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1.
Toxicol Pathol ; 51(6): 313-328, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-38288712

RESUMO

Digital pathology workflows in toxicologic pathology rely on whole slide images (WSIs) from histopathology slides. Inconsistent color reproduction by WSI scanners of different models and from different manufacturers can result in different color representations and inter-scanner color variation in the WSIs. Although pathologists can accommodate a range of color variation during their evaluation of WSIs, color variability can degrade the performance of computational applications in digital pathology. In particular, color variability can compromise the generalization of artificial intelligence applications to large volumes of data from diverse sources. To address these challenges, we developed a process that includes two modules: (1) assessing the color reproducibility of our scanners and the color variation among them and (2) applying color correction to WSIs to minimize the color deviation and variation. Our process ensures consistent color reproduction across WSI scanners and enhances color homogeneity in WSIs, and its flexibility enables easy integration as a post-processing step following scanning by WSI scanners of different models and from different manufacturers.


Assuntos
Inteligência Artificial , Patologistas , Humanos , Reprodutibilidade dos Testes
2.
Zhonghua Bing Li Xue Za Zhi ; 52(9): 912-917, 2023 Sep 08.
Artigo em Zh | MEDLINE | ID: mdl-37670620

RESUMO

Objective: To investigate the evolution and clinical significance of HER2 low expression status in HER2 negative patients in primary and recurrent/metastatic breast cancers. Methods: The data and archived sections of 259 breast cancer patients with recurrence/metastasis and HER2-negative primary foci were collected from January 2015 to January 2022 at the Fourth Hospital of Hebei Medical University, and the HER2 status of primary and recurrence/metastasis foci was determined by immunohistochemistry (IHC), among which IHC 2+patients were subject to fluorescence in situ hybridization (FISH). The HER2 status was classified as HER2-0 group; patients with IHC 1+, IHC 2+and no FISH amplification were classified as HER2 low expression group; and patients with IHC 3+, IHC 2+and FISH amplified were classified as HER2-positive group. The changes of HER2 status in patients with HER2 low expression in primary versus recurrent/metastatic breast cancer foci were compared, and their clinicopathologic characteristics and prognosis were analyzed. Results: The overall concordance rate between primary and recurrent/metastatic HER2 status in breast cancer was 60.6% (157/259, κ=0.178). A total of 102 patients (102/259, 39.4%) had inconsistent primary and recurrent/metastatic HER2 status; 37 patients (37/259, 14.3%) had HER2-0 at the primary foci and HER2-low expression at the recurrent/metastatic; and 56 patients (56/259, 21.6%) had HER2-low expression in the primary foci and HER2-0 in the recurrent/metastatic. The recurrent/metastatic foci became low-expressing compared with the recurrent/metastatic foci which remained HER2-0 patients, with longer overall survival time, higher ER and PR positivity, lower Ki-67 positivity index, and lower tumor histological grade; all with statistically significant differences (all P<0.05). In the primary HER2-low group, patients with recurrent/metastatic foci became HER2-0 while those with recurrent/metastatic foci remained low expression; there were no statistically significant differences in clinicopathological features and overall survival time (all P>0.05). Conclusions: Unstable HER2 status in patients with HER2-0 and low expression in primary versus recurrent/metastatic breast cancer foci, and HER2-0 in the primary foci but low HER2 expression status in recurrence/metastasis is associated with favourable prognosis, and testing HER2 status in recurrence/metastasis can provide more treatment options for such patients.


Assuntos
Neoplasias da Mama , Relevância Clínica , Humanos , Neoplasias da Mama/genética , Hibridização in Situ Fluorescente , Feminino
3.
Climacteric ; 25(2): 128-140, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34346265

RESUMO

This systematic review provides an overview of the effects of menopausal symptom treatment options on palpitations, defined as feelings of missed or exaggerated heart beats, reported by perimenopausal and postmenopausal women. Guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searches were conducted in PubMed, CINAHL and PsycINFO to identify articles meeting pre-specified inclusion criteria. Of 670 unique articles identified, 37 were included in the review. Treatments included drug therapies and non-drug therapies. Palpitations were studied as an outcome in 89% of articles and as an adverse effect in 11%. Articles provided mostly level II/III evidence due to their design and/or small sample sizes. Based on available evidence, no therapies can be fully recommended for clinical practice. Only some hormonal agents (e.g. estradiol) can be recommended with caution based on some positive evidence for reducing palpitation prevalence or severity. However, other drug therapies (e.g. moxonidine, atenolol), dietary supplementary treatments (e.g. isoflavones, Rheum rhaponticum, sage), cognitive-behavioral intervention and auricular acupressure cannot be recommended given the existing evidence. Additional well-designed randomized controlled treatment trials focusing on palpitations during the menopause transition as an inclusion criteria and outcome are needed to advance the field.


Assuntos
Terapia Cognitivo-Comportamental , Isoflavonas , Feminino , Humanos , Menopausa
4.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(9): 1333-1340, 2022 Sep 06.
Artigo em Zh | MEDLINE | ID: mdl-36207900

RESUMO

This research and development of MenB meningococcal vaccines includes two technical routes: outer membrane vesicle (OMV) vaccines and recombinant protein vaccines. This article intends to review the development, production and application of MenB meningococcal OMV vaccines in order to provide a reference for the development of MenB meningococcal OMV vaccine in China.


Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis Sorogrupo B , Antígenos de Bactérias , Humanos , Infecções Meningocócicas/prevenção & controle , Sorogrupo , Vacinas Sintéticas
5.
Entropy (Basel) ; 23(4)2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33801733

RESUMO

Transfer learning seeks to improve the generalization performance of a target task by exploiting the knowledge learned from a related source task. Central questions include deciding what information one should transfer and when transfer can be beneficial. The latter question is related to the so-called negative transfer phenomenon, where the transferred source information actually reduces the generalization performance of the target task. This happens when the two tasks are sufficiently dissimilar. In this paper, we present a theoretical analysis of transfer learning by studying a pair of related perceptron learning tasks. Despite the simplicity of our model, it reproduces several key phenomena observed in practice. Specifically, our asymptotic analysis reveals a phase transition from negative transfer to positive transfer as the similarity of the two tasks moves past a well-defined threshold.

6.
Ecol Lett ; 22(4): 583-592, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30687985

RESUMO

Phylogenetically informed trait comparisons across entire communities show promise in advancing community ecology. We use this approach to better understand the composition of a community of winter annual plants with multiple decades of monitoring and detailed morphological, phenological and physiological measurements. Previous research on this system revealed a physiological trade-off among dominant species that accurately predicts population and community dynamics. Here we expanded our investigation to 51 species, representing 96% of individual plants recorded over 30 years, and analysed trait relationships in the context of species abundance and phylogenetic relationships. We found that the functional-trait trade-off scales to the entire community, albeit with diminished strength. It is strongest for dominant species and weakens as progressively rarer species are included. The trade-off has been consistently expressed over three decades of environmental change despite some turnover in the identity of dominant species.


Assuntos
Fenótipo , Plantas , Filogenia , Estações do Ano
7.
Zhonghua Gan Zang Bing Za Zhi ; 27(10): 793-798, 2019 Oct 20.
Artigo em Zh | MEDLINE | ID: mdl-31734995

RESUMO

Objective: To investigate the tumor necrosis factor receptor superfamily 1B gene (TNFRSF1B) polymorphism in relation to the outcomes of hepatitis C virus (HCV) infection. Methods: One thousand six hundred and forty-five cases without HCV infection, 545 cases with HCV clearance, and 783 cases with chronic HCV infection were enrolled. TaqMan probe method was used to investigate genotype rs1061622 (T > G) and rs1061624 (G > A). Two single nucleotide polymorphisms (SNPs) sites were genotyped and haplotypes were constructed to evaluate their relation with the outcome of HCV infection. Results: Logistic regression analysis showed that there was no relation to the two SNPs with HCV infection susceptibility and chronicity (P > 0.05). Haplotype analysis showed that carrier TA had an increased susceptibility to HCV infection [adjusted odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.01 to 1.30, P = 0.038)]. Carrier TA and GG haplotypes were conducive to chronic HCV infection (adjusted OR = 1.28, 95% CI: 1.08 to 1.53, P = 0.006; OR = 1.31, 95% CI: 1.03 to 1.66, P = 0.026). Conclusion: The combinational effects of rs1061622 and rs1061624 in TNFRSF1B gene may increase the risk of HCV chronicity and infection.


Assuntos
Hepatite C/genética , Receptores Tipo II do Fator de Necrose Tumoral/genética , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único
8.
Proc IEEE Inst Electr Electron Eng ; 106(8): 1293-1310, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30828106

RESUMO

For many modern applications in science and engineering, data are collected in a streaming fashion carrying time-varying information, and practitioners need to process them with a limited amount of memory and computational resources in a timely manner for decision making. This often is coupled with the missing data problem, such that only a small fraction of data attributes are observed. These complications impose significant, and unconventional, constraints on the problem of streaming Principal Component Analysis (PCA) and subspace tracking, which is an essential building block for many inference tasks in signal processing and machine learning. This survey article reviews a variety of classical and recent algorithms for solving this problem with low computational and memory complexities, particularly those applicable in the big data regime with missing data. We illustrate that streaming PCA and subspace tracking algorithms can be understood through algebraic and geometric perspectives, and they need to be adjusted carefully to handle missing data. Both asymptotic and non-asymptotic convergence guarantees are reviewed. Finally, we benchmark the performance of several competitive algorithms in the presence of missing data for both well-conditioned and ill-conditioned systems.

9.
Zhonghua Bing Li Xue Za Zhi ; 47(3): 196-200, 2018 Mar 08.
Artigo em Zh | MEDLINE | ID: mdl-29534360

RESUMO

Objective: To investigate the effect of extensive retraction clefts (RC, >20% of tumor volume) on prognosis in invasive breast carcinoma of no specific type (IBC-NST). Methods: A total of 2 184 cases of IBC-NST diagnosed at the Fourth Hospital of Hebei Medical University from January 2006 to December 2008 were collected. All the cases were diagnosed according to the latest guideline and standard. After excluding cases of shrinkage due to tissue fixation, 483 cases with RC were identified, and the clinical and pathological features were retrospectively analyzed. Results: Among the 483 cases, the mean tumor size was 2.0 cm (range 0.8 to 4.8 cm). Two hundred and thirty-two cases were moderately differentiated (48.0%), 97 were well differentiated (20.1%), 154 were poorly differentiated (31.9%); 382 (79.1%) cases were of stages Ⅰ and Ⅱ. A total of 177 cases (36.7%) had lymphatic invasion; nodal metastasis were found in 202 cases (41.8%). Extensive RC was found in 237 of 483 cases (49.1%). Follow-up information was available in 407 patients, and 46 died of breast cancer with survival time from 37 to 103 months. Multivariate analysis of extensive RC showed that tumor size, histological grade and nodal metastasis were risk factors of patients with IBC-NST (P<0.05). Lymphatic invasion and nodal metastasis were risk factors for extensive RCs in patients with IBC-NST (P<0.05). There was a high probability of lymph node metastasis in patients of extensive RC without lymphatic invasion, and the difference was statistically significant (P<0.05). Conclusions: Both lymphatic invasion and nodal metastasis are risk factors of extensive RC. The presence of extensive RC in IBC-NST patients is correlated with poor outcome. Tumors with lymphatic invasion are more likely to show extensive RC.


Assuntos
Neoplasias da Mama/patologia , Carga Tumoral , Neoplasias da Mama/mortalidade , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fixação de Tecidos
10.
Zhonghua Zhong Liu Za Zhi ; 39(10): 754-758, 2017 Oct 23.
Artigo em Zh | MEDLINE | ID: mdl-29061019

RESUMO

Objective: To investigate the grading system for lymph vessel tumor emboli and its prognostic value in patients with invasive carcinomas of no special type (ICNST) of the breast. Methods: Clinical data of 466patients with ICNST were collected from January 2006 to December 2008 in the Fourth Hospital of Hebei Medical University. The expression levels of D2-40, estrogen receptor(ER), progesterone receptor(PR) and human epidermal growth factor receptor 2 (HER-2) were analyzed using immunohistochemical staining. Grades for lymph vessel tumoremboli were classified based on the number of mitotic and apoptotic figures in tumor cells under a high-power field. Correlation analysis was performed using Spearman rank correlation test. Kaplan-meier curves and Log-rank tests were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Results: Among the 466 patients, grades for lymph vessel tumor emboli were categorized as follows: 280 cases were grade 0 (60.1%); 112 cases were grade 1 (24.0%); 58 cases were grade 2 (12.5%); 16 cases were grade 3 (3.4%). Correlation analyses showed that lymph vessel tumor emboli grading system was positively correlated with lymph node metastasis (r=0.365, P<0.001). Kaplan-Meier univariant analysis showed that histological grading, lymph vessel tumor emboli grading system, lymph node metastasis, the expression levels of ER, PR and HER-2 and molecular typing were associated with prognosis of patients (P<0.05 for all). Multivariate analysis of Cox proportional hazard model showed that lymph vessel tumor emboli grading system and lymph node metastasis were independent prognostic factors in patients with ICNST(P<0.05 for all). Conclusion: Grading system for lymph vessel tumor emboli canpredict the clinical outcome of patients with ICNST.


Assuntos
Neoplasias da Mama/patologia , Carcinoma/patologia , Vasos Linfáticos/patologia , Gradação de Tumores/métodos , Células Neoplásicas Circulantes/patologia , Apoptose , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Carcinoma/química , Carcinoma/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Índice Mitótico , Prognóstico , Modelos de Riscos Proporcionais , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Taxa de Sobrevida
11.
Neuroimage ; 125: 587-600, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26481679

RESUMO

Motivated by recent progress in signal processing on graphs, we have developed a matched signal detection (MSD) theory for signals with intrinsic structures described by weighted graphs. First, we regard graph Laplacian eigenvalues as frequencies of graph-signals and assume that the signal is in a subspace spanned by the first few graph Laplacian eigenvectors associated with lower eigenvalues. The conventional matched subspace detector can be applied to this case. Furthermore, we study signals that may not merely live in a subspace. Concretely, we consider signals with bounded variation on graphs and more general signals that are randomly drawn from a prior distribution. For bounded variation signals, the test is a weighted energy detector. For the random signals, the test statistic is the difference of signal variations on associated graphs, if a degenerate Gaussian distribution specified by the graph Laplacian is adopted. We evaluate the effectiveness of the MSD on graphs both with simulated and real data sets. Specifically, we apply MSD to the brain imaging data classification problem of Alzheimer's disease (AD) based on two independent data sets: 1) positron emission tomography data with Pittsburgh compound-B tracer of 30 AD and 40 normal control (NC) subjects, and 2) resting-state functional magnetic resonance imaging (R-fMRI) data of 30 early mild cognitive impairment and 20 NC subjects. Our results demonstrate that the MSD approach is able to outperform the traditional methods and help detect AD at an early stage, probably due to the success of exploiting the manifold structure of the data.


Assuntos
Doença de Alzheimer/diagnóstico , Mapeamento Encefálico/métodos , Encéfalo/patologia , Interpretação de Imagem Assistida por Computador/métodos , Modelos Neurológicos , Algoritmos , Humanos , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Modelos Teóricos , Tomografia por Emissão de Pósitrons
12.
J Neurophysiol ; 115(1): 39-59, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26467513

RESUMO

Perceptual decision making is fundamental to a broad range of fields including neurophysiology, economics, medicine, advertising, law, etc. Although recent findings have yielded major advances in our understanding of perceptual decision making, decision making as a function of time and frequency (i.e., decision-making dynamics) is not well understood. To limit the review length, we focus most of this review on human findings. Animal findings, which are extensively reviewed elsewhere, are included when beneficial or necessary. We attempt to put these various findings and data sets, which can appear to be unrelated in the absence of a formal dynamic analysis, into context using published models. Specifically, by adding appropriate dynamic mechanisms (e.g., high-pass filters) to existing models, it appears that a number of otherwise seemingly disparate findings from the literature might be explained. One hypothesis that arises through this dynamic analysis is that decision making includes phasic (high pass) neural mechanisms, an evidence accumulator and/or some sort of midtrial decision-making mechanism (e.g., peak detector and/or decision boundary).


Assuntos
Encéfalo/fisiologia , Tomada de Decisões , Percepção , Animais , Humanos , Limiar Sensorial
13.
Proc Natl Acad Sci U S A ; 110(30): 12186-91, 2013 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-23776236

RESUMO

Imagine that you are blindfolded inside an unknown room. You snap your fingers and listen to the room's response. Can you hear the shape of the room? Some people can do it naturally, but can we design computer algorithms that hear rooms? We show how to compute the shape of a convex polyhedral room from its response to a known sound, recorded by a few microphones. Geometric relationships between the arrival times of echoes enable us to "blindfoldedly" estimate the room geometry. This is achieved by exploiting the properties of Euclidean distance matrices. Furthermore, we show that under mild conditions, first-order echoes provide a unique description of convex polyhedral rooms. Our algorithm starts from the recorded impulse responses and proceeds by learning the correct assignment of echoes to walls. In contrast to earlier methods, the proposed algorithm reconstructs the full 3D geometry of the room from a single sound emission, and with an arbitrary geometry of the microphone array. As long as the microphones can hear the echoes, we can position them as we want. Besides answering a basic question about the inverse problem of room acoustics, our results find applications in areas such as architectural acoustics, indoor localization, virtual reality, and audio forensics.

14.
Eye Contact Lens ; 42(1): 35-42, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26704136

RESUMO

OBJECTIVES: The aim of this review is to evaluate the ocular safety of orthokeratology (OrthoK) treatment of myopia correction and retardation. DATA SOURCES: Clinical studies published in English and Chinese were identified from MEDLINE, EMBASE CNKI, CQVIP, and WANFANG DATA (all from 1980 to April 2015). The reference lists of the studies and the Science Citation Index were also searched. SELECTION CRITERIA: Relevant clinical studies including case series, case reports, patient/practitioner surveys, retrospective and prospective cohort studies, and clinical trials were all included in the review. The material of OrthoK lenses was limited to gas-permeable lens. MAIN RESULTS: This review incorporated a total of 170 publications, including 58 English and 112 Chinese literature. The risk of microbial keratitis in overnight OrthoK was similar to that of other overnight modality. The most common complication was corneal staining. Other clinically insignificant side effects included epithelial iron deposit, prominent fribrillary lines, and transient changes of corneal biomechanical properties. There was no long-term effect of OrthoK on corneal endothelium. CONCLUSIONS: There is sufficient evidence to suggest that OrthoK is a safe option for myopia correction and retardation. Long-term success of OrthoK treatment requires a combination of proper lens fitting, rigorous compliance to lens care regimen, good adherence to routine follow-ups, and timely treatment of complications.


Assuntos
Lentes de Contato , Miopia/terapia , Procedimentos Ortoceratológicos/métodos , Criança , Pré-Escolar , Estudos Clínicos como Assunto , Lentes de Contato/efeitos adversos , Doenças da Córnea/etiologia , Infecções Oculares/etiologia , Humanos , Miopia/prevenção & controle , Procedimentos Ortoceratológicos/efeitos adversos , Acuidade Visual
15.
Zhonghua Zhong Liu Za Zhi ; 38(5): 325-32, 2016 May 23.
Artigo em Zh | MEDLINE | ID: mdl-27188603

RESUMO

OBJECTIVE: To investigate the effect of bufalin on proliferation and apoptosis through ERK/RSK2 pathway in esophageal squamous cell carcinoma xenografts in nude mice. METHODS: The subcutaneous xenograft model of esophageal cancer ECA109 cells in nude mice was established. The mice were divided into the model group, low-dose bufalin group, medium-dose bufalin group, high-dose bufalin group, PD98059 group and combination group to evaluate the effect of bufalin on the xenografts. The morphology of xenografts was observed by microscopy. The cell apoptosis index of xenografts was detected by TUNEL assay. The expression of ERK and RSK2 mRNA of human ECA109 cell transplantation tumor in nude mice was examined by real-time quantitative PCR. The protein levels of ERK, p-ERK, RSK2, p-RSK2, GSK3ß, p-GSK3ß, Bad and p-Bad in the xenografts were examined by Western blot and Immunohistochemistry. RESULTS: The tumor size of nude mice in the model group, low-dose bufalin group (BL), medium -dose bufalin group (BM), high-dose bufalin group (BH), PD98059 group and combined therapy group (BP) was (1.758±0.181) cm(3,) (1.680±0.150) cm(3,) (1.285±0.134) cm(3,) (0.873±0.095) cm(3,) (0.815±0.108) cm(3) and (0.530±0.104) cm(3,) respectively. Histological examination showed that the xenografts of each group had varying degrees of necrosis, and the most extensive necrosis was observed in the BP group. The TUNEL assay showed that the cell apoptosis index of xenografts in the model, BL, BM, BH, PD98059 and BP groups was (6.0±0.6)%, (11.0±0.7)%, (19.1±0.9)%, (25.1±1.4)%, (20.0±1.2)% and (17.1±0.7)%, respectively, which is highest in the BH group. The real-time quantitative PCR results showed that the ΔCT values of ERK mRNA in the model, BL, BM, BH, PD98059 and BP groups were 0.270±0.084, 0.293±0.081, 0.596±0.224, 0.857±0.183, 0.868±0.187 and 1.313±0.282, respectively. The ΔCT values of RSK2 mRNA in the model, BL, BM, BH, PD98059 and BP groups were 0.340±0.062, 0.337±0.071, 0.642±0.226, 0.915±0.170, 0.923±0.176 and 1.413±0.269, respectively. The relative expression of ERK and RSK2 mRNA was gradually decreased. Western blot and immunohistochemistry results showed that the protein levels of ERK, RSK2 and Bad in each group were not significantly different (P>0.05). The protein levels of p-ERK in the model, BL, BM, BH, PD98059 and BP groups were 0.721±0.094, 0.695±0.095, 0.555±0.080, 0.388±0.052, 0.341±0.060, 0.235± 0.056, respectively. The median immunoreactivity scores of p-ERK in each group were 8, 8, 6, 4, 5 and 3. The protein levels of p-RSK2 in the model, BL, BM, BH, PD98059 and BP groups were 0.613±0.085, 0.612±0.084, 0.427±0.089, 0.305±0.056, 0.258±0.051, 0.158±0.058, respectively. The median immunoreactivity scores of p-RSK in each group were 8, 8, 5, 3, 3 and 1. The protein level of GSK3ß in the model, BL, BM, BH, PD98059 and BP groups were increased gradually, while the protein level of p-GSK3ß and p-Bad were decreased gradually. CONCLUSIONS: Bufalin exerts significant inhibitory effect on the esophageal squamous cell carcinoma xenogragts in nude mice. Bufalin may suppress the growth of xenogragts in nude mice by down-regulating the level of ERK and RSK2 phosphorylation, inhibit the proliferation of xenogragts via inactivating GSK3ß and promote apoptosis through down-regulation of p-Bad.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Bufanolídeos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Antineoplásicos/administração & dosagem , Bufanolídeos/administração & dosagem , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Flavonoides/farmacologia , Xenoenxertos , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , Camundongos Nus , Necrose , Transplante de Neoplasias , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/metabolismo , Transplante Heterólogo , Carga Tumoral
16.
Neurobiol Dis ; 78: 172-95, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25836420

RESUMO

Mutations in the LRRK2 gene represent the most common genetic cause of late onset Parkinson's disease. The physiological and pathological roles of LRRK2 are yet to be fully determined but evidence points towards LRRK2 mutations causing a gain in kinase function, impacting on neuronal maintenance, vesicular dynamics and neurotransmitter release. To explore the role of physiological levels of mutant LRRK2, we created knock-in (KI) mice harboring the most common LRRK2 mutation G2019S in their own genome. We have performed comprehensive dopaminergic, behavioral and neuropathological analyses in this model up to 24months of age. We find elevated kinase activity in the brain of both heterozygous and homozygous mice. Although normal at 6months, by 12months of age, basal and pharmacologically induced extracellular release of dopamine is impaired in both heterozygous and homozygous mice, corroborating previous findings in transgenic models over-expressing mutant LRRK2. Via in vivo microdialysis measurement of basal and drug-evoked extracellular release of dopamine and its metabolites, our findings indicate that exocytotic release from the vesicular pool is impaired. Furthermore, profound mitochondrial abnormalities are evident in the striatum of older homozygous G2019S KI mice, which are consistent with mitochondrial fission arrest. We anticipate that this G2019S mouse line will be a useful pre-clinical model for further evaluation of early mechanistic events in LRRK2 pathogenesis and for second-hit approaches to model disease progression.


Assuntos
Encéfalo/enzimologia , Dopamina/metabolismo , Mitocôndrias/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/fisiologia , Animais , Autofagia/genética , Encéfalo/metabolismo , Encéfalo/ultraestrutura , Neurônios Dopaminérgicos/metabolismo , Feminino , Técnicas de Introdução de Genes , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias/ultraestrutura , Atividade Motora/genética , Teste de Desempenho do Rota-Rod , Proteínas tau/metabolismo
17.
Tissue Antigens ; 86(2): 134-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26104599

RESUMO

Our recent targeted sequencing study identified a missense single-nucleotide polymorphism rs72474224 (c.324C>T) in GJB2. To investigate the correlation between rs72474224 (c.324C>T) and subphenotypes of psoriasis, genotype data for rs72474224 (c.324C>T, p.Val37Ile) was analyzed in 9946 cases and 9906 controls. The additive model provided the best fit for rs72474224 (P = 7.34 × 10(-9)). The genotypic and allelic frequency distributions were associated with plaque psoriasis in case-only (Pgenotype = 2.67 × 10(-3), Pallele = 6.22 × 10(-4)) and subphenotype-control (Pgenotype = 1.58 × 10(-11), Pallele = 8.16 × 10(-12)) analyses. No other significant difference was found in case-only analyses. Rs72474224 in GJB2 is preferentially associated with plaque psoriasis in Chinese population and might contribute to the complexity of psoriasis clinical features.


Assuntos
Conexinas/genética , Éxons , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Povo Asiático , Estudos de Casos e Controles , Criança , Pré-Escolar , Conexina 26 , Conexinas/imunologia , Feminino , Expressão Gênica , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Psoríase/etnologia , Psoríase/imunologia , Psoríase/patologia
18.
Eur J Clin Microbiol Infect Dis ; 34(7): 1309-18, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25759111

RESUMO

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and the varied outcomes of the infection depend on both viral and host factors. We have demonstrated that the HCV alternate reading frame protein (F protein) is related to Th1/Th2 bias which is involved in virus persistence in chronic hepatitis C (CHC) patients. The purpose of this study was to test the hypothesis that genetic variants of TBX21 (T cell specific T-box transcription factor) were associated with the outcomes of HCV infection and F protein generation. Three single nucleotide polymorphisms (SNPs) (rs17250932, rs2074190, rs4794067) in the TBX21 gene were genotyped in a case-control study in a cohort of a high-risk group, including 354 healthy controls and 747 CHC patients (190 anti-F protein antibody seronegative patients and 557 anti-F protein antibody seropositive patients). Results showed that the rs4794067 C allele in the TBX21 promoter was significantly more common in CHC patients (OR = 1.335, 95% CI = 1.058-1.684, P = 0.015), exceptionally in anti-F protein seropositive patients (OR = 1.547, 95% CI = 1.140-2.101, P = 0.005), compared with healthy controls. And the risk effect was also significantly high in patients with HCV 1b genotype and mild fibrosis (P = 0.021, P = 0.010, respectively). Compared with the most frequent haplotype TAT, haplotype analysis showed that the distribution of TAC was significantly different between the chronic HCV carrier group and the healthy group, and so was the anti-F antibody seronegativity group and the anti-F antibody seronegativity group (all P < 0.001). Our results suggested that TBX21 variants may be involved in the etiology of this disease.


Assuntos
Predisposição Genética para Doença , Hepacivirus , Hepatite C/genética , Hepatite C/virologia , Polimorfismo de Nucleotídeo Único , Proteínas com Domínio T/genética , Alelos , Estudos de Casos e Controles , China , Feminino , Genótipo , Haplótipos , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/diagnóstico , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco
19.
Epidemiol Infect ; 143(13): 2827-36, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25600557

RESUMO

Limited information is available on the prevalence of hepatitis C virus (HCV) in the general population in China. A community-based epidemiological study was conducted in three counties in eastern China. A total of 149 175 individuals were investigated in 60 communities in three counties in Jiangsu province, eastern China, of whom 1175 subjects [0·79%, 95% confidence interval (CI) 0·74-0·83] were HCV antibody positive. The prevalence was low in children (0·09%, 95% CI 0·04-0·17), but increased progressively from adolescents (0·20%, 95% CI 0·15-0·28) to adults aged ⩾21 years (95% CI 0·15-1·64). Women had a higher prevalence of HCV infection than men in most age groups. In a multilevel regression analysis, age, sex, education, occupation, blood transfusion [odds ratio (OR) 2·91, 95% CI 1·09-5·37], invasive testing (OR 1·28, 95% CI 1·14-1·61), and dental therapy (OR 2·27, 95% CI 1·41-3·42) were associated with HCV infection. In conclusion, although the prevalence of HCV in this population was lower than reported from national levels, the total reservoir of infection is significant and warrants public health measures, such as health education to limit the magnitude of the problem.


Assuntos
Hepatite C/epidemiologia , Adolescente , Adulto , Idoso , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
20.
Genet Mol Res ; 14(4): 15349-55, 2015 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-26634500

RESUMO

Liver cancers are characterized by high morbidity and mortality owing to few effective drugs for its treatment. Wilfortrine has several pharmacological effects, including an inhibitory effect on liver cancer cell proliferation. However, whether wilfortrine can induce liver cancer cell apoptosis has not been elucidated. We investigated the role of wilfortrine on liver cancer cell HepG2 apoptosis and analyzed its possible mechanisms to provide a theoretical basis for clinical analysis of liver cancer pathogenesis. The liver cancer cell line HepG2 was treated with 40 mM wilfortrine for 48 h. Flow cytometry was applied to detect HepG2 cell apoptosis and cell cycle changes. Western blot was used to analyze Bcl-2 and Bax expression. The HepG2 cell apoptosis rate increased significantly after treatment with wilfortrine, especially the early apoptosis rate (P < 0.05). However, wilfortrine did not change the cell cycle of HepG2 cells. After wilfortrine treatment, Bcl- 2 expression decreased significantly (P < 0.05); on the contrary, Bax expression increased noticeably compared with the control group (P < 0.05). Wilfortrine can induce liver cancer cell HepG2 apoptosis, but with no effect on the cell cycle, mainly by promoting Bax expression and inhibiting anti-apoptotic protein Bcl-2 expression.


Assuntos
Alcaloides/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Hep G2/efeitos da radiação , Neoplasias Hepáticas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
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