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OBJECTIVES: The purpose of this study was to (i) develop a protocol that supports decision making for prehospital spinal immobilization in pediatric trauma patients based on evidence from current scientific literature and (ii) perform an applicability test on emergency medicine personnel. METHODS: A structured search of the literature published between 1980 and 2019 was performed in MEDLINE using PubMed. Based on this literature search, a new Emergency Medicine Spinal Immobilization Protocol for pediatric trauma patients (E.M.S. IMMO Protocol Pediatric) was developed. Parameters found in the literature, such as trauma mechanism and clinical findings that accounted for a high probability of spinal injury, were included in the protocol. An applicability test was administered to German emergency medicine personnel using a questionnaire with case examples to assess correct decision making according to the protocol. RESULTS: The E.M.S. IMMO Protocol Pediatric was developed based on evidence from published literature. In the applicability test involving 44 emergency medicine providers revealed that 82.9% of participants chose the correct type of immobilization based on the protocol. A total of 97.8% evaluated the E.M.S. IMMO Protocol Pediatric as helpful. CONCLUSIONS: Based on the current literature, the E.M.S. IMMO Protocol Pediatric was developed in accordance with established procedures used in trauma care. The decision regarding immobilization is made on based on the cardiopulmonary status of the patient, and life-threatening injuries are treated with priority. If the patient presents in stable condition, the necessity for full immobilization is assessed based upon the mechanisms of injury, assessment of impairment, and clinical examination.
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Serviços Médicos de Emergência , Medicina de Emergência , Traumatismos da Coluna Vertebral , Criança , Humanos , Imobilização , Traumatismos da Coluna Vertebral/diagnóstico , Traumatismos da Coluna Vertebral/terapia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The diagnosis of instability of the injured upper cervical spine remains controversial, due to its complicated anatomical configuration and biomechanical property. Since identifying unstable injuries of the upper cervical spine is essential for immediate stabilizing therapy, this article reviews the current classification systems of upper cervical spine injuries and their statements towards instability. METHODS: A systematic review of literature concerning upper cervical spine injuries was performed on the PubMed database from inception to December 2019. An English literature search was conducted using various combinations of keyword terms. RESULTS: Numerous separate classification systems for each specific injury of the upper cervical spine were obtained. The early classifications are based primarily on injury morphology and mechanism. The recent classifications pay more attention to the investigation of ligamentous status. Various instability criteria were established as well. The determinants involve translation, vertical distraction, angulation, rotation, obliquity of fracture line, comminution, and ligamentous disruption. The status of crucial ligaments plays a key role in determining instability of upper cervical spine injuries. CT scan is more sensitive and reliable than X-ray in detecting misalignment of the upper cervical spine. CONCLUSION: Only a few classification systems support decision-making concerning instability leading to early operative treatment. The ligamentous integrity is the key element of impacting the stability of the upper cervical spine injuries. The transverse ligament serves as the most crucial element in determining the stability of occipital condyle fractures and atlas fractures as well as atlanto-axial injury. The integrity of anterior longitudinal ligament, disc, and facet joint attributes to the stability of axis fractures. The integrity of tectorial membrane and alar ligaments determines the stability of atlanto-occipital dislocation. The development of a newly classification system concerning ligamentous instability with a high clinical and scientific impact is recommended.
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Fraturas Ósseas , Luxações Articulares , Traumatismos da Coluna Vertebral , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/lesões , Humanos , Ligamentos Articulares/diagnóstico por imagem , Traumatismos da Coluna Vertebral/diagnósticoRESUMO
BACKGROUND: To protect the spine from secondary damage, spinal immobilization is a standard procedure in prehospital trauma management. Immobilization protocols aim to support emergency medicine personnel in quick decision making but predominantly focus on the adult spine; however, trauma mechanisms and injury patterns in adults differ from those in children and applying adult prehospital immobilization protocols to pediatric patients may be insufficient. Adequate protocols for children with spinal injuries are currently unavailable. OBJECTIVE: The aim of this study was (i) to develop a protocol that supports decision making for prehospital spinal immobilization in pediatric trauma patients based on evidence from current scientific literature and (ii) to perform a first analysis of the quality of results if the protocol is used by emergency personnel. MATERIAL AND METHODS: Based on a structured literature search a new immobilization protocol was developed. Analysis of the quality of results was performed by a questionnaire containing four case scenarios in order to assess correct decision making. The decision about spinal immobilization was made without and with the utilization of the protocol. RESULTS: The E.M.S. IMMO Protocol Pediatric was developed based on the literature. The analysis of the quality of results was performed involving 39 emergency medicine providers. It could be shown that if the E.M.S. IMMO Protocol Pediatric was used, the correct type of immobilization was chosen more frequently. A total of 38 out of 39 participants evaluated the protocol as helpful. CONCLUSION: The E.M.S. IMMO Protocol Pediatric provides decision-making support whether pediatric spine immobilization is indicated with respect to the cardiopulmonary status of the patient. In a first analysis, the E.M.S. IMMO Protocol Pediatric improves decision making by emergency medical care providers.
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Serviços Médicos de Emergência , Traumatismos da Coluna Vertebral , Vértebras Cervicais , Criança , Protocolos Clínicos , Serviço Hospitalar de Emergência , Humanos , Imobilização , Traumatismos da Coluna Vertebral/terapiaRESUMO
PURPOSE: To analyze the compression of the dural sac and the cervical spinal movement during performing different airway interventions in case of atlanto-occipital dislocation. METHODS: In six fresh cadavers, atlanto-occipital dislocation was performed by distracting the opened atlanto-occipital joint capsule and sectioning the tectorial membrane. Airway management was done using three airway devices (direct laryngoscopy, video laryngoscopy, and insertion of a laryngeal tube). The change of dural sac's width and intervertebral angulation in stable and unstable atlanto-occipital conditions were recorded by video fluoroscopy with myelography. Three-dimensional overall movement of cervical spine was measured in a wireless human motion track system. RESULTS: Compared with a mean dural sac compression of - 0.5 mm (- 0.7 to - 0.3 mm) in stable condition, direct laryngoscopy caused an increased dural sac compression of - 1.6 mm (- 1.9 to - 0.6 mm, p = 0.028) in the unstable atlanto-occipital condition. No increased compression on dural sac was found using video laryngoscopy or the laryngeal tube. Moreover, direct laryngoscopy caused greater overall extension and rotation of cervical spine than laryngeal tube insertion in both stable and unstable conditions. Among three procedures, the insertion of a laryngeal tube took the shortest time. CONCLUSION: In case of atlanto-occipital dislocation, intubation using direct laryngoscopy exacerbates dural sac compression and may cause damage to the spinal cord.
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Manuseio das Vias Aéreas/efeitos adversos , Articulação Atlantoccipital/fisiopatologia , Vértebras Cervicais/fisiopatologia , Luxações Articulares/fisiopatologia , Compressão da Medula Espinal/etiologia , Idoso , Idoso de 80 Anos ou mais , Manuseio das Vias Aéreas/métodos , Cadáver , Dura-Máter/patologia , Feminino , Fluoroscopia , Humanos , Luxações Articulares/terapia , Masculino , Mielografia , Pressão , Amplitude de Movimento ArticularRESUMO
Small-interfering RNAs (siRNAs) offer promising prospects for treating pyroptosis-related autoimmune diseases. However, poor stability and off-target effects during in vivo transportation hinder their practical clinical applications. Precision delivery and adaptive release of siRNAs into inflamed tissues and immune cells could unleash their full therapeutic potential. This study establishes a pyroptotic-spatiotemporally selective siRNA delivery system (PMRC@siGSDME) that selectively targets inflammatory tissues, responds to pyroptosis, and exhibits remarkable therapeutic efficacy against various autoimmune diseases. Novel hybrid nanovesicles (NVs) are designed as a combination of pyroptotic macrophage membranes (PMs) and R8-cardiolipin-containing nanovesicles (RC-NVs). Evidence provides that PM-derived proteins involved in cell-cell interactions and membrane trafficking may contribute to the specificity of NVs to inflammatory tissue. In addition, cardiolipin anchored in the hybrid NVs increases its affinity for activated gasdermin E (GSDME) and achieves pyroptosis-adaptive release of siGSDME for the spatiotemporally selective suppression of immune responses. More importantly, PMRC@siGSDME displays significant anti-inflammatory and therapeutic effects in multiple mouse autoimmune disease models, including arthritis and inflammatory bowel disease (IBD). Collectively, an innovative siRNA delivery strategy precisely tailored for pyroptotic cells has been developed, paving the way for new treatments for autoimmune inflammatory diseases with minimal side effects and wide clinical applicability.
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OBJECTIVE: Osteoarthritis (OA) is one of the most common degenerative joint diseases and is associated with autophagy suppression. However, the molecular mechanism of autophagy regulation in the context of OA is not fully understood. In this study, we sought to determine the role that HECTD1 plays in the pathogenesis of OA. METHODS: We used RNA sequencing analysis to explore the differential expression of E3 ubiquitin ligase genes in healthy human cartilage and human cartilage affected by OA. Using surgery- and aging-induced OA mouse models, we comprehensively analyzed the function of the screened gene Hectd1 in the development of OA; furthermore, we dissected the mechanism by which HECTD1 regulates autophagy and OA progression using a combination of molecular biologic, cell biologic, and biochemical approaches. RESULTS: HECTD1 was significantly down-regulated in human OA cartilage samples compared to healthy cartilage samples. Overexpression of HECTD1 in mouse joints alleviated OA pathogenesis, whereas conditional depletion of Hectd1 in cartilage samples aggravated surgery- and aging-induced OA pathogenesis. Mechanistically, HECTD1 bound to Rubicon and ubiquitinated Rubicon at lysine residue 534, which targets Rubicon for proteasomal degradation. More importantly, HECTD1-mediated Rubicon degradation regulated chondrocyte autophagy, leading to mitigation of stress-induced chondrocyte death and the subsequent progression of OA. CONCLUSION: HECTD1 plays a crucial role in the pathogenesis of OA, in that HECTD1 regulates chondrocyte autophagy by ubiquitinating and targeting Rubicon for proteasomal degradation.
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Produtos Biológicos , Osteoartrite , Humanos , Animais , Camundongos , Ubiquitinação , Condrócitos , Autofagia/genética , Osteoartrite/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
This study was designed to investigate the biological functions of LINC00482 in prostate cancer (PCa) with bone metastasis. TCGA dataset of PCa was applied for LINC00482 expression analysis and real time PCR was used to verify the expression level of LINC00482 in PCa tissues as well as PCa bone metastatic tissues. To detect the biological functions of LINC00482 in vitro, various assays were used including CCK-8, EdU, colony formation and transwell assays. The biological functions of LINC00482 were also identified in vivo by inoculating PCa cells into the left cardiac ventricle of mice, followed by evaluating the osteolytic lesions and osteolytic score. In addition, Starbase and Lncbase databases were applied for predicting the potential target miRNA of LINC00482, while TargetScan and Starbase databases were used for predicting the potential target of miRNA. The luciferase reporter assay was utilized to determine the interactions among these molecules and western blotting was employed to verified the targeted proteins. Results showed that high expression level of LINC00482 was observed in bone metastatic PCa tissues and associated with PCa progression. Silencing of LINC00482 inhibited cell proliferation, migration and invasion in PCa. Furthermore, LINC00482 was proved to act as a competing endogenous RNA by sponging miR-2467-3p to activate Wnt/ß-catenin signaling pathway, which may be a promising therapeutic target for PCa with bone metastasis.
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BACKGROUND: Bladder urothelial carcinoma (BLCA) is one of the most common urinary system malignancies with a high metastasis rate. Cancer stem cells (CSCs) play an important role in the occurrence and progression of BLCA, however, its roles in bone metastasis and the prognostic stemness biomarkers have not been identified in BLCA. METHOD: In order to identify the roles of CSC in the tumorigenesis, bone metastasis and prognosis of BLCA, the RNA sequencing data of patients with BLCA were retrieved from The Cancer Genome Atlas (TCGA) databases. The mRNA expression-based stemness index (mRNAsi) and the differential expressed genes (DEGs) were evaluated and identified. The associations between mRNAsi and the tumorigenesis, bone metastasis, clinical stage and overall survival (OS) were also established. The key prognostic stemness-related genes (PSRGs) were screened by Lasso regression, and based on them, the predict model was constructed. Its accuracy was tested by the area under the curve (AUC) of the receiver operator characteristic (ROC) curve and the risk score. Additionally, in order to explore the key regulatory network, the relationship among differentially expressing TFs, PSRGs, and absolute quantification of 50 hallmarks of cancer were also identified by Pearson correlation analysis. To verify the identified key TFs and PSRGs, their expression levels were identified by our clinical samples via immunohistochemistry (IHC). RESULTS: A total of 8,647 DEGs were identified between 411 primary BLCAs and 19 normal solid tissue samples. According to the clinical stage, mRNAsi and bone metastasis of BLCA, 2,383 stage-related DEGs, 3,680 stemness-related DEGs and 716 bone metastasis-associated DEGs were uncovered, respectively. Additionally, compared with normal tissue, mRNAsi was significantly upregulated in the primary BLCA and also associated with the prognosis (P = 0.016), bone metastasis (P < 0.001) and AJCC clinical stage (P < 0.001) of BLCA patients. A total of 20 PSRGs were further screened by Lasso regression, and based on them, we constructed the predict model with a relatively high accuracy (AUC: 0.699). Moreover, we found two key TFs (EPO, ARID3A), four key PRSGs (CACNA1E, LINC01356, CGA and SSX3) and five key hallmarks of cancer gene sets (DNA repair, myc targets, E2F targets, mTORC1 signaling and unfolded protein response) in the regulatory network. The tissue microarray of BLCA and BLCA bone metastasis also revealed high expression of the key TFs (EPO, ARID3A) and PRSGs (SSX3) in BLCA. CONCLUSION: Our study identifies mRNAsi as a reliable index in predicting the tumorigenesis, bone metastasis and prognosis of patients with BLCA and provides a well-applied model for predicting the OS for patients with BLCA based on 20 PSRGs. Besides, we also identified the regulatory network between key PSRGs and cancer gene sets in mediating the BLCA bone metastasis.
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Lumbar disc degeneration is a common cause of chronic low back pain and an important contributor to various degenerative lumbar spinal disorders. However, currently there is currently no effective therapeutic strategy for treating disc degeneration. The pro-inflammatory cytokine interleukin-1ß (IL-1ß) mediates disc degeneration by inducing apoptotic death of nucleus pulposus (NP) cells and degradation of the NP extracellular matrix. Here, we confirmed that extracellular secretion of IL-1ß via secretory autophagy contributes to disc degeneration, and demonstrate that a thermosensitive reactive oxygen species (ROS)-responsive hydrogel loaded with a synthetic growth hormone-releasing hormone analog (MR409) can protect against needle puncture-induced disc degeneration in rats. Methods: The expression levels of proteins related to secretory autophagy such as tripartite motif-containing 16 (TRIM16) and microtubule-associated protein light chain 3B (LC3B) were examined in human and rat disc tissues by histology and immunofluorescence. The effects of TRIM16 expression level on IL-1ß secretion were examined in THP-1 cells transfected with TRIM16 plasmid or siRNA using ELISA, immunofluorescence, and immunoblotting. The in vitro effects of MR409 on IL-1ß were examined in THP-1 cells and primary rat NP cells using ELISA, immunofluorescence, immunoblotting, and qRT-PCR. Further, MR409 was subcutaneously administered to aged mice to test its efficacy against disc degeneration using immunofluorescence, X-ray, micro-CT, and histology. To achieve controllable MR409 release for intradiscal use, MR409 was encapsulated in an injectable ROS-responsive thermosensitive hydrogel. Viscosity, rheological properties, release profile, and biocompatibility were evaluated. Thereafter, therapeutic efficacy was assessed in a needle puncture-induced rat model of disc degeneration at 8 and 12 weeks post-operation using X-ray, magnetic resonance (MR) imaging, histological analysis, and immunofluorescence. Results: Secretory autophagy-related proteins TRIM16 and LC3B were robustly upregulated in degenerated discs of both human and rat. Moreover, while upregulation of TRIM16 facilitated, and knockdown of TRIM16 suppressed, secretory autophagy-mediated IL-1ß secretion from THP-1 cells under oxidative stress, MR409 inhibited ROS-induced secretory autophagy and IL-1ß secretion by THP-1 cells as well as IL-1ß-induced pro-inflammatory and pro-catabolic effects in rat NP cells. Daily subcutaneous injection of MR409 inhibited secretory autophagy and ameliorated age-related disc degeneration in mice. The newly developed ROS-responsive MR409-encapsulated hydrogel provided a reliable delivery system for controlled MR409 release, and intradiscal application effectively suppressed secretory autophagy and needle puncture-induced disc degeneration in rats. Conclusion: Secretory autophagy and associated IL-1ß secretion contribute to the pathogenesis of disc degeneration, and MR409 can effectively inhibit this pathway. The ROS-responsive thermosensitive hydrogel encapsulated with MR409 is a potentially efficacious treatment for disc degeneration.
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Autofagia/genética , Interleucina-1beta/metabolismo , Degeneração do Disco Intervertebral/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Núcleo Pulposo/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Idoso , Animais , Autofagia/efeitos dos fármacos , Feminino , Imunofluorescência , Humanos , Hidrogéis , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/patologia , Imageamento por Ressonância Magnética , Masculino , Camundongos , Pessoa de Meia-Idade , Núcleo Pulposo/diagnóstico por imagem , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Células THP-1 , Proteínas com Motivo Tripartido/metabolismo , Microtomografia por Raio-XRESUMO
BACKGROUND: To date, the literature directly comparing early carotid endarterectomy (CEA) and delayed CEA in patients with symptomatic carotid stenosis (CS) is limited. We aimed to evaluate the efficacy and safety of early CEA and delayed CEA in patients with symptomatic CS by performing a meta-analysis. MATERIAL AND METHOD: The PubMed, Cochrane Library (last searched in May 2020) and relevant websites such as Web of Science and EMBASE (1990 to May 2020) were searched. All meta-analyses of eligible results were conducted using the STATA version 12.0 (Stata Corporation, College Station, Texas, USA). RESULTS: A total of 7 articles were included in the study hailing from the New Scotland, Chicago, Sweden, UK, Italy, and France. In this study, the early CEA meant that the procedure was performed within the first 14 days or first 30 days. And the delayed CEA meant the procedure was performed more than 14 days or 30 days after the symptom occurrence. Referring to the latter early CEA group and delayed CEA group, there were three publications. The results illustrated that the early CEA group was not associated with a higher incidence of stroke (ORâ¯=â¯0.77, 95 % CI: 0.273-2.170; Pâ¯=â¯0.620). And no statistic difference was found on the incidence of postoperative 30-day mortality and stroke or mortality. Meanwhile, referring to the former early CEA group and delayed CEA group, there were six articles. The results demonstrated that the early CEA group was associated with a higher rate of postoperative 30-day mortality (RDâ¯=â¯0.010, 95 % CI: 0.002 to 0.019; Pâ¯=â¯0.022). CONCLUSION: The meta-analysis of these related studies suggests that, compared to the delayed CEA group, the early CEA performed in patients with the acute post stroke phase resulted in a higher risk of postoperative mortality. Therefore, the delayed CEA was safer than early CEA for patients with symptomatic CS.
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Estenose das Carótidas/mortalidade , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/mortalidade , Endarterectomia das Carótidas/métodos , Tempo para o Tratamento/tendências , Endarterectomia das Carótidas/tendências , Humanos , Mortalidade/tendências , Estudos Retrospectivos , Resultado do TratamentoRESUMO
E-cadherin and SDC1 are markers of epithelial-to-mesenchymal transition (EMT) that can be used to assess tumour prognosis. SDC1 has different effects in various types of cancers. On the one hand, reduced expression of SDC1 can leads to advantage stages of some cancers, such as gastric and colorectal cancer. On the other hand, SDC1 overexpression can also promote the growth and proliferation of cancer cells in pancreatic and breast cancer. However, the function of SDC1 is influenced and regulated by many factors. Exfoliated extracellular domain HS chain can mediate the function of SDC1 and play an important role in the occurrence and development of cancer. SDC1 binds to various ligands and influences the growth and reproduction of cancer cells via the activation of Wnt, the long isoform of FLICE-inhibitory protein (FLIP long), vascular endothelial growth factor receptor (VEGFR), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and MAPK/c-Jun N-terminal kinase (JNK) and other pathways. Cadherins occur in several types, but this review focuses on classical cadherins. N-cadherin and P-cadherin are activated during tumour development, whereas E-cadherin is a tumour suppressor. The cellular signalling pathways involved in classical cadherins, such as Wnt and VEGFR pathways, are also related to SDC1. The activation of E-cadherin caused by SDC1 knockdown has also been observed. Despite this evidence, no articles regarding the relationship of SDC1 and cadherin activation have been published. This review summarises the expressions of these two molecules in different cancers and analyses their possible relationship to provide insights into future cancer research and clinical treatment.
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Caderinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Transdução de Sinais/fisiologia , Sindecana-1/metabolismo , Adesão Celular/fisiologia , Humanos , Sindecana-1/genéticaRESUMO
BACKGROUND: Unstable conditions of the craniocervical junction such as atlanto-occipital dislocation (AOD) or atlanto-axial instability (AAI) are severe injuries with a high risk of tetraplegia or death. Immobilization by a cervical collar to protect the patient from secondary damage is a standard procedure in trauma patients. If the application of a cervical collar to a patient with an unstable craniocervical condition may cause segmental motion and secondary injury to the spinal cord is unknown. The aim of the current study is (i) to analyze compression on the dural sac and (ii) to determine relative motion of the cervical spine during the procedure of applying a cervical collar in case of ligamentous unstable craniocervical junction. METHODS AND FINDINGS: Ligamentous AOD as well as AOD combined with ligamentous AAI was simulated in two newly developed cadaveric trauma models. Compression of the dural sac and segmental angulation in the upper cervical spine were measured on video fluoroscopy after myelography during the application of a cervical collar. Furthermore, overall three-dimensional motion of the cervical spine was measured by a motion tracking system. In six cadavers each, the two new trauma models on AOD and AOD combined with AAI could be implemented. Mean dural sac compression was significantly increased to -1.1 mm (-1.3 to -0.7 mm) in case of AOD and -1.2 mm (-1.6 to -0.6 mm) in the combined model of AOD and AAI. Furthermore, there is a significant increased angulation at the C0/C1 level in the AOD model. Immense three-dimensional movement up to 22.9° of cervical spine flexion was documented during the procedure. CONCLUSION: The current study pointed out that applying a cervical collar in general will cause immense three-dimensional movement. In case of unstable craniocervical junction, this leads to a dural sac compression and thus to possible damage to the spinal cord.
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Articulação Atlantoaxial/lesões , Articulação Atlantoaxial/patologia , Articulação Atlantoaxial/fisiopatologia , Luxações Articulares/patologia , Luxações Articulares/fisiopatologia , Instabilidade Articular , Amplitude de Movimento Articular , Animais , Articulação Atlantoaxial/diagnóstico por imagem , Cadáver , Modelos Animais de Doenças , Feminino , Fluoroscopia , Humanos , Luxações Articulares/complicações , Luxações Articulares/etiologia , Masculino , Radiografia , Ferimentos e LesõesRESUMO
INTRODUCTION: Emergency management of upper cervical spine injuries often requires cervical spine immobilisation and some critical patients also require airway management. The movement of cervical spine created by tracheal intubation and cervical spine immobilisation can potentially exacerbate cervical spinal cord injury. However, the evidence that previous studies have provided remains unclear, due to lack of a direct measurement technique for dural sac's space during dynamic processes. Our study will use myelography method and a wireless human motion tracker to characterise and compare the change of dural sac's space during tracheal intubations and cervical spine immobilisation in the presence of unstable upper cervical spine injury such as atlanto-occipital dislocation or type II odontoid fracture. METHODS AND ANALYSIS: Perform laryngoscopy and intubation, video laryngoscope intubation, laryngeal tube insertion, fiberoptic intubation and cervical collar application on cadaveric models of unstable upper cervical spine injury such as atlanto-occipital dislocation or type II odontoid fracture. The change of dural sac's space and the motion of unstable cervical segment are recorded by video fluoroscopy with previously performing myelography, which enables us to directly measure dural sac's space. Simultaneously, the whole cervical spine motion is recorded at a wireless human motion tracker. The maximum dural sac compression and the maximum angulation and distraction of the injured segment are measured by reviewing fluoroscopic and myelography images. ETHICS AND DISSEMINATION: This study protocol has been approved by the Ethics Committee of the State Medical Association Rhineland-Palatinate, Mainz, Germany. The results will be published in relevant emergency journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: DRKS00010499.
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Vértebras Cervicais/lesões , Serviços Médicos de Emergência/métodos , Imobilização/métodos , Intubação Intratraqueal , Cadáver , Protocolos Clínicos , Estudos Cross-Over , Humanos , Imobilização/efeitos adversos , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Movimento , Mielografia , Estudos ProspectivosRESUMO
Osteoarthritis is a degenerative joint disease that is characterized by the inflammation of synovium. Schisantherin A (SchA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been shown to have anti-inflammatory activity. The aim of this study was to investigate the anti-inflammatory effects of SchA on interleukin-1ß (IL-1ß)-stimulated human osteoarthritis chondrocytes. Human osteoarthritis chondrocytes were pretreated with SchA 1h before IL-1ß treatment. The effects of SchA on NO, PGE2, iNOS, COX-2, and TNF-α production were detected in this study. The production of MMP-1, MMP3, MMP13 were measured by ELISA. The expression of NF-κB and MAPKs were detected by western blotting. Our results showed that SchA inhibited IL-1ß-induced NO, PGE2, and TNF-α production in a dose-dependent manner. Moreover, IL-1ß-induced MMP1, MMP3, and MMP13 expression were significantly inhibited by treatment of SchA. In addition, SchA significantly inhibited IL-1ß-induced NF-κB and MAPKs activation. Taken together, these results suggest that SchA exhibits anti-inflammatory effects against IL-1ß-stimulated chondrocytes by blocking NF-κB and MAPKs signaling pathways.
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Anti-Inflamatórios não Esteroides/farmacologia , Condrócitos/efeitos dos fármacos , Ciclo-Octanos/farmacologia , Dioxóis/farmacologia , Interleucina-1beta/farmacologia , Lignanas/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Osteoartrite/patologia , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Ciclo-Oxigenase 2/genética , Dinoprostona/biossíntese , Ativação Enzimática/efeitos dos fármacos , Humanos , Metaloproteinases da Matriz/biossíntese , Pessoa de Meia-Idade , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Osteoartrite/induzido quimicamente , Fator de Necrose Tumoral alfa/biossínteseRESUMO
BACKGROUND: Multiple trauma normally leads to acute lung injury (ALI) and other multiple organ dysfunction syndrome (MODS). Finding effective treatments for ALI remains a medical as well as socioeconomic challenge. Several studies show that bone marrow mesenchymal stem cells (BMSCs) have the potent anti-inflammation activity and transfusion of BMSCs can effectively inhibit inflammatory and autoimmune diseases. METHODS: In this study, we investigated the TLR2, 4/NF-κB signaling pathway to determine the therapeutic value of BMSCs on lipopolysaccharide (LPS)-induced ALI. To investigate the immunosuppression effects of BMSCs, rats subjected to multiple trauma were administrated with LPS to induce ALI and then treated with BMSCs. The histology of the lung was examined. Serum levels of the pro-inflammatory factors TNFα, interleukin (IL)-6, and IL-1ß, as well as anti-inflammatory factor IL-10 were measured at 3, 6, 12, and 24âh after the treatment. Moreover, expressions of TLR2 and TLR4 at the mRNA and protein levels, as well as phosphorylation of p65 in the lungs, were assessed at these time points. RESULTS: We found that BMSCs reduced inflammatory injury, inhibited LPS-induced upregulation of TLR2 and TLR4 expression at the mRNA and protein levels, and compromised p65 phosphorylation. In addition, infusion of BMSCs also downregulated the abundance of pro-inflammatory TNFα, IL-6, and IL-1ß and upregulated the abundance of anti-inflammatory IL-10 levels in the serum. CONCLUSIONS: Our results suggest that BMSCs suppress the inflammatory reactions through inhibition of the TLR2, 4 mediated NF-κB signal pathway, which hints that BMSCs can potentially be used to treat ALI in multiple trauma.