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Rational construction of high-efficiency photoelectrodes with optimized carrier migration to the ideal active sites, is crucial for enhancing solar water oxidation. However, complexity in precisely modulating interface configuration and directional charge transfer pathways retards the design of robust and stable artificial photosystems. Herein, a straightforward yet effective strategy is developed for compact encapsulation of metal oxides (MOs) with an ultrathin non-conjugated polymer layer to modulate interfacial charge migration and separation. By periodically coating highly ordered TiO2 nanoarrays with oppositely charged polyelectrolyte of poly(dimethyl diallyl ammonium chloride) (PDDA), MOs/polymer composite photoanodes are readily fabricated under ambient conditions. It is verified that electrons photogenerated from the MOs substrate can be efficiently extracted by the ultrathin solid insulating PDDA layer, significantly boosting the carrier transport kinetics and enhancing charge separation of MOs, and thus triggering a remarkable enhancement in the solar water oxidation performance. The origins of the unexpected electron-withdrawing capability of such non-conjugated insulating polymer are unambiguously uncovered, and the scenario occurring at the interface of hybrid photoelectrodes is elucidated. The work would reinforce the fundamental understanding on the origins of generic charge transport capability of insulating polymer and benefit potential wide-spread utilization of insulating polymers as co-catalysts for solar energy conversion.
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A highly enantioselective cobalt-catalyzed desymmetrizing reductive cyclization of alkynyl cyclodiketones has been developed. Under mild reaction conditions by employing HBpin as a reducing agent and ferrocene-based PHOX as a chiral ligand, a series of polycyclic tertiary allylic alcohols bearing contiguous quaternary stereocenters are achieved in moderate to excellent yields with excellent enantioselectivities (up to 99%). Broad substrate scope and high functional group compatibility are observed in this reaction. A CoH-catalyzed pathway involving alkyne hydrocobaltation followed by nucleophilic addition to the C[double bond, length as m-dash]O bond is proposed. Synthetic transformations of the product are conducted to demonstrate the practical utilities of this reaction.
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The advent of immunotherapy and the development of immune checkpoint inhibitors (ICIs) are changing the way we think about cancer treatment. ICIs have shown clinical benefits in a variety of tumor types, and ICI-based immunotherapy has shown effective clinical outcomes in immunologically "hot" tumors. However, for immunologically "cold" tumors such as colorectal cancer (CRC), only a limited number of patients are currently benefiting from ICIs due to limitations such as individual differences and low response rates. In this review, we discuss the classification and differences between hot and cold CRC and the current status of research on cold CRC, and summarize the treatment strategies and challenges of immunotherapy for cold CRC. We also explain the mechanism, biology, and role of immunotherapy for cold CRC, which will help clarify the future development of immunotherapy for cold CRC and discovery of more emerging strategies for the treatment of cold CRC.
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PURPOSE: To investigate the application value of nitrous oxide/oxygen inhalation comfort technique during tooth extraction in elderly patients with hypertension under electrocardiographic(ECG) monitoring. METHODS: According to the inclusion and exclusion criteria, sixty elderly patients (over 65 years old) with hypertension for tooth extraction were randomly divided into 2 groups: the experimental group(nitrous oxide/oxygen inhalation combined with ECG monitoring group, n=30) and the control group (routine ECG monitoring group, n=30). Mean arterial pressure (MAP) and heart rate (HR) at T0 (baseline values before surgery), T1 (on local anesthesia), T2 (during operation) and T3(5 minutes after operation) were recorded. SPSS 25.0 software package was used for statistical analysis. RESULTS: There was no significant difference in MAP and HR at each time point in the experimental group(Pï¼0.05). There was no significant difference in MAP and HR at T0 and T3 time points in the control group(Pï¼0.05). At other time points, MAP and HR were significantly different (Pï¼0.05). There was no significant differences in MAP and HR between the two groups at T0 and T3(Pï¼0.05). MAP and HR at T1 and T2 in the experimental group were significantly less than those in the control group(Pï¼0.05). CONCLUSIONS: Nitrous oxide/oxygen inhalation comfort technology can stabilize patients' emotions and maintain stable blood pressure and heart rate in elderly patients with hypertension during tooth extraction, thus improving the safety of tooth extraction.
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Hipertensión , Óxido Nitroso , Humanos , Anciano , Óxido Nitroso/efectos adversos , Oxígeno , Extracción Dental/efectos adversos , Atención OdontológicaRESUMEN
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Its invasiveness and ability to metastasize contributes to an extremely high patient mortality. However, the molecular mechanisms that underlie the characteristics of HCC progression are not well understood. BRF2 has been shown to be an oncogene in a number of tumors; however, its role in HCC has not yet been thoroughly examined. In this study, we identified and validated BRF2 as an oncogene in HCC, providing a new insight into HCC pathogenesis and therapeutic possibilities. We showed that BRF2 expression was significantly upregulated in HCC cell lines and tissues, while BRF2 depletion suppressed HCC metastasis and invasion. We then examined the upstream regulation of BRF2 and identified miR-409-3p as being predicted to bind to the 3' UTR of BRF2. We used a luciferase activity assay and functional verification to show that BRF2 is downregulated by miR-409-3p. Finally, we used bioinformatic analysis to show that BRF2 may be related to early HCC development through the Wnt/ß-catenin signaling pathway.
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OBJECTIVE: Ubiquitin conjugate enzyme E2O (UBE2O) is a ubiquitin-conjugating enzyme that has been reported to be involved in tumorigenesis. This study investigated the role of UBE2O in hepatocellular carcinoma (HCC). METHODS: The expression of UBE2O was detected using qRT-PCR, Western blotting, and immunohistochemical staining. Cell proliferation and Transwell assays were used to detect proliferation, migration, and invasion of HCC cells, respectively. Bioinformatic analysis was performed to analyze the relationship between UBE2O and the clinical features, prognosis, and immune cell infiltration of HCC. RESULTS: UBE2O was significantly over-expressed in HCC tissues. High expression of UBE2O was associated with poor tumor grade and poor prognosis. Functional experiments showed that down-regulation of UBE2O inhibited HCC cell proliferation, migration, and invasion. Co-expression gene analysis and gene set enrichment analysis showed that UBE2O was associated with protein hydrolysis, cell cycle, and cancer-related pathways in HCC. The results of immune analysis revealed that the expression of UBE2O was positively correlated with the immune infiltration and expression of immune-related chemokines of HCC. CONCLUSIONS: UBE2O is significantly correlated with the prognosis of HCC and may be a valuable prognostic biomarker for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/metabolismo , Ubiquitina , Pronóstico , Línea Celular , Enzimas Ubiquitina-ConjugadorasRESUMEN
This study aimed to investigate time trends in diet quality and the consumption of major food groups and nutrients by race/ethnicity among adults in the United States. Dietary data from 19,192 adults aged ≥ 20 years from four National Health and Nutrition Survey (NHANES) cycles (2011-2018) were included. The Healthy Eating Index (HEI) 2015 scores (range: 0-100; higher scores indicate better diet quality) and dietary consumption of food groups and nutrients were estimated for each cycle. Linear regression was used to test trends. For the overall population, the estimated overall HEI-2015 scores significantly decreased (p for trend = 0.011). However, decreases were observed in the estimated consumption of added sugars and total carbohydrates, while the estimated consumption of soy products and polyunsaturated fatty acids was significantly increased. A significant decrease in overall HEI-2015 score was observed in the non-Hispanic white group, but not in other racial/ethnic groups. Decreases in added sugar intake were found in the non-Hispanic black and Hispanic groups; sodium intake significantly decreased in the non-Hispanic Asian group. From 2011 to 2018, there was a decrease in estimated overall diet quality in US adults; however, there were improvements in certain nutrients and dietary components. Nevertheless, disparities in diet quality exist among racial/ethnic groups.
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Etnicidad , Sodio en la Dieta , Adulto , Dieta , Carbohidratos de la Dieta , Humanos , Encuestas Nutricionales , Azúcares , Estados UnidosRESUMEN
PURPOSE: To compare the effect of two comfort techniques of nitrous oxide/oxygen inhalation and dexmedetomidine combined with flurbiprofen axetil sedation and analgesia in impacted teeth extraction among patients with hypertension. METHODS: According to the inclusion and exclusion criteria, sixty patients undergoing impacted teeth extraction with hypertension were randomly divided into 2 groups: X group( nitrous oxide/oxygen inhalation, n=30) and Y group(dexmedetomidine combined with flurbiprofen axetil assisted sedation and analgesia, n=30). The following parameters at T0(preoperative), T1(local anesthesia), T2 (surgical operation), and T3 (5 minutes after surgery) were recorded: mean arterial pressure(MAP), heart rate (HR), Ramsay sedation score, VAS pain score. SPSS 20.0 software package was used for statistical analysis. RESULTS: The parameters at each time point between the two groups were not significantly different (Pï¼0.05). Mood and hemodynamics at T1, T2 and T3 in each group were more stable compared with those at T0(Pï¼0.05). CONCLUSIONS: The two comfort techniques can stabilize the patients' mood, keep the patients' hemodynamics stable, and are safe and effective in extraction of impacted teeth among patients with hypertension.
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Dexmedetomidina , Hipertensión , Diente Impactado , Humanos , Óxido Nitroso , Oxígeno , Diente Impactado/cirugíaRESUMEN
Enantioselective [3 + 2] annulation of N-heteroarenes with alkynes has been developed via a cobalt-catalyzed dearomative umpolung strategy in the presence of chiral ligand and reducing reagent. A variety of electron-deficient N-heteroarenes, including quinolines, isoquinolines, quinoxaline, and pyridines, and internal or terminal alkynes are employed in this reaction, showing a broad substrate scope and good functionality tolerance. Annulation of electron-rich indoles with alkynes is also developed. This protocol provides a straightforward access to a variety of N-spiroheterocyclic molecules in excellent enantioselectivities (76 examples, up to 99% ee).
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PURPOSE: To investigate the influence of maxillary molars on the thickening of maxillary sinus mucosa by cone-beam CT (CBCT). METHODS: A total of 72 patients with periodontitis were included in the study and 137 cases of maxillary sinus were evaluated using CBCT for the following parameters: location, tooth, maximal mucosal thickness, alveolar bone loss, vertical intrabony pockets and minimal residual bone height. The maxillary sinus mucosal thickness ≥2 mm was defined as mucosal thickening. The parameters that could influence the dimensions of the maxillary sinus membrane were assessed. The data were analyzed using univariate analysis and binary logistic regression by SPSS 25.0 software package. RESULTS: Mucosal thickening was present in 56.2% of 137 cases and increased in frequency as the alveolar bone loss of the corresponding molar progressed from mild (21.1%) to moderate (56.1%) to severe (69.2%), and the risk of maxillary sinus mucosal thickening increased by 6-7 times (moderate OR=7.13, 95%CI: 1.37-37.21; severe OR=6.29, 95%CI: 1.06-37.37). The severity of vertical intrabony pockets was correlated with the presence of mucosal thickness (no intrabony pockets 38.7%; type â 63.4%; type â ¡ 79.4%), with an increased risk of maxillary sinus mucosal thickening (type â OR=3.72, 95%CI: 1.01-13.70; type â ¡ OR=5.39, 95%CI: 1.15-25.30). The minimal residual bone height was negatively correlated with the presence of mucosal thickness(≤4 mm OR=99.00, 95%CI: 17.42-562.79). CONCLUSIONS: Alveolar bone loss, vertical intrabony pockets and the minimal residual bone height in maxillary molars were significantly associated with mucosal thickening of the maxillary sinus.
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Pérdida de Hueso Alveolar , Periodontitis , Humanos , Seno Maxilar/diagnóstico por imagen , Membrana Mucosa , Periodontitis/complicaciones , Diente Molar/diagnóstico por imagen , Tomografía Computarizada de Haz Cónico/métodos , Estudios RetrospectivosRESUMEN
Plexiform neurofibroma (pNF) in the head and neck is a characteristic feature in patients with neurofibromatosis type 1 (NF1) and is associated with significant disfigurement and psychological distress. Yes-associated protein (YAP), the key molecule involved in the Hippo pathway, is a vital transductor that regulates the proliferation and remyelinating of Schwann cells. The functional status of YAP and its feasibility as a potential target are still unknown in pNF. A total of 17 pNF tumor tissue specimens from the head and neck were collected at the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Histologically, diagnosis of the Schwann cell region in pNF was achieved with hematoxylin-eosin staining, positive reactions for S100, SOX10, ERK and p-ERK, and low identification of Ki67 and SMA. Compared with normal nerve tissue, obviously increased nuclear YAP was detected in the Schwann cell region of pNF, with a mean nuclear staining rate of 67.11%. Based on the shNF1 Schwann cell model (the RSC96 cell line), with upregulated expression of RAS, ERK and p-ERK, p-YAP (Ser127) and p-YAP (Ser397) were significantly decreased and total YAP and nuclear YAP were increased. According to a confocal assay, the interference of shNF1 substantially promoted YAP nuclear translocation. Compared with control Schwann cells, the YAP inhibitor CA3 might have a more sensitive effect (IC50: NC=0.96±0.04, shNF1=0.71±0.02, P<0.05) on the shNF1 Schwann cell model than the classic MEK1/2 inhibitor selumetinib (IC50: NC=14.36±0.95, shNF1=24.83±0.98, P>0.05). For in vivo inhibition, the CA3 group and the selumetinib group displayed a similar inhibition effect with no significant difference. Increased nuclear translation and the functional state of YAP implies that the YAP-Hippo pathway might play an important role in the formation and remyelination of pNF. Compared with selumetinib, the YAP inhibitor can exhibit a similar but more sensitive effect on NF1-/- Schwann cells. These observations imply that YAP as a novel or adjuvant therapy target in the treatment of pNF.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Antineoplásicos/farmacología , Neurofibroma Plexiforme/genética , Neurofibromatosis 1/complicaciones , Células de Schwann/patología , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Adolescente , Adulto , Animales , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Niño , Preescolar , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Terapia Molecular Dirigida/métodos , Neurofibroma Plexiforme/tratamiento farmacológico , Neurofibroma Plexiforme/patología , Neurofibromatosis 1/tratamiento farmacológico , Neurofibromatosis 1/genética , Factores de Transcripción/antagonistas & inhibidores , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas Señalizadoras YAP , Adulto JovenRESUMEN
OBJECTIVE: Common venous malformations (VMs) are a frequent sporadic subtype of vascular malformations. Given the TEK and PIK3CA mutations identified, this study aims to investigate the genetic landscape of VMs in the head and neck. METHODS: Patients from published sequencing studies related to common VMs were reviewed. Detailed data regarding clinical characteristics, sequencing strategies, and mutation frequency were synthesized. Lesion distribution of common VMs in the head and neck were further retrospectively analyzed by the pathologic database of the Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital. For the frequently affected sites in the head and neck, patients were selected for targeted sequencing with a designed vascular malformation-related gene panel or whole exome sequencing. Detected variants were analyzed by classical bioinformatic algorithms (SIFT23, PolyPhen-2 HDIV, LRT, MutationTaster, Mutation Assessor, and GERP++). To confirm the expression pattern of particular candidate gene, specimens were examined histochemically. Gene ontology enrichment analysis and a protein-protein interaction network were also constructed. RESULTS: Three hundred patients from eight sequencing studies related to common VMs were reviewed. The total prevalence rates of TEK and PIK3CA mutations were 41.3% and 26.7%, respectively. The most frequent TEK/PIK3CA mutations were TEK-L914F/PIK3CA-H1047R. TEK/PIK3CA mutations existed in 70.3% and 2.7% of VMs in the head and neck. In retrospective data from 649 patients carrying cervicofacial VMs at Shanghai Ninth Hospital, the most frequent sites were the maxillofacial region (lips, cheek, parotid-masseteric region, submandibular region) and the oral and oropharyngeal region (buccal mucosa, tongue). Targeted sequencing for 14 frequent lesions detected TEK variants in three patients (21.4%), but no PIK3CA mutations. On whole exome sequencing of two patients without TEK/PIK3CA mutations, CDH11 was the only shared deleteriously mutated gene. Bioinformatic analyses of CDH11 implied that genes involved in cellular adhesion and junctions formed a significant portion. CONCLUSIONS: Common VMs of the head and neck have a unique genetic landscape. Novel CDH11 and TEK variants imply that pathogenesis is mediated by the regulatory relationship between endothelial cells and extracellular components.
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Fosfatidilinositol 3-Quinasa Clase I/genética , Células Endoteliales/fisiología , Cabeza/irrigación sanguínea , Mutación , Cuello/irrigación sanguínea , Receptor TIE-2/genética , Malformaciones Vasculares/genética , Cadherinas/genética , Humanos , Estudios Retrospectivos , Malformaciones Vasculares/patologíaRESUMEN
The widely usage of silver nanoparticles in a range of consumer products inevitably results in its being released to the wastewater. As a result, the potential negative effects associated with AgNPs on wastewater treatment systems need to be assessed to develop the regulatory guidelines. In this paper, the exposure experiment at environmentally relevant concentration (100⯵gâ¯L-1) were conducted to demonstrate the effects of AgNPs on the pollutant removals in constructed wetlands (CWs) with different plants and the spatial distribution of silver. Before adding AgNPs, the system with Arundo donax (VF2) had the better nitrogen removal than Cyperus alternifolius (VF1). After exposure for about 94â¯d, the average removal efficiencies of NH4+-N significantly reduced by 32.43% and 23.92%, TN of 15.82% and 17.18% and TP of 22.74% and 20.46% in VF1 and VF2, respectively, while the COD removal had no difference. However, presence of 100⯵gâ¯L-1 AgNPs for about 450â¯d showed no inhibition effects on nutrient removals in two experimental CWs. Two wetlands showed high removal efficiencies of about 98% on AgNPs, indicating CWs could play a crucial role to control the AgNPs release to environment. It was found that AgNPs mainly accumulated in the soil layer with the Ag content of 0.45-5.96⯵gâ¯g-1 dry weight in lower soil and 2.84-11.37⯵gâ¯g-1 dry weight in upper soil. The roots of Cyperus alternifolius absorbed more AgNPs, with higher bioconcentration factors (1.32-1.44) than that of 0.59 in Arundo donax. The differences of translocation factors on leaves and stems in two test plants showed that AgNPs assimilated by roots in Cyperus alternifolius were more easily transferred to the leaves. The obtained results showed that the macrophyte Cyperus alternifolius could be better choice for immobilization of AgNPs.
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Biodegradación Ambiental , Cyperus/metabolismo , Nanopartículas del Metal/toxicidad , Poaceae/metabolismo , Plata/toxicidad , Contaminantes Químicos del Agua/análisis , Nitrógeno/análisis , Suelo/química , Eliminación de Residuos Líquidos/métodos , Aguas Residuales/química , HumedalesRESUMEN
Analysis and characterization of micro/nano-sized pore structure are critical issues in shale geology and engineering. Scanning electron microscopy (SEM) imaging is one of the most widespread methods for the analysis of the micro/nano-sized pores in shale, but precise identification of the ultrafine pore structure in shale is still a big challenge because shale is so complex that some components may have overlap with pores based on the simple discrimination of gray scale under SEM microscopy. Here, Fe3O4/Au nanocomposite with magnetic properties is synthesized, characterized, and introduced as a novel pore-marker to improve SEM identification and quantitation of micro/nano-sized pores in shale. Due to the superparamagnetic property, the nanomarker is conveniently controlled by an external magnetic field to fill into pores and offers a sharp contrast imaging between matrix of shale (various gray) and pores (bright), which makes the identification of micro/nano-sized pores in shale much more straightforward and reliable. Furthermore, because gold, as a noble metal, is particularly rare in shale, energy-dispersive X-ray spectroscopy mapping of Au is delicately used to precisely calculate area porosity in shale. Combining with the aforementioned merits of the nanomarker, a precise and practical technique is proposed to promote characterization of micro/nano-sized pores in shale.
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Analysis of complex pore structure of geomaterials is a fundamental issue in geoscience. Here bifunctional nanoparticles with magnetic and fluorescent properties are introduced as novel markers for optical imaging of pore structure in geomaterials. Using the paramagnetic property, powder of the nanoparticle is driven into pores under an external magnetic field, avoiding a tedious sample preparation and eliminating artificial damage of sample preparation in conventional methods. Meanwhile, the fluorescent nanoparticle marker offers a sharp contrast imaging between the rock matrix (black) and pores (bright) under microscopy. Furthermore, fluorescent nanoparticles with different sizes and colors are designed to demonstrate the potential of the method for describing pore throat sizes. Combining the merits of the paramagnetic and fluorescent properties of nanoparticles, a convenient and practical sample preparation is proposed to promote optical imaging analysis of the pore structure in geomaterials.
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BACKGROUND: Treatment-experienced chronic hepatitis C (CHC) genotype (GT) 1b represents a major medical burden in China. We evaluate the efficacy, safety and cost-effectiveness of ribavirin (RBV)-free pan-oral direct-acting antivirals (DAAs) in treatment-experienced Chinese with GT1b CHC, including patients with cirrhosis. METHODS: One hundred forty treatment-experienced GT1b CHC Chinese with and without cirrhosis were included in this study. Ninety-four patients were treated with either daclatasvir (DCV, 60 mg)-sofosbuvir (SOF, 400 mg) (group 1, n = 46) or ledipasvir (LDV, 90 mg)-SOF (400 mg) (group 2, n = 48) for 12 weeks. Forty-six patients treated with pegylated interferon and RBV therapy for 72 weeks were enrolled as the control group (group 3). Patients were followed at 4-weekly intervals till 24 weeks after the end of treatment. RESULTS: All patients in group 1 (46/46, 100 %) and 2 (48/48, 100 %) had achieved sustained virologic response at 24 weeks after the end of treatment (SVR 24), which was significantly higher than that of group 3 (13/46, 28.3 %) (p < 0.001). The SVR 24 rates of cirrhotic patients in group 1 (27/27, 100 %) and 2 (27/27, 100 %) were also significantly higher than that of group 3 (3/25, 12 %) (p < 0.001). Twelve weeks of RBV-free LDV-SOF and DCV-SOF was either cost-saving or cost-effective. Adverse events were significantly lower in group 1 and 2 compared with group 3 (p < 0.001). CONCLUSION: Compared with standard therapies, 12 weeks of RBV-free DAA therapies is highly effective, well tolerated and cost-effective in treatment-experienced Chinese with GT1b CHC including patients with cirrhosis.
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Antivirales/administración & dosificación , Quimioterapia Combinada/economía , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antivirales/economía , China , Análisis Costo-Beneficio , Femenino , Genotipo , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/economía , Hepatitis C Crónica/virología , Humanos , Cirrosis Hepática/economía , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ribavirina/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions. METHODS: A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable. RESULTS: Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US$21,612. It varied by economic regions. The probability of cost-effectiveness was 18% and 47% for treatment-naive and experienced patients, and it ranged from 15% in treatment-naïve patients in Central-China to 64% in treatment-experienced patients in Eastern-China. The price of 12-week sofosbuvir/ledipasvir treatment needs to be reduced by at least 81% to US$18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US$105 to make the regimen affordable in average patients in China. CONCLUSION: Sofosbuvir/ledipasvir regimen is not cost-effective in most Chinese patients with genotype 1b HCV infection. The results vary by economic regions. Drug price of sofosbuvir/ledipasvir needs to be substantially reduced when entering the market in China to ensure the widest accessibility.
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Bencimidazoles/economía , Fluorenos/economía , Hepacivirus , Hepatitis C/economía , Modelos Económicos , Sofosbuvir/economía , Pueblo Asiatico , Bencimidazoles/administración & dosificación , China/epidemiología , Costos y Análisis de Costo , Femenino , Fluorenos/administración & dosificación , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Humanos , Masculino , Cadenas de Markov , Sofosbuvir/administración & dosificaciónRESUMEN
Superparamagnetic iron oxide (SPIO) nanoparticles generate superparamagnetism, thereby resulting in an inhomogeneous local magnetic field, which shortens the T2 value on magnetic resonance imaging (MRI). The purpose of the present study was to use MRI to track bone marrow mesenchymal stem cells (BMSCs) labeled with SPIO in a rat model of myocardial infarction. The BMSCs were isolated from rats and labeled with SPIO. The anterior descending branch of the coronary artery was ligated under anesthesia. Two weeks later, the rats received, at random, 5 x 10(7) SPIO-labeled BMSCs, 5 x 10(7) unlabeled BMSCs or a vehicle (100 µl phosphate-buffered saline) via direct injection into the ischemic area (20 animals/group). MRI was used to track the SPIOlabeled BMSCs and the rats were then sacrificed to verify the presence of BMSCs using immunohistochemistry with an anti-CD90 antibody. The procedure labeled 99% of the BMSCs with SPIO, which exhibited low-intensity signals on T2 and T2* MRI imaging. At 24 h post-BMSC transplantation, low-intensity MRI signals were detected on the T2 and T2* sequences at the infarction margins. After 3 weeks following transplantation, low-intensity signals started to appear within the infarcted area; however, the signal intensity subsequently decreased and became indistinct. Immunohistochemistry revealed that the SPIO-labeled BMSCs migrated from the margin into the infarcted region. In conclusion, the BMSCs were readily labeled with SPIO and in vivo and MRI tracking demonstrated that the SPIO-labeled BMSCs established and grew in the infarcted myocardium.
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Imagen por Resonancia Magnética , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/terapia , Animales , Técnicas de Cultivo de Célula , Separación Celular , Supervivencia Celular , Rastreo Celular , Modelos Animales de Enfermedad , Femenino , Óxido Ferrosoférrico , Infarto del Miocardio/diagnóstico , RatasRESUMEN
Transplantation of bone marrow mesenchymal stem cells is a promising new strategy for the repair of infarcted cardiac tissue. However, the majority of transplanted bone marrow mesenchymal stem cells (BMSCs) die soon after transplantation, due in part to oxidative stress in the ischemic region. Oxidative stress is known to induce apoptosis through the activation of caspase-3. The aim of this study is to determine whether small interfering RNA targeting caspase-3 can inhibit the apoptosis of rat BMSCs in vitro. Caspase-3 siRNA expression vectors were prepared and transfected into rat BMSCs in the presence of liposomes. Western blot assay and real-time polymerase chain reaction (RT-PCR) were performed to detect caspase-3 expression. A retrovirus packaging system was employed to package 293FT cells producing caspase-3 siRNA virus, which were transfected into rat BMSCs. Those stably expressing caspase-3 siRNA were screened by Western blot assay and RT-PCR to determine caspase-3 expression levels. Stable transfection of caspase-3 siRNA significantly decreased caspase-3 protein (0.26 ± 0.001 vs. 0.42 ± 0.004, P < 0.05) and mRNA expression (0.19 ± 0.002 vs. 1, P < 0.05) in BMSCs compared to non-transfected BMSCs. Cells were incubated in H2O2 to induce apoptosis, which was detected by TUNEL staining, and BMSC morphology was not altered by either transient or stable transfection of caspase-3 siRNA. H2O2-induced apoptosis of BMSCs stably transfected with caspase-3 siRNA was dramatically reduced compared to that of normal BMSCs (11.0 ± 3.2 vs. 25.8 ± 4.2, P < 0.05). Caspase-3 knockdown BMSCs are thus more resistant to apoptosis than normal BMSCs, potentially increasing their survival rates under conditions that cause oxidative stress.