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Reactive oxygen species (ROS)-dependent monotherapy usually demonstrates poor therapeutic outcomes, due to the accompanied activation of protective autophagy in tumor cells, which results in ROS tolerance and immune suppression. In this study, a bimetallic electro-sensitizer, Pt-Ir NPs is constructed, loaded with the autophagy inhibitor chloroquine (Pt-Ir-CQ NPs), to enhance the effectiveness of electrotherapy by inhibiting autophagy and activating anti-tumor immune responses. This novel electrotherapy platform demonstrates unique advantages, particularly in the treatment of hypoxic and immunosuppressive tumors. First, the electro-sensitizer catalyzes water molecules into ROS under electric field, achieving tumor ablation through electrotoxicity. Second, the incorporated CQ inhibits the protective autophagy induced by electrotherapy, restoring the sensitivity of tumor cells to ROS and thereby enhancing the anti-tumor effects of electrotherapy. Third, Pt-Ir-CQ NPs enhance the functionality of antigen-presenting cells and immunogenic cells through inhibiting autophagy, synergistically activating the anti-tumor immune responses along with the immunogenic cell death (ICD) effect induced by electrotherapy. This study provides a novel approach for the effective ablation and long-term inhibition of solid tumors through flexible modulation by an exogenous electric field.
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Two-dimensional (2D) 1H-13C heteronuclear single quantum coherence (HSQC) has been increasingly applied to metabolomics studies because it can greatly improve the resolving capability compared with one-dimensional (1D) 1H NMR. However, preprocessing methods such as peak matching and alignment tools for 2D NMR-based metabolomics have lagged behind similar methods for 1D 1H NMR-based metabolomics. Correct matching and alignment of 2D NMR spectral features across multiple samples are particularly important for subsequent multivariate data analysis. Considering different intensity dynamic ranges of a variety of metabolites and the chemical shift variation across the spectra of multiple samples, here, we developed an efficient peak matching and alignment algorithm for 2D 1H-13C HSQC-based metabolomics, called global intensity-guided peak matching and alignment (GIPMA). In GIPMA, peaks identified in all spectra are pooled together and sorted by intensity. Chemical shift of a stronger peak is regarded to be more accurate and reliable than that of a weaker peak. The strongest undesignated peak is chosen as the reference of a new cluster if it is not located within the chemical shift tolerance of any existing peak cluster (PC), or otherwise it is matched to an existing PC and the aligned chemical shift of the PC is updated as the intensity-weighted average of the chemical shifts of all peaks in the cluster. Setting an optimum chemical shift tolerance (Δδo) is critical for the peak matching and alignment across multiple samples. GIPMA dynamically searches for and intelligently selects the Δδo for peak matching to maximize the number of valid peak clusters (vPC), that is, spectral features, among multiple samples. By GIPMA, fully automatic peakwise matching and alignment do not require any spectrum as initial reference, while the chemical shift of each PC is updated as the intensity-weighted average of the chemical shifts of all peaks in the same PC, which is warranted to be statistically more accurate. Accurate chemical shifts for each representative spectral feature will facilitate subsequent peak assignment and are essential for correct metabolite identification and result interpretation. The proposed method was demonstrated successfully on the spectra of six model mixtures consisting of seven typical metabolites, yielding correct matching of all known spectral features. The performance of GIPMA was also demonstrated on 2D 1H-13C HSQC spectra of 87 real extracts of 29 samples of five Dendrobium species. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) of the 87 matched and aligned spectra by GIPMA generates correct classification of the 29 samples into five groups. In summary, the proposed algorithm of GIPMA provided a practical peak matching and alignment method to facilitate 2D NMR-based metabolomics studies.
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Algoritmos , Metabolómica , Metabolómica/métodos , Espectroscopía de Resonancia Magnética/métodos , Análisis por ConglomeradosRESUMEN
As a new type of energetic material, cocrystal explosives demonstrate many excellent properties, such as high energy density and low sensitivity, due to the interaction between the molecules of the two components. The known decomposition temperature is 235 °C for CL-20/HMX cocrystals at a faster heating rate. CL-20 molecules could separate from the cocrystal matrix and decompose at a higher temperature, much lower than the decomposition temperature. The current work provided deep insight into the isothermal structural evolution of CL-20/HMX cocrystals with slow roasting at 190 °C. We found that the initial decomposition originates from separating CL-20 molecules from the surface along the (010) plane of the cocrystals. The gas products, such as NO2 and NO, escape from the largest exposed surface of the (010) plane and generates microbubbles and microholes. At the same time, the residual HMX molecules form δ-phase HMX crystals and shrink the volume by 72%. By increasing the time held at 190 °C, the decomposition of CL-20 molecules and recrystallization of the residual HMX molecules form a gully-like structure on the (010) plane of the CL-20/HMX cocrystal. After a long time at 190 °C, the CL-20 component completely decomposes, and all HMX molecules recrystallize in the δ-HMX form. The interaction between HMX and CL-20 molecules makes the decomposition rate of the CL-20/HMX cocrystal much slower than that of the CL-20 pure crystal with a similar decomposition activation energy during isothermal heating. This work can help to deeply understand the safety of CL-20/HMX cocrystal explosives at a temperature lower than the recognized decomposition temperature.
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Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 has rapidly expanded into a serious global pandemic. Due to the high morbidity and mortality of COVID-19, there is an urgent need to develop safe and effective vaccines. AdC68-19S is an investigational chimpanzee adenovirus serotype 68 (AdC68) vector-based vaccine which encodes the full-length spike protein of SARS-CoV-2. Here, we evaluated the immunogenicity, biodistribution and safety profiles of the candidate vaccine AdC68-19S in Sprague Dawley (SD) rat and rhesus macaque under GLP conditions. To characterize the biodistribution profile of AdC68-19S, SD rats were given a single intramuscular injection of AdC68-19S 2 × 1011 VP/dose. Designated organs were collected on day 1, day 2, day 4, day 8 and day 15. Genomic DNA was extracted from all samples and was further quantified by real-time quantitative polymerase chain reaction (qPCR). To characterize the toxicology and immunogenicity profiles of AdC68-19S, the rats and rhesus macaques were injected intramuscularly with AdC68-19S up to 2 × 1011vp/dose or 4 × 1011vp/dose (2 and fourfold the proposed clinical dose of 1 × 1011vp/dose) on two or three occasions with a 14-day interval period, respectively. In addition to the conventional toxicological evaluation indexes, the antigen-specific cellular and humoral responses were evaluated. We proved that multiple intramuscular injections could elicit effective and long-lasting neutralizing antibody responses and Th1 T cell responses. AdC68-19S was mainly distributed in injection sites and no AdC68-19S related toxicological reaction was observed. In conclusion, these results have shown that AdC68-19S could induce an effective immune response with a good safety profile, and is a promising candidate vaccine against COVID-19.
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Vacunas contra la COVID-19 , COVID-19 , Adenoviridae/genética , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Humanos , Macaca mulatta , Pan troglodytes , Ratas , Ratas Sprague-Dawley , SARS-CoV-2 , Distribución TisularRESUMEN
Transplantation of neural stem cells (NSCs) is a promising treatment paradigm to replace lost neurons and reconstruct the damaged neural circuit after ischemic stroke. However, most transplanted NSCs often differentiate into astrocytes rather than functional neurons, and the poor neuronal differentiation adversely affects the therapeutic outcome of NSCs and limits their clinical translation for stroke therapy. Herein, a theranostic nanomedicine is developed to codeliver superparamagnetic iron oxide nanoparticles (SPIO) and small interfering RNA/antisense oligonucleotides (siRNA/ASO) against Pnky long noncoding RNA (lncRNA) into NSCs. This nanomedicine not only directs neuronal differentiation of NSCs through silencing the Pnky lncRNA but also allows an in vivo tracking of NSCs with magnetic resonance imaging. The enhanced neuronal differentiation of NSCs significantly improved the structural and functional recovery of the damaged brain after a stroke. The results demonstrate the great potential of the multifunctional nanomedicine targeting lncRNA to enhance stem cell-based therapies for a stroke.
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Células-Madre Neurales , ARN Largo no Codificante , Accidente Cerebrovascular , Diferenciación Celular , Humanos , Nanomedicina , ARN Largo no Codificante/genética , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/terapiaRESUMEN
Scrophulariae Radix (SR) is one of the oldest and most frequently used Chinese herbs for oriental medicine in China. Before clinical use, the SR should be processed using different methods after harvest, such as steaming, "sweating", and traditional fire-drying. In order to investigate the difference in chemical constituents using different processing methods, the two-dimensional (2D) 1H-13C heteronuclear single quantum correlation (1H-13C HSQC)-based metabolomics approach was applied to extensively characterize the difference in the chemical components in the extracts of SR processed using different processing methods. In total, 20 compounds were identified as potential chemical markers that changed significantly with different steaming durations. Seven compounds can be used as potential chemical markers to differentiate processing by sweating, hot-air drying, and steaming for 4 h. These findings could elucidate the change of chemical constituents of the processed SR and provide a guide for the processing. In addition, our protocol may represent a general approach to characterizing chemical compounds of traditional Chinese medicine (TCM) and therefore might be considered as a promising approach to exploring the scientific basis of traditional processing of TCM.
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Medicamentos Herbarios Chinos , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Medicina Tradicional China , Metabolómica/métodos , Raíces de Plantas/químicaRESUMEN
Mutations in the synaptic nuclear envelope protein 1 (SYNE1) gene have been reported to cause autosomal recessive cerebellar ataxia (ARCA) type 1 with highly variable clinical phenotypes. The aim of this study was to describe the phenotypic-genetic spectrum of SYNE1-related ARCA1 patients in the Chinese population. We screened 158 unrelated patients with autosomal recessive or sporadic ataxia for variants in SYNE1 using next-generation sequencing. Pathogenicity assessment of SYNE1 variants was interpreted according to the American College of Medical Genetics standards and guidelines. We identified eight truncating variants and two missense variants spreading throughout the SYNE1 gene from six unrelated families, including nine novel variants and one reported variant. Of the six index patients, two patients showed the classical pure cerebellar ataxia, while four patients exhibited non-cerebellar phenotypes, including motor neuron symptoms, cognitive impairment, or mental retardation. The variants associated with motor neuron or cognition involvement tend to be located in the C-terminal region of SYNE1 protein, compared with the variants related to pure cerebellar ataxia. Our data indicating SYNE1 mutation is one of the more common causes of recessive ataxia in the Chinese population. The use of next-generation sequencing has enabled the rapid analysis of recessive ataxia and further expanded our understanding of genotype-phenotype correlation.
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Ataxia Cerebelosa/genética , Proteínas del Citoesqueleto/genética , Proteínas del Tejido Nervioso/genética , Adolescente , Adulto , Edad de Inicio , Pueblo Asiatico/genética , Ataxia Cerebelosa/patología , Niño , China , Disfunción Cognitiva/etiología , Disfunción Cognitiva/genética , Disfunción Cognitiva/patología , Femenino , Genes Recesivos , Variación Genética , Genotipo , Humanos , Discapacidad Intelectual/etiología , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Imagen por Resonancia Magnética , Masculino , Enfermedad de la Neurona Motora/etiología , Enfermedad de la Neurona Motora/genética , Enfermedad de la Neurona Motora/patología , Mutación Missense , Linaje , Fenotipo , Secuenciación del Exoma , Adulto JovenRESUMEN
BACKGROUND: To investigate whether quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) pharmacokinetic parameters can be used to predict the pathologic stages of oral tongue squamous cell carcinoma (OTSCC). METHODS: For this prospective study, DCE-MRI was performed in participants with OTSCC from May 2016 to June 2017. The pharmacokinetic parameters, including Ktrans, Kep, Ve, and Vp, were derived from DCE-MRI by utilizing a two-compartment extended Tofts model and a three-dimensional volume of interest. The postoperative pathologic stage was determined in each patient based on the 8th AJCC cancer staging manual. The quantitative DCE-MRI parameters were compared between stage I-II and stage III-IV lesions. Logistic regression analysis was used to determine independent predictors of tumor stages, followed by receiver operating characteristic (ROC) analysis to evaluate the predictive performance. RESULTS: The mean Ktrans, Kep and Vp values were significantly lower in stage III-IV lesions compared with stage I-II lesions (p = 0.013, 0.005 and 0.011, respectively). Kep was an independent predictor for the advanced stages as determined by univariate and multivariate logistic analysis. ROC analysis showed that Kep had the highest predictive capability, with a sensitivity of 64.3%, a specificity of 82.6%, a positive predictive value of 81.8%, a negative predictive value of 65.5%, and an accuracy of 72.5%. CONCLUSION: The quantitative DCE-MRI parameter Kep can be used as a biomarker for predicting pathologic stages of OTSCC.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Imagen por Resonancia Magnética/métodos , Neoplasias de la Lengua/diagnóstico por imagen , Neoplasias de la Lengua/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/cirugía , Medios de Contraste , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Interpretación de Imagen Radiográfica Asistida por Computador , Neoplasias de la Lengua/cirugía , Adulto JovenRESUMEN
BACKGROUND: Salt stress is one of the environmental factors that greatly limits crop production worldwide because high salt concentrations in the soil affect morphological responses and physiological and metabolic processes, including root morphology and photosynthetic characteristics. Soil aeration has been reported to accelerate the growth of plants and increase crop yield. The objective of this study was to examine the effects of 3 NaCl salinity levels (28, 74 and 120 mM) and 3 aeration volume levels (2.3, 4.6 and 7.0 L/pot) versus non-aeration and salinity treatments on the root morphology, photosynthetic characteristics and chlorophyll content of potted tomato plants. RESULTS: The results showed that both aeration volume and salinity level affected the root parameters, photosynthetic characteristics and chlorophyll content of potted tomato plants. The total length, surface area and volume of roots increased with the increase in aeration volume under each NaCl stress level. The effect was more marked in the fine roots (especially in ≤1 mm diameter roots). Under each NaCl stress level, the photosynthetic rate and chlorophyll content of tomato significantly increased in response to the aeration treatments. The net photosynthetic rate and chlorophyll a and t content increased by 39.6, 26.9, and 17.9%, respectively, at 7.0 L/pot aeration volume compared with no aeration in the 28 mM NaCl treatment. We also found that aeration could reduce the death rate of potted tomato plants under high salinity stress conditions (120 mM NaCl). CONCLUSIONS: The results suggest that the negative effect of NaCl stress can be offset by soil aeration. Soil aeration can promote root growth and increase the photosynthetic rate and chlorophyll content, thus promoting plant growth and reducing the plant death rate under NaCl stress conditions.
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Fotosíntesis , Raíces de Plantas/anatomía & histología , Solanum lycopersicum/fisiología , Clorofila/metabolismo , Solanum lycopersicum/anatomía & histología , Solanum lycopersicum/crecimiento & desarrollo , Solanum lycopersicum/metabolismo , Raíces de Plantas/fisiología , Salinidad , Estrés Salino , SueloRESUMEN
T cells are involved in bone marrow failure in aplastic anemia (AA). MEG3 is a long, non-coding RNA that can modulate target gene expression and T cell differentiation by acting as a microRNA sponge. Our previous study showed that T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domain (TIGIT) plays a critical role in regulating CD4 + T cell functions. In this study, we found that MEG3 expression was significantly downregulated in CD4 + T cells derived from AA patients. MEG3 modulated CD4 + T cell proliferation and IFN-γ and TNF-α levels, as well as TIGIT, T-bet, and orphan nuclear receptor (RORγt) expression. Furthermore, MEG3 overexpression sequestered miR-23a and prompted TIGIT expression in CD4 + T cells. CD4 + T cells with MEG3 overexpression impeded expansion of Th1 and Th17 cells, restored the decreased red blood cell count, attenuated the increase in serum INF-γ and TNF-α levels, and lengthened median survival time, as well as upregulated mRNA levels of CD34, stem cell factor (SCF), and granulocyte/macrophage-colony-stimulating factor (GM-CSF) in bone marrow mononuclear cells of a mouse model. In conclusion, our study provides evidence that MEG3 regulated TIGIT expression and CD4 + T cell activation by absorbing miR-23a. These findings provide novel insight into autoimmune-mediated AA.
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Anemia Aplásica/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Activación de Linfocitos , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Receptores Inmunológicos/genética , Adulto , Anemia Aplásica/genética , Anemia Aplásica/inmunología , Animales , Linfocitos T CD4-Positivos/inmunología , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Ratones , Adulto JovenRESUMEN
OBJECTIVES: Cardiac lead perforation is a rare but potentially life-threatening event. The purpose of this study was to investigate the diagnostic performances of chest radiography, transthoracic echocardiography (TTE) and electrocardiography (ECG)-gated contrast-enhanced cardiac CT in the assessment of cardiac lead perforation. METHODS: This retrospective study was approved by the ethics review board of Sun Yat-Sen Memorial Hospital at Sun Yat-Sen University (Guangzhou, China), and the need to obtain informed consent was waived. Between May 2010 and Oct 2017, 52 patients were clinically suspected to have a cardiac lead perforation and received chest radiography, TTE and ECG-gated contrast-enhanced cardiac CT. Among them, 13 patients were identified as having cardiac lead perforation. The diagnostic performances of these three modalities were evaluated by receiver-operating characteristic (ROC) curves using a composite reference standard of surgical and electrophysiological results and clinical follow-up. The areas under ROCs (AUROCs) were compared with the McNemar test. RESULTS: The accuracies of chest radiography, TTE and ECG-gated contrast-enhanced cardiac CT imaging for the diagnosis of cardiac lead perforation were 73.1%, 82.7% and 98.1%, respectively. ECG-gated contrast-enhanced cardiac CT had a higher AUROC than chest radiography (p < 0.001) and TTE (p < 0.001). CONCLUSIONS: ECG-gated contrast-enhanced cardiac CT is superior to both chest radiography and TTE imaging for the assessment of cardiac lead perforation. KEY POINTS: ⢠ECG-gated contrast-enhanced cardiac CT has an accuracy of 98.1% in the diagnosis of cardiac lead perforation. ⢠The AUROC of ECG-gated contrast-enhanced cardiac CT is higher than those of chest radiography and TTE imaging. ⢠ECG-gated contrast-enhanced cardiac CT imaging has better diagnostic performance than both chest radiography and TTE imaging for the assessment of cardiac lead perforation.
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Técnicas de Imagen Cardíaca/métodos , Lesiones Cardíacas/diagnóstico por imagen , Heridas Penetrantes/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Técnicas de Imagen Sincronizada Cardíacas/métodos , Ecocardiografía/métodos , Electrocardiografía/métodos , Electrodos Implantados/efectos adversos , Análisis de Falla de Equipo/métodos , Femenino , Lesiones Cardíacas/etiología , Humanos , Masculino , Persona de Mediana Edad , Marcapaso Artificial/efectos adversos , Curva ROC , Radiografía Torácica/métodos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Heridas Penetrantes/etiologíaRESUMEN
OBJECTIVES: To determine the predictive value of pretreatment MRI texture analysis for progression-free survival (PFS) in patients with primary nasopharyngeal carcinoma (NPC). METHODS: Ethical approval by the institutional review board was obtained for this retrospective analysis. In 79 patients with primary NPC, texture analysis of the primary tumour was performed on pretreatment T2 and contrast-enhanced T1-weighted images (T2WIs and CE-T1WIs). The Cox proportional hazards model was used to determine the association of texture features, tumour volume and the tumour-node-metastasis (TNM) stage with PFS. Survival curves were plotted using the Kaplan-Meier method. The prognostic performance was evaluated with the receiver operating characteristic (ROC) analyses and C-index. RESULTS: Tumour volume (hazard ratio, 1.054; 95% confidence interval [CI], 1.016-1.093) and CE-T1WI-based uniformity (hazard ratio, 0; 95% CI, 0-0.001) were identified as independent predictors for PFS (p < 0.05). Kaplan-Meier analysis showed that smaller tumour volume (less than the cut-off value, 11.699 cm3) and higher CE-T1WI-based uniformity (greater than the cut-off value, 0.856) were associated with improved PFS (p < 0.05). The combination of CE-T1WI-based uniformity with tumour volume and the overall stage predicted PFS better (area under the curve [AUC], 0.825; Cindex, 0.794) than the tumour volume (AUC, 0.659; C-index, 0.616) or the overall stage (AUC, 0.636; C-index, 0.627) did (p < 0.05). CONCLUSIONS: A texture parameter of pretreatment CE-T1WI-based uniformity improves the prediction of PFS in NPC patients. KEY POINTS: ⢠Higher CE-T1WI-based uniformity and smaller tumour volume are predictive of improved PFS in NPC patients. ⢠The combination of CE-T1WI-based uniformity with tumour volume and the overall stage has a better predictive ability for PFS than the tumour volume or the overall stage alone. ⢠Pretreatment MRI texture analysis has a prognostic value for NPC patients.
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Imagen por Resonancia Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/patología , Adolescente , Adulto , Anciano , Medios de Contraste , Femenino , Humanos , Aumento de la Imagen/métodos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Nasofaringe/diagnóstico por imagen , Nasofaringe/patología , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Estudios Retrospectivos , Carga Tumoral , Adulto JovenRESUMEN
It is very important to improve the electrical conductivities of polymer nanocomposites (PNCs) as this can widen their application. In this work, by employing a coarse-grained molecular dynamics simulation, we investigated the effect of the amphiphilic diblock copolymer (BCP)-mediated nanoparticle (NP) on the conductive probability of polymer nanocomposites (PNCs) in the quiescent state and under a shear field. The conductive probability of PNCs first increases and then decreases with increasing content of BCPs while, interestingly, it exhibits an N-type dependence on the A-Block-NP interaction. Furthermore, the conductive probability shows a non-monotonic dependence on the fraction of A block (fA) in the BCPs, which reaches the maximum value at moderate fA. Under the shear field, NPs self-assemble to form the sandwich-like structures in the matrix above a critical concentration of BCPs, which leads to the anisotropic conductive probability of PNCs. In addition, the sandwich-like structures of NPs will be broken down at a high shear rate, which reduces the difference of the directional conductive probabilities. Last, the mechanism of the formation of the sandwich-like structures of NPs is discussed. In summary, this work presents a simple method to control the conductive network formation, which can help to design PNCs with high electrical conductivity, and especially anisotropy.
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OBJECTIVE. The purpose of this study was to investigate the performance of quantitative parameters derived from dual-energy CT (DECT) in the preoperative diagnosis of regional metastatic lymph nodes (LNs) in patients with colorectal cancer. SUBJECTS AND METHODS. Triphasic contrast-enhanced DECT was performed for 178 patients with colon or high rectal cancer. The morphologic criteria, short-axis diameter, and quantitative DECT parameters of the largest regional LN were measured and compared between pathologically metastatic and nonmetastatic LNs. Univariate and multivariable logistic regression analyses were used to determine the independent DECT parameters for predicting LN metastasis. Diagnostic performance measures were assessed by ROC curve analysis and compared by McNemar test. RESULTS. A total of 178 largest LNs (72 metastatic, 106 nonmetastatic) were identified in 178 patients. The best single DECT parameter for differentiation between metastatic and nonmetastatic LNs was normalized effective atomic number (Zeff) in the portal venous phase (AUC, 0.871; accuracy, 84.8%). These values were higher than those of morphologic criteria (AUC, 0.505-0.624; accuracy, 47.8-62.4%) and short-axis diameter (AUC, 0.647; accuracy, 66.3%) (p < 0.05). The diagnostic accuracy of combined normalized iodine concentration in the arterial phase and normalized effective atomic number in the portal venous phase was further improved to 87.1% (AUC, 0.916). CONCLUSION. Quantitative parameters derived from DECT can be used to improve preoperative diagnostic accuracy in evaluation for regional metastatic LNs in patients with colorectal cancer.
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OBJECTIVE: To explore the clinical, neuropathological and genetic characteristics of a patient with Perrault syndrome caused by TWNK mutation. METHODS: Potential variation of the TWNK gene was detected by next-generation sequencing (NGS) and verified by Sanger sequencing. RESULTS: The patient has featured primary amenorrhoea and progressive sensorineural hearing loss since childhood. She also had gait anormaly, distal limb atrophy and weakness, and nystagmus. Further study confirmed sensory neuronopathy accompanied with upper and lower motor neuron involvement as well as cerebellum atrophy. NGS has identified two heterozygous variants of the TWNK gene, namely c.794G>A (p.Arg265His) and c.1181G>A (p.Arg394His). Sanger sequencing confirmed that c.1181G>A (p.Arg394His), a known pathogenic variant, was derived from her farther, while c.794G>A(p.Arg265His), a novel variant, was derived from her mother and likely pathogenic according to the ACMG guidelines. CONCLUSION: Perrault syndrome is a group of disorders with a high phenotypic heterogeneity. The compound heterozygous variation of c.794G>A (p.Arg265His) and c.1181G>A(p.Arg394His) of the TWNK gene may underlie Perrault syndrome in the patient.
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Disgenesia Gonadal 46 XX , Pérdida Auditiva Sensorineural , Niño , Femenino , Pruebas Genéticas , Humanos , LinajeRESUMEN
Mesenchymal stem cells (MSCs) have emerged as a promising cellular vehicle for gene therapy of malignant gliomas due to their property of tumor tropism. However, MSCs may show bidirectional and divergent effects on tumor growth. Therefore, a robust surveillance system with a capacity for noninvasive monitoring of the homing, distribution and fate of stem cells in vivo is highly desired for developing stem cell-based gene therapies for tumors. In this study, we used ferritin gene-based magnetic resonance imaging (MRI) to track the tumor tropism of MSCs in a rat orthotopic xenograft model of malignant glioma. MSCs were transduced with lentiviral vectors expressing ferritin heavy chain (FTH) and enhanced green fluorescent protein (eGFP). Intra-arterial, intravenous and intertumoral injections of these FTH transgenic MSCs (FTH-MSCs) were performed in rats bearing intracranial orthotopic C6 gliomas. The FTH-MSCs were detected as hypointense signals on T2- and T2*-weighted images on a 3.0 T clinical MRI. After intra-arterial injection, 17% of FTH-MSCs migrated toward the tumor and gradually diffused throughout the orthotopic glioma. This dynamic process could be tracked in vivo by MRI up to 10 days of follow-up, as confirmed by histology. Moreover, the tumor tropism of MSCs showed no appreciable impact on the progression of the tumor. These results suggest that FTH reporter gene-based MRI can be used to reliably track the tropism and fate of MSCs after their systemic transplantation in orthotopic gliomas. This real-time in vivo tracking system will facilitate the future development of stem cell-based therapies for malignant gliomas.
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Neoplasias Encefálicas/patología , Ferritinas/metabolismo , Genes Reporteros , Glioma/patología , Imagen por Resonancia Magnética/métodos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/patología , Animales , Apoptosis , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Proliferación Celular , Glioma/metabolismo , Glioma/terapia , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Masculino , Células Madre Mesenquimatosas/metabolismo , Ratas , Ratas Wistar , Tropismo , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND/AIMS: Acute pancreatitis contributes to high mortality in pancreatitis patients, and miRNAs play a vital role in the development of acute pancreatitis (AP), however, its precise biological role remains largely elusive. METHODS: To clarify the potential mechanisms of miRNAs in AP, we built mouse models of mild acute pancreatitis (MAP) and moderate/ severe acute pancreatitis (SAP). MiRNA microarray analysis and Real-time quantitative PCR (qRT-PCR) were used to analyze the expression of miRNA in MAP/SAP. TargetScan software, dual-luciferase gene reporter assays and Western blotting were used to assess the target genes of miR-155-5p in AP. RESULTS: miR-155-5p was significantly decreased in MAP/SAP mice compared to controls. In pancreatic acinar AR42J cells transfected with miR-155-5p mimic, the expression of Rela and Traf3 notably decreased in both the caerulein- and TLC-S-induced groups compared with the negative control (NC); however, the expression of Rela and Traf3 notably increased after transfection with miR-155-5p inhibitor. Combined analysis using the TargetScan software and dual-luciferase gene reporter assays indicated that Rela and Traf3 were both targeted by miR-155-5p. Meanwhile, the expression of Ptgs2 also decreased after transfection of the AR42J cells with miR-155-5p mimic. The opposite results were found when miR-155-5p inhibitor was transfected into the AR42J cells. In addition, we treated caerulein- and TLC-S-induced AR42J cells with the Rela inhibitor helenalin and found that the expression of Rela, Traf3 and Ptgs2 decreased compared with the NC, while the expression of miR-155-5p did not show any significant difference. Furthermore, we found that miR-155-5p was significantly down-regulated in pancreatitis patients. CONCLUSION: miR-155-5p inversely regulated AP development through the Rela/Traf3/Ptgs2 signaling pathway.
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Células Acinares/patología , MicroARNs/genética , Pancreatitis/genética , Factor 3 Asociado a Receptor de TNF/genética , Factor de Transcripción ReIA/genética , Células Acinares/metabolismo , Adulto , Anciano , Animales , Línea Celular , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Pancreatitis/patología , Ratas , TranscriptomaRESUMEN
Purpose To evaluate the diagnostic performance of quantitative parameters derived from dual-energy CT for the preoperative diagnosis of metastatic sentinel lymph nodes (SLNs) in participants with breast cancer. Materials and Methods For this prospective study, dual-phase contrast agent-enhanced CT was performed in female participants with breast cancer from June 2015 to December 2017. Quantitative dual-energy CT parameters and morphologic parameters were compared between metastatic and nonmetastatic SLNs. The quantitative parameters were fitted to univariable and multivariable logistic regression models. The diagnostic role of morphologic and quantitative parameters was analyzed by receiver operating characteristic curves and compared by using the McNemar test. Results This study included 193 female participants (mean age, 47.6 years ± 10.1; age range, 22-79 years). Quantitative dual-energy CT parameters including slope of the spectral Hounsfield unit curve (λHu) measured at both arterial and venous phases, normalized iodine concentration at both arterial and venous phase, and normalized effective atomic number at the venous phase were higher in metastatic than in nonmetastatic SLNs (P value range, ≤.001 to .031). Univariable and multivariable logistic regression analyses showed that venous phase λHu (in Hounsfield units per kiloelectron-volt) was the best single parameter for the detection of metastatic SLNs. The accuracy of the venous phase λHu for detecting metastatic SLNs was 90.5% on a per-lymph node basis and 87.0% on a per-patient basis. The accuracy and specificity at venous phase λHu was higher than their counterparts in the morphologic parameters (P < .001). Conclusion Dual-energy CT is a complementary means for the preoperative identification of sentinel lymph nodes metastases in participants with breast cancer. © RSNA, 2018 Online supplemental material is available for this article.
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Neoplasias de la Mama/patología , Ganglio Linfático Centinela/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Axila , Diagnóstico Diferencial , Estudios de Evaluación como Asunto , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
INTRODUCTION: The immune system plays a pivotal role in nerve injury. The aim of this study was to determine the role of multiparametric magnetic resonance imaging (MRI) in evaluation of the synergic effect of immunomodulation on nerve regeneration in neurotmesis. METHODS: Rats with sciatic nerve neurotmesis and surgical repair underwent serial multiparametric MR examinations over an 8-week period after subepineurial microinjection of lipopolysaccharide (LPS) and subsequent subcutaneous injection of FK506 or subepineurial microinjection of LPS or phosphate-buffered saline (PBS) alone. RESULTS: Nerves treated with immunomodulation showed more prominent regeneration than those treated with LPS or PBS alone and more rapid restoration toward normal T2, fractional anisotropy (FA), and radial diffusivity (RD) values than nerves injected with LPS or PBS. DISCUSSION: Nerves treated with immunomodulation exert synergic beneficial effects on nerve regeneration that can be predicted by T2 measurements and FA and RD values. Muscle Nerve 57: E38-E45, 2018.
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Inmunomodulación , Traumatismos de los Nervios Periféricos/inmunología , Traumatismos de los Nervios Periféricos/patología , Animales , Anisotropía , Imagen de Difusión Tensora , Procesamiento de Imagen Asistido por Computador , Inmunosupresores/farmacología , Lipopolisacáridos/farmacología , Imagen por Resonancia Magnética , Masculino , Regeneración Nerviosa/efectos de los fármacos , Traumatismos de los Nervios Periféricos/fisiopatología , Ratas , Ratas Sprague-Dawley , Recuperación de la Función , Nervio Ciático/lesiones , Nervio Ciático/fisiopatología , Tacrolimus/farmacologíaRESUMEN
INTRODUCTION: Macrophage recruitment is critical for nerve regeneration after an injury. The aim of this study was to investigate whether ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle-based MRI could be used to monitor the enhanced macrophage recruitment by Toll-like receptor 4 (TLR4) activation in nerve injury. METHODS: Rats received intraperitoneal injections of either lipopolysaccharide (LPS) or phosphate buffered saline (PBS) or no injection (controls) after a sciatic nerve crush injury. After intravenous injection of the USPIOs (LPS and PBS groups) or PBS (control group), MRI was performed and correlated with histological findings. RESULTS: LPS group showed more remarkable hypointense signals on T2*-weighted imaging and lower T2 values in the crushed nerves than PBS group. The hypointense signal areas were associated with an enhanced recruitment of iron-loaded macrophages to the injured nerves. DISCUSSION: USPIO-enhanced MRI can be used to monitor the enhanced macrophage recruitment by means of TLR4 signal pathway activation in nerve injury. Muscle Nerve, 2018.