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1.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3384-3390, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602899

RESUMO

Rheumatoid arthritis( RA) is an autoimmune disease characterized by chronic and aggressive polyarthritis. The innate immunity mechanism plays a key role in the pathogenesis of RA. Tripterygium wilfordii and its extracts have regulatory effects on innate immune cells including macrophages,dendritic cells,neutrophils,mast cells,NK cells,NKT cells,etc.,as well as a variety of innate immune molecules including cytokines,adhesion molecules,patterns recognition receptor( PRR) and the complement molecules,showing a regulatory effect in the pathogenesis of RA innate immunity. In this paper,the recent domestic and foreign researches on the pathogenesis of RA with innate immunity involved were reviewed and the research status of T. wilfordii and its extracts on the regulation of innate immunity involved in RA was summarized.

2.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3415-3422, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602903

RESUMO

Growing clinical evidence shows that a partial rheumatoid arthritis( RA) patient treated with Tripterygium Glycosides Tablets( TGT) may fail to achieve clinical improvement. It is of great clinical significance to predict the therapeutic effect of TGT in RA. Therefore,the aim of the current study was to identify potential biomarkers for TGT treatment in RA. Affymetrix EG1.0 arrays were applied to detect gene expression in peripheral blood mononuclear cells obtained from 6 RA patients( 3 responders and 3 non-responders) treated with TGT. By integrating differential expression data analysis and biomolecular network analysis,360 mRNAs( 185 up-regulated and 175 down-regulated) and 24 miRNAs( 7 up-regulated and 17 down-regulated) which were differentially expressed between TGT responder and non-responder groups were identified. A total of 206 candidate target genes for the differentially expressed miRNAs were obtained based on miRanada and Target Scan databases,and then the miRNA target gene coexpression network and miRNA-mediated gene signal transduction network were constructed. Following the network analyses,three candidate miRNAs biomarkers( hsa-miR-4720-5 p,hsa-miR-374 b-5 p,hsa-miR-185-3 p) were identified as candidate biomarkers predicting individual response to TGT. Partialleast-squares( PLS) was applied to construct a model for predicting response to TGT based on the expression levels of the candidate gene biomarkers in RA patients. The five-fold cross-validation showed that the prediction accuracy( ACC) of this PLS-based model efficacy was 100.00%,100.00%,100.00%,66.67% and 66.67% respectively,and all the area under the receiver operating characteristic curve( AUC) were 1.00,indicating the highly predictive efficiency of this PLS-based model. In conclusion,the integrating transcription data mining and biomolecular network investigation show that hsa-mir-4720-5 p,hsa-mir-374 b-5 p and hsa-mir-185-3 p may be candidate biomarkers predicting individual response to TGT. In addition,the PLS model based on the expression levels of these candidate biomarkers may be helpful for the clinical screen of RA patients,which potentially benefit individualized therapy of RA in a daily clinical setting.

3.
J Neurosci Methods ; : 108441, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31574288

RESUMO

BACKGROUND: Recombinant adeno-associated virus (rAAV) is increasingly applied in neuroscience research or gene therapy. However, there is no simple and efficient tool for specific transfection of rAAV into cerebrovascular tissues. It has been reported that fluorescent tracers or beta-amyloid protein can enter the brain through perivascular spaces, named as "glymphatic system". The purpose of this study was to explore whether rAAV could transduce the cerebral vasculature through the glymphatic pathway. NEW METHOD: An AAV1-GFP vector suspension (15 µL) was injected into the intracisternal space of anesthetized mice (n = 2) and 5 µL was injected into the bulbus medullae (n = 2). As controls, 15 µL of artificial cerebrospinal fluid (aCSF) was injected into the cisterna magna. The endothelial specific transduction was verified by Glut1 or PDGFRß immunofluorescent staining. Immunofluorescence images for all groups were captured with a laser microscope. RESULTS: It was observed that infection with rAAV1 vectors encoding green fluorescence protein resulted in a successful cerebrovascular transduction when injected into cisterna magna, compared to aCSF or intra-parenchymal injection at 30 days post-transduction in adult mice. In addition, GFP was co-localized with Glut1 based on immuno-fluorescence. These results indicate that glymphatic system delivery enhances the transduction efficiency of AAV1 to brain endothelial cells. COMPARISON WITH EXISTING METHODS: The AAV1vector is simple and efficiently transduces the cerebral endothelial cells through the glymphatic pathway. CONCLUSION: The findings of this study reveal that rAAV1-based vectors have high application potential for endothelial-targeted neurologic disease research or gene-based therapies.

5.
Theranostics ; 9(19): 5672-5680, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534510

RESUMO

Autophagy is a dynamic and complicated catabolic process. Imaging autophagic flux can clearly advance knowledge of its pathophysiology significance. While the most common way autophagy is imaged relies on fluorescent protein-based probes, this method requires substantial genetic manipulation that severely restricts the application. Small fluorescent probes capable of tracking autophagic flux with good spatiotemporal resolution are highly demanable. Methods: In this study, we developed a small-molecule fluorogenic probe (AFG-1) that facilitates real-time imaging of autophagic flux in both intact cells and live mice. AFG-1 is inspired by the cascading nitrosative and acidic microenvironments evolving during autophagy. It operates over two sequential steps. In the first step, AFG-1 responds to the up-regulated peroxynitrite at the initiation of autophagy by its diphenylamino group being oxidatively dearylated to yield a daughter probe. In the second step, the daughter probe responds to the acidic autolysosomes at the late stage of autophagy by being protonated. Results: This pathway-dependent mechanism has been confirmed first by sequentially sensing ONOO- and acid in aqueous solution, and then by imaging autophagic flux in live cells. Furthermore, AFG-1 has been successfully applied to visualize autophagic flux in real-time in live mice following brain ischemic injury, justifying its robustness. Conclusion: Due to the specificity, easy operation, and the dynamic information yielded, AFG-1 should serve as a potential tool to explore the roles of autophagy under various pathological settings.

6.
Clin Exp Rheumatol ; 37 Suppl 118(3): 209-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31376261

RESUMO

Sjögren's syndrome (SS) is a chronic autoimmune disease characterised by lymphocytic infiltration in exocrine glands with secretory dysfunction. Although both environmental triggers and genetic predisposition have been recognised as important factors in the initiation and development of SS, the pathogenesis of SS is complex and still largely unclear. Animal models have served as useful tools for studying SS pathogenesis with several advantages. A number of animal models recapitulating key characteristics of primary SS patients including secretory dysfunction, glandular inflammation and presence of autoantibodies were developed in the past years. The studies based on the animal models of SS have provided significant insight in SS pathogenesis and therapeutic intervention. This review summarises current animal models with primary SS-like symptoms including spontaneous models, genetically modified models, induced models and humanised models, and discusses their contribution to the understanding of SS aetiology and therapies.


Assuntos
Doenças Autoimunes , Modelos Animais de Doenças , Síndrome de Sjogren , Animais , Autoanticorpos , Humanos
7.
Brain Res ; 1724: 146407, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31465773

RESUMO

Normal aging is a risk factor for metabolic disorders such as diabetes, and diabetes is also a recognized cause of accelerated aging. Being able to distinguish changes caused by normal aging from those caused by diabetes, would provide insight into how the aging brain interacts with diabetes. Eight types of MRI metric maps (magnetization relaxation time constants of T1 and T2, cerebral blood flow, cerebrovascular permeability, mean diffusivity, diffusion fractional anisotropy, mean diffusion kurtosis and diffusion directional entropy) were generated for all rats from the three groups of normal young, healthy and 1.5-month diabetic middle-aged rats under investigation. Measurements of multiple MRI indices of cerebral white and gray matter from animals of the three groups provide complementary results and insight into differences between healthy and diabetic white / gray matter in the mid-aged rats. Our data indicate that MRI may distinguish between the normal and diabetes in mid-aged rat brains by measuring either T1 and T2 of gray matter, or fractional anisotropy of white matter and gray matter. Therefore, MRI can distinguish changes of cerebral tissue due to the normal aging from diabetic aging, which may lead to be able to better understand how diabetes accelerates aging in normal brain.

8.
Br J Pharmacol ; 176(16): 2922-2944, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31124139

RESUMO

BACKGROUND AND PURPOSE: Celastrol exhibits anti-arthritic effects in rheumatoid arthritis (RA), but the role of celastrol-mediated Ca2+ mobilization in treatment of RA remains undefined. Here, we describe a regulatory role for celastrol-induced Ca2+ signalling in synovial fibroblasts of RA patients and adjuvant-induced arthritis (AIA) in rats. EXPERIMENTAL APPROACH: We used computational docking, Ca2+ dynamics and functional assays to study the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA). In rheumatoid arthritis synovial fibroblasts (RASFs)/rheumatoid arthritis fibroblast-like synoviocytes (RAFLS), mechanisms of Ca2+ -mediated autophagy were analysed by histological, immunohistochemical and flow cytometric techniques. Anti-arthritic effects of celastrol, autophagy induction, and growth rate of synovial fibroblasts in AIA rats were monitored by microCT and immunofluorescence staining. mRNA from joint tissues of AIA rats was isolated for transcriptional analysis of inflammatory genes, using siRNA methods to study calmodulin, calpains, and calcineurin. KEY RESULTS: Celastrol inhibited SERCA to induce autophagy-dependent cytotoxicity in RASFs/RAFLS via Ca2+ /calmodulin-dependent kinase kinase-ß-AMP-activated protein kinase-mTOR pathway and repressed arthritis symptoms in AIA rats. BAPTA/AM hampered the in vitro and in vivo effectiveness of celastrol. Inflammatory- and autoimmunity-associated genes down-regulated by celastrol in joint tissues of AIA rat were restored by BAPTA/AM. Knockdown of calmodulin, calpains, and calcineurin in RAFLS confirmed the role of Ca2+ in celastrol-regulated gene expression. CONCLUSION AND IMPLICATIONS: Celastrol triggered Ca2+ signalling to induce autophagic cell death in RASFs/RAFLS and ameliorated arthritis in AIA rats mediated by calcium-dependent/-binding proteins facilitating the exploitation of anti-arthritic drugs based on manipulation of Ca2+ signalling.

9.
Brain Res ; 1717: 127-135, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31009610

RESUMO

Diffuse white matter (WM) response to traumatic brain injury (TBI) and transplantation of human bone marrow stromal cells (hMSCs) after the injury were non-invasively and dynamically investigated. Male Wistar rats (300-350 g) subjected to TBI were intravenously injected with 1 ml of saline (n = 10) or with hMSCs in suspension (∼3 × 106 hMSCs, n = 10) 1-week post-TBI. MRI measurements of T2-weighted imaging and diffusional kurtosis imaging (DKI) were acquired on all animals at multiple time points up to 3-months post-injury. Functional outcome was assessed using the Morris water maze test. DKI-derived metrics of fractional anisotropy (FA), axonal water fraction (AWF) and radial kurtosis (RK) longitudinally reveal an evolving pattern of structural alteration post-TBI occurring in the brain region remote from primary impact site. The progressive structural change is characterized by gradual disruption of WM integrity at an early stage (weeks post-TBI), followed by spontaneous recovery at a later stage (months post-TBI). Transplantation of hMSCs post-TBI promotes this structural plasticity as indicated by significantly increased FA and AWF in conjunction with substantially elevated RK at the later stage. Our long-term imaging data demonstrate that hMSC therapy leads to modified temporal profiles of these metrics, inducing an earlier presence of enhanced structural remodeling, which may contribute to improved functional recovery.

10.
Zhongguo Zhong Yao Za Zhi ; 44(2): 381-387, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30989961

RESUMO

The data mining method was used to analyze and summarize the prescription and medicate regularities of chief physician Jiang Quan in the treatment of rheumatoid arthritis,in order to provide references for the clinical treatment of rheumatoid arthritis. Totally 121 prescriptions of rheumatoid arthritis treated by chief physician Jiang Quan from 2007 to 2017 were collected and input into the Chinese medicine inheritance auxiliary system. The " prescription statistics" function of the software " statistical report" system,and the " prescription analysis" function of the " data analysis" system,the data mining methods such as rule analysis,integration correlation,complex system entropy clustering,and unsupervised entropy hierarchical clustering,were used to analyze the prescription regularity of chief physician Jiang Quan. A total of 121 prescriptions were included,involving 144 herbs,in which 30 herbs had a higher frequency of more than 20 times,20 two-herb combinations had a frequency of more than 59 times; after evolution,14 core combinations and 7 new prescriptions were obtained. Among the prescriptions in the treatment of rheumatoid arthritis,those for clearing heat and dampness,promoting blood circulation and removing blood stasis had a higher frequency,and the core prescriptions were modified " Qingre Huoxue Decoction" and modified " Ermiao Pills". The newly evolved prescriptions not only reflected director Jiang Quan' s method of treating rheumatoid arthritis by clearing away heat and dampness and promoting blood circulation by the,but also included the treatment methods of removing wind and removing dampness,dredging collaterals and removing phlegm,nourishing Yin and clearing heat,nourishing Yin and nourishing kidney,nourishing blood and nourishing Qi. The method can be used to analyze the pathogenetic changes of the mutual knot of phlegm and blood stasis,injury of Qi and blood,long-term implication on liver and kidney. At the same time,it also reflects the treatment principles of treating phlegm and strengthening the evil.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Mineração de Dados , Medicamentos de Ervas Chinesas/uso terapêutico , Análise por Conglomerados , Humanos , Medicina Tradicional Chinesa
11.
Mol Psychiatry ; 24(10): 1461-1477, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30886335

RESUMO

Anxiety disorders are the most prevalent psychiatric disorders, but their pathogenic mechanism remains poorly understood. Here, we report that transmembrane protein 74 (TMEM74), which contains two putative transmembrane domains and exhibits high levels of mRNA in the brain, is closely associated with the pathogenesis of anxiety disorders. TMEM74 was decreased in the serum of patients with anxiety and the basolateral amygdaloid nucleus (BLA) in chronic stress mice. Furthermore, genetic deletion of Tmem74 or selective knockdown of Tmem74 in BLA pyramidal neurons resulted in anxiety-like behaviors in mice. Whole-cell recordings in BLA pyramidal neurons revealed lower hyperpolarization-activated cation current (Ih) and greater input resistance and excitability in Tmem74-/- neurons than in wild-type neurons. Accordingly, surface expression of hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels was also lower in the BLA of Tmem74-/- mice. The Ih current blocker ZD7288 mimicked these effects in BLA pyramidal neurons in wild-type mice but not in Tmem74-/- mice. Consistent with the improvement in anxiety-like behaviors, Tmem74 overexpression restored HCN1 channel trafficking and pyramidal neuron excitability in the BLA of Tmem74-/- and chronic stress mice. Mechanistically, we demonstrate that interactions between Tmem74 and HCN1 are physiologically relevant and that transmembrane domain 1 (TM1) is essential for the cellular membrane localization of Tmem74 to enhance Ih. Together, our findings suggest that Tmem74 coupling with HCN1 acts as a critical component in the pathophysiology of anxiety and is a potential target for new treatments of anxiety disorders.

12.
Clin Exp Rheumatol ; 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30789154

RESUMO

OBJECTIVES: Fibromyalgia is a chronic debilitating pain syndrome. There has been growing interest in the development of non-pharmacological therapies. Ba-Duan-Jin is an ancient Chinese exercise for health promotion, yet easy to learn. The purpose of this study is to evaluate the effectiveness of Ba-Duan-Jin in managing fibromyalgia symptoms experienced by Chinese patients. METHODS: In this randomised, usual therapy-controlled study, patients with fibromyalgia practiced Ba-Duan-Jin for one hour, twice a week for 12 weeks. The primary outcome measure was change in the Visual Analogue Scale for pain (pain VAS). Secondary outcomes included the Fibromyalgia Impact Questionnaire (FIQ), the Multidimensional Assessment of Fatigue (MAF), the Pittsburgh Sleep Quality Index (PSQI), the Beck Depression Inventory (BDI), the Perceived Stress Scale (PSS), and the Tender Point Count (TPC). These measures were assessed at baseline and after 4, 8, and 12 weeks. The Patient Global Impression of Change (PGIC) was collected at week 12. The Mann-Whitney U-test was performed using the intention-to-treat population. RESULTS: A total of 62 fibromyalgia patients were randomised to the Ba-Duan-Jin or the control groups. For the Ba-Duan-Jin group, significant improvement in pain VAS, FIQ, MAF, PSQI, and TPC were documented at weeks 4 (p≤0.046) and continued at week 8 (p≤0.003). At week 12, all of the outcome measures including BDI and PSS exhibited significant improvement (p≤0.004), and PGIC ratings were significantly better (p<0.001). No significant changes in the control group were observed. CONCLUSIONS: This study suggests that Ba-Duan-Jin exercise has the potential to be a valuable non-pharmacological intervention among Chinese fibromyalgia patients.

13.
Clin Hemorheol Microcirc ; 72(2): 129-138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30636730

RESUMO

BACKGROUND: Plasma cell mastitis (PCM), a common type of mastitis often mimics malignancy clinically and radiologically. OBJECTIVE: The study was designed to explore the diagnostic value of superb microvascular imaging (SMI) in differentiating PCM from malignant breast lesions. METHODS: A total of 95 breast lesions underwent conventional ultrasound (US) and SMI examination between May 2016 and April 2018. Vessels were detected in SMI in a quantitative manner. Blood flow parameters including systolic peak velocity (SPV), resistance index (RI), and pulsatility index (PI) were evaluated. We further assessed the diagnostic performances of US and US+SMI. RESULTS: The majority of PCM were in regular shape and displayed no calcification compared with malignant breast lesions. Regarding blood flow parameters, PCM obtained significantly lower mean value of RI and PI compared with malignant lesions (P < 0.05). The sensitivity, specificity and accuracy rate of US+SMI (84.62%, 76.47%, 83.16%) was significantly higher than those of US (78.21%, 64.71%, 75.59%). CONCLUSIONS: The present study supports that SMI is a novel ultrasound technology in revealing micro-vessels in breast lesions. The combined modality of US+SMI presented a better diagnostic performance in making a distinction between PCM and malignant breast carcinomas.

14.
Angew Chem Int Ed Engl ; 58(11): 3421-3425, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30675976

RESUMO

Undirected C(sp3 )-H functionalization reactions often follow site-selectivity patterns that mirror the corresponding C-H bond dissociation energies (BDEs). This often results in the functionalization of weaker tertiary C-H bonds in the presence of stronger secondary and primary bonds. An important, contemporary challenge is the development of catalyst systems capable of selectively functionalizing stronger primary and secondary C-H bonds over tertiary and benzylic C-H sites. Herein, we report a Cu catalyst that exhibits a high degree of primary and secondary over tertiary C-H bond selectivity in the amidation of linear and cyclic hydrocarbons with aroyl azides ArC(O)N3 . Mechanistic and DFT studies indicate that C-H amidation involves H-atom abstraction from R-H substrates by nitrene intermediates [Cu](κ2 -N,O-NC(O)Ar) to provide carbon-based radicals R. and copper(II)amide intermediates [CuII ]-NHC(O)Ar that subsequently capture radicals R. to form products R-NHC(O)Ar. These studies reveal important catalyst features required to achieve primary and secondary C-H amidation selectivity in the absence of directing groups.

15.
Neuroimage ; 188: 616-627, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30578928

RESUMO

The glymphatic system is functional waste clearance path from the brain parenchyma through dynamic exchange of cerebrospinal fluid (CSF) with interstitial fluid (ISF). Impairment of glymphatic waste clearance is involved in the development of neurodegenerative conditions. Despite many recent studies investigating the glymphatic system, few studies have tried to use a mathematical model to describe this system, quantitatively. In this study, we aim to model the glymphatic system from the kinetics of Gd-DTPA tracer measured using MRI in order to: 1) map the glymphatic system path, 2) derive kinetic parameters of the glymphatic system, and 3) provide quantitative maps of the structure and function of this system. In the proposed model, the brain is clustered to similar regions with respect to the profile of contrast agent (CA) density measured by MRI. Then, each region is described as a two-compartment kinetic model 'derived from' or 'clears to' its neighbors with local input function. We thus fit our model to the local cerebral regions rather than to the averaged time signal curve (TSC) of the whole brain. The estimated parameters showed distinctive differences between diabetes mellitus (DM) and control rats. The results suggest that in a typical DM brain the CSF bulk speed in the para-vasculature network is low. In addition, the resulting maps indicate that there may be increased binding and decreased absorbing of large molecules in a diabetic compared with a non-diabetic brain. The important contribution of this work was to fit the model to the local regions rather than to the averaged time signal curve (TSC) of the whole brain. This enabled us to derive quantitative maps of the glymphatic system from MRI.

16.
J Stroke Cerebrovasc Dis ; 28(3): 830-837, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30563776

RESUMO

BACKGROUND: The present study aimed to explore the efficacy of atorvastatin on patients with carotid plaque, applying superb microvascular imaging (SMI), and contrast-enhanced ultrasound (CEUS) for evaluating carotid intraplaque neovascularization. METHODS: A total of 82 patients (82 carotid plaques) who were randomized into treatment group and control group underwent conventional ultrasound, CEUS, and SMI examinations. Patients in treatment group received a dose of 20 mg atorvastatin per day for 6 months while those in control group received placebo instead. Lipid parameters were assessed and intraplaque neovascularization were evaluated by CEUS and SMI before and 6 months after atorvastatin treatment. RESULTS: No significant differences were found between the 2 groups at the study entry. Patients with atorvastatin treatment received marked improvement in total cholesterol, triglyceride, and LDL-cholesterol compared with those in control group (P < .001). In treatment group, SMI-detected intraplaque neovascularization reduced from 69.23% to 48.72% while CEUS-detected ones reduced from 76.92% to 69.23%. By contrast, the percentage of intraplaque neovascularization in control group did not change too much either by SMI (65.12%, 67.44%) or CEUS (74.41%, 74.41%). The consistency between CEUS and SMI was above .75 at all assessments (P < .001). CONCLUSIONS: Atorvastatin treatment works for patients with carotid plaque by reducing LDL-cholesterol and improving plaque regression. Second, the consistency between SMI and CEUS in visualizing intraplaque neovascularization is good. That indicates a high possibility to identify carotid plaque instability by a safer and cheaper ultrasonography without contrast agent.


Assuntos
Atorvastatina/uso terapêutico , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ultrassonografia Doppler em Cores/métodos , Idoso , Idoso de 80 Anos ou mais , Atorvastatina/efeitos adversos , Biomarcadores/sangue , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/patologia , China , LDL-Colesterol/sangue , Meios de Contraste/administração & dosagem , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica , Fosfolipídeos/administração & dosagem , Placa Aterosclerótica , Valor Preditivo dos Testes , Estudos Prospectivos , Hexafluoreto de Enxofre/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
17.
Nat Commun ; 9(1): 5404, 2018 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-30573726

RESUMO

Peach (Prunus persica) is an economically important fruit crop and a well-characterized model for studying Prunus species. Here we explore the evolutionary history of peach using a large-scale SNP data set generated from 58 high-coverage genomes of cultivated peach and closely related relatives, including 44 newly re-sequenced accessions and 14 accessions from a previous study. Our analyses suggest that peach originated about 2.47 Mya in southwest China in glacial refugia generated by the uplift of the Tibetan plateau. Our exploration of genomic selection signatures and demographic history supports the hypothesis that frugivore-mediated selection occurred several million years before the eventual human-mediated domestication of peach. We also identify a large set of SNPs and/or CNVs, and candidate genes associated with fruit texture, taste, size, and skin color, with implications for genomic-selection breeding in peach. Collectively, this study provides valuable information for understanding the evolution and domestication of perennial fruit tree crops.


Assuntos
Genoma de Planta , Prunus persica/genética , Evolução Biológica , China , Produtos Agrícolas/genética , Domesticação , Frutas/genética , Polimorfismo de Nucleotídeo Único , Seleção Genética , Sequenciamento Completo do Genoma
18.
Med Sci Monit ; 24: 9223-9231, 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30563959

RESUMO

BACKGROUND This study aimed to compare superb microvascular imaging (SMI) with grayscale ultrasound (US) and color Doppler flow imaging (CDFI) to evaluate vascular distribution and morphology to distinguish between benign and malignant thyroid nodules. MATERIAL AND METHODS Seventy-one patients with 76 thyroid nodules underwent grayscale US, CDFI, and SMI thyroid imaging. CDFI and SMI assessed vascular quantity, morphology, and distribution, and was graded according to Adler's method, as absent (grade 0), minimal (grade 1), moderate (grade 2), or marked (grade 3). The detection of malignancy was compared between the following imaging groups, grayscale US alone, US combined with CDFI, and US combined with SMI. RESULTS SMI was significantly more accurate in identifying malignant thyroid nodules (79.3%) compared with CDFI (55.2%) (P<0.001). In malignant thyroid nodules, penetrating blood vessels were identified by SMI in 62.1% and by CDFI in 41.4%; there was no significant difference in vascular distribution between SMI (P=0.835) and CDFI (P=0.806). Grayscale US with SMI resulted in the greatest diagnostic sensitivity, accuracy, and specificity (86.21%, 85.53%, and 85.11%) compared with grayscale US with CDFI (75.86%, 82.89%, and 87.23%). Receiver operating characteristic (ROC) area under the curve (AUC) values of US with SMI, US with CDFI, and US alone were 0.918 (95% CI, 0.856-0.979), 0.911 (95% CI, 0.849-0.973), and 0.847 (95% CI, 0.762-0.932), respectively (P<0.001). CONCLUSIONS SMI as an adjunct to grayscale US provided significantly more information on vascularity associated with malignancy in thyroid nodules, when compared with grayscale US or with US and CDFI.


Assuntos
Microvasos/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia Doppler em Cores/métodos , Adulto , Idoso , Área Sob a Curva , China , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Nódulo da Glândula Tireoide/irrigação sanguínea
19.
Med Sci Monit ; 24: 7891-7897, 2018 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-30391992

RESUMO

BACKGROUND This study explored symptoms and signs of pelvic organ prolapse (POP) evaluated by 4-dimensional pelvic floor ultrasonography and analyzed the relationship between delivery mode and POP. MATERIAL AND METHODS A total of 578 women who underwent 4-dimensional transperineal ultrasound were enrolled in this study. Obstetric history together with other clinical information were gathered from clinical questionnaires and gynecologists. Patients were thereafter classified into 4 groups: women with normal vaginal delivery, women with forceps delivery, women with cesarean, and nullipara women. We assessed symptoms and signs of POP among these 4 groups by use of 2 evaluation methods. The first method was clinical assessment applying International Continence Society (ICS) pelvic organ prolapse quantification (POP-Q). The second method was the use of ultrasonography in the quantification of anterior, middle, and posterior compartment prolapse. RESULTS Nulliparae women exhibited the lowest probability of POP (POP-Q: cystocele of 15.6%, uterine prolapse of 11.1%, rectocele of 20.0%; ultrasound exam: 6.7%, 8.9%, 13.3% in sequence), while women with forceps delivery had the highest probability of POP (POP-Q: 59.6%, 50.8%, 63.2% in sequence; ultrasound exam: 45.6%, 52.6%, 42.1% in sequence). Regarding the correlation between POP and delivery mode, the adjusted odds ratio was 2.40 (95%CI: 1.301~4.590) and 3.20 (95%CI: 1.651~6.121) in the normal vaginal delivery group and forceps group, respectively, compared with the cesarean group. CONCLUSIONS Four-dimensional pelvic floor ultrasonography can be used as a preferred method in evaluating POP. Regarding the relationship between delivery mode and POP, there is a significant correlation between vaginal delivery and POP.

20.
J Intensive Care Med ; : 885066618803062, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30270720

RESUMO

BACKGROUND: The efficacy of low-dose hydrocortisone therapy in the management of septic shock remains controversial in critical care for many years. Hence, we performed this meta-analysis of randomized controlled trials (RCTs) with trial sequential analysis (TSA) to evaluate its effect on clinical outcome among adult patients with septic shock. METHODS: We identified relevant RCTs published from inception to March 7, 2018 comparing low-dose hydrocortisone with placebo or no intervention in adults admitted to the intensive care unit (ICU) for septic shock. Meta-analyses were performed for the primary and secondary outcomes. The risk of bias was assessed using the Cochrane Collaboration's instrument. Trial sequential analysis was used to pool the results from the included studies for the primary outcomes. RESULTS: Thirteen studies were retrieved by our literature search strategy. There were no significant differences in 28-day mortality (odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.81-1.00; P = .05) and hospital mortality (OR = 0.91, 95% CI = 0.82-1.02; P = .09) between the 2 groups, which were confirmed by TSA. However, there was a significant improvement in shock reversal in the hydrocortisone group (OR = 1.33, 95% CI = 1.02-1.72; P = .03). Furthermore, subgroup analyses revealed that hydrocortisone plus fludrocortisone statistically reduced the rate of 28-day mortality (OR = 0.79, 95% CI = 0.64-0.97; P = .03), ICU mortality (OR = 0.77, 95% CI = 0.63-0.95; P = .02), and hospital mortality (OR = 0.77, 95% CI = 0.63-0.95; P = .01) in comparison with the placebo, the results were also confirmed by TSA. CONCLUSION: Among adult patients with septic shock, the use of low-dose hydrocortisone compared with control did not confer overall survival benefits, albeit improving shock reversal rate. The benefit of reducing 28-day mortality, ICU mortality, and hospital mortality was observed in combination use of hydrocortisone and fludrocortisone.

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