Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
Filtros adicionais











Tipo de estudo
Intervalo de ano
1.
J Magn Reson Imaging ; 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30408268

RESUMO

BACKGROUND: Precise diagnosis and early appropriate treatment are of importance to reduce neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) morbidity. Distinguishing NMOSD from MS based on clinical manifestations and neuroimaging remains challenging. PURPOSE: To investigate radiomic signatures as potential imaging biomarkers for distinguishing NMOSD from MS, and to develop and validate a diagnostic radiomic-signature-based nomogram for individualized disease discrimination. STUDY TYPE: Retrospective, cross-sectional study. SUBJECTS: Seventy-seven NMOSD patients and 73 MS patients. FIELD STRENGTH/SEQUENCE: 3T/T2 -weighted imaging. ASSESSMENT: Eighty-eight patients and 62 patients were respectively enrolled in the primary and validation cohorts. Quantitative radiomic features were automatically extracted from lesioned regions on T2 -weighted imaging. A least absolute shrinkage and selection operator analysis was used to reduce the dimensionality of features. Finally, we constructed a radiomic nomogram for disease discrimination. STATISTICAL TESTS: Features were compared using the Mann-Whitney U-test with a nonnormal distribution. We depicted the nomogram on the basis of the results of the logistic regression using the rms package in R. The Hmisc package was used to investigate the performance of the nomogram via Harrell's C-index. RESULTS: A total of 273 quantitative radiomic features were extracted from lesions. A multivariable analysis selected 11 radiomic features and five clinical features to be included in the model. The radiomic signature (P < 0.001 for both the primary and validation cohorts) showed good potential for building a classification model for disease discrimination. The area under the receiver operating characteristic curve was 0.9880 for the training cohort and 0.9363 for the validation cohort. The nomogram exhibited good discrimination, a concordance index of 0.9363, and good calibration in the primary cohort. The nomogram showed similar discrimination, concordance (0.9940), and calibration in the validation cohort. DATA CONCLUSION: The diagnostic radiomic-signature-based nomogram has potential utility for individualized disease discrimination of NMOSD from MS in clinical practice. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

2.
Zhongguo Zhong Yao Za Zhi ; 43(13): 2817-2823, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30111036

RESUMO

Combined use of drugs is a hot spot in the research of new drugs nowadays, and traditional Chinese medicine (TCM) is a classic practice in the combined use of drugs. In this paper, the compatibility of TCM prescriptions and the related properties of composed herbs were calculated and studied to verify and discuss the feasibility of the results in guiding compatibility. Research Group on New Drug Design, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences had established a structured database of TCM prescriptions by using traditional Chinese medicine inheritance support system (TCMISS V2.0), including 4 012 prescription compatibilities, 2 072 drug components, 381 kinds of TCM diseases, 316 kinds of TCM syndromes and 26 kinds of drug properties. On the basis of the created database above, Support Vector Machine (SVM) was used to analyze the prescription compatibility data and establish a model for predicting feasibility of drug compatibilities. Analytic Hierarchy Process (AHP) and cluster analysis were used to study the influence of drug properties in the rationality of prescription compatibility. The computational results showed that the accuracy in efficacy prediction of two data sets, i.e. prescription-disease and prescription-syndrome, was up to 90% in the linear SVM model. The macro₋averaging and micro₋averaging of the two models were around 0.92, 0.46, respectively. After AHP mapping, most of the incompatible combinations showed significant difference with other drug combinations during the clustering process in the vertical icicle, indicating that the proper machine learning algorithm can be used to lay the foundation for further exploring the combination rules in TCM and establishing more detailed drug-disease and syndrome predicting models, and provide theoretical guidance for the study of the combined use of drugs to a certain degree.

3.
Chembiochem ; 19(13): 1444-1451, 2018 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-29633462

RESUMO

Cyclic adenosine diphosphate ribose (cADPR) is an endogenous Ca2+ mobilizer involved in diverse cellular processes. Mimics of cADPR play a crucial role in investigating the molecular mechanism(s) of cADPR-mediated signaling. Here, compound 3, a mimic of cADPR in which a neutral triazole moiety and an ether linkage were introduced to substitute the pyrophosphate and "northern" ribose components, respectively, was synthesized for the first time. The pharmacological activities in Jurkat cells indicated that this mimic is capable of penetrating plasma membrane and inciting Ca2+ release from the endoplasmic reticulum (ER) through the action of ryanodine receptors (RyRs) and triggering Ca2+ influx. Furthermore, a uridine moiety was introduced in place of adenine and the new cADPR mimics 4 and 5 were synthesized. The results of biological investigation showed that these mimics also targeted RyRs and retained moderate Ca2+ agonistic activities. The results indicated that the neutral cADPR mimics had the same targets for inducing Ca2+ signaling.

4.
J Med Chem ; 61(7): 2865-2874, 2018 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-29569910

RESUMO

Antibiotic resistance is one of the biggest threats to public health, and new antibacterial agents hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Utilizing dimerization strategy, we rationally designed and efficiently synthesized a new series of small molecule dimeric lysine alkylamides as mimics of AMPs. Evaluation of these mimics against a panel of Gram-positive and Gram-negative bacteria including MDR strains was performed, and a broad-spectrum and potent compound 3d was identified. This compound displayed high specificity toward bacteria over mammalian cell. Time-kill kinetics and mechanistic studies suggest that compound 3d quickly eliminated bacteria in a bactericidal mode by disrupting bacterial cell membrane. In addition, lead compound 3d could inhibit biofilm formation and did not develop drug resistance in S. aureus and E. coli over 14 passages. These results suggested that dimeric lysine nonylamide has immense potential as a new type of novel small molecular agent to combat antibiotic resistance.

5.
PLoS One ; 12(2): e0171433, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28196116

RESUMO

Target fishing often relies on the use of reverse docking to identify potential target proteins of ligands from protein database. The limitation of reverse docking is the accuracy of current scoring funtions used to distinguish true target from non-target proteins. Many contemporary scoring functions are designed for the virtual screening of small molecules without special optimization for reverse docking, which would be easily influenced by the properties of protein pockets, resulting in scoring bias to the proteins with certain properties. This bias would cause lots of false positives in reverse docking, interferring the identification of true targets. In this paper, we have conducted a large-scale reverse docking (5000 molecules to 100 proteins) to study the scoring bias in reverse docking by DOCK, Glide, and AutoDock Vina. And we found that there were actually some frequency hits, namely interference proteins in all three docking procedures. After analyzing the differences of pocket properties between these interference proteins and the others, we speculated that the interference proteins have larger contact area (related to the size and shape of protein pockets) with ligands (for all three docking programs) or higher hydrophobicity (for Glide), which could be the causes of scoring bias. Then we applied the score normalization method to eliminate this scoring bias, which was effective to make docking score more balanced between different proteins in the reverse docking of benchmark dataset. Later, the Astex Diver Set was utilized to validate the effect of score normalization on actual cases of reverse docking, showing that the accuracy of target prediction significantly increased by 21.5% in the reverse docking by Glide after score normalization, though there was no obvious change in the reverse docking by DOCK and AutoDock Vina. Our results demonstrate the effectiveness of score normalization to eliminate the scoring bias and improve the accuracy of target prediction in reverse docking. Moreover, the properties of protein pockets causing scoring bias to certain proteins we found here can provide the theory basis to further optimize the scoring functions of docking programs for future research.


Assuntos
Algoritmos , Biologia Computacional/métodos , Simulação de Acoplamento Molecular/métodos , Mapeamento de Interação de Proteínas/métodos , Proteínas/química , Viés , Sítios de Ligação , Bases de Dados de Proteínas , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Ligação Proteica , Conformação Proteica , Proteínas/metabolismo , Reprodutibilidade dos Testes , Software
6.
Int Braz J Urol ; 42(1): 101-6, 2016 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27136474

RESUMO

OBJECTIVE: To evaluate the clinical efficiency of alpha1-adrenergic antagonists on stentless ureteroscopic lithotripsy treating uncomplicated lower ureteral stones. MATERIALS AND METHODS: From January 2007 to January 2013, 84 patients who have uncomplicated lower ureteral stones treated by ureteroscopic intracorporeal lithotripsy with the holmium laser were analyzed. The patients were divided into two groups, group A (44 patients received indwelled double-J stents) and group B (40 patients were treated by alpha1-adrenergic antagonists without stents). All cases of group B were treated with alpha1 blocker for 1 week. RESULTS: The mean operative time of group A was significantly longer than group B. The incidences of hematuria, flank/abdominal pain, frequency/urgency after surgery were statistically different between both groups. The stone-free rate of each group was 100%. CONCLUSIONS: The effect of alpha1-adrenergic antagonists is more significant than indwelling stent after ureteroscopic lithotripsy in treating uncomplicated lower ureteral stones.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Litotripsia/métodos , Sulfonamidas/uso terapêutico , Cálculos Ureterais/cirurgia , Ureteroscopia/métodos , Adulto , Feminino , Humanos , Lasers de Estado Sólido/uso terapêutico , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Medição da Dor , Complicações Pós-Operatórias , Período Pós-Operatório , Estudos Prospectivos , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Tansulosina , Resultado do Tratamento , Adulto Jovem
7.
Int. braz. j. urol ; 42(1): 101-106, Jan.-Feb. 2016. tab
Artigo em Inglês | LILACS-Express | ID: lil-777316

RESUMO

ABSTRACT Objective To evaluate the clinical efficiency of alpha1-adrenergic antagonists on stentless ureteroscopic lithotripsy treating uncomplicated lower ureteral stones. Materials and Methods From January 2007 to January 2013, 84 patients who have uncomplicated lower ureteral stones treated by ureteroscopic intracorporeal lithotripsy with the holmium laser were analyzed. The patients were divided into two groups, group A (44 patients received indwelled double-J stents) and group B (40 patients were treated by alpha1-adrenergic antagonists without stents). All cases of group B were treated with alpha1 blocker for 1 week. Results The mean operative time of group A was significantly longer than group B. The incidences of hematuria, flank/abdominal pain, frequency/urgency after surgery were statistically different between both groups. The stone-free rate of each group was 100%. Conclusions The effect of alpha1-adrenergic antagonists is more significant than indwelling stent after ureteroscopic lithotripsy in treating uncomplicated lower ureteral stones.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA