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1.
Materials (Basel) ; 13(18)2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-32961783

RESUMO

Various defects during the manufacture of a high-energy laser monocrystalline silicon reflector will increase the energy absorption rate of the substrate and worsen the optical properties. Micron-scale or larger manufacturing defects have been inhibited by mechanism study and improvement in technology, but the substrate performance still fails to satisfy the application demand. We focus on the changes in the optical properties affected by nanoscale and Angstrom lattice defects on the surface of monocrystalline silicon and acquire the expected high reflectivity and low absorptivity through deterministic control of its defect state. Based on the first principles, the band structures and optical properties of two typical defect models of monocrystalline silicon-namely, atomic vacancy and lattice dislocation-were analyzed by molecular dynamics simulations. The results showed that the reflectivity of the vacancy defect was higher than that of the dislocation defect, and elevating the proportion of the vacancy defect could improve the performance of the monocrystalline silicon in infrared (IR) band. To verify the results of simulations, the combined Ion Beam Figuring (IBF) and Chemical Mechanical Polishing (CMP) technologies were applied to introduce the vacancy defect and reduce the thickness of defect layer. After the process, the reflectivity of the monocrystalline silicon element increased by 5% in the visible light band and by 12% in the IR band. Finally, in the photothermal absorption test at 1064 nm, the photothermal absorption of the element was reduced by 80.5%. Intense laser usability on the monocrystalline silicon surface was achieved, and the effectiveness and feasibility of deterministic regulation of optical properties were verified. This concept will be widely applied in future high-energy laser system and X-ray reflectors.

2.
Clin Epidemiol ; 12: 737-744, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765108

RESUMO

Purpose: To assess the relative risk of metabolic risk factors in patients stratified by psoriasis severity compared with population controls. Patients and Methods: A retrospective cohort study was conducted using national Swedish registers. Adult patients with psoriasis were selected if they had a dispensing of anti-psoriasis prescription (2007-2013) and at least one diagnosis within five years before the dispensing date. The patients with psoriasis were matched 1:10 to controls from the general population on birth year, sex, and county. The cohort was further divided into three disease severity groups (mild, moderate, or severe) based on their dispensed anti-psoriasis medication. Subjects were followed from the index date until censoring. We applied flexible parametric modeling to understand the risks of the incident comorbidities hypertension, hypercholesterolemia, and diabetes mellitus among patients with psoriasis from 6 months through 10 years. Hazard ratios and predicted risk (ie, 1 minus the survival probability) of comorbidities were reported. Results: The hazard of hypertension, hypercholesterolemia, and diabetes mellitus is higher among psoriasis patients compared with population controls, and the hazard ratio increases with psoriasis severity. For example, HRs of hypertension for patients with mild, moderate, and severe psoriasis are 1.29 (95% CI: 1.27-1.32), 1.35 (95% CI: 1.32-1.38), and 1.73 (95% CI: 1.64-1.82), respectively. The predicted risk of hypertension, hypercholesterolemia, and diabetes mellitus among patients with severe psoriasis at year ten was 0.58 (95% CI: 0.56, 0.59), 0.33 (95% CI: 0.32, 0.35), and 0.21 (95% CI: 0.20, 0.23), respectively, while it was 0.42 (0.41, 0.43), 0.23 (0.22, 0.23), 0.11 (0.10, 0.11) among controls, respectively. The predicted risk at year ten was similar among patients with mild or moderate psoriasis. Conclusion: The HRs and predicted risks of metabolic risk factors are higher among patients with psoriasis compared with matched controls and are more prominent among the severe psoriasis group.

3.
Medicine (Baltimore) ; 99(29): e21179, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702877

RESUMO

Nowadays most of the hepatitis B virus (HBV) infected population are adults, among which hepatitis B e antigen (HBeAg) negative infection occupied the largest proportion of HBV infection in China. HBeAg-negative patients are heterogeneous, and the corresponding interventions are different. Therefore, it is worth researching the infection characteristics of HBeAg-negative patients to help guide the interventions.A total of 11,738 treatment-naïve HBeAg-negative adult patients were randomly selected, and their demographic and medical history information were collected. The liver biochemistry, and HBV infection biomarkers including hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), HBeAg, hepatitis B e antibody (anti-HBe), hepatitis B core antibody (anti-HBc), and hepatitis B virus deoxyribonucleic acid (HBV-DNA) levels were tested. The infection characteristics and their influencing factors were explored.Sixty percent of the patients presented HBV-DNA-positive, of which 31.2% had HBV-DNA level higher than 2000 IU/mL, and 16.5% had HBV-DNA level higher than 20,000 IU/mL. HBV-DNA levels tended to increase along with the increasing of age, and the male patients had significant higher HBV-DNA levels than the female patients. Twenty-four percent of the patients had abnormal transaminase. The male patients were more vulnerable to abnormal transaminase (30.0%) than the female patients (18.4%). Fifty-five percent patients with HBV-DNA ≥20,000 IU/mL presented abnormal alanine aminotransferase (ALT) or aspartate transaminase (AST), which was significantly higher than that of patients with HBV-DNA levels below 20,000 IU/mL (19.0-21.7%). Multivariate logistic regression analyses revealed that the male patients and the patients with higher viral load had higher risk of having abnormal liver function.A considerable number of HBeAg-negative patients were virological active and had liver damage. It is necessary and urgent to carry out regular active interventions for the chronic HBV-infected patients.


Assuntos
Antígenos E da Hepatite B/análise , Vírus da Hepatite B/classificação , Hepatite B/virologia , Adulto , Idoso , Distribuição de Qui-Quadrado , China , Feminino , Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/patogenicidade , Humanos , Fígado/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Testes Sorológicos
4.
Int J Infect Dis ; 97: 47-53, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32531432

RESUMO

PURPOSE: To explore the molecular genetic mechanisms underlying different responsiveness to Enterovirus 71 (EV71) vaccine. METHODS: We recruited 10,245 healthy children into a phase 3 clinical trial to evaluate the efficacy of EV71 vaccine in 2012. Fifty subjects from the trial were divided into the potent immune response group (20 subjects) and the ineffective immune response group (30 subjects). Whole-exome sequencing was performed for these 50 samples and we conducted bioinformatics analyses based on online public database. RESULTS: A total of 222,180 germline variants were detected across 50 subjects. Single nucleotide variant (SNV)-based screening of the subjects with potent or ineffective immune response allowed the identification of a potentially detrimental heterozygous missense variant (c.3784C>T) in EEA1. We also retained TRIM59 and ABCA7 genes that contain different loss of function (LoF) variants shared in two cases and involved in the immune response process. Then, we conducted high-resolution typing of 9 classical HLA genes, HLA-DRB1*03:01, HLA-DQA1*05:01 and HLA-DQB1*02:01 alleles were frequently (recurrence ≥5) observed only in ineffective immune responders. CONCLUSIONS: Our study is a meaningful attempt on the comparison of genomic profiles between potent and ineffective immune responders induced by EV71 vaccine, and several candidate potentially detrimental genes were identified.


Assuntos
Enterovirus Humano A/imunologia , Vacinas Virais/imunologia , Transportadores de Cassetes de Ligação de ATP/genética , Alelos , Pré-Escolar , China , Feminino , Variação Genética , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteínas com Motivo Tripartido/genética , Sequenciamento Completo do Exoma
5.
Int J Cancer ; 147(11): 3075-3084, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32478856

RESUMO

The relationship between hepatitis B virus (HBV) and nonhepatocellular cancers remains inconclusive. This large case-control study aimed to assess the associations between HBV infection status and multiple cancers. Cases (n = 50 392) and controls (n = 11 361) were consecutively recruited from 2008 to 2016 at the First Affiliated Hospital of Nanjing Medical University. Multivariable adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression by adjusting age and gender. A meta-analysis based on published studies was also performed to verify the associations. Of these, 12.1% of cases and 5.5% of controls were hepatitis B surface antigen (HBsAg) seropositive. We observed significant associations between HBsAg seropositivity and esophagus cancer (aOR [95% CI] = 1.32 [1.13-1.54]), stomach cancer (1.46 [1.30-1.65]), hepatocellular carcinoma (HCC; 39.11 [35.08-43.59]), intrahepatic and extrahepatic bile duct carcinoma (ICC and ECC; 3.83 [2.58-5.67] and 1.72 [1.28-2.31]), pancreatic cancer (PaC; 1.37 [1.13-1.65]), non-Hodgkin lymphoma (NHL; 1.88 [1.61-2.20]) and leukemia (11.48 [4.05-32.56]). Additionally, compared to participants with HBsAg-/anti-HBs-/anti-HBc-, participants with HBsAg-/anti-HBs-/anti-HBc+, indicating past HBV-infected, had an increased risk of esophagus cancer (aOR [95% CI] = 1.46 [1.24-1.73]), stomach cancer (1.20 [1.04-1.39]), HCC (4.80 [3.95-5.84]) and leukemia (15.62 [2.05-119.17]). Then the overall meta-analysis also verified that HBsAg seropositivity was significantly associated with stomach cancer (OR [95% CI] = 1.23 [1.14-1.33]), ICC (4.05 [2.78-5.90]), ECC (1.73 [1.30-2.30]), PaC (1.26 [1.09-1.46]), NHL (1.95 [1.55-2.44]) and leukemia (1.54 [1.26-1.88]). In conclusion, both our case-control study and meta-analysis confirmed the significant association of HBsAg seropositivity with stomach cancer, ICC, ECC, PaC, NHL and leukemia. Of note, our findings also suggested that the risk of stomach cancer elevated for people whoever exposed to HBV.

6.
J Dig Dis ; 21(7): 406-415, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32407579

RESUMO

OBJECTIVE: In this prospective cohort study, we aimed to evaluate the association between dietary habits and the risk of developing hepatocellular carcinoma (HCC) in hepatitis B surface antigen (HBsAg)-positive carriers in Qidong, an hepatitis B virus (HBV)-epidemic area in China. METHODS: A total of 3199 HBsAg carriers aged 30-70 years in a prospective cohort in Qidong, China from 2007 to 2011 were included in the study. At baseline, all participants self-reported their dietary habits in a questionnaire interview. A follow-up check-up was performed every 6 months to identify HCC cases until November 2017. Cox's regression analysis and an interaction analysis were performed to estimate the relative risks of HCC in terms of baseline diet. RESULTS: Among 3199 HBsAg-positive participants, 270 developed HCC (143.86/100 000 person-years [PYs]). Compared with participants who rarely consume garlic, the risk of HCC in those who consumed it ≥ once per week decreased along with the increase in frequency (HR = 1.00, 0.90 and 0.62 in those who consumed it rarely vs those who consumed it 1-6 times per week and ≥ 7 times per week, respectively). This study found a synergistic effect between garlic and tea consumption on the risk of HCC (P = 0.039 for a multiplicative interaction). CONCLUSIONS: HBsAg carriers should improve their diet. Regular consumption of garlic and tea drinking may reduce the HCC incidence in HBsAg carriers.

9.
Sci China Life Sci ; 63(5): 706-711, 2020 05.
Artigo em Inglês | MEDLINE | ID: covidwho-5706

RESUMO

Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P=0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Overall, the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.


Assuntos
Infecções Assintomáticas , Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus , Pandemias , Pneumonia Viral , China , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/transmissão , Humanos , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/transmissão , Tomografia Computadorizada por Raios X
10.
Sci China Life Sci ; 63(5): 706-711, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32146694

RESUMO

Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P=0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Overall, the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.


Assuntos
Infecções Assintomáticas , Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus , Pandemias , Pneumonia Viral , China , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/transmissão , Humanos , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/transmissão , Tomografia Computadorizada por Raios X
11.
Nat Commun ; 11(1): 650, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005847

RESUMO

Inadequate water quality can mean that water is unsuitable for a variety of human uses, thus exacerbating freshwater scarcity. Previous large-scale water scarcity assessments mostly focused on the availability of sufficient freshwater quantity for providing supplies, but neglected the quality constraints on water usability. Here we report a comprehensive nationwide water scarcity assessment in China, which explicitly includes quality requirements for human water uses. We highlight the necessity of incorporating water scarcity assessment at multiple temporal and geographic scales. Our results show that inadequate water quality exacerbates China's water scarcity, which is unevenly distributed across the country. North China often suffers water scarcity throughout the year, whereas South China, despite sufficient quantities, experiences seasonal water scarcity due to inadequate quality. Over half of the population are affected by water scarcity, pointing to an urgent need for improving freshwater quantity and quality management to cope with water scarcity.


Assuntos
Água Doce/análise , Abastecimento de Água/normas , China , Humanos , Estações do Ano , Fatores Socioeconômicos , Poluição da Água , Qualidade da Água
13.
Sci Rep ; 10(1): 2579, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054930

RESUMO

This paper presented a conformal smoothing theory, and smoothing capability evaluation was established on the proposed theory. According to pressure distribution model, processing parameters have been optimized and the CPP sample with a size of 340 × 340 mm was applied in conformal smoothing. The middle spatial frequency was effectively corrected with the total polishing time of 750 min, and energy was constringed 32.2 times (improved from 57.68 nm2·mm to 1.79 nm2·mm). Meanwhile, surface roughness RMS (root mean square) maintained at the same scale (changed from 265.4 nm to 265.2 nm). Parametric conformal smoothing was proven to be an effective method to control the middle spatial frequency error of CPPs.

14.
Sci Adv ; 6(1): eaau3798, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31921997

RESUMO

Increased human activity threatens inland water quality in China. Major efforts have been made to alleviate water pollution since 2001. Understanding how water quality responds to these forces can help to guide future efforts to maintain water security and sustainability. We here analyzed the nationwide variability of inland water quality across China from 2003 to 2017 and its responses to anthropogenic discharges. We show that water quality has been improved markedly or was maintained at favorable levels over the country because of reduced discharges in the industrial, rural, and urban residential sectors. However, growing discharges from the agricultural sector threaten these gains. Moreover, the present status of water pollution is relatively severe in north and northeast China. Our findings suggest that China's water quality would further benefit from more flexible strategies for mitigation measures, which respond to regional differences in the factors that influence water pollution levels in specific regions.

15.
J Oral Maxillofac Surg ; 78(3): 350-356, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31785248

RESUMO

The main complications of tooth extraction include jaw fracture, maxillary sinus damage, adjacent teeth damage, nerve damage, root fracture, infection, bleeding, and swelling. Despite the theoretical possibility that tooth extraction could result in nasolacrimal duct obstruction, to the best of our knowledge, no cases have yet been reported. In the present study, we describe a case in which the nasolacrimal duct was partially obstructed after extraction of an impacted maxillary canine, causing paranasal discomfort and lower eyelid swelling.

16.
Epigenetics ; 15(1-2): 183-198, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31282290

RESUMO

DNA methylation (DNAm) and microRNAs (miRNAs) have been implicated in a wide-range of human diseases. While often studied in isolation, DNAm and miRNAs are not independent. We analyzed associations of expression of 283 miRNAs with DNAm at >400K CpG sites in whole blood obtained from 3565 individuals and identified 227 CpGs at which differential methylation was associated with the expression of 40 nearby miRNAs (cis-miR-eQTMs) at FDR<0.01, including 91 independent CpG sites at r2 < 0.2. cis-miR-eQTMs were enriched for CpGs in promoter and polycomb-repressed state regions, and 60% were inversely associated with miRNA expression. Bidirectional Mendelian randomization (MR) analysis further identified 58 cis-miR-eQTMCpG-miRNA pairs where DNAm changes appeared to drive miRNA expression changes and opposite directional effects were unlikely. Integration of genetic variants in joint analyses revealed an average partial between cis-miR-eQTM CpGs and miRNAs of 2% after conditioning on site-specific genetic variation, suggesting that DNAm is an important epigenetic regulator of miRNA expression. Finally, two-step MR analysis was performed to identify putatively causal CpGs driving miRNA expression in relation to human complex traits. We found that an imprinted region on 14q32 that was previously identified in relation to age at menarche is enriched with cis-miR-eQTMs. Nine CpGs and three miRNAs at this locus tested causal for age at menarche, reflecting novel epigenetic-driven molecular pathways underlying this complex trait. Our study sheds light on the joint genetic and epigenetic regulation of miRNA expression and provides insights into the relations of miRNAs to their targets and to complex phenotypes.

17.
Dev Sci ; 23(1): e12856, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31081980

RESUMO

Diminished social motivation is hypothesized to explain abnormal face scanning pattern in individuals with autism spectrum disorder (ASD), especially reduced eye-looking time in ASDs than typically developing (TD) people. Here, we tested an alternative explanation that children with ASD may use a compensatory strategy to avoid direct eye contact by processing the eyes through peripheral vision. We compared the face scanning patterns of children with and without ASD in two conditions: in the clear condition, the face was completely visible; in the blur condition, by using the gaze-contingent paradigm, the whole face was blurred except for a small region being fixated at, thus children could not rely on the peripheral information to process the eyes. We found that children with ASD fixated less on the eyes than TD children in both conditions. Temporal-course analyses further revealed the possible motivation-based guidance of attention to process the eyes in the TD group but not in the ASD group. Additionally, we found that children with ASD scanned faces more randomly and less strategically than TD children. These results have ruled out the alternative hypothesis that the abnormal face scanning pattern in ASDs was due to their compensatory strategy to process eyes through peripheral vision, furthering our understanding of the mechanisms underlying their abnormal face scanning.


Assuntos
Atenção , Transtorno do Espectro Autista/fisiopatologia , Face , Fixação Ocular , Criança , Desenvolvimento Infantil , Feminino , Humanos , Masculino , Motivação , Percepção Visual
18.
Front Pediatr ; 7: 425, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737586

RESUMO

Backgrounds and Objectives: The north-south height distinctions in Chinese children suggest that some geographical-climatic factors could determine height variation of short stature. In a national health survey, we aimed to explore the spatial distribution of short stature on city scales, and detect its socio-economic and geographical-climatic factors. Methods: Data on the prevalence of short stature were obtained from a 2014 cross-sectional survey of China (CNSSCH). In total, 213,795 Han Chinese students aged 7-18 years, from 106 cities across 30 provinces, were included. Both China and World Health Organization (WHO) growth references were adopted to define short stature. Results: A spatial clustering was apparent in the distribution of short stature. After multivariable adjustment, altitude and humidity significantly increased the risk of high prevalence in short stature, according to the WHO (odds ratio [OR] = 1.61 and 1.26, 95% confidence interval [CI]: 1.20-2.17 and 1.03-1.54) and China (OR = 1.54 and 1.26; 95% CI: 1.15-2.05 and 1.02-1.55) growth references. Additionally, education significantly decreased the risk of high prevalence in short stature according to the WHO (OR = 0.40; 95% CI: 0.22-0.74) and China (OR = 0.42; 95% CI: 0.22-0.77) growth references. Combining both altitude >400 m and education <9 years, as well as education <9 years and humidity >70%, received the largest effect-size estimate, and significance retained after multivariable adjustment. Conclusions: Our findings indicate that high altitude and humidity increased the risk of high prevalence in short stature, high education was associated with low prevalence. Additionally, we observed possible interactions between education and altitude/humidity. They may interactively explain spatial discrepancy and predict short stature in Chinese school children. Further validations are necessary.

19.
Nat Genet ; 51(11): 1580-1587, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31659325

RESUMO

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification.


Assuntos
Aterosclerose/patologia , Predisposição Genética para Doença , Histona Desacetilases/metabolismo , Histona Desacetilases/fisiologia , Contração Muscular , Músculo Liso Vascular/patologia , Proteínas Repressoras/metabolismo , Proteínas Repressoras/fisiologia , Calcificação Vascular/patologia , Idoso , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/genética , Aterosclerose/metabolismo , Estudos de Coortes , Feminino , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Estudo de Associação Genômica Ampla , Histona Desacetilases/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Músculo Liso Vascular/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética , Calcificação Vascular/genética , Calcificação Vascular/metabolismo
20.
Eur J Haematol ; 103(6): 614-619, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31536656

RESUMO

OBJECTIVE: To estimate survival in Swedish and Norwegian myelofibrosis (MF) patients who received ruxolitinib. METHODS: Swedish and Norwegian patients with MF diagnosis in the National Cancer Registries (Sweden: 2001-2015; Norway: 2002-2016) and ≥1 record of ruxolitinib in the Prescribed Drug Registries (2013-2017) were included. Patients were followed from ruxolitinib initiation until death or end of follow-up; those who discontinued ruxolitinib were followed from ruxolitinib discontinuation. Relative survival (RS) and excess mortality rate ratios (EMRRs) were calculated vs a matched general population. Average loss in life expectancy (LEL) was predicted using flexible parametric models. RESULTS: Among patients who initiated ruxolitinib (n = 190), 1- and 4-year RS were 0.80 (95% confidence interval [CI]: 0.74, 0.86) and 0.52 (95% CI: 0.42, 0.64), respectively, and LEL was 11 years. EMRR was greater in patients aged >70 vs <60 years (3.16; 95% CI: 1.34-7.40). Among patients who discontinued ruxolitinib (n = 71), median RS was 16.0 months (95% CI: 6.3, NE), and LEL was 12 years. After ruxolitinib treatment discontinuation, Swedish patients (n = 37) received glucocorticoids, hydroxyurea, busulfan, danazol and lenalidomide. CONCLUSION: Swedish and Norwegian MF patients who discontinued ruxolitinib had dismal survival outcomes and limited subsequent treatment options, highlighting the need for improved therapies.


Assuntos
Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/mortalidade , Pirazóis/administração & dosagem , Sistema de Registros , Idoso , Bussulfano/administração & dosagem , Danazol/administração & dosagem , Intervalo Livre de Doença , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Humanos , Hidroxiureia/administração & dosagem , Lenalidomida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Gravidez , Taxa de Sobrevida , Suécia/epidemiologia
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