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1.
Hepatology ; 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31677282

RESUMO

Free and bioavailable 25-hydroxyvitamin D (25OHD) are emerging measurements of vitamin D status. It remains unclear whether circulating free or bioavailable 25OHD are relevant to hepatocellular carcinoma (HCC) prognosis. Our aim was to test the hypothesis that bioavailable 25OHD may be a better serum biomarker of vitamin D status than total 25OHD on the association with HCC survival. We included 1031 newly diagnosed, previously untreated patients with HCC from the Guangdong Liver Cancer Cohort (GLCC) enrolled between September 2013 and April 2017. Serum total 25OHD levels were measured using an electrochemiluminescence immunoassay. Serum free 25OHD levels were measured using a two-step enzyme-linked immunosorbent assay. Bioavailable 25OHD levels were calculated from measured free 25OHD and albumin using a previously validated equation. Primary outcomes were liver cancer-specific (LCSS) and overall survival (OS). Cox proportional hazards models were performed to calculate the multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 726 days, 430 patients had deceased, including 393 deaths from HCC. In multivariable analyses, higher bioavailable 25OHD levels were significantly associated with better survival, independent of nonclinical and clinical prognostic factors including serum C-reactive protein, Barcelona Clinic Liver Cancer (BCLC) stage, and cancer treatment. The multivariable-adjusted HRs in the highest vs. lowest quartile of bioavailable 25OHD levels were 0.69 (95% CI: 0.51, 0.93; P for trend=0.014) for LCSS and 0.71 (95% CI: 0.53, 0.94; P for trend=0.013) for OS. In contrast, neither total nor free 25OHD levels were associated with LCSS or OS. CONCLUSION: Higher bioavailable, rather than total, 25OHD levels were independently associated with improved survival in a population-based HCC cohort, suggesting a potential utility of bioavailable 25OHD in HCC prognosis.

2.
Br J Cancer ; 121(8): 640-646, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31523058

RESUMO

BACKGROUND: Small-cell lung cancer (SCLC) remains an aggressive cancer with short-term survival due to limited therapeutic options. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor-2. This study aimed to investigate the efficacy and safety of apatinib in patients with extensive-stage (EC) SCLC who had progressed after two or three previous therapies. METHODS: Eligible patients were histologically confirmed ES-SCLC after two or three previous treatments, including a platinum-based regimen. Patients received apatinib at an initial dose of 500 mg once daily. The primary endpoint was the objective response rate. RESULTS: Forty patients were enrolled. At the data cut-off time (November 15, 2018), the median follow-up was 7.4 months; no patients remained on treatment, and five were still in follow-up. An objective response was achieved in 7 of 40 patients (17.5%) in the intention-to-treat population, and 7 of 38 patients (18.4%) in the per-protocol population. The median progression-free survival and overall survival were 3.0 months and 5·8 months, respectively. The most commonly observed grade 3 or greater treatment-related adverse events were hypertension, hand-foot syndrome, increased L-gamma-glutamyltransferase. CONCLUSIONS: Apatinib exhibited efficacy and an acceptable safety profile in previously heavily-treated ES-SCLC patients. Further exploration of apatinib in phase III trials is warranted. TRIAL REGISTRATION: NCT02945852.

3.
Med Ultrason ; 21(3): 327-335, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31476213

RESUMO

AIM: To evaluate the diagnostic accuracy of real-time elastography as a method for detecting prostate cancer. MATERIAL AND METHODS: Relevant studies applying real-time elastography as the diagnostic modality and biopsy as the reference standard, published by March 1, 2018 were retrieved from PubMed, EMBASE, Web of Science and Cochrane Library databases. Two independent reviewers inspected all these articles to confirm the matching of the inclusion criteria. One reviewer with methodological expertise extracted the data from the included studies. Sensitivity, specificity and diagnostic odds ratio (DOR) were used to obtain overall estimates. Randomized effect method, meta-regression and subgroup analysis were performed. RESULTS: Twenty-four studies out of 1156 identified articles met the inclusion criteria. Three groups were set: analysisby patient (Group 1), by core (Group 2), and by image (Group 3) and subgroups set in Group 1. The pooled estimate ofreal-time elastography sensitivity/ specificity/ DOR calculated with the identical P-value 0.00. Within subgroups "Asia" and"PSA>=10 ng/ml", the pooled sensitivity, specificity and DOR were 0.83, 0.65 (p=0.01, I2=73.40%; p=0.02, I2=69.5%), 0.80, 0.82 (p=0.66, I2=0.00%; p=0.58, I2=0.00%) and 20.2, 8.67 (p=0.09, I2=54.2%; p=0.20, I2=35.5%), respectively. In these three groups, the areas under the SROC curve were 0.7417, 0.9246, and 0.6213 independently. CONCLUSIONS: Real-time elastography is a promising, reliable modality for the non-invasive diagnosis of patients with prostate cancer. The diagnostic accuracy of real-time elastography correlates tightly to the presence of higher PSA level and may help avoid unnecessary biopsy. It seems to be a useful tool in systemic biopsy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31369714

RESUMO

Lysophosphatidic acid (LPA) is an important lipid molecule for signal transduction in cell proliferation. Although the effects of LPA on vascular smooth muscle (VSM) cell growth have been reported previously, the underlying mechanisms of its action are not fully understood. The present study was undertaken to investigate the effects of some inhibitors of different protein kinases and other molecular targets on LPA-induced DNA synthesis as well as gene expression in the aortic VSM cells. The DNA synthesis was studied by [3H]-thymidine incorporation method and the gene expression was investigated by real time PCR technique. It was observed that the LPA-induced DNA synthesis was attenuated by inhibitors of protein kinase C (PKC; staurosporine, calphostin C and bisindolylmaleimide), phosphoinositide 3-kinase (PI3K; wortmannin, and LY294002), and ribosomal p70S6 kinase (p70S6K; rapamycin). The inhibitors of guanine protein coupled receptors (GPCR; pertussis toxin), phospholipase C (PLC; U73122 and D609), and sodium-hydrogen exchanger (NHE; amiloride and dimethyl amiloride) were also shown to depress the LPA-induced DNA synthesis. Furthermore, gene expressions for PLC ß1 isoform, PKC δ and ε isoforms, casein kinase II ß isoform and endothelin-1A receptors were elevated by LPA. These results suggest that the LPA-induced proliferation of VSM cells is mediated through the activation of GPCR and multiple protein kinases as well as gene expressions of their some specific isoforms.

5.
Genes (Basel) ; 10(9)2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466383

RESUMO

Breast cancer has become the most common cancer that leads to women's death. Breast cancer is a complex, highly heterogeneous disease classified into various subtypes based on histological features, which determines the therapeutic options. System identification of effective drugs for each subtype remains challenging. In this work, we present a computational network biology approach to screen precision drugs for different breast cancer subtypes by considering the impact intensity of candidate drugs on the pathway crosstalk mediated by miRNAs. Firstly, we constructed and analyzed the subtype-specific risk pathway crosstalk networks mediated by miRNAs. Then, we evaluated 36 Food and Drug Administration (FDA)-approved anticancer drugs by quantifying their effects on these subtype-specific pathway crosstalk networks and combining with survival analysis. Finally, some first-line treatments of breast cancer, such as Paclitaxel and Vincristine, were optimized for each subtype. In particular, we performed precision screening of subtype-specific therapeutic drugs and also confirmed some novel drugs suitable for breast cancer treatment. For example, Sorafenib was applicable for the basal subtype treatment, Irinotecan was optimum for Her2 subtype treatment, Vemurafenib was suitable for the LumA subtype treatment, and Vorinostat could apply to LumB subtype treatment. In addition, the mechanism of these optimal therapeutic drugs in each subtype of breast cancer was further dissected. In summary, our study offers an effective way to screen precision drugs for various breast cancer subtype treatments. We also dissected the mechanism of optimal therapeutic drugs, which may provide novel insight into the precise treatment of cancer and promote researches on the mechanisms of action of drugs.

6.
J Transl Med ; 17(1): 255, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387579

RESUMO

BACKGROUND: Individualized drug response prediction is vital for achieving personalized treatment of cancer and moving precision medicine forward. Large-scale multi-omics profiles provide unprecedented opportunities for precision cancer therapy. METHODS: In this study, we propose a pipeline to identify subpathway signatures for anticancer drug response of individuals by integrating the comprehensive contributions of multiple genetic and epigenetic (gene expression, copy number variation and DNA methylation) alterations. RESULTS: Totally, 46 subpathway signatures associated with individual responses to different anticancer drugs were identified based on five cancer-drug response datasets. We have validated the reliability of subpathway signatures in two independent datasets. Furthermore, we also demonstrated these multi-omics subpathway signatures could significantly improve the performance of anticancer drug response prediction. In-depth analysis of these 46 subpathway signatures uncovered the essential roles of three omics types and the functional associations underlying different anticancer drug responses. Patient stratification based on subpathway signatures involved in anticancer drug response identified subtypes with different clinical outcomes, implying their potential roles as prognostic biomarkers. In addition, a landscape of subpathways associated with cellular responses to 191 anticancer drugs from CellMiner was provided and the mechanism similarity of drug action was accurately unclosed based on these subpathways. Finally, we constructed a user-friendly web interface-CancerDAP ( http://bio-bigdata.hrbmu.edu.cn/CancerDAP/ ) available to explore 2751 subpathways relevant with 191 anticancer drugs response. CONCLUSIONS: Taken together, our study identified and systematically characterized subpathway signatures for individualized anticancer drug response prediction, which may promote the precise treatment of cancer and the study for molecular mechanisms of drug actions.

7.
Environ Int ; 130: 104882, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202028

RESUMO

BACKGROUND: Experimental studies have indicated that alterations in the gut microbiota might play a role in the pathway of diabetes induction resulting from particulate matter pollution with aerodynamic diameters < 2.5 µm (PM2.5). However, few human studies have examined such experimental findings. Here, we examine the mediating effects of gut microbial dysbiosis on the associations between PM2.5 and particulate matter pollution with aerodynamic diameters < 1 µm (PM1) on diabetes using the Guangdong Gut Microbiome Project (GGMP) dataset. METHODS: A multistage cluster sampling method was employed to recruit adult participants from communities in Guangdong. Each participant was interviewed using a questionnaire, fasting blood and stool samples were collected, and the exposure to air pollutants was assessed using a spatiotemporal land-use regression model. The mediation analysis was conducted to estimate the associations among air pollutants, gut microbiota diversity and diabetes. RESULTS: Both PM2.5 and PM1 were positively associated with the risks of impaired fasting glucose (IFG) or type 2 diabetes and negatively associated with alpha diversity indices of the gut microbiota. The mediation analyses indicated that the associations of PM2.5 and PM1 with the risk of type 2 diabetes were partially mediated by the decrease in gut microbiota diversity. Moreover, we found that 79 (PM2.5 on IFG), 84 (PM2.5 on type 2 diabetes), 83 (PM1 on IFG) and 89 (PM1 on type 2 diabetes) bacterial taxa could partially mediate the associations of PM2.5 and PM1 with IFG and type 2 diabetes, respectively. The relative abundance of most Firmicutes, Proteobacteria and Verrucomicrobia bacteria were negatively associated with particulate matter (PM) concentrations and the risks of diabetes. CONCLUSIONS: Long-term exposure to PM may increase the risk of diabetes, and alterations in the gut microbiota partially explained these associations.

8.
Brief Bioinform ; 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31155677

RESUMO

Alterations of biological pathways can lead to oncogenesis. An overview of these oncogenic pathways would be highly valuable for researchers to reveal the pathogenic mechanism and develop novel therapeutic approaches for cancers. Here, we reviewed approximately 8500 literatures and documented experimentally validated cancer-pathway associations as benchmarking data set. This data resource includes 4709 manually curated relationships between 1557 paths and 49 cancers with 2427 upstream regulators in 7 species. Based on this resource, we first summarized the cancer-pathway associations and revealed some commonly deregulated pathways across tumor types. Then, we systematically analyzed these oncogenic pathways by integrating TCGA pan-cancer data sets. Multi-omics analysis showed oncogenic pathways may play different roles across tumor types under different omics contexts. We also charted the survival relevance landscape of oncogenic pathways in 26 tumor types, identified dominant omics features and found survival relevance for oncogenic pathways varied in tumor types and omics levels. Moreover, we predicted upstream regulators and constructed a hierarchical network model to understand the pathogenic mechanism of human cancers underlying oncogenic pathway context. Finally, we developed `CPAD' (freely available at http://bio-bigdata.hrbmu.edu.cn/CPAD/), an online resource for exploring oncogenic pathways in human cancers, that integrated manually curated cancer-pathway associations, TCGA pan-cancer multi-omics data sets, drug-target data, drug sensitivity and multi-omics data for cancer cell lines. In summary, our study provides a comprehensive characterization of oncogenic pathways and also presents a valuable resource for investigating the pathogenesis of human cancer.

9.
BMC Public Health ; 19(1): 599, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101032

RESUMO

BACKGROUND: Drowning is a leading cause of accidental death in children under 14 years of age in Guangdong, China. We developed a statistical model to classify the risk of drowning among children based on the risk factors. METHODS: A multiple-stage cluster random sampling was employed to select the students in Grades 3 to 9 in two townships in Qingyuan, Guangdong. Questionnaire was a self-reported measure consisting of general information, knowledge, attitudes and activities. A univariate logistic regression model was used to preliminarily select the independent variables at a P value of 0.1 for multivariable model. Three-quarters of the participants were randomly selected as a training sample to establish the model, and the remaining were treated as a testing sample to validate the model. RESULTS: A total of 8390 children were included in this study, about 12.18% (1013) experienced drowning during the past one year. In the univariate logistic regression model, introvert personality, unclear distributions of water areas on the way to school, and bad relationships with their classmates and families were positively associated with drowning. However, females, older age and lower swimming skills were negatively associated with drowning. After employing the prediction model with these factors to estimate drowning risk of the students in the testing samples, the results of Hosmer-Lemeshow tests showed non-significant differences between the predictive results and actual risk (χ2 = 5.97, P = 0.65). CONCLUSIONS: Male, younger children, higher swimming skills, bad relationship with their classmates and families, introvert personality and unclear distributions of water areas on the way to school were important risk factors of non-fatal drowning among children. The prediction model based on these variables has an acceptable predictive ability.


Assuntos
Afogamento/etiologia , Modelos Estatísticos , Medição de Risco/métodos , Estudantes/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , China , Análise por Conglomerados , Feminino , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Fatores de Risco , Instituições Acadêmicas , Autorrelato , Natação
10.
J Org Chem ; 84(11): 7207-7218, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31070913

RESUMO

Diastereoselective α-amination of N- tert-butanesulfinyl imidates has been developed using N-aryl (or N- tert-butyl) N-diphenylphosphinyldiazenes as nitrogen sources. The chiral 1-azaenolates derived from imidates undergo nucleophilic addition with diazenes to give α-hydrazino imidates in good yields.

11.
Sci Rep ; 9(1): 6989, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31061470

RESUMO

Obesity is a progressive, chronic disease, which can be caused by long-term miscommunication between organs. It remains challenging to understand how chronic dysfunction in a particular tissue remotely impairs other organs to eventually imbalance organismal energy homeostasis. Here we introduce RNAi Pulse Induction (RiPI) mediated by short hairpin RNA (shRiPI) or double-stranded RNA (dsRiPI) to generate chronic, organ-specific gene knockdown in the adult Drosophila fat tissue. We show that organ-restricted RiPI targeting Stromal interaction molecule (Stim), an essential factor of store-operated calcium entry (SOCE), results in progressive fat accumulation in fly adipose tissue. Chronic SOCE-dependent adipose tissue dysfunction manifests in considerable changes of the fat cell transcriptome profile, and in resistance to the glucagon-like Adipokinetic hormone (Akh) signaling. Remotely, the adipose tissue dysfunction promotes hyperphagia likely via increased secretion of Akh from the neuroendocrine system. Collectively, our study presents a novel in vivo paradigm in the fly, which is widely applicable to model and functionally analyze inter-organ communication processes in chronic diseases.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30965596

RESUMO

Few studies have focused on the potential relationship between secondhand smoke (SHS) exposure and depressive symptoms. This study aimed to explore the potential association between SHS exposure and depressive symptoms and differentiate this association in setting-specific exposure and symptom-specific outcomes. A cross-sectional study was conducted in Guangdong province of China from September to December 2010 using a multistage sampling method to randomly sample adults aged 18 years and older. SHS exposure was defined as inhalation by non-smokers of the smoke exhaled from smokers for at least 1 day a week in the past 30 days. Depressive symptoms were measured using the nine-item Patient Health Questionnaire. The zero-inflate negative binomial regression models were used to explore the associations between SHS exposure and depressive symptoms. A total of 2771 non-smokers were included in this study, with mean age of 49.6 ± 14.0 years and 70.3% of females. The prevalence of depressive symptoms was significantly higher in participants with SHS exposure than in those without exposure (incidence rate ratio (IRR) = 1.32, 95% confidence interval (CI) 1.16⁻1.51), and there were similar positive associations for SHS exposure in medical facilities (IRR = 1.37, 95% CI 1.17⁻1.61) and in schools (IRR = 1.46, 95% CI 1.20⁻1.77). Notably, there was a monotonically increasing dose-response relationship between frequency of SHS exposure and depressive symptoms. When differentiating this relationship by the dimensions of depressive symptoms, there were similar dose-response relationships for cognitive-affective and somatic symptoms. When differentiating this relationship by sex, only females showed a significant dose-response relationship. Our findings suggest dose-response relationships between SHS exposure and depressive symptoms in sex-specific and symptom-specific manners. Future longitudinal studies are needed to establish the biological mechanisms of the impact of SHS exposure.


Assuntos
Depressão/etiologia , Exposição Ambiental , Poluição por Fumaça de Tabaco/análise , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Fumantes , Inquéritos e Questionários , Adulto Jovem
13.
Br J Nutr ; 121(12): 1376-1388, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30935429

RESUMO

Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.

14.
Chem Commun (Camb) ; 55(26): 3777-3780, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30864606

RESUMO

Products derived from the reaction between N-tert-butanesulfinyl imidates and acylsilanes can be tuned by choosing appropriate bases and solvents. Here we show that in the presence of NaHMDS/THF, addition of enolized N-tert-butanesulfinyl imidates to acylsilanes and subsequent [1,2]-Brook rearrangement generate ß-silyloxy anion intermediates that undergo intramolecular cyclization to afford polysubstituted cyclopropanes. In the presence of tBuOK/toluene, the reaction generates ß-silyloxy imidates as the protonation products of the ß-silyloxy anion intermediates. Both reactions are highly diastereoselective.

15.
Artigo em Inglês | MEDLINE | ID: mdl-30699991

RESUMO

(1) Background: Although the health effects of future climate change have been examined in previous studies, few have considered additive impacts of population expansion, ageing, and adaptation. We aimed to quantify the future heat-related years of life lost (YLLs) under different Representative Concentration Pathways (RCP) scenarios and global-scale General Circulation Models (GCMs), and further to examine relative contributions of population expansion, ageing, and adaptation on these projections. (2) Methods: We used downscaled and bias-corrected projections of daily temperature from 27 GCMs under RCP2.6, 4.5, and 8.5 scenarios to quantify the potential annual heat-related YLLs in Guangzhou, China in the 2030s, 2060s, and 2090s, compared to those in the 1980s as a baseline. We also explored the modification effects of a range of population expansion, ageing, and adaptation scenarios on the heat-related YLLs. (3) Results: Global warming, particularly under the RCP8.5 scenario, would lead to a substantial increase in the heat-related YLLs in the 2030s, 2060s, and 2090s for the majority of the GCMs. For the total population, the annual heat-related YLLs under the RCP8.5 in the 2030s, 2060s, and 2090s were 2.2, 7.0, and 11.4 thousand, respectively. The heat effects would be significantly exacerbated by rapid population expansion and ageing. However, substantial heat-related YLLs could be counteracted by the increased adaptation (75% for the total population and 20% for the elderly). (4) Conclusions: The rapid population expansion and ageing coinciding with climate change may present an important health challenge in China, which, however, could be partially counteracted by the increased adaptation of individuals.


Assuntos
Adaptação Fisiológica , Envelhecimento , Mudança Climática , Temperatura Alta/efeitos adversos , Mortalidade , Crescimento Demográfico , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Aquecimento Global , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Chemosphere ; 222: 665-670, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30735966

RESUMO

The World Health Organization sets up the Ambient Air Quality Guidelines mainly based on short-term and long-term health effects of air pollution. Previous studies, however, have generally revealed a non-threshold concentration-response relationship between air pollution and health, making it difficult to determine a concentration, below which no obvious health effects can be observed. Here we proposed a novel approach based on the concept of "number needed to treat", specifically, we calculated the reduction in air pollution concentrations needed to avoid one death corresponding to different hypothetical concentration standards; the one with the smallest value would be the most practical concentration standard. As an example, we applied this approach to the daily standard of ambient PM2.5 (particulate matter with aerodynamic diameter ≤2.5 µm) in four Chinese cities. The calculation was based on the association between daily mortality and ambient PM2.5, which was examined by a generalized additive model with adjustment of important covariates. Significant associations were observed between PM2.5 and mortality. Our analyses suggested that it is appropriate to have 50 µg/m3 as the daily standard of ambient PM2.5 for the study area, compared to the current standard of which were directly adopted from the national standard of 75 µg/m3. This novel approach should be considered when planning and/or revising the ambient air quality guidelines/standards.


Assuntos
Poluição do Ar , Mortalidade , Material Particulado/normas , China , Cidades , Humanos , Material Particulado/efeitos adversos , Organização Mundial da Saúde
17.
BMC Public Health ; 19(1): 142, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30709390

RESUMO

BACKGROUND: As the fourth leading cause of death, injury is an important public health concern in Guangdong Province, China. The epidemiological characteristics of injury mortality is changing along with the social development. This study described the epidemiological characteristics of injury mortality in Guangdong Province by analyzing the death surveillance data in a few areas in Guangdong Province in 2015. METHODS: Using the mortality data from the Disease Surveillance Points (DSP) system, injury deaths were classified according to the International Classification of Disease-10th Revision (ICD-10). The data were stratified by areas (urban/rural), gender, age groups, injury types, and then overall and type-specific injury mortality rates were estimated for the whole Guangdong Province, China. RESULTS: We estimated that about 38,200 individuals died from injury in Guangdong Province in 2015, producing a mortality rate of 43.11/100,000. The overall age-standardized injury mortality in men was higher in rural areas compared with urban areas (41.29/100,000 versus 24.89/100,000). In terms of injury intent, unintentional injuries were the commonnest injury type, which accounted for 83.93% of the overall injury deaths, however, the deaths caused by suicide should not be ignored, which occupied 12.67% of the total injury deaths. In terms of injury cause type, falls, road-traffic accidents, suicide, drowning, and accidental poisoning were the top five leading types of injury deaths. CONCLUSIONS: In Guangdong Province, injury is an important cause of death. Road-traffic accidents, falls, suicide, drowning, and accidental poisoning should be the priorities of intervention. Moreover, in rural areas, the men were the most targeted subpopulation of the prevention activities.


Assuntos
Vigilância da População , Ferimentos e Lesões/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte/tendências , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
18.
Int J Nanomedicine ; 14: 271-288, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30643406

RESUMO

Background: The intrinsic properties of Prussian blue (PB) nanoparticles make them an attractive tool in nanomedicine, including magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and photothermal therapy (PTT) properties. However, there still remains the challenge of their poor dispersible stability in the physiological environment. In this study, we developed an efficient hydrothermal method to address the poor dispersible stability of PB nanoparticles in the physiological environment. Materials and methods: The concentration of H+, the mass of polyvinylpyrrolidone (PVP), and iron sources (K3[Fe(CN)6]) are very vital in the preparation of PB nanoparticles. Through exploring the preparation process, optimized PB nanoparticles (OPBs) with excellent physiological stability were prepared. Hydrodynamic diameter and UV-vis absorption properties were measured to verify the stability of the prepared OPBs. Properties of dual-mode imaging, including MRI/PAI, and PTT of OPBs were investigated both in vitro and in vivo. In addition, the in vivo biosafety of OPBs was systematically assessed. Results: OPBs were stable in different environments including various media, pH, and temperatures for at least 90 days, indicating that they are suitable for biomedical application via intravenous administration and easily stored in a robust environment. Compared with other research into the synthesis of PB nanoparticles, the "in situ modification" synthesis of PB nanoparticles had advantages, including a simple process, low cost, and easy mass preparation. OPBs showed no significant signs of toxicity for 90 days. As a proof of concept, the OPBs served as dual-mode image contrast agents and photothermal conversion agents for cancer diagnosis and therapy both in vitro and in vivo. Conclusion: Our findings suggest a facile but efficient strategy with low cost to address the poor dispersible stability of PB nanoparticles in physiological environments. This will promote the development of further clinical transformations of PB nanoparticles, especially in cancer theranostics.


Assuntos
Antídotos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Ferrocianetos/administração & dosagem , Nanopartículas/administração & dosagem , Nanomedicina Teranóstica , Administração Intravenosa , Animais , Antídotos/química , Apoptose , Neoplasias da Mama/patologia , Feminino , Ferrocianetos/química , Humanos , Camundongos , Camundongos Nus , Nanopartículas/química , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Chem Commun (Camb) ; 55(4): 478-481, 2019 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-30547169

RESUMO

A small Fe3O4 nanoparticles-based T1 contrast agent was assembled into a pH- and glutathione-responsive T2-T1 switching contrast agent, Fe3O4-ZIF-8. In vivo T1-weighted images of mice showed that Fe3O4-ZIF-8 displayed darkening contrast enhancement for liver sites, while darkening to brightening contrast enhancement at tumor sites, giving large inverse contrast for distinguishing the normal and tumor tissues.


Assuntos
Meios de Contraste/química , Óxido Ferroso-Férrico/química , Glutationa/química , Imidazóis/química , Neoplasias Hepáticas/diagnóstico por imagem , Nanopartículas/química , Zeolitas/química , Animais , Humanos , Concentração de Íons de Hidrogênio , Imagem por Ressonância Magnética , Camundongos , Tamanho da Partícula , Propriedades de Superfície
20.
J Org Chem ; 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30407820

RESUMO

A diastereoselective α-fluorination of N- tert-butanesulfinyl imidates was developed. Deprotonation of N- tert-butanesulfinyl imidates with lithium hexamethyldisilazide generates aza-enolates that can be intercepted, with excellent diastereocontrol, by the inexpensive electrophilic fluorinating agent NFSI. This protocol was applied to the preparation of synthetically useful trans-2-fluoro-cyclohexamine with high enantiomeric purity (99.5% ee).

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