RESUMEN
Current models of somatosensory perception emphasize transmission from primary sensory neurons to the spinal cord and on to the brain1-4. Mental influence on perception is largely assumed to occur locally within the brain. Here we investigate whether sensory inflow through the spinal cord undergoes direct top-down control by the cortex. Although the corticospinal tract (CST) is traditionally viewed as a primary motor pathway5, a subset of corticospinal neurons (CSNs) originating in the primary and secondary somatosensory cortex directly innervate the spinal dorsal horn via CST axons. Either reduction in somatosensory CSN activity or transection of the CST in mice selectively impairs behavioural responses to light touch without altering responses to noxious stimuli. Moreover, such CSN manipulation greatly attenuates tactile allodynia in a model of peripheral neuropathic pain. Tactile stimulation activates somatosensory CSNs, and their corticospinal projections facilitate light-touch-evoked activity of cholecystokinin interneurons in the deep dorsal horn. This touch-driven feed-forward spinal-cortical-spinal sensitization loop is important for the recruitment of spinal nociceptive neurons under tactile allodynia. These results reveal direct cortical modulation of normal and pathological tactile sensory processing in the spinal cord and open up opportunities for new treatments for neuropathic pain.
Asunto(s)
Vías Nerviosas/fisiopatología , Neuralgia/fisiopatología , Tractos Piramidales/fisiopatología , Tacto/fisiología , Animales , Axones , Colecistoquinina/metabolismo , Femenino , Miembro Posterior/fisiopatología , Hiperalgesia/patología , Hiperalgesia/fisiopatología , Interneuronas/metabolismo , Masculino , Ratones , Neuralgia/patología , Nocicepción/fisiología , Tractos Piramidales/patología , Corteza Somatosensorial/patología , Corteza Somatosensorial/fisiopatología , Asta Dorsal de la Médula Espinal/patología , Asta Dorsal de la Médula Espinal/fisiopatologíaRESUMEN
Motor recovery after severe spinal cord injury (SCI) is limited due to the disruption of direct descending commands. Despite the absence of brain-derived descending inputs, sensory afferents below injury sites remain intact. Among them, proprioception acts as an important sensory source to modulate local spinal circuits and determine motor outputs. Yet, it remains unclear whether enhancing proprioceptive inputs promotes motor recovery after severe SCI. Here, we first established a viral system to selectively target lumbar proprioceptive neurons and then introduced the excitatory Gq-coupled Designer Receptors Exclusively Activated by Designer Drugs (DREADD) virus into proprioceptors to achieve specific activation of lumbar proprioceptive neurons upon CNO administration. We demonstrated that chronic activation of lumbar proprioceptive neurons promoted the recovery of hindlimb stepping ability in a bilateral hemisection SCI mouse model. We further revealed that chemogenetic proprioceptive stimulation led to coordinated activation of proprioception-receptive spinal interneurons and facilitated transmission of supraspinal commands to lumbar motor neurons, without affecting the regrowth of proprioceptive afferents or brain-derived descending axons. Moreover, application of 4-aminopyridine-3-methanol (4-AP-MeOH) that enhances nerve conductance further improved the transmission of supraspinal inputs and motor recovery in proprioception-stimulated mice. Our study demonstrates that proprioception-based combinatorial modality may be a promising strategy to restore the motor function after severe SCI.
Asunto(s)
Aminopiridinas/administración & dosificación , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Neuronas Motoras/fisiología , Traumatismos de la Médula Espinal/terapia , Aminopiridinas/farmacología , Animales , Terapia Combinada , Dependovirus/genética , Modelos Animales de Enfermedad , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Humanos , Ratones , Neuronas Motoras/metabolismo , Conducción Nerviosa/efectos de los fármacos , Propiocepción/efectos de los fármacos , Recuperación de la Función , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/fisiopatologíaRESUMEN
BACKGROUND: The establishment of precise and personalized prediction systems for chondroblastic osteosarcoma patients is important for guiding the treatment. METHODS: The univariate logrank test and multivariate Cox regression analysis were performed to identify independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Nomograms were constructed to estimate the OS and CSS based on these factors. Internal and external validation was performed. The predictive power of the nomograms was determined by C-index and calibration plots. RESULTS: A total of 401 chondroblastic osteosarcoma cases were identified. Univariate and multivariate analysis revealed that age at diagnosis, histological grade, tumor size, Surveillance, Epidemiology, and End Results stage, and surgical resection were independent prognostic factors for OS and CSS. The five factors were incorporated to construct the nomograms for estimating the 3- and 5-year OS and CSS. The C-index values for the internal validation of the OS and CSS nomogram were 0.732 and 0.746, respectively, and for the external validation were 0.780 and 0.808, respectively. The calibration curves revealed that the predicted OS and CSS could well match the actual survival rate. CONCLUSIONS: The nomograms for predicting 3- and 5-year OS and CSS were constructed and were proved to be accurate and reliable by the internal and external validation.
Asunto(s)
Neoplasias Óseas/mortalidad , Condroblastoma/mortalidad , Nomogramas , Osteosarcoma/mortalidad , Adolescente , Adulto , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Condroblastoma/patología , Condroblastoma/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Osteosarcoma/patología , Osteosarcoma/cirugía , Pronóstico , Estudios Retrospectivos , Programa de VERF , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Irreversible electroporation (IRE) is an emerging tissue ablation technique, which is safe for sites where thermal-basis techniques are not suitable. The aim of this study is to evaluate the safety and efficacy of magnetic anchoring electrode (MAE)-assisted IRE for normal gastric tissue ablation in a rabbit model. METHODS: IRE (500 V, 100 µs, 99 pulses, 1 Hz) of the gastric wall was performed in 24 adult New Zealand rabbits with a novel catheter-mounted MAE with fluoroscopy and a surgical approach. Procedure time, procedure-related bleeding, perforation, and other complications were recorded. Animals were sacrificed at 30 min, 1 day, 3 days, 7 days, 14 days, and 28 days post-IRE. The stomach was removed en bloc, and the diameter of each lesion was measured. Histopathological analyses by Hematoxylin-Eosin (H&E), masson trichrome, alpha-smooth muscle action (α-SMA), and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) were performed. RESULTS: Gastric tissue ablation with MAE-assisted IRE was successfully performed without any interruption. No perforation or bleeding was observed during IRE or throughout the follow-up period. A demarcated hemorrhage was found in the ablated area upon gross examination. H&E staining showed complete cell death with inflammatory infiltration, edema, and hemorrhaging. TUNEL presented diffuse positive cells in the ablated area. The tissue scaffold was well preserved without damage as indicated by Masson trichrome staining. Ulceration was observed starting from 3 days post-IRE. The mucosal layer was gradually recovered and regenerated within 14-28 days. No other complication was observed post-IRE. CONCLUSIONS: MAE-assisted IRE is safe and effective for normal gastric tissue ablation and the gastric wall recovered in 14-28 days post-IRE.
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Técnicas de Ablación/instrumentación , Electrodos , Electroporación/instrumentación , Mucosa Gástrica/cirugía , Magnetismo , Animales , Modelos Animales de Enfermedad , Electroporación/métodos , Fenómenos Magnéticos , Conejos , Coloración y Etiquetado , Estómago/cirugíaRESUMEN
BACKGROUND Anterior cervical plate and cage fixation system (ACPC) used in anterior cervical corpectomy and fusion (ACCF) is reported to incur excess complications. This study aimed to introduce integrated fixation cage (IFC) into ACCF to eliminate the anterior cervical plate (ACP)-related complications. MATERIAL AND METHODS One validated intact and 3 ACCF-simulated C3-C7 cervical spine models were developed. In ACCF models, C5 was corpectomied and fixed by IFC or ACPC. For each model, 1.0 Nm moments of flexion, extension, lateral bending, and torsion were imposed on the C3 vertebra. The range of motion (ROM) of each segment and the stress distribution on screw-vertebra interface, bone graft, and cage-endplate were recorded and analyzed. RESULTS ROMs of C3-C7 were not different in any motion condition between IFC and ACPC models. The maximal von Mises stress on screw-vertebra interface of the IFC model was lower than that of the ACPC models in flexion, extension, and lateral bending, but higher in rotation. The maximal von Mises stress on bone graft of the IFC model was higher compared with the ACPC models, except in flexion. The IFC model showed a higher maximal von Mises stress on cage-endplate interface in all motion planes. CONCLUSIONS Based on finite element analysis, IFC provided identical C3-C7 construct stability as ACPC. Compared with ACPC, IFC showed better biomechanical performance on screw-vertebra interface and bone graft, but worse biomechanical performance on cage-endplate interface.
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Vértebras Cervicales/cirugía , Fusión Vertebral/métodos , Adulto , Fenómenos Biomecánicos , Placas Óseas , Tornillos Óseos , Cadáver , Análisis de Elementos Finitos , Humanos , Masculino , Dolor de Cuello , Rango del Movimiento Articular , RotaciónRESUMEN
BACKGROUND This study aimed to verify the anti-subsidence ability of dome-shaped titanium mesh cage (TMC) used in anterior cervical corpectomy and fusion (ACCF). MATERIAL AND METHODS Thirty fresh human cervical vertebrae specimens were collected and randomly harvested into 2 groups: the traditional TMC group and the dome-shaped TMC group. The bone mineral density (BMD) of the specimens was recorded. Each group was biomechanically tested in axial compression with a cyclically loading range from 60 to 300 N at 0.5Hz for 10 000 cycles. The displacement data of the 2 groups were recorded every 10 cycles. RESULTS There was no significant difference in bone mineral density between the 2 groups of cervical specimens. The traditional TMC group stabilized at 535±35 cycles while the dome-shaped TMC group stabilized at 1203±57 cycles, which showed that the rate of subsidence of the dome-shaped TMC group was significantly slower than that of the traditional TMC group (p<0.05). After reaching stability, both groups had a more gradual and sustained growth. The peak displacement during fatigue testing was -2.064±0.150mm in the traditional TMC group and -0.934±0.086mm in the dome-shaped TMC group, which showed a significant difference (p<0.05). CONCLUSIONS The dome-shaped TMC showed a smaller subsidence displacement and a gentler subsidence tendency following the same cyclic loading (compared to the traditional TMC). From a biomechanical point of view, the dome-shaped TMC has stronger anti-subsidence ability due to its unique structural design that closely matches the vertebral endplate.
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Vértebras Cervicales/fisiología , Fusión Vertebral/métodos , Adulto , Fenómenos Biomecánicos , Densidad Ósea , Cadáver , Vértebras Cervicales/anatomía & histología , Fuerza Compresiva/fisiología , Femenino , Humanos , Masculino , Cuello/fisiología , Prótesis e Implantes , Mallas Quirúrgicas , TitanioRESUMEN
BACKGROUND The goal of this study was to determine the prognostic factors exclusive for high-grade chondrosarcoma and whether adjuvant radiotherapy could achieve better overall survival (OS) or cancer-specific survival (CSS) for patients with high-grade chondrosarcoma. MATERIAL AND METHODS Surveillance, Epidemiology, and End Results (SEER) cancer registry database was utilized to extract the chondrosarcoma cases diagnosed between 1973 and 2014. Among these cases, the histological grades of poorly differentiated (grade 3) and undifferentiated (grade 4) were categorized as high-grade and included in this study. Chondrosarcoma OS and CSS were the primary outcomes in the present study. The log-rank test was performed for univariate analysis, and the Cox regression model was conducted for multivariate analysis. RESULTS A total of 743 patients with high-grade chondrosarcoma were identified in this study (430 cases were poorly differentiated tumors, and 313 cases were undifferentiated tumors). Age at diagnosis, pathological grade, histo-type, SEER stage, tumor size and surgical resection were identified as independent predictors in both OS and CSS analysis of high-grade chondrosarcoma. When stratified by histological grade, surgical resection remained the effective treatment. Strikingly, radiotherapy was determined as an independent protective factor in both OS and CSS analysis of undifferentiated (grade 4) dedifferentiated chondrosarcoma, and adjuvant radiotherapy combined surgical resection could improve both the OS and CSS of patients with undifferentiated myxoid and dedifferentiated chondrosarcoma compared with other treatment regimens. CONCLUSIONS Our study first demonstrated that adjuvant radiotherapy combined surgery could improve the survival of patients with undifferentiated myxoid and dedifferentiated chondrosarcoma. These results encourage the application of adjuvant radiotherapy for patients with high-grade chondrosarcoma and maximize the patients' outcome.
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Condrosarcoma/cirugía , Condrosarcoma/terapia , Análisis de Supervivencia , Adulto , Anciano , China , Condrosarcoma/clasificación , Condrosarcoma/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Radioterapia Adyuvante/métodos , Sistema de Registros , Programa de VERF , Resultado del TratamientoRESUMEN
BACKGROUND Previous studies have shown that differences in marital status contribute to different prognoses for certain cancers, but the relationship between marital status and the prognosis of chondrosarcoma has not been reported previously. MATERIAL AND METHODS In this study, we selected 4502 eligible cases through the Surveillance, Epidemiology, and End Results (SEER) database from 1977 to 2014 to analyze the impact of marital status on chondrosarcoma cancer-specific survival (CSS) by Kaplan-Meier method and Cox regression model. RESULTS The sex, age, histotype, pathological grade, tumor location, tumor size, SEER stage, socioeconomic status, marital status, and treatment were identified as independent prognostic factors for chondrosarcoma CSS. Widowed patients presented the worst CSS compared with their married, divorced, and single counterparts (P<0.001). Subgroup analyses showed widowed patients also had a significantly higher risk of cancer-specific mortality compared with married patients in localized stage (HR: 1.971, 95% CI: 1.298-2.994, P=0.001), regional stage (HR: 1.535, 95% CI: 1.094-2.154, P=0.013), low pathological grade (HR: 1.866, 95% CI: 1.332-2.613, P<0.001), and high pathological grade (HR: 1.662, 95% CI: 1.139-2.426, P=0.008). CONCLUSIONS Marital status was first identified as an independent prognostic factor for chondrosarcoma CSS, and widowhood was always associated with a high risk of cancer-specific mortality. It is necessary to provide timely psychological treatment for widowed patients in clinical practice, which can improve the survival of chondrosarcoma patients.
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Neoplasias Óseas/mortalidad , Condrosarcoma/mortalidad , Estado Civil/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/psicología , Condrosarcoma/psicología , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Programa de VERF , Análisis de Supervivencia , Estados Unidos/epidemiología , Viudez/estadística & datos numéricosRESUMEN
Over the years, the oblique lateral interbody fusion (OLIF) technique has gained significant recognition for treating various spinal conditions in lumbar segments L2-L5. However, the adoption of OLIF for the L5-S1 segment has not been widely embraced by the spinal surgery community, given that significant concerns remain regarding the applicability of OLIF for lumbosacral fusion. In this study, a cohort of 20 patients underwent interbody fusion at the L5-S1 level using the OLIF technique through a single retroperitoneal oblique approach positioned between the Psoas muscle and the great vessels. The procedure involved discectomy and endplate preparation accomplished through a surgical window created on the anterolateral side of the L5-S1 disc. For secure interbody fusion cage placement, a supplementary cage insertion approach was employed. All patients were followed up for a minimum of 12 months. The mean preoperative visual analog scale (VAS) score for lower back pain was 6.3 ± 1.5 and experienced a significant reduction to 1.2 ± 0.8 at 12 months. The VAS score for lower limb pain significantly decreased from 5.6 ± 1.4 preoperatively to 0.8 ± 0.3 at 12 months after the surgery. Furthermore, the preoperative Oswestry disability index (ODI) improved from 82.4% ± 16.2% to 8.1% ± 2.0% at 12 months. Radiographic evaluations after surgery confirmed improved lumbosacral junction reconstruction for all patients. At the final follow-up, successful bony fusion was observed in all cases. Based on these findings, the OLIF technique for L5-S1 fusion represents an attainable approach for lumbosacral reconstruction. The procedure's success hinges on a comprehensive preoperative plan and precise intraoperative techniques.
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Dolor de la Región Lumbar , Fusión Vertebral , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Músculos Psoas/diagnóstico por imagen , Músculos Psoas/cirugía , Región Lumbosacra , Fusión Vertebral/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Neuromodulatory techniques have been proven to enhance functional recovery after stroke in patients and animals, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). However, the success and feasibility of these approaches were often variable, largely due to a lack of target specificity. OBJECTIVE: We explored the effects of specific chemogenetic stimulation of intact corticospinal tract during rehabilitative training on functional recovery after stroke in mice. METHODS: We developed a viral-based intersectional targeting approach that allows specific chemogentic activation of contralateral hindlimb corticospinal neurons (CSNs) in a photothrombotic stroke model. RESULTS: We demonstrated that specific chemogenetic activation of CSNs, when combined with daily rehabilitation training, leads to significant skilled motor functional recovery via promoting corticospinal tract (CST) axons midline crossing sprouting from intact to the denervated spinal hemicord, and rewiring new functional circuits by new synapse formation. Mechanistically, we revealed that combined chemogenetic stimulation of CSNs and daily rehabilitation training significantly enhanced the mTOR activity of CSNs. CONCLUSIONS: Our findings highlight the great potential of specific neural activation protocols in combination with motor training for the recovery of skilled motor functions after stroke.
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Accidente Cerebrovascular , Estimulación Transcraneal de Corriente Directa , Humanos , Ratones , Animales , Tractos Piramidales , Regeneración Nerviosa/fisiología , Neuronas/fisiología , Recuperación de la Función/fisiologíaRESUMEN
Characterized by nucleus pulposus (NP) cell senescence and extracellular matrix (ECM) degradation, disc degeneration is a common pathology for various degenerative spinal disorders. To date, effective treatments for disc degeneration are absent. Here, we found that Glutaredoxin3 (GLRX3) is an important redox-regulating molecule associated with NP cell senescence and disc degeneration. Using a hypoxic preconditioning method, we developed GLRX3+ mesenchymal stem cell-derived extracellular vehicles (EVs-GLRX3), which enhanced the cellular antioxidant defense, thus preventing reactive oxygen species (ROS) accumulation and senescence cascade expansion in vitro. Further, a disc tissue-like biopolymer-based supramolecular hydrogel, which was injectable, degradable, and ROS-responsive, was proposed to deliver EVs-GLRX3 for treating disc degeneration. Using a rat model of disc degeneration, we demonstrated that the EVs-GLRX3-loaded hydrogel attenuated mitochondrial damage, alleviated the NP senescence state, and restored ECM deposition by modulating the redox homeostasis. Our findings suggested that modulation of redox homeostasis in the disc can rejuvenate NP cell senescence and thus attenuate disc degeneration.
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Vesículas Extracelulares , Degeneración del Disco Intervertebral , Núcleo Pulposo , Ratas , Animales , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patología , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/patología , Degeneración del Disco Intervertebral/terapia , Especies Reactivas de Oxígeno/metabolismo , Hidrogeles/farmacología , Senescencia Celular , Oxidación-Reducción , Vesículas Extracelulares/metabolismo , HomeostasisRESUMEN
Mismatch between the titanium mesh cage and cervical geometries is an important factor that induces subsidence in anterior cervical corpectomy and fusion (ACCF). The aim of the present study was to construct a new quadrate anatomically adaptive titanium mesh cage (AA-TMC) that matches well with the cervical geometries and segmental alignment in one- and two-level ACCF. Computed tomography (CT) scans of 54 individuals were used to measure the cervical endplate geometries. X-rays of 74 young individuals were used to measure the intervertebral body angle (IBA) and intervertebral body height (IBH) of the surgical segments. The AA-TMC was designed based on these measured parameters. A total of 18 cervical cadaveric specimens underwent successive one- and two-level ACCF using the AA-TMC. Postoperatively, the specimens underwent CT scanning to assess the degree of matching of the TMC-endplate interface (TEI), IBA and IBH. A TEI interval <0.5 mm was considered well matching. In the sagittal plane, 93.8% of the inferior endplates were arched, whereas 94.8% of the superior endplates were flat. In the coronal plane, 82.9% of the inferior endplates and 93.8% of the superior endplates were flat. A total of 91.7 and 94.4% of the TEIs were well matched in one- and two-level ACCF, respectively. The postoperative IBA and IBH values were consistent with the values of young individuals. The AA-TMC achieved good matching with cervical geometries and segmental alignment in one- and two-level ACCF, and is proposed for use in ACCF to increase the contact at the TEI and achieve sufficient lordosis restoration.
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The particle size multiplier is a valuable parameter for depicting the particle size distribution characteristics of road dust and calculating road dust emissions. In order to realize the localization of the particle size multiplier, the AP-42 and TRAKER methods were used for sampling on typical and different types of roads in Baoding in March 2019. Then, the particle size multiplier of road dust PM2.5 (K2.5) was calculated using the correction formula, and the characteristics were analyzed. The results indicated:â The K2.5 obtained separately by AP-42 and TRAKER were 0.21 g·VKT-1 and 0.23 g·VKT-1 on average, which correlated well, with a high correlation coefficient of 0.6. The PM2.5 emission factors calculated using the K2.5 of the different methods were almost at the same value, indicating that TRAKER method based on a laser sensor could measure and calculate the K2.5 and could be directly used to obtain the particle size multiplier or be converted using the fitting equation. â¡ The characteristics of the K2.5 in Baoding were ranked as:Expressway
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After sciatic nerve injury, Schwann cells in the distal segments of injury site undergo apoptosis and meanwhile proliferation. Although apoptosis-induced proliferation (AiP) has been characterized in various models, whether the proliferation of Schwann cells in the distal segments is triggered by apoptosis remains unelucidated. In this study, we used small interfering RNA to knock down the expression of TNFR1 and TNFR2 in primarily cultured Schwann cells, respectively and observed its effects on apoptosis and proliferation. The downregulation of TNFR1 or TNFR2 resulted in a remarkable decrease of cell viability and dramatically increased the apoptosis of Schwann cells. In contrast, the cell apoptosis induced by the knockdown of TNFR2, but not TNFR1, promoted the Schwann cell proliferation. Together, these observations indicated that Schwann cells can undergo AiP, and TNFR2 knockdown triggers the process. Additionally, we established the sciatic nerve injury model on TNF-α knock-out (KO) mice, and found that the Schwann cells of KO mice occurred significantly less apoptosis and proliferation than that of wild-type mice in the distal segments, which indicated TNF-α and its receptors were essential in the massive apoptosis and the apoptosis-induced proliferation of Schwann cells after sciatic nerve injury. The finding of AiP in Schwann cells may be beneficial to develop new approaches to promote axon regeneration and thereby improve the functional recovery after peripheral nerve injury.
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Receptores Tipo II del Factor de Necrosis Tumoral/genética , Receptores Tipo II del Factor de Necrosis Tumoral/metabolismo , Células de Schwann/citología , Células de Schwann/metabolismo , Animales , Apoptosis/fisiología , Axones/metabolismo , Proliferación Celular/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Regeneración Nerviosa/fisiología , Traumatismos de los Nervios Periféricos/metabolismo , Cultivo Primario de Células , Ratas , Ratas Sprague-Dawley , Células de Schwann/patología , Nervio Ciático/metabolismo , Factor de Necrosis Tumoral alfa/deficiencia , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
MicroRNAs (miRNAs) function as gene expression switches, and participate in diverse pathophysiological processes of spinal cord injury (SCI). Olfactory ensheathing cells (OECs) can alleviate pathological injury and facilitate functional recovery after SCI. However, the mechanisms by which OECs restore function are not well understood. This study aims to determine whether silencing miR-199a-5p would enhance the beneficial effects of the OECs. In this study, we measured miR-199a-5p levels in rat spinal cords with and without injury, with and without OEC transplants. Then, we transfected OECs with the sh-miR-199a-5p lentiviral vector to reduce miR-199a-5p expression and determined the effects of these OECs in SCI rats by Basso-Beattie-Bresnahan (BBB) locomotor scores, diffusion tensor imaging (DTI), and histological methods. We used western blotting to measure protein levels of Slit1, Robo2, and srGAP2. Finally, we used the dual-luciferase reporter assay to assess the relationship between miR-199-5p and Slit1, Robo2, and srGAP2 expression. We found that SCI significantly increased miR-199a-5p levels (P < 0.05), and OEC transplants significantly reduced miR-199a-5p expression (P < 0.05). Knockdown of miR-199a-5p in OECs had a better therapeutic effect on SCI rats, indicated by higher BBB scores and fractional anisotropy values on DTI, as well as histological findings. Reducing miR-199a-5p levels in transplanted OECs markedly increased spinal cord protein levels of Slit1, Robo2, and srGAP2. Our results demonstrated that transplantation of sh-miR-199a-5p-modified OECs promoted functional recovery in SCI rats, suggesting that miR-199a-5p knockdown was more beneficial to the therapeutic effects of OEC transplants. These findings provided new insights into miRNAs-mediated therapeutic mechanisms of OECs, which helps us to develop therapeutic strategies based on miRNAs and optimize cell therapy for SCI.
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MicroARNs/farmacología , Bulbo Olfatorio/trasplante , Recuperación de la Función/efectos de los fármacos , Traumatismos de la Médula Espinal/terapia , Médula Espinal/cirugía , Animales , Trasplante de Células/métodos , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Células Cultivadas , Modelos Animales de Enfermedad , Masculino , MicroARNs/genética , Bulbo Olfatorio/efectos de los fármacos , Ratas Sprague-Dawley , Receptores Inmunológicos/metabolismo , Recuperación de la Función/fisiología , Médula Espinal/patologíaRESUMEN
OBJECTIVE: To assess the geometrical matching of a new anatomical adaptive titanium mesh cage (AA-TMC) with the endplate and its effect on cervical segmental alignment reconstruction in single- and two-level anterior cervical corpectomy and fusion (ACCF) and compare the compressive load at the endplate between the AA-TMC and the conventional titanium mesh cage (TMC). METHODS: Twelve cervical cadaveric specimens were used to perform single- and two-level ACCF. The interbody angle (IBA), interbody height (IBH) and the interval between the AA-TMC and the endplate were evaluated by comparison of the pre- and postoperative X-ray images. The maximum load at the endplate was compared between the AA-TMC and TMC based on American Society for Testing and Materials (ASTM) F2267 standard. RESULTS: No significant differences were found between the preoperative and postoperative IBA and IBH in either single-level ACCF (11.62°±2.67° vs 12.13°±0.69° and 23.90±2.18 mm vs 24.23±1.13 mm, respectively; P > 0.05) or two-level ACCF (15.63°±5.06° vs 16.16°±1.05°and 42.93±3.51 mm vs 43.04±1.70 mm, respectively; P > 0.05). The mean interval between the AA-TMC and the endplate was 0.37 ± 0.3 mm. Compared to the conventional TMC, the use of AA-TMC significantly increased the maximum load at the endplate in both single-level ACCF (719.7±5.5 N vs 875.8±5.2 N, P < 0.05) and two-level ACCF (634.3±5.9 N vs 873±6.1 N, P < 0.05). CONCLUSIONS: The use of AA-TMC in single-level and two-level ACCF can significantly increase the maximum load at the endplate to lower the possibility of implant subsidence and allows effective reconstruction of the cervical alignment.
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Vértebras Cervicales , Fusión Vertebral , Fenómenos Biomecánicos , Humanos , Prótesis e Implantes , Mallas Quirúrgicas , Titanio , Resultado del TratamientoRESUMEN
Osteosarcoma (OS) is the major type of primary bone tumor and is associated with a poor prognosis due to chemotherapy resistance. Accumulating evidence indicates that microRNAs (miRNAs/miRs) may influence the tumor progression of OS and cell sensitivity to chemotherapy. In the present study, a total of 7 patients with OS and 7 healthy volunteers were recruited. Reverse transcriptionquantitative polymerase chain reaction and ELISA were performed to determine the expression of miRNAs and mRNAs in the serum of participants. Furthermore, the biological function of miR22 and S100A11 was examined in MG63 cells using Cell Counting Kit8 assays, Transwell migration assays and western blot analysis to determine the effects on cell proliferation, migration and protein expression, respectively, while MG63 cell sensitivity to cisplatin was assessed by measuring cell viability following cisplatin treatment and calculating the half maximal inhibitory concentration (IC50). Additionally, the association between miR22 and S100 calciumbinding protein A11 (S100A11) was validated using a luciferase reporter assay. The results demonstrated that miR22 expression was significantly reduced in patients with OS and the MG63 OS cell line, compared with healthy volunteers and the normal osteoblast hFOB 1.19 cell line, respectively, while the expression of S100A11 was negatively associated with miR22 levels in the MG63 cell line. Furthermore, overexpression of miR22 inhibited the proliferation and migratory ability of MG63 cells, and increased the sensitivity of MG63 cells to cisplatin treatment; however, overexpression of S100A11 partially attenuated the alterations in proliferation, migratory ability and chemosensitivity that were induced by miR22 overexpression. In addition, it was confirmed that S100A11 is a direct target gene of miR22 in MG63 cells. In conclusion, to the best of our knowledge, the present study is the first to demonstrate that miR22 may be a promising therapeutic target and may have potential as part of a combination treatment alongside chemotherapeutic agents for OS.
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Antineoplásicos/farmacología , Neoplasias Óseas/genética , Cisplatino/farmacología , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Osteosarcoma/genética , Adolescente , Adulto , Apoptosis/efectos de los fármacos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Niño , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Proteínas S100/genética , Adulto JovenRESUMEN
In the past two decades, many tools have been reported to measure the cervical range of motion (CROM), but most of the results are controversial in healthy individuals and/or individuals with neck pain. The Coda Motion 3-D Analysis system is a new instrument that measures three-dimensional joint movement. However, measurements of CROM using this system have yet to be conducted. Here, we investigate the reliability and validity of the Coda Motion 3-D Analysis System for measuring CROM in healthy adults. Sixty healthy volunteers were involved in this reliability study. Two trained investigators (M1 and M2) used the Coda Motion 3-D Analysis System to measure CROM. M1 and M2 measured all the volunteers once independently; after a short rest, M1 then measured all of them again. The intraclass correlation coefficient (ICC), standard error of the measurements (SEM), smallest detectable difference (SDD), a scatter diagram, and the limits of agreement (LoAs) were applied to evaluate the inter-tester and intra-tester reliability. Thirty healthy volunteers were involved in this validity study. The cervical flexion and extension ranges of motion were measured simultaneously with both the Coda Motion 3-D Analysis System and X-ray. A scatter diagram, the Pearson correlation coefficient and LoAs were used to evaluate the validity. Excellent intra-tester and inter-tester reliabilities were observed for the Coda Motion 3-D Analysis System (intra-tester ICC: 0.84-0.95, inter-tester ICC: 0.84-0.90). Good validity was achieved in extension and flexion with Pearson correlation coefficients ranging from 0.78 to 0.91. The Coda Motion 3-D Analysis System has excellent reliability for the measurement of CROM and good validity for measurements of flexion and extension in healthy subjects. This system has the potential to be used to measure the normal active CROM in the clinic and is accurate, safe, non-invasive, and radiation free.
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Vértebras Cervicales/fisiología , Examen Neurológico/instrumentación , Rango del Movimiento Articular , Adulto , Femenino , Humanos , Masculino , Cuello/fisiología , Examen Neurológico/métodos , Examen Neurológico/normas , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: To study the change trend of cervical range of motion(ROM) after single-level anterior cervical corpectomy and fusion(ACCF) in treating cervical spondylotic myelopathy. METHODS: The clinical data of 23 patients with cervical spondylotic myelopathy was retrospectively analyzed from February 2015 to April 2016. There were 11 males and 12 females, with an average age of (54.6±13.3) years. All the patients were diagnosed as cervical spondylotic myelopathy by interrogation, physical examination and radiology, and were treated by ACCF. The Coda motion system was applied to assess the cervical range of motion pre-and post-operation. JOA and VAS scores were used to evaluate the clinical outcomes. RESULTS: The mean follow-up time was (9.4±1.6) months. Cervical ROM in all directions at 3 months postoperatively were significantly lower except for the left rotation(P<0.05). There was significant difference of cervical ROM in all directions between preoperative and 6 months postoperatively(P>0.05). The right lateral bending and the left rotation at 9 months postoperatively increased significantly(P<0.05). Postoperative extension at 6 months was significantly better than that of 3 months postoperatively(P<0.05). The extension, left and right lateral bending and left rotation at 9 months postoperatively were significantly better than of 6 months postoperatively(P<0.05). Postoperative JOA scores at each time points were significantly higher than that of preoperative(P<0.05) and VAS scores at each time points were significantly lower than that of preoperative(P<0.05). CONCLUSIONS: The change trend of three-dimensional cervical ROM after single-level ACCF revealed that the ROM decreased in short term, and later increased and was better than the preoperative level. Meanwhile, the neurological function improved significantly. But the short-term and long-term change trend of ROM postoperatively and the change trend of ROM after multi-level ACCF need to be further studied.
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Vértebras Cervicales/cirugía , Rango del Movimiento Articular , Enfermedades de la Médula Espinal/cirugía , Fusión Vertebral , Espondilosis/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The aim of the present study was to investigate the racial disparities in the presentation, treatment and survival time of patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) between Chinese and other racial groups from the Surveillance, Epidemiology, and End Results (SEER) database between January 1st 2004, and December 31st 2013. Key covariates, including clinical presentation, treatment and survival time, were recorded and compared, demonstrating the racial differences. Kaplan-Meier analysis and Cox regression models were performed to identify these disparities in survival time. A total of 30,954 patients were identified in the SEER database. Among these, 27,767 (89.7%) had HCC and 3,187 (10.3%) had ICC. In the HCC cohort, Chinese patients had the highest survival time. Compared with the mortality risk of Chinese patients, the mortality risk of Other Asian, non-Hispanic white, Hispanic and African-American patients increased by 16.8, 35.1, 28.3 and 33.3%, respectively. Compared with other groups, Chinese patients were more likely to present with localized stage, and without vascular invasion, adjacent invasion and metastasis. In the ICC cohort, the Chinese group had improved survival time, compared with the other groups following univariate analysis, although no significant differences were observed between Chinese and Other Asian and Hispanic patients following adjusting for contributing factors. Furthermore, there was no significant differences in the presentation between the groups, which differed from the HCC analysis. In conclusion, race/ethnicity was a significant independent prognostic factor in the HCC cohort, whereas it was not significant in the ICC cohort. The synergistic effect of contributing factors, including demographic, socioeconomic, biological and treatment differences, caused the racial disparity observed in primary liver cancer survival time.