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1.
World J Gastroenterol ; 30(16): 2209-2219, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38690022

RESUMEN

Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition in the laryngopharynx and upper aerodigestive tract mucosa caused by reflux of stomach contents beyond the esophagus. LPRD commonly presents with sym-ptoms such as hoarseness, cough, sore throat, a feeling of throat obstruction, excessive throat mucus. This complex condition is thought to involve both reflux and reflex mechanisms, but a clear understanding of its molecular mechanisms is still lacking. Currently, there is no standardized diagnosis or treatment protocol. Therapeutic strategies for LPRD mainly include lifestyle modifications, proton pump inhibitors and endoscopic surgery. This paper seeks to provide a comprehensive overview of the existing literature regarding the mechanisms, patho-physiology and treatment of LPRD. We also provide an in-depth exploration of the association between LPRD and gastroesophageal reflux disease.


Asunto(s)
Reflujo Gastroesofágico , Reflujo Laringofaríngeo , Inhibidores de la Bomba de Protones , Humanos , Reflujo Laringofaríngeo/fisiopatología , Reflujo Laringofaríngeo/diagnóstico , Reflujo Laringofaríngeo/terapia , Reflujo Gastroesofágico/fisiopatología , Reflujo Gastroesofágico/terapia , Reflujo Gastroesofágico/diagnóstico , Inhibidores de la Bomba de Protones/uso terapéutico , Resultado del Tratamiento , Estilo de Vida
2.
Mitochondrial DNA B Resour ; 9(2): 257-261, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38348095

RESUMEN

The genome-level features are crucial genetic resources for species identification and phylogenetic analysis. Here, the complete mitochondrial genome of Aphidius colemani Viereck 1912 (Hymenoptera: Braconidae: Aphidiinae) was sequenced, determined and analyzed. The circular genome is 16,372 bp in length with an overall base composition of 38.9% for A, 46.2% for T, 6.7% for C, and 8.2% for G. The mitochondrial genome of A. colemani contained 13 protein-coding genes that initiated by the ATN codon, 22 transfer RNA genes, two ribosomal RNA genes (rRNAs), and a control region (CR). It shared the same gene arrangement patterns that occurred in two tRNA clusters of trnI-trnQ-trnM and trnW-trnC-trnY with Aphidius gifuensis. Phylogenetic analyses using Bayesian inference and Maximum-likelihood methods supported that the two species of Aphidiinae formed a clade and sister to other subfamilies of Braconidae.

4.
ACS Appl Mater Interfaces ; 15(21): 25744-25751, 2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37199533

RESUMEN

Quantum dot light-emitting diodes (QLEDs) are an emerging class of optoelectronic devices with a wide range of applications. However, there still exist several drawbacks preventing their applications, including long-term stability, electron leakage, and large power consumption. To circumvent the difficulties, QLEDs based on a self-assembled hole transport layer (HTL) with reduced device complexity are proposed and demonstrated. The self-assembled HTL is prepared from poly[3-(6-carboxyhexyl)thiophene-2,5-diyl] (P3HT-COOH) solution in N,N-dimethylformamide (DMF) forming a well-ordered monolayer on an indium-tin-oxide (ITO) anode. The P3HT-COOH monolayer has a smaller HOMO band offset and a sufficiently large electron barrier with respect to the CdSe/ZnS quantum dot (QD) emission layer, and thus it is beneficial for hole injection into and electron leakage blocking from the QD layer. Interestingly, the QLEDs exhibit an excellent conversion efficiency (97%) in turning the injected electron-hole pairs into light emission. The performance of the resulting QLEDs possesses a low turn-on voltage of +1.2 V and a maximum external quantum efficiency of 25.19%, enabling low power consumption with high efficiency. Additionally, those QLEDs also exhibit excellent long-term stability without encapsulation with over 90% luminous intensity after 200 days and superior durability with over 70% luminous intensity after 2 h operation under the luminance of 1000 cd m-2. The outstanding device features of our proposed QLEDs, including low turn-on voltage, high efficiency, and long-term stability, can advance the development of QLEDs toward facile large-area mass production and cost-effectiveness.

5.
Front Psychol ; 14: 1094138, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36923137

RESUMEN

This study proposed and tested a model adapted from Biggs' 3P model that quantifies the behaviors of students who completed MOOCs (Massive Open Online Courses) in order to design intervention measures for low retention rates. Psychomotor domain data from 300 MOOC learners was analyzed in a covariance-based structural equation model (CB-SEM) to analyze the direct and indirect effects of various factors. Results show the basic psychological needs theory (BPNT) in the presage stage significantly positively correlated with engagement in the process stage. Meanwhile, the process stage exhibited a significantly positive correlation with the product stage, representing persistence intention (PI). Furthermore, a full mediation effect was observed among the presage, process, and product stages. The mediating effect demonstrates that higher student engagement leads to more positive exertion on BNPT and PI to complete the course. Moreover, results show bolstering students' behavioral, emotional, and cognitive engagement strengthens their PIs.

6.
Environ Res ; 222: 115346, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36702189

RESUMEN

Large amounts of microplastics (MPs) enter the soil along with the amendment of sludge to soil. However, it is still unclear about the response of MPs occurrence and the adsorption behaviors of cadmium (Cd)on MPs to typical agricultural environmental scenarios. In present work, three kinds of MPs (polyethylene, polypropylene, and polystyrene) were chosen to investigate that response in three agricultural environmental scenarios with sludge-amended soil, including dry-wet alteration (7 d, five cycles), microbial addition (Bacillus subtilis, 0.05 g/g soil), and Ultraviolet (UV) irradiation (340 nm, 4 × 15 W, 4 d). The results showed that there was the highest adsorption capacity of Cd on MPs (36.21, 45.15, 12.43 µg/g for PE, PP, PS, respectively) after UV irradiation exceeding those from MPs triggered by other two scenarios). UV irradiation caused an increase in the abundance of Streptomyces, an expansion in specific surface area, a significant change in surface morphologies, an improvement in crystallinity or the formation of new crystals, and an enhancement in C-O and CO content, and then resulted in the incremental adsorption capacity of Cd on MPs. The findings are important of significance for controlling the environmental risks from sludge MPs via carrying heavy metals in the soil-plant systems.


Asunto(s)
Microplásticos , Contaminantes del Suelo , Plásticos , Cadmio , Suelo , Aguas del Alcantarillado , Contaminantes del Suelo/análisis
7.
J Environ Manage ; 322: 116113, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36055089

RESUMEN

The complicated contamination of microplastics (MPs) and heavy metals in sludge has garnered substantial attention in recent years; however, research on the behavior of MPs loading of heavy metals in sludge after sludge treatment methods is limited. Four representative sludge treatment methods were selected herein: anaerobic digestion, thermal drying, thermal hydrolysis (TH), and aerobic composting. Before and after sludge treatment, the chemical bonding of MPs, cadmium (Cd) adsorption properties, and metabolic changes in the microbial community succession was analyzed, and the factors influencing differences in Cd sorption by sludge MPs were explored. The results revealed that Cd adsorption by MPs occurs as multilayer physical adsorption that can be well fitted by Freundlich isotherms. Compared with the other three treatments, TH led to the most significant effect on the chemical bonding properties of the MPs, with a more than two-fold increase in C-O single bonds and CO double bonds, as well as adsorption of the highest amount of Cd at 767 µg/g. In addition, sludge conductivity and water content also affected Cd sorption capacity, with correlation coefficients of 0.405 and -0.384. Pedobacter, Flavobacterium, Lysobacter, and Sphingobacterium in the sludge presented a high degree of coupling with adsorption capacity, it was inferred that the above dominant species of bacteria may affect the adsorption of Cd by microplastics through the production of extracellular enzyme forms.


Asunto(s)
Metales Pesados , Contaminantes Químicos del Agua , Adsorción , Cadmio/química , Microplásticos , Plásticos/química , Aguas del Alcantarillado , Agua , Contaminantes Químicos del Agua/análisis
8.
Chemosphere ; 307(Pt 4): 136092, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35995191

RESUMEN

Environmental pollution by microplastics (MPs) is a significant and complex global issue. Existing MPs identification methods have demonstrated significant limitations such as low resolution, long imaging time, and limited particle size analysis. New and improved methods for MPs identification are topical research areas, with machine learning (ML) algorithms proven highly useful in recent years. Critical literature reviews on the latest developments in this area are limited. This study closes this gap and summarizes the progress made over the last 10 years in using ML algorithms for identifying and quantifying MPs. We identified diverse combinations of ML methods and fundamental techniques for MPs identification, such as Fourier-transform infrared spectroscopy, Raman spectroscopy, and near-infrared spectroscopy. The most widely used ML model is the support vector machine, which effectively improves the conventional analysis method for spectral quality defects and improves detection accuracy. Artificial neural network models exhibit improved recognition effects, with shorter detection times and better MPs recognition efficiency. Our review demonstrates the potential of ML in improving the identification and quantification of MPs.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Monitoreo del Ambiente/métodos , Aprendizaje Automático , Plásticos/química , Contaminantes Químicos del Agua/análisis
9.
ACS Appl Mater Interfaces ; 14(23): 26895-26903, 2022 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-35658400

RESUMEN

Multilevel and flexible nonvolatile memory (NVM) is a promising candidate for data storage in next-generation devices but its high bias and low mobility of conducting channels are often its drawbacks. In this study, we demonstrate a low bias of smaller than 0.1 V and a high-mobility graphene layer as a conducting channel for flexible optoelectronic NVM based on a composite thin film of indium-based MOF-derived InCl3 and 4,4-oxydiphthalic anhydride (odpta), Na[In3(odpt)2(OH)2(H2O)2](H2O)4, and reduced graphene oxide (rGO). The optoelectronic NVM device can be encoded and erased optically by ultraviolet (UV) light and visible light, respectively. Our device also achieves memory states over 192 (6-bit storage) distinct levels, which can emerge as mass data storage. It also shows an excellent endurance of write-erase cycles under irradiation with a laser of varying wavelengths, the mechanical stability of more than 1000 bending cycles, and stable retention for longer than 10 000 s. These results open an alternative route for developing low bias and innovative optoelectronic technologies.

10.
J Transl Med ; 20(1): 218, 2022 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-35562743

RESUMEN

BACKGROUND: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. METHODS: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. RESULTS: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. CONCLUSION: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.


Asunto(s)
Células Acinares , Endorribonucleasas , Animales , Humanos , Ratones , Células Acinares/metabolismo , Ácido Araquidónico/metabolismo , Proteínas Portadoras/metabolismo , Endorribonucleasas/metabolismo , Fibrosis , Radioisótopos de Galio , Ratones Noqueados , Tomografía Computarizada por Tomografía de Emisión de Positrones , Proteínas Serina-Treonina Quinasas , Tripsina/metabolismo , Proteínas Supresoras de Tumor/metabolismo
11.
Front Med (Lausanne) ; 9: 754341, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35280902

RESUMEN

Both interleukin (IL)-7 and human periodontal ligament cells (hPDLCs) have immunomodulatory properties. However, their combined effect on CD4+T cells has never been studied. In this study, we aimed to investigate the effect of conditioned medium of hPDLCs treated with rhIL-7 on the differentiation of CD4+T cells into regulatory T cells/T helper 17 cells (Treg/Th17 cells) and observe the effect of IL-7 on the immunomodulatory properties of PDLCs. After hPDLCs were treated with different concentrations of rhIL-7 for 24 h, the collected supernatants were used to incubate CD4+T cells for 3 days. A gamma-secretase inhibitor (DAPT) was used to suppress the activation of the Notch1 signaling pathway. Cell proliferation, apoptosis, and necrosis were determined using the cell counting kit-8 (CCK-8) and flow cytometry (FCM). The expressions of forkhead box P3 (Foxp3) in CD4+T cells and transforming growth factor (TGF-ß) and IL-6 in the supernatants were determined by ELISA. Reverse transcription-quantitative PCR (RT-qPCR), and the Western blot (WB) determined the mRNA levels and protein expression of various target factors. FCM was used to detect the mean fluorescence intensity of PD-L1 in hPDLCs and to analyze the differentiation of Treg/Th17 cells. Our results showed that IL-7 promoted proliferation and inhibited apoptosis in hPDLCs, promoted the expression of TGF-ß, PD-L1, Notch1, Jagged1, and Hes1, and inhibited the levels of hypoxia-inducible factor (HIF)-1α and TCF7, whereas the addition of DAPT effectively reversed these effects. Importantly, we found that the conditioned medium of hPDLCs treated with rhIL-7 promoted the polarization of CD4+T cells into Treg cells but had no significant effect on the differentiation of Th17 cells. Our study indicated that treatment of PDLCs with IL-7 can promote the polarization of CD4+T cells into Treg cells by modulating the expression of inflammatory factors and signaling molecules through activating the Notch1 signaling pathway, thus participating in the regulation of immune homeostasis in the periodontal microenvironment.

12.
Ying Yong Sheng Tai Xue Bao ; 32(8): 3023-3030, 2021 Aug.
Artículo en Chino | MEDLINE | ID: mdl-34664477

RESUMEN

Stone buildings exposed to natural environment inevitably subject to various factors. Among which, biodeterioration caused by bacteria, fungi, algae, lichen, and moss is widespread. The long-term cumulative effect of biodeterioration will lead to irreversible changes in the aesthetic characteristics, physical and chemical properties of stone buildings. Therefore, it is necessary to control the biodeterioration of stone buildings. Here, we summarized four traditional methods including heat shock treatments, laser and ultraviolet radiation, application of biocides, and presented typical examples. We analyzed several emerging techniques, such as synergistic effect of physical and chemical methods, plant extracts and nanomaterials biocides, and reviewed their advantages, disadvantages as well as applicability. Aiming to provide a reference for the research of biodeterioration prevention and conservation of stone buildings, we discussed the preventive methods for biodeterioration of stone building and the assessment methods to test the effects of such methods, and prospected the future research direction.


Asunto(s)
Líquenes , Rayos Ultravioleta , Bacterias , Ambiente , Hongos
13.
ACS Sens ; 6(9): 3424-3435, 2021 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-34415143

RESUMEN

Dynamic changes in the tumor-associated fibroblast activation protein (FAP) expression in tumors of different stages may be helpful for prognostic evaluation and treatment response monitoring, making this protein a promising surveillance biomarker for timely diagnosis of malignant tumors and effective planning of patient care. To prospectively verify the diagnostic efficacy value of the developed FAP tracers, [68Ga]Ga-FAPtp and [68Ga]Ga-Alb-FAPtp-01, dynamic/static positron emission tomography (PET)/computed tomography scans were acquired for tumor-targeting studies in vivo and in comparison with the well-established clinically used tracer [68Ga]Ga-FAPI-04. The optimized rationally designed FAP-targeting PET tracer, [68Ga]Ga-Alb-FAPtp-01, with albumin-binding capability demonstrated prominent tumor uptake over time. The mean standard uptake value (SUV) and the tumor/muscle (T/M) ratio were as high as 1.775 ± 0.179 SUV and T/M = 5.9, 1.533 ± 0.222 SUV and T/M = 6.7, and 1.425 ± 0.204 SUV and T/M = 9.5, respectively, at 1, 2, and 3 h. Its improved tumor uptake and pharmacokinetics suggest that the [68Ga]Ga-Alb-FAPtp-01 tracer can noninvasively detect FAP activation in vivo, permitting a precise definition of its roles in tumors of different stages and yielding insights regarding FAP-targeted radiotherapeutic strategies at the molecular level.


Asunto(s)
Fibroblastos Asociados al Cáncer , Glioma , Radioisótopos de Galio , Humanos , Tomografía de Emisión de Positrones , Quinolinas
14.
Yi Chuan ; 43(1): 52-65, 2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33509774

RESUMEN

Male sterility refers to the phenomenon that stamens cannot grow normally and produce viable pollen grains in plants. Hybrid seed production by taking advantage of the trait of male sterility is an effective and quick strategy to increase crop yield. Up to date, the yield of rice (Oryza sativa L.), maize (Zea mays L.), wheat (Triticum aestivum L.) and other crops has been greatly increased based on hybrid vigor utilization. Soybean (Glycine max (L.) Merr.) is a self-pollination species, artificial emasculation is not only time-consuming, but also labor-intensive and economically impracticable. So far, large scale hybrid breeding has not been performed in soybean due to the shortage of male sterile lines suitable for hybrid production. Therefore, it is urgent to identify a stable male sterile system for the rapid utilization of heterosis in soybean. In this review, we summarize the progress on the discovery of soybean genic male sterility (GMS) mutants and GMS genes. Combining with the investigation of GMS genes in Arabidopsis, rice and maize, we provide important insights into the identification and potential utilization of GMS genes in soybean in the perspective of reverse genetics.


Asunto(s)
Glycine max/genética , Vigor Híbrido , Fitomejoramiento , Infertilidad Vegetal/genética , Genética Inversa
15.
Cell Death Dis ; 11(11): 966, 2020 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-33177505

RESUMEN

Treatment of acute pancreatitis (AP) and chronic pancreatitis (CP) remains problematic due to a lack of knowledge about disease-specific regulatory targets and mechanisms. The purpose of this study was to screen proteins related to endoplasmic reticulum (ER) stress and apoptosis pathways that may play a role in pancreatitis. Human pancreatic tissues including AP, CP, and healthy volunteers were collected during surgery. Humanized PRSS1 (protease serine 1) transgenic (PRSS1Tg) mice were constructed and treated with caerulein to mimic the development of human AP and CP. Potential regulatory proteins in pancreatitis were identified by proteomic screen using pancreatic tissues of PRSS1Tg AP mice. Adenoviral shRNA-mediated knockdown of identified proteins, followed by functional assays was performed to validate their roles. Functional analyses included transmission electron microscopy for ultrastructural analysis; qRT-PCR, western blotting, co-immunoprecipitation, immunohistochemistry, and immunofluorescence for assessment of gene or protein expression, and TUNEL assays for assessment of acinar cell apoptosis. Humanized PRSS1Tg mice could mimic the development of human pancreatic inflammatory diseases. EMC6 and APAF1 were identified as potential regulatory molecules in AP and CP models by proteomic analysis. Both EMC6 and APAF1 regulated apoptosis and inflammatory injury in pancreatic inflammatory diseases. Moreover, APAF1 was regulated by EMC6, induced apoptosis to injure acinar cells and promoted inflammation. In the progression of pancreatitis, EMC6 was activated and then upregulated APAF1 to induce acinar cell apoptosis and inflammatory injury. These findings suggest that EMC6 may be a new therapeutic target for the treatment of pancreatic inflammatory diseases.


Asunto(s)
Factor Apoptótico 1 Activador de Proteasas/metabolismo , Proteínas de la Membrana/metabolismo , Pancreatitis Crónica/metabolismo , Pancreatitis Crónica/patología , Enfermedad Aguda , Animales , Apoptosis/fisiología , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Biología Molecular/métodos , Pancreatitis Crónica/genética , Proteómica/métodos
16.
Theranostics ; 10(18): 8298-8314, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32724472

RESUMEN

Background: There is no curative therapy for severe acute pancreatitis (SAP) due to poor understanding of its molecular mechanisms. Endoplasmic reticulum (ER) stress is involved in SAP and increased expression of ATF6 has been detected in SAP patients. Here, we aimed to investigate the role of ATF6 in a preclinical SAP mouse model and characterize its regulatory mechanism. Methods: Pancreatic tissues of healthy and SAP patients were collected during surgery. Humanized PRSS1 transgenic mice were treated with caerulein to mimic the SAP development, which was crossed to an ATF6 knockout mouse line, and pancreatic tissues from the resulting pups were screened by proteomics. Adenovirus-mediated delivery to the pancreas of SAP mice was used for shRNA-based knockdown or overexpression. The potential functions and mechanisms of ATF6 were clarified by immunofluorescence, immunoelectron microscopy, Western blotting, qRT-PCR, ChIP-qPCR and luciferase reporter assay. Results: Increased expression of ATF6 was associated with elevated apoptosis, ER and mitochondrial disorder in pancreatic tissues from SAP patients and PRSS1 mice. Knockout of ATF6 in SAP mice attenuated acinar injury, apoptosis and ER disorder. AIFM2, known as a p53 target gene, was identified as a downstream regulatory partner of ATF6, whose expression was increased in SAP. Functionally, AIFM2 could reestablish the pathological disorder in SAP tissues in the absence of ATF6. p53 expression was also increased in SAP mice, which was downregulated by ATF6 knockout. p53 knockout significantly suppressed acinar apoptosis and injury in SAP model. Mechanistically, ATF6 promoted AIFM2 transcription by binding to p53 and AIFM2 promoters. Conclusion: These results reveal that ATF6/p53/AIFM2 pathway plays a critical role in acinar apoptosis during SAP progression, highlighting novel therapeutic target molecules for SAP.


Asunto(s)
Factor de Transcripción Activador 6/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Mitocondriales/genética , Páncreas/patología , Pancreatitis/genética , Proteína p53 Supresora de Tumor/genética , Células Acinares/patología , Factor de Transcripción Activador 6/genética , Adulto , Animales , Apoptosis/genética , Estudios de Casos y Controles , Ceruletida/administración & dosificación , Ceruletida/toxicidad , Modelos Animales de Enfermedad , Estrés del Retículo Endoplásmico , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Ratones Noqueados , Persona de Mediana Edad , Páncreas/citología , Pancreatitis/inducido químicamente , Pancreatitis/patología , Activación Transcripcional , Tripsina/genética
17.
PLoS One ; 14(12): e0225938, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31830075

RESUMEN

OBJECTIVE: This study is aimed toward establishing a decision-making model with multiple criteria for appraisal and reimbursement to compare the attitudes of different stakeholders toward various dimensions and criteria and to evaluate the five targeted therapies (bevacizumab, cetuximab, panitumumab, aflibercept, and regorafenib) for metastatic colorectal cancer. METHOD: This study is a multi-criteria decision analysis (MCDA) using a model that includes three dimensions and nine criteria. Both the overall and individual scores of the respective targeted therapies in different dimensions and criteria were calculated. A sensitivity analysis was carried out in order to evaluate the robustness of the research results. An interview-based questionnaire survey was applied to obtain the performance information for the targeted therapies and the weights of the dimensions and criteria. RESULTS: Overall, the clinical dimension had the highest weight, followed by the economic dimension, and finally, the social dimension. In the clinical dimension, the "comparative efficacy" criterion had the highest weight; in the economic dimension, the "cost-effectiveness" criterion" was given the greatest importance; in the social dimension, the "social concern and patient needs" criterion was given more emphasis. The overall values ranked from high to low as follows: cetuximab (overall score 3.3666), bevacizumab (3.3043), panitumumab (3.2030), aflibercept (2.8923) and regorafenib (2.8366). CONCLUSIONS: A comprehensive value assessment system combining "multi-dimensional criteria," "multi-perspectives," and an "integrative assessment" is necessary to evaluate the value of medicines. The results showed not only the order of weights of different dimensions or criteria, but also the rankings of the value of the targeted therapies.


Asunto(s)
Antineoplásicos/economía , Neoplasias Colorrectales/epidemiología , Toma de Decisiones , Costos de los Medicamentos , Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/tratamiento farmacológico , Análisis Costo-Beneficio , Encuestas de Atención de la Salud , Humanos , Terapia Molecular Dirigida/economía , Metástasis de la Neoplasia , Estadificación de Neoplasias , República de Corea/epidemiología
18.
Oncol Rep ; 41(1): 213-223, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30542709

RESUMEN

Ursodeoxycholic acid (UDCA) is a type of hydrophilic bile acid extracted from animal bile with a wide range of biological functions. The present results demonstrated that UDCA could effectively inhibit the proliferation of two human melanoma cell line (M14 and A375) with time­ and concentration­dependence. Following exposure to various concentrations of UDCA, M14 cells exhibited typical morphological changes and weaker ability of colony forming. Flow cytometry analysis demonstrated that UDCA could induce a decrease of mitochondrial membrane potential and an increase in reactive oxygen species (ROS) levels in M14 cells. The cell cycle was arrested in the G2/M phase, which was confirmed by the decrease of cyclin­dependent kinase 1 and cyclinB1 at the protein level. However, when M14 cells were treated with UDCA and Z­VAD­FMK (caspase inhibitor) synchronously, the apoptosis rate of the cells was reduced significantly. In addition, it was demonstrated that UDCA induced apoptosis of human melanoma M14 cells through the ROS­triggered mitochondrial­associated pathway, which was indicated by the increased expression of cleaved­caspase­3, cleaved­caspase­9, apoptotic protease activating factor­1, cleaved­poly (ADP­ribose) polymerase 1 and the elevation of B cell lymphoma­2 (Bcl­2) associated X protein/Bcl­2 ratio associated with apoptosis. Therefore, UDCA may be a potential drug for the treatment of human melanoma.


Asunto(s)
Apoptosis/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Ácido Ursodesoxicólico/farmacología , Clorometilcetonas de Aminoácidos/farmacología , Inhibidores de Caspasas/farmacología , Caspasas/metabolismo , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Melanoma/tratamiento farmacológico , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Microscopía Electrónica de Transmisión , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias Cutáneas/tratamiento farmacológico , Ácido Ursodesoxicólico/uso terapéutico
19.
Mar Pollut Bull ; 136: 84-91, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30509845

RESUMEN

Many shipwreck events occur in the neighboring areas of Taiwan due to the volume of maritime traffic and geographical conditions around Taiwan. The oil spills from such events can be devastating for the surrounding sea and coastal areas. The government realized the importance of marine pollution prevention and enforced the Marine Pollution Control Act and the Major Marine Oil Pollution Emergency Response Plan to mitigate the impact of oil spill pollution. The T.S. Taipei shipwreck highlighted the effectiveness of the national marine pollution prevention system. Inter-departmental cooperation and collaboration with private sectors are the keys for effective response. This article is the first detailed documentation of an oil spill response for a maritime incident from the beginning to the final termination of shipwreck removal. It shows the people in Taiwan intend to collaborate with other states to make a significant contribution to marine environment conservation and sustainability.


Asunto(s)
Conservación de los Recursos Hídricos/métodos , Planificación en Desastres/legislación & jurisprudencia , Contaminación por Petróleo/prevención & control , Navíos , Contaminación del Agua/prevención & control , Conservación de los Recursos Hídricos/legislación & jurisprudencia , Planificación en Desastres/organización & administración , Regulación Gubernamental , Cooperación Internacional , Océanos y Mares , Contaminación por Petróleo/análisis , Contaminación por Petróleo/legislación & jurisprudencia , Taiwán , Contaminación del Agua/análisis , Contaminación del Agua/legislación & jurisprudencia
20.
PLoS One ; 13(8): e0202725, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30142174

RESUMEN

BACKGROUND: Since 2012, several immune checkpoint inhibitors have been approved by the Taiwan FDA for various types of cancer treatment. However, none of them are covered by Taiwan National Health Insurance due to the fact that they are expensive, and there is a lack of clinical evidence as to their effectiveness. OBJECTIVES: This study was aimed toward an exploration of clinical experiences with use of immune checkpoint inhibitors, including indications, prescription types, drug effectiveness, adverse drug event types, and incidence, all of which shall serve as references for future clinical drug use. METHODS: This is a retrospective study focusing on three immune checkpoint inhibitors (ipilimumab, nivolumab, and pembrolizumab), which are available for cancer treatment in Taiwan. We collected data from medical records for the period from January 1st, 2015 to January 12th, 2017 at National Cheng Kung University Hospital (NCKUH), a medical center in southern Taiwan, and recorded these cases until May 31st, 2017. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and adverse drug reaction odds ratios were analyzed using a chi-square analysis. RESULTS: The 50 patients under consideration in this study had used any one of the immune checkpoint inhibitors in NCKUH. Non-small cell lung cancer (n = 24, 48%) accounted for the highest percentage, followed by hepatocellular carcinoma (n = 4, 8%). The median OS was not reached, and the PFS for all immunotherapies was 4.9 months. The median OS period and PFS for non-small cell lung cancer (NSCLC) patients were 13 and 4.9 months, respectively, which were similar to those in many clinical trials. For NSCLC patients, the OS and PFS were only 0.63 and 1.37 months for squamous cell type NSCLC, and for patients who were PD-L1 negative, the OS and PFS were only 11.53 and 2.6 months, respectively. The most common adverse events in this study included fatigue (42%), rashes (22%), nausea (20%), and fever (20%), while one patient developed severe deep venous thrombosis and tissue inflammation, which was not confirmed in previous clinical trials. CONCLUSIONS: The histological subtype, the intensity of the PD-L1 expression, and the timing of treatment affected the NSCLC therapeutic results. It is recommended that clinical tests be conducted in order to enhance therapeutic effectiveness. It is expected that more testing, observation-based studies, and research results will validate their efficacy and the tolerance levels of patients.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Fatiga/etiología , Femenino , Humanos , Inmunoterapia , Ipilimumab/efectos adversos , Ipilimumab/uso terapéutico , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Nivolumab/efectos adversos , Nivolumab/uso terapéutico , Estudios Retrospectivos , Taiwán , Resultado del Tratamiento
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