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Congenital disorders of glycosylation (CDG) are a group of genetic, mostly multisystem disorders, which often involve the central nervous system. ALG3-CDG is one the some 130 known CDG. Here we report two siblings with a severe phenotype and intrauterine death. Whole-exome sequencing revealed two novel variants in ALG3: NM_005787.6:c.512G>T (p.Arg171Leu) inherited from the mother and NM_005787.6:c.511C>T (p.Arg171Trp) inherited from the father.
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Sistema Nervoso Central/metabolismo , Defeitos Congênitos da Glicosilação/genética , Genes Letais/genética , Manosiltransferases/genética , Feto Abortado/patologia , Sistema Nervoso Central/patologia , Defeitos Congênitos da Glicosilação/metabolismo , Defeitos Congênitos da Glicosilação/patologia , Feminino , Humanos , Masculino , Mães , Mutação/genética , Fenótipo , Irmãos , Sequenciamento do ExomaRESUMO
PURPOSE: To evaluate conventional ultrasonography (US), US elasticity imaging (EI), and acoustic radiation force impulse (ARFI) imaging in thyroid nodule malignancy prediction. MATERIALS AND METHODS: This prospective study was institutional review board approved; informed consent was obtained. Study included 375 patients (mean age, 51 years; range, 18-75 years) with 441 pathologically proven thyroid nodules. In 281 women (mean age, 50 years; range, 18-75 years) and 94 men (mean age, 53 years; range, 18-74 years), conventional US, EI, Virtual Touch tissue imaging (VTi; Siemens, Mountain View, Calif), and Virtual Touch tissue quantification (VTq; Siemens) of ARFI imaging were performed for each nodule. Multivariate logistic regression analysis was performed to assess 17 independent variables for malignancy prediction. Diagnostic performance was evaluated with receiver operating characteristic (ROC) curve analysis. RESULTS: There were 325 benign and 116 malignant nodules. Marked hypoechogenicity (odds ratio [OR]: 83.88; 95% confidence interval [CI]: 17.81, 394.99) was the strongest independent predictor for thyroid malignancy, followed by shape taller than wide (OR: 8.69; 95% CI: 2.87, 26.31), VTi (OR: 6.54; 95% CI: 3.61, 11.88), moderate hypoechogenicity (OR: 3.98; 95% CI: 1.13, 14.05), poorly defined margin (OR: 3.27; 95% CI: 1.22, 8.77), female sex (OR: 2.55; 95% CI: 1.33, 4.91), coarse background of surrounding thyroid tissue (OR: 2.01; 95% CI: 1.12, 3.62), and VTq (OR: 1.78; 95% CI: 1.28, 2.47) (all P < .05). EI was not significantly associated with thyroid malignancy (P = .855). Area under the ROC curve (Az) for VTq and VTi was higher than that with other significant independent variables. Az, sensitivity, and specificity were 0.91 (95% CI: 0.87, 0.94) and 0.86 (95% CI: 0.82, 0.90), 80% and 71.6%, and 93.8% and 83.4%, respectively, for VTi and VTq. VTq of at least 2.87 m/sec and VTi of at least grade IV were the best cutoff values for malignant thyroid nodules. CONCLUSION: ARFI imaging is promising for malignant thyroid nodule prediction, with higher diagnostic performance than conventional US or EI. ARFI can be used to supplement conventional US to diagnose thyroid nodules in patients referred for surgery.
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Técnicas de Imagem por Elasticidade , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem , Adolescente , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologiaRESUMO
A novel multifunctional nanotheranostic agent with targeting, redox-responsive ultrasound imaging and ultrasound imaging-guided high-intensity focused ultrasound (HIFU) therapy (MSNC-PEG-HA(SS)-PFH, abbreviated as MPH(SS)-PFH) capabilities is developed. The redox-responsive guest molecule release and ultrasound imaging functions can be both integrated in such a "smart" theranostic agent, which is accomplished by the redox-triggered transition from the crosslinking state to retrocrosslinking state of the grafted polyethylene glycol-disulfide hyaluronic acid molecules on the particle surface when reaching a reducing environment in vitro. More importantly, under the tailored ultrasound imaging guiding, in vivo Hela tumor-bearing nude mice can be thoroughly and spatial-accurately ablated during HIFU therapy, due to the targeted accumulation, responsive ultrasound imaging guidance and the synergistic ablation functions of nanotheranostic agent MPH(SS)-PFH in the tumors. This novel multifunctional nano-platform can serve as a promising candidate for further studies on oncology therapy, due to its high stability, responsive and indicative ultrasound imaging of tumors, and enhanced HIFU therapeutic efficiency and spatial accuracy under ultrasound-guidance.
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Diagnóstico por Imagem , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Polímeros/uso terapêutico , Adsorção , Animais , Células HeLa , Células Hep G2 , Humanos , Camundongos Nus , Nanocápsulas/química , Nanocápsulas/ultraestrutura , Oxirredução , Polímeros/síntese química , Polímeros/química , Porosidade , Dióxido de Silício/química , TemperaturaRESUMO
The pulsed optically pumped (POP) atomic clock has demonstrated unexpected performance in terms of frequency stability and drift. However, it remains a huge challenge to make this type of atomic clock more compact. Herein, we report the design of a miniaturized physics package, which is equipped with a magnetron microwave cavity holding a vapor cell of 1.3 cm internal diameter. The Zeeman transition spectrum reveals that the microwave cavity resonates in TE011-like mode. Based on a low-noise testbed, we also quantitatively analyze the relaxation time, linewidth, and noise sources of the resulting POP atomic clock. The population and coherence relaxation time are measured to be 3.16(0.16) and 2.97(0.03) ms under the temperature of 333 K, which are compatible well with the theoretical calculation. The Ramsey signal shows a contrast of 35% and a linewidth of 192 Hz. The total volume of the physics package is about 44 cm3, including a layer of magnetic shielding. The short-term frequency stability is measured to be 4.8 × 10-13τ-1/2 (where τ is the averaging time), which is mainly limited by the relative intensity noise of the laser system.
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ETHNOPHARMACOLOGICAL RELEVANCE: The Gu Yan Xiao tincture, a blend of traditional Chinese herbs, is traditionally used for osteoarthritis and related pain. This study investigated its mechanism of action in order to rationalize and validate its therapeutic use. AIM OF THE STUDY: This study analyzed, in a rabbit model of knee osteoarthritis, whether and how Gu Yan Xiao tincture exerts therapeutic benefits by modulating chondrocyte autophagy. MATERIALS AND METHODS: The active constituents within the GYX tincture were identified using liquid chromatography-mass spectrometry. The rabbit model was established by injecting animals with type II collagenase intra-articularly, and the effects of topically applied tincture were examined on osteoarthritis lesions of the knee using histopathology, micro-computed tomography and x-ray imaging. Effects of the tincture were also evaluated on levels of inflammatory cytokines, matrix metalloproteases, and autophagy in chondrocytes. As a positive control, animals were treated with sodium diclofenac. RESULTS: The tincture mitigated the reduction in joint space, hyperplasia of the synovium and matrix metalloproteases in serum that occurred after injection of type II collagenase in rabbits. These therapeutic effects were associated with inhibition of mTOR and activation of autophagy in articular chondrocytes. Inhibiting mTOR with rapamycin potentiated the therapeutic effects of the tincture, while inhibiting autophagy with 3-methyladenine antagonized them. CONCLUSIONS: Gu Yan Xiao tincture mitigates tissue injury in a rabbit model of osteoarthritis, at least in part by inhibiting mTOR and thereby promoting autophagy in chondrocytes. These results rationalize the use of the tincture not only against osteoarthritis but also potentially other diseases involving inhibition of autophagy in bones and joints.
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Cartilagem Articular , Osteoartrite do Joelho , Animais , Coelhos , Condrócitos , Microtomografia por Raio-X , Serina-Treonina Quinases TOR , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/patologia , Metaloproteases/farmacologia , Metaloproteases/uso terapêutico , Autofagia , ColagenasesAssuntos
Acro-Osteólise/genética , Deformidades Congênitas dos Membros/genética , Mutação , Progéria/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Acro-Osteólise/diagnóstico , Adolescente , Biópsia , Análise Mutacional de DNA , Predisposição Genética para Doença , Humanos , Deformidades Congênitas dos Membros/diagnóstico , Masculino , Fenótipo , Progéria/diagnósticoRESUMO
BACKGROUND: Radiofrequency ablation (RFA) is a widely applied treatment for hepatocellular carcinoma (HCC), but insufficient RFA can promote rapid progression of the residual tumor through the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA) pathway. Although sorafenib has been successfully applied to advanced HCC, the use of sorafenib in residual tumor cells after RFA has rarely been tested. PURPOSE: To evaluate the potential role of sorafenib as an adjunct to RFA to reduce the recurrence rate after insufficient RFA. MATERIAL AND METHODS: Xenograft tumors of SMMC 7721 were created by subcutaneously inoculating nude mice with hepatoma cells (5 × 10(6) cells per mouse). Fourteen days after inoculation, all mice were divided into three groups (control group [sham puncture], RFA group, and RFA combined with sorafenib treatment group) with six mice in each group. Each group was given a different treatment procedure. After treatment, the volume of the tumors was calculated from the resected specimens. The mRNA and protein expression of HIF-1α and VEGFA was quantified by real-time PCR and immunohistochemistry analysis. The micro-vessel density (MVD) was determined by CD34 immunohistochemistry. RESULTS: Real-time PCR and immunohistochemistry analysis showed that, compared to the RFA group, HIF-1α and VEGFA expression were significantly decreased in the group that received RFA combined with sorafenib treatment (P < 0.05). By comparing the control group with the RFA group, we found that insufï¬cient RFA promoted HIF-1α and VEGFA expression (P < 0.05). Similar results were obtained for MVD expression. Additionally, the combination of RFA with sorafenib therapy resulted in a synergistic reduction in tumor growth compared to insufficient RFA and sham puncture (P < 0.05). CONCLUSION: Sorafenib was able to inhibit the expression of HIF-1α and VEGFA, and sorafenib was able to increase time to recurrence when used as an adjunct to RFA.
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Antineoplásicos/uso terapêutico , Ablação por Cateter , Neoplasias Hepáticas Experimentais/cirurgia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Animais , Terapia Combinada , Progressão da Doença , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Neovascularização Patológica/patologia , Niacinamida/uso terapêutico , Reação em Cadeia da Polimerase em Tempo Real , Sorafenibe , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The purpose of this study was to distinguish passive retention of microbubbles in liver sinusoids from active intracellular retaining, and to provide further evidence of post vascular liver specific phase of perflubutane microbubble contrast-enhanced ultrasound for potential use in the detection of focal liver lesions. Fifty-four rats were divided into three groups: saline group (G1, as a control, n=6), sulphur hexafluoride microbubble group (G2, n=24) and perflubutane microbubble group (G3, n=24). The livers were perfused at 2, 5, 10 and 20 min after injection of perflubutane or sulphur hexafluoride gas-filled microbubbles or normal saline. Changes in contrast-enhanced images within the liver were quantified. After perfusion, the echogenicity of the liver in the saline group increased from -49.44 ± 0.08 dB to - 44.37 ± 1.02 dB (p< 0.05). In G2, the enhancement decreased significantly after perfusion at 2 and 5 min, and increased at 10 and 20 min (all p< 0.05). In G3, the enhancement decreased from -18.05 ± 2.28 dB to - 26.76 ± 1.69 dB only at 2 min after perfusion (p < 0.05). Perflubutane microbubbles provided a post vascular liver specific phase on contrast-enhanced ultrasound, which could begin as early as 5 min after administration of the contrast agent in rats. This study suggests that perflubutane microbubbles could result in a liver specific phase and provide valuable information for diagnosis and detection of focal liver lesions which may improve the efficiency of contrast-enhanced ultrasound in clinical diagnoses of liver diseases.
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Fluorocarbonos/química , Aumento da Imagem/métodos , Fígado/química , Microbolhas , Imagem de Perfusão/métodos , Animais , Meios de Contraste/administração & dosagem , Meios de Contraste/química , Fluorocarbonos/administração & dosagem , Fígado/cirurgia , Masculino , Ratos , Ratos WistarRESUMO
The cement and asphalt mortar (CA mortar) used in the China Railway Track System (CRTS) I ballastless slab track may encounter a coupling fatigue effect under the high-frequency vibration, load and high-and-low temperature cycles, and the deterioration under fatigue may happen during service of the high-speed railway. In this study, the performance degradation and its mechanism of the CA mortar with and without polymer emulsion incorporated under the coupling fatigue effects of the high-frequency vibration, load and temperature were studied by using an anti-fatigue testing device specially developed for the CA mortar used in the ballastless slab track of the high-speed railway. The results showed that the deformation capacity of the CA mortar for CRTS I slab ballastless slab track decreased after fatigue test under simulated service environment, presenting a typical brittle characteristic and an obvious reduction of the ductility and toughness. The Scanning Electron Microscopy (SEM) observation and the mercury intrusion porosimetry (MIP) analysis showed that the volume of the macropore decreased whereas that of the micropore increased after the fatigue test. The asphalt in the hardened CA mortar revealed a softening and migration from the bulk paste to fill the pore and make the structure denser and even ooze out of the CA mortar under the high-frequency vibration and high temperature. Through incorporating the polymer emulsion, the anti-fatigue property of the CA mortar was obviously improved, which can prevent the CA mortar from losing its elastic adjustment function too early. Though increase of the strength and elastic modulus for the CA mortar after severe service is beneficial to the stability of train running, the comfort level and safety of the train operation may decline due to the gradual reduction of the ductility & toughness and the gradual loss of the elastic damping adjustment function of the CA mortar between the base concrete slab and the track slab.
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Henoch-Schönlein purpura (HSP) with involvement of the testes is extremely rare. Here, we present a pediatric case of HSP involving testicular ischemic necrosis in an 8-year-old child. Ultrasonography plays an important role not only in the differential diagnosis at onset, but also in the assessment of treatment response and prognosis during treatment and at follow-up. In this case report, we present the sonographic images for the entire course of testicular involvement in HSP and reveal histopathologically the pathogeny as testicular autoimmune vasculitis caused by the deposition of immunoglobulin A-containing immune complexes in the testicular vessels.
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Vasculite por IgA/complicações , Metilprednisolona/administração & dosagem , Doenças Testiculares/diagnóstico , Testículo/diagnóstico por imagem , Ultrassonografia Doppler em Cores/métodos , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Biópsia , Criança , Diagnóstico Diferencial , Relação Dose-Resposta a Droga , Seguimentos , Glucocorticoides/administração & dosagem , Humanos , Vasculite por IgA/diagnóstico , Vasculite por IgA/terapia , Masculino , Necrose/diagnóstico , Necrose/etiologia , Necrose/terapia , Doenças Testiculares/etiologia , Doenças Testiculares/terapiaRESUMO
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer related death worldwide. HCC develops through a multistep process that involves genetic and epigenetic changes. In addition to genetic and epigenetic mechanisms, recent studies have shown that microRNAs (miRNAs) play essential roles in hepatocellular carcinogenesis through the post-transcriptional regulation of tumor associated-genes. In this review, we summarize the role of miRNAs in HCC and its microenvironment, and discuss the implications for HCC therapy.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Apoptose/genética , Biomarcadores Tumorais , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/fisiologia , Invasividade Neoplásica/genética , Células-Tronco Neoplásicas/metabolismo , Neovascularização Patológica/genética , Prognóstico , Microambiente TumoralRESUMO
Noninvasive and targeted physical treatment is still desirable especially for those cancerous patients. Herein, we develop a new physical treatment protocol by employing CO2 bubbling-based 'nanobomb' system consisting of low-intensity ultrasound (1.0 W/cm(2)) and a well-constructed pH/temperature dual-responsive CO2 release system. Depending on the temperature elevation caused by exogenous low-intensity therapeutic ultrasound irradiation and the low pH caused by the endogenous acidic-environment around/within tumor, dual-responsive CO2 release system can quickly release CO2 bubbles, and afterwards, the generated CO2 bubbles waves will timely explode before dissolution due to triggering by therapeutic ultrasound waves. Related bio-effects (e.g., cavitation, mechanical, shock waves, etc) caused by CO2 bubbles' explosion effectively induce instant necrosis of panc-1 cells and blood vessel destruction within panc-1 tumor, and consequently inhibit the growth of panc-1 solid tumor, simultaneously minimizing the side effects to normal organs. This new physiotherapy employing CO2 bubbling-based 'nanobomb' system promises significant potentials in targetedly suppressing tumors, especially for those highly deadly cancers.
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Antineoplásicos/metabolismo , Dióxido de Carbono/metabolismo , Microbolhas , Neoplasias Pancreáticas/terapia , Ultrassom/métodos , Animais , Modelos Animais de Doenças , Humanos , Concentração de Íons de Hidrogênio , Camundongos Nus , Som , Temperatura , Resultado do TratamentoRESUMO
Hepatocellular carcinoma (HCC) is the sixth most common neoplasm and the third cause of cancer death worldwide. Contrast enhanced ultrasound (CEUS) has been applied for more than ten years and plays increasingly important roles in the management of HCC. On the basis of the Guideline and Good Clinical Practice Recommendations for CEUS in the liver-update 2012 and related literature about the management of HCC, we summarize the main roles and applications of CEUS in the management of HCC, including HCC surveillance, diagnosis, CEUS-guided treatment, treatment response evaluation and follow-up. The diagnostic algorithm for HCC is also suggested. Meanwhile, the comparisons between CEUS and contrast enhanced computed tomography/magnetic resonance imaging (CECT/CEMRI) in these areas are made. Although CEUS is subject to the same limitation as ordinary US and is inferior to CECT/CEMRI in some aspects, CEUS has proved to be of great value in the management of HCC with inherent advantages, such as sufficient high safety profile making it suitable for patients with renal failure or allergic to iodine, absence of radiation, easy reproducibility and high temporal resolution. The tremendous application of CEUS to the diagnosis and treatment of HCC provides more opportunities for patients with HCC diagnosed at different stages.
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OBJECTION: To investigate the safety and treatment response of radioimmunotherapy (RIT) in combination with radiofrequency ablation (RFA) for the treatment of VX2 tumor on rabbit. MATERIALS AND METHODS: A total of 36 rabbits bearing VX2 tumor on the thigh were randomly assigned into 3 groups (group I: 1-2 cm; group II: 2-3 cm; group III: 3-4 cm) and 4 subgroups (A: as control, just puncture the tumor using the RFA electrode without power output; B: RFA alone; C: 131I-chTNT intratumoral injection alone; D: RFA+131I-chTNT intratumoral injection 3 days later). The variation of blood assay, weight and survival among different groups and subgroups were used to assess the treatment safety. Ultrasound (US) was used to monitor and assess the tumor response after treatment. RESULTS: According to the results of the weight and the blood assay among different groups, subgroups, and at two time points (one day before and the 16th day after treatment), no damages to the liver, kidney function and myelosuppression resulting from the treatment were found. No significant differences in survivals among the four subgroups (p = 0.087) were found. In addition, 131I-chTNT did not show significant inhibition effect on VX2 tumor progression according to US measurements. CONCLUSION: 131I-chTNT intratumoral injection alone or in combination with RFA is relatively safe for rabbit without significant toxicity and shows no significant effect on the survival. The treatment response is not as satisfactory as anticipated.
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Ablação por Cateter/métodos , Neoplasias Experimentais/terapia , Radioimunoterapia/métodos , Animais , Linhagem Celular Tumoral , Terapia Combinada , Estimativa de Kaplan-Meier , Neoplasias Experimentais/diagnóstico por imagem , Coelhos , Distribuição Aleatória , Fatores de Tempo , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga TumoralRESUMO
OBJECTIVE: The aim of the study was to assess the role of contrast-enhanced ultrasound (CEUS) in treatment response evaluation after percutaneous bipolar radiofrequency ablation (BRFA) for liver tumors. METHODS: From May 2012 to May 2014, 39 patients with 73 tumors were treated by BRFA. One month after the treatment, CEUS and CEMRI/CECT were conducted to evaluate the treatment response. The results of CEUS were compared with CEMRI/CECT. RESULTS: Of the 73 tumors ablated, eight (11.0%) were found to have residual viable tumor tissue and 65 (89.0%) were successfully ablated based on CEMRI/CECT within 1-month after ablation. CEUS detected seven of the eight residual tumors and 63 of 65 completely ablated tumors. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CEUS were 87.5% (7/8), 96.9% (63/65), 77.8% (7/9), 98.4% (63/64) and 95.9% (70/73), respectively. The complete ablation (CR) rates for the tumors ≤ 3.0 cm, 3.1-5.0 cm, and >5.0 cm were 96.6% (58/60), 63.6% (7/11), and 0% (0/2), respectively (P<0.001). CR rates were 94.7% (36/38) for primary liver tumors and 82.9% (29/35) for metastatic liver tumors (P=0.212), and were 97.4% (38/39) for the tumors with curative treatment intention and 79.4% (27/34) for those with palliative treatment intention (P=0.037). Major complication was not encountered in this series. CONCLUSIONS: BRFA is an effective technique of percutaneous ablation for liver tumors and CEUS can be used to assess its therapeutic effect accurately.
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Ablação por Cateter , Meios de Contraste , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Fosfolipídeos , Hexafluoreto de Enxofre , Tomografia Computadorizada por Raios X , Idoso , Ablação por Cateter/efeitos adversos , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Neoplasia Residual , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do Tratamento , UltrassonografiaRESUMO
The synergistic effect of chemotherapy and ablation using high-intensity focused ultrasound (HIFU) is realized with a newly developed drug-delivery system. The system comprises an ultrathin silica shell surrounding a poly(lactic-co-glycolic acid) nanoemulsion core containing the drug (CPT) and a perfluorocarbon (PFOB). This nanosystem presents many advantages in drug delivery, such as excellent structural stability, high drug-loading capacity, and rapid HIFU-mediated drug release.
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Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Fluorocarbonos/química , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Nanopartículas/química , Dióxido de Silício/química , Animais , Antineoplásicos/farmacocinética , Bovinos , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada/métodos , Fluorocarbonos/síntese química , Fluorocarbonos/farmacocinética , Humanos , Ácido Láctico/síntese química , Ácido Láctico/química , Ácido Láctico/farmacocinética , Fígado/efeitos dos fármacos , Imagem por Ressonância Magnética Intervencionista/métodos , Transplante de Neoplasias , Ácido Poliglicólico/síntese química , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Dióxido de Silício/síntese químicaRESUMO
Aiming at substantially enhanced efficacy and biosafety of clinical HIFU therapy, a natural solid medium, L-menthol (LM), characteristic of mild and controllable "solid-liquid-gas" (SLG) tri-phase transition, was adopted, instead of those conventional explosive liquid-gas (LG) bi-phase transitional media, in constructing a multifunctional theranostic system. Owing to the continuous and controllable characteristics of SLG tri-phase transition, such a novel tri-phase transition-based theranostic system has been demonstrated of the repeatedly enhanced HIFU efficacy ex vivo and in vivo under once intravenous injection and the significantly improved treatment precision, controllability and biosafety when comparing to the traditional bi-phase transition medium, perfluorohexane (PFH), thus promising great application potential in clinical HIFU treatment. Moreover, this theranostic system has been demonstrated a long blood-circulation lifetime and continuous accumulation in tumor in 24 h, which is very beneficial for the enhanced tumor ablation in vivo along with SLG tri-phase transition. More importantly, after loading multiple model drugs and real drug, such a theranostic system presents a HIFU-mediated temperature-responsive drug release property, and depending on the versatile miscibility of LM, co-loadings with hydrophobic and hydrophilic drugs are also achieved, which provides the possibility of synergistic treatment combining HIFU therapy and chemotherapy.
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Sistemas de Liberação de Medicamentos/métodos , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Neoplasias/terapia , Animais , Bovinos , Sobrevivência Celular , Corantes/administração & dosagem , Células HeLa , Humanos , Neoplasias/diagnóstico , Transição de Fase , CoelhosRESUMO
PURPOSE: To evaluate the diagnostic performance of ARFI imaging in differentiating between benign and malignant thyroid nodules <1 cm. MATERIALS AND METHODS: 173 pathologically proven thyroid nodules (77 benign, 96 malignant) in 157 patients were included in this study. Receiver-operating characteristic curve (ROC) analyses were performed to assess the diagnostic performance of conventional ultrasound (US) and ARFI imaging in papillary thyroid microcarcinoma (PTMC). The independent risk factors for predicting PTMC were evaluated. RESULTS: The mean SWV value of benign and malignant thyroid nodules were 2.57 ± 0.79 m/s (range: 0.90-4.92 m/s) and 3.88 ± 2.24 m/s (range: 1.49-9.00 m/s) (P = 0.000). Az for VTI elastography score was higher than that for hypoechoic, absence of halo sign, and type III vascularity (P < 0.05). The optimal cut-offs for VTI elastography score and SWV were score 4 and 3.10 m/s. Gender, hypoechoic, taller than wide, VTI elastography score ≥ 4, and SWV > 3.10 m/s had been found to be independent risk factors for predicting PTMC. CONCLUSION: ARFI elastography can provide elasticity information of PTMC quantitatively (VTQ) and directly reflects the overall elastic properties (VTI). Gender, hypoechogenicity, taller than wide, VTI elastography score ≥ 4, and SWV > 3.10 m/s are independent risk factors for predicting PTMC. ARFI elastography seems to be a new tool for the diagnosis of PTMC.
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Carcinoma Papilar/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem , Adulto , Idoso , Carcinoma Papilar/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologiaRESUMO
A novel modification route integrating the copolymers of positive charged quaternary amines and polyethylene glycol (PEG) units using a combination of reversible addition-fragmentation chain-transfer polymerization (RAFT) and "Graft From" strategy, has been proposed and developed, for the first time, to decorate the surface of mesoporous silica nanoparticles (MSNs). These MSNs are shown to have a greatly reduced hydrodynamic particle size in physiological solution. It is demonstrated that such an efficient copolymer surface modification strategy, resulting in PEG coating with high positive zeta potential, can achieve a nearly 2-fold enhanced permeability and retention (EPR) effect, and longer blood half-life compared to coating with PEG only. Besides, the in vivo results demonstrated that this surface modification strategy could lead to a higher efficacy of doxorubicin (DOX) drug delivery and greater suppression of side effects compared to the free drug. Based on this novel strategy of combining "RAFT" and "Graft From" polymerization, it is anticipated that this efficient modification of tumor-specific targeting of MSNs can be widely used in future nanomedicine research.
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Hypoxia and hypoxia-driven angiogenesis play an important role on the recurrence of hepatocellular carcinoma after insufficient radiofrequency ablation. The hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor-A (VEGFA) pathway plays an important part in this process. Sorafenib is a multikinase inhibitor with activity against several receptor tyrosine kinases. However, it is unclear whether sorafenib can affect the HIF-1α/VEGFA pathway. Here, we explore whether sorafenib affects HIF-1α and the change of invasion ability in this process. In this experiment, the control group, cobalt chloride (CoCl2)-treated group, sorafenib-treated group, and cobalt chloride combined with sorafenib-treated group were adopted. Western blot and PCR were performed to detect the protein and mRNA expression of HIF-1α and VEGFA in different groups. Transwell assay was used to test the changes of invasion ability. Flow cytometry was adopted to detect the apoptotic role of sorafenib on hepatoma cells. Cobalt chloride upregulated the expression of HIF-1α protein, and the upregulation effect was more obvious when the concentration was increased gradually. Sorafenib inhibited cobalt-induced HIF-1α and VEGFA expression in hepatoma cells. Sorafenib decreased the tumor cell invasiveness induced by cobalt chloride in vitro. Sorafenib inhibited cell proliferation and induced apoptosis in hepatoma cells. These results showed that sorafenib was an effective inhibitor of the HIF-1α/VEGFA pathway, which can provide new insight into the mechanism of its anticancer activity.