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1.
Clin Immunol ; 214: 108387, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32194234

RESUMO

Biallelic variants in BLNK cause primary B-cell immunodeficiency that usually results in absence of B cells and immunoglobulin. Here, we identified disease-causing variant(s) in two unrelated Chinese patients with agammaglobulinemia. Patient 1 showed a moderate reduction in total B-cell count but demonstrated both extremely low levels of memory B-cells and lower levels of memory T cells relative to those in healthy controls. Whole-exome sequencing (WES) revealed a novel heterozygous splice variant (c.676+1G>A), and suggested exon 9 deletion from BLNK, which was subsequently validated by quantitative polymerase chain reaction. For Patient 2, WES revealed novel compound heterozygous of a frameshift variant (p.T152Pfs*6) and a synonymous variant (c.525G>A) that resulted in exon 6 skipping, according to cDNA sequencing. These findings represent the first report of a BLNK-deficient patient presenting with impaired memory B-cell and memory T-cell development. Furthermore, this study is the first reporting a pathogenic synonymous splice variant in BLNK.

2.
Eur J Med Chem ; 190: 112105, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32035399

RESUMO

A novel series of shikonin-benzo[b]furan derivatives were designed and synthesized as tubulin polymerization inhibitors, and their biological activities were evaluated. Most compounds revealed the comparable anti-proliferation activities against the cancer cell lines to that of shikonin and simultaneously low cytotoxicity to non-cancer cells. Among them, compound 6c displayed powerful anti-cancer activity with the IC50 value of 0.18 µM against HT29 cells, which was significantly better than that of the reference drugs shikonin and CA-4. What's more, 6c could inhibit tubulin polymerization and compete with [3H] colchicine in binding to tubulin. Further biological studies depicted that 6c can induce cell apoptosis and cell mitochondria depolarize, regulate the expression of apoptosis related proteins in HT29 cells. Besides, 6c actuated the HT29 cell cycle arrest at G2/M phase, and influenced the expression of the cell-cycle related protein. Moreover, 6c displayed potent inhibition on cell migration and tube formation that contributes to the antiangiogenesis. These results prompt us to consider 6c as a potential tubulin polymerization inhibitor and is worthy for further study.

3.
BMC Med Imaging ; 20(1): 12, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024469

RESUMO

BACKGROUND: We aimed to develop radiomic models based on different phases of computed tomography (CT) imaging and to investigate the efficacy of models for diagnosing mediastinal metastatic lymph nodes (LNs) in non-small cell lung cancer (NSCLC). METHODS: Eighty-six NSCLC patients were enrolled in this study, and we selected 231 mediastinal LNs confirmed by pathology results as the subjects which were divided into training (n = 163) and validation cohorts (n = 68). The regions of interest (ROIs) were delineated on CT scans in the plain phase, arterial phase and venous phase, respectively. Radiomic features were extracted from the CT images in each phase. A least absolute shrinkage and selection operator (LASSO) algorithm was used to select features, and multivariate logistic regression analysis was used to build models. We constructed six models (orders 1-6) based on the radiomic features of the single- and dual-phase CT images. The performance of the radiomic model was evaluated by the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: A total of 846 features were extracted from each ROI, and 10, 9, 5, 2, 2, and 9 features were chosen to develop models 1-6, respectively. All of the models showed excellent discrimination, with AUCs greater than 0.8. The plain CT radiomic model, model 1, yielded the highest AUC, specificity, accuracy and PPV, which were 0.926 and 0.925; 0.860 and 0.769; 0.871 and 0.882; and 0.906 and 0.870 in the training and validation sets, respectively. When the plain and venous phase CT radiomic features were combined with the arterial phase CT images, the sensitivity increased from 0.879 and 0.919 to 0.949 and 0979 and the NPV increased from 0.821 and 0.789 to 0.878 and 0.900 in the training group, respectively. CONCLUSIONS: All of the CT radiomic models based on different phases all showed high accuracy and precision for the diagnosis of LN metastasis (LNM) in NSCLC patients. When combined with arterial phase CT, the sensitivity and NPV of the model was be further improved.

4.
Basic Res Cardiol ; 115(2): 15, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932910

RESUMO

Myocardial ischemia-reperfusion (I/R) injury leads to intensive sympathetic nervous system (SNS) activation and inflammatory reactions. Whether renal sympathetic denervation (RDN) could be a new therapeutic strategy to modulate I/R inflammation and reduce infarct size after myocardial I/R injury needs to be explored. First, we investigated the correlation between plasma norepinephrine concentrations and circulating myeloid cell numbers in patients with acute myocardial infarction. And then, C57BL/6 mice underwent a "two-hit" operation, with 10% phenol applied to bilateral renal nerves to abrogate sympathoexcitation, and a 45-min ligation of the left coronary artery to induce myocardial I/R injury. The effects of RDN on the mobilization of immune cells in mice following myocardial I/R injury were explored. We observed a strong association between SNS overactivation and myeloid cell excessive accumulation in patients. In animal experiments, there was a significant reduction in infarct size per area at risk in the denervated-I/R group when compared to that of the innervated-I/R group (39.2% versus 49.8%; p < 0.005), and RDN also improved the left ventricular ejection fraction by 20% after 1 week. Furthermore, the denervated-I/R group showed a decrease in the number of neutrophils and macrophages in the blood and the myocardium as reflected by immunohistochemical staining and flow cytometry analysis (p < 0.05); the decrease was associated with a significant reduction in the circulating production of IL-1, IL-6 and TNF-α (p < 0.05). In summary, our study reveals a novel link between the SNS activity and inflammatory response undergoing myocardium I/R injury and identifies RDN as a potential therapeutic strategy against myocardium I/R injury via preserving the spleen immune cells mobilization.

5.
J Hazard Mater ; 386: 121659, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31776080

RESUMO

Although in-vivo exposure of PM2.5 has been suggested to initiate a disorder on vascular permeability, the effects and related mechanism has not been well defined. In this work, an obvious increase on vascular permeability has been confirmed in vivo by vein injection of PM2.5 into Balb/c mouse. Human umbilical vein vascular endothelial cells and the consisted ex-vivo vascular endothelium were used as model to investigate the effects of PM2.5 on the vascular permeability and the underlying molecular mechanism. Upon PM2.5 exposure, the vascular endothelial growth factor receptor 2 on cell membrane phosphorylates and activates the downstream mitogen-activated protein kinase (MAPK)/ERK signaling. The adherens junction protein VE-cadherin sheds and the intercellular junction opens, damaging the integrity of vascular endothelium via paracellular pathway. Besides, PM2.5 induces the intracellular reactive oxygen species (ROS) production and triggers the oxidative stress including activity decrease of superoxide dismutase, lactate dehydrogenase release and permeability increase of cell membrane. Taken together, the paracellular and transcellular permeability enhancement jointly contributes to the significant increase of endothelium permeability and thus vascular permeability upon PM2.5 exposure. This work provides an insight into molecular mechanism of PM2.5 associated cardiovascular disease and offered a real-time screening method for the health risk of PM2.5.

6.
J Hazard Mater ; 384: 121379, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31611019

RESUMO

Mercury (Hg) speciation and isotopic compositions in a large-scale food web and seawater from Chinese Bohai Sea were analyzed to investigate methylmercury (MeHg) sources and Hg cycling. The biota showed ∼5‰ variation in mass dependent fractionation (MDF, -4.57 to 0.53‰ in δ202Hg) and mostly positive odd-isotope mass independent fractionation (odd-MIF, -0.01 to 1.21‰ in Δ199Hg). Both MDF and odd-MIF in coastal biota showed significant correlations with their trophic levels and MeHg fractions, likely reflecting a preferential trophic transfer of MeHg with higher δ202Hg and Δ199Hg than inorganic Hg. The MDF and odd-MIF of biota were largely affected by their feeding habits and living territories, and MeHg in pelagic food web was more photodegraded than in coastal food web (21-31% vs. 9-11%). From the Hg isotope signatures of pelagic biota and extrapolated coastal MeHg, we suggest that MeHg in the food webs was likely derived from sediments. Interestingly, we observed complementary even-MIF (mainly negative Δ200Hg of -0.36 to 0.08‰ and positive Δ204Hg of -0.05 to 0.82‰) in the biota and a significant linear slope of -0.5 for Δ200Hg/Δ204Hg. This leads us to speculate that atmospheric Hg0 is an important source to bioaccumulated MeHg, although the exact source-receptor relationships need further investigation.

7.
Sci Total Environ ; 706: 135975, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31841850

RESUMO

BACKGROUND: Non-optimal weather conditions and air pollution pose a significant threat to children's health. However, the relative impact of different environmental exposures on childhood allergic diseases remains unclear. OBJECTIVES: This study aimed to quantify the relative impact of meteorological factors and air pollutants on childhood allergic diseases in Shanghai, China. METHODS: Data on clinical visits due to childhood asthma, allergic rhinitis (AR) and atopic dermatitis (AD) from 2007 to 2017 in Shanghai were collected from Shanghai Children's Medical Center and Xinhua Hospital. The meteorological data (i.e. daily mean temperature, temperature difference, air pressure, air pressure difference, precipitation, relative humidity, sunshine and wind speed) for the same period were obtained from the Shanghai Meteorological Center. Air pollution data (PM10, PM2.5, NO2, SO2 and O3) were provided by the Shanghai Environmental Protection Agency. Quasi-Poisson regression with distributed lag non-linear models and Poisson regression combined with generalized linear models were used to assess the relative impact of meteorological factors and air pollutants on childhood allergic diseases. RESULTS: There were a total of 2,410,392 cases of childhood allergic diseases, including 975,771 asthma, 646,975 AR and 787,646 AD. Most of environmental factors were significantly associated with childhood allergic diseases. Daily mean temperature (standard ß: -0.076 (95% confidence interval (CI): -0.086, -0.067)) and air pressure (standard ß: 0.075 (95% CI: 0.068, 0.082)) seemed to play more important roles than other environmental factors in the occurrence of these allergic diseases. The numbers of these allergic diseases attributable to an interquartile range (IQR) change in meteorological factors also appeared to be greater than those attributable to an IQR change in air pollutants. CONCLUSIONS: Both climatic variation and air pollution were associated with childhood allergic diseases, but the former appeared to play a more important role in the occurrence of these diseases. These findings may have significant implications for the development of tailored strategies to prevent these rapidly-increasing diseases worldwide.


Assuntos
Hipersensibilidade , Poluentes Atmosféricos , Poluição do Ar , Criança , China , Hipersensibilidade a Drogas , Humanos , Conceitos Meteorológicos , Material Particulado , Tempo (Meteorologia)
8.
Plant Sci ; 290: 110304, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31779894

RESUMO

Glutathione (GSH) is a thiol-containing compound involved in many aspects of plant metabolism. In the present study, we investigated how enhancing endogenous and exogenous GSH affects cadmium (Cd) movement and distribution in Arabidopsis plants cultured hydroponically. Transgenic Arabidopsis plants with a strong ability to synthesize GSH in roots were generated by transforming the gene encoding the bifunctional γ-glutamylcysteine synthetase-glutathione synthetase enzyme from Streptococcus thermophiles (StGCS-GS). Enhancing endogenous and exogenous GSH decreased the Cd translocation ratio in different ways. Only exogenous GSH significantly inhibited Cd translocation from roots to shoots in wild-type and transgenic Arabidopsis plants. Our study demonstrated that GSH mainly functions outside root cells to inhibit Cd translocation from roots to shoots.


Assuntos
Arabidopsis/metabolismo , Cádmio/metabolismo , Glutationa/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Poluentes do Solo/metabolismo , Arabidopsis/efeitos dos fármacos , Transporte Biológico , Glutationa/farmacologia , Hidroponia , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/genética
9.
Chin J Nat Med ; 17(12): 912-917, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31882045

RESUMO

Six new trichilin-type limonoids (1-6) with C-19/29 lactol or acetal bridge and a new ring intact limonoid (7) were isolated from the desiccative ripe fruits of Trichilia sinensis. Their structures were determined by extensive spectroscopic methods including 1H NMR, 13C NMR, HSQC, HMBC, ROESY experiments as well as HRESI-MS data. All isolated compounds were evaluated for toxicities against human pulmonary carcinoma A549 and Hela cell lines by sulforhodamine B (SRB) method. Compound 7 showed weak inhibitory activity in Hela cell line at 40 µmol·L-1.

10.
Radiat Oncol ; 14(1): 242, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881901

RESUMO

BACKGROUND: Cardiac activity could impact the accuracy of dose assessment for the heart, pericardium and left ventricular myocardium (LVM). The purpose of this study was to explore whether it is possible to perform dose assessment by contouring the cardiac structures on specific three-dimensional computed tomography (3DCT) images to reduce the impact of cardiac activity. METHODS: Electrocardiograph-gated 4DCT (ECG-gated 4DCT) images of 22 patients in breath-hold were collected. MIM Maestro 6.8.2 (MIM) was used to reconstruct specific 3DCT images to obtain the Maximal intensity projection (MIP) image, Average intensity projection (AIP) image and Minimum intensity projection (Min-IP) image. The heart, pericardium and LVM were contoured in 20 phases of 4DCT images (0, 5%... 95%) and the MIP, AIP and Min-IP images. Then, a radiotherapy plan was designed at the 0% phase of the 4DCT images, and the dose was transplanted to all phases of 4DCT to acquire the dose on all phases, the accumulated dose of all phases was calculated using MIM. The dose on MIP, AIP and Min-IP images were also obtained by deformable registration of the dose. The mean dose (Dmean), V5, V10, V20, V30 and V40 for the heart, pericardium and LVM in MIP, AIP and Min-IP images were compared with the corresponding parameters after dose accumulation. RESULTS: The mean values of the difference between the Dmean in the MIP image and the Dmean after accumulation for the heart, pericardium and LVM were all less than 1.50 Gy, and the dose difference for the pericardium and LVM was not statistically significant (p > 0.05). For dose-volume parameters, there was no statistically significant difference between V5, V10, and V20 of the heart and pericardium in MIP, AIP, and Min-IP images and those after accumulation (p > 0.05). For the LVM, only in the MIP image, the differences of V5, V10, V20, V30 and V40 were not significant compared to those after dose accumulation (p > 0.05). CONCLUSIONS: There was a smallest difference for the dosimetry parameters of cardiac structures on MIP image compared to corresponding parameters after dose accumulation. Therefore, it is recommended to use the MIP image for the delineation and dose assessment of cardiac structures in clinical practice.

11.
Front Oncol ; 9: 1057, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681593

RESUMO

Purpose: The purpose of the research was to assess the prognostic value of three-dimensional (3D) texture features based on diffusion-weighted magnetic resonance imaging (DWI) for esophageal squamous cell carcinoma (ESCC) patients undergoing concurrent chemo-radiotherapy (CRT). Methods: We prospectively enrolled 82 patients with ESCC into a cohort study. Two DWI sequences (b = 0 and b = 600 s/mm2) were acquired along with axial T2WI and T1WI before CRT. Two groups of features were examined: (1) clinical and demographic features (e.g., TNM stage, age and sex) and (2) changes in spatial texture characteristics of the apparent diffusion coefficient (ADC), which characterizes gray intensity changes in tumor areas, spatial pattern and distribution, and related changes caused by CRT. Reproducible feature sets without redundancy were statistically filtered and validated. The prognostic values associated with overall survival (OS) for each parameter were studied using Kaplan-Meier and Cox regression models for univariate and multivariate analyses, respectively. Results: Both univariate and multivariate Cox model analyses showed that the energy of intensity histogram texture (IHIST_energy), radiation dose, mean of the contrast in distance 1 of 26 directions (m_contrast_1), extreme difference of the homogeneity in distance 2 of 26 directions (Diff_homogeneity_2), mean of the inverse variance in distance 2 of 26 directions (m_lnversevariance_2), high-intensity small zone emphasis (HISE), and low-intensity large zone emphasis (LILE) were significantly associated with survival. The results showed that 6 texture parameters extracted from the ADC images before treatment could distinguish among high-, medium-, and low-risk groups (log-rank χ2 = 9.7; P = 0.00773). The biased C-index value was 0.715 (95% CI: 0.708 to 0.732) based on bootstrapping validation. Conclusions: The ADC 3D texture feature can be used as a useful biomarker to predict the survival of ESCC patients undergoing CRT. Combining ADC 3D texture features with conventional prognostic factors can generate reliable survival prediction models.

12.
BMC Pediatr ; 19(1): 410, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684895

RESUMO

BACKGROUND: Primary immunodeficiency disease (PID) is a disorder caused by an inherited flaw in the immune system that increases the susceptibility to infections. METHODS: In this study, 112 children with PID were diagnosed and classified based on the 2017 criteria presented by the International Union of Immunological Societies (IUIC) in a single tertiary care center from January 2013 to November 2018. We retrospectively studied the clinical features of those PID children and followed-up them as well. RESULTS: It was revealed that male/female ratio was 6:1. The most frequent diagnosed PID was severe combined immunodeficiency (SCID) (28.6%) and hyper-IgM (HIGM) syndrome (24.1%), followed by predominantly antibody deficiencies (17.8%). Combined immunodeficiencies with associated or syndromic features (12.5%) and congenital defects of phagocyte number, function, or both (10.7%) were less common in our center compared with SCID and HIGM syndrome. Besides, we found that 20 children (17.8%) had a positive family history of PID, and almost all cases (97.3%) had a history of recurrent infection. Recurrent respiratory tract infection was among the most common symptoms, followed by the bacterial infection of the skin and mucous membranes and diarrhea. Additionally, adverse event following immunization (AEFI) was found in 20.5% of the patients, and immune disorder was commonly observed in PID patients. In the present study, 47 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 2-year overall survival (OS) rate for these patients was 78.7% (37/47). It is noteworthy that OS widely differed among PID patients with different phenotypes who underwent allo-HSCT. The 2-year OS rate for SCID, HIGM syndrome, and the remaining of PID patients who underwent allo-HSCT was 14.3, 83.3, and 100%, respectively. CONCLUSIONS: PID typically emerges at early age. Recurrent infection and serious infection were the most common clinical manifestations. Allo-HSCT is a relatively effective therapeutic strategy for PID patients.

13.
J Bone Oncol ; 19: 100263, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31667064

RESUMO

Objective: Osteosarcoma often requires multidisciplinary treatment including surgery, chemotherapy and radiotherapy. However, tumor behavior can vary widely among patients and selection of appropriate therapies in any individual patient remains a critical challenge. Radiomics seeks to quantify complex aspects of tumor images under the assumption that this information is related to tumor biology. This study tested the hypothesis that a radiomic signature extracted from Diffusion-weighted magnetic resonance images (DWI-MRI) can improve prediction of overall survival (OS) compared with clinical factors alone in localised osteosarcoma. Materials/Methods: Pre-treatment DWI-MRI were collected from 112 patients (9-67 years of age) with histological-proven osteosarcoma that were treated with curative intent. The entire dataset was divided in two subsets: the training and validation cohorts containing 76 and 24% of the data respectively. Clinical data were extracted from our medical record. Two experienced radiotherapists evaluated DWI-MRIs for quality and segmented the tumor. A total of 103 radiomic features were calculated for each image. Least absolute shrinkage and selection operator (LASSO) regression was applied to select features. Association between the radiomics signature and OS was explored. Further validation of the radiomics signature as an independent biomarker was performed by using multivariate Cox regression. The Cox proportional-hazard regression model was also used to analyze the correlation between the prognostic factor and the survival for the clinical (C) model after the univariate analysis. Radiomics (R) model identified radiomics signature, which is the best predictor from the radiomic variable classes based on LASSO regression. Harrell's C-index was used to demonstrate the incremental value of the radiomics signature to the traditional clinical risk factors for the individualized prediction performance. Results: Cox proportional-hazard regression model shows that: Tumor size, alkaline phosphatase (ALP) status before treatment and number of courses of chemotherapy were proven as the dependent clinical prognostic factors of osteosarcoma's overall survival time. The radiomics signature was significantly associated with OS, independent of clinical risk factors (radiomics signature: HR: 5.11, 95% CI: 2.85, 9.18, P < 0.001). Incorporating the radiomics signature into the coalition (C+R) model resulted in better performance (P < .001) for the estimation of OS (C-index: 0.813; 95% CI: 0.75, 0.89) than with the clinical (C) model (C-index: 0.764; 95% CI: 0.69, 0.85), or the single radiomics (R) model (C-index: 0.712; 95% CI: 0.65, 0.78). Conclusion: This study shows that the radiomics signature extracted from pre-treatment DWI-MRI improve prediction of OS over clinical features alone. Combination of the radiomics signature and the traditional clinical risk factors performed better for individualized OS estimation in patients with osteosarcoma, which might enable a step forward precise medicine. This method may help better select patients most likely to benefit from intensified multimodality diagnosis and therapies. Future studies will focus on multi-center validation of an optimized model.

14.
J Cancer ; 10(24): 6135-6141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31762823

RESUMO

Purpose: Varian Halcyon is a novel machine with dual-layer leaves, single flattening filter free (FFF) energy and an enclosed bore. The purpose of this study was to compare the differences in dosimetry and plan parameters of intensity-modulated radiation therapy (IMRT) plans between the Halcyon and Trilogy accelerators. Methods and Materials: A total of 30 IMRT plans from cervical carcinoma patients were retrospectively analyzed on the Trilogy and Eclipse v13.5 treatment planning systems (TPSs). For each patient, a new plan based on Halcyon was created with the same planning parameters and optimization constraints using the Eclipse Version 15.1 TPS. To compare plan qualities, dosimetry parameters regarding planning target volume (PTV), organs at risk (OARs), monitor unit (MU) efficiency, segment size and treatment time were evaluated. Evaluation of the helical diode array system was performed with gamma-index analysis. Results: The dose distribution of the target volume of the Halcyon and Trilogy plans showed no significant difference (p > 0.05). The mean doses of rectum and both femoral heads for Halcyon plans were significantly reduced compared to those for Trilogy plans (p < 0.05). Compared to Trilogy, Halcyon increased the number of MUs from 1542.9±248.3 MU to 2514.9±328.2 MU (p = 0.00) and decreased the delivery time from 11.28±1.36 min to 3.26±0.26 min (p = 0.00). The average segment areas of Halcyon plans for proximal and distal multileaf collimators (MLCs) were 42.1 ± 31.2 cm2 and 28.4 ± 23.7 cm2, respectively, and that of Trilogy plans was 27.3 ± 16.9 cm2. The mean gamma index (3 mm/3%) results for the Halcyon and Trilogy plans were 99.41±0.26 and 99.76±0.32 (p > 0.05), respectively. Conclusions: All Halcyon treatment plans were recognized as clinically acceptable and had statistically better OAR sparing with higher delivery efficiency. The Halcyon system exhibited fast treatment delivery of IMRT with good dosimetric agreement using ArcCHECK.

15.
BMC Pregnancy Childbirth ; 19(1): 429, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752736

RESUMO

BACKGROUND: Previous studies suggested that maternal subjective feeling of stress seemed to be involved in the incidence of congenial heart disease in offspring. To better understand the findings, our study would discuss the relationships of maternal exposure to stressful life event and social support, which are more objective and comprehensive indicators of stress, around periconceptional period with the risk of ventricular septal defect (VSD), the most popular subtype of congenital heart disease. METHODS: A hospital-based case-control study was conducted through June, 2016 to December, 2017. We collected maternal self-reports of 8 social support questions in 3 aspects and 8 stressful life events among mothers of 202 VSD cases and 262 controls. Social support was categorized into low, medium high, and high (higher is better), and stressful life event was indexed into low, medium low, and high (higher is worse). Logistic regression models were applied to estimate adjusted odds ratios and 95% confidence intervals (95% CI). RESULTS: The adjusted odds ratio of high stressful life event was 2.342 (95% CI: 1.348, 4.819) compared with low stressful life event. After crossover analysis, compared with low event & high support, the adjusted odds ratio of low event & low support, high event & high support, and high event & low support were 2.059 (95% CI: 1.104, 3.841), 2.699 (95% CI: 1.042, 6.988) and 2.781 (95% CI: 1.033, 7.489), respectively. CONCLUSIONS: In summary, we observed an increased risk of VSD when pregnant women exposed to stressful life events, however, social support could, to some extent, reduce the risk of stressful life event.

16.
Food Funct ; 10(12): 8116-8128, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31746888

RESUMO

It has been revealed in our previous studies that trypsin scavenges superoxide anions. In the current study, the mechanisms of storage quality improvement by trypsin were evaluated in H. undatus. Strikingly, the improvement is due not to its antibacterial or antifungal activity but to its superoxide scavenging activity. Moreover, trypsin significantly decreased the levels of ROS, cell permeability and membrane lipid peroxidation. The activities of major antioxidant enzymes were significantly improved by trypsin treatment. Transcriptome profiles of H. undatus treated with trypsin revealed the pathways and regulatory mechanisms of antioxidant genes up or down-regulated following trypsin treatment by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses. The results of protein-protein interaction networks indicated that CAT is the key among the enzymes of the complicated antioxidant system. In addition, the current results showed that the synergistic effect of trypsin with antioxidant enzymes can regulate the levels of endogenous active oxygen species, reduce malondialdehyde content, improve cell membrane integrity, alleviate cell damage and delay fruit ageing.

17.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(5): 879-884, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31631639

RESUMO

Radiotherapy is one of the main treatments for tumor with increasingly high request for technique precision and the equipment stability. Machine learning may bring radiotherapy simplicity, individualization and precision, and may improve the automatic level of planning and quality assurance. Based on the process of radiotherapy, this paper reviews the applications and researches on machine learning, with an emphasis on deep learning, and proposes the prospects in the following aspects: segmentation of normal tissue and tumor, planning, treatment delivery, quality assurance and prognosis prediction.


Assuntos
Aprendizado de Máquina , Neoplasias/radioterapia , Aprendizado Profundo , Humanos
18.
Bioorg Chem ; 93: 103319, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31585270

RESUMO

A novel series of resveratrol-cinnamoyl hybrids as tubulin polymerization inhibitors were designed and synthesized, and evaluated for their anti-proliferative activities against A549, MCF-7, HepG2, HeLa and MDA-MB-231 five cancer cell lines. Most designed compounds showed better anti-proliferative activities. Particularly, compound 6h exhibited the potent anti-proliferative activities with the IC50 value of 0.12, 0.016, 0.44, 0.37 and 0.78 µΜ against A549, MCF-7, HepG2, HeLa and MDA-231, respectively, which was superior to that of reference drug colchicine. Besides, compound 6h displayed a remarkable inhibition of tubulin polymerization and a great potency to compete with [3H] colchicine in binding to tubulin. Further studies indicated that compound 6h could induce the MCF-7 cells arrest in the G2/M phase. What' more, compound 6h induced cell apoptosis in a dose-dependent manner, and regulated the expression level of apoptosis-related proteins. These results revealed that compound 6h is a promising tubulin polymerization inhibitor for treatment of cancer and it is worthy of further exploitation.

19.
Theranostics ; 9(21): 6334-6353, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534554

RESUMO

Rationale: Activating transcription factor 4 (ATF4) is a central regulator of the cellular stress response and reduces tumor burden by controlling the expression of target genes implicated in the induction of apoptosis. Evidence shows ATF4 activation is responsible for proteasome inhibitor bortezomib (BTZ)-induced osteosarcoma (OS) cell death. However, it remains unclear how such suppressive function is impaired during prolonged therapeutic interventions. Methods: Stable cells and in vivo xenograft models were generated to reveal the essential role of ATF4 in cell apoptosis and tumor growth. Fluorescence in situ hybridization (FISH) and immunohistochemistry were employed to detect the expression and significance of ATF4 in the specimens from osteosarcoma patients. Biochemical differences between chemoresistant and chemosensitive cancer cells were determined by proliferation, apoptosis, real-time PCR, immunoblotting and immunofluorescence. Promoter activity was analysed using the luciferase reporter assay. Immunoprecipitation was used to explore the interaction of proteins with other proteins or DNAs. Results: ATF4 significantly inhibited OS tumorigenesis, whereas knockdown of ATF4 prevented the antitumor effects of BTZ. Normal osteoblasts are supposed to preferentially express ATF4, but ATF4 silencing was detected in both OS clinical samples and BTZ-resistant sublines (OS/BTZ). We found that ATF4 downregulation was tightly linked to the aberrant expression of RET, primarily due to RET stabilization in OS/BTZ cells. Loss of RET upregulated ATF4 and potentiated the apoptotic response to BTZ. ATF4 recognized the TK domain of RET by recruiting its transactivated E3 ligase Cbl-c to accelerate RET proteasomal turnover, which in turn prevented BTZ resistance. In contrast, the chaperone GRP78 bound to RET and interfered with ATF4/RET interactions, promoted RET stabilization. Intriguingly, ATF4 repressed GRP78 transcription in OS/BTZ cells via the first ERSE, instead of transactivating GRP78 in wild-type OS via classical CRE element, revealing a dual targeting of RET and GRP78 to overcome chemoresistance. Conclusion: The results uncover a crucial role for ATF4 in blocking the progression and resistance response in RET/GRP78-positive human osteosarcoma.

20.
Technol Cancer Res Treat ; 18: 1533033819875136, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31526114

RESUMO

PURPOSE: To analyze the correlation of hepatitis B virus reactivation with patient-related and treatment-related dose-volume factors and to describe the feasibility of hepatitis B virus reactivation analyzed by a normal tissue complication probability model for patients with hepatocellular carcinoma treated with radiotherapy. MATERIALS AND METHODS: Ninety patients with hepatitis B virus-related hepatocellular carcinoma treated with radiotherapy were enrolled in this retrospective study and were followed from June 2009 to December 2015. Of the 90 patients, 78 had received conventional fractionation radiotherapy to a mean dose of 39.6 to 50.4 Gy and 12 patients were scheduled to receive hypofractionation. The physical doses were converted into 2 Gy equivalents for analysis. The parameters, TD50 (1), n, and m, of the Lyman-Kutcher-Burman normal tissue complication probability model were derived using maximum likelihood estimation. Bootstrap and leave-one-out were employed to against model overfitting and improve the model stability. RESULTS: Radiation-induced liver diseases were 17.8%, hepatitis B virus reactivation was 22.2%, and hepatitis B virus reactivation-induced hepatitis was 21.1%, respectively. In multivariate analysis, the V 5Gy was associated with hepatitis B virus reactivation; TD50 (1), m, and n were 32.3, 0.55, and 0.71 Gy, respectively, for hepatitis B virus reactivation. Bootstrap and leave-one-out results showed that the hepatitis B virus parameter fits were extremely robust. CONCLUSION: A Lyman-Kutcher-Burman normal tissue complication probability model has been established to predict hepatitis B virus reactivation for patients with hepatocellular carcinoma who received radiotherapy.


Assuntos
Carcinoma Hepatocelular/radioterapia , Vírus da Hepatite B/fisiologia , Vírus da Hepatite B/efeitos da radiação , Hepatite B Crônica/virologia , Neoplasias Hepáticas/radioterapia , Ativação Viral/efeitos da radiação , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Feminino , Hepatite B Crônica/complicações , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Curva ROC , Lesões por Radiação , Dosagem Radioterapêutica , Radioterapia Conformacional/efeitos adversos , Tomografia Computadorizada por Raios X
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