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1.
Brain ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31504254

RESUMO

N-methyl d-aspartate receptors are ligand-gated ionotropic receptors mediating a slow, calcium-permeable component of excitatory synaptic transmission in the CNS. Variants in genes encoding NMDAR subunits have been associated with a spectrum of neurodevelopmental disorders. Here we report six novel GRIN2D variants and one previously-described disease-associated GRIN2D variant in two patients with developmental and epileptic encephalopathy. GRIN2D encodes for the GluN2D subunit protein; the GluN2D amino acids affected by the variants in this report are located in the pre-M1 helix, transmembrane domain M3, and the intracellular carboxyl terminal domain. Functional analysis in vitro reveals that all six variants decreased receptor surface expression, which may underline some shared clinical symptoms. In addition the GluN2D(Leu670Phe), (Ala675Thr) and (Ala678Asp) substitutions confer significantly enhanced agonist potency, and/or increased channel open probability, while the GluN2D(Ser573Phe), (Ser1271Phe) and (Arg1313Trp) substitutions result in a mild increase of agonist potency, reduced sensitivity to endogenous protons, and decreased channel open probability. The GluN2D(Ser573Phe), (Ala675Thr), and (Ala678Asp) substitutions significantly decrease current amplitude, consistent with reduced surface expression. The GluN2D(Leu670Phe) variant slows current response deactivation time course and increased charge transfer. GluN2D(Ala678Asp) transfection significantly decreased cell viability of rat cultured cortical neurons. In addition, we evaluated a set of FDA-approved NMDAR channel blockers to rescue functional changes of mutant receptors. This work suggests the complexity of the pathological mechanisms of GRIN2D-mediated developmental and epileptic encephalopathy, as well as the potential benefit of precision medicine.

2.
Sci Rep ; 9(1): 11371, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31388081

RESUMO

The measurements of lysine metabolites provide valuable information for the rapid diagnosis of pyridoxine-dependent epilepsy (PDE). Here, we aimed to develop a sensitive method to simultaneously quantify multiple lysine metabolites in PDE, including α-aminoadipic semialdehyde (a-AASA), piperideine-6-carboxylate (P6C), pipecolic acid (PA) and α-aminoadipic acid (α-AAA) in plasma, serum, dried blood spots (DBS), urine and dried urine spots (DUS). Fifteen patients with molecularly confirmed PDE were detected using liquid chromatography-mass spectrometry (LC-MS/MS) method. Compared to the control groups, the concentrations of a-AASA, P6C and the sum of a-AASA and P6C (AASA-P6C) in all types of samples from PDE patients were markedly elevated. The PA and a-AAA concentrations ranges overlapped partially between PDE patients and control groups. The concentrations of all the analytes in plasma and serum, as well as in urine and DUS were highly correlated. Our study provided more options for the diverse sample collection in the biochemical tests according to practical requirements. With treatment modality of newly triple therapy investigated, biomarker study might play important role not only on diagnosis but also on treatment monitoring and fine tuning the diet. The persistently elevated analytes with good correlation between plasma and DBS, as well as urine and DUS made neonatal screening using DBS and DUS possible.

3.
Clin Rheumatol ; 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31273636

RESUMO

OBJECTIVES: To investigate the clinical features and potential risk factors of coronary involvement in Behçet's disease (BD). METHOD: In this case-control study, we retrospectively reviewed medical records of BD patients admitted to our institute from 2000 to 2016. Coronary involvement was documented by coronary angiography and (or) computed tomography angiography. We analyzed the demographic, clinical, and laboratory data and compared with age- and gender-matched BD patients without coronary involvement. RESULTS: Among 476 BD patients (296 males) enrolled, 19 (4.0%) patients (17 males) were diagnosed with coronary involvement. The median duration from onset of BD to coronary involvement was 2.8 years. Coronary stenosis, aneurysm, and occlusion were presented in 13, 9, and 3 patients, respectively. Multiple coronary artery stenoses and aneurysms were observed in 9 and 3 patients, respectively. Smoking (36.8%) was the major traditional risk factors. Male gender (89.5% vs 61.1%, p = 0.01), skin lesions (78.9% vs 55.3%, p = 0.08), pathergy reactions (36.8% vs 10.5%, p = 0.01), extra-cardiac vasculitis (36.8% vs 6.6% p < 0.01), elevated ESR (57.9% vs 34.2%, p = 0.01), and elevated CRP (63.2% vs 42.1%, p < 0.01) were more common in BD patients with coronary involvement comparing with those without coronary involvement. Multivariate analysis confirmed pathergy reaction (OR = 3.81, 95% CI 1.08-13.47) was the independent risk factor. CONCLUSIONS: Coronary involvement in BD patients is rare and male-predominant and is characterized by the aneurysm and multivessel involvement. Elevated ESR and CRP are frequent, and the pathergy reaction is the independent risk factor. Key Points • Coronary involvement in BD patients is rare and male-predominant. • Pathergy reaction is the risk factor for coronary involvement in BD patients.

4.
Biomed Pharmacother ; 118: 109225, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31325705

RESUMO

Lung cancer remains the leading cause of cancer associated deaths worldwide. Recent efforts have been focused on combinational and nanoparticulate therapies that can efficiently deliver multiple therapeutics. Herein, we reported cetuximab (CET) functionalized, paclitaxel (PTX) and 5-Demethylnobiletin (DMN) co-loaded nanostructured lipid carriers (NLCs) (CET-PTX/DMN-NLCs). The morphology, particle size, zeta potential, stability and drug release were tested. Cellular uptake, cell viability, synergistic effects and in vivo anti-tumor effects were evaluated on human lung adenocarcinoma cells (A549 cells), human embryonic lung cells (MRC-5 cells) and A549 paclitaxel-resistant cells bearing mice models. NLCs had sizes of around 130 nm and zeta potentials of +20-30 mV. The release of drugs from NLCs was relatively fast at the first 12 h and then became slow until completion of sustained release behavior. Cells uptake of CET-PTX/DMN-NLCs (65.8%) was remarkably higher than that of PTX/DMN-NLCs (35.5%) in A549 cells. The combination treatment with PTX and DMN synergistically decreases the viability of cells than the single PTX-NLCs and DMN-NLCs. CET-PTX/DMN-NLCs exhibited the most remarkable in vivo tumor inhibition efficiency, which suspended the tumor growth from 1010.23 to 211.18 mm3 at the end of the study. The highest tumor accumulation amount and low toxicity made CET-PTX/DMN-NLCs a promising system for the synergistic combination therapy of lung cancer.

5.
Seizure ; 69: 228-234, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31112829

RESUMO

PURPOSE: To summarize the clinical features and neuroimaging changes of epilepsy associated with TBC1D24 mutations. METHODS: Genetic testing was conducted in all epilepsy patients without acquired risk factors for epilepsy. Epilepsy patients identified with TBC1D24 compound heterozygous mutations by next-generation sequencing (NGS) epilepsy panel or whole exome sequencing (WES) were enrolled. The enrolled patients were followed up to summarize the clinical features. RESULTS: Nineteen patients were identified with TBC1D24 compound heterozygous mutations. Nine patients carried the same pathogenic variant c.241_252del. The seizure onset age ranged from 1 day to 8 months of age (median age 75 days). The most prominent features were multifocal myoclonus and epilepsia partialis continua (EPC). Myoclonus could be triggered by fever or infection in 15 patients, and could be terminated by sleep or sedation drugs. Psychomotor developmental delay was presented in 11 patients. Six patients exhibited hearing loss. Brain MRIs were abnormal in eight patients. Twelve patients were diagnosed with epilepsy syndromes including one patient who was diagnosed with Dravet syndrome. Two patients died due to status epilepticus at 4 months and 19 months of age, respectively. CONCLUSION: TBC1D24 mutation related epilepsy was drug-resistant. Multifocal myoclonus, EPC, and fever-induced seizures were common clinical features. Most patients presented psychomotor developmental delay. The neuroimaging abnormality and hearing loss could exacerbate during follow-up.

6.
Clin Genet ; 96(3): 207-215, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31066047

RESUMO

Congenital muscular dystrophies (CMDs) are clinically and genetically heterogeneous conditions. We launched a nationwide study to determine the frequency of CMD in the Chinese population and assess the status of diagnosis and disease management for CMD in China. Cases were chosen from databases in 34 tertiary academic hospitals from 29 first-level administrative divisions (provinces, municipalities, autonomous regions, and special administrative regions), and medical records were reviewed to confirm the diagnoses. The study included 409 patients, of those patients who consented to genetic testing (n = 340), mutations were identified in 286 of them. The most common forms identified were LAMA2-related CMD (36.4%), followed by COL6-related CMD (23.2%) and α-dystroglycanopathy (21.0%). The forms of CMD related to mutations in LMNA and SEPN1 were less frequent (12.5% and 2.4%, respectively). We also recorded a significant difference in the diagnostic capabilities and disease management of CMD, with this being relatively backward in research centers from less developed regions. We provide, for the first time, comprehensive epidemiologic information of CMD in a large cohort of Chinese people. To our knowledge, this is the largest sample size of its kind so far highlighting the prevalence of CMD in China.

7.
Epilepsy Res ; 154: 55-61, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31054517

RESUMO

This study aimed to identify monogenic mutations from Chinese patients with childhood absence epilepsy (CAE) and summarize their characteristics. A total of 100 patients with CAE were recruited in Peking University First Hospital from 2005 to 2016 and underwent telephone and outpatient follow-up review. We used targeted disease-specific gene capture sequencing (involving 300 genes) to identify pathogenic variations for these patients. We identified three de novo epilepsy-related gene mutations, including missense mutations of SCN1A (c. 5399 T > A; p. Val1800Asp), SCN8A (c. 2371 G > T; p. Val791Phe), and CLCN2 (c. 481 G > A; p. Gly161Ser), from three patients, separately. All recruited patients presented typical CAE features and good prognosis. To date, CAE has been considered a complex disease caused by multiple susceptibility genes. In this study, we observed that 3% of typical CAE patients had a de novo mutation of a known monogenic epilepsy-related gene. Our study suggests that a significant proportion of typical CAE cases may be monogenic forms of epilepsy. For genetic generalized epilepsies, such as CAE, further studies are needed to clarify the contributions of de novo or inherited rare monogenic coding, noncoding and copy number variants.

8.
Carbohydr Polym ; 213: 228-235, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30879664

RESUMO

As energy storage devices are becoming more highly integrated, it is inevitable that heat accumulation will occur under high power working conditions. Finding efficient thermal management materials for cooling down electronic components is an urgent problem for energy storage devices. In this work, a thermally conductive film with tailorable macroproperties is fabricated by using a simple vacuum filtration method, using cellulose nanofibrils as the polymer substrate and assembly with aluminum nitride nanosheets. The interaction between the cellulose nanofibrils and aluminum nitride nanosheets is studied, and the electronic components made using the composite exhibit excellent thermal conductivity, thermal stability and mechanical flexibility. A high thermal conductivity is achieved along the film surface (up to 4.20 W/mK for 25 wt.% of aluminum nitride). This green material can effectively promote potential applications as lateral heat spreaders in flexible energy storage devices and the thermal conductivity may facilitate the applications in thermal management.

9.
Clin Genet ; 96(1): 43-52, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30891744

RESUMO

Alternating hemiplegia of childhood (AHC) is a rare and severe neurodevelopmental disorder characterized by recurrent hemiplegic episodes. Most AHC cases are sporadic and caused by de novo ATP1A3 pathogenic variants. In this study, the aim was to identify the origin of ATP1A3 pathogenic variants in a Chinese cohort. In 105 probands including 101 sporadic and 4 familial cases, 98 patients with ATP1A3 pathogenic variants were identified, and 96.8% were confirmed as de novo. Micro-droplet digital polymerase chain reaction was applied for detecting ATP1A3 mosaicism in 80 available families. In blood samples, four asymptomatic parents, including two paternal and two maternal, and one proband with a milder phenotype were identified as mosaicism. Six (7.5%) parental mosaicisms were identified in multiple tissues, including four previously identified in blood and two additional cases identified from paternal sperms. Mosaicism was identified in multiple tissues with varied mutant allele fractions (MAFs, 0.03%-33.03%). The results suggested that MAF of mosaicism may be related to phenotype severity. This is the first systematic report of ATP1A3 mosaicism in AHC and showed mosaicism as an unrecognized source of previously considered "de novo" AHC. Identifying ATP1A3 mosaicism provides more evidence for estimating recurrence risk and has implications in genetic counseling of AHC.

10.
Carbohydr Polym ; 214: 1-7, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30925976

RESUMO

In this work, cellulase, low-concentration cold alkali and cellulase combined with cold alkali were used to pretreat unbleached bagasse pulp from which cellulose nanofibrils (CNFs), about 30 nm in diameter, were successfully prepared through ultrafine grinding and high-pressure homogenization. X-ray diffraction analysis showed that cellulase pretreatment increased the crystallinity of CNFs. After low-concentration cold alkali pretreatment, the crystallinity of CNFs significantly reduced and the crystal structure of the cellulose changed from type I to type II. Thermogravimetric analysis showed that CNFs prepared by cellulase combined with cold alkali treatment produced more regenerated cellulose and had lower thermal stability. The use of cellulase and low-concentration cold alkali pretreatments combined with ultrafine grinding and high-pressure homogenization is an environment-friendly method for preparing CNFs. The use of low-concentration cold alkali reduces the consumption of alkali and clean water.


Assuntos
Celulase/química , Celulose/química , Química Verde/métodos , Nanofibras/química , Cristalização , Estrutura Molecular , Tamanho da Partícula , Saccharum/química , Hidróxido de Sódio/química , Temperatura Ambiente
11.
Seizure ; 66: 26-30, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30776697

RESUMO

PURPOSE: This study aimed to investigate the genetic etiology of epilepsy in a cohort of Chinese children. METHODS: Targeted next-generation sequencing (NGS) was performed for 120 patients with unexplained epilepsy, including 71 patients with early-onset epileptic encephalopathies, and 16 patients with Dravet syndrome (including three patients with a Dravet-like phenotype) but without SCN1A pathogenic variants. RESULTS: Pathogenic variants of 14 genes were discovered in 22 patients (18%). A de novo KCND3 pathogenic variant (c.1174G > A, p.Val392Ile) was identified in a boy with refractory epilepsy, psychomotor regression, attention deficit, and visual decline. Pathogenic variants in other coding genes were excluded via whole exome sequencing. This KCND3 variant was previously confirmed to be pathogenic by Giudicessi, et al. However, the clinical profile was different: sudden death at 20 years old without any medical history of neurological disorders, nor with any diseases typically caused by KCND3 pathogenic variants such as Brugada syndrome, spinocerebellar ataxia type 19/22 or ataxia accompanied by epilepsy. This indicates that we have identified a new KCND3 phenotype. In addition, we also uncovered a GRIN1 pathogenic variant and a novel HCN1 pathogenic variant in the Dravet cohort. CONCLUSION: Our study highlights the significant utility of NGS panels in the genetic diagnosis of pediatric epilepsy. Our findings indicate that KCND3 pathogenic variants may be responsible for a wider phenotypic spectrum than previously thought, by including childhood epileptic encephalopathy. Furthermore, this study provides evidence that GRIN1 and HCN1 are candidate genes for Dravet and Dravet-like phenotypes.


Assuntos
Epilepsias Mioclônicas/genética , Mutação/genética , Canais de Potássio Shal/genética , Análise de Variância , Pré-Escolar , China , Estudos de Coortes , Análise Mutacional de DNA , Epilepsias Mioclônicas/diagnóstico por imagem , Feminino , Frequência do Gene , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Lactente , Imagem por Ressonância Magnética , Masculino , Proteínas do Tecido Nervoso/genética , Canais de Potássio/genética , Receptores de N-Metil-D-Aspartato/genética
12.
Spectrochim Acta A Mol Biomol Spectrosc ; 212: 300-307, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30660062

RESUMO

A novel fluorescent sensor based on g-C3N4 nanofibers for the sensitive detection of dopamine (DA) has been proposed. We synthesized g-C3N4 nanofibers by directly hydrolyzing bulk g-C3N4 in the alkaline atmosphere (3 M NaOH). The obtained ultrathin g-C3N4 nanofibers were verified by characterizations of Transmission electronic microscope (TEM), X-ray diffractometer (XRD), Fourier transformation-infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS). It was found that the fluorescence intensity of g-C3N4 nanofibers was obviously quenched by DA. Fluorescence resonance energy transfer (FRET) between DA and g-C3N4 nanofibers led to the fluorescence reduction of g-C3N4 nanofibers. The fluorescent probe based on g-C3N4 nanofibers exhibits linear responses to the concentration of DA in the range from 0 to 4 µM and 4 to 20 µM, the limit of detection is 17 nM. The fluorescent probe shows excellent stability, good selectivity with its application in serums.


Assuntos
Dopamina/análise , Corantes Fluorescentes/química , Grafite/química , Nanofibras/química , Compostos de Nitrogênio/química , Espectrometria de Fluorescência/métodos , Dopamina/sangue , Humanos , Concentração de Íons de Hidrogênio , Nanofibras/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
13.
Mult Scler Relat Disord ; 28: 4-10, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30529926

RESUMO

BACKGROUND: Some studies have reported clinical features of relapsing MOG-IgG-associated CNS demyelination principally in Caucasians children. It is not clear whether Chinese children share the same phenotype. OBJECTIVE: To delineate the clinical characteristics in Chinese children with relapsing MOG-IgG-associated demyelination. METHODS: A follow-up study on 23 Children with relapsing MOG-IgG-associated demyelination from two Chinese tertiary hospitals was performed. Phenotypic features at each demyelinating attacks, neuroimaging characteristics, autoimmune antibodies in CSF/serum, response to disease modifying drugs and functional deficits during the disease course were analyzed. RESULTS: The median age at disease onset was 5.38 (2.33-12.75) years. The male to female ratio was 1:1.30. The disease duration was 2.33(1.00-8.92) years at the last follow-up. (1) Clinical phenotypes: ADEM was the most common initial presentation (12/23, 52.17%). In 82 attacks during disease course, ADEM was also the most common phenotype (30/82, 36.59%), followed by ON (24/82, 29.27%). (2) Imaging findings: 57/70 (81.43%) brain MRI scans during acute attacks showed new lesions. The most common location of new lesions in brain was the juxtacortical white matter (45/57, 78.95%). In 46 brain MRI scans with supratentorial white matter lesions, ADEM-like patterns were most common (25/46, 54.35%), and 5/46 (10.87%) scans exhibited leukodystrophy-like patterns. (3) Laboratory examinations: Anti-NMDA receptor IgG in CSF was detected in two patients (2/12, 16.67%), with one patient presented with anti-NMDAR encephalitis associated symptoms. (4) Therapeutic responses and outcomes: In 19 patients treated with disease-modifying drugs (including rituximab, mycophenolate mofetil, azathioprine and so on) longer than 6 months, median annualised relapse rates decreased from 1.71 before treatment to 0.44 during treatment (P < 0.05), with eleven patients (11/19, 57.89%) having no relapses. Median EDSS score at the last follow-up was 1.0(0-3.5). Visual dysfunction (12/23, 52.17%) was the most common neurological sequela, with cognitive dysfunction and epilepsy in some of patients. CONCLUSIONS: The phenotypic features of Chinese children with relapsing MOG-IgG-associated CNS demyelination were similar to that in Caucasian children. ADEM was the most common phenotype in all demyelinating attacks, followed by ON. Cerebral lesions were common and extensive, manifested as ADEM-like or even leukodystrophy-like patterns. Visual dysfunction was the most common neurological sequela. Although some disease-modifying drugs could reduce ARR, optimal treatment needs future study.


Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Idade de Início , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , China , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/diagnóstico por imagem , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/epidemiologia , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/terapia , Feminino , Seguimentos , Humanos , Masculino , Recidiva , Resultado do Tratamento
14.
Adv Neurobiol ; 21: 247-266, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30334225

RESUMO

Epilepsy is one of the most common complex neurological diseases. It is frequently associated with intellectual and developmental disabilities (ID/DD). In recent years, copy number variation (CNV), especially microdeletion, was proven to be a potential key factor of genetic epilepsy. In this paper, the authors tested the hypothesis that the large de novo rare CNV is an important cause of epilepsy with ID/DD. We performed a custom array comparative genomic hybridization (aCGH) to detect the CNVs of 96 Chinese epileptic patients with ID/DD. The aCGH was designed with a higher density probe coverage of 320 genes known to be involved in epilepsy and ID/DD with lower density whole-genome backbone coverage. We detected 9 large de novo rare microdeletions from 8 patients. These CNVs are located on 2q24.1, 2q33.1-q34, 5q13.2 (2 similar CNVs), 5q33.1-q34, 17p13.2, 22q11.21-q11.22 (2 identical CNVs) and Xp22.31. We also found that only a few genes in the CNVs are known epilepsy related genes. By analysis with systems biology, we found most of the genes are interacting genes known to be epilepsy related genes. We also found a gene motif "BGNADP", constructed by BTD, GALNT10, NMUR2, AUTS2, DLG2 and PTPRD, would be a key motif in epilepsy and ID/DD. These findings strongly indicate that some large de novo rare microdeletion is an important pathological cause of epilepsy with ID/DD. Our study also found a gene motif "BGNADP" should be a key small network in epilepsy with ID/DD.

15.
J Med Genet ; 2018 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-30287595

RESUMO

BACKGROUND: Mutations in the PCDH19 gene have mainly been reported in female patients with epilepsy. To date, PCDH19 mutations have been reported in hundreds of females and only in 10 mosaic male epileptic patients with mosaicism. OBJECTIVE: We aimed to investigate the occurrence of mosaic PCDH19 mutations in 42 families comprising at least one patient with PCDH19-related epilepsy. METHODS: Two male patients with mosaic PCDH19 variants were identified using targeted next-generation sequencing. Forty female patients with PCDH19 variants were identified by Sanger sequencing and Multiple Ligation Probe Amplification (MLPA). Microdroplet digital PCR was used to quantify the mutant allelic fractions (MAFs) in 20 families with PCDH19 variants. RESULTS: Five mosaic individuals, four males and one female, were identified in total. Mosaic variant was confirmed in multiple somatic tissues from one male patient and in blood from the other male patient. Among 22 female patients harbouring a newly occurred PCDH19 variant identified by Sanger sequencing and MLPA, Sanger sequencing revealed two mosaic fathers (9%, 2/22), one with two affected daughters and the other with an affected child. Two asymptomatic mosaic fathers were confirmed as gonosomal mosaicism, with MAFs ranging from 4.16% to 37.38% and from 1.27% to 19.13%, respectively. In 11 families with apparent de novo variants, 1 female patient was identified as a mosaic with a blood MAF of 26.72%. CONCLUSION: Our study provides new insights into phenotype-genotype correlations in PCDH19 related epilepsy and the finding of high-frequency mosaicism has important implications for genetic counselling.

16.
BMJ Open ; 8(9): e021768, 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30269064

RESUMO

OBJECTIVE: Type 2 diabetes mellitus is increasing in young adults, and greater adiposity is considered a major risk factor. However, whether there is an association between obesity and diabetes and how this might be impacted by age is not clear. Therefore, we investigated the association between body mass index (BMI) and diabetes across a wide range of age groups (20-30, 30-40, 40-50, 50-60, 60-70 and ≥70 years old). DESIGN: We performed a retrospective cohort study using healthy screening programme data. SETTING: A total of 211 833 adult Chinese persons >20 years old across 32 sites and 11 cities in China (Shanghai, Beijing, Nanjing, Suzhou, Shenzhen, Changzhou, Chengdu, Guangzhou, Hefei, Wuhan, Nantong) were selected for the study; these persons were free of diabetes at baseline. PRIMARY AND SECONDARY OUTCOME MEASURES: Fasting plasma glucose levels were measured and information regarding the history of diabetes was collected at each visit. Diabetes was diagnosed as fasting plasma glucose ≥7.00 mmol/L and/or self-reported diabetes. Patients were censored at the date of diagnosis or the final visit, whichever came first. RESULTS: With a median follow-up of 3.1 years, 4174 of the 211 833 participants developed diabetes, with an age-adjusted incidence rate of 7.35 per 1000 persons. The risk of incident diabetes increased proportionally with increasing baseline BMI values, with a 23% increased risk of incident diabetes with each kg/m2 increase in BMI (95% CI 1.22 to 1.24). Across all age groups, there was a linear association between BMI and the risk of incident diabetes, although there was a stronger association between BMI and incident diabetes in the younger age groups (age×BMI interaction, p<0.0001). CONCLUSIONS: An increased BMI is also independently associated with a higher risk of developing diabetes in young adults and the effects of BMI on incident diabetes were accentuated in younger adults.

17.
Sci Rep ; 8(1): 12445, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30127385

RESUMO

Graphene has been widely utilized in optoelectronic applications due to its high carrier mobility, and extremely fast optical response. Microcavity-integrated graphene waveguide structure is one basic module of integrated photonic devices which can greatly improve the light-matter interaction strength. The enhanced optical absorption in the undoped graphene layer results from the light trapping and the corresponding long light-graphene interaction length. Tuning the Fermi energy level of the graphene layer enables the electro-optical modulation. We report the realization of reconfigurable electro-optical attenuator and switch with unity-order modulation depth in light reflection and transmission at near-infrared frequency. The transformation from a lossy absorber to a quasi-perfect transparent condition of the monolayer graphene by tuning the Fermi level leads to the unity-order tunability of the electro-optical attenuator and switch. We investigate theoretically and numerically the absorption properties of the designed microcavity-integrated graphene with respect to different graphene Fermi levels. Electro-optical attenuator with attenuating coefficient from 10% to 98.29% is fulfilled. On-off electro-optical switching with a switching contrast larger than 21 dB is demonstrated. Our approach provides the possibilities of graphene photonics applied in communications, and sensing.

18.
Int J Genomics ; 2018: 2361068, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30057904

RESUMO

Objective: Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA) that leads to severe physiologic and developmental problems. Our study is aimed at elucidating the clinical and genetic characteristics of Chinese MLD patients. Methods: Clinical data of 21 MLD patients was collected. All coding exons of ARSA and their flanking intronic sequences were amplified by polymerase chain reaction and subjected to direct sequencing. Results: All 21 patients were diagnosed with MLD clinically and genetically, out of which 17 patients were late infantile and 4 were juvenile types. A total of 34 ARSA mutations, including 28 novel mutations (22 missense, 1 splicing, 1 nonsense, 3 small insertions, and 1 small deletion mutation) and 6 known mutations (5 missense and 1 small insertion mutation), were identified. Prenatal diagnosis was performed for four pedigrees. One fetus was a patient, two fetuses were carriers, and two were wild type. Conclusions: The present study discovered 28 novel ARSA mutations and widely expanded the mutation spectrum of ARSA. Four successful prenatal diagnoses provided critical information for MLD families.

19.
Can Respir J ; 2018: 6328127, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29887927

RESUMO

Background/Aim: Few studies have reported the prognostic value of pretreatment hemoglobin levels in patients with lung adenocarcinoma (LA). In the present study, we retrospectively reviewed 306 LA patients for their prognosis associated with the pretreatment hemoglobin levels. Methods: Person-years and case fatality rate (CFR) were calculated from May 2010 to June 2017. Hazard ratio (HR) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazards regression analysis. Survival curves were generated using the Kaplan-Meier analysis. Results: Patients with low pretreatment hemoglobin (LPHb) levels had a higher CFR than did patients with normal pretreatment hemoglobin (NPHb) levels (HR = 1.48, 95% CI = 1.06-2.08, and P=0.023). Overall survival of NPHb patients was significantly higher than that of LPHb patients (P < 0.05). Conclusion: Low pretreatment hemoglobin level was demonstrated to be an independent biomarker for poor prognosis in patients with LA.

20.
Mol Clin Oncol ; 9(1): 44-49, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29896399

RESUMO

To date, few studies have reported the prognostic value of pre-treatment hemoglobin levels in patients with non-small cell lung cancer (NSCLC). In the present study, 416 patients with NSCLC were retrospectively reviewed. Univariate Cox proportional hazards regression analysis demonstrated that patients with normal pre-treatment hemoglobin (NPHb) levels had a greater chance of surviving for longer period, than did patients with low pre-treatment hemoglobin (LPHb) levels (HR, 2.05; 95% CI, 1.63-2.57; P<0.001). After adjustment for age, sex, tumor-node-metastasis stage, Karnofsky performance status, lung lobectomy, chemotherapy and radiotherapy, multivariate Cox proportional hazards regression analysis revealed that LPHb was an independent predictor for the poor prognosis of patients with NSCLC (HR, 1.86; 95% CI, 1.47-2.36; P<0.001). Estimation of the cumulative survival revealed that the overall survival of NPHb patients was significantly higher than that for LBHb patients (P<0.05), independent of whether the patients had received lung lobectomy or chemotherapy treatments. In conclusion, low pre-treatment hemoglobin levels were demonstrated to be an independent biomarker for poor prognosis in patients with NSCLC.

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