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The pair-contact process with diffusion (PCPD), a generalized model of the ordinary pair-contact process (PCP) without diffusion, exhibits a continuous absorbing phase transition. Unlike the PCP, whose nature of phase transition is clearly classified into the directed percolation (DP) universality class, the model of PCPD has been controversially discussed since its infancy. To our best knowledge, there is so far no consensus on whether the phase transition of the PCPD falls into the unknown university classes or else conveys a new kind of non-equilibrium phase transition. In this paper, both unsupervised and supervised learning are employed to study the PCPD with scrutiny. Firstly, two unsupervised learning methods, principal component analysis (PCA) and autoencoder, are taken. Our results show that both methods can cluster the original configurations of the model and provide reasonable estimates of thresholds. Therefore, no matter whether the non-equilibrium lattice model is a random process of unitary (for instance the DP) or binary (for instance the PCP), or whether it contains the diffusion motion of particles, unsupervised learning can capture the essential, hidden information. Beyond that, supervised learning is also applied to learning the PCPD at different diffusion rates. We proposed a more accurate numerical method to determine the spatial correlation exponent [Formula: see text], which, to a large degree, avoids the uncertainty of data collapses through naked eyes.
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Aprendizaje Automático , Humanos , Difusión , Transición de Fase , Análisis de Componente PrincipalRESUMEN
The latest advances of statistical physics have shown remarkable performance of machine learning in identifying phase transitions. In this paper, we apply domain adversarial neural network (DANN) based on transfer learning to studying nonequilibrium and equilibrium phase transition models, which are percolation model and directed percolation (DP) model, respectively. With the DANN, only a small fraction of input configurations (two-dimensional images) needs to be labeled, which is automatically chosen, to capture the critical point. To learn the DP model, the method is refined by an iterative procedure in determining the critical point, which is a prerequisite for the data collapse in calculating the critical exponent ν_{â¥}. We then apply the DANN to a two-dimensional site percolation with configurations filtered to include only the largest cluster which may contain the information related to the order parameter. The DANN learning of both models yields reliable results which are comparable to the ones from Monte Carlo simulations. Our study also shows that the DANN can achieve quite high accuracy at much lower cost, compared to the supervised learning.
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Direct delivery of drugs into the nucleus is a promising nanotechnology therapy, since the nucleus is one of the most important organelles controlling cell proliferation and apoptosis. Here, we report a nucleus-targeting nanocarrier for nuclear drug delivery using a pH/enzyme dual sensitive strategy. The specific ligand PGM (PKKKRKV-GFLG-Mp), composed of nuclear localization sequence (PKKKRKV), enzyme-sensitive tetrapeptide (Gly-Phe-Leu-Gly, GFLG), and pH-sensitive molecules morpholine (Mp), was modified on poly (amidoamine) (PAMAM) by maleimide active polyethylene glycol ester (NHS-PEG-MAL) to form PAMAM-PEG-PGM. Doxorubicin (DOX) was loaded into the cavity of PAMAM to prepare DOX/PAMAM-PEG-PGM. In vitro release study suggested DOX release from DOX/PAMAM-PEG-PGM nanoparticles followed pH and enzyme-triggered manner. In vitro studies showed DOX/PAMAM-PEG-PGM nanoparticles could not only promote cell internalization through the charge switching of morpholine, but also achieve nuclear internalization by the mediation of composite formed by NLS and importin α/ß receptor. Further, employing H22 tumour-bearing BALB/c mice as a model, the systemic distribution and anticancer effects of nanoparticles were studied in vivo. The results indicated the nanoparticles could preferentially accumulate in the tumour site in vivo, and the tumour inhibition rate was 88.47%. In short, the nanoparticles developed could be promising in application to nucleus-targeting therapy to enhance antitumour activity.
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Dendrímeros , Nanopartículas , Animales , Línea Celular Tumoral , Dendrímeros/química , Doxorrubicina , Portadores de Fármacos/química , Concentración de Iones de Hidrógeno , Ratones , Morfolinas , Nanopartículas/química , Polietilenglicoles/químicaRESUMEN
Considering the insufficient understanding of pulmonary cryptococcosis (PC) with consolidation, 22 patients were evaluated based on the chest computed tomography (CT) images and clinical manifestation. The clinical symptoms were mild, mainly manifesting as cough and sputum. Pulmonary lesions mostly involved a single lobe in a single lung with multiple lesions. Specifically, single lung involvement was observed in 17 cases, single lobe in 16 cases and multiple lesions in 14 case. Fifteen cases were mainly distributed in the periphery and 17 cases in the long axis in parallel to the pleura. Nineteen cases had air bronchograms. Eight cases displayed cavitation inside the lesions and 18 cases had surrounding halo signs. Seventeen cases had pleural thickening, of which 10 cases had "pasting wall" signs. The clinical symptoms of PC with consolidation were relatively mild. Comprehensive clinical and imaging performance could improve the diagnosis of the disease.
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Criptococosis , Enfermedades Pulmonares Fúngicas , Criptococosis/diagnóstico por imagen , Humanos , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares Fúngicas/diagnóstico por imagen , Estudios Retrospectivos , Tórax , Tomografía Computarizada por Rayos XRESUMEN
Machine learning (ML) has been well applied to studying equilibrium phase transition models by accurately predicating critical thresholds and some critical exponents. Difficulty will be raised, however, for integrating ML into nonequilibrium phase transitions. The extra dimension in a given nonequilibrium system, namely time, can greatly slow down the procedure toward the steady state. In this paper we find that by using some simple techniques of ML, non-steady-state configurations of directed percolation (DP) suffice to capture its essential critical behaviors in both (1+1) and (2+1) dimensions. With the supervised learning method, the framework of our binary classification neural networks can identify the phase transition threshold, as well as the spatial and temporal correlation exponents. The characteristic time t_{c}, specifying the transition from active phases to absorbing ones, is also a major product of the learning. Moreover, we employ the convolutional autoencoder, an unsupervised learning technique, to extract dimensionality reduction representations and cluster configurations of (1+1) bond DP. It is quite appealing that such a method can yield a reasonable estimation of the critical point.
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In the present study, the three functions, including enhanced permeability and retention (EPR) effect, deep penetration within tumor, and receptor-mediated endocytosis, were integrated into a single platform in order to improve antitumor efficiency. A novel nanoparticle (dendrigraft poly-L-lysine@glycyrrhetinic acid@cyclohexane dicarboxylic anhydride@doxorubicin@ hyaluronic acid composite) has been successfully developed and was denoted as DGL-GA-CDA-DOX-HA. The transmission electron microscope (TEM), dynamic light scattering (DLS), polymer dispersity index (PDI), fourier transform infrared spectrometer (FTIR), and zeta potentials were used to characterize the physicochemical properties of the nanoparticles. According to the results of TEM and DLS, the DGL-GA-CDA-DOX-HA nanoparticles could be rapidly degraded with a size shrink from 182.5 nm to 47.7 nm by hyaluronidase (HAase) added in the medium. The loading amount of DOX reached 252.03 ± 36.38 mg/g for DGL-GA-CDA-DOX nanoparticles. When the nanoparticles were in a medium with HAase at pH 5.0, the drug quickly released. However, when the nanoparticles were exposed to a medium without HAase at pH 5.0, or a neutral medium containing HAase, drug release slowed down. The modification of GA on nanoparticles significantly enhanced their affinity and cytotoxicity to hepatocellular carcinoma HepG2 cells. The study showed that the penetrability of DGL-GA-CDA-DOX and DGL-GA-CDA DOX-HA nanoparticles pre-degraded by HAase in vitro multicellular tumor spheroids were always better than that of DGL-GA-CDA-DOX-HA nanoparticles untreated by HAase. The imaging in vivo and ex vivo exhibited that DGL-GA-CDA-DOX-HA nanoparticles could preferentially accumulate in the tumor site. Correspondingly, the DGL-GA-CDA-DOX-HA displayed the preferable antitumor efficiency to other experimental groups in H22 tumor-bearing mice, with a tumor inhibition rate of 71.6%. In short, these results suggested that DGL-GA-CDA-DOX-HA nanoparticles could promote therapeutic effects by modulating particle size and GA receptor-mediated endocytosis.
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Portadores de Fármacos , Ácido Glicirretínico , Nanopartículas , Neoplasias/tratamiento farmacológico , Animales , Doxorrubicina , Liberación de Fármacos , Ácido Hialurónico , Ratones , Proteína Quinasa C-alfaRESUMEN
Antisense oligodeoxynucleotide (ASODN) can directly interfere a series of biological events of the target RNA derived from tumor cells through Watson-Crick base pairing, in turn, plays antitumor therapeutic roles. In the study, a novel HIF-1α ASODN-loaded nanocomposite was formulated to efficiently deliver gene to the target RNA. The physicochemical properties of nanocomposite were characterized using TEM, FTIR, DLS and zeta potentials. The mean diameter of resulting GEL-DGL-FA-ASODN-DCA nanocomposite was about 170-192â¯nm, and according to the agarose gel retardation assay, the loading amount of ASODN accounted for 166.7â¯mg/g. The results of cellular uptake showed that the nanocomposite could specifically target to HepG2 and Hela cells. The cytotoxicity assay demonstrated that the toxicity of vectors was greatly reduced by using DCA to reversibly block the cationic DGL. The subcellular distribution images clearly displayed the lysosomal escape ability of the DCA-modified nanocomposite. In vitro exploration of molecular mechanism indicated that the nanocomposite could inhibit mRNA expression and HIF-1α protein translation at different levels. In vivo optical images and quantitative assay testified that the formulation accumulated preferentially in the tumor tissue. In vivo antitumor efficacy research confirmed that this nanocomposite had significant antitumor activity and the tumor inhibitory rate was 77.99%. These results manifested that the GEL-DGL-FA-ASODN-DCA nanocomposite was promising in gene therapeutics for antitumor by interacting directly with target RNA.
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Data on occupational radiation exposure of radiation workers at a tertiary hospital in China during 2013-18 were analyzed to provide decision-making advice for hospitals and health administrative departments. A total of 1255 exposure records of radiation workers were collected. The average annual effective doses of radiation workers during 2013-18 was 0.4977 mSv, with 1150 (91.63%) records ranging between 0 and 1 mSv, 91 (7.25%) between 1 and 2 mSv, 10 (0.80%) between 2 and 5 mSv and 4 (0.32%) records exceeding 5 mSv. There was a significant difference in the average annual effective dose of radiation workers among different occupational categories except in 2015 indicating that hospitals and administrative authorities should pay more attention to the radiation workers in the nuclear medicine and intervention department. The average annual effective doses did not show significant differences between male and female workers except in 2017; in that year the average individual dose of female workers was higher than male workers'. There were no significant differences in the average annual effective doses among doctors, nurses and radiologic technologists except in 2016 and 2017; during that period the individual dose of nurses was higher than doctors' and radiologic technologists'.
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Exposición Profesional , Exposición a la Radiación , Monitoreo de Radiación , China , Femenino , Humanos , Masculino , Exposición Profesional/análisis , Dosis de Radiación , Centros de Atención TerciariaRESUMEN
To investigate the characteristics of diffusion tensor imaging (DTI) of the central nervous system in children with Tourette syndrome (TS).Fifteen children with TS (TS group) and 15 normal children (control group) were studied, and all of them underwent DTI. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) parameters were calculated using the DTIStudio software. The region of interest was delineated manually. The ADC and FA values of the bilateral caudate nucleus, bilateral globus pallidus, bilateral putamen, bilateral thalamus, and bilateral frontal lobe white matter were measured using the region of interest editor software. The differences of FA values and ADC values between the same brain areas were compared. The associations between ADC, FA values and Yale Global Tic Severity Scale (YGTSS) scores were evaluated by Pearson correlation analyses.The FA values of left globus pallidus and left thalamus were significantly lower in the TS group than in the control group (Pâ<â.05), while the ADC values of the right caudate nucleus and bilateral thalamus were significantly higher in the TS group than in the control group (Pâ<â.05). The decrease in FA in the left thalamus significantly correlated with the YGTSS score (râ=â0.692; Pâ<â.05). No correlation was found between FA and ADC values in other brain regions and the YGTSS score (Pâ>â.05).After the DTI analyses, abnormalities were found in the left globus pallidus, right caudate nucleus, and bilateral thalamus in children with TS. Especially the changes in the left thalamus structure was crucial in the pathophysiological clock of TS.
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Sistema Nervioso Central/diagnóstico por imagen , Sistema Nervioso Central/fisiopatología , Imagen de Difusión Tensora/métodos , Síndrome de Tourette/diagnóstico por imagen , Síndrome de Tourette/fisiopatología , Anisotropía , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
An enzyme-free, metal-free, and preconcentration-free electrochemical sensor for pentachlorophenol assay has been fabricated. The interface of the sensor is based on a hollow zeolitic imidazolate framework-derived mesoporous carbon material (denoted as HZC/SPCE). The sensor exhibits linear amperometric response upon pentachlorophenol at 0.82 V (vs. Ag/AgCl) in the concentration range 0.001 to 26.8 mg L-1 (3.75 × 10-8~1.006 × 10-4 M) (R2 = 0.997). The sensitivity of HZC/SPCE is 3.53 × 102 µA mM-1 cm-2 with a detection limit of 2.05 × 10-9 M (S/N = 3) for pentachlorophenol. The method has been applied to the determination of pentachlorophenol in spiked food packaging samples with recoveries in the range 92.0 to 107.0%. Graphical abstract Schematic representation of the synthesis of hollow ZIFs-derived hollow carbon material. Free protons derived from tannic acid penetrated into ZIF-8 to destroy its solid framework and the outer parts covered by tannic acid were protected from further etching. After pyrolysis, the morphology of HZC remained similar to that of HZIF-8. Abbreviation: CTAB: hexadecyl trimethyl ammonium bromide; Melm: 2-methylimidazole; ZIF-8: zeolitic imidazolate framework-8; TA: tannic acid; HZIF-8: hollow zeolitic imidazolate framework-8; HZC: hollow zeolitic imidazolate frameworks (ZIFs)-derived mesoporous carbon material.
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Técnicas Biosensibles , Carbono/química , Técnicas Electroquímicas , Contaminación de Alimentos/análisis , Pentaclorofenol/análisis , Zeolitas/química , Electrodos , Embalaje de Alimentos , Tamaño de la Partícula , Porosidad , Propiedades de SuperficieRESUMEN
Herein, a smart pH-sensitive nanoparticle (DGL-PEG-Tat-KK-DMA-DOX) was prepared to achieve the selective intracellular drug delivery. In this nanoparticle, a PEG-grafted cell penetrating peptide (PEG-Tat-KK) was designed and acted as the cell penetrating segment. By introducing the pH-sensitive amide bonds between the peptide and blocking agent (2,3-dimethylmaleic anhydride, DMA), the controllable moiety (PEG-Tat-KK-DMA) endowed the nanoparticle with a charge-switchable shell and temporarily blocked penetrating function, thus improving the specific internalization. Besides, dendrigraft poly-L-lysine (DGL) used as the skeleton can greatly improve the drug loading because of the highly dendritic framework. Under the stimuli of acidic pH, this nanoparticle exhibited a remarkable charge-switchable property. The drug release showed an expected behavior with little release in the neutral pH media but relatively fast release in the acidic media. The in vitro experiments revealed that the cellular uptake and cytotoxicity were significantly enhanced after the pH was decreased. In vivo biodistribution and antitumor research indicated that the nanoparticle had noteworthy specificity and antitumor efficacy with a tumor inhibition rate of 79.7%. These results verified this nanoparticle could efficiently improve the selective intracellular delivery and possessed a great potential in tumor treatment.
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Antibióticos Antineoplásicos/administración & dosificación , Péptidos de Penetración Celular/metabolismo , Doxorrubicina/administración & dosificación , Portadores de Fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Anhídridos Maleicos/química , Nanopartículas , Fragmentos de Péptidos/metabolismo , Polietilenglicoles/química , Polilisina/química , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/metabolismo , Animales , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Péptidos de Penetración Celular/química , Relación Dosis-Respuesta a Droga , Doxorrubicina/química , Doxorrubicina/farmacocinética , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Células Hep G2 , Humanos , Concentración de Iones de Hidrógeno , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Ratones , Nanotecnología , Fragmentos de Péptidos/química , Tecnología Farmacéutica/métodos , Distribución Tisular , Carga Tumoral/efectos de los fármacos , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/químicaRESUMEN
OBJECTIVE: The purpose of the study was to evaluate the value of high-resolution three-dimensional fast low angle shot (3D-FLASH) and three-dimensional constructive interference in steady-state (3D-CISS) MRI sequence solely or the combination of both in the visualization of neurovascular relationship in patients with trigeminal neuralgia (TN). METHODS: 65 patients with unilateral TN underwent 3D-FLASH and 3D-CISS imaging were retrospectively studied. Neurovascular relationship at the intracisternal segment of trigeminal nerve was reviewed by two experienced neuroradiologist, who was blinded to the clinical details. The imaging results were compared with the operative findings in all patients. RESULTS: The accuracy and positive rates of the 3D-FLASH + CISS imaging (98.46, 92.31%) in judging the symptomatic side according to the presence of vascular contacts were higher than those of 3D-CISS (90.77%, 84.62) or 3D-FLASH (89.23, 83.08%) sequence. In addition, the statistical analysis showed the sensitivity and accuracy of 3D-FLASH + CISS imaging was higher than that of 3D-FLASH (p < 0.05). The 3D-FLASH + CISS imaging was more accurate in determining the type of offending vessel than 3D-CISS or 3D-FLASH imaging. CONCLUSION: The retrospective study demonstrates that the combination of 3D-FLASH with 3D-CISS sequence well delineates the relationship between intracisternal segment of trigeminal nerve and adjacent vessels in terms of increased positive rates and accuracy. Advances in knowledge: The study firstly dealt with the combination of 3D-CISS and 3D-FLASH imaging in TN.
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Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Cuidados Preoperatorios/métodos , Nervio Trigémino/irrigación sanguínea , Neuralgia del Trigémino/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Nervio Trigémino/diagnóstico por imagen , Nervio Trigémino/fisiopatología , Neuralgia del Trigémino/fisiopatologíaRESUMEN
A novel nanoscale molecular probe is formulated in order to reduce toxicity and side effects of antitumor drug doxorubicin (DOX) in normal tissues and to enhance the detection sensitivity during early imaging diagnosis. The mechanism involves a specific targeting of Arg-Gly-Asp peptide (RGD)-GX1 heterogeneous dimer peptide-conjugated dendrigraft poly-l-lysine (DGL)-magnetic nanoparticle (MNP) composite by αvß3-integrin/vasculature endothelium receptor-mediated synergetic effect. The physicochemical properties of the nanoprobe were characterized by using transmission electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction, dynamic light scattering (DLS), and vibrating sample magnetometer. The average diameter of the resulting MNP-DGL-RGD-GX1-DOX nanoparticles (NPs) was ~150-160 nm by DLS under simulate physiological medium. In the present experimental system, the loading amount of DOX on NPs accounted for 414.4 mg/g for MNP-DGL-RGD-GX1-DOX. The results of cytotoxicity, flow cytometry, and cellular uptake consistently indicated that the MNP-DGL-RGD-GX1-DOX NPs were inclined to target HepG2 cells in selected three kinds of cells. In vitro exploration of molecular mechanism revealed that cell apoptosis was associated with the overexpression of Fas protein and the significant activation of caspase-3. In vivo magnetic resonance imaging and biodistribution study showed that the MNP-DGL-RGD-GX1-DOX formulation had high affinity to the tumor tissue, leading to more aggregation of NPs in the tumor. In vivo antitumor efficacy research verified that MNP-DGL-RGD-GX1-DOX NPs possessed significant antitumor activity and the tumor inhibitory rate reached 78.5%. These results suggested that NPs could be promising in application to early diagnosis and therapy in hepatocellular carcinoma as a specific nanoprobe.
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Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamiento farmacológico , Dendrímeros/química , Diagnóstico Precoz , Neoplasias Hepáticas/tratamiento farmacológico , Nanopartículas de Magnetita/química , Sondas Moleculares/química , Péptidos/química , Polilisina/química , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Liberación de Fármacos , Citometría de Flujo , Células Hep G2 , Humanos , Neoplasias Hepáticas/diagnóstico , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/ultraestructura , Masculino , Ratones Endogámicos BALB C , Espectroscopía Infrarroja por Transformada de Fourier , Distribución Tisular/efectos de los fármacos , Receptor fas/metabolismoRESUMEN
Doped ZnS quantum dots (QDs) have a longer dopant emission lifetime and potentially lower cytotoxicity compared to other doped QDs. The liver is the key organ for clearance and detoxification of xenobiotics by phagocytosis and metabolism. The present study was designed to synthesize and evaluate the hepatotoxicity of Mn-doped ZnS QDs and their polyethylene glycol-coated counterparts (1 mg/kg and 5 mg/kg) in mice. The results demonstrated that daily injection of Mn-doped ZnS QDs and polyethylene glycol-coated QDs via tail vein for 7 days did not influence body weight, relative liver weight, serum aminotransferases (alanine aminotransferase and aspartate aminotransferase), the levels of antioxidant enzymes (catalase, glutathione peroxidase, and superoxide dismutase), or malondialdehyde in the liver. Analysis of hepatocyte ultrastructure showed that Mn-doped ZnS QDs and polyethylene glycol-coated QDs mainly accumulated in mitochondria at 24 hours after repeated intravenous injection. No damage to cell nuclei or mitochondria was observed with either of the QDs. Our results indicate that Mn-doped ZnS QDs did not cause obvious damage to the liver. This study will assist in the development of Mn-doped ZnS QDs-based bioimaging and biomedical applications in the future.
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Fosfatidiletanolaminas/administración & dosificación , Fosfatidiletanolaminas/toxicidad , Compuestos de Zinc/administración & dosificación , Compuestos de Zinc/toxicidad , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Peso Corporal/efectos de los fármacos , Catalasa/metabolismo , Materiales Biocompatibles Revestidos/química , Relación Dosis-Respuesta a Droga , Glutatión Peroxidasa/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Tamaño de los Órganos/efectos de los fármacos , Polietilenglicoles/química , Puntos Cuánticos , Superóxido Dismutasa/metabolismoRESUMEN
The aim of this study was to evaluate the significance of using multi-row spiral computed tomography (CT) to scan for pulmonary artery thrombosis and lower limb deep vein thrombosis (LVT) in patients with suspected LVT. A total of 110 patients underwent a contrast-enhanced spiral CT inspection of the pulmonary artery and lower extremity veins. Three-dimensional digital image processing, including multi-planar reconstruction (MPR), maximum intensity projection (MIP) and volume rendering (VR), was also conducted; two groups of experienced radiologists analyzed the CT images to evaluate the postprocessing techniques of these CT images. Seventy-five patients were diagnosed with LVT with or without pulmonary embolism (PE); out of these 75, 34 patients were diagnosed with PE and LVT together and 41 patients were diagnosed with LVT alone. A further 31 patients were diagnosed with iliac vein compression syndrome (IVCS), and no embolisms were detected in the remaining four patients. With regard to PE, MPR and MIP demonstrated an accuracy of 100%, while MPR also showed images of LVT with an accuracy of 100%. The follow-up results at 12 months were consistent with the CT scan results. The clinical use of 128-slice spiral CT combination scanning in the detection of PE and LVT has significant potential to improve upon the present methods of diagnosis.
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In the present study, ZnS and ZnO quantum dots (QDs) were synthesized via an all-aqueous process with polyethylene glycol (PEG) chains on their surface, and their toxicity as well as biodistribution were evaluated. No haemolysis occurred at a high concentration of 1600 µg/mL in vitro haemolytic assay, which demonstrated that the QDs-PEG displayed good blood compatibility. Following intravenous administration at 2, 6, and 20 mg/kg of the QDs-PEG in mice, the biodistribution, excretion and biocompatibility were characterized at 1 h, 24 h and 7 days, respectively. Quantitative analysis results indicated that the biodistribution trend of ZnS QDs-PEG was similar to that of ZnO QDs-PEG. The QDs-PEG were mainly trapped in the lung and liver, and almost removed from blood within 1 h. QDs-PEG were primarily excreted in faeces at the 2 and 6 mg/kg doses. Coefficients, haematology, blood biochemistry and histopathology results indicated that the QDs-PEG were safe and biocompatible.
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Puntos Cuánticos/toxicidad , Sulfuros/farmacocinética , Sulfuros/toxicidad , Compuestos de Zinc/farmacocinética , Compuestos de Zinc/toxicidad , Óxido de Zinc/farmacocinética , Óxido de Zinc/toxicidad , Animales , Eritrocitos , Hemólisis/efectos de los fármacos , Histocitoquímica , Humanos , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Ratones , Polietilenglicoles , Puntos Cuánticos/administración & dosificación , Puntos Cuánticos/química , Bazo/efectos de los fármacos , Bazo/patología , Sulfuros/administración & dosificación , Sulfuros/química , Distribución Tisular , Compuestos de Zinc/administración & dosificación , Compuestos de Zinc/química , Óxido de Zinc/administración & dosificación , Óxido de Zinc/químicaRESUMEN
We develop paclitaxel (PTX) and magnetic nanoparticles (MNPs) coencapsulated, surface charge-switchable, thermosensitive poly(d,l-lactic-co-glycolic acid)-l-lysine-d-galactose (PTX-MNP-PLGA-Lys-Gal) NPs for the controlled release of the anticancer drug. The novel dual signal-responsive nanovehicle is formulated to shield off target at pH 7.4 but bind avidly to tumor cells in acidity, alleviating toxicity and side effects of the drug to normal tissues. The mechanism involves pH-sensitive NPs surface charge switching by the deblocking process of galactose molecules followed by protonation of ε-NH2 in lysine residue at acidic pH. Magnetic hyperthermia under near infrared (NIR) irradiation induced the contraction of PTX-MNP-PLGA-Lys-Gal NPs and, in turn, triggered burst release of PTX. Transmission electron microscopy (TEM), fluorescence microscope analyses, Fourier transform infrared (FTIR), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), dynamic light scattering (DLS), and ξ-potential analyses were performed to characterize physicochemical properties of the as-prepared NPs. The size range of the globule PTX-MNP-PLGA-Lys-Gal NPs after being prescreened was from 130 to 150 nm under simulated physiological medium. The high encapsulation efficiencies of MNPs and PTX were obtained, reaching 85 and 78 wt % for PTX-MNP-PLGA-Lys-Gal NPs, respectively. The tumor inhibitory rate of 78.8% reflected that the resulting NPs could be promising to treat cancer by specific binding and targeting release drug to tumor.
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Antineoplásicos/farmacología , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Paclitaxel/administración & dosificación , Línea Celular Tumoral , Química Física/métodos , Eritrocitos/citología , Calor , Humanos , Concentración de Iones de Hidrógeno , Lisina/química , Magnetismo , Nanopartículas del Metal/química , Microscopía Electrónica de Transmisión/métodos , Ácido Oléico/química , Polímeros/química , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Espectroscopía Infrarroja Corta/métodos , Propiedades de Superficie , Difracción de Rayos XRESUMEN
Focused metabolic profiling is a powerful tool for the determination of biomarkers. Here, a more global proton nuclear magnetic resonance ((1)H NMR)-based metabolomic approach coupled with a relative simple ultra high performance liquid chromatography (UHPLC)-based focused metabolomic approach was developed and compared to characterize the systemic metabolic disturbances underlying esophageal cancer (EC) and identify possible early biomarkers for clinical prognosis. Serum metabolic profiling of patients with EC (n=25) and healthy controls (n=25) was performed by using both (1)H NMR and UHPLC, and metabolite identification was achieved by multivariate statistical analysis. Using orthogonal projection to least squares discriminant analysis (OPLS-DA), we could distinguish EC patients from healthy controls. The predictive power of the model derived from the UHPLC-based focused metabolomics performed better in both sensitivity and specificity than the results from the NMR-based metabolomics, suggesting that the focused metabolomic technique may be of advantage in the future for the determination of biomarkers. Moreover, focused metabolic profiling is highly simple, accurate and specific, and should prove equally valuable in metabolomic research applications. A total of nineteen significantly altered metabolites were identified as the potential disease associated biomarkers. Significant changes in lipid metabolism, amino acid metabolism, glycolysis, ketogenesis, tricarboxylic acid (TCA) cycle and energy metabolism were observed in EC patients compared with the healthy controls. These results demonstrated that metabolic profiling of serum could be useful as a screening tool for early EC diagnosis and prognosis, and might enhance our understanding of the mechanisms involved in the tumor progression.
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Neoplasias Esofágicas/sangre , Suero/metabolismo , Aminoácidos/metabolismo , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/metabolismo , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión/métodos , Metabolismo Energético , Neoplasias Esofágicas/metabolismo , Femenino , Glucólisis/fisiología , Humanos , Metabolismo de los Lípidos , Masculino , Metaboloma , Metabolómica/métodos , Persona de Mediana Edad , Análisis Multivariante , Resonancia Magnética Nuclear Biomolecular/métodos , Pronóstico , Ácidos Tricarboxílicos/metabolismoRESUMEN
Arthus reaction (AR), a type of unconventional immune complex-mediated inflammation, is likely accompanied by alterations in circulating metabolites. Here, a proton nuclear magnetic resonance ((1)H NMR) spectroscopy method coupled with a rapid resolution liquid chromatography (RRLC) method was developed to evaluate the systemic metabolic consequences of AR and characterize metabolic aberrations. Serum and urine samples from AR rats and normal controls were compared to determine whether there were significant alterations associated with AR. The partial least squares discriminant analysis (PLS-DA) models of metabolomic results demonstrated good intergroup separations between AR rats and normal controls. Multivariate statistical analysis revealed significant alterations in the levels of 34 metabolites, which were termed as the disease-associated biomarkers. Differential metabolites identified from the metabolomic analysis suggested that AR caused dysfunctions of kidney and liver accompanied with changes in widespread metabolic pathways including the tricarboxylic acid (TCA) cycle, gut microbiota metabolism, lipids and cell membranes metabolism, glucose metabolism, fatty acid ß-oxidation, amino acids metabolism and ketogenesis. This study assessed and provided important metabolomic variations in serum and urine associated with AR and, therefore, demonstrated metabolomics as a powerful approach for the complete elucidation of the underlying pathophysiologic mechanisms of AR.
Asunto(s)
Reacción de Arthus/metabolismo , Biomarcadores/análisis , Inflamación/metabolismo , Metaboloma , Aminoácidos/sangre , Animales , Reacción de Arthus/inducido químicamente , Biomarcadores/sangre , Biomarcadores/orina , Proteínas Sanguíneas/análisis , Cromatografía Liquida , Adyuvante de Freund , Perfilación de la Expresión Génica , Glicoproteínas/sangre , Inflamación/inducido químicamente , Lípidos/sangre , Metabolómica , Resonancia Magnética Nuclear Biomolecular , Análisis de Componente Principal , Ratas , Albúmina Sérica BovinaRESUMEN
In this paper we give a method of integrated treatment for cancer and drug-induced complications in the process of cancer therapy through dual-drug delivery system (DDDS). Two hydrophilic drugs, doxorubicin (an antitumor drug) and verapamil (an antiangiocardiopathy drug) combined preliminarily with chitosan shell coated on magnetic nanoparticles (MNPs), followed by entrapping into the PLGA nanoparticles. Further modification was conducted by conjugating tumor-targeting ligand, cyclo(Arg-Gly-Asp-D-Phe-Lys) (c(RGDfK)) peptide, onto the end carboxyl groups on the PLGA-NPs. The size of the resulting cRGD-DOX/VER-MNP-PLGA NPs was approximately 144nm under simulate physiological environment. Under present experiment condition, the entrapment efficiencies of DOX and VER were approximately 74.8 and 53.2wt% for cRGD-DOX/VER-MNP-PLGA NPs. This paper contains interesting pilot data such as NIR-triggered drug release, in vivo drug distribution studies and whole-mouse optical imaging. Histopathological examinations and electrocardiogram comparison demonstrated that the intelligent DDDS could markedly inhibit the growth of tumor and potentially offer an approach for safe cancer therapy.