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1.
J Clin Neurosci ; 87: 59-65, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33863535

RESUMO

OBJECTIVE: This study aimed to assess the prevalence of developmental venous anomaly (DVA) in patients with thalamic glioma. Furthermore, we explored the association between DVA and some important biomarkers, such as IDH1 mutation, and H3K27M mutation. PATIENTS AND METHODS: Patients who received tumor resection in West China Hospital between August 2009 and October 2017 were enrolled. Propensity score matching was conducted based on a logistic regression model and 1:1 matching for case and control was used to generate a new cohort from patients with meningioma. Chi-square test, t-test, univariate and multivariate analyses were employed to assess the prevalence of DVA in thalamic glioma and meningioma and to identify risk factors associated with DVA. RESULTS: Ninety-nine patients with thalamic glioma were enrolled in the current study (male, n = 54; female, n = 45). The mean age was 42.9 ± 15.3 years old. We identified a higher prevalence of DVA in 99 patients with thalamic glioma when compared with 99 patients with meningioma (18.18% vs. 7.07%), which was slightly lower than the prevalence of DVA in glioma reported in previous studies. Furthermore, the distribution of gender, age, and tumor grade in DVA did not reach statistical significance. Chi-square test, univariate and multivariate analyses showed that IDH1 mutation, ATRX mutation, MGMT promoter methylation, p53 mutation, MMP9, EGFR, and Top II positive expression, TERT mutation, and H3K27M mutation were not associated with the development of DVA in thalamic glioma. CONCLUSION: A higher prevalence of DVA was found in thalamic glioma compared with meningioma.

2.
Dev Cell ; 56(6): 811-825.e6, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33725483

RESUMO

Neuronal activity increases energy consumption and requires balanced production to maintain neuronal function. How activity is coupled to energy production remains incompletely understood. Here, we report that Rheb regulates mitochondrial tricarboxylic acid cycle flux of acetyl-CoA by activating pyruvate dehydrogenase (PDH) to increase ATP production. Rheb is induced by synaptic activity and lactate and dynamically trafficked to the mitochondrial matrix through its interaction with Tom20. Mitochondria-localized Rheb protein is required for activity-induced PDH activation and ATP production. Cell-type-specific gain- and loss-of-function genetic models for Rheb reveal reciprocal changes in PDH phosphorylation/activity, acetyl-CoA, and ATP that are not evident with genetic or pharmacological manipulations of mTORC1. Mechanistically, Rheb physically associates with PDH phosphatase (PDP), enhancing its activity and association with the catalytic E1α-subunit of PDH to reduce PDH phosphorylation and increase its activity. Findings identify Rheb as a nodal point that balances neuronal activity and neuroenergetics via Rheb-PDH axis.

3.
Blood ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33728448

RESUMO

Current prognostic scoring systems based on clinicopathologic variables are inadequate in predicting the survival and treatment response of extranodal natural killer/T-cell lymphoma (ENKTL) patients undergoing non-anthracyline-based treatment. We aimed to construct a classifier based on single-nucleotide polymorphisms (SNPs) for improving predictive accuracy and guiding clinical decision-making. The data of 722 patients with ENKTL from international multicenters were analyzed. A 7-SNP-based classifier was constructed using LASSO Cox regression in the training cohort (n=336) and further validated in the internal testing (n=144) and two external validation cohorts (n=142; n=100). The 7-SNP-based classifier showed good prognostic predictive efficacy in the training cohort and the three validation cohorts. Patients with high and low risk scores calculated by the classifier exhibited significantly different progression-free survival (PFS) and overall survival (OS) (all p<0.001). The 7-SNP-based classifier was further proved to be an independent prognostic factor by multivariate analysis, and its predictive accuracy was significantly better than clinicopathological risk variables. The application of the 7-SNP-based classifier was not affected by sample types. Notably, chemotherapy combined with radiotherapy significnalty improved PFS and OS versus radiotherapy alone in high risk Ann Anbor stage I patients, while there was no statistical difference between the two therapeutic modalities among low risk patients. A nomogram was constructed comprised of the classifier and clinicopathological variables, and showed remarkably better predictive accuracy than that of each variable alone. The 7-SNP-based classifier is a complement to existing risk stratification systems in ENKTL, which could have significant implications for clinical decision-making for ENKTL patients.

4.
Comp Biochem Physiol C Toxicol Pharmacol ; 246: 109023, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33647480

RESUMO

Cyprinid herpesvirus 3 (CyHV-3) causes high mortality in carp. Emodin has been shown of the effects of antioxidant, anti-inflammatory and antiviral. In present study, we investigated the preventive effects and mechanism of emodin on CyHV-3 infection. The ornamental koi carp (Cyprinus carpio haematopterus) were intraperitoneally injected with emodin (10 mg/kg, 20 mg/kg, or 40 mg/kg). 72 h later, an intraperitoneal injection of CyHV-3 was administered, and collected the samples one week later to detect the antioxidant parameters, antioxidant genes, inflammatory genes and to perform histopathology assays. The results showed that emodin significantly suppressed CyHV-3 replication (P < 0.05), improved the koi survival rate and slowed the damage caused by CyHV-3. Emodin treatment increased the antioxidant activity and decreased the lipid peroxidation level of the koi. Compared to the CyHV-3 group, emodin treatment resulted in the same antioxidant parameters after CyHV-3 infection. Emodin treatment activated the Nuclear factorery throid 2-related factor 2/Kelch-like ECH-associated protein 1-antioxidatant response element (Nrf2/Keap1-ARE) pathway and upregulated the expression of heme oxygenase 1 (HO-1), superoxide dismutase (SOD), and catalase (CAT) in the hepatopancreas after CyHV-3 infection. Emodin activated the nuclear factor kappa-B (NF-κB) pathway and decreased the expression of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-α (TNF-α) in the koi induced by CyHV-3. In conclusion, emodin treatment can suppress CyHV-3 replication and reduce the mortality of koi caused by CyHV-3. Emodin improves antioxidant function, relieves oxidative stress and inflammation cytokines via Nrf2/Keap1-ARE and NF-κB pathways, and protects against the adverse effects induced by CyHV-3.

5.
Eur J Pharm Sci ; 162: 105814, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33753216

RESUMO

Biapenem is a carbapenem antibiotic. It is excreted predominantly through the kidney as unchanged forms. However, the molecular mechanism of renal excretion of biapenem and potential drug-drug interactions (DDIs) were still unknown. In the present study, the role of organic anion transporters (OAT) 1/3 and organic cation transporters (OCT) 2 in the renal excretion of biapenem, and the potential DDIs between biapenem and six clinical commonly prescribed antibiotics and antiviral drugs that acted as substrates or inhibitors of OAT3 were evaluated in vitro. Further, the effect of probenecid on the pharmacokinetics of biapenem was explored in the rats. We observed that biapenem could not inhibit the transport activities of OAT1 or OCT2, while mildly inhibited OAT3 (IC50 >500 µM). Among the tested antibiotics and antiviral drugs, the relatively high DDI index values (maximal unbound plasma concentration over IC50, Imax,u/IC50) were found for piperacillin, linezolid and benzylpenicillin, which were 2.84, 1.7 and 0.62, respectively. Although probenecid had the highest DDI index (27.1) in vitro, no significant impact of it on the pharmacokinetics of biapenem was observed in the rats. Our results indicated that biapenem was primarily eliminated by the glomerular filtration, while OAT3-mediated renal tubular secretion was a minor route. Biapenem is not a clinically relevant substrate or inhibitor because of its low affinity to OAT3. According to current results, it would be safe to use biapenem with other antibiotics and antiviral drugs that acted as substrates or inhibitors of OAT3.

6.
J Phys Condens Matter ; 33(18)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33711825

RESUMO

OxDNA, as a successful coarse-grain model, has been applied to reproduce the thermodynamic and mechanical properties of both single- and double-stranded DNA. In current simulation, oxDNA is extended to explore the combined effects of temperature and force on the stability of DNA hairpin and its free energy landscape. Simulations were carried out at different forces and temperatures, at each temperature, a 18-base-pair DNA hairpin dynamically transited between folded state and unfolded state, and the separation between two states is consistent with the full contour length of single-stranded DNA in the unfolded state. Two methods were used to identify the critical force of DNA hairpin at each temperature and the critical forces obtained from two methods were consistent with each other and gradually decreased with the increasing temperature from 300 K to 326 K. The critical force at 300 K is reasonably consistent with the single molecule result of DNA hairpin with the same stem length. The two-state free energy landscape can be elucidated from the probability distribution of DNA hairpin extension and its dependence on the force and temperature is totally different. The increasing temperature not only reduces the free energy barrier, but also alters the position of transition point along the extension coordinate, resulting in the reduction of folding distance and the extension of unfolding distance, but their sum is not obviously dependent on the temperature. Generally, an assumption that the location of transition state in two-state energy landscape is independent of the stretching force is used to analyze the data of the single molecule experiment, but current simulation results indicate that effects of stretching forces on the location of transition state in two-state energy landscape are dependent on temperature. At relatively high temperature, stretching force can also change the location of transition state in the free energy landscape.

7.
Bull Environ Contam Toxicol ; 106(5): 792-798, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33759007

RESUMO

Zinc pollution impairs neural processes and protein function and also effects calcium-related transcriptional regulation and enzyme activity. In this study, we investigated pathways that potentially respond to calcium signaling under Zn2+ stress. Specifically we measured relative expressions of GeCNAα, GeCNB, GeMT, GeTNF-α, GeIL-1ß, and GeHsp90 in gills, livers, and kidneys of the indicator species Gymnocypris eckloni and found wide variation in their expression between tissues during the course of Zn2+ exposure. Notably, GeCNAα, GeCNB, GeTNF-α, GeIL-1ß, and GeMT were rapidly and strongly up-regulated in gills; GeIL-1ß and GeHsp90 transcription was quickly induced in kidneys; and GeCNB, GeTNF-α, GeIL-1ß, and GeHsp90 were most rapidly up-regulated in livers. GeCNAα and GeMT showed a contrasting late transcriptional up-regulation. These results suggest independent branches for chelation and immune responses during self-protection against Zn2+ toxicity, and the immune response appears to be faster than metal chelation.


Assuntos
Carpas , Cyprinidae , Animais , Calcineurina , Brânquias , Zinco/toxicidade
8.
Sci Rep ; 11(1): 5411, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686159

RESUMO

Cataracts are a common cause of visual impairment and blindness in mammals. They are usually associated with aging, but approximately one third of cases have a significant genetic component. Cataracts are increasingly prevalent among aging populations of captive giant pandas (Ailuropoda melanoleuca) and it is therefore important to identify genetic determinants that influence the likelihood of cataract development in order to distinguish between congenital and age-related disease. Here we screened for cataract-related genetic effects using a functional candidate gene approach combined with bioinformatics to identify the underlying genetic defect in a giant panda with congenital cataracts. We identified a missense mutation in exon 10 of the HSF4 gene encoding heat shock transcription factor 4. The mutation causes the amino acid substitution R377W in a highly conserved segment of the protein between the isoform-specific and downstream hydrophobic regions. Predictive modeling revealed that the substitution is likely to increase the hydrophobicity of the protein and disrupt interactions with spatially adjacent amino acid side chains. The mutation was not found in 13 unaffected unrelated animals but was found in an unrelated animal also diagnosed with senile congenital cataract. The novel missense mutation in the HSF4 gene therefore provides a potential new genetic determinant that could help to predict the risk of cataracts in giant pandas.

10.
Int J Nurs Pract ; : e12914, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33657667

RESUMO

AIMS: This study aimed to systematically evaluate the effectiveness of patient decision aids on knowledge, decisional conflict and decisional self-efficacy outcomes in patients with diabetes. METHODS: A comprehensive database search was performed using the Web of Science, Cochrane Library, PubMed, Embase, PsycINFO (Ovid), CINAHL (EBASCO), CNKI, VIP, Wan Fang Database and the Ottawa Decision Aid Library Inventory (http://decisionaid.ohri.ca/index.html) from inception to 13 October 2019. Two reviewers independently searched databases, screened articles, extracted data and evaluated the risk bias of included studies. Then Rev Man 5.3 software was adopted for statistical analysis. RESULTS: Ten articles containing 1,452 people with diabetes were selected. The results of meta-analysis showed that patient decision aids had a positive effect on reducing decisional conflict and improving decisional self-efficacy among patients with type 2 diabetes. Meanwhile, this article also revealed that patient decision aids have beneficial short-term effects on improving knowledge, but there was no significant long-term effect. CONCLUSION: Patient decision aids are capable of becoming support tools to improve shared decision making. Further implementation studies are required to transform patient decision aids tools into clinical practice.

11.
Sci Total Environ ; 772: 144829, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578154

RESUMO

This study reports on the first continuous measurements of ambient OH and HO2 radicals at a suburban site in Chengdu, Southwest China, which were collected during 2019 as part of a comprehensive field campaign 'CompreHensive field experiment to explOre the photochemical Ozone formation mechaniSm in summEr - 2019 (CHOOSE-2019)'. The mean concentrations (11:00-15:00) of the observed OH and HO2 radicals were 9.5 × 106 and 9.0 × 108 cm-3, respectively. To investigate the state-of-the-art chemical mechanism of radical, closure experiments were conducted with a box model, in which the RACM2 mechanism updated with the latest isoprene chemistry (RACM2-LIM1) was used. In the base run, OH radicals were underestimated by the model for the low-NO regime, which was likely due to the missing OH recycling. However, good agreement between the observed and modeled OH concentrations was achieved when an additional species X (equivalent to 0.25 ppb of NO mixing ratio) from one new OH regeneration cycle (RO2 + X â†’ HO2, HO2 + X â†’ OH) was added into the model. Additionally, in the base run, the model could reproduce the observed HO2 concentrations. Discrepancies in the observed and modeled HO2 concentrations were found in the sensitivity runs with HO2 heterogeneous uptake, indicating that the impact of the uptake may be less significant in Chengdu because of the relatively low aerosol concentrations. The ROx (= OH + HO2 + RO2) primary source was dominated by photolysis reactions, in which HONO, O3, and HCHO photolysis accounted for 34%, 19%, and 23% during the daytime, respectively. The efficiency of radical cycling was quantified by the radical chain length, which was determined by the NO to NO2 ratio successfully. The parameterization of the radical chain length may be very useful for the further determinations of radical recycling.

12.
Toxicol Lett ; 341: 68-79, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33548343

RESUMO

BACKGROUND: General anesthetics such as sevoflurane interfere with dendritic development and synaptogenesis, resulting in cognitive impairment. The collapsin response mediator protein2 (CRMP2) plays important roles in dendritic development and synaptic plasticity and its phosphorylation is regulated by cycline dependent kinase-5 (Cdk5) and glycogen synthase kinase-3ß (GSK-3ß). Here we investigated whether Cdk5/CRMP2 or GSK-3ß/CRMP2 pathway is involved in sevoflurane-induced developmental neurotoxicity. METHODS: Rats at postnatal day 7 (PND7) were i.p. injected with Cdk5 inhibitor roscovitine, GSK-3ß inhibitor SB415286 or saline 20 min. before exposure to 2.8% sevoflurane for 4 h. Western-blotting was applied to measure the expression of Cdk5/CRMP2 and GSK-3ß/CRMP2 pathway proteins in the hippocampus 6 h after the sevoflurane exposure. When rats grew to adolescence (from PND25), they were tested for open-field and contextual fear conditioning, and then long term potentiation (LTP) from hippocampal slices was recorded, and morphology of pyramidal neuron was examined by Golgi staining and synaptic plasticity-related proteins expression in hippocampus were measured by western-blotting. In another batch of experiment, siRNA-CRMP2 or vehicle control was injected into hippocampus on PND5. RESULTS: Sevoflurane activated Cdk5/CRMP2 and GSK-3ß/CRMP2 pathways in the hippocampus of neonatal rats, reduced dendritic length, branches and the density of dendritic spine in pyramidal neurons. It also reduced the expressions of PSD-95, drebrin and synaptophysin in hippocampus, impaired memory ability of rats and inhibited LTP in hippocampal slices. All the impairment effects by sevoflurane were attenuated by pretreatment with inhibitor of Cdk5 or GSK-3ß. Furthermore, rat transfected with siRNA-CRMP2 eliminated the neuroprotective effects of Cdk5 or GSK-3ß blocker in neurobehavioral and LTP tests. CONCLUSION: Cdk5/CRMP2 and GSK-3ß/CRMP2 pathways participate in sevoflurane-induced dendritic development abnormalities and cognitive dysfunction in developing rats.


Assuntos
Disfunção Cognitiva/induzido quimicamente , Quinase 5 Dependente de Ciclina/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Sevoflurano/toxicidade , Aminofenóis/farmacologia , Animais , Quinase 5 Dependente de Ciclina/antagonistas & inibidores , Quinase 5 Dependente de Ciclina/genética , Dendritos/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/genética , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Maleimidas/farmacologia , Proteínas do Tecido Nervoso/genética , Inibidores de Proteínas Quinases/farmacologia , Células Piramidais/efeitos dos fármacos , Ratos , Roscovitina/farmacologia
13.
J Pharm Sci ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33640336

RESUMO

Affinity chromatography is widely used for antibody purification in biopharmaceutical production. Although there is evidence suggesting that affinity chromatography might induce structural changes in antibodies, allosteric changes in structure have not been well-explored. Here, we used hydrogen exchange-mass spectrometry (HX-MS) to reveal conformational changes in the NIST mAb upon binding with a protein A (ProA) matrix. HX-MS measurements of NIST mAb bound to in-solution and resin forms of ProA revealed regions of the CH2 and CH3 domains with increased protection from HX upon ProA binding, consistent with the known ProA binding region. In-solution ProA experiments revealed regions in the Fab with increased HX uptake when the ProA:mAb molar ratio was increased to 2:1, suggesting an allosterically induced increase in backbone flexibility. Such effects were not observed with lower ProA concentration (1:1 molar ratio) or when ProA resin was used, suggesting some kind of change in binding mode. Since all pharmaceutical processes use ProA bound to resin, our results rule out reversible allosteric effects on the NIST mAb during interaction with resin ProA. However, irreversible effects cannot be ruled out since the NIST mAb was previously exposed to ProA during its original purification.

14.
Neurosurg Rev ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33598819

RESUMO

Epithelioid glioblastoma is a new variant of glioblastoma that has been recently recognized in the 2016 WHO classification of brain tumors. Given the rarity of epithelioid glioblastoma, the clinical characteristics, pathological features, radiological findings, and treatment outcomes are still not well characterized. Therefore, we identified eighty-four epithelioid glioblastoma cases to investigate these characteristics and identify the possible prognostic factors of survival. There were 55 male and 29 female patients with a mean age of 33.6 years. Headache (77.3%) was the most common clinical symptom, and other common symptoms included nausea or vomiting (34%), dizziness (20.5%), seizures (13.6%), and limb weakness (13.6%). Most lesions (88.1%) were located in cerebral lobes, especially in the frontal lobe and temporal lobe. One hundred percent of the patients were IDH1 wild-type (75/75) and INI-1 positive (58/58), and 57.3% (47/82) of patients harbored BRAFV600E mutation. The median overall survival (OS) of all patients was 10.5 months. Patients who received chemotherapy (p = 0.006) or radiotherapy (p = 0.022) had a longer survival than patients who did not. In addition, the K-M curve showed that the BRAFV600E mutation status was not associated with survival (p = 0.724). These findings may assist clinicians with better understanding and management of epithelioid glioblastoma.

15.
Food Chem ; 348: 129150, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33513529

RESUMO

Selenium-enriched potato is a good supplement for selenium-deficient populations. This study evaluated the influence of two most common cooking methods, including boiling and frying, on selenium content, speciation, and in vitro bioaccessibility of selenium-biofortified potato tubers. After foliar application of 200 µg/mL sodium selenite, potato tubers with 1.33 µg Se/g were obtained. Peeling resulted in 53.4%-69.9% loss of selenium in tubers. The total selenium content decreased by approximately 43.3% after boiling, among which up to 38.5% of the lost selenium is found in the boiling water. Nearly 31.7% of selenium was lost via volatilization during frying. Both cooking methods significantly enhanced the bioaccessibility of Se(IV) in tubers. Whereas SeMeCys became less bioaccessible after boiling. SeMet and SeCys2 in fired tubers were not accessible after digestion. This study suggested that boiling is more appropriate for cooking selenium-enriched potatoes.


Assuntos
Culinária/métodos , Selênio/análise , Solanum tuberosum/química , Digestão , Tubérculos/química , Tubérculos/metabolismo , Selênio/metabolismo , Selenito de Sódio/química , Selenito de Sódio/metabolismo , Solanum tuberosum/metabolismo , Espectrofotometria Atômica
16.
Genet Med ; 23(4): 669-678, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33402738

RESUMO

PURPOSE: To examine the overall genomic copy-number variant (CNV) landscape of Chinese pediatric patients with developmental disorders. METHODS: De-identified chromosomal microarray (CMA) data from 10,026 pediatric patients with developmental disorders were collected for re-evaluating the pathogenic CNV (pCNV) yields of different medical conditions and for comparing the frequency and phenotypic variability of genomic disorders between the Chinese and Western patient populations. RESULTS: The overall yield of pCNVs in the Chinese pediatric patient cohort was 21.37%, with variable yields for different disorders. Yields of pCNVs were positively associated with phenotypic complexity and intellectual disability/developmental delay (ID/DD) comorbidity for most disorders. The genomic burden and pCNV yield in neurodevelopmental disorders supported a female protective effect. However, the stratification analysis revealed that it was seen only in nonsyndromic ID/DD, not in nonsyndromic autism spectrum disorders or seizure. Furthermore, 15 known genomic disorders showed significantly different frequencies in Chinese and Western patient cohorts, and profiles of referred clinical features for 15 known genomic disorders were also significantly different in the two cohorts. CONCLUSION: We defined the pCNV yields and profiles of the Chinese pediatric patients with different medical conditions and uncovered differences in the frequency and phenotypic diversity of genomic disorders between Chinese and Western patients.

17.
Nurse Educ Today ; 98: 104734, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33465678

RESUMO

BACKGROUND: Cultivating the professional knowledge and professional identity of nursing students is important for nursing education. The degree of professional identity of nursing students will directly affect their career options and work performance after graduation. Clinical practice is a learning process of combining the knowledge and the practical techniques of nursing. It is the important way to cultivate the students' comprehensive ability, professional attitude and professional emotion. Effective clinical supervision during the clinical practice plays an important role in guaranteeing clinial practice quality and cultivating professional nursing students. Active teaching supervision is helpful to achieve the expected learning effect. Therefore, it is vital to evaluate the clinical supervision ability of the clinical nursing teachers. However, there is no special assessment instrument available in China. OBJECTIVES: To assess the validity and reliability of the Chinese version of the modified Clinical Supervision Self-Assessment Tool (mCAST). DESIGN: A cross sectional survey design with a convenience sample was used in this study. This cross-sectional psychometric instrumental study determined the reliability and validity of the Chinese version of the modified Clinical Supervision Self-Assessment Tool (mCAST). SETTINGS: Twelve hospitals in Tianjin, China. PARTICIPANTS: A total of 350 registered nurses who perform teaching tasks in clinical practice were recruited. METHODS: The Chinese version of the mCSAT was translated and tested by obtaining the authorization of the developer of the mCAST using Brislin's model (that is, translation, back translation, cultural adaptation and pilot study). A total of 350 registered nurses who perform teaching tasks in clinical practice were recruited by convenience sampling for the assessment of construct validity using exploratory factor analysis (EFA). Moreover, item analysis, internal correlation coefficients, Cronbach's alpha coefficients, test-retest realibility and split-half reliability were conducted to test the psychometric properties of the Chinese version of the mCSAT. RESULTS: The Chinese version of the mCSAT contained 2 subscales, namely, mCSAT-Knowledge and mCSAT-Skills. Exploratory factor analysis of the knowledge and skills subscales explained 63.26% and 63.60% of the total variances, respectively. The mCSAT-Knowledge subscale contains 3 dimensions, namely, evaluating learning (10 items), facilitating learning (9 items) and problem solving (10 items); the mCSAT-Skills subscale contains 3 dimensions, namely, evaluating learning (10 items), facilitating learning (9 items) and problem solving (10 items). The Cronbach's α coefficients of the mCSAT-Knowledge and mCSAT-Skills subscales were both 0.95. The split-half reliability of the mCSAT-Knowledge and mCSAT-Skills subscales were 0.88 and 0.89, respectively. CONCLUSION: The Chinese version of the mCSAT was reliable and valid in the evaluation of the knowledge and skills for the clinical supervision of registered nurses. Further validation of the Chinese version of the mCSAT requires a more representative and larger sample. Also, the confirmatory factor analysis should be conducted in future study.

18.
Mol Med ; 27(1): 7, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509092

RESUMO

BACKGROUND: Malignant glioma exerts a metabolic shift from oxidative phosphorylation (OXPHOs) to aerobic glycolysis, with suppressed mitochondrial functions. This phenomenon offers a proliferation advantage to tumor cells and decrease mitochondria-dependent cell death. However, the underlying mechanism for mitochondrial dysfunction in glioma is not well elucidated. MTCH2 is a mitochondrial outer membrane protein that regulates mitochondrial metabolism and related cell death. This study aims to clarify the role of MTCH2 in glioma. METHODS: Bioinformatic analysis from TCGA and CGGA databases were used to investigate the association of MTCH2 with glioma malignancy and clinical significance. The expression of MTCH2 was verified from clinical specimens using real-time PCR and western blots in our cohorts. siRNA-mediated MTCH2 knockdown were used to assess the biological functions of MTCH2 in glioma progression, including cell invasion and temozolomide-induced cell death. Biochemical investigations of mitochondrial and cellular signaling alternations were performed to detect the mechanism by which MTCH2 regulates glioma malignancy. RESULTS: Bioinformatic data from public database and our cohort showed that MTCH2 expression was closely associated with glioma malignancy and poor patient survival. Silencing of MTCH2 expression impaired cell migration/invasion and enhanced temozolomide sensitivity of human glioma cells. Mechanistically, MTCH2 knockdown may increase mitochondrial OXPHOs and thus oxidative damage, decreased migration/invasion pathways, and repressed pro-survival AKT signaling. CONCLUSION: Our work establishes the relationship between MTCH2 expression and glioma malignancy, and provides a potential target for future interventions.

19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(1): 63-66, 2021 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-33423261

RESUMO

OBJECTIVE: To explore the genotype-phenotype correlation of a case with Sifrim-Hitz-Weiss syndrome (SIHIWES) caused by a novel CHD4 gene variant. METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and her parents. Whole-exome sequencing (WES) was carried out for the patient.Suspected variant was verified by Sanger sequencing. RESULTS: The proband, a 2-year-old Chinese girl, presented with global developmental delay, intellectual disability, distinctive facial features and multiple congenital anomalies. Her prenatal manifestations included increased nuchal thickness, cranial and facial anomalies, and decreased fetal movement. WES has identified a novel variant in the CHD4 gene, namely NM_001273:c.2989C>G (p.Leu997Val) (GRCh37/hg19).Comparison of her phenotype with previously reported SIHIWES cases suggested that our patient's prenatal presentations were unreported before, with novel features including funduscopic anomaly, facial dysmorphisms such as asymmetrical ears, drooping eyelid, long philtrum and downturned mouth. CONCLUSION: Above findings have expanded the mutational spectrum of the CHD4 gene and revealed novel phenotypes in Chinese patients with SIHIWES.


Assuntos
Anormalidades Congênitas , Testes Genéticos , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase , Pré-Escolar , China , Anormalidades Congênitas/genética , Feminino , Estudos de Associação Genética , Humanos , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/genética , Fenótipo , Gravidez , Síndrome , Sequenciamento Completo do Exoma
20.
Nanoscale ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33433555

RESUMO

Stretchable electrodes are essential components for wearable electronics. However, the stretchability of the electrodes is often achieved with the sacrifice of electronic conductivity along with huge variation in resistance. In this work, stretchable metallic glass electrodes (MG-electrodes) that have both high electronic conductivity and excellent electronic stability are developed. The stretchability of the MG-electrode is significantly improved by shrinking MG films deposited on substrates with pre-strain. We demonstrate two types of MG-electrodes. One is a transparent MG-electrode for uniaxial stretching, and the other with better conductivity is for biaxial stretching. Compared with previous electrodes, the MG-electrodes exhibit a combination of high conductivity and negligible resistivity change (<5%), making them promising candidates for interconnections. Along with the excellent corrosion resistance of metallic glasses, the electrodes may be used in harsh environments.

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