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1.
Pathol Oncol Res ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31482398

RESUMO

Retinoblastoma (RB) is a malignant intraocular tumor that frequently occurs in infants and toddlers. Although the most of RB patients in the developed countries could survival from this cancer, the patients in undeveloped areas are still suffering. The human retinal pigment epithelial cell line ARPE-19 and human retinoblastoma (RB) cell lines HXO-RB44, Y79, and WERI-Rb1 were cultured. The mRNA levels of BANCR and miR-204-3p in these cell lines were measured by qRT-PCR. After transfection with sh-BANCR or treatment with miR-204-3p inhibitor in Y79 cells, the cell proliferation rate, growth, invasion, migration, apoptosis and Wnt/ß-catenin signaling pathway activity were measured. The regular Y79 and Y79 cells stably expressed sh-BANCR were injected subcutaneously into nude mice, respectively. The volumes and pathohistological futures of tumors were compared. The biochemical features similar to the cell culture were detected and compered. The mRNA measurements showed that BANCR negatively modulate miR-204-3p expression via directly integration with it. Besides, miR-204-3p and Wnt/ß-catenin signalling pathway were found to participate in the oncogenic effects of BANCR on RB cell line by Hoechst staining, cell Counting Kit-8 (CCK-8) assay, wound healing assay, transwell assay, and Western blot analysis in vitro. In addition, an in vivo tumorigenesis experiment in nude mice injected with Y79 cells stably expressed sh-BANCR conformed in the effects of BANCR on RB. Taken together, the knockdown of BANCR inhibited cell proliferation, apoptosis, invasion, and migration in RB via targeting miR-204-3p, the mechanism may involve inhibiting Wnt/ß-catenin signaling pathway.

2.
Anatol J Cardiol ; 22(3): 102-111, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31475956

RESUMO

OBJECTIVE: Trimetazidine is a piperazine-derived metabolic agent. It exerts cardioprotective effects against myocardial ischemia/reperfusion (I/R) injury. In addition, studies confirm that the cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway serves a beneficent role in attenuating myocardial I/R injury. However, the underlying role of the CSE/H2S pathway in the trimetazidine-induced protection against myocardial I/R injury remains elusive. Therefore, this study investigated whether trimetazidine ameliorates hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocyte injuries in an in vitro cell model of myocardial I/R injury, by enhancing the CSE/H2S pathway. METHODS: The H9c2 cell viability was determined with a cell counting Kit-8. RESULTS: Trimetazidine significantly increased the cell viability and decreased lactate dehydrogenase (LDH) release in H/R-treated H9c2 cells. Additionally, trimetazidine increased the H2S levels and the CSE mRNA and protein levels, promoting the CSE/H2S pathway under H/R conditions. The inhibition of the CSE/H2S pathway, induced by transfection with specific siRNA against human CSE (si-CSE), eliminated the trimetazidine-induced upregulation of cell viability, downregulation of LDH release, increase of caspase-3 activity and apoptosis regulator BAX expression, and the decrease of apoptosis regulator Bcl-2 expression, which suggests involvement of the CSE/H2S pathway in trimetazidine-induced cardioprotection. Furthermore, trimetazidine mitigated the H/R-induced increase in reactive oxygen species production and NADPH oxidase 2 expression, and decrease in superoxide dismutase activity and glutathione level, in H9c2 cells. These effects were also reversed by si-CSE. CONCLUSION: This study revealed that the CSE/H2S pathway mediates the trimetazidine-induced protection of H9c2 cardiomyocytes against H/R-induced damage by inhibiting apoptosis and oxidative stress.

3.
J Exp Clin Cancer Res ; 38(1): 384, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477177

RESUMO

BACKGROUND: Aberrant activation of Notch signaling has been causally linked to the metastasis of hepatocellular carcinoma (HCC), however the underlying molecular mechanisms are still poorly understood. RING finger protein 187 (RNF187) was recently revealed to be a driver of several cancers, but its expression pattern and biological function in HCC are unknown. METHODS: The expression levels of Notch1 and RNF187 were assessed in two independent cohorts of HCC tissues, and modulation of Notch1 in HCC cells was performed to explore the regulatory role of Notch1 in HCC metastasis. RNA-sequencing (RNA-seq), bioinformatics analysis, luciferase reporter analysis, and chromatin immunoprecipitation assay (ChIP) were used to clarify the relationship between Notch1 signaling and its potential target Ring finger protein 187 (RNF187). Gain- and loss-of-function studies were used to dissect the role of Notch1-RNF187 signaling in promoting HCC metastasis. The impact of Notch1-RNF187 activity in determining clinical prognosis for HCC patients was evaluated by multivariate Cox regression. RESULTS: By RNA-seq, luciferase reporter analysis, and ChIP assay, RNF187 was confirmed to be a direct transcriptional target of Notch1, as Notch1 could activate RNF187 promoter whereas the pro-migratory and pro-invasive effects of Notch1 were significantly attenuated by RNF187 knockdown. Meanwhile, RNF187 silencing could attenuate the Notch1-dependent epithelial-mesenchymal transition (EMT). Moreover, overexpression of RNF187 counteracted the inhibitory effect of Notch1 knockdown on cancer progression. Importantly, HCC patients with high level of hepatic Notch1 expression had shorter disease-free survival (DFS) than those with low level of hepatic Notch1 expression. Furthermore, patients with high level of Notch1 and RNF187 co-expression showed the shortest DFS. The expression level of Notch1 and RNF187 was an independent prognostic factor for HCC. CONCLUSIONS: For the first time we identified that RNF187 is an essential factor for Notch1 to promote invasion and metastasis of HCC. Of highly clinical relevance, we found that activation of Notch1-RNF187 correlates with a worse prognosis of HCC patients. These findings provide a solid foundation for developing novel strategies to tackle HCC metastasis.

4.
Biophys J ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31474305

RESUMO

Glioblastoma is a primary malignant brain tumor characterized by highly infiltrative glioma cells. Vasculature and white matter tracts are considered to be the preferred and fastest routes for glioma invasion through brain tissue. In this study, we systematically quantified the routes and motility of the U251 human glioblastoma cell line in mouse brain slices by multimodal imaging. Specifically, we used polarization-sensitive optical coherence tomography to delineate nerve fiber tracts while confocal fluorescence microscopy was used to image cell migration and brain vasculature. Somewhat surprisingly, we found that in mouse brain slices, U251 glioma cells do not follow white matter tracts but rather preferentially migrate along vasculature in both gray and white matter. In addition, U251 cell motility is ∼2-fold higher in gray matter than in white matter (91 vs. 43 µm2/h), with a substantial fraction (44%) of cells in both regions invading without close association with vasculature. Interestingly, within both regions, the rates of migration for the perivascular and televascular routes of invasion were indistinguishable. Furthermore, by imaging of local vasculature deformation dynamics during cell migration, we found that U251 cells are capable of exerting traction forces that locally pull on their environment, suggesting the applicability of a "motor-clutch"-based model for migration in vivo. Overall, by quantitatively analyzing the migration dynamics along the diverse pathways followed by invading U251 glioma cells as observed by our multimodal imaging approach, our studies suggest that effective antiinvasive strategies will need to simultaneously limit parallel routes of both perivascular and televascular invasion through both gray and white matter.

5.
Sci Total Environ ; 697: 134142, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484087

RESUMO

The formation of iodinated disinfection byproducts (I-DBPs) in drinking waters is of a concern due to their higher cyto- and genotoxicity than their chlorinated and brominated analogues. This study investigated the formation of I-DBPs under chloramination conditions using preformed chloramine and associated cyto- and geno-toxicities obtained with Chinese Hamster Ovary (CHO) cell assay. Cyto- and geno-toxicity of the samples were also calculated using DBP toxicity index values and correlated with total organic halide (TOX) formation. In low iodide (I-) (0.32 µM, 40 µg L-1) water, increasing dissolved organic carbon (DOC) concentration of selected waters from 0.1 to 0.25 mg L-1 increased the formation of iodinated trihalomethanes (I-THMs), while further increases from 0.25 to 4 mg L-1 produced an opposite trend. In high iodide water (3.2 µM, 400 µg L-1), increasing DOC from 0.5 to 4 mg L-1 gradually increased the I-THM formation, while a decrease was observed at 5.4 mg L-1 DOC. Iodoform was the most influenced species from the changes in DOC concentration. While increasing the initial iodide concentration from 0 to 5 µM increased the formation of iodoform, it did not make any considerable impact on the formation of other I-THMs. The measured cytotoxicity of samples was significantly correlated with increasing DOC concentration. Unknown TOCl and TOI showed a high correlation with measured cytotoxicity, while calculated total organic chlorine (TOCl) and total organic iodine (TOI) did not correlate. The comparison of measured and calculated cytotoxicity values showed that the calculated values do not always represent the overall cytotoxicity, since the formation of unknown DBPs are not taken into consideration during the toxicity calculations.

6.
Sensors (Basel) ; 19(15)2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31362439

RESUMO

In real-world robotic navigation, some ambiguous environments contain symmetrical or featureless areas that may cause the perceptual aliasing of external sensors. As a result of that, the uncorrected localization errors will accumulate during the localization process, which imposes difficulties to locate a robot in such a situation. Using the ambiguity grid map (AGM), we address this problem by proposing a novel probabilistic localization method, referred to as AGM-based adaptive Monte Carlo localization. AGM has the capacity of evaluating the environmental ambiguity with average ambiguity error and estimating the possible localization error at a given pose. Benefiting from the constructed AGM, our localization method is derived from an improved Dynamic Bayes network to reason about the robot's pose as well as the accumulated localization error. Moreover, a portal motion model is presented to achieve more reliable pose prediction without time-consuming implementation, and thus the accumulated localization error can be corrected immediately when the robot moving through an ambiguous area. Simulation and real-world experiments demonstrate that the proposed method improves localization reliability while maintains efficiency in ambiguous environments.

8.
Sci Adv ; 5(8): eaax1101, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31453335

RESUMO

Meiosis is a specialized type of cell division that creates haploid germ cells and ensures their genetic diversity through homologous recombination. We show that the H3K4me3 reader ZCWPW1 is specifically required for meiosis prophase I progression in male but not in female germ cells in mice. Loss of Zcwpw1 in male mice caused a complete failure of synapsis, resulting in meiotic arrest at the zygotene to pachytene stage, accompanied by incomplete DNA double-strand break repair and lack of crossover formation, leading to male infertility. In oocytes, deletion of Zcwpw1 only somewhat slowed down meiosis prophase I progression; Zcwpw1-/- oocytes were able to complete meiosis, and Zcwpw1-/- female mice had normal fertility until mid-adulthood. We conclude that the H3K4me3 reader ZCWPW1 is indispensable for meiosis synapsis in males but is dispensable for females. Our results suggest that ZCWPW1 may represent a previously unknown, sex-dependent epigenetic regulator of germ cell meiosis in mammals.

9.
Genes (Basel) ; 10(8)2019 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-31426485

RESUMO

Circadian rhythms are biological rhythms with a period of approximately 24 h. While canonical circadian clock genes and their regulatory mechanisms appear highly conserved, the evolution of clock gene families is still unclear due to several rounds of whole genome duplication in vertebrates. The spotted gar (Lepisosteus oculatus), as a non-teleost ray-finned fish, represents a fish lineage that diverged before the teleost genome duplication (TGD), providing an outgroup for exploring the evolutionary mechanisms of circadian clocks after whole-genome duplication. In this study, we interrogated the spotted gar draft genome sequences and found that spotted gar contains 26 circadian clock genes from 11 families. Phylogenetic analysis showed that 9 of these 11 spotted gar circadian clock gene families have the same number of genes as humans, while the members of the nfil3 and cry families are different between spotted gar and humans. Using phylogenetic and syntenic analyses, we found that nfil3-1 is conserved in vertebrates, while nfil3-2 and nfil3-3 are maintained in spotted gar, teleost fish, amphibians, and reptiles, but not in mammals. Following the two-round vertebrate genome duplication (VGD), spotted gar retained cry1a, cry1b, and cry2, and cry3 is retained in spotted gar, teleost fish, turtles, and birds, but not in mammals. We hypothesize that duplication of core clock genes, such as (nfil3 and cry), likely facilitated diversification of circadian regulatory mechanisms in teleost fish. We also found that the transcription factor binding element (Ahr::Arnt) is retained only in one of the per1 or per2 duplicated paralogs derived from the TGD in the teleost fish, implicating possible subfuctionalization cases. Together, these findings help decipher the repertoires of the spotted gar's circadian system and shed light on how the vertebrate circadian clock systems have evolved.

10.
Clin Cancer Res ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444252

RESUMO

On December 20, 2018, the Food and Drug Administration approved calaspargase pegol-mknl (CALASP), an asparagine specific enzyme, as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in pediatric and young adult patients age 1 month to 21 years. Efficacy was determined based on achievement and maintenance of steady-state nadir serum asparaginase activity (NSAA) above 0.1 U/mL when using CALASP, 2500 U/m2 intravenously, every 3 weeks. In a randomized comparison to pegaspargase (PEGASP) every 2 weeks, treatment with CALASP every 3 weeks had a similar safety profile and no substantial impairment in event-free survival. The pharmacokinetics of CALASP were studied when administered in combination with multiagent chemotherapy in 124 patients with B-cell ALL in Study AALL07P4 and Study DFCI 11-001. The results showed that 123 (99%, 95% confidence interval (CI): 96%-100%) of the 124 patients maintained NSAA > 0.1 U/mL at weeks 6, 12, 18, 24 and 30 of post-induction phase. Maintaining adequate NSAA levels is critical to successful treatment of ALL. Herein we describe the FDA review and approval of CALASP.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31454447

RESUMO

An unprecedented stereoselective synthesis of trisubstituted vinylboronates was reported from the direct borylation of lithium ketone enolates under transition-metal-free conditions. The stereospecific C-O borylation of lithium enolates was triggered by a carbonyl-induced 1,3- metalate rearrangement through C -bound boron enolate. DFT calculations and control experiments revealed that the stereoselectivity was controlled by steric hindrance. A variety of stereospecific trisubstituted vinylboronates, together with several tetrasubstituted vinylboronates, were conveniently synthesized with the newly developed methodology. Based on the transformation of stereospecific vinylboronate, a single isomeric Dienestrol was efficiently obtained. Previously, this compound could only be synthesized as a mixture of stereoisomers.

12.
Talanta ; 205: 120136, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450434

RESUMO

Investigating the kinetics of biochemical reactions plays vital roles in understanding the reaction mechanism. However, many biochemical reactions occur in the time scale of millisecond or even microsecond, which is out of the time-resolution limit of traditional methods. Microfluidic mixers, also referred to micromixers, have been widely developed to resolve the kinetics of biochemical reactions, due to their short mixing time (down to microsecond scale), low sample consumption (as low as several microliters), capability of mixing high-viscosity fluids (up to 35.25 mPa s) and ease of integration with different detection techniques. In this review, we briefly introduced mixing mechanism in micromixers, and discussed the mixing principle of four main types of micromixers: hydrodynamic focusing micromixer, chaotic convection micromixer, droplet micromixer and acoustic micromixer. We then presented how these micromixers applied in investigating enzymatic constant, resolving the kinetics of biomolecule folding or studying biomolecular interactions. At last we summarized the detection technologies used in micromixers for measuring the kinetics and predicted the potential future development on micromixers. We anticipated that micromixers would attract more attentions and would advance the field of kinetics study of biochemical reactions in future.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31437470

RESUMO

PURPOSE: We evaluated survival of patients with pulmonary recurrence-based oligometastatic non-small cell lung cancer (NSCLC) whose lesions were all treated with stereotactic ablative radiotherapy (SABR) and the prognostic value of peripheral immune cells. METHODS AND MATERIALS: In this prospective observational cohort study, we prospectively enrolled 63 patients with oligometastatic NSCLC, for whom all metastases were treated with SABR. Peripheral blood samples were collected 3 days before treatment began, and flow cytometry was used to identify proportions of regulatory T cells (Tregs; CD4+CD25+CD127low), B cells, NK cells, γδT cells, CD8+CD28+ T cells, and CD8+CD28- T cells. Overall survival (OS) and progression-free survival (PFS) was estimated by the Kaplan-Meier method, and the potential prognostic value of clinicopathologic factors was evaluated by Cox proportional hazards regression. RESULTS: At a median follow-up time of 19.1 months, estimated OS rates were 84.3% at 1 year, 63.4% at 2 years, and 44.0% at 3 years; corresponding PFS rates were 55.2%, 30.9%, and 25.7%. Estimated local control rates were 96.7% at 1 year and 92.7% at both 2 years and 3 years. Patients with high numbers of Tregs had poorer OS and PFS than did those with low numbers of Tregs (OS: 16.1 months vs. not reached, P=0.006; PFS: 11.0 vs. 21.7 months, P=0.013). Treg level was found to be an independent predictor of both OS and PFS in multivariate analyses (OS: hazard ratio [HR] 2.68, P=0.038; PFS: HR 2.35, P=0.011). CONCLUSIONS: Our results revealed the independent prognostic value of Treg in patients treated with SABR for pulmonary recurrence-based oligometastatic NSCLC. Additional treatments may be needed for patients with oligometastatic NSCLC and poor outcomes.

14.
ISA Trans ; 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31420125

RESUMO

In recent years, an increasing popularity of deep learning model for intelligent condition monitoring and diagnosis as well as prognostics used for mechanical systems and structures has been observed. In the previous studies, however, a major assumption accepted by default, is that the training and testing data are taking from same feature distribution. Unfortunately, this assumption is mostly invalid in real application, resulting in a certain lack of applicability for the traditional diagnosis approaches. Inspired by the idea of transfer learning that leverages the knowledge learnt from rich labeled data in source domain to facilitate diagnosing a new but similar target task, a new intelligent fault diagnosis framework, i.e., deep transfer network (DTN), which generalizes deep learning model to domain adaptation scenario, is proposed in this paper. By extending the marginal distribution adaptation (MDA) to joint distribution adaptation (JDA), the proposed framework can exploit the discrimination structures associated with the labeled data in source domain to adapt the conditional distribution of unlabeled target data, and thus guarantee a more accurate distribution matching. Extensive empirical evaluations on three fault datasets validate the applicability and practicability of DTN, while achieving many state-of-the-art transfer results in terms of diverse operating conditions, fault severities and fault types.

15.
Mol Genet Genomic Med ; : e933, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429529

RESUMO

BACKGROUND: This study was aimed to explore the METTL3 and METTL14 expressions in children with ETV6/RUNX1(E/R)-positive acute lymphoblastic leukemia (ALL) and investigate the relation between the METTL3 and METTL14 expressions with clinical features. METHODS: Thirty-seven newly diagnosed E/R-positive ALL children and six controls were included in this study. Real-time quantitative polymerase chain reaction (RT-PCR) was used to detect the mRNA expression level of METTL3 and METTL14. RESULTS: Among the 37 cases, 51.35% (n = 19) were boys and 48.65% (n = 18) were girls and the median age was 4.72 (1.72-11.99) years. Among the six controls, 50% (n = 3) were boys and 50% (n = 3) were girls and the median age was 5.24 (1.53-13.17) years. The expression level of METTL3 and METTL14 in E/R-positive ALL patients were lower than in controls (p < .05). Although failed to achieve statistical significance, the expression level of METTL3 and METTL14 in relapse patients were lower than nonrelapse patients (p = .171, p = .150, respectively). CONCLUSION: The reduced levels of METTL3 and METTL14 suggest a possible role in the pathogenesis and course of E/R-positive ALL. METTL3 and METTL14 may become new prognostic factors, and rationalize specific treatment intensification in possible E/R-positive relapse patients.

16.
Nat Commun ; 10(1): 3404, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363125

RESUMO

We describe pLink 2, a search engine with higher speed and reliability for proteome-scale identification of cross-linked peptides. With a two-stage open search strategy facilitated by fragment indexing, pLink 2 is ~40 times faster than pLink 1 and 3~10 times faster than Kojak. Furthermore, using simulated datasets, synthetic datasets, 15N metabolically labeled datasets, and entrapment databases, four analysis methods were designed to evaluate the credibility of ten state-of-the-art search engines. This systematic evaluation shows that pLink 2 outperforms these methods in precision and sensitivity, especially at proteome scales. Lastly, re-analysis of four published proteome-scale cross-linking datasets with pLink 2 required only a fraction of the time used by pLink 1, with up to 27% more cross-linked residue pairs identified. pLink 2 is therefore an efficient and reliable tool for cross-linking mass spectrometry analysis, and the systematic evaluation methods described here will be useful for future software development.

17.
Future Oncol ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31373223

RESUMO

Aim: To evaluate the value of pretreatment blood biomarkers in predicting pathologic responses to neoadjuvant chemoradiotherapy (neo-CRT) in patients with locally advanced rectal cancer. Materials & methods: We conducted logistic regression analysis and receiver operating characteristic to assess the predictive value of blood biomarkers. The outcome was defined by the pathologic complete response and good response. Results: Carcinoembryonic antigen (CEA) (p < 0.001), neutrophil-to-lymphocyte ratio (p = 0.024), platelet-to-lymphocyte ratio (p = 0.006) and lymphocyte-to-monocyte ratio (LMR) (p < 0.001) were significant predictors of pathologic complete response, with area under the curve of 0.785, 0.794, 0.740 and 0.913, respectively; CEA (p = 0.007) and LMR (p < 0.001) correlated significantly with good response, with area under the curve of 0.743 and 0.771, respectively. Conclusion: Lower LMR and higher CEA, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio before treatment could predict poorer pathologic response to neo-CRT in patients with locally advanced rectal cancer.

18.
JAMA Cardiol ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31365039

RESUMO

Importance: Whether optimal cardiovascular health metrics may counteract the risk of cardiovascular events among patients with prediabetes or diabetes is unclear. Objective: To investigate the associations of ideal cardiovascular health metrics (ICVHMs) with subsequent development of cardiovascular disease (CVD) among participants with prediabetes or diabetes as compared with participants with normal glucose regulation. Design, Setting, and Participants: The China Cardiometabolic Disease and Cancer Cohort Study was a nationwide, population-based, prospective cohort study of 20 communities from various geographic regions in China. The study included 111 765 participants who were free from CVD or cancer at baseline. Data were analyzed between 2011 and 2016. Exposures: Prediabetes and diabetes were defined according to the American Diabetes Association 2010 criteria. Seven ICVHMs were adapted from the American Heart Association recommendations. Main Outcomes and Measures: The composite of incident fatal or nonfatal CVD, including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure. Results: Of the 111 765 participants, 24 881 (22.3%) had normal glucose regulation, 61 024 (54.6%) had prediabetes, and 25 860 (23.1%) had diabetes. Mean (SD) age ranged from 52.9 (8.6) years to 59.4 (8.7) years. Compared with participants with normal glucose regulation, among participants with prediabetes, the multivariable-adjusted hazard ratio for CVD was 1.34 (95% CI, 1.16-1.55) for participants who had 1 ICVHM or less and 0.57 (95% CI, 0.43-0.75) for participants who had at least 5 ICVHMs; among participants with diabetes, the hazard ratios for CVD were 2.05 (95% CI, 1.76-2.38) and 0.80 (95% CI, 0.56-1.15) for participants who had 1 ICVHM or less and at least 5 ICVHMs, respectively. Such pattern of association between ICVHM and CVD was more prominent for participants younger than 55 years (prediabetes and at least 5 ICVHMs: hazard ratio [HR], 0.32; 95% CI, 0.16-0.63; 1 ICVHM or less: HR, 1.58, 95% CI, 1.13-2.21; diabetes and at least 5 ICVHMs: HR, 0.99; 95% CI, 0.44-2.26; 1 ICVHM or less: HR, 2.46; 95% CI, 1.71-3.54; compared with normal glucose regulation) than for participants 65 years or older (prediabetes and at least 5 ICVHMs: HR, 0.80; 95% CI, 0.50-1.26; 1 ICVHM or less: HR, 1.01; 95% CI, 0.79-1.31; diabetes and at least 5 ICVHMs: HR, 0.79; 95% CI, 0.46-1.35; 1 ICVHM or less: HR, 1.73; 95% CI, 1.36-2.22, compared with normal glucose regulation; P values for interaction ≤.02). Additionally, the hazard ratio for CVD per additional ICVHM was 0.82 (95% CI, 0.79-0.86) among participants with prediabetes and was 0.85 (95% CI, 0.80-0.89) among participants with diabetes. Conclusions and Relevance: Participants with prediabetes or diabetes who had 5 or more ICVHMs exhibited lower or no significant excess CVD risks compared with the participants with normal glucose regulation.

19.
J Dig Dis ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31414725

RESUMO

OBJECTIVE: As a result of resection, artificial ulcers were created after Endoscopic submucosal dissection (ESD). In order to heal the ulcers as soon as possible, vonoprazan, a novel potassium competitive acid blocker, which may have a better efficacy, was used in some studies. A meta-analysis was performed to evaluate the efficacy and safety of vonoprazan on the healing of artificial ulcers after ESD compared to PPIs. METHODS: Embase, Medline, Scopus and Cochrane Library were searched for all studies that associated with the treatment of post-ESD ulcers. A meta-analysis was performed to compare the efficacy between PPIs and vonoprazan on the coalescence of post-ESD ulcers. RESULTS: 14 citations consisted of 1429 patients were involved in this study. When comparing ulcer contraction rate, Vonoprazan showed a better efficacy than PPIs (MD [95% CI] = 0.56 [0.18-0.93]). Vonoprazan also led to a higher scar formation rate when the treatment course was equal (OR [95% CI] =1.58 [1.00-2.47]) and showed a potential superiority on reducing the risk of post-ESD bleeding rate than those who used PPIs with a pooled OR of 0.69 but without statistically significant difference. CONCLUSION: Vonoprazan showed a better efficacy in ulcer size contraction rate and achieved more completely healing in the treatment of post-ESD ulcers, and didn't induce any incremental risk of post-ESD bleeding compared with PPIs. Vonoprazan can be an appropriate choice in the management of artificial ulcers after ESD. This article is protected by copyright. All rights reserved.

20.
Plant Biotechnol J ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31368610

RESUMO

China is the origin and evolutionary centre of Oriental pears. Pyrus betuleafolia is a wild species native to China and distributed in the northern region, and it is widely used as rootstock. Here, we report the de novo assembly of the genome of P. betuleafolia-Shanxi Duli using an integrated strategy that combines PacBio sequencing, BioNano mapping and chromosome conformation capture (Hi-C) sequencing. The genome assembly size was 532.7 Mb, with a contig N50 of 1.57 Mb. A total of 59 552 protein-coding genes and 247.4 Mb of repetitive sequences were annotated for this genome. The expansion genes in P. betuleafolia were significantly enriched in secondary metabolism, which may account for the organism's considerable environmental adaptability. An alignment analysis of orthologous genes showed that fruit size, sugar metabolism and transport, and photosynthetic efficiency were positively selected in Oriental pear during domestication. A total of 573 nucleotide-binding site (NBS)-type resistance gene analogues (RGAs) were identified in the P. betuleafolia genome, 150 of which are TIR-NBS-LRR (TNL)-type genes, which represented the greatest number of TNL-type genes among the published Rosaceae genomes and explained the strong disease resistance of this wild species. The study of flavour metabolism-related genes showed that the anthocyanidin reductase (ANR) metabolic pathway affected the astringency of pear fruit and that sorbitol transporter (SOT) transmembrane transport may be the main factor affecting the accumulation of soluble organic matter. This high-quality P. betuleafolia genome provides a valuable resource for the utilization of wild pear in fundamental pear studies and breeding.

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