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1.
BMJ Evid Based Med ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34789473

RESUMO

OBJECTIVES: To assess the beneficial and harmful effects of adding ivabradine to usual care in participants with heart failure. DESIGN: A systematic review with meta-analysis and trial sequential analysis. ELIGIBILITY CRITERIA: Randomised clinical trials comparing ivabradine and usual care with usual care (with or without) placebo in participants with heart failure. INFORMATION SOURCES: Medline, Embase, CENTRAL, LILACS, CNKI, VIP and other databases and trial registries up until 31 May 2021. DATA EXTRACTION: Primary outcomes were all-cause mortality, serious adverse events and quality of life. Secondary outcomes were cardiovascular mortality, myocardial infarction and non-serious adverse events. We performed meta-analysis of all outcomes. We used trial sequential analysis to control risks of random errors, the Cochrane risk of bias tool to assess the risks of systematic errors and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of the evidence. RESULTS: We included 109 randomised clinical trials with 26 567 participants. Two trials were at low risk of bias, although both trials were sponsored by the company that developed ivabradine. All other trials were at high risk of bias. Meta-analyses and trial sequential analyses showed that we could reject that ivabradine versus control reduced all-cause mortality (risk ratio (RR)=0.94; 95% CI 0.88 to 1.01; p=0.09; high certainty of evidence). Meta-analysis and trial sequential analysis showed that ivabradine seemed to reduce the risk of serious adverse events (RR=0.90; 95% CI 0.87 to 0.94; p<0.00001; number needed to treat (NNT)=26.2; low certainty of evidence). This was primarily due to a decrease in the risk of 'cardiac failure' (RR=0.83; 95% CI 0.71 to 0.97; p=0.02; NNT=43.9), 'hospitalisations' (RR=0.89; 95% CI 0.85 to 0.94; p<0.0001; NNT=36.4) and 'ventricular tachycardia' (RR=0.59; 95% CI 0.43 to 0.82; p=0.001; NNT=212.8). However, the trials did not describe how these outcomes were defined and assessed during follow-up. Meta-analyses showed that ivabradine increased the risk of atrial fibrillation (RR=1.19; 95% CI 1.04 to 1.35; p=0.008; number needed to harm (NNH)=116.3) and bradycardia (RR=3.95; 95% CI 1.88 to 8.29; p=0.0003; NNH=303). Ivabradine seemed to increase quality of life on the Kansas City Cardiomyopathy Questionnaire (KCCQ) (mean difference (MD)=2.92; 95% CI 1.34 to 4.50; p=0.0003; low certainty of evidence), but the effect size was small and possibly without relevance to patients, and on the Minnesota Living With Heart Failure Questionnaire (MLWHFQ) (MD=-5.28; 95% CI -6.60 to -3.96; p<0.00001; very low certainty of evidence), but the effects were uncertain. Meta-analysis showed no evidence of a difference between ivabradine and control when assessing cardiovascular mortality and myocardial infarction. Ivabradine seemed to increase the risk of non-serious adverse events. CONCLUSION AND RELEVANCE: High certainty evidence shows that ivabradine does not seem to affect the risks of all-cause mortality and cardiovascular mortality. The effects on quality of life were small and possibly without relevance to patients on the KCCQ and were very uncertain for the MLWHFQ. The effects on serious adverse events, myocardial infarction and hospitalisation are uncertain. Ivabradine seems to increase the risk of atrial fibrillation, bradycardia and non-serious adverse events.PROSPERO registration number: CRD42018112082.

2.
Mil Med ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34791377

RESUMO

INTRODUCTION: Spinal cord injuries (SCI) in military personnel, veterans, and others require an evidence-based, multidisciplinary approach to their care. This appraisal used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument to evaluate the methodological quality of clinical guidelines for the management of SCI published by the Paralyzed Veterans of America (PVA) organization. MATERIALS AND METHODS: We searched clinical guidelines on SCI published by PVA until December 2019. Four appraisers across three international centers independently evaluated the quality of eligible clinical guidelines using AGREE II. Mean AGREE II scores for each domain were calculated. In higher quality domains, scores for individual items were analyzed. RESULTS: A total of 12 guidelines published by PVA on SCI were assessed. Mean scores for all six domains were as follows: Scope and Purpose (78.8%), Stakeholder Involvement (63.7%), Rigor of Development (68.4%), Clarity of Presentation (80.1%), Applicability (53.0%), and Editorial Independence (28.5%). The mean score for the overall quality of all PVA guidelines was 71.9% (95% CI: 69.7-74.1). No guideline was assessed as "not recommended" by any appraiser. Overall quality was significantly associated with year of publication (rs = 0.754, P = 0.0046). Overall agreement among appraisers was excellent (intraclass correlation coefficients for each guideline ranged from 0.96 to 0.99). CONCLUSIONS: PVA guidelines for the management of SCI demonstrated acceptable or good quality across most domains. We recommend the use of PVA guidelines for the assessment and treatment of SCI and related disorders. The quality of PVA guidelines for the management of SCI have improved over time.

3.
Transbound Emerg Dis ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34821052

RESUMO

Tembusu virus (TMUV)-associated disease is a growing cause of egg production decrease and encephalitis in domestic waterfowl, with expanding distribution. In previous studies, TMUV isolates were phylogenetically classified into two genetic lineages and different clusters with varied pathogenicity. However, little is known about the phenotypic and virulence characteristics of cluster 3 isolates within the duck TMUV lineage. In this study, the etiological agent causing egg drop in a laying chicken farm in southern China was investigated and a TMUV was isolated from pooled tissue samples. Genome sequencing and phylogenetic analysis grouped the isolate into TMUV cluster 3 with closest relation to the mosquito-origin TMUV YN12193. Cross-neutralization testing using convalescent sera revealed significant antigenic variation between the isolate and a representative strain of cluster 2.2. The experimental infection of SPF hens confirmed the ability of the isolate to replicate in multiple tissues and led to ovary damage. Additionally, high seroconversion rates (95.83%-100%) were detected in the three flocks following retrospective investigation. Our study demonstrates the occurrence of cluster 3 TMUV infection in laying chickens and that the virus exhibits significant antigenic variation compared with cluster 2 TMUV. This article is protected by copyright. All rights reserved.

4.
Front Neurol ; 12: 719849, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712197

RESUMO

Background: Mild cognitive impairment (MCI) is an important stage between the normal cognitive decline of aging and dementia. The aim of this study was to compare and harmonize the recommendations for the diagnosis and treatment of MCI based on current clinical practice guidelines. Methods: We searched the PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, and Chinese Biological Medicine Database from their inception date to April 24, 2021 to identify all published guidelines on MCI. The qualities of the eligible guidelines were appraised by two reviewers using the Appraisal of Guidelines for Research and Evaluation II instrument. Results: Thirteen guidance documents (four guidelines and nine consensus statements) with specific recommendations were included. Nine guidelines and consensus statements covered the screening and diagnosis of MCI. The evaluation of the documents showed that neuropsychological testing and biomarker assessments were the most common recommendations for the diagnosis of MCI. Nine of the 13 guidance documents covered the treatment and management of MCI. The recommendations for the treatment and management were classified into four categories, namely: intervention for risk reduction, pharmacologic interventions, non-pharmacologic interventions, and counseling. Regarding pharmacological interventions, three guidelines recommend no pharmacologic intervention. The use of cholinesterase inhibitors for MCI is contraindicated in three guidance documents, whereas one proposes that cholinesterase inhibitors and memantine should be deprescribed. EHb761®, Chinese herbal decoctions, and Chinese traditional patent medicine are recommended in two documents. A total of seven guidance documents recommend non-pharmacological interventions, including physical activity interventions, cognitive interventions, dietary and nutritional interventions, and acupuncture. Conclusion: An updated search for possible evidence on the diagnosis and treatment of MCI is needed. Potentially effective diagnoses and treatments, either conventional or complementary, and alternative therapies should be highly valued and addressed in correlation with the supporting evidence.

5.
Opt Lett ; 46(17): 4100-4103, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469949

RESUMO

We present a firmly arranged dielectric regular hexagonal pyramid array to generate lattice light sheets with high conversion efficiency and low stray light. Both the size and working distance of the lattice light sheets can be modulated by changing the structural parameters. We experimentally recorded the lattice light sheets illumination, which is consistent with the corresponding simulation. To evaluate the imaging quality, we compared the light field generated with and without structure by using polystyrene fluorescent microspheres. This study provides a potential method for the building of light sheet fluorescence microscopy with high resolution and low phototoxicity.

6.
PLoS One ; 16(9): e0257081, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34543314

RESUMO

PURPOSE: To perform a systemic literature search to identify Chinese cross culturally adapted and new designed Patient Reported Outcome Measures (PROMs) used for hip assessment, then a standardized evaluation of available instruments in order to provide evidence of high-quality PROMs for clinical use and adoption in future hip registries. METHODS: A Systematic Review of the following databases: PUBMED, CINAHL, EMBASE, CNKI was performed to identify relevant PROMs. Instruments underwent standardized assessment and scoring using the EMPRO tool by two independent reviewers. Inter-rater reliability was assessed using intra-class correlation coefficients (ICC). RESULTS: 2188 articles were retrieved, with seven articles fitting the inclusion criteria consisting of six hip PROMs. Five PROMs were cross culturally adapted and one was originally designed in Mandarin Chinese. Total scores (/100) after EMPRO evaluation: Osteoarthritis of Knee and Hip Quality of Life (OAKHQOL): 55; Copenhagen Hip and Groin Outcome Score (HAGOS): 52; International Hip Outcome Tool (SC-iHOT-33): 45; Hip Disability and Osteoarthritis Outcome Score (HOOS): 37; Questionnaire on the Perceptions and Functions of Patients about Total Hip Arthroplasty (QPFPTHA): 36; Oxford Hip Score (OHS): 35. ICC values were 0.73 for the SC-iHOT-33 and ranged between 0.83-0.93 for the other PROMs indicating good to excellent inter-rater agreement. CONCLUSION: Among the commonly used hip-specific PROMs found in arthroplasty registries, none of the Chinese adapted versions evaluated by EMPRO is currently rated acceptable for clinical use. Only OAKHQOL and HAGOS reached acceptability threshold. Further research on the attributes of cross-cultural adaptation, interpretability and burden assessment would be helpful.


Assuntos
Comparação Transcultural , Quadril/patologia , Medidas de Resultados Relatados pelo Paciente , Humanos , Internacionalidade , Variações Dependentes do Observador , Padrões de Referência , Reprodutibilidade dos Testes
7.
Anal Methods ; 13(29): 3282-3291, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34226905

RESUMO

A simple, quick, effective turn-on fluorescence assay for the determination of fipronil (FIP) was built based on the yellow fluorescence of FAM-aptamer and excellent quenching capability of the oxidized single-walled carbon nanohorns (The oxidized SWCNHs). Oxidized SWCNHs with the great advantage of good dispersibility in solution were generated by link to carboxyl group and were added to a specific FAM-aptamer at an optimal concentration to form an "on-off" oxidized SWCNH/FAM-aptamer fluorescent sensor. The structures of the oxidized SWCNHs were verified, and the comprehensive properties were evaluated by characterization techniques. This paper has exploited oxidized SWCNHs as a quenching agent to detect fipronil for the first time. Under the optimized conditions, the limit of detection (LOD) for fipronil was 3 nM, and the recovery of fipronil varied from 88.6% to 112.7% in different real samples with relative standard deviations (RSDs) not more than 5%. The developed method could be successfully applied for the determination of fipronil in tap water, honey and corn samples.


Assuntos
Aptâmeros de Nucleotídeos , Nanotubos de Carbono , Limite de Detecção , Pirazóis
8.
Molecules ; 26(12)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205604

RESUMO

Rutin (R) and quercetin (Q) are two widespread dietary flavonoids. Previous studies regarding the plasma cholesterol-lowering activity of R and Q generated inconsistent results. The present study was therefore carried out to investigate the effects of R and Q on cholesterol metabolism in both HepG2 cells and hypercholesterolemia hamsters. Results from HepG2 cell experiments demonstrate that both R and Q decreased cholesterol at doses of 5 and 10 µM. R and Q up-regulated both the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), and liver X receptor alpha (LXRα). The immunofluorescence study revealed that R and Q increased the LDLR expression, while only Q improved LDL-C uptake in HepG2 cells. Results from hypercholesterolemia hamsters fed diets containing R (5.5 g/kg diet) and Q (2.5 g/kg diet) for 8 weeks demonstrate that both R and Q had no effect on plasma total cholesterol. In the liver, only Q reduced cholesterol significantly. The discrepancy between the in vitro and in vivo studies was probably due to a poor bioavailability of flavonoids in the intestine. It was therefore concluded that R and Q were effective in reducing cholesterol in HepG2 cells in vitro, whereas in vivo, the oral administration of the two flavonoids had little effect on plasma cholesterol in hamsters.


Assuntos
Colesterol/sangue , Colesterol/metabolismo , Quercetina/farmacologia , Rutina/farmacologia , Administração Oral , Animais , Linhagem Celular Tumoral , Cricetinae , Flavonoides/farmacologia , Células Hep G2 , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Receptores X do Fígado/metabolismo , Masculino , RNA Mensageiro/metabolismo , Receptores de LDL/sangue , Receptores de LDL/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Regulação para Cima/efeitos dos fármacos
9.
J Hepatol ; 75(5): 1142-1153, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34217777

RESUMO

BACKGROUND & AIMS: Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) both exhibit notable cancer stem cell (CSC) features. Moreover, the development of both diseases is closely associated with the presence of CSCs. We investigated the role of brain-expressed X-linked protein 1 (BEX1) in regulating the CSC properties of HB and a subtype of HCC with high CSC features (CSC-HCC). METHODS: Stemness scores were analyzed in 5 murine HCC models. A subpopulation of BEX1-positive cells and BEX1-negative cells were sorted from HCC cell lines, and subjected to transcriptome analysis. The expression and function of BEX1 was examined via western blotting, sphere formation assays, and xenograft tumor models. RESULTS: We identified BEX1 as a novel CSC marker that was required for the self-renewal of liver CSCs. Furthermore, zebularine, a potent DNMT1 inhibitor, can induce the reactivation of BEX1 by removing epigenetic inhibition. Notably, BEX1 was highly expressed in patients with HB and CSC-HCC, but not in patients with non-CSC HCC. Moreover, DNMT1-mediated methylation of the BEX1 promoter resulted in differential BEX1 expression patterns in patients with HB, CSC-HCC, and non-CSC-HCC. Mechanistically, BEX1 interacted with RUNX3 to block its inhibition of ß-catenin transcription, which led to the activation of Wnt/ß-catenin signaling, and stemness maintenance in both HB and CSC-HCC. In contrast, downregulated BEX1 expression released RUNX3 and inhibited the activation of Wnt/ß-catenin signaling in non-CSC-HCC. CONCLUSION: BEX1, under the regulation of DNMT1, is necessary for the self-renewal and maintenance of liver CSCs through activation of Wnt/ß-catenin signaling, rendering BEX1 a potentially valuable therapeutic target in both HB and CSC-HCC. LAY SUMMARY: Cancer stem cells (CSCs) contribute to a high rate of cancer recurrence, as well as resistance to conventional therapies. However, the regulatory mechanisms underlying their self-renewal remains elusive. Herein, we have reported that BEX1 plays a key role in regulating CSC properties in different types of liver cancer. Targeting BEX1-mediated Wnt/ß-catenin signaling may help to address the high rate of recurrence, and heterogeneity of liver cancer.

10.
BMC Musculoskelet Disord ; 22(1): 566, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34154594

RESUMO

BACKGROUND: Patient Reported Outcome Measures (PROMs) are widely used in Europe and North America in a variety of areas including research, clinical governance, clinical registries and insurance ascertainment. The aim of this study was to assess commonly used knee and hip PROMs among Chinese surgeons and to gain an insight into their impact on evaluation of clinical outcomes. METHODS: 1. A systematic literature search of databases Medline, EMBASE, CINAHL and CNKI was performed from the earliest records to 22/07/2020 for knee instruments and 22/08/2020 for hip instruments, to retrieve Chinese Mandarin cross culturally adapted and validated knee and hip PROMs. 2. An 11-item electronic questionnaire was then designed under four domain categories. The survey was distributed via a ubiquitous online social media platform to orthopaedic surgeons. Responses were collected and analyzed. Output from 1. was used to populate parts of the survey questionnaire. RESULTS: The systematic online search yielded a total of 41 evaluation instruments, (10 hip and 31 knee); all of which were incorporated as response options. 234 viable questionnaires were retrieved with the largest group representing attending surgeons. 59.0% were familiar with the concept of PROMs among which 78.4% reported to have used PROMs themselves. In order of frequency of use, PROMs were purposed for clinical assessment (55.6%), research (40.7%), health regulation policies (18.6%) and insurance service requirements (10.6%). Implementation was prompted by both departmental (43.4%) and institutional policy (34.5%). 89.4% of PROMs users reported difficulties in the use of PROMs, with major barriers including license fees, limited access, inadequate training and burden of fill-out time (all > 40%). CONCLUSION: There is evidence of limited familiarity with knee and hip PROMs among orthopaedic surgeons. Barriers to their use are significant. Development of a Chinese language PROMs database would be helpful.


Assuntos
Cirurgiões Ortopédicos , China/epidemiologia , Europa (Continente) , Humanos , América do Norte , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Inquéritos e Questionários
11.
Oncol Lett ; 22(1): 495, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33981357

RESUMO

Double homeobox A pseudogene 8 (DUXAP8) has been reported to regulate the growth of several types of cancers, such as breast cancer and ovarian cancer. However, its role in melanoma remains unclear. In the present study, the mechanism through which DUXAP8 regulates melanoma progression was explored. The expression levels of DUXAP8 were determined in 43 samples from patients with melanoma in different stages, as well as human epidermal melanocytes cells and malignant melanoma cell lines using reverse transcription-quantitative PCR (RT-qPCR). The prognosis of patients was analyzed using the Kaplan-Meier method. The relationship between lncRNA DUXAP8 expression and microRNA (miR)-3182 or nuclear protein 1 transcriptional regulator (NUPR1) levels was analyzed using Pearson's correlation. Luciferase reporter and RNA pull-down were used to examine the interactions between these molecules. Proliferation was assessed using Cell Counting-Kit-8. Transwell assays were used to examine cell migration and invasion. lncRNA DUXAP8 was upregulated in melanoma tissue and cells compared with normal tissues and cells. The levels of DUXAP8 inversely correlated with survival time of patients with melanoma. Knockdown of lncRNA DUXAP8 inhibited proliferation, migration and invasion of melanoma cells. lncRNA DUXAP8 targeted miR-3182, while miR-3182 targeted NUPR1. The overexpression of NUPR1 reversed the effects of DUXAP8 knockdown or miR-3182 mimic on melanoma progression. In conclusion, lncRNA DUXAP8 downregulation inhibits the development of melanoma by regulating the miR-3182/NUPR1 axis.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33977038

RESUMO

The 18th International Symposium on Geo-disaster Reduction (ISGdR) was held on 20-22 November in Beijing, China, focusing on the theme of "Improving the Relationship between Geoenvironment and Society". In this symposium, a high-level Gu Dezhen Lecture and a number of keynote and invited lectures provided a platform for scientists, industrial professionals and students to share their researches and exchange novel ideas on geo-disaster reduction in a hybrid way of offline and online.

13.
Transl Lung Cancer Res ; 10(3): 1424-1443, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33889520

RESUMO

Background: Neutrophils can play a pro-tumor or anti-tumor role depending on the tumor microenvironment. The effects of concurrent treatment with granulocyte colony-stimulating factor (G-CSF) and radiotherapy (RT) on neutrophils have not yet to be described. Methods: Hypofractionated radiation of 8 Gy ×3 fractions was administered with or without recombinant G-CSF to Lewis lung carcinoma tumor-bearing C57BL/6 model mice. The activation status of cytotoxic T cells in the mice was measured, along with the levels of tumor-associated neutrophils, cytotoxic T cells, and Treg cells. Tumor growth, survival, cytokine expression, and signaling pathways underlying anti-tumor effects of tumor-associated neutrophils after treatment were also studied. To ascertain the effects of concurrent RT and G-CSF on tumor-associated neutrophils, neutrophil depletion was performed. Results: RT affected early neutrophil infiltration, which is the first-line immune response. Subsequently, enhanced accumulation of lymphocytes, particularly CD8 cytotoxic T cells, was observed. Notably, lymphocytic infiltration was inhibited by neutrophil depletion but enhanced by G-CSF treatment. RT generated persistent DNA damage, as evidenced by an accumulation of phosphorylation of histone H2AX (γH2AX), and subsequently triggered inflammatory chemokine secretion. The chemokines CXCL1, CXCL2, and CCL5 were upregulated in both radiation-treated cells and the corresponding supernatants. Neutrophils that were newly recruited after RT improved radiosensitivity by inhibiting epithelial-mesenchymal transition via the reactive oxygen species-mediated PI3K/Akt/Snail signaling pathway, and G-CSF treatment enhanced this effect. Conclusions: The results of this study suggest that RT activates neutrophil recruitment and polarizes newly recruited neutrophils toward an antitumor phenotype, which is enhanced by the concurrent administration of G-CSF. Mesenchymal-epithelial transition induced by reactive oxygen species accumulation plays a major role in this process. Thus, the polarization of tumor-associated neutrophils might play a role in future cancer immunotherapies.

14.
Front Plant Sci ; 12: 622429, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33643352

RESUMO

This study aims to provide an effective image analysis method for clover detection and botanical composition (BC) estimation in clover-grass mixture fields. Three transfer learning methods, namely, fine-tuned DeepLab V3+, SegNet, and fully convolutional network-8s (FCN-8s), were utilized to detect clover fractions (on an area basis). The detected clover fraction (CF detected ), together with auxiliary variables, viz., measured clover height (H clover ) and grass height (H grass ), were used to build multiple linear regression (MLR) and back propagation neural network (BPNN) models for BC estimation. A total of 347 clover-grass images were used to build the estimation model on clover fraction and BC. Of the 347 samples, 226 images were augmented to 904 images for training, 25 were selected for validation, and the remaining 96 samples were used as an independent dataset for testing. Testing results showed that the intersection-over-union (IoU) values based on the DeepLab V3+, SegNet, and FCN-8s were 0.73, 0.57, and 0.60, respectively. The root mean square error (RMSE) values for the three transfer learning methods were 8.5, 10.6, and 10.0%. Subsequently, models based on BPNN and MLR were built to estimate BC, by using either CF detected only or CF detected , grass height, and clover height all together. Results showed that BPNN was generally superior to MLR in terms of estimating BC. The BPNN model only using CF detected had a RMSE of 8.7%. In contrast, the BPNN model using all three variables (CF detected , H clover , and H grass ) as inputs had an RMSE of 6.6%, implying that DeepLab V3+ together with BPNN can provide good estimation of BC and can offer a promising method for improving forage management.

15.
Int Immunopharmacol ; 95: 107561, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33744778

RESUMO

Influenza A viruses (IAVs) are highly contagious pathogens infecting human and numerous animals. The viruses cause millions of infection cases and thousands of deaths every year, making IAVs a continual threat to global health. Our study demonstrated the virucidal activity of Moringa A as a new compound from Moringa oleifera seeds against IAVs. It inhibits virus replication in host cells and protects infected cells from the cytopathic effect induced by IAVs. The EC50andEC90 values of Moringa A for IAVs were 1.27 and 5.30 µM, respectively, when RAW264.7 cells were infected at MOI of 1. The different treatment experiments revealed that Moringa A has a significant inhibitory effect on the IAVs both before and afterdrug addition. Moringa A was observed to decrease the inflammatory cytokines TNF-α, IL-6, IL-1ß, and IFN-ß in H1N1 infected RAW264.7 cells. Finally, Moringa A was found to inhibit the expression and nuclear transfer of the cellular protein transcription factor EB (TFEB) and weaken the autophagy in infected cells, which could be an important antiviral mechanism. Our study demonstrates Moringa A has potent antiviral activity against IVAs, which could be due to the autophagy inhibition property.


Assuntos
Antivirais/farmacologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/imunologia , Vírus da Influenza A/efeitos dos fármacos , Moringa oleifera , Animais , Citocinas/imunologia , Camundongos , Células RAW 264.7 , Sementes
16.
J Clin Epidemiol ; 135: 29-41, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33561529

RESUMO

OBJECTIVE: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions. STUDY DESIGN AND SETTING: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups. RESULTS: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters. CONCLUSION: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis.


Assuntos
Metanálise como Assunto , Projetos de Pesquisa/estatística & dados numéricos , Viés , Humanos , Reprodutibilidade dos Testes
17.
Artigo em Inglês | MEDLINE | ID: mdl-33540148

RESUMO

A rapid, reliable and eco-friendly method for the determination of three sex hormones in five kinds of milk was developed and validated by combining vortex-assisted liquid-liquid microextraction (VALLME) and magnetic solid-phase extraction (MSPE). Deep eutectic solvents (DESs) such as choline chloride/urea were considered as the extraction solvent in VALLME and multi-walled carbon nanotubes (MMWCNTs) were used as the adsorbent which could adsorb DESs on the surface. The optimum experimental conditions were as follows: amount of MMWCNTs for 10 mg, volume of acetone for 4 mL, no sodium chloride and extraction pH at 7. After the optimization of several main variables, satisfactory sensitivity levels were achieved as low as 1.0-1.3 ng mL-1 and 2.5-4.5 ng mL-1 for the limit of method detections and the limit of method quantitation, respectively. The recoveries of the three hormones in different milk samples were in the range of 80.1%-116.4%. Consequently, this method is suitable for monitoring the trace amount of sex hormones in milk matrices.


Assuntos
Hormônios Esteroides Gonadais/análise , Microextração em Fase Líquida/métodos , Nanopartículas de Magnetita/química , Leite/química , Extração em Fase Sólida/métodos , Animais , Bovinos , Resíduos de Drogas/análise , Resíduos de Drogas/química , Resíduos de Drogas/isolamento & purificação , Hormônios Esteroides Gonadais/química , Hormônios Esteroides Gonadais/isolamento & purificação , Limite de Detecção , Modelos Lineares , Nanotubos de Carbono/química , Reprodutibilidade dos Testes , Solventes
18.
Mol Cell ; 81(5): 953-968.e9, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33503407

RESUMO

While the role of transcription factors and coactivators in controlling enhancer activity and chromatin structure linked to gene expression is well established, the involvement of corepressors is not. Using inflammatory macrophage activation as a model, we investigate here a corepressor complex containing GPS2 and SMRT both genome-wide and at the Ccl2 locus, encoding the chemokine CCL2 (MCP-1). We report that corepressors co-occupy candidate enhancers along with the coactivators CBP (H3K27 acetylase) and MED1 (mediator) but act antagonistically by repressing eRNA transcription-coupled H3K27 acetylation. Genome editing, transcriptional interference, and cistrome analysis reveals that apparently related enhancer and silencer elements control Ccl2 transcription in opposite ways. 4C-seq indicates that corepressor depletion or inflammatory signaling functions mechanistically similarly to trigger enhancer activation. In ob/ob mice, adipose tissue macrophage-selective depletion of the Ccl2 enhancer-transcribed eRNA reduces metaflammation. Thus, the identified corepressor-eRNA-chemokine pathway operates in vivo and suggests therapeutic opportunities by targeting eRNAs in immuno-metabolic diseases.


Assuntos
Quimiocina CCL2/genética , Proteínas Correpressoras/genética , Elementos Facilitadores Genéticos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Correpressor 2 de Receptor Nuclear/genética , Obesidade/genética , Elementos Silenciadores Transcricionais , Tecido Adiposo/imunologia , Tecido Adiposo/patologia , Animais , Sistemas CRISPR-Cas , Quimiocina CCL2/imunologia , Proteínas Correpressoras/imunologia , Edição de Genes , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Histona Acetiltransferases/genética , Histona Acetiltransferases/imunologia , Histonas/genética , Histonas/imunologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Subunidade 1 do Complexo Mediador/genética , Subunidade 1 do Complexo Mediador/imunologia , Camundongos , Camundongos Obesos , Correpressor 2 de Receptor Nuclear/imunologia , Obesidade/imunologia , Obesidade/patologia , Células RAW 264.7 , RNA não Traduzido/genética , RNA não Traduzido/imunologia , Transdução de Sinais
19.
Placenta ; 103: 199-205, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33160253

RESUMO

INTRODUCTION: The negative relationship between maternal high-density lipoprotein-cholesterol (HDL-c) level during pregnancy and infant birth weight has been found. Syncytialization (differentiation and fusion) of trophoblast cells is important to fetal development. HDL has an antioxidant effect, and has been proved to protect trophoblast functions including hormone secretion and invasion. However, HDL is susceptible to oxidation, and high concentrations of HDL impair cell growth and oxidized HDL (oxHDL) inhibits cell proliferation and migration. Moreover, the effects of HDL and oxHDL on trophoblast syncytialization have not been characterized. The aim of this study was to investigate the effects of HDL and oxHDL on trophoblast syncytialization. METHODS: Human choriocarcinoma trophoblasts (BeWo cells) were treated with human HDL or oxHDL and then induced to differentiate by forskolin in syncytialization assays. Expression levels of mRNAs and proteins regulating syncytialization were detected by real-time PCR and western blotting, respectively. RESULTS: Treatments of HDL at high concentrations reduced human chorionic gonadotropin (hCG) secretion, placental alkaline phosphatase activity and fusion rates, and decreased the expressions of GCM1 and ERVW-1 mRNA as well as phospho-MAPK1/3 (p-MAPK1/3) and total MAPK1/3 protein in the forskolin-induced syncytialization of BeWo cells. Furthermore, treatment of oxHDL (20 µg/ml) decreased hCG secretion, but increased the expression of p-MAPK1/3 protein. DISCUSSION: These data suggested that both HDL at high concentrations and oxHDL inhibited BeWo cells syncytialization, and might be harmful to placental and fetal development.

20.
J Obstet Gynaecol ; 41(7): 1001-1009, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33228406

RESUMO

Danggui Sini Decoction (DSD), a traditional herbal prescription, has been commonly used in the treatment of primary dysmenorrhoea (PD). We investigated the current evidence of randomised controlled trials (RCTs) and performed a systematic review to evaluate the efficacy of DSD in the treatment of PD. We registered the protocol for this systemic review in PROSPERO with the registration number CRD 42017074062 on August 10, 2017. Nine databases were searched from inception to August 2019. Eleven RCTs with 1005 patients were included. DSD was shown to have more favourable effects on the clinical effective rate than western medicine, which support the clinical use of DSD in the treatment of PD. However, considering the high risk of bias in the included studies, more well-designed RCTs are needed to further evaluate the efficacy of DSD in the treatment of PD.

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