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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(2): 156-161, 2021 Feb 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33678652

RESUMO

OBJECTIVES: Pulmonary alveolar proteinosis (PAP) is a rare disease with non-specific and various clinical manifestations, often leading to misdiagnosis. This study aims to raise the awareness of this disease via summarizing the clinical characteristics, diagnosis, and therapy of PAP. METHODS: We retrospectively analyzed clinical data of 25 hospitalized cases of PAP during 2008 and 2019 in the Department of Respiratory and Critical Care Medicine of the Second Xiangya Hospital of Central South University. RESULTS: Cough with unkown reason and dyspnea were common clinical manifastations of PAP. Five patients had a history of occupational inhalational exposure. Sixteen patients had typical image features including ground-glass opacification of alveolar spaces and thickening of the interlobular and intralobular septa, in typical shapes called crazy-paving and geographic pattern. Fourteen patients underwent pulmonary function tests, revealing a reduction in the diffusing capacity for carbon monoxide. The positive rate of transbronchial biopsy was 95%. Five patients received the whole lung lavage and the symptoms and imaging fcauters significantly relieved after five-years follow-up. CONCLUSIONS: PAP is characterized by radiographic pattern and pathology. Transbronchial lung biopsy is effective to make diagnosis of PAP. The whole lung lavage remains a efficient therapy.


Assuntos
Proteinose Alveolar Pulmonar , Biópsia , Lavagem Broncoalveolar , Tosse , Dispneia , Humanos , Proteinose Alveolar Pulmonar/diagnóstico por imagem , Proteinose Alveolar Pulmonar/terapia , Estudos Retrospectivos
2.
J Int Med Res ; 49(3): 300060521994925, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33729859

RESUMO

OBJECTIVE: To investigate the relationship between peroxisome proliferator-activated receptor gamma (PPARγ) mRNA, serum adiponectin (ADP) and lipids in paediatric patients with Kawasaki disease (KD). METHODS: This prospective study enrolled paediatric patients with KD and grouped them according to the presence or absence of coronary artery lesions (CAL). A group of healthy age-matched children were recruited as the control group. The levels of PPARγ mRNA, serum ADP and lipids were compared between the groups. Receiver operating characteristic (ROC) curve analysis was undertaken to determine if the PPARγ mRNA level could be used as a predictive biomarker of CAL prognosis. RESULTS: The study enrolled 42 patients with KD (18 with CAL [CAL group] and 24 without CAL [NCAL group]) and 20 age-matched controls. PPARγ mRNA levels in patients with KD were significantly higher than those in the controls; but significantly lower in the CAL group than the NCAL group. ROC curve analysis demonstrated that the PPARγ mRNA level provided good predictive accuracy for the prognosis of CAL. There was no association between PPARγ, ADP and lipid levels. CONCLUSION: There was dyslipidaemia in children with KD, but there was no correlation with PPARγ and ADP. PPARγ may be a predictor of CAL in patients with KD with good predictive accuracy.

3.
Appl Microbiol Biotechnol ; 105(7): 2841-2854, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33763710

RESUMO

The genus Citrobacter is commonly found in environmental and industrial settings, some members of which have been used for bioremediation of heavy metals owing to the absorption ability of their biofilms. Although our previous studies have found that the outer membrane protein A (OmpA) contributes to the process of Citrobacter werkmanii biofilm formation, the underlying mechanisms remain elusive. Therefore, we deleted ompA from the genome of C. werkmanii and investigated its phenotypes in comparison to the wild type strain (WT) and the complementary strain using biochemical and molecular techniques including RNA-Seq. Our results demonstrated that the deletion of ompA led to an increase in biofilm formation on both polystyrene and glass surfaces due to upregulation of some biofilm formation related genes. Meanwhile, swimming ability, which is mediated by activation of flagellar assembly genes, was increased on semi-solid plates in the ∆ompA strain when compared with WT. Additionally, inactivation of ompA also caused increased 1,2-benzisothiazolin-3-one (BIT) resistance, differential responses to Ca2+ stress, curli protein expression and cellulose production. Finally, ∆ompA caused differential expression of a total of 1470 genes when compared with WT, of which 146 were upregulated and 1324 were downregulated. These genes were classified into different Gene Ontology (GO) and KEGG pathways. In summary, ompA in C. werkmanii contributes to a variety of biological functions and may act as a target site to modulate biofilm formation. KEY POINTS: • ompA is a negative regulator for biofilm formation by C. werkmanii. • ompA inhibits swimming motility of C. werkmanii. • ompA deletion causes different expression profiles in C. werkmanii.

4.
Comput Biol Med ; 132: 104338, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33780870

RESUMO

Epileptic seizure detection is of great significance in the diagnosis of epilepsy and relieving the heavy workload of visual inspection of electroencephalogram (EEG) recordings. This paper presents a novel method for seizure detection using the Stein kernel-based sparse representation (SR) for EEG recordings. Different from the traditional SR scheme that works with vector data in Euclidean space, the Stein kernel-based SR framework is constructed for seizure detection in the space of the symmetric positive definite (SPD) matrices, which form a Riemannian manifold. Due to the non-Euclidean geometry of the Riemannian manifold, the Stein kernel on the manifold permits the embedding of the manifold in a high-dimensional reproducing kernel Hilbert space (RKHS) to perform SR. In the Stein kernel-based SR framework, EEG samples are described by SPD matrices in the form of covariance descriptors (CovDs). Then, a test EEG sample is sparsely represented on the training set, and the test sample is classified as a member of the class, which leads to the minimum reconstructed residual. Finally, by using three widely used EEG datasets to evaluate the detection performance of the proposed method, the experimental results demonstrate that it achieves good classification accuracy on each dataset. Furthermore, the fast computational speed of the Stein kernel-based SR also meets the basic requirements for real-time seizure detection.

5.
J Diabetes Res ; 2021: 7830136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33506052

RESUMO

Backgrounds: Diabetes mellitus (DM) is one of the most common comorbidities in patients with coronavirus disease (COVID-19). We aim to summarize the clinical features of DM patients with COVID-19 and find out potential factors associated with severe disease. Methods: In this retrospective, single-center study, the medical records of patients with COVID-19 in Changsha, Hunan, China, from January 21, 2020, to February 19, 2020, were reviewed. Epidemiological information, clinical features, and outcomes were compared between DM patients admitted to the intensive care unit (ICU) or not. Results: A total of 241 patients confirmed with COVID-19 were enrolled, including 19 DM patients. There were more patients in DM group admitted to the ICU than non-DM group (36.8% vs. 15.8%, P = 0.045). Compared with non-DM group in the ICU, there were more female patients from DM group in the ICU (85.7% vs. 31.4%, P = 0.024). On admission, the mean level of glycated hemoglobin A1c (HbA1c) was higher in the ICU DM patients than that in the non-ICU DM patients (8.5% vs. 7.1%). There were more DM patients with proteinuria in the ICU group than the non-ICU group (57.1% vs. 33.3%). Twelve DM patients (63.2%) changed diabetic therapy during hospitalization, and all DM patients admitted to the ICU used insulin. As of March 14, all 19 DM patients have been discharged, and no death occurred. Conclusions: DM patients with COVID-19 are vulnerable to severe disease, especially for female patients. High levels of HbA1c and proteinuria could be potential risk factors for severe COVID-19 in DM patients. In addition to timely systemic therapy, the control of blood glucose and proper diabetic therapy is essential to improve the prognosis of severe DM patients with COVID-19.


Assuntos
/complicações , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Criança , Pré-Escolar , China , Cuidados Críticos , Feminino , Hemoglobina A Glicada/análise , Hospitalização , Humanos , Lactente , Unidades de Terapia Intensiva , Masculino , Registros Médicos , Pessoa de Meia-Idade , Proteinúria , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
Mol Med Rep ; 23(3): 1, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33495827

RESUMO

MicroRNAs (miRs) are essential regulators of atherosclerosis (AS) development; however, the pathogenic roles of miR-140-5p during AS development are not completely understood. The present study investigated the effects of miR­140-5p on human vascular smooth muscle cells (VSMCs) and its target gene. miR-140-5p and roundabout guidance receptor 4 (ROBO4) mRNA expression levels were determined by performing reverse transcription-quantitative PCR. ROBO4 protein expression levels were analyzed via western blotting. Cell viability, migration, invasion and apoptosis were evaluated by conducting Cell Counting Kit-8, Transwell and flow cytometry assays, respectively. The binding of miR-140-5p to ROBO4 mRNA was verified using the dual-luciferase reporter assay. miR-140-5p was highly expressed in the plaque-containing artery tissues of patients with AS compared with healthy control tissues. Oxidized-low density lipoprotein (ox-LDL) treatment increased miR-140-5p expression and decreased ROBO4 expression in human VSMCs, which promoted VSMC viability, migration and invasion, but suppressed apoptosis compared with the control group. The effects of ox-LDL treatment on VSMCs were attenuated by miR-140-5p inhibitor. miR-140-5p directly bound to the 3'-untranslated region of ROBO4 mRNA. ROBO4 overexpression mitigated the effects of ox-LDL treatment on VSMC viability, migration, invasion and apoptosis. Therefore, the present study suggested that high level miR-140-5p expression promoted VSMC viability, migration, and invasion, and suppressed VSMC apoptosis by reducing ROBO4 gene expression. The present study provided novel insights into AS pathogenesis that may aid the development of new strategies for the treatment and prevention of AS.

7.
Bioresour Technol ; 323: 124607, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33385629

RESUMO

The high cost of carbon source limits the heterotrophic culture of Chlorella. In this study, broken rice was hydrolyzed into glucose. Then, the broken rice hydrolysate (BRH) was utilized for heterotrophic cultivation of C. vulgaris instead of glucose. Results showed that algal cells released H+ when they consumed NH4+, leading to a sharp decrease in pH. Growth inhibition by acid could be avoided by using a pH buffer. Adding alkaline reagents intermittently during culture could not only reduce the amount of pH stabilizer but also obtain increased biomass production. When using Tris as pH stabilizer, the biomass productivity of C. vulgaris in BRH was the largest (1.01 g/L/d), followed by NaOH (1.00 g/L/d), and Na2CO3 (0.95 g/L/d). Using BRH instead of glucose for heterotrophic cultivation of C. vulgaris could save 89.58% of the cost of culture medium. This study developed a novel strategy for cultivating C. vulgaris heterotrophically using BRH.


Assuntos
Chlorella vulgaris , Oryza , Biomassa , Carbono , Processos Heterotróficos
8.
J AOAC Int ; 104(1): 16-28, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33439979

RESUMO

BACKGROUND: Rice is an important staple food that is consumed around the world. Like many foods, the price of rice varies considerably, from very inexpensive for a low-quality product to premium pricing for highly prized varieties from specific locations. Therefore, like other foods it is vulnerable to economically motivated adulteration through substitution or misrepresentation of inferior-quality rice for more expensive varieties. OBJECTIVE: In this article we describe results of a research project focused on addressing potential food fraud issues related to rice supplies in China, India, Vietnam, and Ghana. Rice fraud manifests differently in each country; therefore, tailored solutions were required. METHOD: Here we describe a two-tiered testing regime of rapid screening using portable Near Infrared technology supported by second tier testing using mass spectrometry-based analysis of suspicious samples. RESULTS: Portable Near Infrared spectroscopy models and laboratory-based Gas Chromatography-Mass Spectrometry methods were developed to differentiate between: high-value Basmati rice varieties and their potential adulterants; six Geographic Indicated protected rice varieties from specific regions within China; various qualities of rice in Ghana and Vietnam; and locally produced and imported rice in Ghana. Furthermore, an Inductively Coupled Plasma-Mass Spectrometry method was developed to support the Chinese rice varieties methods as well as a Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry method for quality differentiation in Vietnam. CONCLUSIONS/HIGHLIGHTS: This two-tier approach can provide a substantially increased level of testing through rapid screening outside of the laboratory with the reassurance of corroborating mass spectrometry-based laboratory analysis to support decision making.

9.
World J Gastroenterol ; 26(46): 7299-7311, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33362385

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in the world. In our early clinical data and questionnaire analysis of NAFLD, it was found that the body mass index of some patients did not meet the diagnostic criteria for overweight or obesity. The consumption of high-temperature-processed foods such as fried food, hot pot and barbecue is closely related to the occurrence of nonobese NAFLD. Reducing the intake of this kind of food can reduce disease severity and improve prognosis. AIM: To explore the untargeted metabolomics characteristics of nonobese nonalcoholic fatty liver disease in Sprague-Dawley rats induced by high-temperature-processed feed. METHODS: Fifty-four male Sprague-Dawley rats were divided into three groups: The control group received a standard diet; the nonfried soybeans (NDFS) group received 60% NDFS and 40% basic feed and the dry-fried soybeans (DFS) group received 60% DFS and 40% basic feed. Six rats were sacrificed at week 4, 8, and 12 in each group. The food intake, body weight, Lee's index, liver index, serological index and hepatic histopathology were assessed. Untargeted metabolomics characteristics were used to analyze the changes in liver metabolites of rats at week 12. Correlations between metabolites and pathology scores between the DFS and control groups and between the DFS and NDFS groups were analyzed. We selected some of the metabolites, both within the pathway and outside of the pathway, to explain preliminarily the difference in liver pathology in the three groups of rats. RESULTS: There were no statistically significant differences in the food intake, body weight, Lee's index or serological index between the DFS group and the control group (P > 0.05). At week 8 and week 12, the steatosis scores in the DFS group were significantly higher than those in the other two groups (P < 0.05). At week 12, the liver index of the DFS group was the lowest (NDFS group vs DFS group, P < 0.05). The fibrosis score in the DFS group was significantly higher than those in the other two groups (P < 0.05). The correlation analysis of the liver pathology score and differential metabolites in the DFS and NDFS groups showed that there were 10 strongly correlated substances: Five positively correlated substances and five negatively correlated substances. The positively correlated substances included taurochenodeoxycholate-3-sulfate, acetylcarnitine, 20a,22b-dihydroxycholesterol, 13E-tetranor-16-carboxy-LTE4 and taurocholic acid. The negatively correlated substances included choline, cholesterane-3,7,12,25-tetrol-3-glucuronide, nicotinamide adenine dinucleotide phosphate, lysoPC [16:1 (9Z)] and glycerol 3-phosphate. The correlation analysis of the liver pathology score and differential metabolites in the DFS and control groups showed that there were 13 strongly correlated substances: Four positively correlated substances and 9 negatively correlated substances. The positively correlated substances included 4-hydroxy-6-eicosanone, 3-phosphoglyceric acid, 13-hydroxy-9-methoxy-10-oxo-11-octadecenoic acid and taurochenodeoxycholate-3-sulfate. The negatively correlated substances included lysoPC [16:1(9Z)], S-(9-hydroxy-PGA1)-glutathione, lysoPC [20:5 (5Z, 8Z, 11Z, 14Z, 17Z)], SM (d18:1/14:0), nicotinamide adenine dinucleotide phosphate, 5,10-methylene-THF, folinic acid, N-lactoyl-glycine and 6-hydroxy-5-methoxyindole glucuronide. CONCLUSION: We successfully induced liver damage in rats by using a specially prepared high-temperature-processed feed and explored the untargeted metabolomics characteristics.

10.
Front Cell Infect Microbiol ; 10: 586466, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33363051

RESUMO

The invasion and egress are two key steps in lytic cycle vital to the propagation of Toxoplasma gondii infection, and phosphorylation is believed to play important roles in these processes. However, the phosphoproteome of T. gondii at these two stages has not been characterized. In this study, we profiled the phosphoproteome of tachyzoites at the stages of "just invading" (JI) and "prior to egress" (PE) based on iTRAQ quantitative analysis, in which a total of 46 phosphopeptides, 42 phosphorylation sites, and 38 phosphoproteins were detected. In the comparison of PE vs. JI, 10 phosphoproteins were detected with their phosphorylation level significantly changed, and four of them were demonstrated to be significantly down-regulated at the transcriptional level. Bioinformatic analysis of these identified phosphoproteins suggested that phosphorylation-mediated modulation of protein function was employed to regulate the pathway of toxoplasmosis and metabolism and cellular processes correlated with tachyzoite's binding, location, and metabolism, and thus play vital roles in the parasite lytic cycle. Moreover, cytoskeletal network (CN)-associated Inner Membrane Complex (IMC1, IMC4, IMC6 and IMC12), Intravascular Network (IVN)-related GRAs (GRA2, GRA3, GRA7 and GRA12), and Parasitophorous Vacuole Membrane (PVM)-localized ROP5 were shown to be enriched at the central nodes in the protein interaction network generated by bioinformatic analysis, in which the phosphorylation level of IMC4, GRA2, GRA3, and GRA12 were found to be significantly regulated. This study revealed the main cellular processes and key phosphoproteins crucial for the invasion and egress of T. gondii, which will provide new insights into the developmental biology of T. gondii in vitro and contribute to the understanding of pathogen-host interaction from the parasite perspective.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33232225

RESUMO

The performance of most the clustering methods hinges on the used pairwise affinity, which is usually denoted by a similarity matrix. However, the pairwise similarity is notoriously known for its venerability of noise contamination or the imbalance in samples or features, and thus hinders accurate clustering. To tackle this issue, we propose to use information among samples to boost the clustering performance. We proved that a simplified similarity for pairs, denoted by a fourth order tensor, equals to the Kronecker product of pairwise similarity matrices under decomposable assumption, or provide complementary information for which the pairwise similarity missed under indecomposable assumption. Then a high order similarity matrix is obtained from the tensor similarity via eigenvalue decomposition. The high order similarity capturing spatial information serves as a robust complement for the pairwise similarity. It is further integrated with the popular pairwise similarity, named by IPS2, to boost the clustering performance. Extensive experiments demonstrated that the proposed IPS2 significantly outperformed previous similarity-based methods on real-world datasets and it was capable of handling the clustering task over under-sampled and noisy datasets.

12.
Aging (Albany NY) ; 122020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33232279

RESUMO

Aging is regarded as a dominant risk factor for cancer. Additionally, inflammation and asthenic immune surveillance with aging may facilitate tumor formation and development. However, few studies have comprehensively analyzed the relationship between aging-related genes (AGs) and the prognosis, inflammation and tumor immunity of head and neck squamous cell carcinoma (HNSCC). Here, we initially screened 41 differentially expressed AGs from The Cancer Genome Atlas (TCGA) database. In the training set, a prognosis risk model with seven AGs (APP, CDKN2A, EGFR, HSPD1, IL2RG, PLAU and VEGFA) was constructed and validated in the TCGA test set and the GEO set (P < 0.05). Using univariate and multivariate Cox regression analyses, we confirmed that risk score was an independent prognostic factor of HNSCC patients. In addition, a high risk score was significantly correlated with immunosuppression, and high expression of PLAU, APP and EGFR was the main factor. Furthermore, we confirmed that a high risk score was significantly associated with levels of proinflammatory factors (IL-1α, IL-1ß, IL-6 and IL-8) in HNSCC samples. Thus, this risk model may serve as a prognostic signature and provide clues for individualized immunotherapy for HNSCC patients.

13.
BMJ Open ; 10(11): e040305, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33234643

RESUMO

INTRODUCTION: Gestational diabetes mellitus (GDM) is a common gestational disease and an important global public health problem. GDM may affect the short-term and long-term health of offspring, but the associations between GDM and the neurodevelopment of offspring of mothers with GDM (OGDM) are still unclear, and studies based on the Chinese population are lacking. We aim to determine the associations between GDM and the neurodevelopment of OGDM by studying a cohort of OGDM and offspring of non-GDM mothers. METHODS AND ANALYSIS: The single-centre prospective cohort study is being conducted in China over 7 years. A total of 490 OGDM (GDM group) and 490 fromof healthy mothers (control group) will be enrolled during the same period. Baseline characteristics, neuropsychological development scores and clinical data at specific time points (at 0, 1, 3, 6, 12, 24, 36, 48, 60 and 72 months old) will be collected from the children in both groups until the age of 6 years. The associations between GDM and the neurodevelopment of OGDM from infancy to preschool age will be analysed using a multiple linear regression model adjusted for confounders. In addition, we will compare longitudinal data to further assess the effects of GDM on neurodevelopmental trajectories. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of the Children's Hospital of Chongqing Medical University (Approval Number: (2019) Institutional Review Board (IRB) (STUDY) No. 85). The findings of this study will be disseminated through open access journals, peer-reviewed journals and scientific meetings. TRIAL REGISTRATION NUMBER: NCT03997396.

14.
Mol Genet Genomic Med ; : e1553, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217155

RESUMO

BACKGROUND: Traboulsi syndrome is a rare disorder characterized by ectopia lentis and facial dysmorphism (large beaked nose), which was only reported in 18 individuals to date. It is caused by homozygous/compound heterozygous variants in the aspartate/asparagine-ß-hydroxylase (ASPH) gene, which hydroxylates the aspartic acid and asparagine in epidermal growth factor-like domains of various proteins. METHODS: Whole-exome and Sanger sequencing were used to identify the disease-causing gene of the patient in a consanguineous Chinese family. Domain analysis was applied to predict the impact of the variant on ASPH protein. RESULTS: Through exome and Sanger sequencing, we identified a novel homozygous ASPH variant (NM_004318.4:c.1910del/NP_004309.2: p.(Asn637MetfsTer15)) in the patient, which may lead to blockage of the ASPH function through truncating the AspH oxygenase domain of the ASPH protein and/or nonsense-mediated decay of the ASPH transcript. This is the first report of Traboulsi syndrome in a Chinese patient who was combined with ventricular septal defect, lung bullae, and recurrent spontaneous pneumothorax. CONCLUSION: Our results revealed the clinical characteristics of the first Chinese patient with Traboulsi syndrome. Additionally, our study expands the mutational spectrum of Traboulsi syndrome and provides information for clinical genetic counseling to this family.

15.
Respir Res ; 21(1): 297, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176795

RESUMO

BACKGROUND: As it is less known about the prevalence and characteristics of pain in the patients with interstitial lung disease (ILD), this paper aims at determining the characteristics of the pain in the patients with ILD. METHODS: Subjects with ILD and health controls with the matched ages and genders completed Short Form McGill Pain Questionnaire (SF-MPQ) and part of the Brief Pain Inventory (BPI) Short Form to elicit the characteristics of the pain. The patients with ILD were also assessed through Pulmonary Function Test, Six Minutes Walking Test (6MWT), modified Medical Research Council Dyspnea Scale (mMRC) for state of the illness and measured health-related quality of life (HRQoL) by Short Form-36 (SF-36) and psychological associations by Hospital Anxiety and Depression Scale (HADS). RESULTS: A total of 63 subjects with ILD and 63 healthy controls (HC) were recruited in our study. The prevalence of the pain was 61.9% in ILD versus 25.3% in HC (P = 0.005) and the median score of the pain rank index (PRI) in ILD was higher than that in HC (P = 0.014). Chest (46.1%) accounted for the highest of overall pain locations in subjects with ILD. Associated clinical factors for pain intensity in the patients with ILD included exposure history of risk factors of ILD, with a longer distance of 6MWD (≥ 250 m), and a higher mMRC score (2-4). The patients with ILD and pain are more likely to suffer impaired HRQoL (P = 0.0014) and psychological problems (P = 0.0017, P = 0.044). CONCLUSION: The pain is common in those with ILD and the pain intensity is associated with exposure history, 6MWD, and mMRC score. The patients with ILD and pain were possibly to suffer depression, anxiety, and impaired HRQoL.

16.
J Virol ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208452

RESUMO

Mites are notorious for being vectors transmitting infectious pathogens and source of allergens causing allergic conditions in animals and humans. However, despite their huge impact on public health, the virome of mites remains unknown. Here we characterized the virus diversity and abundance of 14 species of medically important mites based on total RNA sequencing data sets generated in this study as well as those deposited in the Sequence Read Archive (SRA) database. A total of 47 genetically distinct viruses were identified and classified into 17 virus families or virus super-groups, and the viral sequences accounted for as much as 29.67% of total non-rRNA transcriptome in one mite library. The most commonly identified viruses are members of Picornavirales, among which we revealed more than one type of viruses that are evolutionarily related to dicistronic viruses but contain a single open reading frame, thus likely representing a recent example of host (i.e., mite)-related parallel evolution from dicistronic to monocistronic genomic form within the family Dicistroviridae To our best knowledge, this is the first time to perform comprehensive and systematic screening of RNA virome in medically important mites including house dust mites (HDM). Overall, the RNA virome identified here provides not only significant insights into the diversity and evolution of RNA viruses in mites, but also a solid knowledge base for studying their roles in human diseases.IMPORTANCE Mites are important group of arthropods that are associated with a variety of human diseases including scrub typhus and asthma. However, it remains unclear whether or not mites carry viruses that might play a role in human infections or allergic disease. In this study, we used a total transcriptomics approach to characterize and compare the complete RNA virome within mites that are relevant to human health and diseases. Specifically, our data revealed a large diversity, a high abundance, and a flexible genomic evolution for these viruses. Although most of the viruses identified here are unknown to associate with human infectious disease, the abundant presence of viral RNAs may play an immunomodulatory role in the development of allergic reactions such as asthma during environmental exposure to mite allergens, and therefore provide important insights into the mite-induced allergy and preparation of mite allergen vaccines.

17.
Science ; 370(6521): 1208-1214, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33154107

RESUMO

We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo human angiotensin-converting enzyme 2 (hACE2) decoys to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The best monovalent decoy, CTC-445.2, bound with low nanomolar affinity and high specificity to the receptor-binding domain (RBD) of the spike protein. Cryo-electron microscopy (cryo-EM) showed that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, showed ~10-fold improvement in binding. CTC-445.2d potently neutralized SARS-CoV-2 infection of cells in vitro, and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge.

18.
Infect Drug Resist ; 13: 3907-3918, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33154656

RESUMO

Purpose: To summarize the clinical features and effective therapy of severe COVID-19 patients. Patients and Methods: In this retrospective, multicenter study, the medical records of COVID-19 patients in Hunan, from January 21, 2020 to February 19, 2020 were reviewed. Results: Of the 350 COVID-19 patients, 13.7% were severe cases. On admission, compared with non-severe patients, more severe patients had a neutrophil/lymphocyte ratio > 3 (58.3% vs 33.8%, P=0.001), D-dimer > 1 mg/L (41.7% vs 13.6%, P<0.0001), higher level of CRP (39.1 mg/L, IQR18.1-75.9 vs 13.4 mg/L, IQR5.0-32.8, P<0.0001), and multiple pneumonia on CT (77.1% vs 18.2%, P<0.0001). All severe patients received oxygen support. 95.8% of them received antivirals, and the most frequent therapy was lopinavir and ritonavir plus human interferon-α2b. Moxifloxacin was used in 70.8% severe patients. The total dosage of methylprednisolone sodium succinate was 640 mg (IQR 360-960) in severe patients, and the duration of use was 8.5 days (IQR 6.8-11.3). The total dosage of immunoglobulin was 80 g (IQR, 60-140) in severe patients, and the duration was 8.0 days (IQR, 6.0-11.5). As of March 15, 2020, 95.8% of the severe patients had been discharged and only two deaths occurred. Conclusion: The rate of severe cases and mortality of COVID-19 in Hunan are lower than those in Wuhan. In addition to antivirals and oxygen support, timely interventions including corticosteroids, immunoglobulin, and antibiotics, contribute to improving the prognosis of severe COVID-19 patients.

19.
J Magn Reson Imaging ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33179832

RESUMO

BACKGROUND: Accurate and noninvasive detection of isocitrate dehydrogenase (IDH, including IDH1 and IDH2) status is clinically meaningful for molecular stratification of glioma, but remains challenging. PURPOSE: To establish a model for classifying IDH status in gliomas based on multiparametric MRI. STUDY TYPE: Retrospective, radiomics. POPULATION: In all, 105 consecutive cases of grade II-IV glioma with 50 IDH1 or IDH2 mutant (IDHm) and 55 IDH wildtype (IDHw) were separated into a training cohort (n = 73) and a test cohort (n = 32). FIELD STRENGTH/SEQUENCE: Contrast-enhanced T1 -weighted (CE-T1 W), T2 -weighted (T2 W), and arterial spin labeling (ASL) images were acquired at 3.0T. ASSESSMENT: Two doctors manually labeled the volume of interest (VOI) on CE-T1 W, then T2 W and ASL were coregistered to CE-T1 W. A total of 851 radiomics features were extracted on each VOI of three sequences. From the training cohort, all radiomics features with age and gender were processed by the Mann-Whitney U-test, Pearson test, and least absolute shrinkage and selection operator to obtain optimal feature groups to train support vector machine models. The accuracy and area under curve (AUC) of all models for classifying the IDH status were calculated on the test cohort. Two subtasks were performed to verify the efficiency of texture features and the Pearson test in IDH status classification, respectively. STATISTICAL TESTS: The permutation test with Bonferroni correction; chi-square test. RESULTS: The accuracy and AUC of the classifier, which combines the features of all three sequences, achieved 0.823 and 0.770 (P < 0.05), respectively. The best model established by texture features only had an AUC of 0.819 and an accuracy of 0.761. The best model established without the Pearson test got an AUC of 0.747 and an accuracy of 0.719. DATA CONCLUSION: IDH genotypes of glioma can be identified by radiomics features from multiparameter MRI. The Pearson test improved the performance of the IDH classification models. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 1.

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