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Gallium oxide (G a 2 O 3) photodetectors have drawn increased interest for their widespread applications ranging from military to civil. Due to the inherent oxygen vacancy defects, they seriously suffer from trade-offs that make them incompetent for high-responsivity, quick-response detection. Herein, a G a 2 O 3 nanocavity photodetector assisted with grating electrodes is designed to break the constraint. The proposed structure supports both the plasmonic mode and the Fabry-Perot (F-P) mode. Numerical calculations show that the absorption of 99.8% is realized for ultra-thin G a 2 O 3 (30 nm), corresponding to a responsivity of 12.35 A/W. Benefiting from optical mechanisms, the external quantum efficiency (EQE) reaches 6040%, which is 466 times higher than that of bare G a 2 O 3 film. Furthermore, the proposed photodetector achieves a polarization-dependent dichroism ratio of 9.1, enabling polarization photodetection. The grating electrodes also effectively reduce the transit time of the photo-generated carriers. Our work provides a sophisticated platform for developing high-performance G a 2 O 3 photodetectors with the advantages of simplified fabrication processes and multidimensional detection.
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Combination cancer therapy with various kinds of therapeutic approaches could improve the effectiveness of treatment while reducing side effects. Herein, we elaborately developed a theranostics nanoplatform based on magnetic polydopamine (MPDA) coated with hyaluronic acid-methotrexate conjugates (MPDA@HA-MTX) for chemo-photothermal treatment (PTT). In this nanoplatform, Fe3O4 served as the core was applied as contrast agent for T2-weighted magnetic resonance imaging (MRI) and early phase magnet targeting. Meanwhile, PDA was used as a versatile shell for effective loading of chemotherapeutic doxorubicin (DOX) to achieve controlled release and PTT simultaneously. Moreover, HA-MTX conjugates could offer later-phase specific cellular dual-targeting ability during the therapy. Both in vitro and in vivo studies demonstrated that DOX-loaded MPDA@HA-MTX (MPDA/DOX@HA-MTX) exhibited the preferential tumor accumulation, enhanced specificity to target tumor cells, pH-/laser-responsive release, and high tumor cell-killing efficiency. By combined chemo-PTT under the guidance of fluorescence/MR imaging, the tumors in mice were completely eliminated after treatment, indicating that MPDA@HA-MTX nanoparticles have great potential as a novel drug-loading platform for imaging-guided multistage targeted chemo-photothermal combination therapy.
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Ácido Hialurónico/química , Indoles/química , Metotrexato/química , Nanopartículas/química , Polímeros/química , Animales , Doxorrubicina/química , Doxorrubicina/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Femenino , Citometría de Flujo , Células HeLa , Humanos , Hipertermia Inducida , Neoplasias Mamarias Animales/tratamiento farmacológico , Neoplasias Mamarias Animales/terapia , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Imagen Multimodal , Fototerapia , ConejosRESUMEN
OBJECTIVE: The ASTRUM-007 study confirmed the significant efficacy and safety of serplulimab plus chemotherapy for patients with locally advanced/metastatic, programmed cell death-ligand 1 positive oesophageal squamous cell carcinoma (OSCC). The economics of this regimen, however, is unclear. Therefore, this study aimed to evaluate the cost-effectiveness of adding serplulimab to chemotherapy for the treatment of advanced OSCC from the perspective of the Chinese healthcare system. DESIGN: A partitioned survival model was established to simulate the costs and outcomes of chemotherapy versus serplulimab plus chemotherapy. The survival data came from the ASTRUM-007 study. Only direct medical costs were considered, and utility values were referred to the literature. Sensitivity analysis was performed to assess the effect of parameter uncertainty on the model. OUTCOME MEASURES: Total costs, incremental costs, life years, quality-adjusted life years (QALYs), incremental QALYs and incremental cost-effectiveness ratio (ICER). RESULTS: The base case analysis showed that the cost of serplulimab plus chemotherapy (US$69 356) was US$41 607 higher than that of chemotherapy (US$27 749), but it also gained 0.38 QALYs more (1.38 vs 1 QALYs), with an ICER of US$110 744.36/QALY, which was higher than the willingness to pay. The factors that most influenced the ICER were the price of serplulimab, weight and utility value of the progression-free survival stage. The subgroup analysis and scenario analysis also demonstrated that serplulimab plus chemotherapy was not economical. CONCLUSIONS: Compared with chemotherapy, serplulimab coupled with chemotherapy was not cost-effective for the treatment of advanced OSCC in China.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neoplasias Pulmonares , Humanos , Análisis Costo-Beneficio , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , China , Anticuerpos Monoclonales , Inhibidores de Puntos de Control Inmunológico , Neoplasias Esofágicas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
A new electrochemical DNA biosensor based on double-probe mode and enzyme-mediated multiple signal electrocatalysis is constructed for the highly sensitive determination of double-stranded (ds-) PML/RARα fusion gene. Through the ingenious design of two groups of detection probes, including two thiolated capture probes anchored on dual standalone detection units integrated into one customized gold electrode and four biotinylated reporter probes, hybridizing with different segments of the same target single-stranded DNA (ssDNA) simultaneously, the hybridization efficiency between the probes and target is improved by preventing the reannealing of the two separate target ssDNA. Compared with a single reporter probe, this method can dramatically increase the amount of biotin and introduce numerous streptavidin-labelled horseradish peroxidase (HRP), thereby significantly amplifying electrochemical signals with low background signals. The combination of the dual-probe mode, multiple signal amplification strategy, and the inherent electrocatalytic activity of the HRP results in the prominent electrochemical sensing performance in detecting large-fragment target dsDNA with a detection limit as low as 71 fM. Furthermore, taking advantage of the new detection strategy, polymerase chain reaction (PCR) products and enzyme-digested PCR products from NB4 cells can be effectively analysed, showing great promise for the development of a new class of point-of-care platforms for disease-/drug-related genes.
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Técnicas Biosensibles , ADN de Cadena Simple , Técnicas Biosensibles/métodos , Biotina , ADN/análisis , ADN/genética , Sondas de ADN/genética , Técnicas Electroquímicas/métodos , Oro , Peroxidasa de Rábano Silvestre , Límite de Detección , EstreptavidinaRESUMEN
Neuroinflammation is thought to contribute to the onset and progression of Alzheimer's disease (AD). Galectin-3 (Gal-3), the only member of the galectin chimeric subfamily, is a key regulator of neuroinflammation and microglial activation. However, the effects of Gal-3 inhibition in AD-related neuroinflammation are unclear. Here, we investigated whether hippocampal Gal-3 knockdown alleviated lipopolysaccharide (LPS)-induced neurotoxicity and cognitive deficits, as well as the underlying mechanisms. First, we bilaterally injected aged mice (23 months old) with anti-Gal-3 short hairpin RNA into the hippocampus dentate gyrus, followed by systemic LPS administration. To determine the effects of hippocampal Gal-3 knockdown on neuroinflammatory response and neuronal apoptosis, we assessed the effects of Gal-3 silencing on the levels of pro-inflammatory cytokines, microglial activation, and apoptosis in the hippocampus of LPS-exposed aged mice. Behavioral tests were used to access the cognitive function of the mice. To explore the potential signaling, protein extracts from the brains of mice were subjected to analyze the expression levels of key molecules (including Toll-like receptor 4 (TLR4), myeloid differentiation factor 88, and nuclear transcription factor-κB (NF-κB) p65) of the TLR4/NF-кB pathway, and BV2 cells were pretreated with TLR4 inhibitor or NF-κB inhibitor before Gal-3 stimulation. These analyses showed that hippocampal Gal-3 knockdown attenuated neuroinflammation and neuronal apoptosis in the hippocampus of LPS-challenged aged mice, and this was associated with improved cognitive function. Hippocampal Gal-3 knockdown may protect against LPS-induced neurotoxicity by inhibiting the TLR4/NF-кB pathway. Our findings highlight Gal-3 as a potential therapeutic target against AD-associated neuroinflammation.
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Enfermedad de Alzheimer , Síndromes de Neurotoxicidad , Animales , Ratones , Receptor Toll-Like 4/genética , FN-kappa B , Lipopolisacáridos/toxicidad , Galectina 3/genética , Galectinas , Hipocampo , CogniciónRESUMEN
Shenmai injection is mainly used for the treatment of heart-related diseases, including coronary heart disease, viral myocarditis, chronic cor pulmonale, and shock in Asia. Medicinal materials from different origins produce Shenmai injections for clinical use, and their protective effects on cardiomyocytes may vary with the choice of raw materials. In this study, we compared the protective effects of Shenmai injections produced from different raw materials on cardiomyocytes. Results showed that the protective effects of various Shenmai injections on hypoxia-reoxygenation-induced cardiomyocyte injury were mainly attributed to total ginsenosides extract, with few differences between them. However, the protective effects of different Shenmai injections on doxorubicin and oxidative stress-induced cardiomyocyte injury were significantly different; the protective effects of Shenmai injection with Zhejiang Ophiopogon japonicus as raw material were significantly better than those with Sichuan Ophiopogon japonicus, consistent with our previous research results. Our study reveals the different cardiomyocyte protective effects of Shenmai injections produced by medicinal materials from different origins, laying a scientific foundation for their clinical selection.
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COVID-19, referred to as new coronary pneumonia, is an acute infectious disease caused by a new type of coronavirus SARS-CoV-2. To evaluate the effect of integrated Chinese medicine and Western medicine in patients with COVID-19 from overseas. Data were collected from 178 COVID-19 patients overseas at First Affiliated Hospital of Xiamen University from April 1, 2021 to July 31, 2021. These patients received therapy of integrated Chinese medicine and western medicine. Demographic data and clinical characteristics were extracted and analyzed. In addition, the prescription which induced less length of PCR positive days and hospitalization days than the median value was obtained. The top 4 frequently used Chinese medicine and virus-related genes were analyzed by network pharmacology and bioinformatics analysis. According to the chest computed tomography (CT) measurement, abnormal lung findings were observed in 145 subjects. The median length of positive PCR/hospitalization days was 7/7 days for asymptomatic subjects, 14/24 days for mild subjects, 10/15 days for moderate subjects, and 14/20 days for severe subjects. The most frequently used Chinese medicine were Scutellaria baicalensis (Huangqin), Glycyrrhiza uralensis (Gancao), Bupleurum chinense (Chaihu), and Pinellia ternata (Banxia). The putative active ingredients were baicalin, stigmasterol, sigmoidin-B, cubebin, and troxerutin. ACE, SARS-CoV-2 3CL, SARS-CoV-2 Spike, SARS-CoV-2 ORF7a, and caspase-6 showed good binding properties to active ingredients. In conclusion, the clinical results showed that integrated Chinese medicine and Western medicine are effective in treating COVID-19 patients from overseas. Based on the clinical outcomes, the putative ingredients from Chinese medicine and the potential targets of SARS-CoV-2 were provided, which could provide a reference for the clinical application of Chinese medicine in treating COVID-19 worldwide.
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COVID-19 , Humanos , SARS-CoV-2 , Estudios Retrospectivos , Medicina Tradicional China , HospitalizaciónRESUMEN
OBJECTIVE: To study the chemical constituents from Sarcopyramis bodinieri var. delicata. METHODS: These compounds were isolated and purified by chromatography with silica gel column combined with Sephadex LH-20 column from high polar extracts. The structures were identified on the basis of extensive spectroscopic data analysis, and by comparison of their spectral data with those reported. RESULTS: Seven compounds were isolated as 3, 3'-di-O-methylellagic acid-4'-O-alpha-L-rhamnopyranoside (I), ellagic acid (II), ferulic acid (III), isoferulic acid (IV), caffeic acid (V), 3, 4-di-hydroxybenzoic acid (VI), p-hydroxycinnamic acid (VII). CONCLUSION: Compound I, III, VI, VII are isolated from the genus for the first time.
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Ácido Elágico/análogos & derivados , Hidroxibenzoatos/aislamiento & purificación , Melastomataceae/química , Monosacáridos/aislamiento & purificación , Plantas Medicinales/química , Ácidos Cumáricos/química , Ácidos Cumáricos/aislamiento & purificación , Ácido Elágico/química , Ácido Elágico/aislamiento & purificación , Etanol/química , Hidroxibenzoatos/química , Espectroscopía de Resonancia Magnética , Monosacáridos/química , PropionatosRESUMEN
The endogenous lipid metabolism network is associated with the occurrence and progression of malignancies. Endocannabinoids and ceramides have demonstrated their anti-proliferative and pro-apoptotic properties in a series of cancer studies. The aim of the present study was to evaluate the expression patterns of endocannabinoids and endogenous ceramides in 67 pairs of human hepatocellular carcinoma (HCC) tissues and non-cancerous counterpart controls. Anandamide (AEA), the major endocannabinoid, was reduced in tumor tissues, probably due to the high expression and activity of fatty acid amide hydrolase. Another important endocannabinoid, 2-arachidonylglycerol (2-AG), was elevated in tumor tissues compared with non-tumor controls, indicating that the biosynthesis of 2-AG is faster than the degradation of 2-AG in tumor cells. Furthermore, western blot analysis demonstrated that cannabinoid receptor 1 was downregulated, while cannabinoid receptor 2 was elevated in HCC tissues, in accordance with the alterations in the levels of AEA and 2-AG, respectively. For HCC tissues, the expression levels of C18:0, 20:0 and 24:0-ceramides decreased significantly, whereas C12:0, 16:0, 18:1 and 24:1-ceramides were upregulated, which may be associated with cannabinoid receptor activation and stearoyl-CoA desaturase protein downregulation. The exact role of endocannabinoids and ceramides in regulating the fate of HCC cells requires further investigation.
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OBJECTIVE: To evaluate current diagnosis and therapeutic effect and outcome of diffuse axonal injury (DAI) in 169 patients. METHODS: The data of 169 DAI patients treated in the Second, Sixth, Eighth and Ninth Hospitals of Shenzhen and Shekou Hospital from January 2001 to January 2005 were collected. The imaging features, classification, GCS (Glasgow coma scale), treatment and outcome of the 169 patients were retrospectively analyzed. RESULTS: The simpler the imaging features, the closer the focus of DAI to the periphery of hemisphere and the higher the GCS score, the better the prognoses of DAI patients will be. CONCLUSIONS: The prognoses of DAI patients are closely related to the imaging features and classification, GCS and clinical treatment.
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OBJECTIVE: To sum up the experience in treating very severe traumatic brain injuries. METHODS: Retrospective analysis of 68 patients with very severe traumatic brain injuries treated in our hospital from 1997 to 2002 was done. RESULTS: Forty-one (60%) patients died. In the 50 patients treated surgically 27 (40%) survived, 8 recovered well, 9 had moderate disability and 10 had severe deficits. The 18 patients treated non-operatively all died. CONCLUSIONS: Much attention should be given to the observation of the changes of severe brain injuries with cranial base injury. Timely operative decompression, basic life support, keeping effective brain blood perfusion and effective oxygen supply, improving cerebral microcirculation and preventing or controlling complications are the main methods to raise the successful rate of treating very severe brain injuries and the life quality of the patients.
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Lesiones Encefálicas/diagnóstico , Lesiones Encefálicas/terapia , Oxígeno/uso terapéutico , Adolescente , Adulto , Anciano , Lesiones Encefálicas/mortalidad , Estudios de Cohortes , Terapia Combinada , Craneotomía , Cuidados Críticos/métodos , Descompresión Quirúrgica , Quimioterapia Combinada , Femenino , Escala de Coma de Glasgow , Humanos , Puntaje de Gravedad del Traumatismo , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: Pulmonary artery (PA) catheterization monitoring (Swan-Ganz) is usually not available to critically high-risk surgical patients before admission to ICU, where action to correct values derived from such monitoring may be too late. To explored the effect of non-invasive monitoring systems that allow hemodynamic monitoring during the early stages after trauma. METHODS: The early temporal hemodynamic patterns after high-risk trauma with non-invasive monitoring systems were evaluated, and compared these to invasive PA monitoring. The study included 156 patients monitored shortly after admission to the emergency department. RESULTS: The non-invasive impedance cardiac output estimations under extenuating emergency conditions were similar to those of the thermodilution method: r=0.69, r(2)=0.87, P<0.001; bias and precision were (0.62+/-0.38)L. min(-1).m(-2). In ICU, these values improved further to: r=0.84, r(2)=0.93, P<0.001; bias and precision were (0.36+/-0.15) L.min(-1).m(-2). Monitoring revealed episodes of hypotension, low cardiac index, arterial hemoglobin desaturation, low transcutaneous oxygen and high transcutaneous carbon dioxide tension, and low oxygen consumption during initial resuscitation. Low flow and poor tissue perfusion were more pronounced in non-survivors by both METHODS. CONCLUSION: Multicomponent non-invasive monitoring systems offer continuous on-line, real-time display of hemodynamic data, they allow early recognition of circulatory dysfunction. Such systems provide information similar to that provided by the invasive thermodilution method, and are more effective and safer.