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1.
Circ Heart Fail ; 12(12): e005962, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31830829

RESUMO

BACKGROUND: Despite its established significance in fibrotic cardiac remodeling, clinical benefits of global inhibition of TGF (transforming growth factor)-ß1 signaling remain controversial. LRG1 (leucine-rich-α2 glycoprotein 1) is known to regulate endothelial TGFß signaling. This study evaluated the role of LRG1 in cardiac fibrosis and its transcriptional regulatory network in cardiac fibroblasts. METHODS: Pressure overload-induced heart failure was established by transverse aortic constriction. Western blot, quantitative reverse transcription polymerase chain reaction, immunofluorescence, and immunohistochemistry were used to evaluate the expression level and pattern of interested targets or pathology during fibrotic cardiac remodeling. Cardiac function was assessed by pressure-volume loop analysis. RESULTS: LRG1 expression was significantly suppressed in left ventricle of mice with transverse aortic constriction-induced fibrotic cardiac remodeling (mean difference, -0.00085 [95% CI, -0.0013 to -0.00043]; P=0.005) and of patients with end-stage ischemic-dilated cardiomyopathy (mean difference, 0.13 [95% CI, 0.012-0.25]; P=0.032). More profound cardiac fibrosis (mean difference, -0.014% [95% CI, -0.029% to -0.00012%]; P=0.048 for interstitial fibrosis; mean difference, -1.3 [95% CI, -2.5 to -0.2]; P=0.016 for perivascular fibrosis), worse cardiac dysfunction (mean difference, -2.5 ms [95% CI, -4.5 to -0.4 ms]; P=0.016 for Tau-g; mean difference, 13% [95% CI, 2%-24%]; P=0.016 for ejection fraction), and hyperactive TGFß signaling in transverse aortic constriction-operated Lrg1-deficient mice (mean difference, -0.27 [95% CI, -0.47 to -0.07]; P<0.001), which could be reversed by cardiac-specific Lrg1 delivery mediated by adeno-associated virus 9. Mechanistically, LRG1 inhibits cardiac fibroblast activation by competing with TGFß1 for receptor binding, while PPAR (peroxisome proliferator-activated receptor)-ß/δ and TGFß1 collaboratively regulate LRG1 expression via SMRT (silencing mediator for retinoid and thyroid hormone receptor). We further demonstrated functional interactions between LRG1 and PPARß/δ in cardiac fibroblast activation. CONCLUSIONS: Our results established a highly complex molecular network involving LRG1, TGFß1, PPARß/δ, and SMRT in regulating cardiac fibroblast activation and cardiac fibrosis. Targeting LRG1 or PPARß/δ represents a promising strategy to control pathological cardiac remodeling in response to chronic pressure overload.

2.
J Environ Sci (China) ; 86: 131-140, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31787177

RESUMO

Ligands may increase the yields of reactive oxygen species (ROS) in zero-valent iron (ZVI)/O2 systems. To clarify the relationship between the properties of ligands and their effects on the oxidative removal of contaminants, five common ligands (formate, acetate, oxalate, ethylenediaminetetraacetic acid (EDTA), and phosphate) as well as acetylacetone (AA) were investigated with arsenite (As(III)) as the target contaminant at three initial pH values (3.0, 5.0, and 7.0). The addition of these ligands to the ZVI/O2 system resulted in quite different effects on As(III) removal. EDTA enhanced the oxidation of As(III) to arsenate (As(V)) but inhibited the removal of As(V). Oxalate was the only ligand in this work that accelerated both the removal of As(III) and As(V). By analyzing the ligand effects from the four aspects: dissolution of surface iron (hydr)oxides, corrosion of ZVI, reaction with ROS, and interference with precipitation, the following properties of ligands were believed to be important: ability to provide dissociable protons, complexation ability with iron, and reactivity with ROS. The complexation ability is a double-edged sword. It could enhance the generation of ROS by reducing the reduction potential of the Fe(III)/Fe(II) redox couple, but also could inhibit the removal of arsenic by coprecipitation. The elucidated relationship between the key property parameters of ligands and their effects on the ZVI/O2 system is helpful for the rational design of effective ZVI/ligand/O2 systems.

3.
Perfusion ; : 267659119890214, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31854226

RESUMO

OBJECTIVE: Mortality of adult postcardiotomy cardiogenic shock patients after successfully weaned from venoarterial extracorporeal membrane oxygenation remains high. The objective of this study is to identify the risk factors associated with mortality after successfully weaning from venoarterial extracorporeal membrane oxygenation in adult postcardiotomy cardiogenic shock patients. METHODS: All consecutive patients who were successfully weaned from venoarterial extracorporeal membrane oxygenation between January 2011 and December 2016 at the Beijing Anzhen Hospital were analyzed retrospectively. Multivariate logistic regression was performed to identify risk factors associated with in-hospital mortality after successfully weaning from venoarterial extracorporeal membrane oxygenation. RESULTS: In total, 212 (58.4%) of 363 postcardiotomy cardiogenic shock patients were successfully weaned from venoarterial extracorporeal membrane oxygenation. The non-survivors had a longer duration of extracorporeal membrane oxygenation than the survivors (120.0 (98.0, 160.50) vs. 100.0 (77.0, 126.0), p = 0.000). Variables associated with mortality of patients successfully weaned from extracorporeal membrane oxygenation by univariable analysis were age, diabetes, vasoactive inotropic score pre-extracorporeal membrane oxygenation, vasoactive inotropic score at weaning, left ventricular ejection fraction at weaning, central venous pressure at weaning, sequential organ failure assessment score pre-extracorporeal membrane oxygenation, sequential organ failure assessment at weaning, survival after venoarterial ECMO pre-extracorporeal membrane oxygenation, and survival after venoarterial ECMO at weaning. In the multivariate analysis, sequential organ failure assessment score at weaning (odds ratio = 1.889, 95% confidence interval = 1.460-2.455, p < 0.001) was an independent risk factor for in-hospital mortality of patients successfully weaned from venoarterial extracorporeal membrane oxygenation. The cumulative 30-day survival rate in patients with a sequential organ failure assessment score < 7 was significantly (p < 0.001) higher than in patients with a sequential organ failure assessment score ⩾ 7 (87% vs. 56.7%, p < 0.001). CONCLUSION: Vasoactive inotropic score, left ventricular ejection fraction, central venous pressure, and sequential organ failure assessment score at weaning were associated with in-hospital mortality for postcardiotomy cardiogenic shock patients successfully weaned from venoarterial extracorporeal membrane oxygenation. Sequential organ failure assessment score might help clinicians to predict in-hospital mortality for patients successfully weaned from venoarterial extracorporeal membrane oxygenation.

4.
BMC Med Genomics ; 12(1): 198, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870357

RESUMO

BACKGROUND: Rhabdomyosarcoma (RMS), a common soft-tissue malignancy in pediatrics, presents high invasiveness and mortality. However, besides known changes in the PAX3/7-FOXO1 fusion gene in alveolar RMS, the molecular mechanisms of the disease remain incompletely understood. The purpose of the study is to recognize potential biomarkers related with RMS and analyse their molecular mechanism, diagnosis and prognostic significance. METHODS: The Gene Expression Omnibus was used to search the RMS and normal striated muscle data sets. Differentially expressed genes (DEGs) were filtered using R software. The DAVID has become accustomed to performing functional annotations and pathway analysis on DEGs. The protein interaction was constructed and further processed by the STRING tool and Cytoscape software. Kaplan-Meier was used to estimate the effect of hub genes on the ending of sarcoma sufferers, and the expression of these genes in RMS was proved by real-time polymerase chain reaction (RT-PCR). Finally, the expression of CDK1 and CCNB1 in RMS was validated by immunohistochemistry (IHC). RESULTS: A total of 1932 DEGs were obtained, amongst which 1505 were up-regulated and 427were down-regulated. Up-regulated genes were largely enriched in the cell cycle, ECM-receptor interaction, PI3K/Akt and p53 pathways, whilst down-regulated genes were primarily enriched in the muscle contraction process. CDK1, CCNB1, CDC20, CCNB2, AURKB, MAD2L1, HIST2H2BE, CENPE, KIF2C and PCNA were identified as hub genes by Cytoscape analyses. Survival analysis showed that, except for HIST2H2BE, the other hub genes were highly expressed and related to poor prognosis in sarcoma. RT-PCR validation showed that CDK1, CCNB1, CDC20, CENPE and HIST2H2BE were significantly differential expression in RMS compared to the normal control. IHC revealed that the expression of CDK1 (28/32, 87.5%) and CCNB1 (26/32, 81.25%) were notably higher in RMS than normal controls (1/9, 11.1%; 0/9, 0%). Moreover, the CCNB1 was associated with the age and location of the patient's onset. CONCLUSIONS: These results show that these hub genes, especially CDK1 and CCNB1, may be potential diagnostic biomarkers for RMS and provide a new perspective for the pathogenesis of RMS.

5.
Cardiovasc Res ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31688905

RESUMO

AIMS: Cardiovascular side effects caused by non-steroidal anti-inflammatory drugs (NSAIDs), which all inhibit cyclooxygenase (COX)-2, have prevented development of new drugs that target prostaglandins to treat inflammation and cancer. Microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors have efficacy in the NSAID arena but their cardiovascular safety is not known. Our previous work identified asymmetric dimethylarginine (ADMA), an inhibitor of eNOS, as a potential biomarker of cardiovascular toxicity associated with blockade of COX-2. Here we have used pharmacological tools and genetically modified mice to delineate mPGES-1 and COX-2 in the regulation of ADMA. METHODS AND RESULTS: Inhibition of COX-2 but not mPGES-1 deletion resulted in increased plasma ADMA levels. mPGES-1 deletion but not COX-2 inhibition resulted in increased plasma prostacyclin levels. These differences were explained by distinct compartmentalisation of COX-2 and mPGES-1 in the kidney. Data from prostanoid synthase/receptor knockout mice showed that the COX-2/ADMA axis is controlled by prostacyclin receptors (IP and PPARß/δ) and the inhibitory PGE2 receptor EP4, but not other PGE2 receptors. CONCLUSIONS: These data demonstrate that inhibition of mPGES-1 spares the renal COX-2/ADMA pathway and define mechanistically how COX-2 regulates ADMA.

6.
Histol Histopathol ; : 18181, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31688946

RESUMO

Ewing's sarcoma (ES) is a small cell malignant tumor that occurs in the bone of children or adolescents. ES can also occur in extraskeletal organs, such as the pancreas, thyroid, liver, proximal phalanx, and, rarely, cervix. Only 15 published case reports have discussed ES arising in the cervix. We report a 76-year-old woman who had groin mass. ES was diagnosed in accordance with morphological and immunohistochemical maps. Fluorescence in situ hybridization and RT-PCR (reverse transcription PCR) revealed ESWR1 gene rearrangement and fusion gene formation (EWS-FLI-1), both of which confirmed the diagnosis of ES. Although the patient underwent surgical resection, the patient died without chemotherapy and radiotherapy. This case is the first one to involve a patient aged over 70 years and the fifth one to show metastasis occurrence.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31694232

RESUMO

Few provinces in China have recently conducted population-based surveys on tuberculosis (TB) awareness at the provincial level. Hence, we conducted a population-based, cross-sectional study to evaluate the level of awareness of TB knowledge among residents of Zhejiang Province, China from October 2018 to December 2018. A total of 7174 individuals were randomly selected to participate in this survey. The rate of awareness of key information on TB was found to be 48.0%. The study's participants exhibited a good understanding of the transmission route (80.8%), curable outcome (78.3%), and designated treatment sites (67.0%) of TB. The rate of awareness of suspicious TB symptoms (36.1%) and the relief policy on diagnosis and first-line therapeutic drugs (38.0%) were found to be relatively low among the respondents. People living in rural areas, those who were less educated, and students all showed a low level of awareness of key knowledge about TB. In conclusion, residents in Zhejiang Province generally lacked key information about TB, which is not conducive to the early detection and treatment of TB. Corresponding efforts should be made for different groups of people to achieve favorable effects on the prevention and control of TB.

8.
Front Oncol ; 9: 1167, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31750252

RESUMO

Background: The efficacy of an EGFR-targeted treatment strategy for non-small cell lung cancer (NSCLC) is reduced by drug resistance. IL-22 enhances tumor growth and induces chemotherapy resistance in human lung cancer cells. The present study elucidated the IL-22-induced mechanism underlying EGFR-tyrosine kinase inhibitor (TKI) resistance in NSCLC. Methods: The plasma and tissues of patients who received EGFR-TKIs were utilized to determine the association between IL-22 expression and gefitinib efficacy. The IL-22 effect on the EGFR/ERK/AKT pathways in NSCLC HCC827 and PC-9 cells was determined using the CCK-8 assay, western blot, and flow cytometric analysis. A PC-9 xenograft model of IL-22 exposure was established. Gefitinib was administered to mice in combination with IL-22 or vehicle. Results: We showed that IL-22 expression was higher in the EGFR-TKI-resistant group compared to EGFR-TKI-sensitive group. IL-22 expression was associated with EGFR-TKI efficacy in plasma. Additional treatment of IL-22 induced gefitinib resistance and reduced apoptosis in PC-9 and HCC827 cell lines. Furthermore, we showed that the effects of IL-22 attributed to p-ERK, p-EGFR, and p-AKT up-regulation. IL-22 neutralizing antibody completely abrogated the effects of IL-22 on apoptosis and AKT/EGFR/ERK signaling. Finally, we showed that IL-22 enhanced tumor growth and induced gefitinib resistance in the PC-9 xenograft model. Moreover, compared with gefitinib alone, the combination of IL-22 and gefitinib led to an increase in Ki67-positive staining and a reduction in TUNEL staining. Conclusions: Our findings indicate that IL-22 plays a role in tumor progression and EGFR-TKI resistance in NSCLC. Thus, IL-22 might serve as a novel biomarker to overcome resistance of EGFR-TKI.

9.
Materials (Basel) ; 12(22)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752232

RESUMO

The strengthening method of using hybrid fiber reinforced polymer is an effective way to increase the strengthening efficiency and lower the cost. This paper focuses on simulating the flexural behavior of reinforced concrete beam strengthened by prestressed C/GFRP (Carbon-Glass hybrid Fiber Reinforced Polymer) with different hybrid ratios and prestress levels. An elastoplastic damage constitution is used to simulate the mechanical behavior of concrete. A cohesive zone model under mixed mode is adopted to describe the debonding behavior of the FRP-concrete and concrete-steel interface. The results show good agreement with the experiment in the load-deflection curve, load-stress curve of steel, and HFRP. Furthermore, the failure mode of concrete and FRP debonding obtained from numerical simulation is the same as the test. Considering the improvement of the bending capacity, stiffness, and ductility of the strengthened beam in this paper, the best hybrid ratio of carbon to glass fiber is 1:1, and the suitable prestress level is between 30 and 50% of its ultimate strength.

10.
BMC Infect Dis ; 19(1): 972, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727001

RESUMO

BACKGROUND: In recent years, tuberculosis outbreaks in schools have occurred more frequently in China than in other parts of the world, and have posed a public health threat to students and their families. This systematic review aimed to understand the epidemiological characteristics of tuberculosis (TB) outbreaks and analyze the factors associated with TB outbreaks in schools in China. METHODS: We conducted this systematic review following the standard procedures of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. The meta-analysis was performed with STATA using a random effects model. RESULTS: We included 107 studies involving 1795 student patients with TB in mainland China. The results of the systematic analysis indicated that TB outbreaks were more frequently reported in senior middle schools and in Eastern China. The outbreaks mainly occurred during the winter and spring, and the median outbreak duration was 4 months. The meta-analysis showed that the total attack rate and the class attack rate of tuberculosis outbreaks among students were 4.60% (95% CI 3.80 to 5.70%) and 22.70% (95% CI 19.20 to 27.00%), respectively. Subgroup analysis showed that outbreaks that occurred at universities or colleges had a relatively higher attack rate than those occurred in senior middle schools. The prevalence of latent tuberculosis infection (LTBI) among close contacts was 23.70% (95% CI 19.50 to 28.90%). The median case-finding interval was 2 months, and 47.40% of the index cases had a case-finding delay. CONCLUSION: The results of our review indicated that school TB outbreaks were reported most frequently in senior middle schools in China. The attack rates of outbreaks at universities or colleges were higher than those in senior middle schools. The TB outbreaks in schools usually occurred over prolonged periods. The case-finding delay in the index cases must be reduced to prevent transmission in classes and schools. Effective surveillance and screening of presumptive TB cases in schools should be strengthened to reduce outbreaks in schools.

11.
Clin Rheumatol ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31760539

RESUMO

In this study, we aimed to explore the expression levels of JAK2 and PTPRC in peripheral blood mononuclear cells (PBMCs) from SLE patients and controls, detect the effects of SLE activity on genes mRNA expression, and find the association between genes mRNA expression and clinical manifestations of patients. We performed quantitative real-time PCR (qRT-PCR) to test differences in the expression levels of JAK2 and PTPRC in PBMCs extracted from 135 patients with SLE and 130 healthy controls. Furthermore, we detected the regulatory effect of SNPs on gene expression by expression quantitative trait loci (eQTL). We also tested whether the genes mRNA expression was affected with the SLE activity and analyzed the relationship between genes mRNA expression and clinical manifestations of patients. The mRNA expression levels of JAK2 in SLE patients were significantly higher than those in healthy controls (P = 0.005), and PTPRC mRNA expression levels were significantly decreased (P < 0.001). However, no other statistical significance was detected. We found that the elevated JAK2 mRNA expression and the decreased PTPRC mRNA expression may play suggestive roles in the pathogenesis of SLE.Key Points• The JAK2 mRNA expression levels in SLE patients were significantly higher than those in healthy controls.• The PTPRC mRNA expression levels in SLE were decreased.• JAK2 and PTPRC mRNA expression may play suggestive roles in the pathogenesis of SLE.

12.
Can J Cardiol ; 35(11): 1483-1490, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31587932

RESUMO

BACKGROUND: Hypothermic circulatory arrest (HCA) with adjunctive unilateral antegrade cerebral perfusion (UACP) is widely used as a cerebral protection strategy during aortic arch surgery. However, the ideal temperature for HCA during UACP remains unknown. The study compared clinical outcomes of patients in different temperature groups for HCA during UACP. METHODS: From January 2009 to January 2016, 1691 patients who underwent aortic arch surgery for HCA during UACP in Beijing Anzhen Hospital were categorized into 2 groups according to nasopharyngeal temperature before initiating systemic circulatory arrest: the low temperature group (≤ 24°C, 22.9°C; 22.0°C-23.5°C; n = 1207) and the high temperature group (24.1°C-28.0°C, 24.6°C; 24.3°C-24.9°C; n = 484). After balancing the differences of baseline conditions by propensity score matching, 473 pairs of patients were matched, and the prognosis was compared with matched patients. RESULTS: The multivariable Cox regression analysis shows the high temperature group was an independent predictor for 30-day mortality (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.33-0.93; P = 0.03). After matching, the high temperature group was still an independent predictor of 30-day mortality (HR, 0.55; 95% CI, 0.32-0.98; P = 0.04). In subgroup analyses, there was an interaction between the high temperature group and UACP > 40 minutes for 30-day mortality (Pfor interaction< 0.05). The high temperature group had a significant protective effect in the UACP ≤ 40 minutes subgroup (HR, 0.30; 95% CI, 0.12-0.74; P = 0.01) but not in the UACP > 40 minutes subgroup (HR, 1.00; 95% CI, 0.46-2.20; P = 0.99). CONCLUSIONS: This study shows that the high temperature (24.1°C-28.0°C) management strategy for HCA during UACP is safer for UACP ≤ 40 minutes. High temperature benefits were not found in patients for UACP > 40 minutes.

13.
Medicine (Baltimore) ; 98(42): e17235, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626084

RESUMO

BACKGROUND: Conflicting results have been reported on the association of poststroke depression with recurrent stroke events. This meta-analysis of prospective studies aims to evaluate whether poststroke depression is an independent predictor of stroke recurrence among stroke patients. METHODS: A systematic search of articles in PubMed and Embase databases from their inception to October 2018 was conducted. Prospective studies reporting risk estimates of stroke recurrence by depression status in stroke patients were included and pooled risk ratio (RR) with 95% confidence intervals (CIs) of stroke recurrence was calculated for patients with or without poststroke depression. RESULTS: Six studies with 4648 stroke patients were finally included, and the prevalence of poststroke depression was found to from 15.9% to 40.5%. The pooled adjusted RR for stroke recurrence in patients suffering from poststroke depression was 1.48 (1.22-1.79) in a fixed-effect model. Subgroup analyses indicated that poststroke depression significantly increased stroke recurrence (RR 1.64; 95% CI, 1.28-2.10) among ischemic stroke patients but not in total stroke patients (RR 1.28; 95% CI, 0.96-1.73). CONCLUSIONS: This meta-analysis suggests that poststroke depression may be an independent predictor of stroke recurrence among ischemic stroke patients. Further studies are required to investigate whether treatment of poststroke depression can reduce the risk of stroke recurrence.


Assuntos
Depressão/epidemiologia , Acidente Vascular Cerebral/psicologia , Idoso , Idoso de 80 Anos ou mais , Depressão/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Recidiva , Fatores de Risco , Sobreviventes/estatística & dados numéricos
14.
Am J Physiol Endocrinol Metab ; 317(6): E1108-E1120, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573842

RESUMO

ß-Cells respond to peripheral insulin resistance by first increasing circulating insulin during diabetes. Islet remodeling supports this compensation, but its drivers remain poorly understood. Infiltrating macrophages have been implicated in late-stage type 2 diabetes, but relatively little is known on islet resident macrophages, especially during compensatory hyperinsulinemia. We hypothesized that islet resident macrophages would contribute to islet vascular remodeling and hyperinsulinemia during diabetes, the failure of which results in a rapid progression to frank diabetes. We used chemical (clodronate), genetics (CD169-diphtheria toxin receptor mice), or antibody-mediated (colony-stimulating factor 1 receptor α) macrophage ablation methods in diabetic (db/db) and diet-induced models of compensatory hyperinsulinemia to investigate the role of macrophages in islet remodeling. We transplanted islets devoid of macrophages into naïve diabetic mice and assessed the impact on islet vascularization. With the use of the above methods, we showed that macrophage depletion significantly and consistently compromised islet remodeling in terms of size, vascular density, and insulin secretion capacity. Depletion of islet macrophages reduced VEGF-A secretion in both human and mouse islets ex vivo, and this functionally translated to delayed revascularization upon transplantation in vivo. We revealed that islet resident macrophages were associated with islet remodeling and increased insulin secretion during diabetes. This suggests utility in harnessing islet macrophages during this phase to promote islet vascularization, remodeling, and insulin secretion.

15.
Clin Neurol Neurosurg ; 186: 105529, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31574360

RESUMO

The efficacy of perioperative seizure prophylaxis in seizure-naïve glioma patients is still controversial. Thus we conducted this meta-analysis to assess the effectiveness of perioperative prophylactic antiepileptic drugs (AEDs) on postoperative seizures in seizure-naïve glioma for the first time. We systematically searched PubMed, Embase, Weipu (VIP) and Chinese National Knowledge Infrastructure (CNKI) until July 5, 2019 for eligible studies. Fixed or random model was used to calculate the odds ratios in STATA 12.0 software. Subgroup analyses of early postoperative seizure, late postoperative seizure, high-grade glioma (WHOIII-IV) and phenytoin (PHT) or phenobarbital (PB) prophylaxis were conducted. Altogether 1143 seizure-naïve glioma patients from 9 studies were included in this meta-analysis, containing 643 prophylaxed and 503 non-prophylaxed patients. No significant association was detected between perioperative seizure prophylaxis and postoperative seizure occurrence in glioma patients without preoperative seizure history (OR = 0.91, 95% CI = 0.65-1.26, P = 0.56). Perioperative AED prophylaxis showed no significant benefit to postoperative seizures when stratified by early postoperative seizure(within the first postoperative week), late postoperative seizure (after the first postoperative week), high-grade glioma and PHT or PB prophylaxis (all P > 0.05). Current evidence indicated that perioperative seizure prophylaxis did not reduce the occurrence of postoperative seizure in seizure-naïve glioma patients. The pros and cons of perioperative seizure prophylaxis should be considered before the start of perioperative AEDs treatment.

16.
Nucleic Acids Res ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642496

RESUMO

De novo mutations (DNMs) significantly contribute to sporadic diseases, particularly in neuropsychiatric disorders. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) provide effective methods for detecting DNMs and prioritizing candidate genes. However, it remains a challenge for scientists, clinicians, and biologists to conveniently access and analyse data regarding DNMs and candidate genes from scattered publications. To fill the unmet need, we integrated 580 799 DNMs, including 30 060 coding DNMs detected by WES/WGS from 23 951 individuals across 24 phenotypes and prioritized a list of candidate genes with different degrees of statistical evidence, including 346 genes with false discovery rates <0.05. We then developed a database called Gene4Denovo (http://www.genemed.tech/gene4denovo/), which allowed these genetic data to be conveniently catalogued, searched, browsed, and analysed. In addition, Gene4Denovo integrated data from >60 genomic sources to provide comprehensive variant-level and gene-level annotation and information regarding the DNMs and candidate genes. Furthermore, Gene4Denovo provides end-users with limited bioinformatics skills to analyse their own genetic data, perform comprehensive annotation, and prioritize candidate genes using custom parameters. In conclusion, Gene4Denovo conveniently allows for the accelerated interpretation of DNM pathogenicity and the clinical implication of DNMs in humans.

18.
Nanoscale ; 11(36): 17041-17051, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31506653

RESUMO

Small interfering RNA (siRNA) is a promising tool for the treatment of skin disorders including skin squamous cell carcinoma (SCC). This article develops a topical formulation for the transdermal delivery of siRNA. The formulation is built on mesoporous silica nanoparticles (MSNPs) with a loading capacity of 1.4 µg of oligonucleotide per mg of MSNPs. Cell experiments are employed to study the functionality of the formulation including the cellular uptake, the qualitative and quantitative detection of specific gene biomarkers. The clinical potential of this system is examined by topically delivering siRNA targeting TGFßR-1 (TGFßR-1) to the SCC in a mouse xenograft model. In comparison to the controls, MSNPs containing TGFßR-1 siRNA show a 2-fold suppression of TGFßR-1.

19.
Mar Pollut Bull ; 149: 110586, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31550572

RESUMO

The objective of this research was to evaluate the capacity of Enteromorpha derived biochar to adsorb heavy metals from seawater. The biochar characteristics were determined, and isothermal and kinetic data were obtained using batch experiments. Copper [Cu(II)] and lead [Pb(II)] adsorption by the biochar was favored by high pH conditions, while elevated salinity had a relatively weak negative effect on adsorption. The Langmuir isotherm and adsorption kinetics pattern enabled interpretation of the equilibrium and kinetics of Cu(II) and Pb(II) removal by the biochar. The maximum removal rates of Cu(II) and Pb(II) by the biochar in 60 min were estimated to be 91% and 54%, respectively. A model describing the adsorption processes was developed to predict the efficiency of heavy metal removal by the biochar. The outcomes of the present study indicate that Enteromorpha derived biochar could be an effective and environmentally friendly adsorbent for removing heavy metals from marine environments.

20.
Biomater Sci ; 7(11): 4603-4614, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31436780

RESUMO

Anti-vascular endothelial growth factor (anti-VEGF) proteins are the gold-standard treatment for posterior eye segment proliferative vascular diseases such as Age-Related Macular Degeneration (AMD) and Diabetic Retinopathy (DR). However, the standard of care requires inconvenient monthly intravitreal injections. This underlies an unmet clinical need to develop alternative solutions for sustained delivery of biologics. In this paper, we demonstrated that anti-VEGFs can be encapsulated by a simple mild process into our polyurethane thermogel depots. By changing the hydrophilic-hydrophobic balance in the copolymer, anti-VEGF release rates can be modulated. The antibody in the thermogel partitions into protein domains which vary in size corresponding to the hydrophilicity balance of the polymer. Anti-VEGFs can be released in a relatively linear manner from the thermogel for up to 40 days in vitro. The encapsulated anti-VEGFs demonstrate anti-angiogenic bioactivity by inhibiting vessel outgrowth in rat ex vivo choroidal explants, and reducing vascular leakage in a VEGF-driven neovascularization rabbit model. In conclusion, we show that these thermogels can be tuned in terms of hydrophilicity and used for sustained delivery of bioactive anti-VEGFs. Physically cross-linked polyurethane thermoresponsive hydrogels could be a promising platform for sustained delivery of biologically active therapeutic proteins.

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