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2.
Dev Biol ; 491: 113-125, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36100084

RESUMO

Epithelial cells form continuous membranous structures for organ formation, and these cells are classified into three major morphological categories: cuboidal, columnar, and squamous. It is crucial that cells transition between these shapes during the morphogenetic events of organogenesis, yet this process remains poorly understood. All three epithelial cell shapes can be found in the follicular epithelium of Drosophila egg chamber during oogenesis. Squamous cells (SCs) are initially restricted to the anterior terminus in cuboidal shape. They then rapidly become flattened to assume squamous shape by stretching and expansion in 12 â€‹h during midoogenesis. Previously, we reported that Notch signaling activated a zinc-finger transcription factor Broad (Br) at the end of early oogenesis. Here we report that ecdysone and JAK/STAT pathways subsequently converge on Br to serve as an important spatiotemporal regulator of this dramatic morphological change of SCs. The early uniform pattern of Br in the follicular epithelium is directly established by Notch signaling at stage 5 of oogenesis. Later, ecdysone and JAK/STAT signaling activities synergize to suppress Br in SCs from stage 8 to 10a, contributing to proper SC squamous shape. During this process, ecdysone signaling is essential for SC stretching, while JAK/STAT regulates SC clustering and cell fate determination. This study reveals an inhibitory role of ecdysone signaling in suppressing Br in epithelial cell remodeling. In this study we also used single-cell RNA sequencing data to highlight the shift in gene expression which occurs as Br is suppressed and cells become flattened.


Assuntos
Carcinoma de Células Escamosas , Proteínas de Drosophila , Animais , Carcinoma de Células Escamosas/genética , Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Ecdisona/metabolismo , Células Epiteliais/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Oogênese/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Zinco
3.
Methods Mol Biol ; 2472: 151-157, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35674898

RESUMO

Many highly conserved pathways control the development and determine cell fate in organisms. One of these pathways is the Notch signaling pathway that allows for local cell-cell communication. Researchers have found that the timing for when Notch signaling activates the target gene is important for maintaining normal gene expression. Any alterations in the downstream gene expression could cause issues with development or certain diseases. The Drosophila oogenesis is a widely used model in developmental biology for analyzing the Notch pathway. However, determining the stage of oogenesis is difficult and varies depending on individual analyzing it. Here, we provide a MATLAB tool to automatically identify the stage of a Drosophila egg chamber and reveal the Notch expression pattern.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Oogênese/genética , Receptores Notch/genética , Receptores Notch/metabolismo
4.
Methods Mol Biol ; 2472: 277-296, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35674906

RESUMO

As a result of the culmination of data, and the fast-paced advancement of new research, all the biological information collected can make it difficult to sort data. This is oftentimes experienced when learning about the human genome. Fortunately, with the advancement of technology, the field of bioinformatics has emerged which has allowed for the creation of a variety of biological databases. These biological databases provide a condensed reservoir of organized information that is easy to use and topic-specific. Here, we provide a list of 39 biological databases that help break down the fundamental details of a gene. This chapter uses the NOTCH1 gene as an example to demonstrate how biological databases can be used to extract gene information. Five sections were created to highlight the major areas needed to build a comprehensive foundation of NOTCH1. The first section lists databases containing basic gene and protein product information. The next section consists of protein interactions and signaling pathway databases which are essential in understanding the biological processes a gene product is involved in. Gene expression and disease databases are the next two sections which are connected since disease results from the aberrant expression of a gene product. The last database section examines model organisms which serve a key role in the study of human genetic diseases. Using these databases, we can elucidate NOTCH1's gene/protein structure, expression, and vital physiological function through the Notch signaling pathway.


Assuntos
Biologia Computacional , Transdução de Sinais , Humanos
5.
medRxiv ; 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32511421

RESUMO

COVID-19 epidemic doubling time by Chinese province was increasing from January 20 through February 9, 2020. The harmonic mean of the arithmetic mean doubling time estimates ranged from 1.4 (Hunan, 95% CI, 1.2-2.0) to 3.1 (Xinjiang, 95% CI, 2.1-4.8), with an estimate of 2.5 days (95% CI, 2.4-2.6) for Hubei.

6.
Sci Rep ; 10(1): 7370, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32355165

RESUMO

Living organisms require complex signaling interactions and proper regulation of these interactions to influence biological processes. Of these complex networks, one of the most distinguished is the Notch pathway. Dysregulation of this pathway often results in defects during organismal development and can be a causative mechanism for initiation and progression of cancer. Despite previous research entailing the importance of this signaling pathway and the organismal processes that it is involved in, less is known concerning the major Notch downstream targets, especially the onset and sequence in which they are modulated during normal development. As timing of regulation may be linked to many biological processes, we investigated and established a model of temporal patterning of major Notch downstream targets including broad, cut, and hindsight during Drosophila melanogaster egg chamber development. We confirmed the sequential order of Broad upregulation, Hindsight upregulation, and Cut downregulation. In addition, we showed that Notch signaling could be activated at stage 4, one stage earlier than the stage 5, a previously long-held belief. However, our further mitotic marker analysis re-stated that mitotic cycle continues until stage 5. Through our study, we once again validated the effectiveness and reliability of our MATLAB toolbox designed to systematically identify egg chamber stages based on area size, ratio, and additional morphological characteristics.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Receptores Notch/metabolismo , Animais , Feminino , Imuno-Histoquímica , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo
7.
Sensors (Basel) ; 20(9)2020 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-32375219

RESUMO

An algorithm to forecast very short-term (30-180 min) surface solar irradiance using visible and near infrared channels (AGRI) onboard the FengYun-4A (FY-4A) geostationary satellite was constructed and evaluated in this study. The forecasting products include global horizontal irradiance (GHI) and direct normal irradiance (DNI). The forecast results were validated using data from Chengde Meteorological Observatory for four typical months (October 2018, and January, April, and July 2019), representing the four seasons. Particle Image Velocimetry (PIV) was employed to calculate the cloud motion vector (CMV) field from the satellite images. The forecast results were compared with the smart persistence (SP) model. A seasonal study showed that July and April forecasting is more difficult than during October and January. For GHI forecasting, the algorithm outperformed the SP model for all forecasting horizons and all seasons, with the best result being produced in October; the skill score was greater than 20%. For DNI, the algorithm outperformed the SP model in July and October, with skill scores of about 12% and 11%, respectively. Annual performances were evaluated; the results show that the normalized root mean square error (nRMSE) value of GHI for 30-180 min horizon ranged from 26.78% to 36.84%, the skill score reached a maximum of 20.44% at the 30-min horizon, and the skill scores were all above 0 for all time horizons. For DNI, the maximum skill score was 6.62% at the 180-min horizon. Overall, compared with the SP model, the proposed algorithm is more accurate and reliable for GHI forecasting and slightly better for DNI forecasting.

9.
J Vis Exp ; (155)2020 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-31984955

RESUMO

Notch signaling is a highly conserved regulatory pathway involved in many cellular processes. Dysregulation of this signaling pathway often leads to interference with proper development and may even result in initiation or progression of cancers in certain cases. Because this pathway serves complex and versatile functions, it can be studied extensively through many different approaches. Of these, bioinformatics provides an undeniably cost-efficient, approachable, and user-friendly method of study. Bioinformatics is a useful way to extract smaller pieces of information from large-scale datasets. Through the implementation of various bioinformatics approaches, researchers can quickly, reliably, and efficiently interpret these large datasets, yielding insightful applications and scientific discoveries. Here, a protocol is presented for integration of bioinformatics approaches to investigate the role of Notch signaling in ovarian cancer. Furthermore, bioinformatics findings are validated through experimentation.


Assuntos
Biologia Computacional/métodos , Neoplasias Ovarianas/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Linhagem Celular Tumoral , Intervalo Livre de Doença , Drosophila/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Receptores Notch/genética , Transdução de Sinais/genética
10.
Medicine (Baltimore) ; 98(50): e18173, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852073

RESUMO

RATIONALE: Coronary artery aneurysms (CAAs) are uncommon in patients with acute coronary syndrome (ACS). We describe the clinical features and outcomes of stent-assisted coil embolization of a CAA in the trigeminal position. PATIENT CONCERNS: We present a 73-year-old woman with a history of paroxysmal episodes of precordial pain since 1 year. Coronary computed tomography angiography (CTA) revealed an aneurysm (diameter: 9 mm) at the junction of the distal left main coronary artery and the anterior descending branch. Troponin I, CK-MB, creatinine and routine blood investigations were within the normal range. DIAGNOSIS: Coronary artery aneurysm in the left main trigeminal position. INTERVENTIONS: The patient was treated with stent-assisted coil embolization. OUTCOMES: After complete filling of the aneurysm with coil, the microcatheter was withdrawn and the stent released in the descending branch. Two stents were successfully implanted. LESSONS: There is no clear consensus on the optimal therapy for patients with CAAs. Clinicians should be aware of the possible complications of stent-assisted coil embolization of CAA in the main trunk of the coronary artery.


Assuntos
Implante de Prótese Vascular/métodos , Aneurisma Coronário/terapia , Estenose Coronária/cirurgia , Vasos Coronários/diagnóstico por imagem , Embolização Terapêutica/métodos , Stents , Idoso , Angiografia Digital , Aneurisma Coronário/complicações , Aneurisma Coronário/diagnóstico , Angiografia Coronária , Estenose Coronária/complicações , Estenose Coronária/diagnóstico , Vasos Coronários/cirurgia , Feminino , Humanos , Doenças Raras
11.
Oncol Lett ; 18(1): 518-528, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31289523

RESUMO

Cancer is essentially a genetic disease. Accumulated gene mutations accelerate genome instability, which eventually leads to uncontrollable growth of the tumor. Bladder cancer is the most common form of urinary tract cancer. This form of cancer has a poor prognosis due to its clinical heterogeneity and molecular diversity. Despite recent scientific advances, the knowledge and treatment of bladder cancer still lags behind that of other types of solid tumor. In the present study, available large data portals and other studies were used to obtain clinically relevant information, and the data were systematically processed to decipher the genes associated with bladder cancer. Genes associated with the survival time of patients with bladder cancer were successfully identified. The genes were enriched in common biological processes and pathways, and upregulated in tumor samples from patients. Among the top genes identified as associated with good or poor survival in bladder cancer, DNA topoisomerase IIα (TOP2α) and RAD21 cohesin complex component (RAD21) were also increased in bladder cancer tissues and cell lines. Therefore, TOP2α and RAD21 could be used as potential therapeutic targets in bladder cancer.

12.
Oncol Lett ; 17(6): 4914-4920, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31186700

RESUMO

Notch signaling is well-known for its role in regulating cell self-renewal and differentiation. Within the cancer research field, it has been identified that dysregulated Notch signaling is involved directly with various types of cancer. Although Notch signaling is generally considered as oncogenic, it sometimes acts as a tumor suppressor, highlighting the complexity of the role of Notch in cancer. A number of studies have associated Notch signaling components with ovarian cancer, but the underlying molecular mechanisms are not well-elucidated. In the present study, the roles of main components of Notch signaling in ovarian cancer were systematically analyzed through large data portals, including Prediction of Clinical Outcomes from Genomic Profiles, Gene Expression across Normal and Tumor tissue, CSIOVDB, Broad Institute Cancer Cell Line Encyclopedia and cBioPortal. Upregulated expression of proteins in the Notch signaling pathway components in ovarian cancer was identified to be generally associated with poor overall and disease-free survival time, and more advanced cancer stages. In addition, Notch components were enriched in ovarian cancer tissues and cell lines. These results led to a proposed neurogenic locus notch homolog protein (NOTCH)2/NOTCH3/Delta-like protein 3/Mastermind-like protein 1/a disintegrin and metalloproteinase domain-containing protein 17 network. Anticancer drugs, developed to target this network, may have high specificity in treating Notch-associated ovarian cancer.

13.
Plants (Basel) ; 8(6)2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234345

RESUMO

Polyamines not only play roles in plant growth and development, but also adapt to environmental stresses. Polyamines can be oxidized by copper-containing diamine oxidases (CuAOs) and flavin-containing polyamine oxidases (PAOs). Two types of PAOs exist in the plant kingdom; one type catalyzes the back conversion (BC-type) pathway and the other catalyzes the terminal catabolism (TC-type) pathway. The catabolic features and biological functions of plant PAOs have been investigated in various plants in the past years. In this review, we focus on the advance of PAO studies in rice, Arabidopsis, and tomato, and other plant species.

14.
Environ Sci Pollut Res Int ; 26(20): 20469-20474, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31102213

RESUMO

The expansion of poisonous plants can change vegetation community structures and affect grassland ecosystem service values. Stellera chamaejasme is one of the most important poisonous plants and has rapidly expanded in the arid areas of Northwest China in recent decades. The objective of this study was to elucidate the expansion process and model of an S. chamaejasme population. Therefore, we classified the S. chamaejasme population into five classes based on coverage: 31-40%, 41-50%, 51-60%, 61-70% and 71-80%. We investigated the spatial distribution patterns and the size compositions of S. chamaejasme under different coverages. The results show that the spatial distribution pattern of S. chamaejasme under low coverage (31-40%) at all study scales (0-100 cm) was random; the spatial distribution pattern translated to a clumped distribution from a random distribution at some scales, and the clumped distributions gradually became obvious, with coverage increasing from 41-50% to 61-70%; the spatial distribution tended to be random at all study scales when coverage was increased further (71-80%). However, the spatial distribution patterns were closely related to the size composition of the S. chamaejasme population. In particular, the quantity of older individuals had a significant impact on the variation of the spatial distribution patterns of S. chamaejasme. The spatial distribution pattern varied from a random distribution to a clumped distribution and then returned to a random distribution with increasing coverage (from 31-40% to 71-80%), and this may indicate that the S. chamaejasme patches experienced patch formation and extension and merged with each other.


Assuntos
Thymelaeaceae/fisiologia , China , Ecossistema , Pradaria , Plantas Tóxicas/fisiologia
15.
J Biomech ; 87: 83-92, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30850176

RESUMO

Local abnormal angiogenesis and cardiovascular system reorganization have been observed in embryos exposed to a simulated microgravity (SM) environment. In this study, changes in key molecular signals and pathways in cardiovascular development have been investigated under microgravity conditions. In particular, the caudal vein plexus (CVP) network, formed by sprouting angiogenesis has been chosen. Zebrafish embryos were exposed to SM using a ground-based microgravity bioreactor for 24 and 36 h. The SM was observed to have no effect on the zebrafish length, tail width and incubation time whereas it was observed to significantly reduce the heart rate frequency and to promote abnormal development of the CVP network in the embryos. Nitric oxide (NO) content demonstrated that the total proteins in zebrafish embryos were significantly higher in SM than in the control group grown under normal conditions. It was then preliminarily determined how NO signals were involved in SM regulated zebrafish CVP network formation. nos2b MO was injected and CVP network evolution was observed in 36 h post fertilization (hpf) under SM condition. The results showed that the CVP network formation was considerably decreased in the nos2b MO treated group. However, this inhibition of the CVP network development was not observed in control MO group, indicating that nos2b is involved in the SM-regulated vascular development process in zebrafish. Moreover, specific phosphoinositide 3-kinase (PI3K) inhibitors such as LY294002 were also tested on zebrafish embryos under SM condition. This treatment significantly inhibited the formation of zebrafish CVP network. Furthermore, overexpression of nos2b partly rescued the LY294002-caused CVP network failure. Therefore, it can be concluded that SM affects zebrafish CVP network remodeling by enhancing angiogenesis. Additionally, the PI3K-nos2b signaling pathway is involved in this process.


Assuntos
Fenômenos Fisiológicos Cardiovasculares , Neovascularização Fisiológica , Óxido Nítrico Sintase Tipo II , Fosfatidilinositol 3-Quinase , Transdução de Sinais , Ausência de Peso , Peixe-Zebra , Animais , Embrião não Mamífero , Morfogênese , Neovascularização Fisiológica/fisiologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Transdução de Sinais/fisiologia , Peixe-Zebra/embriologia
16.
Sci Rep ; 8(1): 12394, 2018 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-30120290

RESUMO

The incidence of ovarian cancer dramatically increases in early menopause but the factors contributing to cancer onset are unclear. Most ovarian cancers originate in the fallopian tube with subsequent implantation of malignant cells into the ovary. However, the events and conditions that lead to cancer cell implantation are unknown. To quantify which conditions are conducive to the seeding of cancer cells in an immunocompetent mouse model, we surgically implanted mouse ovarian cancer cells into the oviducts of syngeneic mice and simulated conditions associated with ovulatory wound repair, incessant ovulation, ovarian surface scarring, and aging. We found that the dominant site of cancer cell seeding was not the ovary but the nearby surgical wound site, which was associated with a strong and persistent inflammatory reaction. Conditions in the ovary associated with inflammation, such as acute ovulatory wound repair, active healing of the scarred ovarian surface, and mouse aging, contributed to increased seeding of the cancer cells to the surgical wound site and tissues surrounding the ovary. Changes in the ovary not accompanied by inflammation, such as completed ovulatory cycles and fully-healed scars on the ovarian surface, did not contribute to increased cancer cell seeding. We conclude that inflammation is the most likely mechanism by which ovulation and postmenopausal events contribute to the increased risk of ovarian cancer.


Assuntos
Inflamação/patologia , Inoculação de Neoplasia , Neoplasias Ovarianas/patologia , Animais , Atrofia , Biópsia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Ovulação
17.
Regen Biomater ; 5(3): 177-187, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29942650

RESUMO

Cardiovascular stent restenosis remains a major challenge in interventional treatment of cardiovascular occlusive disease. Although the changes in arterial mechanical environment due to stent implantation are the main causes of the initiation of restenosis and thrombosis, the mechanisms that cause this initiation are still not fully understood. In this article, we reviewed the studies on the issue of stent-induced alterations in arterial mechanical environment and discussed their roles in stent restenosis and late thrombosis from three aspects: (i) the interaction of the stent with host blood vessel, involve the response of vascular wall, the mechanism of mechanical signal transmission, the process of re-endothelialization and late thrombosis; (ii) the changes of hemodynamics in the lumen of the vascular segment and (iii) the changes of mechanical microenvironment within the vascular segment wall due to stent implantation. This review has summarized and analyzed current work in order to better solve the two main problems after stent implantation, namely in stent restenosis and late thrombosis, meanwhile propose the deficiencies of current work for future reference.

19.
J Plant Physiol ; 228: 1-11, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29793152

RESUMO

Polyamines (PAs) are implicated in developmental processes and stress responses of plants. Polyamine oxidases (PAOs), flavin adenine dinucleotide-dependent enzymes that function in PA catabolism, play a critical role. Even though PAO gene families of Arabidopsis and rice have been intensely characterized and their expression in response to developmental and environmental changes has been investigated, little is known about PAOs in tomato (Solanum lycopersicum). We found seven PAO genes in S. lycopersicum and named them SlPAO1∼7. Plant PAOs form four clades in phylogenetic analysis, of which SlPAO1 belongs to clade-I, SlPAO6 and SlPAO7 to clade-III, and the residual four (SlPAO2∼5) to clade-IV, while none belongs to clade-II. All the clade-IV members in tomato also retain the putative peroxisomal-targeting signals in their carboxy termini, suggesting their peroxisome localization. SlPAO1 to SlPAO5 genes consist of 10 exons and 9 introns, while SlPAO6 and SlPAO7 are intronless genes. To address the individual roles of SlPAOs, we analyzed their expression in various tissues and during flowering and fruit development. The expression of SlPAO2∼4 was constitutively high, while that of the other SlPAO members was relatively lower. We further analyzed the expressional changes of SlPAOs upon abiotic stresses, oxidative stresses, phytohormone application, and PA application. Based on the data obtained, we discuss the distinctive roles of SlPAOs.


Assuntos
Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Proteínas de Plantas/metabolismo , Solanum lycopersicum/enzimologia , Éxons/genética , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Íntrons/genética , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Filogenia , Proteínas de Plantas/genética , Poliaminas/metabolismo , Poliamina Oxidase
20.
J Zhejiang Univ Sci B ; 18(12): 1113-1122, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29204991

RESUMO

OBJECTIVE: The relative preventative efficacy of amiodarone and lidocaine for ventricular fibrillation (VF) after release of an aortic cross-clamp (ACC) during open heart surgery has not been determined. This meta-analysis was designed to systematically evaluate the influence of amiodarone, lidocaine, or placebo on the incidence of VF after ACC. METHODS: Prospective randomized controlled trials (RCTs) that compared the VF-preventative effects of amiodarone with lidocaine, or amiodarone or lidocaine with placebo were included. PubMed, EMBASE, and the Cochrane Library were searched for relevant RCTs. Fixed or randomized effect models were applied according to the heterogeneity of the data from the selected studies. RESULTS: We included eight RCTs in the analysis. Pooled results suggested that the preventative effects of amiodarone and lidocaine were comparable (relative risk (RR)=1.12, 95% confidence interval (CI): 0.70 to 1.80, P=0.63), but both were superior to the placebo (amiodarone, RR=0.71, 95% CI: 0.51 to 1.00, P=0.05; lidocaine, RR=0.63, 95% CI: 0.46 to 0.88, P=0.006). The percentage of patients requiring electric defibrillation counter shocks (DCSs) did not differ significantly among patients administered amiodarone (RR=0.21, 95% CI: 0.04 to 1.19, P=0.08), lidocaine (RR=2.44, 95% CI: 0.13 to 44.02, P=0.55), or the placebo (RR=0.56, 95% CI: 0.25 to 1.25, P=0.16). CONCLUSIONS: Amiodarone and lidocaine are comparably effective in preventing VF after ACC, but the percentage of patients who subsequently require DCSs does not differ among those administered amiodarone, lidocaine, or placebo.


Assuntos
Amiodarona/administração & dosagem , Antiarrítmicos/uso terapêutico , Aorta/efeitos dos fármacos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Lidocaína/administração & dosagem , Fibrilação Ventricular/tratamento farmacológico , Adulto , Idoso , Cardioversão Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
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