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1.
Cancer Control ; 27(1): 1073274820922553, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32420748

RESUMEN

Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) are highly expressed in nasopharyngeal carcinoma; therefore, blocking the binding of VEGF and VEGFR may be a potential way to treat nasopharyngeal carcinoma. Apatinib inhibits tumor angiogenesis. Previous studies have suggested that treatment with apatinib has an antitumor effect on nasopharyngeal carcinoma. This study will investigate the effect of apatinib combined with radiotherapy. In this study, nude mice injected with CNE-2 nasopharyngeal carcinoma cells were randomly divided into 6 groups. Therapeutic effects were assessed by evaluating tumor inhibition rate, phosphorylation of VEGFR-2, CD31, partial oxygen pressure, and tumor metabolism. We found that the tumor inhibition of mice in the treated groups was better compared to that of the control group. In mice treated with apatinib alone, angiogenesis was prevented, and the tumor tissue partial oxygen pressure was reduced, thereby achieving an antitumor effect. Moreover, the tumor inhibitory effect of combined treatment was stronger than treatment with either apatinib or radiotherapy alone. Compared with monotherapy treatment, combined treatment better resisted angiogenesis. Apatinib combined with radiotherapy to treat nasopharyngeal carcinoma has synergistic effects, which may be related to enhanced antiangiogenesis.

2.
Artículo en Inglés | MEDLINE | ID: mdl-32396105

RESUMEN

Electronic medical records (EMRs) play an important role in medical data mining and sequential data learning. In this article, we propose to use a sequential neural network with dynamic content-based memories to predict future medications, given EMRs. The local-global memory neural network contains two layers of memories: the local memory and the global memory. Particularly, our method learns the hidden knowledge within EMRs by locally remembering individual patterns of a patient (via local memory) and globally remembering group evidence of disease (via global memory). In addition, we show how our model can be modified to classify the hidden states of EMRs from different patients at each time step into different phases that indicate the progressions of medications in terms of a specific disease, in an unsupervised manner. Experimental results on real EMRs data sets show that, by learning EMRs with external local and global memories, with regard to a given disease, our model improves the prediction performance compared with several alternative methods.

3.
Respir Res ; 21(1): 113, 2020 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-32404117

RESUMEN

BACKGROUND: High FiO2 during one-lung ventilation (OLV) can improve oxygenation, but increase the risk of atelectasis and oxidative stress. The aim of this study was to analyze whether Prostaglandin E1 (PGE1) can improve oxygenation and attenuate oxidative stress during OLV under a lower FiO2. METHOD: Ninety patients selectively undergoing thoracotomy for esophageal cancer were randomly divided into three groups (n = 30/group): Group P (FiO2 = 0.6, inhaling PGE1 0.1 µg/kg), Group L (FiO2 = 0.6) and Group C (FiO2 = 1.0). The primary outcomes were oxygenation and pulmonary shunt during OLV. Secondary outcomes included haemodynamics, respiratory mechanics and oxidative stress in serum. RESULTS: Patients in Group P had significantly higher PaO2 and lower shunt fraction in 30 min of OLV compared with Group L. Compared with Group C, patients in Group P had similar levels of PaO2/FiO2 in 60 min and higher levels of PaO2/FiO2 at 2 h during OLV. The levels of PvO2 and SvO2 in Group P and Group L were significantly lower than Group C. Patients in Group P and Group L had significantly higher levels of superoxide dismutase and lower levels of malondialdehyde than Group C. No significant differences were found in SPO2, ETCO2, PaCO2, Paw, HR and MAP among the three groups. The complications in Group C were significantly higher than another two groups. CONCLUSION: PGE1 can maintain adequate oxygenation in patients with low FiO2 (0.6) during OLV. Reducing FiO2 to 0.6 during OLV can decrease the levels of oxidative stress and complications after OLV. TRIAL REGISTRATION: chictr.org.cn identifier: ChiCTR1800017100.

4.
Sci Rep ; 10(1): 8578, 2020 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-32444672

RESUMEN

To estimate the incidence of pulmonary tuberculosis (PTB) in Chinese diabetes patients and to evaluate the effect of blood glucose on PTB risk, a retrospective cohort study was built based on the diabetes management system in Shanghai and included 240,692 adults aged 35 or above. Incidences of PTB in all diabetes patients and by subgroups were calculated and compared. Multivariable Cox regression models with restricted cubic splines were used to evaluate the association of fasting plasma glucose (FPG) with the risk of PTB. A total of 439 incident PTB cases were identified in the cohort after an average of 3.83 years of follow-up. The overall PTB incidence rate was 51.3/100,000 in diabetes patients, and annual incidence remained higher than that in general population. The PTB incidence rate of diabetes patients was higher in men than in women (86.2 vs. 22.1 per 100,000) and was highest in patients with body mass index (BMI) < 18.5 kg/m2 (215.2/100,000) or FPG ≥ 10 mmol/L (143.2/100,000). Our results suggest that the risk of tuberculosis may be greater at higher levels of FPG in diabetes patients of normal weight. Specific tuberculosis screening strategies for different characteristic diabetes population should be provided to prevent and control tuberculosis in China.

5.
Cell Death Dis ; 11(5): 302, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32358484

RESUMEN

Tumor-associated neutrophils (TANs) are important inflammatory infiltrating cells in the tumor microenvironment and are closely related to the development of human tumor. However, the underlying mechanism of TANs recruiting to glioma remains unknown. Herein, we identified that LINC01116 was significantly upregulated in glioma, and positively correlated with clinical malignancy and survival prognosis. LINC01116 regulated the progression of glioma in vitro and in vivo. RNA-seq analysis demonstrated that LINC01116 knockdown affected the expression of IL-1ß, which promoted glioma proliferation and neutrophil recruitment. Furthermore, the co-culture of glioma cells and neutrophils showed that the accumulation of TANs promoted tumor proliferation via producing a host of cytokines. Mechanistically, LINC01116 activated IL-1ß expression by recruiting the transcriptional regulator DDX5 to the IL-1ß promoter. Our findings reveal that LINC01116 can promote glioma proliferation and neutrophil recruitment by regulating IL-1ß, and may be served as a novel target for glioma therapy and prognosis.

6.
Heart Surg Forum ; 23(2): E101-E106, 2020 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-32364892

RESUMEN

BACKGROUND: Anomalous left coronary artery from the pulmonary artery (ALCAPA), a very rare congenital cardiac anomaly, is associated with a high mortality rate among infants who are not diagnosed or treated in a timely manner. Surgical intervention with the reconstruction for a two-coronary-system circulation is the main treatment; however, there have been very few reported cases from Taiwan. In this study, we aim to describe the clinical manifestations, diagnostic methods, surgery types, and surgical outcomes in patients with ALCAPA from a single Taiwanese medical center. METHODS: We retrospectively reviewed patients diagnosed with ALCAPA who underwent surgery at our institution between January 2001 and October 2018. Clinical presentations, noninvasive and invasive study results, surgical methods, and postoperative follow-up results were assessed from medical records. Moreover, literature on this particular cardiovascular anomaly was reviewed. RESULTS: The study included 6 patients (5 children and 1 adult). The diagnosis was confirmed using cardiac catheterization and coronary angiography in four patients and only echocardiography in two patients. All patients underwent surgical correction and survived. Four patients showed improvements in left ventricular function and mitral regurgitation (MR). CONCLUSION: Early diagnosis and timely surgical intervention could avoid mortality regardless of the method of operation. ALCAPA can be definitively diagnosed using noninvasive echocardiography. Both left ventricular systolic function and mitral insufficiency could improve after the surgical intervention in pediatric patients. Repair or replacement of the mitral valve could be reserved for persistent MR complicated with congestive heart failure, particularly in patients who received the initial operation beyond infancy.

7.
Clin Nutr ; 2020 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-32359931

RESUMEN

BACKGROUND & AIMS: Evidence linking individual cooking oil consumption with total mortality is limited in China. The aim of this study was to examine the associations of intakes of plant-sourced and animal-sourced cooking oils with total mortality in a Chinese nationwide cohort. METHODS: We analyzed data from 14,305 adults aged ≥20 y at entry in the China Health and Nutrition Survey (CHNS). The 3-day 24-h dietary records were used to collect dietary information. Cox proportional hazards regression models were established to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause death. RESULTS: Overall 1006 deaths were documented during a median of 14 years (199,091 person-years) of follow-up. Multivariate-adjusted HRs (95% CIs) of total mortality via comparing the highest tertile of cooking oil consumption with no consumption were 0.86 (0.70-1.06) for lard, 0.59 (0.47-0.74) for peanut oil, 0.71 (0.54-0.93) for soybean oil, 0.76 (0.61-0.94) for canola oil, 0.71 (0.50-0.99) for salad oil, and 0.59 (0.44-0.79) for other plant cooking oils. Replacing animal cooking oils with 1 tablespoon/d of total plant cooking oils or other plant cooking oils was related to 4% or 17% lower total mortality, respectively, while consumption of peanut oil or salad oil in replacement of animal cooking oils had a marginal inverse association with total mortality. CONCLUSIONS: Intakes of plant-sourced cooking oils, including peanut oil, soybean oil, canola oil, salad oil, and other plant cooking oils and substituting plant cooking oils for animal cooking oils were associated with lower total mortality among general Chinese population (NCT03259321).

8.
J Nutr ; 2020 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-32364230

RESUMEN

BACKGROUND: Evidence suggests that the relations between intakes of individual fatty acids and risk of type 2 diabetes (T2D) vary. However, associations between intakes of different cooking oils as sources of fatty acids and incident T2D remain largely unknown. OBJECTIVES: We aimed to evaluate relations between intakes of individual cooking oils and incident T2D in a nationwide Chinese cohort. METHODS: Overall 15,022 Chinese adults aged ≥20 y from the China Health and Nutrition Survey (CHNS) without self-reported T2D at entry in the 1997, 2000, 2004, 2006, or 2009 rounds were followed up until 2011. Consumption of various cooking oils/fats including lard, peanut oil, soybean oil, canola oil, sesame oil, and refined blended plant oil was assessed using 3-d 24-h records in each survey and the cumulative mean intake was calculated. Multivariable-adjusted Cox proportional hazards regression models were constructed to estimate the HRs of T2D. RESULTS: A total of 1014 cases were recorded after a median follow-up of 14 y. The intakes of animal and plant cooking oils/fats were both associated with higher T2D risk. Compared with nonconsumers, multivariable-adjusted HRs and 95% CIs for the highest tertiles were 1.31 (1.03, 1.67) for lard, 1.36 (1.10, 1.66) for peanut oil, 1.14 (0.91, 1.43) for soybean oil, 1.11 (0.87, 1.43) for canola oil, 1.02 (0.79, 1.32) for sesame oil, and 1.42 (1.12, 1.82) for refined blended plant oil. Substituting 1 tablespoon/d (8 g · 2000 kcal-1 · d-1) of soybean oil for the sum of lard, peanut oil, refined blended plant oil, and other plant oils was associated with a 3% (HR: 0.97; 95% CI: 0.95, 0.99) lower risk of T2D. CONCLUSIONS: Intakes of lard, peanut oil, and refined blended plant oil but not soybean oil, canola oil, and sesame oil are associated with higher T2D risk. Reducing the consumption of cooking oils in general may be protective against T2D among the Chinese population.This trial was registered at clinicaltrials.gov as NCT03259321.

9.
Mol Cell Biochem ; 469(1-2): 53-64, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32279149

RESUMEN

It has been shown that the conditioned medium of bone mesenchymal stem cells (BMSC-CM) can inhibit apoptosis of neural cells exposed to 2,5-hexanedione (HD), but its protective mechanism remains unclear. To investigate the underlying mechanism, VSC4.1 cells were given HD and 5, 10 and 15% BMSC-CM (v/v) in the current experiment. Our data showed that BMSC-CM concentration-dependently attenuated HD-induced cell apoptosis. Moreover, BMSC-CM remarkably decreased the mitochondrial cytochrome c (Cyt C) release and the caspase-3 activity in HD-given VSC4.1 cells. Given a relatively high expression of NGF in BMSCs and BMSC-CM, we hypothesized that NGF might be an important mediator of the protection of BMSC-CM against apoptosis induced by HD. To verify our hypothesis, the VSC4.1 cells were administrated with NGF and anti-NGF antibody in addition to HD. As expected, NGF could perfectly mimic BMSC-CM's protective role and these beneficial effects were abolished by anti-NGF antibody intervention. To further explore its mechanism, inhibitors of TrkA and Akt were given to the VSC4.1 cells and NGF/Akt/Bad pathway turned out to be involved in anti-apoptotic role of BMSC-CM. Based on these findings, it was revealed that BMSC-CM beneficial role was mediated by NGF and relied on the Akt/Bad pathway.

11.
Artículo en Inglés | MEDLINE | ID: mdl-32343466

RESUMEN

Biological ion channels and ion pumps with sub-nanometer sizes modulate ion transport in response to external stimuli. Realizing such functions with sub-nanometer solid-state nanopores has been an important topic with wide practical applications. Herein, we demonstrate a biomimetic photoresponsive ion channel and photodriven ion pump using a porphyrin-based metal-organic framework membrane with pore sizes comparable to hydrated ions. We show that the molecular-size pores enable precise and robust optoelectronic ion transport modulation in a broad range of concentrations, unparalleled with conventional solid-state nanopores. Upon decoration with platinum nanoparticles to form a Schottky barrier photodiode, photovoltage across the membrane is generated with "uphill" ion transport from low concentration to high concentration. These results may spark applications in energy conversion, ion sieving, and artificial photosynthesis.

12.
Chem Commun (Camb) ; 56(38): 5115-5118, 2020 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-32319464

RESUMEN

Graphdiyne (GDY) is a new recently-synthesized carbon allotrope. We find here that graphdiyne oxide (GDYO), the oxidized form of GDY, can serve as a new kind of carbon nanozyme mimicking peroxidase. This finding essentially offers a new platform for fundamental understanding of carbon nanozymes and broadens the application of GDY.

13.
Cell Commun Signal ; 18(1): 55, 2020 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-32245484

RESUMEN

BACKGROUND: IDH2/R140Q mutation is frequently detected in acute myeloid leukemia (AML). It contributes to leukemia via accumulation of oncometabolite D-2-HG. Therefore, mutant IDH2 is a promising target for AML. Discovery of IDH2 mutant inhibitors is in urgent need for AML therapy. METHODS: Structure-based in silico screening and enzymatic assays were used to identify IDH2/R140Q inhibitors. Molecular docking, mutant structure building and molecular dynamics simulations were applied to investigate the inhibitory mechanism and selectivity of CP-17 on IDH2/R140Q. TF-1 cells overexpressed IDH2/R140Q mutant were used to study the effects of CP-17 on cellular proliferation and differentiation, the wild-type TF-1 cells were used as control. The intracellular D-2-HG production was measured by LC-MS. The histone methylation was evaluated with specific antibodies by western blot. RESULTS: CP-17, a heterocyclic urea amide compound, was identified as a potent inhibitor of IDH2/R140Q mutant by in silico screening and enzymatic assay. It exhibits excellent inhibitory activity with IC50 of 40.75 nM against IDH2/R140Q. More importantly, it shows poor activity against the wild-type IDH1/2, resulting in a high selectivity of over 55 folds, a dramatic improvement over previously developed inhibitors such as AGI-6780 and Enasidenib. Molecular simulations suggested that CP-17 binds to IDH2/R140Q at the allosteric site within the dimer interface through extensive polar and hydrophobic interactions, locking the enzyme active sites in open conformations with abolished activity to produce D-2-HG. Cellular assay results demonstrated that CP-17 inhibits intracellular D-2-HG production and suppresses the proliferation of TF-1 erythroleukemia cells carrying IDH2/R140Q mutant. Further, CP-17 also restores the EPO-induced differentiation that is blocked by the mutation and decreases hypermethylation of histone in the TF-1(IDH2/R140Q) cells. CONCLUSIONS: These results indicate that CP-17 can serve as a lead compound for the development of inhibitory drugs against AML with IDH2/R140Q mutant. Video abstract.

14.
Artículo en Inglés | MEDLINE | ID: mdl-32331821

RESUMEN

OBJECTIVES: We sought to demonstrate in an animal model that helical stents made from a nickel titanium alloy called nitinol (NiTi) and designed for malacic airways could be delivered and removed without significant trauma while minimally impeding mucus clearance during the period of implantation. METHODS: Stents were delivered and removed from the tracheas of healthy 20 kg swine (n = 5) using tools designed to minimize trauma. In 4-week experiments, the stents were implanted on day 0, removed after 3 weeks, and swine were put to death after 4 weeks. Weekly bronchoscopies, radiographs, and mucus clearance examinations were performed in vivo. Hematoxylin and eosin staining and scanning electron microscopy imaging were used to evaluate foreign body response, tracheal tissue reaction, and damage and to measure unciliated regions. RESULTS: In all in vivo experiments, the stent was implanted and removed atraumatically. Mucus clearance was maintained throughout the experiment period. Hematoxylin and eosin-stained slides showed that foreign body response and tracheal tissue damage were localized to the stented subsections. Tracheal tissue reaction and damage was further restricted to the epithelium and submucosal layers. Scanning electron microscopy imaging revealed that the cilia were absent only over the contact area between the trachea and the wire forming the helical stent. CONCLUSIONS: Helical nitinol stents designed to provide radial support for malacic airways were well tolerated in a porcine model, providing for mucus clearance while also enabling atraumatic removal.

16.
Biomed Res Int ; 2020: 2137319, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32309427

RESUMEN

Clear cell renal cell carcinoma (ccRCC) is a major histological subtype of renal cell carcinoma and can be clinically divided into four stages according to the TNM criteria. Identifying clinical stage-related genes is beneficial for improving the early diagnosis and prognosis of ccRCC. By using bioinformatics analysis, we aim to identify clinical stage-relevant genes that are significantly associated with the development of ccRCC. First, we analyzed the gene expression microarray data sets: GSE53757 and GSE73731. We divided these data into five groups by staging information-normal tissue and ccRCC stages I, II, III, and IV-and eventually identified 500 differentially expressed genes (DEGs). To obtain precise stage-relevant genes, we subsequently applied weighted gene coexpression network analysis (WGCNA) to the GSE73731 dataset and KIRC data from The Cancer Genome Atlas (TCGA). Two modules from each dataset were identified to be related to the tumor TNM stage. Several genes with high inner connection inside the modules were considered hub genes. The intersection results between hub genes of key modules and 500 DEGs revealed UBE2C, BUB1B, RRM2, and TPX2 as highly associated with the stage of ccRCC. In addition, the candidate genes were validated at both the RNA expression level and the protein level. Survival analysis also showed that 4 genes were significantly correlated with overall survival. In conclusion, our study affords a deeper understanding of the molecular mechanisms associated with the development of ccRCC and provides potential biomarkers for early diagnosis and individualized treatment for patients at different stages of ccRCC.

17.
Artículo en Inglés | MEDLINE | ID: mdl-32328768

RESUMEN

PURPOSE: To assess the added value of susceptibility-weighted imaging (SWI) to diffusion-weighted imaging (DWI) in the characterization of parotid gland tumors. METHODS: Seventy-eight patients with pathologically confirmed parotid gland tumors, who underwent DWI and SWI for pre-surgery evaluation, were enrolled. Apparent diffusion coefficient (ADC) and degree of intratumoral susceptibility signal intensity (ITSS) were measured and compared between benign and malignant groups, and among pleomorphic adenoma (PA), Warthin tumor (WT) and malignant tumor (MT). Independent sample t test, one-way analysis of variance and receiver operating characteristic curve analysis were used for statistical analyses. RESULTS: Benign parotid gland tumor showed a significantly higher mean ADC value than malignant tumors (0.836 ± 0.350 vs 0.592 ± 0.163, p = 0.001). Setting an average ADC value of 0.679 as the cut-off value, optimal differentiating performance could be obtained (AUC, 0.700; sensitivity, 62.69%; specificity, 81.82%) for differentiating malignant from benign tumors. PA showed significantly higher mean ADC and less ITSS than WT (ADC, p < 0.001; ITSS, p = 0.033) and MT (ADC, p < 0.001; ITSS, p = 0.024), while the difference between WT and MT was not significant (ADC, p = 0.826; ITSS, p = 0.539). After integration with ITSS, the diagnostic performance of ADC was improved for differentiating PA from WT (AUC 0.921 vs 0.873) and from MT (AUC 0.906 vs 0.882). CONCLUSION: SWI could provide added information to DWI and serve as a supplementary imaging marker for the characterization of parotid gland tumors.

18.
Channels (Austin) ; 14(1): 141-150, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32274960

RESUMEN

Transient receptor potential vanilloid subfamily member 1 (TRPV1) is a nonselective cation channel, that is mainly distributed in sensory nerve endings and can release a variety of neurotransmitters after activation. Early studies showed that it mainly conducts pain sensation, but research has demonstrated that it also plays an important role in cardiovascular diseases. Notably, in atherosclerosis, the activation of TRPV1 can regulate lipid metabolism, reduce foam cell formation, protect endothelial cells, inhibit smooth muscle cell proliferation and inhibit inflammation and oxidation. In this review, the role of the TRPV1 channel in atherosclerosis was discussed to provide new ideas for the prevention and treatment of atherosclerotic diseases.

19.
Artículo en Inglés | MEDLINE | ID: mdl-32249515

RESUMEN

DJ-1 protein deficiency caused by PARK7 gene mutation has been suggested to closely relate to Parkinson's disease (PD), mainly through the attenuation D2 dopamine receptor activity in mice; however, whether or how it affects the vesicular storage and exocytosis of neurochemicals remains unclear. By using electrochemical methods at a single vesicle/cell level with nano/micro-tip electrodes, we for the first time find that DJ-1 protein deficiency caused by PARK7 gene knockout (KO) in mice has little effect on vesicular catecholamine content but significantly prolongs the exocytotic events, especially the closing time of exocytotic fusion pores. Further studies suggest the inhibition of α-synuclein aggregation by DJ-1 protein might be one way that DJ-1 protein acts on neurotransmission. This finding offers the first direct link between DJ-1 protein deficiency and vesicular chemical storage and release of chemicals, providing a new chemical insight into the pathology of PD caused by PARK7 gene mutation.

20.
PLoS One ; 15(4): e0231497, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32287291

RESUMEN

Salt stress is one of the major environmental constraints for plant growth. Although the ways in which mycorrhizal plants deal with salt stress have been well documented, it still is blank for Euonymus maackii, an important local ecological restoration tree, to arbuscular mycorrhizal fungi (AMF) inoculation and salt stress. In this study, we tested the effect of different salt levels (0, 50, 100,150 and 200 mM) and AMF inoculation on E. maackii growth rate, photosynthesis, antioxidant enzymes, nutrient absorption and salt ion distribution. The results indicated negative effect of salt on height, photosynthesis capacity, nutrition accumulation, while salt stimulated the antioxidant defense system and salt ions accumulation. The toxic symptom by excessive accumulation of salt ions worsen with salt level increased gradually (except for the 50 mM NaCl treatment). AMF inoculation alleviated the toxic symptom under moderate salt levels (100 and 150 mM) by increasing photosynthesis capacity, accelerating nutrient absorption and activating antioxidant enzyme activities under salt stress. Meanwhile, effect of AMF was not detected on seedlings under slight (0 and 50 mM) and high (200 mM) NaCl concentration. Our study indicated AMF had positive impact on E. maackii subjected to salt, which suggested potential application of AMF- E. maackii on restoration of salt ecosystems.

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