 13.844, P = 0.029), ALL disrupted in T1-weighted sequence (aOR = 18.349, P < 0.001), and high signal area in T2-weighted sequence (aOR = 20.898, P = 0.002) had significantly higher diagnostic accuracy. The scoring system's sensitivity and specificity were 94.0% and 88.1%, respectively, and the accuracy was 90.8%. Conclusion: The study established a new scoring system for ALL injuries based on the analysis of a series of clinical data and statistics. A total of five scoring items, a total score of 7 points, and an ALL injury may be diagnosed when the score is not less than 3 points. This scoring system enables an efficient and accurate diagnosis of all injuries.

11.
Front Bioeng Biotechnol ; 12: 1360902, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38605994

RESUMO

Introduction: This paper presents the Reconfigurable Multi-Terrain Adaptive Casualty Transport Aid (RMTACTA), an innovative solution addressing the critical need for rapid and safe pre-hospital casualty transport in industrial environments. The RMTACTA, leveraging the Watt II six-bar linkage, offers enhanced adaptability through six modes of motion, overcoming the limitations of traditional stretchers and stretcher vehicles by facilitating navigation across narrow and challenging terrains. Methods: The RMTACTA's design incorporates two branching four-bar mechanisms to form a compact, reconfigurable Watt II six-bar linkage mechanism. This setup is controlled via a single remote rope, allowing for easy transition between its multiple operational modes, including stretcher, stretcher vehicle, folding, gangway-passing, obstacle-crossing, and upright modes. The mechanical design and kinematics of this innovative linkage are detailed, alongside an analysis of the optimal design and mechanical evaluation of rope control. Results: A prototype of the RMTACTA was developed, embodying the proposed mechanical and kinematic solutions. Preliminary tests were conducted to verify the prototype's feasibility and operability across different terrains, demonstrating its capability to safely and efficiently transport casualties. Discussion: The development of the proposed Reconfigurable Multi-Terrain Adaptive Casualty Transport Aid (RMTACTA) introduces a novel perspective on the design of emergency medical transport robots and the enhancement of casualty evacuation strategies. Its innovative application of the Watt II six-bar linkage mechanism not only showcases the RMTACTA's versatility across varied terrains but also illuminates its potential utility in critical scenarios such as earthquake relief, maritime rescue, and battlefield medical support.

12.
Global Spine J ; : 21925682241255894, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38757696

RESUMO

STUDY DESIGN: Bioinformatics analysis of Gene Expression Omnibus (GEO). OBJECTIVE: Ossification of the ligamentum flavum (OLF) and ankylosing spondylitis (AS) represent intricate conditions marked by the gradual progression of endochondral ossification. This investigation endeavors to unveil common biomarkers associated with heterotopic ossification and explore the potential molecular regulatory mechanisms. METHODS: Microarray and RNA-sequencing datasets retrieved from the Gene Expression Omnibus (GEO) repository were harnessed to discern differentially expressed genes (DEGs) within the OLF and AS datasets. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) was implemented to pinpoint co-expression modules linked to OLF and AS. Common genes were further subjected to an examination of functional pathway enrichment. Moreover, hub intersection genes were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) regression, followed by an evaluation of diagnostic performance in external OLF and AS cohorts. Lastly, an analysis of immune cell infiltration was conducted to scrutinize the correlation of immune cell presence with shared biomarkers in OLF and AS. RESULTS: A total of 1353 and 91 Differentially Expressed Genes (DEGs) were identified in OLF and AS, respectively. Using the Weighted Gene Co-expression Network Analysis (WGCNA), 2 modules were found to be notably significant for OLF and AS. The integrative bioinformatic analysis revealed 3 hub genes (MAB21L2, MEGF10, ISLR) as shared risk biomarkers, with MAB21L2 being the central focus. Receiver Operating Characteristic (ROC) analysis exhibited a strong diagnostic potential for these hub genes. Gene Ontology (GO) analysis indicated their involvement in the positive regulation of myoblast proliferation. Notably, MAB21L2 was singled out as the optimal common biomarker for OLF and AS. Furthermore, an analysis of immune infiltration demonstrated a correlation between MAB21L2 expression and changes in immune cells. Activated CD8 T cells were identified as shared differential immune infiltrating cells significantly linked to MAB21L2 in both OLF and AS. CONCLUSION: This study represents the first instance of identifying MAB21L2 as a prospective diagnostic marker for patients contending with OLF associated with AS. The research results indicate that the ECM-receptor interaction and the cell-cell adhesion may play a role in both disease processes. This newfound knowledge not only enhances our understanding of the pathogenesis behind spinal ligament ossification but also uncovers potential targets for therapeutic interventions.

13.
Int Immunopharmacol ; 130: 111738, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38428149

RESUMO

BACKGROUND: Neuroinflammation, a critical component of the secondary injury cascade post-spinal cord injury, involves the activation of pro-inflammatory cells and release of inflammatory mediators. Resolution of neuroinflammation is closely linked to cellular autophagy. This study investigates the potential of Fisetin, a natural anti-inflammatory compound, to ameliorate neuroinflammation and confer spinal cord injury protection through the regulation of autophagy in pro-inflammatory cells. METHODS: Utilizing a rat T10 spinal cord injury model with distinct treatment groups (Sham, Fisetin-treated, and Fisetin combined with autophagy inhibitor), alongside in vitro models involving lipopolysaccharide (LPS)-stimulated microglial cell activation and co-culture with neurons, we employed techniques such as transcriptomic sequencing, histological assessments (immunofluorescence staining, etc.), molecular analyses (PCR, WB, ELISA, etc.), and behavioral evaluations to discern differences in neuroinflammation, autophagy, neuronal apoptosis, and neurological function recovery. RESULTS: Fisetin significantly augmented autophagic activity in injured spinal cord tissue, crucially contributing to neurological function recovery in spinal cord-injured rats. Fisetin's autophagy-dependent effects were associated with a reduction in neuronal apoptosis at the injury site. The treatment reduced the population of CD68+ and iNOS+ cells, coupled with decreased pro-inflammatory cytokines IL-6 and TNF-α levels, through autophagy-dependent pathways. Fisetin pre-treatment attenuated LPS-induced pro-inflammatory polarization of microglial cells, with this protective effect partially blocked by autophagy inhibition. Fisetin-induced autophagy in the injured spinal cord and pro-inflammatory microglial cells was associated with significant activation of AMPK and inhibition of mTOR. CONCLUSION: Fisetin orchestrates enhanced autophagy in pro-inflammatory microglial cells through the AMPK-mTOR signaling pathway, thereby mitigating neuroinflammation and reducing the apoptotic effects of neuroinflammation on neurons. This mechanistic insight significantly contributes to the protection and recovery of neurological function following spinal cord injury, underscoring the vital nature of Fisetin as a potential therapeutic agent.


Assuntos
Flavonóis , Doenças Neuroinflamatórias , Traumatismos da Medula Espinal , Ratos , Animais , Lipopolissacarídeos/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Inflamação/metabolismo , Traumatismos da Medula Espinal/complicações , Serina-Treonina Quinases TOR/metabolismo , Medula Espinal/patologia , Microglia , Autofagia
14.
Eur Spine J ; 22(7): 1539-46, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23568254

RESUMO

PURPOSE: Anterior cervical discectomy and fusion (ACDF) with titanium- or polyetheretherketone (PEEK)-cage reconstruction is widely used in the treatment of cervical spondylotic myelopathy (CSM). This study was to compare outcomes of titanium and PEEK cages in the treatment of multilevel CSM. METHODS: Between November 2002 and December 2004, a total of 80 patients with 3-level CSM were randomized in a 1:1 ratio to titanium group and PEEK group. The overall follow-up period of the patients ranged from 86 to 116 months (average 99.7 months). Clinical and radiological results were compared between titanium group and PEEK group. RESULTS: At the final follow-up, the clinical outcomes including JOA score, NDI score, and the excellent and good rates of clinical outcomes in the PEEK group were better than those in the titanium group. More loss of the Cobb angles and the intervertebral height was observed in the titanium group, resulting in the radiological parameters in the titanium group becoming inferior to the PEEK group at the final follow-up. Cage subsidence rates were 34.5 and 5.4% in the titanium and PEEK groups, respectively. Fusion was observed in all patients of two groups at the final follow-up. Two patients presented with cage dislocation without clinical symptoms in the titanium group. CONCLUSIONS: In surgical treatment of multilevel CSM, PEEK cage is superior to titanium cage in maintenance of intervertebral height and cervical lordosis, resulting in better clinical outcomes in the long-term follow-up.


Assuntos
Vértebras Cervicais/cirurgia , Fixadores Internos , Fusão Vertebral/instrumentação , Espondilose/cirurgia , Benzofenonas , Discotomia , Feminino , Seguimentos , Humanos , Cetonas , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis , Polímeros , Titânio , Resultado do Tratamento
15.
Arch Orthop Trauma Surg ; 133(4): 473-80, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23392650

RESUMO

OBJECTIVE: To evaluate the clinical outcomes and radiographic results of patients who underwent single-level cervical arthroplasty using the Prestige LP. METHOD: Thirty-one patients with single-level cervical disc disease received the Prestige LP disc replacement from June 2008 to December 2009. The neck disability index (NDI), Japanese Orthopedic Association score (JOA) and visual analogue scale (VAS) were used to assessed clinical outcomes pre-operatively and post-operatively at 24 months. The overall cervical alignment (C2-7 Cobb angle), the functional segmental unit (FSU) curvature, the range of motion (ROM) of treated and adjacent levels were measured, and the evidence of heterotopic ossification (HO) was observed from static and dynamic radiographs. RESULTS: There was a statistically significant improvement in the NDI from 20.2 ± 7.5 to 6.4 ± 3.5 (P < 0.000), JOA from 12.8 ± 2.2 to 16.6 ± 0.6 (P < 0.000), the neck VAS score from 4.1 ± 2.5 to 1.4 ± 1.1 (P < 0.000), the arm VAS score from 4.6 ± 2.5 to 0.7 ± 1.1 (P < 0.000). The post-operative overall cervical alignment (9.3° ± 7.2°), ROM of treated level (7.6°) and adjacent level (upper level 9.4° ± 3.1°, lower level 9.1° ± 3.5°) are well maintained. The FSU were 0.2° ± 5.4° and 1.9° ± 5.5° at pre-operation and final follow-up with statistical significance (P = 0.011). Heterotopic ossification was evidenced in five operated segment (16 %). CONCLUSIONS: The Prestige LP disc arthroplasty maintains favorable clinical outcomes, preserves the overall cervical alignment, FSU curvature, ROM of treated level and adjacent levels.


Assuntos
Artroplastia de Substituição , Vértebras Cervicais/diagnóstico por imagem , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Disco Intervertebral/diagnóstico por imagem , Adulto , Vértebras Cervicais/cirurgia , Feminino , Humanos , Disco Intervertebral/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Amplitude de Movimento Articular
16.
World Neurosurg ; 170: e622-e628, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36410702

RESUMO

OBJECTIVE: Some atlantoaxial rotatory fixations (AARFs) cannot be classified according to the Fielding and Hawkins classification. This study aimed to introduce a new subtype of AARF (type IIIa AARF) with a C1 anterior displacement >5 mm, but with one lateral mass being displaced anteriorly and another posteriorly. METHODS: Data from 10 cases of AARF with anterior C1 displacement of >5 mm were retrospectively reviewed. The exclusion criteria were as follows: 1) type I, II, or IV AARF according to the Fielding and Hawkins classification; 2) cases caused by trauma, tumor, or infection; 3) AARF with os odontoideum or odontoid fracture; and 4)age ≥18 years. Imaging features were analyzed. The atlanto-dental interval was measured to evaluate C1 anterior displacement. RESULTS: Three cases that did not match type III AARF were classified under type IIIa AARF. They had the following common imaging features: 1) atlanto-dental interval of >5 mm, being similar to type III AARF; 2) one lateral mass of C1 displaced anteriorly and the other posteriorly (the most important feature distinguishing the type from type III AARF in which both C1 lateral masses displaced anteriorly); and 3) C1-C2 separation angle (mean 44.2 ± 2.9°) being larger than that in type III AARF. CONCLUSIONS: AARF with anterior C1 displacement of >5 mm, but with one lateral mass displaced anteriorly and the other posteriorly, was defined as type IIIa AARF. It should not be confused with type III AARF because these 2 types differ in biomechanics and imaging parameters.


Assuntos
Articulação Atlantoaxial , Vértebra Cervical Áxis , Luxações Articulares , Fusão Vertebral , Humanos , Adolescente , Estudos Retrospectivos , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/cirurgia , Articulação Atlantoaxial/lesões , Rotação , Fusão Vertebral/métodos , Luxações Articulares/cirurgia
17.
Front Mol Biosci ; 10: 1184767, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37234919

RESUMO

Based on a working fluid consisting of a poorly water-soluble drug and a pharmaceutical polymer in an organic solvent, electrospinning has been widely exploited to create a variety of amorphous solid dispersions However, there have been very few reports about how to prepare the working fluid in a reasonable manner. In this study, an investigation was conducted to determine the influences of ultrasonic fluid pretreatment on the quality of resultant ASDs fabricated from the working fluids. SEM results demonstrated that nanofiber-based amorphous solid dispersions from the treated fluids treated amorphous solid dispersions exhibited better quality than the traditional nanofibers from untreated fluids in the following aspects: 1) a straighter linear morphology; 2) a smooth surface; and 3) a more evener diameter distribution. The fabrication mechanism associated with the influences of ultrasonic treatments of working fluids on the resultant nanofibers' quality is suggested. Although XRD and ATR-FTIR experiments clearly verified that the drug ketoprofen was homogeneously distributed all over the TASDs and the traditional nanofibers in an amorphous state regardless of the ultrasonic treatments, the in vitro dissolution tests clearly demonstrated that the TASDs had a better sustained drug release performance than the traditional nanofibers in terms of the initial release rate and the sustained release time periods.

18.
Front Surg ; 10: 1129809, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37228764

RESUMO

Background: This study aimed to investigate the safety and efficacy of the halo-vest in the treatment of cervical fracture in patients with ankylosing spondylitis (AS) and kyphosis. Methods: From May 2017 to May 2021, 36 patients with cervical fractures with AS and thoracic kyphosis were included in this study. The patients with cervical spine fractures with AS underwent preoperative reduction by halo-vest or skull tractions. Instrumentation internal fixation and fusion surgery were then performed. The level of cervical fractures, the operative duration, blood loss, and treatment outcomes were investigated preoperatively and postoperatively. Results: A total of 25 cases were included in the halo-vest group and 11 cases were included in the skull tractions group. The intraoperative blood loss and the surgery duration were significantly less in the halo-vest group than in the skull traction group. A comparison of American Spinal Injury Association scores at admission and final follow-up showed that the neurological function of patients improved in both groups. All patients had reached solid bony fusion during the follow-up. Conclusion: This study presented a unique approach to use halo-vest treatment fixation of unstable cervical fracture in patients with AS. The patient should also have early surgical stabilization with a halo-vest to correct spinal deformity and avoid worsening of neurological status.

19.
Int J Biol Macromol ; 235: 123847, 2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-36863672

RESUMO

In this study, a composite hydrogel (QMPD hydrogel) composed of methacrylate anhydride (MA) grafted quaternary ammonium chitosan (QCS-MA), polyvinylpyrrolidone (PVP), and dopamine (DA) was designed for the sequential wound inflammation elimination, infection inhibition, and wound healing. The QMPD hydrogel formation was initiated by the ultraviolet light-triggered polymerization of QCS-MA. Furthermore, hydrogen bonds, electrostatic interactions, and "π-π" stacking between QCS-MA, PVP, and DA were involved in the hydrogel formation. In this hydrogel, the quaternary ammonium groups of quaternary ammonium chitosan and the photothermal conversion of polydopamine are capable of killing bacteria on wounds, which showed the bacteriostatic ratios of 85.6 % and 92.5 % toward Escherichia coli and Staphylococcus aureus, respectively. Moreover, the oxidation of DA sufficiently scavenged free radicals and introduced the QMPD hydrogel with good anti-oxidant and anti-inflammatory abilities. Together with the extracellular matrix-mimic tropical structure, the QMPD hydrogel significantly promoted the wound management of mice. Therefore, the QMPD hydrogel is expected to provide a new method for the design of wound healing dressings.


Assuntos
Quitosana , Hidrogéis , Animais , Camundongos , Hidrogéis/farmacologia , Anidridos , Antioxidantes , Dopamina , Escherichia coli , Metacrilatos , Povidona , Inflamação , Antibacterianos/farmacologia
20.
Oper Neurosurg (Hagerstown) ; 25(4): 365-371, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37432014

RESUMO

BACKGROUND AND OBJECTIVES: Posterior C1-C2 interlaminae compression fusion with iliac bone graft may lead to donor site complications and recurrent C1 posterior dislocation for posterior atlantoaxial dislocation (AAD) secondary to os odontoideum. C1-C2 intra-articular fusion often needs C2 nerve ganglion transection to facilitate exposing and manipulating the facet joint, leading to bleeding from the venous plexus and suboccipital numbness or pain. Therefore, this study was conducted to evaluate the outcomes of posterior C1-C2 intra-articular fusion with a C2 nerve root preservation technique in the treatment of posterior AAD secondary to os odontoideum. METHODS: Data of the 11 patients who underwent C1-C2 posterior intra-articular fusion because of posterior AAD secondary to os odontoideum were retrospectively reviewed. Posterior reduction was performed using C1 transarch lateral mass screws and C2 pedicle screws. Intra-articular fusion was performed using a polyetheretherketone cage filled with autologous bone from the caudal edge of the C1 posterior arch and cranial edge of the C2 laminar. Outcomes were evaluated by using the Japanese Orthopaedics Association score, Neck Disability Index, and visual analog scale for neck pain. Bone fusion was evaluated by using computed tomography and 3-dimensional reconstruction. RESULTS: The average follow-up duration was 43.9 ± 9.5 months. All patients achieved good reduction and bone fusion, without transection of the C2 nerve roots. The mean bone fusion time was 4.3 ± 1.1 months. There was no complication related to the surgical approach and instrumentation. Function of the spinal cord manifested by the Japanese Orthopaedics Association score significantly improved ( P < .05). The Neck Disability Index score and visual analog scale for neck pain markedly decreased (all P < .05). CONCLUSION: Posterior reduction and intra-articular cage fusion with a C2 nerve root preservation technique was a promising treatment of posterior AAD secondary to os odontoideum.


Assuntos
Vértebra Cervical Áxis , Luxações Articulares , Parafusos Pediculares , Fusão Vertebral , Humanos , Vértebras Cervicais/cirurgia , Cervicalgia , Estudos Retrospectivos , Fusão Vertebral/métodos , Luxações Articulares/complicações , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia
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