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1.
Am J Ophthalmol ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32059979

RESUMO

PURPOSE: To demonstrate the proper use of the Phansalkar's local thresholding method (Phansalkar method) in choriocapillaris (CC) quantification with optical coherence tomography angiography (OCTA). DESIGN: Retrospective, observational case series. METHODS: Swept source OCTA imaging was performed using 3x3 mm and 6x6 mm scanning patterns. The CC slab was extracted following semi-automatic segmentation of the retinal pigment epithelium/Bruch's membrane complex. Retinal projection artifacts were removed before further analysis, and CC OCTA images from drusen eyes were compensated using a previously published strategy. CC flow deficits (FDs) were segmented with two previously published algorithms: fuzzy C-means approach (FCM method) and Phansalkar method. With the Phansalkar method, different parameters were tested and a local window radius of 1-15 pixels was used. FD density (FDD), mean FD size (MFDS) and FD number (FDN) were calculated for comparison. RESULTS: Six normal eyes from six subjects and six eyes with drusen secondary to age-related macular degeneration from six subjects were analyzed. With both 3x3 mm and 6x6 mm scans from all eyes, the FD metrics were highly dependent on the selection of the local window radius when using the Phansalkar method. Larger window radii resulted in higher FDD values. FDN increased with the increase in the window radius but then decreased, with an inflection point at about 1 - 2 inter-capillary distances (ICDs). MFDS decreased then increased with increasing window radii. CONCLUSIONS: Multiple parameters, especially the local window radius, should be optimized before using the Phansalkar method for the quantification of CC FDs with OCTA imaging. It is recommended that the proper use of the Phansalkar method should include the selection of the window radius that is related to the expected ICD in normal eyes.

2.
Int J Infect Dis ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32068096

RESUMO

OBJECTIVE: We investigated the epidemiological characteristics of drug resistance and virulence factors of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from paediatric patients in Shanghai. METHODS: CRKP strains were consecutively collected between January and December in 2018. Antimicrobial susceptibility was determined by VITEK 2 compact. Polymerase chain reaction (PCR) was used to analyse drug resistance determinants, virulence genes and plasmid types. wzi sequencing and multilocus sequence typing was used to determinate clonal relatedness. RESULTS: Among 172 CRKP strains, blaKPC-2 and blaNDM-5 were the predominant carbapenemase genes. Compared with NDM-5, KPC-2 producers showed higher resistance rates to fluoroquinolones and aminoglycosides. Majority of KPC-2 producers belonged to KL64-ST11 background, while NDM-5 producers were mainly identified as KL62-ST48. Plasmid typing shown that IncF and IncFIB were the most prevalent plasmids in KPC-2 producers and IncX3 was widely spread in NDM-5-KP. Thirty-seven isolates carried various hypervirulence genes and the profiles of these genes showed high diversity. CONCLUSIONS: The predominant carbapenemase of CRKP strains from paediatric patients in Shanghai were KPC-2 and NDM-5. KL47-ST11 KPC-2-KP and KL62-ST48 NDM-5-KP were representative clonal lineages. Although not prevalent, hypervirulence associated genes have begun to spread. Active long-term surveillance should be performed in both drug resistance characteristics and virulence factors.

3.
Ophthalmol Retina ; 4(2): 204-215, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32033714

RESUMO

PURPOSE: To determine age-related changes in choroidal thickness and the volume of choroidal vessels and stroma using automated algorithms based on structural swept-source OCT (SS-OCT) scans. DESIGN: Prospective and observational study. PARTICIPANTS: The study included 144 normal participants with ages ranging from 20 to 88 years. METHODS: A previously reported strategy was used to automatically segment the choroid using SS-OCT structural images. Attenuation correction was applied on B-scans to enhance the choroidal contrast and facilitate more accurate automatic segmentation of the 3-dimensional choroidal vessel and stroma. The parameters that we investigated included mean choroidal thickness (MCT), choroidal vessel volume (CVV), choroidal stroma volume (CSV), choroid vascularity index (CVI), and the choroidal stroma-to-vessel volume ratio (CSVR). Correlations between MCT and choroidal vessel metrics of CVV, CSV, CVI, and CSVR were studied. Regional distributions of MCT and CVI were analyzed using a grid centered on the fovea. Age-related changes in MCT, CVV, CSV, and CVI were studied in the entire scanning region, as well as in the subregions of the grids. MAIN OUTCOME MEASURES: Age-related changes in MCT, CVV, CSV, and CVI using 6×6-mm and 12×12-mm SS-OCT scans. RESULTS: The automated choroid segmentations were validated against manual segmentations, and MCT measurements were shown to be in good agreement (P < 0.0001). Choroidal vessel volume and CSV showed significant correlations with MCT (all P < 0.0001). Interestingly, CVI and CSVR were constant, with little variation among all participants regardless of age and MCT (61.1±1.8% and 0.64±0.05, respectively). Measurements on 12×12-mm and 6×6-mm scans showed excellent agreement in all scan regions (all P < 0.0001). While choroidal thickness and choroidal volume, which includes both choroidal vessels and stroma, decrease with age (all P < 0.0001), the CVI and CSVR vary little among all ages in all regions. CONCLUSIONS: Whereas MCT, CVV, and CSV decrease with age, the CVI and CSVR remain constant in all regions with age. Ongoing studies are using these automated algorithms on SS-OCT structural datasets to investigate the diagnostic usefulness of these choroidal parameters in a myriad of ocular and systemic diseases.

4.
Am J Ophthalmol ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32006481

RESUMO

PURPOSE: Wide field swept source OCT angiography (WF SS-OCTA) imaging was compared with ultrawide-field (UWF) fluorescein angiography (FA) imaging to better understand changes in retinal non-perfusion before and after panretinal photocoagulation (PRP) in treatment-naïve eyes with proliferative diabetic retinopathy (PDR). DESIGN: Prospective, observational, consecutive case series. PARTICIPANTS: Patients with treatment-naïve PDR. METHODS: Patients were imaged using the SS-OCTA 12x12mm scan pattern at baseline and 1 week, 1 month, and 3 months after PRP. UWF FA was obtained at baseline and 3 months after PRP. Selected eyes were imaged using five SS-OCTA 12x12mm scans to create a posterior pole montage, and 5 eyes also underwent SS-OCTA imaging at 6 months and 1 year. Areas of retinal non-perfusion (RNP) were drawn independently by two masked graders, and analysis of variance (ANOVA) tests were used to compare areas of RNP over time. MAIN OUTCOME MEASURES: Area and boundaries of RNP visualized using WF SS-OCTA and UWF FA RESULTS: From January 2018 through January 2019, WF SS-OCTA was performed on 20 eyes with treatment-naïve PDR from 15 patients. Areas of RNP identified on UWF FA images co-localized with RNP areas visualized on WF SS-OCTA images. There were no statistically significant changes in RNP area on WF SS-OCTA images through 3 months after PRP. Even eyes that were severely ischemic at baseline had no significant changes in RNP area one year after PRP. CONCLUSIONS: RNP in PDR can be identified at baseline and imaged serially after PRP using WF SS-OCTA. Retinal perfusion in PDR does not change significantly after PRP. The ability of WF SS-OCTA to longitudinally evaluate RNP areas provides additional justification for adopting WF SS-OCTA as the sole imaging modality for clinical management of PDR.

5.
mSphere ; 5(1)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915216

RESUMO

The continuous emergence of novel New Delhi metallo-ß-lactamase-5 (NDM-5)-producing Enterobacteriaceae isolates is receiving more and more public attention. Twenty-two NDM-5-producing strains were identified from 146 carbapenemase-producing Enterobacteriaceae (CRE) strains isolated from pediatric patients between January and March 2017, indicating that the bla NDM-5 gene has spread to children. All 22 isolates, including 16 Klebsiella pneumoniae strains, four Klebsiella aerogenes strains, and two Escherichia coli strains, showed significantly high resistance to ß-lactam antibiotics (except aztreonam) but remained susceptible to tigecycline and colistin. K. pneumoniae and K. aerogenes strains were respectively defined as homologous clonal isolates by pulsed-field gel electrophoresis (PFGE). Multilocus sequence typing (MLST) results confirmed the genetic relatedness with all K. pneumoniae strains belonging to sequence type (ST) 48. Two E. coli isolates (ST617 and ST1236) were considered genetically unrelated. Twenty-two bla NDM-5 plasmids were positive for the IncX3 amplicon and showed almost identical profiles after digestion with HindIII and EcoRI. Four representative strains (K. pneumoniae K725, K. aerogenes CR33, E. coli Z214, and E. coli Z244) were selected for further study. Plasmids harboring bla NDM-5 showed strong stability in both clinical isolates and transconjugants, without apparent plasmid loss after 100 serial generations. S1-PFGE followed by Southern blot analysis demonstrated that the bla NDM-5 gene was located on an ∼46-kb plasmid. Plasmid sequences of pNDM-K725, pNDM-CR33, and pNDM-Z214 were almost identical but were slightly different from that of pNDM-Z244. Compared with pNDM-Z244, ΔISAba125 and partial copies of IS3000 were missing. The genetic backgrounds of the bla NDM-5 gene in four strains were slightly different from that of the typical pNDM_MGR194. This study comprehensively characterized the horizontal gene transfer of the bla NDM-5 gene among different Enterobacteriaceae isolates in pediatric patients, and the IncX3-type plasmid was responsible for the spread.IMPORTANCE The emergence of CRE strains resistant to multiple antibiotics is considered a substantial threat to human health. Therefore, all the efforts to provide a detailed molecular transmission mechanism of specific drug resistance can contribute positively to prevent the further spread of multidrug-resistant bacteria. Although the new superbug harboring bla NDM-5 has been reported in many countries, it was mostly identified among E. coli strains, and the gene transfer mechanism has not been fully recognized and studied. In this work, we identified 22 bla NDM-5-positive strains in different species of Enterobacteriaceae, including 16 Klebsiella pneumoniae strains, four Klebsiella aerogenes strains, and two Escherichia coli strains, which indicated the horizontal gene transfer of bla NDM-5 among Enterobacteriaceae strains in pediatric patients. Moreover, bla NDM-5 was located on a 46-kb IncX3 plasmid, which is possibly responsible for this widespread horizontal gene transfer. The different genetic contexts of the bla NDM-5 gene indicated some minor evolutions of the plasmid, based on the complete sequences of the bla NDM-5 plasmids. These findings are of great significance to understand the transmission mechanism of drug resistance genes, develop anti-infection treatment, and take effective infection control measures.

6.
Fitoterapia ; 140: 104431, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31759031

RESUMO

Two novel heptanornemoralisin-type diterpenoids nornemoralisins A (1) and B (2), together with two known compounds nemoralisin (3) and nemoralisin A (4), were isolated from the stem bark and leaves of Aphanamixis polystachya (Wall.) R. Parker. Their structures were established through comprehensive analyses of NMR spectroscopic data and high resolution mass spectrometric (HR-ESI-MS) data. The absolute configurations of carbon stereocenters were elucidated by circular dichroism (CD) analyses. The four compounds were tested for their potential cytotoxic effects against ACHN, HeLa, SMMC-7721, and MCF-7 cell lines. Nornemoralisins A (1) and B (2) exhibited significant cytotoxicity on ACHN with an IC50 value of 13.9 ± 0.8 and 10.3 ± 0.4 µM, respectively, and other compounds failed to reveal obvious cytotoxicity on the tested cell lines, compared to positive control vinblastine (IC50, 28.0 ± 0.9 µM).


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Meliaceae/química , Antineoplásicos Fitogênicos/isolamento & purificação , China , Diterpenos/isolamento & purificação , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Folhas de Planta/química
7.
Am J Ophthalmol ; 209: 18-26, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31562858

RESUMO

PURPOSE: Choriocapillaris (CC) imaging of normal eyes with swept-source optical coherence tomographic angiography (SS-OCTA) was performed, and the percentage of CC flow deficits (FD%) and the average area of CC flow deficits (FDa) were compared within the given macular regions. DESIGN: A prospective, cross-sectional study. METHODS: Subjects with normal eyes ranging in age from their 20s through their 80s were imaged with SS-OCTA (PLEX Elite 9000; Carl Zeiss Meditec, Dublin, California, USA) using both 3×3-mm and 6×6-mm macular scan patterns. The CC images were generated using a previously published and validated algorithm. In both 3×3-mm and 6×6-mm scans, the CC FD% and FDa were measured in circular regions centered on the fovea with diameters as 1 mm and 2.5 mm (C1 and C2.5). In 6×6-mm scans, the FD% and FDa were measured within an additional circular region with diameter as 5 mm (C5). The correlations between FD% and FDa from each region were analyzed with Pearson correlation coefficients. RESULTS: A total of 164 eyes were analyzed. There was excellent correlation between CC FDa and FD% measurements from each region. In the 3×3-mm scans, the correlations in the C1 and C2.5 regions were 0.83 and 0.90, respectively. In the 6×6-mm scans, the correlations in C1, C2.5, and C5 regions were 0.90, 0.89, and 0.89, respectively. CONCLUSIONS: When measuring CC FDs, we found excellent correlations between FDa and FD% in regions from 3×3-mm and 6×6-mm scans. Further studies are needed to determine if one parameter is more useful when studying diseased eyes.

8.
J Alzheimers Dis ; 73(3): 909-917, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31884461

RESUMO

 Exosomes are nano-sized extracellular vesicles that are secreted by cells and usually found in body fluids. Since they freely cross the blood-brain barrier, neuronal exosomes respond directly to changes in the brain's environment. Recent studies have shown that exosomes contain both amyloid-ß (Aß) and tau proteins and have a controversial role in the Alzheimer's disease (AD) process. In this study, enzyme-linked immunosorbent assay was used to detect the levels of P-S396-tau and Aß1-42 in plasma exosomes. We found that levels of P-S396-tau and Aß1-42 in plasma exosomes of AD patients were significantly higher compared to those in matched healthy controls. The difference between plasma exosomes of AD patients and those of matched healthy controls was determined using transmission electron microscopy and nanoparticle tracking analysis. Exosomes from AD patients were smaller and lower in quantity. These data together may provide a basis for early diagnosis of AD.

9.
Epidemiol Infect ; 147: e325, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31858924

RESUMO

Influenza activity is subject to environmental factors. Accurate forecasting of influenza epidemics would permit timely and effective implementation of public health interventions, but it remains challenging. In this study, we aimed to develop random forest (RF) regression models including meterological factors to predict seasonal influenza activity in Jiangsu provine, China. Coefficient of determination (R2) and mean absolute percentage error (MAPE) were employed to evaluate the models' performance. Three RF models with optimum parameters were constructed to predict influenza like illness (ILI) activity, influenza A and B (Flu-A and Flu-B) positive rates in Jiangsu. The models for Flu-B and ILI presented excellent performance with MAPEs <10%. The predicted values of the Flu-A model also matched the real trend very well, although its MAPE reached to 19.49% in the test set. The lagged dependent variables were vital predictors in each model. Seasonality was more pronounced in the models for ILI and Flu-A. The modification effects of the meteorological factors and their lagged terms on the prediction accuracy differed across the three models, while temperature always played an important role. Notably, atmospheric pressure made a major contribution to ILI and Flu-B forecasting. In brief, RF models performed well in influenza activity prediction. Impacts of meteorological factors on the predictive models for influenza activity are type-specific.

10.
Sci Rep ; 9(1): 19571, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31862956

RESUMO

We depicted the epidemiological characteristics of infectious diarrhoea in Jiangsu Province, China. Generalized additive models were employed to evaluate the age-specific effects of etiological and meteorological factors on prevalence. A long-term increasing prevalence with strong seasonality was observed. In those aged 0-5 years, disease risk increased rapidly with the positive rate of virus (rotavirus, norovirus, sapovirus, astrovirus) in the 20-50% range. In those aged > 20 years, disease risk increased with the positive rate of adenovirus and bacteria (Vibrio parahaemolyticus, Salmonella, Escherichia coli, Campylobacter jejuni) until reaching 5%, and thereafter stayed stable. The mean temperature, relative humidity, temperature range, and rainfall were all related to two-month lag morbidity in the group aged 0-5 years. Disease risk increased with relative humidity between 67-78%. Synchronous climate affected the incidence in those aged >20 years. Mean temperature and rainfall showed U-shape associations with disease risk (with threshold 15 °C and 100 mm per month, respectively). Meanwhile, disease risk increased gradually with sunshine duration over 150 hours per month. However, no associations were found in the group aged 6-19 years. In brief, etiological and meteorological factors had age-specific effects on the prevalence of infectious diarrhoea in Jiangsu. Surveillance efforts are needed to prevent its spread.

11.
J Sep Sci ; 2019 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-31867785

RESUMO

Garcinia multiflora is a kind of evergreen tree which is widely distributed in the south of China. However, few researches focused on the constituents in different parts of G. multiflora as well as their potential targets and pathways in vivo. To clarify the chemical constituents of G. multiflora rapidly and predict the potential targets as well as pathways in vivo that this plant may have effects on, a feasible and accurate strategy was developed to identify the chemical constituents in fruits, leaves, and branches of G. multiflora by ultra-high performance liquid chromatography with Q-Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry. Network pharmacology was then employed and a "compounds-targets-diseases" network was established. Sixty-one compounds including polycyclic polyprenylated acylphloroglucinols, xanthones, and flavonoids were finally identified in different parts of G. multiflora, and the contents of seven constituents were quantified, respectively. On the basis of the network pharmacology analysis results, compounds in this plant were speculated to have potential pharmacodynamic effect on cancer, inflammatory, respiratory diseases, cardiovascular diseases, and metabolic diseases. This research will provide a new method for the advanced study on the pharmacodynamic materials basis of G. multiflora, and offer valuable evidences for medicinal purpose of this plant.

12.
Front Pharmacol ; 10: 1266, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749700

RESUMO

Trepibutone was widely used for cholelithiasis, cholecystitis, biliary tract dyskinesia, cholecystectomy syndrome, and chronic pancreatitis in clinic. However, few investigations on trepibutone have been conducted. In this study, an accurate, sensitive, and selective analytical method was developed and successfully applied to assess the pharmacokinetic behavior of trepibutone in rats. Trepibutone and carbamazepine (internal standard, IS) were quantified using multiple reaction monitoring (MRM) mode with the transitions of m/z 311.09→265.08 and m/z 237.06→194.08, respectively. The linearity, precision, accuracy, extraction recovery, matrix effect, and stability of the established method were all excellent within acceptable range. A total of 30 metabolites were identified in plasma and urine by Q-Exactive high resolution mass spectrometry, and several common metabolic pathways were observed such as dealkylation, oxidation, reduction, glucuronidation, and so on. This research provides more information on trepibutone in pharmacodynamics and toxicology and will assist the usage of trepibutone in clinical.

13.
ACS Appl Mater Interfaces ; 11(50): 46536-46547, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31751119

RESUMO

Local hypoxia in solid malignancies often results in resistance to radiotherapy (RT) and chemotherapy (CT), which may be one of the main reasons for their failure in clinical application. Especially, oxygen is an essential element for enhancing DNA damage caused by ionizing radiation in radiotherapy. Here, two biomimetic oxygen delivery systems were designed by encapsulating hemoglobin (Hb) alone into a liposome (Hb-Lipo) or co-encapsulating Hb and doxorubicin (DOX) into a liposome (DOX-Hb-Lipo). Our data indicated that both Hb-Lipo and DOX-Hb-Lipo could effectively alleviate hypoxia in tumors. We demonstrated that RT plus tumor-targeting delivery of oxygen mediated by Hb-Lipo could significantly overcome the tolerance of hypoxic cancer cells to RT, showing significantly enhanced cancer-cell killing and tumor growth inhibition ability, mainly attributing to hypoxia alleviation and increased reactive oxygen species production under RT in cancer cells. Furthermore, a melanoma model that was quite insensitive to both RT and CT was used to test the efficacy of chemoradiotherapy combined with hypoxia alleviation. RT plus Hb-Lipo only caused a limited increase in antitumor activity. However, extremely strong tumor inhibition could be obtained by RT combined with DOX-Hb-Lipo-mediated CT, attributed to radio-triggered DOX release and enhanced immunogenic cell death induced by RT under an oxygen supplement. Our study provided a valuable reference for overcoming hypoxia-induced radioresistance and a useful therapeutic strategy for cancers that are extremely insensitive to chemo- or radiotherapy.

14.
ACS Omega ; 4(17): 17295-17300, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31656903

RESUMO

Au2n Cl- (n = 1-4) clusters are investigated by both laser ablation mass spectrometry and theoretical calculations. It is interesting to find that the electron affinities of neutral Au2n Cl (n = 1-4) clusters are much larger than those of corresponding pure Au2n clusters. Among them, the electron affinity of Au2Cl is 4.02 eV, which can be defined as a very unique superhalogen that is quite different from classical ones of M n X m (M = metal, X = halogen, and n < m). Natural bond orbital and highest occupied molecular orbital analyses indicate that the extra electron is predominantly delocalized over the positively charged metal moiety in these anionic Au2n Cl- clusters, which is the main reason for the large electron affinities of the corresponding neutral species.

15.
BMC Infect Dis ; 19(1): 828, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590636

RESUMO

BACKGROUND: Hand, foot and mouth disease (HFMD) is a rising public health problem and has attracted considerable attention worldwide. The purpose of this study was to develop an optimal model with meteorological factors to predict the epidemic of HFMD. METHODS: Two types of methods, back propagation neural networks (BP) and auto-regressive integrated moving average (ARIMA), were employed to develop forecasting models, based on the monthly HFMD incidences and meteorological factors during 2009-2016 in Jiangsu province, China. Root mean square error (RMSE) and mean absolute percentage error (MAPE) were employed to select model and evaluate the performance of the models. RESULTS: Four models were constructed. The multivariate BP model was constructed using the HFMD incidences lagged from 1 to 4 months, mean temperature, rainfall and their one order lagged terms as inputs. The other BP model was fitted just using the lagged HFMD incidences as inputs. The univariate ARIMA model was specified as ARIMA (1,0,1)(1,1,0)12 (AIC = 1132.12, BIC = 1440.43). And the multivariate ARIMAX with one order lagged temperature as external predictor was fitted based on this ARIMA model (AIC = 1132.37, BIC = 1142.76). The multivariate BP model performed the best in both model fitting stage and prospective forecasting stage, with a MAPE no more than 20%. The performance of the multivariate ARIMAX model was similar to that of the univariate ARIMA model. Both performed much worse than the two BP models, with a high MAPE near to 40%. CONCLUSION: The multivariate BP model effectively integrated the autocorrelation of the HFMD incidence series. Meanwhile, it also comprehensively combined the climatic variables and their hysteresis effects. The introduction of the climate terms significantly improved the prediction accuracy of the BP model. This model could be an ideal method to predict the epidemic level of HFMD, which is of great importance for the public health authorities.


Assuntos
Epidemias , Previsões/métodos , Doença de Mão, Pé e Boca/epidemiologia , China/epidemiologia , Confiabilidade dos Dados , Humanos , Incidência , Modelos Estatísticos , Estudos Prospectivos , Chuva , Temperatura Ambiente
16.
Med Sci Monit Basic Res ; 25: 199-209, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31554780

RESUMO

BACKGROUND This study aimed to identify NOTCH3 mutations and describe the genetic and clinical features and magnetic resonance imaging results in 11 unrelated patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) from Henan province in China. MATERIAL AND METHODS NOTCH3 was directly sequenced in 11 unrelated patients of Chinese descent. The clinical presentations and magnetic resonance imaging features were retrospectively analyzed in the 11 index patients with a definite diagnosis. RESULTS Seven different mutations were identified in 11 unrelated patients, including 4 novel mutations (p.P167S, p.P652S, p.C709R, and p.R1100H) in China and 3 reported mutations (p.C117R, p.R578C, and p.R607C). Four novel mutations (p.P167S, p.P652S, p.C709R, and p.R1100H) were predicted to be probably pathogenic using an online pathogenicity prediction program through comprehensive analysis. Clinical presentations in symptomatic patients included stroke, cognitive decline, psychiatric disturbances, and migraine. Multiple lacunars infarcts and leukoaraiosis were detected on MRI in most symptomatic patients, while white-matter lesions were identified in the temporal pole or the external capsule in all affected patients. CONCLUSIONS The mutation spectrum of CADASIL patients from Henan province in China displayed some differences from that of those reported previously. DNA sequencing was used to diagnose all 11 patients as having CADASIL, and we found 4 novel mutations. The present results further contribute to the enrichment of NOTCH3 mutation databases.

17.
Food Funct ; 10(10): 6644-6654, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31556417

RESUMO

Sulfated polysaccharides (CCPS) obtained from Cipangopaludina chinensis have a certain protective effect on cardiovascular diseases, but whether they can slow down the development of atherosclerosis (AS) and how they work are still unclear. In this study, we aimed to determine the preventive effects of CCPS on high-fat-diet (HFD)-induced AS in mice and the underlying mechanism focusing on gut microbiota profile modulation. First, male apolipoprotein E knockout mice were fed HFD or normal diet and simultaneously intervened by a blank solvent, CCPS or atorvastatin to last for 12 weeks. Then, the histopathological characteristics, biochemical parameters and gut microbiota compositions of the experimental groups were compared. The results demonstrated that the CCPS supplementation significantly improved HFD-induced AS of the mice, which was mainly manifested by regulating the plasma lipid balance, decreasing the atherosclerotic index and reducing the atherosclerotic plaque area in a dose-dependent manner. Mechanistic analysis revealed that CCPS regulated the bacterial composition including reducing the ratio of Firmicutes/Bacteroidetes, decreasing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria. Furthermore, through environmental factor correlation analysis, we found that the preventive effects of CCPS on AS in mice induced by HFD were closely related to reshaping the composition of gut microbiota.

18.
Environ Sci Pollut Res Int ; 26(30): 31434-31448, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31478176

RESUMO

As the pillar of national economy, manufacturing industry is the largest primary energy consumer and emitter of carbon dioxide (CO2) in China. Therefore, capturing the determinants of CO2 emissions in manufacturing industry is extremely important for national efforts to mitigate carbon emissions. This paper explores the major driving forces behind CO2 emission changes in China's manufacturing industry during 2000-2015 from perspectives of the whole sector and 28 subsectors, by applying the temporal logarithmic mean Divisia index (LMDI) method. Moreover, an intersectoral LMDI model is built to uncover the intersectoral discrepancies of CO2 emissions among 28 subsectors. The temporal analysis indicates that industrial activity and energy intensity are crucial factors respectively contributing to the increase and mitigation of CO2 emissions. The intersectoral analysis reveals that energy intensity is the dominant factor responsible for the intersectoral discrepancies of CO2 emissions among 28 subsectors. The great mitigation towards CO2 emissions can be achieved if energy efficiency is largely improved in carbon-intensive subsectors. Priority should be given by governments to the industrial technology advancement, such as subsidies for energy-saving technological transformation and promotion of international advanced techniques and equipment, which can greatly improve production efficiency and mitigate emissions in manufacturing industry.


Assuntos
Dióxido de Carbono/análise , Indústria Manufatureira/estatística & dados numéricos , China , Comércio , Indústrias , Tecnologia
19.
Ophthalmic Surg Lasers Imaging Retina ; 50(8): 474-484, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415693

RESUMO

BACKGROUND AND OBJECTIVE: To demonstrate the utility of widefield swept-source optical coherence tomography angiography (SS-OCTA) for the diagnosis and management of proliferative diabetic retinopathy (PDR). PATIENTS AND METHODS: Consecutive patients with vision-threatening diabetic retinopathy were imaged with widefield SS-OCTA using the 12 mm × 12 mm scan pattern. RESULTS: Twenty-four eyes of 12 patients underwent SS-OCTA imaging. In all 24 eyes, the en face total retinal flow images detected areas of decreased retinal perfusion, and the en face vitreoretinal interface (VRI) slabs detected foci of retinal neovascularization (NV). NV was treated and followed using the VRI images. CONCLUSIONS: Widefield SS-OCTA is a useful, noninvasive technology for the detection and monitoring of NV in PDR. Features of interest, such as areas of decreased retinal perfusion, increased retinal thickness, and NV, can be identified from different en face slabs extracted from a single 12 mm × 12 mm scan. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:474-484.].


Assuntos
Diabetes Mellitus , Retinopatia Diabética/diagnóstico , Técnicas de Diagnóstico Oftalmológico , Angiofluoresceinografia/métodos , Neovascularização Retiniana/diagnóstico , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vasos Retinianos/fisiopatologia
20.
Curr Alzheimer Res ; 16(8): 764-769, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31385772

RESUMO

BACKGROUND: The rate of occurrence of Alzheimer's disease is increasing around the world. However, there is still no significant breakthrough in the study of its etiology and pathogenesis. OBJECTIVE: To screen Alzheimer's disease pathogenic genes, which may be conducive to the elucidation of the pathogenic mechanisms of Alzheimer's disease And predict the pathogenicity by various computer software. METHODS: Clinical and neuroimaging examination, Whole Exome Sequencing, and Sanger sequencing were performed in the proband. Mutation sites were verified in 158 subjects. RESULTS: We reported a proband carrying a probably novel pathogenic mutation, which clinically manifests as progressive memory loss, visual-spatial disorders, apraxia, psychobehavioral disorders, and temperamental and personality changes. Whole Exome Sequencing detected a novel missense mutation at codon 222 (Q222L), which is a heterozygous A to T point mutation at position 665 (c.665A>T) in exon 5 of the presenilin 1 leading to a glutamine-to-leucine substitution. The mutation was also identified by Sanger sequencing in one family member; nevertheless, it was not detected in the other 7 unaffected family members, 50 sporadic Alzheimer's disease patients and 100 control subjects. CONCLUSION: A novel mutation in exon 5 of the presenilin 1 gene (Gln222Leu) in a Chinese family with early-onset Alzheimer's disease has been reported, besides, it was predicted that the missense mutation was probably a novel pathogenic mutation that was reported for the first time in a Chinese family with early-onset Alzheimer's disease.

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