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As a representative of the fourth-generation light sources, the High Energy Photon Source (HEPS) in Beijing, China, utilizes a multi-bend achromat lattice to obtain an approximately 100 times emittance reduction compared with third-generation light sources. New technologies bring new challenges to operate the storage ring. In order to meet the beam commissioning requirements of HEPS, a new framework for the development of high-level applications (HLAs) has been created. The key part of the new framework is a dual-layer physical module to facilitate the seamless fusion of physical simulation models with the real machine, allowing for fast switching between different simulation models to accommodate the various simulation scenarios. As a framework designed for development of physical applications, all variables are based on physical quantities. This allows physicists to analytically assess measurement parameters and optimize machine parameters in a more intuitive manner. To enhance both extensibility and adaptability, a modular design strategy is utilized, partitioning the entire framework into discrete modules in alignment with the requirements of HLA development. This strategy not only facilitates the independent development of each module but also minimizes inter-module coupling, thereby simplifying the maintenance and expansion of the entire framework. To simplify the development complexity, the design of the new framework is implemented using Python and is called Python-based Accelerator Physics Application Set (Pyapas). Taking advantage of Python's flexibility and robust library support, we are able to develop and iterate quickly, while also allowing for seamless integration with other scientific computing applications. HLAs for both the HEPS linac and booster have been successfully developed. During the beam commissioning process at the linac, Pyapas's ease of use and reliability have significantly reduced the time required for the beam commissioning operators. As a development framework for HLA designed for the new-generation light sources, Pyapas has the versatility to be employed with HEPS, as well as with other comparable light sources, due to its adaptability.
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Dark photons have emerged as promising candidates for dark matter, and their search is a top priority in particle physics, astrophysics, and cosmology. We report the first use of a tunable niobium superconducting radio-frequency cavity for a scan search of dark photon dark matter with innovative data analysis techniques. We mechanically adjusted the resonant frequency of a cavity submerged in liquid helium at a temperature of 2 K, and scanned the dark photon mass over a frequency range of 1.37 MHz centered at 1.3 GHz. Our study leveraged the superconducting radio-frequency cavity's remarkably high quality factors of approximately 10^{10}, resulting in the most stringent constraints to date on a substantial portion of the exclusion parameter space on the kinetic mixing coefficient ε between dark photons and electromagnetic photons, yielding a value of ε<2.2×10^{-16}.
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Despite the availability of various 11C-labeled positron emission tomography (PET) tracers for assessing P-glycoprotein (P-gp) function, there are still limitations related to complex metabolism, high lipophilicity, and low baseline uptake. This study aimed to address these issues by exploring a series of customized dihydropyridines (DHPs) with enhanced stability and reduced lipophilicity as alternative PET tracers for P-gp dysfunction. Compared with verapamil and the rest DHPs, dimethyl 4-(4-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (1) exhibited superior cellular uptake differences between the human gastric cancer cell line SGC7901 and its drug-resistant counterpart. [18F]1 is successfully synthesized using a novel "hot-Hantzsch" approach in 22.1 ± 0.1 % radiochemical yields. MicroPET/CT imaging demonstrated that the uptake of [18F]1 in the brains of P-gp blocked mice increased by > 3 times compared to the control group. Additionally, [18F]1 displayed favorable lipophilicity (log D = 2.3) and excellent clearance characteristics, making it a promising tracer candidate with low background noise and high contrast.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Dihidropiridinas , Radioisótopos de Flúor , Tomografía de Emisión de Positrones , Dihidropiridinas/química , Dihidropiridinas/síntesis química , Dihidropiridinas/farmacología , Humanos , Animales , Radioisótopos de Flúor/química , Ratones , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Línea Celular Tumoral , Estructura Molecular , Radiofármacos/química , Radiofármacos/síntesis química , Radiofármacos/farmacología , Relación Estructura-Actividad , Distribución TisularRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with poor prognosis. Evidence has shown that vimentin is a key regulator of lung fibrogenesis. 99mTc-labeled N-acetylglucosamine-polyethyleneimine (NAG-PEI), a vimentin-targeting radiotracer, was used for the early diagnosis of IPF, and NAG-PEI was also used as a therapeutic small interfering RNA (siRNA) delivery vector for the treatment of IPF in this study. Single-photon emission-computed tomography (SPECT) imaging of bleomycin (BM)- and silica-induced IPF mice with 99mTc-labeled NAG-PEI was performed to visualize pulmonary fibrosis and monitor the treatment efficiency of siRNA-loaded NAG-PEI, lipopolysaccharide (LPS, a tolerogenic adjuvant), or zymosan (ZYM, an immunostimulant). The lung uptakes of 99mTc-NAG-PEI in the BM- and silica-induced IPF mice were clearly and directly correlated with IPF progression. The lung uptake of 99mTc-NAG-PEI in the NAG-PEI/TGF-ß1-siRNA treatment group or LPS treatment group was evidently lower than that in the control group, while the lung uptake of 99mTc-NAG-PEI was significantly higher in the ZYM treatment group compared to that in the control group. These results demonstrate that NAG-PEI is a potent MicroSPECT imaging-guided theranostic platform for IPF diagnosis and therapy.
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Fibrosis Pulmonar Idiopática/tratamiento farmacológico , ARN Interferente Pequeño/administración & dosificación , Radiofármacos/administración & dosificación , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Vimentina/antagonistas & inhibidores , Acetilglucosamina/administración & dosificación , Acetilglucosamina/química , Animales , Biodiversidad , Bleomicina/administración & dosificación , Bleomicina/toxicidad , Modelos Animales de Enfermedad , Femenino , Humanos , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/patología , Pulmón/diagnóstico por imagen , Pulmón/efectos de los fármacos , Pulmón/patología , Ratones , Polietileneimina/administración & dosificación , Polietileneimina/química , ARN Interferente Pequeño/genética , Radiofármacos/química , Radiofármacos/farmacocinética , Dióxido de Silicio/administración & dosificación , Dióxido de Silicio/toxicidad , Tecnecio , Tomografía Computarizada de Emisión de Fotón Único , Factor de Crecimiento Transformador beta1/metabolismo , Vimentina/metabolismoRESUMEN
To determine the epidemiology of coronavirus disease (COVID-19) in a remote region of China, far from Wuhan, we analyzed the epidemiology of COVID-19 in Gansu Province. From January 23 through February 3, 2020, a total of 35 (64.8%) of 54 reported cases were imported from COVID-19-epidemic areas. Characteristics that differed significantly during the first and second waves of illness in Gansu Province were mean patient age, occupation, having visited epidemic areas, and mode of transportation. Time from infection to illness onset for family clusters was shorter in Gansu Province than in Wuhan, consistent with shortened durations from onset to first medical visit or hospitalization. Spatial distribution pattern analysis indicated hot spots and spatial outliers in Gansu Province. As a result of adequate interventions, transmission of the COVID-19 virus in Gansu Province is decreasing.
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Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus , COVID-19 , Niño , Preescolar , China/epidemiología , Femenino , Sistemas de Información Geográfica , Hospitalización , Humanos , Lactante , Masculino , Persona de Mediana Edad , Pandemias , SARS-CoV-2 , Análisis Espacial , Factores de Tiempo , Adulto JovenRESUMEN
The outbreak of the novel coronavirus disease (COVID-19) quickly spread all over China and to more than 20 other countries. Although the virus (severe acute respiratory syndrome coronavirus [SARS-Cov-2]) nucleic acid real-time polymerase chain reaction (PCR) test has become the standard method for diagnosis of SARS-CoV-2 infection, these real-time PCR test kits have many limitations. In addition, high false-negative rates were reported. There is an urgent need for an accurate and rapid test method to quickly identify a large number of infected patients and asymptomatic carriers to prevent virus transmission and assure timely treatment of patients. We have developed a rapid and simple point-of-care lateral flow immunoassay that can detect immunoglobulin M (IgM) and IgG antibodies simultaneously against SARS-CoV-2 virus in human blood within 15 minutes which can detect patients at different infection stages. With this test kit, we carried out clinical studies to validate its clinical efficacy uses. The clinical detection sensitivity and specificity of this test were measured using blood samples collected from 397 PCR confirmed COVID-19 patients and 128 negative patients at eight different clinical sites. The overall testing sensitivity was 88.66% and specificity was 90.63%. In addition, we evaluated clinical diagnosis results obtained from different types of venous and fingerstick blood samples. The results indicated great detection consistency among samples from fingerstick blood, serum and plasma of venous blood. The IgM-IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test. It can be used for the rapid screening of SARS-CoV-2 carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories.
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Anticuerpos Antivirales/inmunología , COVID-19/diagnóstico , COVID-19/inmunología , Inmunoensayo , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , COVID-19/virología , Humanos , Inmunoensayo/métodos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Pruebas en el Punto de Atención , Juego de Reactivos para Diagnóstico , Tiras Reactivas , Sensibilidad y EspecificidadRESUMEN
Complement factor H (CFH) is a soluble complement regulatory protein essential for the down-regulation of the alternative pathway on interaction with specific markers on the host cell surface. It recognizes the complement component 3b (C3b) and 3d (C3d) fragments in addition to self cell markers (i.e. glycosaminoglycans, sialic acid) to distinguish host cells that deserve protection from pathogens that should be eliminated. The Staphylococcus aureus surface protein serine-aspartate repeat protein E (SdrE) was previously reported to bind human CFH as an immune-evasion tactic. However, the molecular mechanism underlying SdrE-CFH-mediated immune evasion remains unknown. In the present study, we identified a novel region at CFH's C-terminus (CFH1206-1226), which binds SdrE N2 and N3 domains (SdrEN2N3) with high affinity, and determined the crystal structures of apo-SdrEN2N3 and the SdrEN2N3-CFH1206-1226 complex. Comparison of the structure of the CFH-SdrE complex with other CFH structures reveals that CFH's C-terminal tail flips from the main body to insert into the ligand-binding groove of SdrE. In addition, SdrEN2N3 adopts a 'close' state in the absence of CFH, which undergoes a large conformational change on CFH binding, suggesting a novel 'close, dock, lock and latch' (CDLL) mechanism for SdrE to recognize its ligand. Our findings imply that SdrE functions as a 'clamp' to capture CFH's C-terminal tail via a unique CDLL mechanism and sequesters CFH on the surface of S. aureus for complement evasion.
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Proteínas Bacterianas/metabolismo , Modelos Moleculares , Staphylococcus aureus , Apoproteínas/química , Apoproteínas/genética , Apoproteínas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Sitios de Unión , Factor H de Complemento/química , Factor H de Complemento/genética , Factor H de Complemento/metabolismo , Cristalografía por Rayos X , Humanos , Enlace de Hidrógeno , Evasión Inmune , Cinética , Ligandos , Mutación , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Conformación Proteica , Pliegue de Proteína , Dominios y Motivos de Interacción de Proteínas , Desplegamiento Proteico , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Staphylococcus aureus/inmunologíaRESUMEN
OBJECTIVE: To explore the protective effect and its mechanism of B7-H4 on the immuno hepatic injury. METHODS: The immuno hepatic injury was induced by Concanavalin A (Con A). Sixty KM mice were randomly divided into 4 groups with 15 mice in each group: Group A (saline), Group B (pcDNA3.1-mB7-H4-Fc), Group C (pcDNA3.1), Group D (Con A). One day before the injection of Con A (25 mg/kg), the mice in Group B and Group C received the injection of 100 pg pcDNA3.1-mB7-H4-Fc and 100 microg pcDNA3.1 respectively. The blood samples were collected at 12 h, 24 h and 48 h after Con A injection, the levels of ALT, AST, IL-4 and IFN-gamma were measured. Five mice in each group were sacrificed at the above 3 time points, the liver tissue were harvested for histopathological detection. RESULTS: After Con A injection, the level of ALT in Group B, C, and D were higher than that in Group A. The level of ALT in Group B was lower than that in Group C and D. The significant difference was found between Group B and Group C. The hepatic injury of Group B was less serious than that of Group C and D. CONCLUSION: B7-H4 may have protection on the immune injury of liver induced by Con A.
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Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Concanavalina A/efectos adversos , Inhibidor 1 de la Activación de Células T con Dominio V-Set/farmacología , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Ratones , Sustancias Protectoras/farmacologíaRESUMEN
OBJECTIVE: The purpose of this study was to determine the causal effect of statins on osteoarthritis (OA) risk using Mendelian randomization (MR). METHODS: Single nucleotide polymorphism-based genome-wide association analyses of statins were collected from the UK Biobank and FinnGen dataset, and OA data were collected from the UK Biobank and Arthritis Research UK Osteoarthritis Genetics (arcOGEN) study. Two-sample MR analyses were performed using the inverse-variance weighted (IVW) technique. MR-Egger, weighted median, and weighted mode served as supplementary analyses. MR-Egger regression, Cochran's Q test, and Mendelian Randomization Pleiotropy Residual Sum and Outlier analysis were performed as sensitivity analyses. Hydroxymethylglutaryl-coenzyme A reductase (HMGCR) expression and OA risk were evaluated using summary data-based MR (SMR). RESULTS: MR analyses consistently supported a causal connection between statin use and OA risk. A causal effect was observed for atorvastatin (IVW: ß = -2.989, P = 0.003) and rosuvastatin (IVW: ß = -14.141, P = 0.006) treatment on hip OA. Meta-analysis showed the association between atorvastatin and knee OA was statistically significant (odds ratio 0.15; P = 0.004). Simvastatin use exhibited a protective effect against knee (IVW: ß = -1.056, P = 0.004) and hip OA (IVW: ß = -1.405, P = 0.001). Statin medication showed a protective effect on hip OA (IVW: ß = -0.054, P = 0.013). HMGCR correlated significantly with a reduced risk of knee OA (ß = -0.193, PSMR = 0.017), rather than hip OA (ß = 0.067, PSMR = 0.502), which suggested that statins' protective effect on OA may not be related to its lipid-lowering effect. CONCLUSION: This MR study provides compelling evidence that statin treatment may be a protective factor for OA. Further research is required to clarify its underlying mechanism.
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Estudio de Asociación del Genoma Completo , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Osteoartritis de la Cadera/genética , Osteoartritis de la Cadera/prevención & control , Osteoartritis de la Cadera/epidemiología , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/prevención & control , Osteoartritis de la Rodilla/epidemiología , Factores de Riesgo , Hidroximetilglutaril-CoA Reductasas/genética , Medición de Riesgo , Masculino , Osteoartritis/genética , Osteoartritis/epidemiología , Osteoartritis/prevención & control , Femenino , Factores Protectores , Rosuvastatina Cálcica/uso terapéutico , Persona de Mediana EdadRESUMEN
OBJECTIVE: To evaluate mindfulness-based intervention for hypertension with depression and/or anxiety. METHODS: 10-week mindfulness-based intervention, including health education for hypertension, exclusively for the control group, was administered to the intervention group to assist sixty hypertension patients with depression/anxiety. Among them, the intervention group comprised 8 men and 22 women, with a mean age of 60.02 years and a mean duration of hypertension of 6.29 years. The control group consisted of 14 men and 16 women with a mean age of 57.68 years and a mean duration of hypertension of 6.32 years. The severity of depressive and/or anxiety symptoms was assessed using the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder scale (GAD-7), along with blood pressure (BP) measurements taken twice daily. The study utilized a self-made self-efficacy scale and awareness of physical and mental health to evaluate mental health and state. RESULTS: The depression PHQ-9 or GAD-7 scores reduced by 21.1% or 17.8% in the mindfulness-based intervention group, compared to the control (Z = -2.040, P = 0.041) post 10-week period, suggesting significant reduction in anxiety/stress. These results were consistent with a reduction in systolic BP of 12.24 mm Hg (t = 6.041, P = 0.000). The self-efficacy score of the mindfulness intervention group significantly improved compared to the control (t = 7.818, P < 0.001), while the awareness of physical and mental health in the mindfulness intervention group significantly improved compared to the control (χ2 = 5.781, P = 0.016). CONCLUSION: Mindfulness-based, short-term focused interventions provide modest relief for depression and/or anxiety and are effective in lowering blood pressure and improving self-efficacy scores. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900028258. Registered 16 December 2019, https://www.chictr.org.cn/showproj.html?proj=43627 .
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Ansiedad , Depresión , Hipertensión , Atención Plena , Humanos , Masculino , Atención Plena/métodos , Femenino , Persona de Mediana Edad , Hipertensión/terapia , Hipertensión/psicología , Depresión/terapia , Depresión/psicología , Ansiedad/terapia , Ansiedad/psicología , Anciano , Resultado del Tratamiento , Presión Sanguínea , Autoeficacia , Factores de Tiempo , Salud MentalRESUMEN
OBJECTIVE: To evaluate the effectiveness of acupuncture in relieving diabetic neuropathic pain and to establish a more reliable and efficient foundation for acupuncture practice in diabetes care. METHODS: The Chinese National Knowledge Infrastructure, Wanfang database, Chongqing Weipu, Chinese Biomedical Literature Database, PubMed, Embase, and Cochrane Library were all searched for a randomized controlled trial research of acupuncture for DNP. Two researchers independently performed literature screening, quality evaluation, and data extraction. After selecting studies and extracting data, we conducted the data analysis using RevMan 5.4 and Stata 14.0. The quality was assessed using the Cochrane Risk of Bias Assessment Tool. RESULTS: An extensive review of 19 studies involving 1276 patients up to April 29, 2023, found that acupuncture was successful in improving pain intensity [MD= -1.09; 95% CI (-1.28, -0.89), P < 0.00001], clinical efficacy indicating pain changes [RR= 1.22; 95% CI (1.15, 1.29), P < 0.00001], and clinical neuropathy [MD= -1.55; 95% CI ( -3.00, -0.09), P = 0.04] in DNP patients. Quality of life was also improved, with few side effects reported. CONCLUSION: According to this meta-analysis, acupuncture therapy significantly improved the clinical efficacy of pain intensity, pain changes, and clinical neuropathy in patients with DNP, improved the quality of life of patients to a certain extent, and had lower side effects. This discovery provides evidence-based and practical recommendations for the treatment of DNP patients.
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Terapia por Acupuntura , Diabetes Mellitus , Neuropatías Diabéticas , Neuralgia , Humanos , Calidad de Vida , Terapia por Acupuntura/efectos adversos , Neuropatías Diabéticas/terapia , Resultado del Tratamiento , Neuralgia/terapia , Neuralgia/etiología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: Hypertension, one of the most common chronic diseases worldwide, usually requires lifetime managing blood pressure (BP) with medications. Due to quite large number of hypertension patients co-exist with depression and/or anxiety, and non-cooperated with medical instruction, consequently management of BP is impaired with serious complications, resulting in compromised quality of life. Consequently quality of life of such patients is impaired with serious complications. Therefore, management of depression and/or anxiety is equally important as the treatment of hypertension. Depression and/or anxiety are independent risk factors of hypertension, which is supported by the finding that there is close correlation between hypertension are depression/or anxiety. Psychotherapy (non-drug treatment) maybe useful for hypertensive patients with depression and/or anxiety to improve their negative emotions. We aim to quantify the effective of psychological therapies in the management of hypertension patients with depression or anxiety, by comparing and ranking a network meta-analysis (NMA). MATERIALS AND METHODS: Literature search for randomized controlled trials (RCTs) will be performed in five electronic databases from inception to December 2021, including PubMed, the Cochrane library, Embase, Web of Science, and China Biology Medicine disc (CBM). The search terms mainly include "hypertension", "mindfulness-based stress reduction" (MBSR), "cognitive behavioral therapy" (CBT) and "dialectical behavior therapy" (DBT). Cochrane Collaboration quality assessment tool will be used for the risk of bias assessment. A Bayesian network meta-analysis will be performed, using WinBUGS 1.4.3, and Stata 14 will be applied to draw the network diagram, while RevMan 5.3.5 will be used to produce funnel plot for assessing the risk of publication bias. Recommended rating, development and grade methodology will also be utilized to assess the quality of evidence. RESULTS: Effect of MBSR, CBT and DBT will be evaluated by traditional meta-analysis directly and Bayesian network meta-analysis indirectly. Our study will provide the evidence on the efficacy and safety of psychological treatments in the hypertension patients with anxiety. There is no research ethical requirement because this is a systematic review of published literature. The results of this study will be published in a peer-reviewed journal. TRIAL REGISTRATION: Prospero registration number: CRD42021248566.
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Terapia Cognitivo-Conductual , Hipertensión , Humanos , Depresión/complicaciones , Depresión/terapia , Metaanálisis en Red , Terapia Cognitivo-Conductual/métodos , Psicoterapia/métodos , Ansiedad/complicaciones , Ansiedad/terapia , Hipertensión/complicaciones , Hipertensión/terapia , Revisiones Sistemáticas como Asunto , Metaanálisis como AsuntoRESUMEN
OBJECTIVE: To evaluate the platelet inhibition efficacy in patients under regular maintenance dose of clopidogrel by VerifyNow-P2Y12 assay and explore the clinical characteristics of clopidogrel non-responders and related predicting factors. METHODS: A total of 99 patients underwent percutaneous coronary intervention procedure and receiving clopidogrel in regular maintenance dose for at least 1 week were enrolled. Platelet reactivity, including baseline, P2Y12 reaction unit (PRU), and platelet inhibition rate were measured with VeifyNow-P2Y12 assay. The dosage of anti-platelet drugs, combination with any other drugs, clinical characters in baseline of all enrolled patients were analyzed. PRU ≤ 240 was used as cut-off to identify clopidogrel responder and clopidogrel non-responder. In the non-responder group, patients were further separated into 3 sub-groups (types) according to the baseline and platelet inhibition rate: type I with high baseline, high inhibition rate, representing false non-responder; type II with low inhibition rate, representing true non-responder and type III mixed type. RESULTS: In this study, 48 of 99 patients were found to be clopidogrel non-responder (48.5%). The ratio of type I, type II and type III in the non-responder group was 9.1% (n = 9), 27.3% (n = 27), and 12.1% (n = 12), respectively. Baseline platelet value in female patients was significantly higher than in males (P < 0.01), number of females with high PRU also is higher than males (P < 0.01), female gender was a predict factor for type I non-responder (OR = 6.5, 95%CI 2.295 - 18.407, P < 0.01). BMI > 24 kg/m(2) was a risk factor for clopidogrel non-responder (P < 0.05), and may be regarded as a predict factor for type II non-responder (OR = 3.207, 95%CI 1.375 - 7.485, P < 0.01). Age, hypertension, diabetics, smoking, hyperlipidemia, CRP and pantoprazole use do not show significant correlation with baseline and platelet inhibition rate. CONCLUSIONS: Clopidogrel responses could be reliably detected by VerifyNow-P2Y12 assay. Female gender and high body weight are independent risk factors for clopidogrel non-responses.
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Angioplastia Coronaria con Balón , Inhibidores de Agregación Plaquetaria/farmacología , Receptores Purinérgicos P2Y12 , Ticlopidina/análogos & derivados , Anciano , Clopidogrel , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacos , Pruebas de Función Plaquetaria , Ticlopidina/farmacologíaRESUMEN
Carotenoid metabolism is critical for diverse physiological processes. The nematode Caenorhabditis elegans has two genes that are annotated as ß-carotene 15,15'-monooxygenase (BCMO) and are 17 centimorgan apart on chromosome II, but the function of BCMO-1 and BCMO-2 remains uncharacterized. Sequence homology indicates that the two enzymes belong to the carotenoid cleavage dioxygenase family that share a seven-bladed ß-propeller fold with a nonheme iron center. Here we determined crystal structures of BCMO-1 and BCMO-2 at resolutions of 1.8 and 1.9 Å, respectively. Structural analysis reveals that BCMO-1 and BCMO-2 are strikingly similar to each other. We also characterized their ß-carotene cleavage activity, but the results suggest that they may not act as ß-carotene 15,15'-oxygenases.
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Riboflavin transporter-3 (RFVT3) is a recently discovered and novel biomarker for the theranostics of nervous system diseases. RFVT3 is significantly overexpressed in cerebral injury after ischemic stroke. Herein, we first reported an RFVT3-targeted tracer 131I-riboflavin (131I-RFLA) for SPECT imaging of ischemic stroke in vivo. 131I-RFLA was radiosynthesized by the iodogen-coating method. 131I-RFLA possessed a radiochemical yield of 69.2 ± 3.7% and greater than 95% radiochemical purity. The representative SPECT/CT images using 131I-RFLA demonstrated the conspicuously increased tracer uptake in the cerebral injury by comparison with the contralateral normal brain at 1 h and 3 and 7 d after stroke. Ex vivo autoradiography demonstrated that the ratio of infarcted to normal brain uptake was 3.63 and it was decreased to 1.98 after blocking, which reconfirmed the results of SPECT images. Importantly, a significant correlation was identified between RFVT3 expression and brain injury by H&E and immunohistochemistry staining. Therefore, RFVT3 is a new and potential biomarker for the early diagnosis of ischemic stroke. In addition, 131I-RFLA is a promising SPECT tracer for imaging RFVT3-related ischemic cerebral injury in vivo.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Animales , Isquemia Encefálica/diagnóstico por imagen , Radioisótopos de Yodo , Proteínas de Transporte de Membrana/metabolismo , Radiofármacos , Ratas , Riboflavina/metabolismo , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
Fibrin glue combined with bone morphogenetic protein (BMP) and recombined bone xenograft (RBX), were compared to evaluate their effect on the tendon-bone interface healing. The interface of fibrin glue-BMP developed new cartilage but the new bone was thinner whereas the interface of RBX had large areas of chondrocyte-like cells, bone formation and an immature neo-enthesis structure. At 12 weeks, bone mineral density of RBX group (152 ± 52 cm(3)) and fibrin glue-BMP group (109 ± 13 cm(3)) was calculated by micro-computed tomography. The ultimate load of fibrin glue-BMP group (60 ± 18 and 51 ± 14 N) and RBX group (65 ± 21 and 57 ± 15 N) was shown by biomechanics at 6 and 12 weeks. RBX thus has an advantage on accelerating tendon-bone interface healing.
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Ligamento Cruzado Anterior , Huesos/metabolismo , Tendones/metabolismo , Andamios del Tejido/normas , Cicatrización de Heridas , Animales , Ligamento Cruzado Anterior/crecimiento & desarrollo , Ligamento Cruzado Anterior/cirugía , Fenómenos Biomecánicos , Proteínas Morfogenéticas Óseas/metabolismo , Proteínas Morfogenéticas Óseas/ultraestructura , Adhesivo de Tejido de Fibrina/química , Conejos , Procedimientos de Cirugía PlásticaRESUMEN
Objective: To determine the relationship between the health literacy of patients with diabetes mellitus (DM) and the accessibility of internet surfing for information concerning DM. Methods: A multistage stratified sampling method was utilized to conduct a questionnaire survey on DM health literacy and internet accessibility among 1,563 patients with DM in Gansu Province in 2020. Logistic regression was performed to analyze the factors that influence health literacy and internet accessibility; while the chi-square test was used to compare the differences in needs. Results: Among 1,563 valid questionnaires collected with an effective rate of 95.7%, there were 65.4, 66.3, or 51.1% of patients with DM were found to have good health knowledge, attitudes, or practice levels, respectively. Occupation, income, disease course of DM, and accessibility to the internet were the main factors influencing health literacy. Age, residency, occupation, education, income, and family history of DM were the factors influencing accessibility to internet surfing for DM. The expectations from patients with DM for the capacity to obtain DM information from traditional sources or through internet sources was 1,465 (93.7%) or 1,145 (73.3%), respectively. Patients with DM had a 2-fold higher desire to obtain DM health information from internet media if the patients had access to the internet than those without (P < 0.05). Conclusions: The socioeconomic status and access to the internet were the main contributing factors for health literacy, as socioeconomic status is closely related to access to the internet.
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Diabetes Mellitus , Alfabetización en Salud , China/epidemiología , Estudios Transversales , Diabetes Mellitus/epidemiología , Humanos , InternetRESUMEN
A circular electron positron collider (CEPC) will adopt hundreds of 650-MHz superconducting cavities with high quality factor (Q) and accelerating gradient (Eacc). Two 650-MHz single-cell cavities made of fine-grain niobium were first treated via buffered chemical polishing (BCP), which was easy and convenient. However, the vertical test results could not meet the specification of the CEPC (4 × 1010 at 22 MV/m). Therefore, electro-polishing (EP) of 650-MHz single-cell cavities was conducted, which was complicated but remarkably effective. Both 650-MHz single-cell cavities achieved state-of-the-art gradients of 35 MV/m after the EP process, which is extremely high for large elliptical cavities (frequency < 1 GHz). One cavity achieved an intrinsic quality factor (Q0) of 4.5 × 1010 at 22.0 MV/m, which was higher than the CEPC spec. The other cavity obtained a lower Q0 of 3.4 × 1010 at 22.0 MV/m, which may have resulted from the cancellation of high-temperature annealing.
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BACKGROUND: Mental health is closely related to the occurrence of hypertension, particularly the prognosis of hypertension patients. The role of psychotherapy in the occurrence, development, prevention, and prognosis of hypertension, remains to be clarified. METHODS/DESIGN: We will conduct a prospective, double-blind, randomized, multiple-centers study. Eighty patients enrolled in this trial will be randomized at 1:1 ratio. The primary endpoint is will be the reduction of the patient psychological scale (PHQ-9) score. Secondary endpoints will be the drop in blood pressure, awareness of physical and mental health and self-efficacy scale. Measurements will be performed at baseline, 5-week (questionnaires only), 10-week (primary endpoint), using the Anxiety Screening Questionnaire (GAD-7) and Depression Scale (PHQ-9). Data analysis will be carried out using the SPSS v.25 software assuming a level of significance of 5%. Results will be analyzed using multilevel, regression analysis and hierarchical linear models. DISCUSSION: We hope to provide some insight in the understanding the underlying mechanism of the novel mindfulness in the management of hypertension related psychological stress/disturbance, and will enable us to develop novel approach to manage essential hypertension and its related psychological disorders. CLINICAL TRIAL REGISTRY:: http://www.chictr.org.cn (ChiCTR1900028258).
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Trastornos de Ansiedad/psicología , Trastornos de Ansiedad/terapia , Trastorno Depresivo/psicología , Trastorno Depresivo/terapia , Hipertensión/psicología , Hipertensión/terapia , Psicoterapia/métodos , Método Doble Ciego , Humanos , Pronóstico , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The Arabidopsis thaliana atypical Cys His-rich thioredoxins (ACHTs) are a small class of atypical thioredoxins (TRXs) located in chloroplasts thylakoids and are characterized by a noncanonical motif at their redox active site, C (G/S)(S/G)C. Previous studies have reported that ACHT1 can interact with A. thaliana 2-Cys peroxiredoxins (2-Cys Prxs, including PrxA and PrxB) to transmit oxidation signals in response to illumination with normal light intensity. In this study, we reported the crystal structure of ACHT1 and show that ACHT1 adopts a canonical TRX fold. Comparison of the structures of ACHT1 in both reducing and oxidizing environments revealed that while the redox environment did not influence the overall structure of ACHT1, it did change the conformation of its catalytic residues. We found that the catalytic C125 of ACHT1 is the target residue for PrxA in vitro. In addition, we found that ACHT1 can reduce the peroxidase activity of PrxA, and further confirmed that the ability of ACHT1 to restore the peroxidase function of PrxA was due to the interaction between the two. Our results provide a structural basis for studying the function of atypical TRXs and the oxidative regulation mechanism of ACHT1 and 2-Cys Prxs in chloroplasts.