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1.
Artigo em Inglês | MEDLINE | ID: mdl-32359824

RESUMO

BACKGROUND: This study aimed to explore the underlying anti-asthma pharmacological mechanisms of Conciliatory Anti-allergic decoction (CAD) with a network pharmacology approach. METHODS: Traditional Chinese medicine related databases were utilized to screen the active ingredients of CAD. Targets of CAD for asthma treatment were also identified based on related databases. The protein-protein interaction network, biological function and KEGG pathway enrichment analysis, and molecular docking of the targets were performed. Furthermore, an asthma mouse model experiment involving HE staining, AB-PAS staining, and ELISA was also performed to assess the anti-asthma effect of CAD. RESULTS: There were 77 active ingredients in CAD, including quercetin, kaempferol, stigmasterol, luteolin, cryptotanshinone, beta-sitosterol, acacetin, naringenin, baicalin, and 48 related targets for asthma treatment, mainly including TNF, IL-4, IL-5, IL-10, IL-13 and IFN-γ, were identified with ideal molecular docking binding scores by network pharmacology analysis. KEGG pathway analysis revealed that these targets were directly involved in the asthma pathway, Th1 and Th2 cell differentiation, and signaling pathways correlated with asthma (NF-κB, IL-17, T cell receptor, TNF, JAK-STAT signaling pathways, etc.). Animal experiments also confirmed that CAD could attenuate inflammatory cell invasion, goblet cell hyperplasia and mucus secretion. The levels of the major targets TNF-α, IL-4, IL-5, and IL-13 can also be regulated by CAD in an asthma mouse model. CONCLUSION: The anti-asthma mechanism of CAD possibly stemmed from the active ingredients targeting asthma-related targets, which are involved in the asthma pathway and signaling pathways to exhibit therapeutic effects.

2.
J Occup Environ Med ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32404835

RESUMO

OBJECTIVE: This study explored whether perceived usefulness and perceived ease-of-use generate mediating effects between personal involvement and attitudes toward paying for usage, and further examining the moderating effects of social influence and company type. METHODS: questionnaires were used. A total of 365 employees, 218 from the private sector and 147 from the municipal government in Taipei City were collected. RESULTS: perceived ease-of-use mediates between personal involvement and attitude toward paying for usage. The social influences of different types of public and private employment differ significantly in terms of their moderating effects on personal involvement and perceived ease-of-use. CONCLUSION: Due to the different workplace characteristics of private sector and government employees, they have different attitudes toward paying for technology-based health management applications in the future, and social influence is also an important moderating factor.

3.
PLoS One ; 15(5): e0233079, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407355

RESUMO

PURPOSE: To evaluate ways to improve the generalizability of a deep learning algorithm for identifying glaucomatous optic neuropathy (GON) using a limited number of fundus photographs, as well as the key features being used for classification. METHODS: A total of 944 fundus images from Taipei Veterans General Hospital (TVGH) were retrospectively collected. Clinical and demographic characteristics, including structural and functional measurements of the images with GON, were recorded. Transfer learning based on VGGNet was used to construct a convolutional neural network (CNN) to identify GON. To avoid missing cases with advanced GON, an ensemble model was adopted in which a support vector machine classifier would make final classification based on cup-to-disc ratio if the CNN classifier had low-confidence score. The CNN classifier was first established using TVGH dataset, and then fine-tuned by combining the training images of TVGH and Drishti-GS datasets. Class activation map (CAM) was used to identify key features used for CNN classification. Performance of each classifier was determined through area under receiver operating characteristic curve (AUC) and compared with the ensemble model by diagnostic accuracy. RESULTS: In 187 TVGH test images, the accuracy, sensitivity, and specificity of the CNN classifier were 95.0%, 95.7%, and 94.2%, respectively, and the AUC was 0.992 compared to the 92.8% accuracy rate of the ensemble model. For the Drishti-GS test images, the accuracy of the CNN, the fine-tuned CNN and ensemble model was 33.3%, 80.3%, and 80.3%, respectively. The CNN classifier did not misclassify images with moderate to severe diseases. Class-discriminative regions revealed by CAM co-localized with known characteristics of GON. CONCLUSIONS: The ensemble model or a fine-tuned CNN classifier may be potential designs to build a generalizable deep learning model for glaucoma detection when large image databases are not available.

4.
Sci Total Environ ; 724: 138375, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32408470

RESUMO

Microplastic pollution in global marine environments has attracted significant concerns; however, the environmental factors that influence the distribution and characteristics of microplastics are still unclear. In this study, 100 L of surface seawater samples collected from 16 different stations of the South Yellow Sea in January, April, and August 2018 were analyzed to investigate the relationship between spatio-temporal distribution of microplastics and environment variables. Results showed that the abundance of microplastics in January (6.5 ± 2.1 items/L) was higher than that in April (4.9 ± 2.1 items/L) and August (4.5 ± 1.8 items/L). On the whole, 78% of the total microplastics were <500 µm, ~90% were fibers, 73.2%-81.7% were transparent, and the two most abundant polymer types were polyethylene and polypropylene. The highest variability of microplastic characteristics (colour, size, and shape) and composition were observed in August, thereby showing the apparent features of terrestrial sources of microplastic pollution. Principal components analysis distinguished the spatio-temporal distribution of the microplastics, and significant difference in plastic sizes was found between microplastics in January and those in the other two months, which could be attributed to the Yellow Sea Warm Current and/or winter monsoon. Additionally, the abundance of microplastics, especially small-sized microplastics (<500 µm), was positively correlated with seawater salinity. These results suggest that microplastic pollution in surface waters of the South Yellow Sea varies with seasons owing to differences in the terrestrial sources and marine hydrological dynamics.

5.
Trials ; 21(1): 406, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410641

RESUMO

BACKGROUND: Previous studies suggested that acupuncture was a promising adjunctive treatment for asthma. However, the underlying mechanism of acupuncture for asthma remains unclear. The aim of the present trial is to explore whether and how specific meridian acupuncture works in quality of life and symptomatic improvement by modulating brain function in patients with asthma. METHODS/DESIGN: This is a randomized controlled functional brain imaging trial currently being conducted in Sichuan, China. In total, 48 patients with mild to moderate persistent asthma will be recruited randomly and allocated to either of two acupuncture groups: acupuncture at the lung meridian or acupuncture at the heart meridian. The treatment period will last 4 weeks. The Asthma Quality of Life Questionnaire is the primary outcome. The Asthma Control Test, peak expiratory flow rate, forced expiratory volume in 1 s, Montreal Cognitive Assessment, Zung Self-rating Anxiety Scale, and Zung Self-rating Depression Scale will also be used to assess the clinical efficacy of different interventions. Functional magnetic resonance imaging (fMRI) will be performed to detect cerebral activity changes in each group. The clinical data and fMRI data will be analyzed between groups, then, the Pearson correlation analysis will be used to assess the association between the changes of cerebral activity features and the improvement of clinical outcomes in each group. DISCUSSION: The present study has been established on the basis of the "meridian-viscera relationship" theory of traditional Chinese medicine and the modern central mechanism of acupuncture. The results of this trial would be useful to identify the efficiency of the specific meridian acupuncture for asthma. The investigation of its central mechanism would further expand knowledge of acupuncture for asthma. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027478. Registered on 15 November 2019.

6.
Int J Mol Sci ; 21(10)2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32414036

RESUMO

Zinc oxide nanoparticles (ZnONPs) are frequently encountered nanomaterials in our daily lives. Despite the benefits of ZnONPs in a variety of applications, many studies have shown potential health hazards of exposure to ZnONPs. We have shown that oropharyngeal aspiration of ZnONPs in mice increases lung inflammation. However, the detailed mechanisms underlying pulmonary inflammatory cell infiltration remain to be elucidated. Endothelium functions as a barrier between the blood stream and the blood vessel wall. Endothelial barrier dysfunction may increase infiltration of immune cells into the vessel wall and underlying tissues. This current study examined the effects of ZnONPs exposure on endothelial barriers. ZnONPs exposure increased leukocyte infiltration in the mouse lungs. In endothelial cells, ZnONPs reduced the continuity of tight junction proteins claudin-5 and zonula occludens-1 (ZO-1) at the cell junctions. ZnONPs induced adherens junction protein VE-cadherin internalization from membrane to cytosol and dissociation with ß-catenin, leading to reduced and diffused staining of VE-cadherin and ß-catenin at cell junctions. Our results demonstrated that ZnONPs disrupted both tight and adherens junctions, compromising the integrity and stability of the junction network, leading to inflammatory cell infiltration. Thus, ZnONPs exposure in many different settings should be carefully evaluated for vascular effects and subsequent health impacts.

7.
J Clin Neurosci ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32418810

RESUMO

To explore the influence of serum lactate dehydrogenase (LDH) level on remote diffusion-weighted imaging lesions (rDWILs) after spontaneous intracerebral hemorrhage (ICH). A consecutive cohort of 160 patients with spontaneous ICH who had brain MRI within 4 weeks of ICH onset were collected and analyzed retrospectively. rDWILs showed high signal on diffusion-weighted image (DWI) while low signal on apparent diffusion coefficient (ADC), and at least 20 mm away from the hemorrhage focus. The blood samples were obtained within 24 h after ICH onset from all patients. Lactate dehydrogenase (LDH) levels in blood were collected from serum biochemical tests. We use multivariate logistic regression analyses to investigate the association between serum LDH level and rDWILs after ICH. The average serum LDH level was 186.5 ± 35.6 U/L. And this level was higher in patients who presented rDWILs than in those without rDWILs. With the best cut-off value of 191 by using receiver operating characteristic (ROC) analysis, elevated LDH was associated with the presence of rDWILs independently (OR = 1.024, 95%CI = 1.011-1.037, P < 0.001) in the bivariate logistic regression analysis with adjustment for age, sex, previous ischemic stroke/TIA, smoker, SBP on admission, hematoma volume, and intraventricular hemorrhage (IVH). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of LDH ≥ 191 U/L for rDWILs were 70.4%, 72.2%, 33.9%, 94.2%, respectively. Our study suggests serum LDH level has a significant correlation with rDWILs after spontaneous ICH. Patients with higher serum LDH level in 24 h after ICH onset may be a useful predictor for rDWILs occurrence.

8.
Disabil Rehabil ; : 1-7, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32372705

RESUMO

Purpose: To examine the relationships among therapist-reported, patient-reported, and objective assessment scores of balance function.Methods: Inpatients with stroke and occupational therapists were recruited. The objective balance scores were measured using the Balance Computerized Adaptive Testing (Balance CAT) system. The therapist and patient-reported scores were evaluated using a visual analogue scale (VAS) and Likert-type scale.Results: Eighty-eight patients and 16 therapists participated. The correlations (r= 0.64 and 0.65; R-squared about 0.42 at baseline and follow-up assessments, respectively) between the therapist-reported VAS scores and the Balance CAT system were larger than those (r = 0.31 and 0.21) between the patient-reported VAS scores and the Balance CAT system. Low correlations (r = 0.27 and 0.26 for VAS and Likert-type scores, respectively) were found between the therapist-reported and patient-reported change scores. Low correlations (r = 0.12-0.17) were found between the change scores of therapist- and patient-reported ratings and those of the Balance CAT system.Conclusions: The therapists' judgments explained <50% of variance of the Balance CAT system scores. Neither therapist-reported nor patient-reported change scores reflected the changes demonstrated by the objective assessments. Further studies are warranted to confirm our findings.Implications for RehabilitationNeither therapist- nor patient-reported balance function and change could effectively reflect the scores resulting from objective assessments.The routine use of objective balance assessments should not be replaced by therapists' subjective judgments.Communications regarding the balance function measured by objective assessments between therapists and patients can help patients to better understand their balance function and progress.

10.
J Environ Manage ; 267: 110649, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32364133

RESUMO

This study used a laboratory-scale system to investigate the effects of calcium magnesium phosphate fertilizer (CaMgP), biochar, and spent mushroom substrate (SMS) on compost maturity and gasous emissions during pig manure composting. The results showed that the addition of CaMgP, Biochar or SMS had no negative effect on the quality and maturity of compost, and all three additives could reduce the emissions of ammonia (NH3), hydrogen sulfide (H2S), dimethyl sulfide (Me2S) and dimethyl disulfide (Me2SS). Among them, the effect of adding CaMgP on NH3 emission reduction was the most obvious, reduced 42.90%. The emission reduction of CaMgP to H2S was similar to that of SMS, which decreased by 34.91% and 32.88% respectively. The emission reduction effects of the three additives on Me2S and Me2SS were obvious, all of which were over 50%. However, only adding SMS reduced the N2O emission by 37.08%.


Assuntos
Agaricales , Compostagem , Animais , Carvão Vegetal , Fertilizantes , Gases , Esterco , Nitrogênio , Fosfatos , Solo , Suínos
11.
Environ Pollut ; 264: 114648, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32380394

RESUMO

BACKGROUND: No information is available on the long-term effects on thyroid and growth hormones of children exposed to phthalate-tainted products, despite the infamous 2011 Taiwan phthalate episode. We investigated estimated daily intake levels and their long-term effects on serum thyroid and growth hormone levels in children. METHODS: We recruited 166 children (2-18 years old) in three visits who provided specimens and filled out a questionnaire from the Risk Assessment of Phthalate Incident in Taiwan (RAPIT) project study from 2012 to 2016. Morning spot urine samples were analyzed for nine phthalate metabolites. Serum thyroid (triiodothyronine [T3], thyroxine [T4], and free T4) and growth hormone (insulin-like growth factor-1 [IGF-1] and its binding protein 3 [IGF-BP3]) levels were measured. A generalized estimating equation model was used to evaluate associations between phthalate metabolite levels and children's thyroid and growth hormone levels. RESULTS: The median metabolite levels of monomethyl phthalate (MMP), Σdibutyl phthalate (DBP), and Σdi-(2-ethylhexyl) phthalate (DEHP) at visits 1, 2, and 3 were 6.59, 10.5, and 21.0 ng/mL, 0.15, 0.24, and 0.20 nmol/mL, and 0.15, 0.17, and 0.12 nmol/mL, respectively. After adjusting for potential confounding factors, we found that levels of urinary MMP were negatively associated with T3 (ß = -0.013, p = 0.047), T4 (ß = -0.016, p = 0.006), free T4 (ß = -0.012, p = 0.002), and IGF-BP3 (ß = -0.025, p = 0.003). Urinary mono-ethyl phthalate (MEP) was negatively associated with IGF-1 (ß = -0.027, p = 0.029) and IGF-BP3 (ß = -0.016, p = 0.018). In addition, serum free T4 was positively associated with urinary mono-2-ethyl-5-hydroxy hexyl phthalate (MEHHP) (ß = 0.016, p = 0.043), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (ß = 0.015, p = 0.024), and ΣDEHPm (ß = 0.019, p = 0.020). CONCLUSIONS: Our findings support the hypothesis that specific phthalates disturb the hemostasis of thyroid and growth hormone levels in children exposed to phthalate-tainted products.

12.
BMC Pediatr ; 20(1): 179, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32326888

RESUMO

BACKGROUND: Thyroid hormones play an important role in the normal growth and maturation of the central nervous system. However, few publications addressed the altered thyroid hormone levels in preterm small for gestational age (SGA) newborns. We hypothesized preterm SGA infants have higher thyroid-stimulating hormone (TSH) concentrations than appropriate for gestational age (AGA) ones within the normal range and an increased incidence of thyroid dysfunction. METHODS: The study was designed to compare thyroid hormone levels within the normal range and the incidence of thyroid dysfunction in the SGA and AGA groups to test the hypothesis. The medical records of all preterm infants admitted to the neonatal intensive care unit (NICU) at the First Affiliated Hospital of Shantou University Medical College, Shantou, China, between January 1, 2015 and December 31, 2018, were reviewed. Blood samples were collected between 72 and 96 h of life and analyzed with TSH, free thyroxine (FT4) and free triiodothyronine (FT3) assays. Thyroid function test (TFT) results, and neonatal demographic and clinical factors were analyzed to identify the associations between SGA birth and altered thyroid concentrations and thyroid dysfunction. RESULTS: TSH and FT4 concentrations were significantly higher in the SGA group than the AGA group ((3.74(interquartile range (IQR):2.28 ~ 6.18) vs. 3.01(IQR: 1.81 ~ 5.41) mU/L, p = 0.018), and (17.76 ± 3.94 vs. 17.42 ± 3.71 pmol/L, p = 0.371), respectively). The higher TSH levels were associated with being SGA or Z-score of birth weight (BW) for GA after adjusting for potential confounders ((ßSGA = 0.68 (95% confidence interval (CI) 0.15 ~ 1.21), p = 0.013) or (ßZ-score = - 0.25 (95%CI -0.48 ~ - 0.03), p = 0.028), respectively). However, we did not find a significant association between SGA birth and altered FT4 concentrations. Furthermore, compared with the AGA group, the SGA group presented an increased incidence of transient hypothyroxinemia with delayed TSH elevation (dTSHe), a higher percentage receiving levothyroxine (L-T4) therapy, and a higher rate of follow-up within the first 6 months of life. CONCLUSIONS: Preterm SGA newborns had significantly higher TSH concentrations within the normal range and an increased incidence of thyroid dysfunction. The SGA newborns with these features should be closely followed up with periodical TFTs and endocrinologic evaluation.

13.
J Viral Hepat ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32343472

RESUMO

Data on direct-acting antiviral agent (DAA) treatment for mixed genotype hepatitis C virus (HCV) infection are scant. This study examined the effectiveness of glecaprevir/pibrentasvir (GLE/PIB) and ledipasvir/sofosbuvir (LDV/SOF) for mixed HCV genotype infection in a real-world setting in Taiwan. We analysed the data from all patients with mixed HCV genotype infections treated with GLE/PIB or LDV/SOF from 2017 to 2019 in three Chang Gung Memorial Hospitals in Taiwan. The primary treatment outcome was sustained virologic response 12 weeks after treatment cessation (SVR12). Adverse events (AEs) were also evaluated. A total of 5190 HCV patients received DAA treatment during this time period. Among them, 116 patients (2.2%) had mixed infections of any 2 or 3 genotypes of 1a, 1b, 2, 3 and 6. Fifty-four patients received GLE/PIB and 62 received LDV/SOF. SVR12 rates for LDV/SOF vs GLE/PIB therapy were 96.6% (56/58) vs 100% (51/51) by the per-protocol analysis and 90.3% (56/62) vs 94.4% (51/54) by the evaluable population analysis. Two patients with 1b + 6 and 1b + 2 genotype infections in the LDV/SOF group had relapse. Evaluating the GLE/PIB vs LDV/SOF groups for the most common AEs revealed pruritus (16.7% vs 4.8%), abdominal discomfort (5.6% vs 8%) and fatigue (5.6% vs 4.8%). One patient with AE-related treatment discontinuation presented with liver decompensation after 4-week GLE/PIB therapy. DAA-related significant laboratory abnormalities occurred in two patients with >3× elevated bilirubin level in the GLE/PIB group. GLE/PIB and LDV/SOF are well tolerated and achieve high SVR12 rates for patients with mixed HCV genotype infection.

14.
J Exp Med ; 217(5)2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32302378

RESUMO

Multidrug resistance-1 (MDR1) acts as a chemotherapeutic drug efflux pump in tumor cells, although its physiological functions remain enigmatic. Using a recently developed MDR1-knockin reporter allele (Abcb1aAME), we found that constitutive MDR1 expression among hematopoietic cells was observed in cytolytic lymphocytes-including CD8+ cytotoxic T lymphocytes (CTLs) and natural killer cells-and regulated by Runt-related (Runx) transcription factors. Whereas MDR1 was dispensable for naive CD8+ T cell development, it was required for both the normal accumulation of effector CTLs following acute viral infection and the protective function of memory CTLs following challenge with an intracellular bacterium. MDR1 acted early after naive CD8+ T cell activation to suppress oxidative stress, enforce survival, and safeguard mitochondrial function in nascent CTLs. These data highlight an important endogenous function of MDR1 in cell-mediated immune responses and suggest that ongoing efforts to intentionally inhibit MDR1 in cancer patients could be counterproductive.

15.
JCO Clin Cancer Inform ; 4: 357-366, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32330068

RESUMO

PURPOSE: Predicting cancer dependencies from molecular data can help stratify patients and identify novel therapeutic targets. Recently available data on large-scale cancer cell line dependency allow a systematic assessment of the predictive power of diverse molecular features; however, the protein expression data have not been rigorously evaluated. By using the protein expression data generated by reverse-phase protein arrays, we aimed to assess their predictive power in identifying cancer dependencies and to develop a related analytic tool for community use. MATERIALS AND METHODS: By using a machine learning schema, we conducted an analysis of feature importance based on cancer dependency and multiomic data from the DepMap and Cancer Cell Line Encyclopedia projects. We assessed the consistency of cancer dependency data between CRISPR/Cas9 and short hairpin RNA-mediated perturbation platforms. For a fair comparison, we focused on a set of genes with robust dependency data and four available expression-related features (copy number alteration, DNA methylation, messenger RNA expression, and protein expression) and performed the same-gene predictions of the cancer dependency using different molecular features. RESULTS: For the genes surveyed, we observed that the protein expression data contained substantial predictive power for cancer dependencies, and they were the best predictive feature for the CRISPR/Cas9-based dependency data. We also developed a user-friendly protein-dependency analytic module and integrated it with The Cancer Proteome Atlas; this module allows researchers to explore and analyze our results intuitively. CONCLUSION: This study provides a systematic assessment for predicting cancer dependencies of cell lines from different expression-related features of a gene. Our results suggest that protein expression data are a highly valuable information resource for understanding tumor vulnerabilities and identifying therapeutic opportunities.

16.
Cell Death Dis ; 11(4): 265, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32327633

RESUMO

RAGE (receptor for advanced glycation end-product) is thought to be associated with metastasis and poor prognosis of various types of cancer. However, RAGE is constitutively expressed in the normal lung and down-regulated in cancerous lung, while the opposite evidence shows that RAGE-mediated signaling contributes to the tumorigenesis of lung cancer. Therefore, the role of RAGE in lung cancer progression is still unclear to be further investigated. In this study, RAGE-overexpressed stable clones of human lung cancer A549 cells and two local lung adenocarcinoma cell lines CL1-0 and CL1-5 were utilized to verify the effect of RAGE on lung cancer cells while the in vivo xenograft animal model was further performed to evaluate the role of RAGE in the progression of lung cancer. The growth of A549 cells was inhibited by RAGE overexpression. p53-dependent p21CIP1 expression contributed to RAGE-induced growth inhibition by suppressing CDK2 kinase activity and retinoblastoma protein (RB) phosphorylation in vitro. On the other hand, RAGE overexpression promoted migration, invasion, and mesenchymal features of lung adenocarcinoma cells through ERK signaling. Furthermore, an in vivo xenograft experiment indicated that RAGE promoted the metastasis of lung cancer cells with p21CIP1 up-regulation, ERK activation, and the changes of EMT markers. Regarding to the involvement of tumor-associated macrophage (TAM) in the microenvironment, we monitored the expressions of TAM markers including CD68 and CD163 as well as angiogenesis marker CD31 in xenograft slice. The data showed that RAGE might induce the accumulation of TAM in lung cancer cells and further accelerate the in vivo tumor growth. In summary, our study provides evidence indicating the distinct in vitro and in vivo effects of RAGE and related mechanisms on tumor growth and metastasis, which shed light on the oncogenic role of RAGE in lung cancer.

17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(2): 588-594, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32319401

RESUMO

OBJECTIVE: To investigate whether miRNA-30a is involved in the pathogenesis of ITP by affecting the differentiation of Th17 cells, and to explore its possible mechanism of miRNA-30a involved in the pathogenesis of ITP through the verification of the target gene SOCS3 for the prediction of miRNA-30a. METHODS: Firstly, a chronic ITP mouse model was established. The expression of miRNA-30a and RORγt in the spleen mononuclear cells were detected and their correlation were analyzed. Secondly, the luciferase vector containing 3'UTR of the target gene and green fluorescent vector containing miRNA were constructed. Luciferase fluorescence detection, real-time fluorescent quantitative PCR (qPCR) and Western blot were used to verify whether SOCS3 is the target gene of miRNA-30a. RESULTS: The platelet count of mice in experimental group decreased to below 20% of normal ones after 48 hours of injection of anti-mouse platelet serum (APS), which was maintained for 14 days at least; the expression of miRNA-30a and RORγt in the spleen mononuclear cells in experimental group were higher than those in the control group(P<0.05), moreover, there was a positive correlation between them (r=0.54); the activity of luciferase in PMDH-GFP-miRNA-30a and pMIR-report-UTR was significantly lower than that in PMDH-GFP empty plasmid and pMIR-report-UTR(P<0.05); The expression of SOCS3 at mRNA and protein level was not different from that in the control group. CONCLUSION: Chronic ITP mouse model has been established successfully; miRNA-30a expression in spleen mononuclear cells of ITP mouse increase, and positively correlated with the expression of RORγt, which contribute to the pathogenesis of ITP by affecting the differentiation of Th17 cells; SOCS3 is able to bind to the target site of miRNA-30a, but might not be its functional target gene.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32291802

RESUMO

OBJECTIVES: Age-related hearing loss (ARHL) is a prevalent condition associated with increased risk for depression and cognitive decline. This 12-week prospective, double-blind pilot randomized controlled trial (RCT) of hearing aids (HAs) for depressed older adults with ARHL evaluated the feasibility of a novel research design. METHODS/DESIGN: N = 13 individuals aged ≥60 years with Major Depressive Disorder or Persistent Depressive Disorder and at least mild hearing loss (pure tone average ≥ 30 dB) were randomized to receive full- (active) vs low-amplification (sham) HAs added to psychiatric treatment as usual. Duration of HA use in hours/day, adverse events frequency, attrition rate, and maintenance of the study blinding were the primary outcome measures. RESULTS: Compliance with HAs was excellent (>9 hours/day for both groups) and rates of adverse events and drop-outs did not differ between groups. Preliminary data demonstrated differential improvement for active vs sham HAs on hearing functioning (Hearing Handicap Inventory for the Elderly [nonparametric effect size (np-ES) = 0.62]), depressive symptoms (Inventory for Depressive Symptomatology [np-ES = 0.31]), cognition (Repeatable Battery for the Assessment of Neuropsychological Status Immediate Memory [np-ES = 0.25]), and general functioning (World Health Organization Disability Assessment Schedule [np-ES = 0.53]). Significantly greater than 50% of both groups correctly guessed their treatment assignment, indicating incomplete concealment of treatment allocation. CONCLUSIONS: This pilot RCT for ARHL and late-life depression was feasible to execute and showed clinical promise, but improved methods of blinding the experimental treatments are needed. Larger studies should investigate whether hearing remediation may be an effective preventative and/or therapeutic strategy for late-life depression and cognitive decline.

19.
Int J Neurosci ; : 1-8, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32315556

RESUMO

Objectives: This study aimed to investigate the influence of neutrophil-to-lymphocyte ratio (NLR) on the severity and short-time curative effect of myasthenia gravis (MG) in children.Methods: Data of 132 MG children were retrospectively analyzed, and data of 140 healthy controls (HC group) in the same period were collected. The data of both groups were compared and analyzed.Results: NLR of MG group was significantly higher than that of HC group (Z = 2.644, p = 0.008). According to NLR level, patients were divided into 3 groups: N1 (NLR < 1.03), N2 (NLR 1.03-2.17), and N3 (NLR > 2.17). Significant differences in white blood cell counts, course of disease, uric acid, albumin and the time of hospital stay among the 3 groups were observed (p < 0.05, 0.01). The results of logistic regression revealed that NLR (adjusted OR = 3.874, 95% CI 1.359-11.045, p = 0.011) was the risk factor of MG, and it was risk factor of higher QMG during admission (adjusted OR = 2.989, 95% CI 1.247-7.160, p = 0.014) as well. Using the NLR level for the MG diagnostic test, the area under the receiver operating characteristic (ROC) curve was 0.765 [95%CI (0.710-0.820), p = 0.000], with a cut-off value of 1.39, sensitivity of 0.833, and specificity of 0.479. Cox regression analysis suggested that NLR (N1: Wald = 9.262, p = 0.010, N2: HR = 12.267, 95%CI 2.432-61.863, p = 0.000, and N3: HR = 8.142, 95%CI 1.209-77.754, p = 0.032) was associated with poor efficacy at discharge. Elevated NLR was considered as an independent risk factor of poor outcomes during discharge.Conclusion: NLR could reflect disease severity and short time curative effect in children with MG to some extent. It may also be a potential marker in indicating diagnosis and severity of MG in children.

20.
Head Neck ; 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32323895

RESUMO

BACKGROUND: Combining photon or proton radiotherapy with targeted therapy shows promise for head and neck cancer (HNSCC). The poly (adenosine diphosphate [ADP]-ribose) polymerase-1/2 inhibitor niraparib targets DNA damage repair (DDR). We evaluated the effects of niraparib in combination with photons or protons, and its effects on the relative biological effectiveness (RBE) of protons, in human HNSCC cell lines. METHODS: Radiosensitivity was assessed and RBE was calculated with clonogenic survival assays; unrepaired DNA double-strand breaks were evaluated using immunocytochemical analysis of 53BP1 foci. RESULTS: Niraparib reduced colony formation in two of the four cell lines tested (P < .05), enhanced radiosensitivity in all four cell lines, delayed DDR (P < .05), and increased proton vs photon RBE. CONCLUSION: Niraparib enhanced the sensitivity of four HNSCC cell lines to both photons and protons and increased the RBE of protons, possibly by inhibiting DDR. Niraparib may enhance the effectiveness of both photon and proton radiotherapy for patients with HNSCC.

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