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Schedule exercise therapy (SET) is a novel nonpharmacological intervention for the treatment of chronic insomnia disorder (CID). The aim of this study was to explore the effects of SET on CID. Methods: One hundred and eighteen CID were recruited and randomized into medication (MED) or medication combined with SET (MSET) groups. Over 12 observational weeks, sleep and mood status were evaluated using the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS). At the end of the observational period, the rates of clinically effective hypnotic use were calculated. At 12 weeks, the PSQI progressively decreased for all subjects combined (Pâ <â .001) as well as ISI (Pâ <â .001), ESS (Pâ <â .001), SDS (Pâ <â .001), and SAS (Pâ <â .001). The decreases in PSQI (Pâ <â .05), ISI (Pâ <â .05), SDS (Pâ <â .01), and SAS (Pâ <â .05) in the MSET group were significantly larger than those in the MED group, but not the same as those in the ESS group (Pâ >â .05). At the trial endpoint, the clinically effective rate was significantly higher (Pâ <â .05) and the hypnotic usage rate was lower (Pâ <â .05) in the MSET group than in the MED group. SET may be an effective treatment for insomnia in patients with CID.
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Trastornos del Inicio y del Mantenimiento del Sueño , Afecto , Terapia por Ejercicio , Humanos , Hipnóticos y Sedantes/uso terapéutico , Sueño , Trastornos del Inicio y del Mantenimiento del Sueño/terapiaRESUMEN
Rare-earth titanate pyrochlores have attracted considerable attention for their unique magnetic frustration. Among those compounds, Yb2Ti2O7, a candidate for quantum spin ice, has been extensively studied in its magnetic ground state. However, works on its dielectric property and structure-property relationship lag far more behind. Here, by preparing and investigating nonstoichiometric Yb2-xTi2O7-δ (x = 0-0.15) ceramics, we demonstrate that the samples with x ≤ 0.05 maintain a single-pyrochlore phase, but the nonstoichiometry arouses significant structural distortion and increased oxygen vacancy. As a result, the ferromagnetism, indicated by a positive Curie-Weiss temperature, decreases almost linearly with increasing x value. Remarkably composition-dependent low-temperature dielectric relaxations have been observed. In addition, through introducing nonstoichiometry, the relaxor degree of dielectric behavior is enhanced, and the dielectric curve shows an altered shape. The origin of this dielectric relaxation is attributed to the increased structural distortion reflected by the changed bond length/angle, since there is no phase transition in 90-300 K. Our work gives a comprehensive view on the structural, magnetic, and dielectric properties of Yb2Ti2O7, which is instructive for further work on pyrochlores.
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INTRODUCTION: To explore the underlying mechanism of electroacupuncture (EA) treatment on central post-stroke pain (CPSP), and provide basic evidence for the EA treatment on CPSP. METHODS: Firstly, 40 male SD rats were successfully established with a model of CPSP, under the intervention of different EA frequencies (2 Hz and 15 Hz) and fluoxetine (5 ml/kg and 0.4 mg/ml), whose brain tissue was then removed for paraffin-embedded sectioning; secondly, LPS induced the primary brain cells in the hippocampus to cause inflammation model which were added NS398 (inhibitor of COX-2) and DKK-1 (inhibitor of ß-catenin) later. The lesion sites of brain tissue were observed by Nissl staining and Transmission Electron Microscope (TEM) and autophagy-related proteins (LC3B, p62, LAMP-1), COX-2 and ß-catenin were detected by Western Blot and immunohistochemical staining. Finally, the correlation between LC3B, COX-2, and ß-catenin was calculated by multispectral quantification. RESULTS: (1) In the EA group (15 Hz), the number of Nissl bodies increased, autophagy-related protein LC3B-â ¡/â , LAMP-1, COX-2, and ß-catenin was lowly expressed, p62 was highly expressed; (2) COX-2, ß-catenin and LC3B are positively correlated with each other (COX-2 & ß-catenin: r = 0.923; COX-2 & LC3B: r = 0.818; ß-catenin & LC3B: r = 0.801); (3) Nissl bodies of primary brain cells of the hippocampus under LPS were like animal experiments; after addition of DKK-1, high expression of ß-catenin and COX-2 induced by LPS was significantly down-regulated, and LC3B-II/I was significantly down-regulated, and p62 protein only had up-regulation trend; after addition of NS398, COX-2 and LC3B-II/I was significantly down-regulated. CONCLUSION: EA may inhibit autophagy in the hippocampus by reducing ß-catenin/COX-2 protein expression and effectively alleviating CPSP. SIGNIFICANCE STATEMENT: Previous studies have found that EA can reduce the expression of NK-1R in damaged rats by inhibition of COX-2 and ß-catenin loops, which controls the activation of glial cells in the damaged area and the apoptosis of neuronal cells, and alleviated pain. In the male SD rat model, we evaluated this effect that EA inhibits autophagy in the hippocampus by reducing ß-catenin/COX-2 protein expression in the brain tissue. In addition, we assessed expression levels of autophagy-related proteins and genes on the inflammatory primary brain cells model. From the experiment, we found EA may inhibit autophagy in the hippocampus by reducing ß-catenin/COX-2 protein expression. These findings provide a foundation for the interpretation of the mechanism of EA on relieving CPSP in clinical practice.
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Autofagia , Electroacupuntura , Hipocampo/metabolismo , Hipocampo/patología , Dolor/metabolismo , Dolor/patología , Accidente Cerebrovascular/complicaciones , Animales , Astrocitos/ultraestructura , Encéfalo/ultraestructura , Encefalitis/complicaciones , Encefalitis/metabolismo , Masculino , Dolor/etiología , Umbral del Dolor , Ratas Sprague-DawleyRESUMEN
How ß-catenin/COX-2 contribute to inflammation-induced fibroblasts migration remains poorly understood. Therefore, in this study, lipopolysaccharide (LPS) was used as a stimulus to accelerate the migration of NIH3T3 cells, which mimicked the tissue repair process. LPS treatment increased the cell migration in concentration-and time-dependent manner. And NS398, a COX-2 inhibitor, inhibited LPS-induced NIH3T3 cells migration. DKK-1, an antagonist of the Wnt/ß-catenin signaling, also inhibited that migration. However, TWS119, an inducer of ß-catenin via GSK-3ß, increased the cell migration. LPS or TWS119 treatment increased COX-2, ß-catenin, TGF-ß1, and HMGB-1 expressions, and that could be attenuated by NS398 or DKK-1 addition. LPS induced the PGE2 production, and PGE2 increased the expression and nuclear translocation of ß-catenin, while EP2 blocker, AH6809, alleviated those effects. TWS119 increased the luciferase activity in the COX-2 promoter. In conclusion, LPS stimulated the NIH3T3 fibroblasts migration through a positive feedback between ß-catenin and COX-2, in which PGE2, EP2, TGF-ß1, and HMGB-1 played as signal molecules.
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Microporous organic capsules with hollow interiors have received enormous attention due to their unusual encapsulation efficiency to confine chemicals within their hollow cavities and prompted controlled release by circumventing their ripening or poisoning. To this end, herein, we report the design and synthesis of carboxylic group functionalized hollow microporous organic capsules (HMOCs) using a facile emulsion polymerization technique that show extraordinary high encapsulation efficiency (up to 98%) of morphine·HCl and its promising prolonged release. The functionalized HMOCs are found to release the drug at a rate which is proportional to the amount of drug remaining in its interior. Due to the presence of hollow and porous morphologies, they possess high BET surface areas, i.e. up to 974 m2 g-1. Moreover, the in vivo results showed that functionalized HMOCs can offer slow release of active drug molecules and attenuate the level of writhing response over 72 h of intraperitoneal injection. The functionalized HMOCs, therefore, present a new class of potential drug delivery systems that can maintain the slow and prolonged release of analgesics by lowering the dosage and avoid frequent administration.
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PURPOSE: Constraint-induced movement therapy (CIMT) is a promising technique for the recovery of upper extremity movement in chronic stroke patients. However, the effectiveness of its use in acute ischemia has not been confirmed. Myelin-associated inhibitors, which have upregulated functions in tissues affected by acute focal infarction, limit axonal regeneration via activation of the Rho-Rho-associated protein kinase (ROCK) pathway. The present study examined whether early CIMT combined with the ROCK inhibitor fasudil promotes motor recovery after acute ischemic stroke. MATERIALS AND METHODS: Rats were trained to perform the skilled-reach test and then subjected to middle cerebral artery occlusion (MCAO), producing a stroke affecting the preferred forelimb. Rats were assigned to one of four groups (N = 6/group): (nontreated) Control, CIMT, Fasudil, or CIMT+fasudil. CIMT and/or intraperitoneal infusion of fasudil were initiated 1 day postMCAO. Skilled reach and foot fault test data were collected once before and repeatedly over 4 weeks after the operation. Infarct volumes were calculated. RESULTS: All four groups showed similar forelimb impairment before treatment. The performance of CIMT alone group was similar to that of controls on both tests. Fasudil alone facilitated recovery in the foot-fault test, but not in the skilled-reach test. Rats in the CIMT+fasudil group demonstrated enhanced recovery in both tests, including better performance over time than the Fasudil group on the foot-fault test. Infarct size did not differ significantly between the groups. CONCLUSIONS: Early CIMT promotes motor recovery after acute ischemic stroke when it is administered with fasudil pharmacotherapy, but not without it.
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1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , Bloqueadores de los Canales de Calcio/uso terapéutico , Terapia por Ejercicio/métodos , Recuperación de la Función/efectos de los fármacos , Accidente Cerebrovascular/terapia , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/uso terapéutico , Análisis de Varianza , Animales , Infarto Encefálico/tratamiento farmacológico , Infarto Encefálico/etiología , Isquemia Encefálica/complicaciones , Modelos Animales de Enfermedad , Conducta Alimentaria/efectos de los fármacos , Masculino , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Accidente Cerebrovascular/etiología , Factores de TiempoRESUMEN
Hyperkinetic extrapyramidal syndrome is the typical clinical characteristic of acquired hepatocerebral degeneration (AHD), but is usually not observed with hepatic encephalopathy (HE). We present a case of AHD coexisting with HE. Both conditions were secondary to liver cirrhosis and hepatitis C virus infection. The brain MRI showed bilateral and symmetric high T1 signal-intensity in the globus pallidus, and diffuse high signal-intensity of the hemispheric white matter on T2-FLAIR images. As we usually neglect the existence of AHD, the diagnosis is often ignored, especially when it coexists with HE. This case highlights the need to distinguish irreversible AHD from HE.
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Encefalopatía Hepática/diagnóstico , Degeneración Hepatolenticular/diagnóstico , Anciano , Enfermedad Crónica , Femenino , Encefalopatía Hepática/complicaciones , Degeneración Hepatolenticular/complicaciones , HumanosRESUMEN
OBJECTIVE: To clone an A3IP gene and investigate its cellular and histological localization based on previous research which has identified part of A3IP sequence interacting with carboxyl-terminal of ataxin-3. METHODS: Bioinformatic and Northern blotting were applied to clone the A3IP gene and detect the expression of its transcripts in various human tissues and brain regions. Western blotting and immunofluorescence staining were applied to detect expression of A3IP protein in cultured cells. Immunohistochemistry staining was applied to study the expression of A3IP protein in various human tissues and brain regions. RESULTS: cDNA cloning of A3IP gene's reading frame and its sequence assembly were completed. Three transcripts (1 kb, 1.35 kb and 6 kb, respectively) of A3IP were found to express in various human tissues and brain regions. A3IP pEGFP expresses in cytoplasm of cultured COS-7 cells and various human tissues and brain regions including cerebral cortex, cerebellum, muscle, peripheral nerve, liver and kidney. CONCLUSION: The cloned A3IP gene encodes A3IP, a novel ataxin-3 interacting protein. Three transcripts of A3IP are expressed in various human tissues and brain regions. A3IP is a cytosolic protein.
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Proteínas Portadoras/metabolismo , Clonación Molecular , Proteínas del Tejido Nervioso/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Represoras/metabolismo , Ataxina-3 , Secuencia de Bases , Proteínas Portadoras/genética , Humanos , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/genética , Proteínas Nucleares/genética , Unión Proteica , Transporte de Proteínas , Proteínas Represoras/genéticaRESUMEN
Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucelotide repeat that encodes an abnormal polyglutamine (PolyQ) tract in the disease protein, ataxin-3. The formation of neuronal intranuclear inclusions in the specific brain regions is one of the pathological hallmarks of SCA3. Acceleration of the degradation of the mutant protein aggregates is proven to produce beneficial effects in SCA3 and other PolyQ diseases. Lithium is known to be neuroprotective in various models of neurodegenerative disease and can reduce the mutant protein aggregates by inducing autophagy. In this study, we explored the therapeutic potential of lithium in a SCA3 Drosophila model. We showed that chronic treatment with lithium chloride at specific doses notably prevented eye depigmentation, alleviated locomotor disability, and extended the median life spans of SCA3 transgenic Drosophila. By means of genetic approaches, we showed that co-expressing the mutant S9E, which mimicked the phosphorylated S9 state of Shaggy as done by lithium, also partly decreased toxicity of gmr-SCA3tr-Q78. Taken together, our findings suggest that lithium is a promising therapeutic agent for the treatment of SCA3 and other PolyQ diseases.
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Glucógeno Sintasa Quinasa 3/metabolismo , Cloruro de Litio/farmacología , Trastornos del Movimiento/prevención & control , Proteínas del Tejido Nervioso/metabolismo , Fármacos Neuroprotectores/farmacología , Proteínas Nucleares/metabolismo , Proteínas Represoras/metabolismo , Factores de Edad , Animales , Animales Modificados Genéticamente , Ataxina-3 , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Drosophila , Activación Enzimática/efectos de los fármacos , Ojo/efectos de los fármacos , Ojo/patología , Ojo/ultraestructura , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Glucógeno Sintasa Quinasa 3/genética , Glucógeno Sintasa Quinasa 3 beta , Humanos , Microscopía Electrónica de Rastreo , Actividad Motora/efectos de los fármacos , Actividad Motora/genética , Trastornos del Movimiento/etiología , Trastornos del Movimiento/genética , Proteínas del Tejido Nervioso/genética , Enfermedades Neurodegenerativas/complicaciones , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/prevención & control , Proteínas Nucleares/genética , Péptidos/genética , Proteínas Represoras/genéticaRESUMEN
Phase correction is one of the key technologies in the spectrum recovery of the Fourier transform imaging spectrometer. The present paper proposes a correction method based on simulated annealing algorithm to calculate phase error, which overcomes the disadvantage of the existing methods that can not correct the interferogram with noise. The method determines the phase optimum solution by controlling the phase decrease function, attaining objective function value by correcting interferogram data with random phase value generated in the phase range, and determining the objective function increment in accordance with the Metropolis criterion. The simulation result of the algorithm indicates that the optimized phase error is less than 0.5%, and both the error accuracy and stability of the spectrum-recovered relative spectrum is less than 1%, which is a great improvement compared with the existing algorithm.