RESUMO
While the auditory and visual systems each provide distinct information to our brain, they also work together to process and prioritize input to address ever-changing conditions. Previous studies highlighted the trade-off between auditory change detection and visual selective attention; however, the relationship between them is still unclear. Here, we recorded electroencephalography signals from 106 healthy adults in three experiments. Our findings revealed a positive correlation at the population level between the amplitudes of event-related potential indices associated with auditory change detection (mismatch negativity) and visual selective attention (posterior contralateral N2) when elicited in separate tasks. This correlation persisted even when participants performed a visual task while disregarding simultaneous auditory stimuli. Interestingly, as visual attention demand increased, participants whose posterior contralateral N2 amplitude increased the most exhibited the largest reduction in mismatch negativity, suggesting a within-subject trade-off between the two processes. Taken together, our results suggest an intimate relationship and potential shared mechanism between auditory change detection and visual selective attention. We liken this to a total capacity limit that varies between individuals, which could drive correlated individual differences in auditory change detection and visual selective attention, and also within-subject competition between the two, with task-based modulation of visual attention causing within-participant decrease in auditory change detection sensitivity.
Assuntos
Atenção , Percepção Auditiva , Eletroencefalografia , Percepção Visual , Humanos , Atenção/fisiologia , Masculino , Feminino , Adulto Jovem , Adulto , Percepção Auditiva/fisiologia , Percepção Visual/fisiologia , Estimulação Acústica/métodos , Estimulação Luminosa/métodos , Potenciais Evocados/fisiologia , Encéfalo/fisiologia , AdolescenteRESUMO
BACKGROUND: Acute ischemic stroke (AIS) is one of the most common cerebrovascular diseases which accompanied by a disruption of aminothiols homeostasis. To explore the relationship of aminothiols with neurologic impairment severity, we investigated four aminothiols, homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CG) and glutathione (GSH) in plasma and its influence on ischemic stroke severity in AIS patients. METHODS: A total of 150 clinical samples from AIS patients were selected for our study. The concentrations of free reduced Hcy (Hcy), own oxidized Hcy (HHcy), free reduced Cys (Cys), own oxidized Cys (cysteine, Cyss), free reduced CG (CG) and free reduced GSH (GSH) were measured by our previously developed hollow fiber centrifugal ultrafiltration (HFCF-UF) method coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The concentration ratio of Hcy to HHcy (Hcy/HHcy), Cys to Cyss (Cys/Cyss) were also calculated. The neurologic impairment severity of AIS was evaluated using National Institutes of Health Stroke Scale (NIHSS). The Spearman correlation coefficient and logistic regression analysis was used to estimate and perform the correlation between Hcy, HHcy, Cys, Cyss, CG, GSH, Hcy/HHcy, Cys/Cyss and total Hcy with NIHSS score. RESULTS: The reduced Hcy and Hcy/HHcy was both negatively correlated with NIHSS score in AIS patients with P = 0.008, r=-0.215 and P = 0.002, r=-0.249, respectively. There was no significant correlation of Cys, CG, GSH, HHcy, Cyss, Cys/Cyss and total Hcy with NIHSS score in AIS patients with P value > 0.05. CONCLUSIONS: The reduced Hcy and Hcy/HHcy, not total Hcy concentration should be used to evaluate neurologic impairment severity of AIS patient.
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Cisteína , Glutationa , Homocisteína , AVC Isquêmico , Oxirredução , Índice de Gravidade de Doença , Humanos , Masculino , Feminino , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , Homocisteína/sangue , Idoso , Pessoa de Meia-Idade , Cisteína/sangue , Glutationa/sangue , Dipeptídeos/sangue , Idoso de 80 Anos ou maisRESUMO
The pathogenesis of overactivated visual perception in attention-deficit hyperactivity disorder (ADHD) remains unclear, which is interpreted as a cognitive compensation. The existing studies have proposed that perceptual abnormalities in neurodevelopmental disorders are associated with dysfunction of the contextual knowledge system, which influences the development and formation of perception. We hypothesized that alterations in contextual states may also be responsible for inducing perceptual abnormalities in ADHD. Therefore, the present study evaluated the characteristics of pre-stimulus alpha and its response to a single dose of methylphenidate (MPH). A total of 135 Chinese children participated in the first study, including 70 children with ADHD (age = 10.61 ± 1.93 years, female = 17) and 65 age- and sex-matched control children (age = 10.73 ± 1.93 years, female = 20). The second clinical trial included 19 Chinese children with ADHD (age = 11.85 ± 1.72 years, female = 4), with an identical visual spatial search task. Pre-stimulus alpha oscillations and P1 activity were significantly greater in children with ADHD than in the controls. Overactivated pre-stimulus alpha positively predicted P1. Both pre-stimulus alpha and P1 overactivation have beneficial effects on cognitive performance in children with ADHD. No intervening effect of a single dose of MPH on the compensatory activation of pre-stimulus alpha and P1 were observed. Our findings extended the perceptual activation to the contextual knowledge system, suggesting that compensatory perception in children with ADHD is more likely to be a top-down regulated cognitive operational process.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Adolescente , Criança , Feminino , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Metilfenidato/farmacologia , Metilfenidato/uso terapêutico , Percepção Visual , Masculino , Ensaios Clínicos como AssuntoRESUMO
Failed skin wound healing, through delayed wound healing or wound dehiscence, is a global public health issue that imposes significant burdens on individuals and society. Although the application of growth factor is an effective method to improve the pace and quality of wound healing, the clinically approved factors are limited. Parathyroid hormone (PTH) demonstrates promising results in wound healing by promoting collagen deposition and cell migration, but its application is limited by potentially inhibitory effects when administered continuously and locally. Through partially replacing and repeating the amino acid domains of PTH(1-34), we previously designed a novel PTH analog, PTH(3-34)(29-34) or MY-1, and found that it avoided the inhibitory effects of PTH while retaining its positive functions. To evaluate its role in wound healing, MY-1 was encapsulated in liposomes and incorporated into the methacryloyl gelatin (GelMA) hydrogel, through which an injectable nanocomposite hydrogel (GelMA-MY@Lipo, or GML) was developed. In vitro studies revealed that the GML had similar properties in terms of the appearance, microstructure, functional groups, swelling, and degradation capacities as the GelMA hydrogel. In vitro drug release testing showed a relatively more sustainable release of MY-1, which was still detectable in vivo 9 days post-application. When the GML was topically applied to the wound areas of rat models, wound closure as well as tensile strength were improved. Further studies showed that the effects of GML on wound repair and tensile strength were closely related to the promotion of fibroblast migration to the wound area through the controlled release of MY-1. Mechanically, MY-1 enhanced fibroblast migration by activating PI3K/AKT signaling and its downstream molecule, Rac1, by which it increased fibroblast aggregation in the early stage and resulting in denser collagen deposition at a later time. Overall, these findings demonstrated that the nanocomposite hydrogel system promoted skin wound healing and increased tensile strength, thus offering new potential in the treatment of wound healing.
Assuntos
Movimento Celular , Fibroblastos , Hidrogéis , Lipossomos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Resistência à Tração , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Lipossomos/química , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Movimento Celular/efeitos dos fármacos , Hidrogéis/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ratos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Ratos Sprague-Dawley , Masculino , Camundongos , Gelatina/química , Pele/efeitos dos fármacos , Pele/metabolismoRESUMO
The development of antibiotic-resistant microorganisms is a major global health concern. Recently, there has been an increasing interest in antimicrobial peptides as a therapeutic option. This study aimed to evaluate the triple-action (broad-spectrum antibacterial, anti-biofilm, and anti-quorum sensing activities) of melittin, a membrane-active peptide present in bee venom. The minimum inhibitory concentration and minimum bactericidal concentration of the melittin were determined using the microdilution method and agar plate counting. Growth curve analysis revealed that melittin showed a concentration-dependent antibacterial activity. Scanning electron microscope analysis revealed that melittin treatment altered the morphology. Confocal laser scanning microscope revealed that melittin increased the membrane permeability and intracellular ROS generation in bacteria, all of which contribute to bacterial cell death. In addition, the crystal violet (CV) assay was used to test the anti-biofilm activity. The CV assay demonstrated that melittin inhibited biofilm formation and eradicated mature biofilms. Biofilm formation mediated by quorum sensing (QS) plays a major role in this regard, so molecular docking and molecular dynamics analysis confirmed that melittin interacts with LasR receptors through hydrogen bonds, and further evaluates the anti-QS activity of melittin through the production of virulence factors (pyocyanin, elastase, and rhamnolipid), exopolysaccharides secretion, and bacterial motility, that may be the key to inhibiting the biofilm formation mechanism. The present findings highlight the promising role of melittin as a broad-spectrum antibacterial, anti-biofilm agent, and potential QS inhibitor, providing a new perspective and theoretical basis for the development of alternative antibiotics.
Assuntos
Meliteno , Percepção de Quorum , Meliteno/farmacologia , Simulação de Acoplamento Molecular , Biofilmes , Antibacterianos/química , Fatores de Virulência/metabolismo , Pseudomonas aeruginosa/fisiologiaRESUMO
Andrographis paniculata is a medicinal plant traditionally used to produce diterpene lactones and flavonoids, which possess various biological activities. Widely distributed in China, India, and other Southeast Asia countries, A. paniculata has become an important economic crop, significantly treating SARS-CoV-2, and is being cultivated on a large scale in southern China. The biosynthesis of active ingredients in A. paniculata are regulated and controlled by genes, but their specific roles are still not fully understood. To further explore the growth regulation factors and utilization of its medicinal parts of this industrial crop, chemical and transcriptome analyses were conducted on the roots, stems, and leaves of A. paniculata to identify the biosynthesis pathways and related candidate genes of the active ingredients. The chemical analysis revealed that the main components of A. paniculata were diterpene lactones and flavonoids, which displayed potential ability to treat SARS-CoV-2 through molecular docking. Moreover, the transcriptome sequencing annotated a total of 40,850 unigenes, including 7962 differentially expressed genes. Among these, 120 genes were involved in diterpene lactone biosynthesis and 60 genes were involved in flavonoid biosynthesis. The expression of diterpene lactone-related genes was the highest in leaves and the lowest in roots, consistent with our content determination results. It is speculated that these highly expressed genes in leaves may be involved in the biosynthesis pathway of diterpenes. Furthermore, two class â terpene synthases in A. paniculata transcriptome were also annotated, providing reference for the downstream pathway of the diterpene lactone biosynthesis. With their excellent market value, our experiments will promote the study of the biosynthetic genes for active ingredients in A. paniculata and provide insights for subsequent in vitro biosynthesis.
Assuntos
Andrographis , Diterpenos , Terpenos/metabolismo , Transcriptoma , Andrographis/genética , Andrographis/química , Flavonoides/metabolismo , Simulação de Acoplamento Molecular , Diterpenos/química , Lactonas/metabolismo , Antivirais/metabolismoRESUMO
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in school-age children. Attentional orientation is a potential clinical diagnostic marker to aid in the early diagnosis of ADHD. However, the underlying pathophysiological substrates of impaired attentional orienting in childhood ADHD remain unclear. Electroencephalography (EEG) was measured in 135 school-age children (70 with childhood ADHD and 65 matched typically developing children) to directly investigate target localization during spatial selective attention through univariate ERP analysis and information-based multivariate pattern machine learning analysis. Compared with children with typical development, a smaller N2pc was found in the ADHD group through univariate ERP analysis. Children with ADHD showed a lower parieto-occipital multivariate decoding accuracy approximately 240-340 ms after visual search onset, which predicts a slower reaction time and larger standard deviation of reaction time. Furthermore, a significant correlation was found between N2pc and decoding accuracy in typically developing children but not in children with ADHD. These observations reveal that impaired attentional orienting in ADHD may be due to inefficient neural encoding responses. By using a personalized information-based multivariate machine learning approach, we have advanced the understanding of cognitive deficits in neurodevelopmental disorders. Our study provides potential research directions for the early diagnosis and optimization of personalized intervention in children with ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Criança , Eletroencefalografia , Tempo de Reação/fisiologiaRESUMO
BACKGROUND: Re-epithelialization is important in the process of wound healing. Various methods have been identified to expedite the process, but their clinical application remains limited. While parathyroid hormone (PTH) has shown promising results in wound healing due to its role in promoting collagen deposition and cell migration, application is limited by its potentially inhibitive effects when being continuously and locally administrated. Herein, we developed a novel PTH analog, Human parathyroid hormone (hPTH) (3-34/29-34) (henceforth MY-1), by partially replacing and repeating the amino acid sequences of hPTH (1-34), and evaluated its effect on skin wound re-epithelialization. METHODS: CCK-8, colony formation unit assay, and Ki67 immunofluorescent staining were performed to evaluate the effect of MY-1 on HaCaT cell proliferation. Then, wound scratch assay, Transwell assay and lamellipodia staining were carried out to evaluate the effect of MY-1 on cell migration. Moreover, the epithelial-mesenchymal transition (EMT) markers were measured using qPCR and western blot analysis. For in-vivo drug delivery, gelatin methacryloyl (GelMA) hydrogel was employed to load the MY-1, with the physicochemical characteristics evaluated prior to its application in wound models. Then, MY-1's role in wound healing was determined via acute skin wound models. Finally, the mechanism that MY-1 activated was also detected on HaCaT cells and in-vivo wound models. RESULTS: In-vitro, MY-1 accelerated the migration and EMT of HaCaT cells, while having little effect on cell proliferation. GelMA and MY-1-incorporated GelMA hydrogels showed similar physicochemical characteristics and were used in the in-vivo studies, where the results revealed that MY-1 led to a stronger re-epithelialization by inducing basal keratinocyte migration and EMT. Further studies on in-vivo wound models and in-vitro HaCaT cells revealed that MY-1 regulated cell migration and EMT through activating PI3K/AKT signaling. The parathyroid hormone type 1 receptor (PTHR1), the main receptor of PTH, was found to be the upstream of PI3K/AKT signaling, through interfering PTHR1 expression with a small interference RNA following detection of the PI3K/AKT activation. CONCLUSION: Collectively, our study demonstrated that MY-1 accelerates skin wound re-epithelialization by inducing keratinocyte migration and EMT via PTHR1-PI3K/AKT axis activation. Video Abstract.
Assuntos
Fosfatidilinositol 3-Quinases , Reepitelização , Humanos , Proteínas Proto-Oncogênicas c-akt , Transição Epitelial-Mesenquimal , Movimento Celular , Células HaCaTRESUMO
Selective attention is thought to involve target enhancement and distractor inhibition processes. Here, we recorded simultaneous electroencephalographic (EEG) and functional near-infrared spectroscopy (fNIRS) data from human adults when they were pre-cued by the visual field of coming target, distractor, or both of them. From the EEG data, we found alpha power relatively decreased contralaterally to the to-be-attended target, as reflected by the positive-going alpha modulation index. Late alpha power relatively increased contralaterally to the to-be-suppressed distractor, as reflected by the negative-going alpha modulation index. From the fNIRS data, we found enhancements of hemodynamic activity over the contralateral hemisphere in response to both the target and the distractor anticipation but within nonoverlapping posterior brain regions. More importantly, we described the specific neurovascular modulation between alpha power and oxygenated hemoglobin signal, which showed a positive coupling effect during target anticipation and a negative coupling effect during distractor anticipation. Such flexible neurovascular couplings between EEG oscillation and hemodynamic activity seem to play an essential role in the final behavioral outcomes. These results provide unique neurovascular evidence for the dissociation of the mechanisms of target enhancement and distractor inhibition. Individual behavioral differences can be related to individual differences in neurovascular coupling.
Assuntos
Acoplamento Neurovascular , Adulto , Humanos , Acoplamento Neurovascular/fisiologia , Atenção/fisiologia , Eletroencefalografia/métodos , Hemodinâmica/fisiologia , Sinais (Psicologia)RESUMO
BACKGROUND: For patients with rotator cuff tear (RCT), the contra-lateral shoulders have higher risk of RCT than general population. It has been proved by several previous studies. The focus of this study is to obtain the data of contra-lateral rotator cuff tear in Chinese population, and to find the rules of contra-lateral rotator cuff tear through statistical analysis. METHODS: From March 2016 to January 2020, patients who underwent shoulder arthroscopic surgery were included in the study, we conduct bilateral shoulder ultrasound before surgery, patients information collection include gender, age, occupation and whether received contra-lateral rotator cuff surgery within 1-3 years. The above information was statistically analyzed. RESULTS: According to the inclusion and exclusion criteria, 401 patients were included. The incidence of contra-lateral rotator cuff tear was 24.3%, 5.58% of them underwent contra-lateral rotator cuff repair surgery within 3 years. The degree of contra-lateral rotator cuff tear was positively correlated with the degree of the primary side; Patients with full-thickness rotator cuff tear were more likely to have contra-lateral rotator cuff tear than patients with partial rotator cuff tear. For patients with supraspinatus tendon tear, the contra-lateral rotator cuff tear risk increases, For patients with subscapularis muscle tear, the contra-lateral rotator cuff tear risk doesn't increases. Contra-lateral rotator cuff tear is related to age, the risk of contra-lateral rotator cuff tear is higher in elderly patients. CONCLUSIONS: The contra-lateral RCT data obtained in our study was 24.3%, significantly lower than that of previous studies. The reasons may include ethnic variation, lifestyle, and proportion of heavy physical labor. The condition of contra-lateral rotator cuff is closely related to affected side rotator cuff tear.
RESUMO
Objective To explore the optimal administration route of tranexamic acid (TXA) in shoulder arthroscopic surgery. Methods Patients undergoing arthroscopic rotator cuff repair were randomly divided into four groups: control group (without TXA treatment), intravenous group (TXA was intravenously administered 10 minutes before surgery), irrigation group (TXA was added to the irrigation fluid during subacromial decompression and acromioplasty), and intravenous plus irrigation group (TXA was applied both intravenously and via intra-articular irrigation). The primary outcome was visual clarity assessed with visual analog scale (VAS) score, and the secondary outcomes included irrigation fluid consumption and time to subacromial decompression and acromioplasty procedure. Results There were 134 patients enrolled in the study, including 33 in the control group, 35 in the intravenous group, 32 in the irrigation group, and 34 in the intravenous plus irrigation group. The median and interquartile range of VAS scores for the intravenous, irrigation, and intravenous plus irrigation groups were 2.70 (2.50, 2.86) (Z = -3.677, P = 0.002), 2.67 (2.50, 2.77) (Z = -3.058, P < 0.001), and 2.91 (2.75, 3.00) (Z = -6.634, P < 0.001), respectively, significantly higher than that of the control group [2.44 (2.37, 2.53)]. Moreover, the control group consumed more irrigation fluid than the intravenous group, irrigation group, and intravenous plus irrigation group (all P < 0.05). The intravenous plus irrigation group consumed less irrigation fluid than either the intravenous group or the irrigation group (both P < 0.001). There was no difference in subacromial decompression and acromioplasty operative time among the four groups. Conclusion TXA applied both topically and systematically can improve intraoperative visual clarity, and the combined application is more effective.
Assuntos
Ácido Tranexâmico , Humanos , Ácido Tranexâmico/uso terapêutico , Ombro , Artroscopia/métodos , Descompressão Cirúrgica/métodos , Resultado do TratamentoRESUMO
Take-out food has become increasingly prevalent due to the fast pace of people's life. However, few study has been done on microplastics in take-out food. Contacting with disposable plastic containers, take-out food may be contaminated with microplastics. In the present study, abundance and characteristics of microplastics in total of 146 take-out food samples including solid food samples and beverage samples (bubble tea and coffee) were determined and identified. The mean abundance of microplastics in take-out food was 639 items kg-1, with the highest value in rice and the lowest value in coffee. Fragments shape, transparent color and sizes ≤ 500 µm were the main characteristics of microplastics in those food, and polyethylene was the main polymer type. Our results indicated that microplastics in take-out food was influenced by food categories and cooking methods, as well as food packaging materials. Approximately 170-638 items of microplastics may be consumed by people who order take-out food 1-2 times weekly.
Assuntos
Microplásticos , Poluentes Químicos da Água , Café , Monitoramento Ambiental , Humanos , Plásticos , Polietileno , Polímeros , Chá , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: Percutaneous screw placement, especially the insertion of LC2 screws, is technically demanding. Although the traditional LC2 bony canal spans the anterior inferior iliac spine (AIIS) to the posterior superior iliac spines (PSIS), a high perforation rate has been reported. OBJECTION: The aim of this research was to design a revised bony canal, measure the canal width and length and guide the insertion of LC2 screws for pelvic fractures. MATERIALS AND METHODS: The plane tool in the Mimics analysis menu was used to draw a midplane connecting the midpoint between the anterior inferior spine and the PSIS upper flat region with pelvic CT data. The minimum widths of the upper, middle, lower surfaces of the tunnel and perforation rate were measured and compared. The ideal screw length was also measured along the longitudinal axis running through the midpoint of the midplane. RESULTS: The minimum widths of the upper, middle and lower surfaces of the revised canal were 3.63 mm, 7.7 mm, and 11.93 mm, respectively, in males and 5.97 mm, 9.93 mm, and 12.45 mm, respectively, in females. Significant differences were observed among the upper, middle and lower surfaces of the revised canal in male patients (P < 0.001). In female subjects, the upper canal surface was significantly different from the middle and lower canal surfaces (P < 0.001). The perforation rate was significantly decreased especially in females pelvic. The channel length passing through the midpoint of the narrowest position of the pelvis was 130.85 ± 8.02 mm in males and 124.30 ± 7.71 mm in females and was significantly different for male and female pelvises (P = 0.004). CONCLUSION: The LC2 screw should be inserted along the intersection line of the AIIS lateral wall and the iliac body. The screw should be inserted under the line between the midpoint of the AIIS and the PSIS upper flat region to ensure accuracy of placement. LC2 screws can be more easily inserted in males than in females, and the rate of cortical perforation can be significantly decreased under the guidance of the newly proposed canal.
Assuntos
Fraturas Ósseas , Ossos Pélvicos , Parafusos Ósseos , Feminino , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Ílio/diagnóstico por imagem , Ílio/cirurgia , Masculino , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/cirurgia , PelveRESUMO
Three new alkaloids (1-3), one new diphenyl ether (4) and fifteen known alkaloids (5-19) were isolated from the rattan stems of Sinomenium acutum. Comprehensive analyses of HR-ESI-MS, 1D (1 H and 13 C), 2D-NMR (1 H-1 H COSY, HSQC, HMBC, NOESY), circular dichroism (CD), UV and IR revealed the structures and absolute configurations of these new compounds. The structures of other compounds were determined by comparison of their 1 H and 13 C-NMR data with previous literature reports. By measuring the amount of NO produced, the anti-inflammatory properties of the isolated compounds were studied. The results showed that compounds 4 and 5 had strong NO inhibitory activity.
Assuntos
Alcaloides , Artrite Reumatoide , Medicamentos de Ervas Chinesas , Alcaloides/química , Alcaloides/farmacologia , Artrite Reumatoide/tratamento farmacológico , China , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional , Estrutura Molecular , Sinomenium/químicaRESUMO
BACKGROUND: With the outbreak of COVID-19, it has become very important to improve biosafety measures taken by medical staff. Fewer pretreatment steps correspond to lower chances of infection. The authors established a direct injection technique to analyze levetiracetam (LEV) concentrations in human serum and studied its application in therapeutic drug monitoring. METHODS: Serum samples were prepared by hollow fiber centrifugal ultrafiltration and the filtrate was directly injected into a ultra-high performance liquid chromatography apparatus (Waters UPLC BEH C18 column: 50 × 2.1 mm, 1.7 µm) for analysis. The mobile phase consisted of acetonitrile and water (8:92) at a flow rate of 1.0 mL/min. The column temperature was maintained at 30°C. The detected wavelength was 210 nm. RESULTS: A linear relationship was obtained for LEV from 0.625 to 80 mcg/mL (r2 = 0.999). The limit of detection for the analysis of LEV was 0.125 mcg/mL. The analysis time was shortened to 4 minutes. The recovery rate of LEV based on the current method was 96.6%-100.1%, whereas the absolute recovery rate was 93.2%-96.8%. The relative SD of intraday and interday precision was <7.3%. Stability was achieved at room temperature for 24 hours after 3 freeze-thaw cycles and at -80°C for 21 days. The method was successfully applied to determine LEV concentrations in the serum of 19 patients. CONCLUSIONS: The present method is simple, accurate, and sensitive, and can improve biosafety with the direct injection technique. It is suitable for the analysis of LEV concentrations in therapeutic drug monitoring.
Assuntos
Coleta de Amostras Sanguíneas/métodos , COVID-19/epidemiologia , Monitoramento de Medicamentos/métodos , Levetiracetam/sangue , Cromatografia Líquida de Alta Pressão , Humanos , Reprodutibilidade dos Testes , SARS-CoV-2 , Fatores de TempoRESUMO
The presence of reduced aminothiols, including homocysteine (Hcy), cysteine (Cys), cysteinyl-glycine (CG), and glutathione (GSH), is significantly increased in the pathological state. However, there have been no reports on the relationship between reduced aminothiols (Hcy, Cys, CG, and GSH) and different genders, ages, and drug combinations in human blood. The accurate quantification of these reduced thiols in biological fluids is important for monitoring some special pathological conditions of humans. However, the published methods typically not only require cumbersome and technically challenging processing procedures to ensure reliable measurements, but are also laborious and time-consuming, which may disturb the initial physiological balance and lead to inaccurate results. We developed a hollow fiber centrifugal ultrafiltration (HFCF-UF) method for sample preparation coupled with a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method and used it to determine four reduced aminothiols (Hcy, Cys, CG, and GSH) in human blood for the first time. A total of 96 clinical patients were enrolled in our study. The influence of different genders, ages, and drug combinations on the levels of four reduced thiols in human blood was also discussed by SPSS 24.0. The sample preparation was simplified to a single 5 min centrifugation step in a sealed system that did not disturb the physiological environment. The validation parameters for the methodological results were excellent. The procedure was successfully applied to monitoring the concentrations of four reduced aminothiols (Hcy, Cys, CG, and GSH) in 96 clinical blood samples. There were no significant differences in Hcy, Cys, CG, or GSH for the different genders, ages, or combinations with methotrexate or vancomycin (P > 0.05). However, there was a significant increase in Hcy concentration in patients treated with valproic acid who were diagnosed with epilepsy (p=0.0007). It is advisable to measure reduced Hcy level in patients taking valproic acid. The developed HFCF-UF method was simple and accurate. It can be easily applied in clinical research to evaluate oxidative stress in further study.
Assuntos
Análise Química do Sangue/métodos , Cisteína/sangue , Dipeptídeos/sangue , Glutationa/sangue , Homocisteína/sangue , Ultrafiltração/métodos , Antibacterianos/sangue , Antibacterianos/química , Cromatografia Líquida de Alta Pressão/métodos , Cisteína/química , Dipeptídeos/química , Inibidores Enzimáticos/sangue , Inibidores Enzimáticos/química , Congelamento , Glutationa/química , Homocisteína/química , Humanos , Limite de Detecção , Metotrexato/sangue , Metotrexato/química , Estrutura Molecular , Espectrometria de Massas em Tandem/métodos , Temperatura , Ácido Valproico/sangue , Ácido Valproico/química , Vancomicina/sangue , Vancomicina/químicaRESUMO
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by cognitive deficits associated with attention. Prior studies have revealed the potential impact of ADHD on basic perception and cognitive ability in patients with ADHD. In this study, bilateral posterior P1 and N1 were measured in 122 Chinese children aged 7-12 years (64 with ADHD) to investigate the developmental characteristics of early perception during visual processing in school-age children with ADHD. For children with ADHD, a larger P1 activity with an atypical developmental pattern was evoked and observed for the visual search performance. These findings offer new insights into the mechanisms of cognitive developmental deficits and intervention techniques in children with ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade , Criança , Cognição , Humanos , Instituições Acadêmicas , Percepção VisualRESUMO
Two known coumarins, scopoletin (SP) and umbelliferone (UB), were isolated from Cortex Mori (CM). Their structures were elucidated by various spectroscopic analyses. Then, their effects on rat glomerular mesangial cells (RGMCs, HBZY-1) proliferation, hypertrophy, extracellular matrix (ECM) proliferation, expression of fibronectin, transforming growth factor-beta (TGF-ß), and connective tissue growth factor (CTGF) induced by high glucose were studied in vitro model of diabetic glomerulosclerosis. The results show that, CM, SP, and UB can inhibit the RGMCs proliferation to attenuate the ECM proliferation and cell hypertrophy, reduced the accumulation of ECM protein fibronectin, and lowered the expression of the key fibrosis factor TGF-ß and CTGF to inhibit the kidney fibrosis and thereby improved diabetic glomerulosclerosis. The two coumarins show great potentialities on treating diabetic glomerulosclerosis, but the animal experiment and mechanism is strongly needed for further proof.
Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Animais , Glucose , Células Mesangiais , Substâncias Protetoras , Ratos , Escopoletina , Umbeliferonas/farmacologiaRESUMO
BACKGROUND: Severe tibial plateau fractures may result in acute compartment syndrome (ACS) of the leg, which is always considered to be an orthopaedic emergency. Blistering is not an uncommon sign and may be related to decreased compartment pressure. No experiments on the risk of ACS based on the presence of blisters after tibial plateau fractures have been conducted, and controversies about the high rate of ACS in patients with tibial plateau fractures still exist. QUESTIONS/PURPOSES: This research retrospectively followed the bicondylar tibial plateau fractures treated with locking plates and verified if the risk of ACS was decreased after a blister was observed. METHODS: A total of 100 patients with closed tibial fractures (63 men and 37 women) were included and divided into with blister (group A, 40) and without blister groups (group B, 60). The creatine kinase (CK), BUN, and chloride levels were recorded on the first day after hospitalization. The hospitalization costs and injury to operation time were collected in the two groups. The Lysholm knee score and a visual analogue scale (VAS) for pain were used to assess the rehabilitation after follow-up. Clinical and serological results of ACS in the two groups were compared. RESULTS: There was significant delay in the time from injury to operation (11.0 ± 3.5 VS 7.6 ± 7.2, Z = - 3.771, P < 0.001) in the with blister (group A) and without blister groups (group B). The levels of chloride and BUN were significantly lower in the with blister group than in the without blister group (102.7 ± 3.0 VS 104.7 ± 2.57 mg/dL, Z = - 3.33, P = 0.001) (10.3 ± 2.5 VS 10.3 ± 2.8 mg/dL, Z = - 2.366, P = 0.018). There were no significant differences in the CK levels in the with blister and without blister groups (285.8 ± 202.6 VS 408.4 ± 633.6 U/L, Z = - 1.379, P = 0.168), but a trend of decreasing to normal was obvious in patients with blisters. There were no significant differences in the Lysholm knee score (40 VS 60, 80 ± 4.9 VS 79.8 ± 3.0, Z = - 0.872, P = 0.383), or the VAS (40 VS 60, 1.6 ± 0.7 VS 2.2 ± 1.3, Z = - 1.568, P = 0.117) for pain compared with patients without blisters. CONCLUSION: In conclusion, the presence of blisters in patients with severe tibial plateau fractures decreases the pressure in the compartment. There was a significant improvement in serological results after blisters appeared, which may be related to the reason for the decreased pressure decreased, and conservative management is recommended for these patients.
Assuntos
Síndromes Compartimentais , Fraturas da Tíbia , Vesícula , Síndromes Compartimentais/diagnóstico , Síndromes Compartimentais/epidemiologia , Síndromes Compartimentais/etiologia , Feminino , Fixação Interna de Fraturas , Humanos , Masculino , Estudos Retrospectivos , Tíbia , Fraturas da Tíbia/complicações , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/epidemiologiaRESUMO
Human monoamine oxidases (MAOs) play important roles in maintaining the homeostasis of biogenic amines. One of its isoforms, monoamine oxidase B (MAOB), is thought to be involved in several neurodegenerative diseases, which make the selective detection of MAOB activity essential. In this work, a novel surface-enhanced Raman scattering (SERS) sensor was fabricated and the MAOB activity was specifically determined by detecting the SERS signals of an enzyme-catalyzed reaction product via an amine-aldehyde click reaction. This process was simply achieved by coating core-shell gold-silver nanoparticles (Au@Ag NPs) on 3-aminopropyl aminopropyl triethoxysilane (APTES)-modified glass, and then, a monolayer of cysteamine (CA) was attached to the nanoparticle surface as a linker through Ag-S bonds. Using phenethylamine (PA) as a specific substrate of MAOB, the enzyme product phenylacetaldehyde (PAA) will produce significant Raman signals via the amine-aldehyde click reaction with CA, while other molecules, such as MAOB and PA, have no signal output because they cannot form close interaction with nanoparticles due to the existence of a CA layer. This sensor was further used for the specific determination of MAOB activity in clinical blood samples and the MAOB inhibitor assessment successfully. Meanwhile, by changing the click reaction types and taking advantage of the SERS fingerprint peaks for the specific click reaction products, this strategy offers huge potential to detect multiple enzyme activities simultaneously and can be used for new click reaction screening, enzyme-related disease diagnosis, drug screening, and clinical diagnosis.