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1.
IEEE Trans Image Process ; 29: 214-224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31331884

RESUMO

Compositing is one of the most important editing operations for images and videos. The process of improving the realism of composite results is often called harmonization. Previous approaches for harmonization mainly focus on images. In this paper, we take one step further to attack the problem of video harmonization. Specifically, we train a convolutional neural network in an adversarial way, exploiting a pixel-wise disharmony discriminator to achieve more realistic harmonized results and introducing a temporal loss to increase temporal consistency between consecutive harmonized frames. Thanks to the pixel-wise disharmony discriminator, we are also able to relieve the need of input foreground masks. Since existing video datasets which have ground-truth foreground masks and optical flows are not sufficiently large, we propose a simple yet efficient method to build up a synthetic dataset supporting supervised training of the proposed adversarial network. The experiments show that training on our synthetic dataset generalizes well to the real-world composite dataset. In addition, our method successfully incorporates temporal consistency during training and achieves more harmonious visual results than previous methods.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31796407

RESUMO

We propose an objective approach to assess the quality of video blending. Blending is a fundamental operation in video editing, which can smooth the intensity changes of relevant regions. However blending also generates artefacts such as bleeding and ghosting. To assess the quality of the blended videos, our approach considers the illuminance consistency as a positive aspect while regard the artefacts as a negative aspect. Temporal coherence between frames is also considered. We evaluate our metric on a video blending dataset where the results of subjective evaluation are available. Experimental results validate the effectiveness of our proposed metric, and shows that this metric gives superior performance over existing video quality metrics.

3.
Org Biomol Chem ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31803894

RESUMO

We developed a facile synthetic method to access cyclopenta[b]naphthalene derivatives via the Lewis or Brønsted acid catalysed cascade nucleophilic addition, electronic cyclization, ring-opening rearrangement of propargylic alcohol-tethered alkylidenecyclopropanes with indole and pyrrole derivatives. The reaction exhibited a broad substrate scope and good functional group tolerance under metal-free conditions, affording the desired products in moderate to good yields.

4.
Theranostics ; 9(25): 7628-7647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695791

RESUMO

Rationale: Peritoneal metastasis is one of the most common and life-threatening metastases in gastric cancer patients. The disseminated gastric cancer cells forming peritoneal metastasis exhibit a variety of characteristics that contrast with those of adjacent epithelial cell of gastric mucosa and even primary gastric cancer cells. We hypothesized that the gene expression profiles of peritoneal foci could reveal the identities of genes that might function as metastatic activator. Methods: In this study, we show, using in vitro, in vivo, in silico and gastric cancer tissues studies in humans and mice, that Homoebox A11 (HOXA11) potently promote peritoneal metastasis of gastric cancer cells. Results: Its mechanism of action involves alternation of cancer stemness and subsequently enhancement of the adhesion, migration and invasion and anti-apoptosis. This is achieved, mainly, through formation of a positive feedback loop between HOXA11 and Stat3, which is involved in the stimulation of Stat3 signaling pathway. Conclusions: These observations uncover a novel peritoneal metastatic activator and demonstrate the association between HOXA11, Stat3 and cancer stemness of gastric cancer cells, thereby revealing a previously undescribed mechanism of peritoneal metastasis.

5.
JAMA Netw Open ; 2(11): e1915245, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31722030

RESUMO

Importance: Multimorbidity is a growing health care problem in aging societies and is strongly associated with epidemiologic characteristics and sociodemographic factors. Knowledge of these associations is important for the design of effective preventive and management strategies. Objectives: To determine the association between multimorbidity and sociodemographic factors (age, socioeconomic status [SES], sex, and race/ethnicity) and the association between mental health diseases and physical diseases, as well as their implications for the types and costs of health care use. Design, Setting, and Participants: This population-based cross-sectional study used deidentified Singapore Eastern Regional Health System data collected between January 1, 2012, and December 31, 2016. Patients who were alive as of January 1, 2016, and residing in the Regional Health System region in 2016 (N = 1 181 024) were included. Patients who had no year of birth records (n = 573), were born in 2017 (n = 93), or died before January 1, 2016 (n = 47 322), were excluded. Main Outcomes and Measures: Multimorbidity, age, sex, SES, mental health, race/ethnicity, and health care use. Results: In the study population of 1 181 024 individuals, the mean (SD) age was 39.6 (22.1) years, 51.2% were women, 70.1% were Chinese, 7.1% were Indian, 13.5% were Malayan, and 9.3% were other races/ethnicities. Multimorbidity, present in 26.2% of the population, was more prevalent in female (26.8%; 95% CI, 26.7%-26.9%) than in male (25.6%; 95% CI, 25.5%-25.7%) patients and among patients with low SES (41.6%) than those with high SES (20.1%). Mental health diseases were significantly more prevalent among individuals with low SES (5.2%; 95% CI, 5.1%-5.2%) than high SES (2.1%; 95% CI, 2.0%-2.1%; P < .001). The 3 most prevalent disease combinations were chronic kidney disease and hypertension, chronic kidney disease and lipid disorders, and hypertension and lipid disorders. Although chronic kidney disease, hypertension, lipid disorders, and type 1 and/or type 2 diabetes-related diseases had a low cost per capita, the large number of patients with these conditions caused the overall proportion of the cost incurred by health care use to be more than twice that incurred in other diseases. Conclusions and Relevance: These findings emphasize the association between multimorbidity and sociodemographic factors such as increasing age, lower SES, female sex, and increasing number of mental disorders. Health care policies need to take sociodemographic factors into account when tackling multimorbidity in a population.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31722493

RESUMO

Network embedding aims to preserve topological structures of a network using low-dimensional vectors and has shown to be effective for driving a myriad of graph mining tasks (e.g., link prediction or classification) free of the stressful feature extraction procedure. Many methods have been proposed to integrate node content and/or label information, with nodes sharing similar content/labels being close to each other in the learned latent space. To date, existing methods either consider networked instances with a single label or consider a set of labels as a whole for node representation learning. Therefore, they cannot handle network of instances containing multiple labels (i.e. multi-labels), which are ubiquitous in describing complex concepts of instances. In this article, we formulate a new multi-label network embedding (MLNE) problem to learn feature representation for networked multi-label instances. We argue that the key to MLNE learning is to aggregate node topology structures, node content, and multi-label correlations. We propose a two-layer network embedding framework to couple information for effective learning. To capture higher order label correlations, we use labels to form a high-level label-label network over a low-level node-node network, in which the label network interacts with the node network through multi-labeling relations. The low-level node-node network can be enhanced by latent label-specific features from high-level label network with well-captured high-order correlations between labels. To enable the multi-label informed network embedding, we force both node and label representations being optimized under the same low-dimensional latent space by a unified training objective. Experiments on real-world data sets demonstrate that MLNE achieves better performance compared with methods with or without considering label information.

7.
Cancer Res ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690668

RESUMO

The tumorigenic role and underlying mechanisms of lipid accumulation, commonly observed in many cancers, remains insufficiently understood. In this study we identified an AMP-activated protein kinase (AMPK)-GATA-binding protein 3 (GATA3)-enoyl-CoA hydratase short-chain 1 (ECHS1) pathway that induces lipid accumulation and promotes cell proliferation in clear cell renal cell carcinoma (ccRCC). Decreased expression of ECHS1, which is responsible for inactivation of fatty acid oxidation (FAO) and activation of de novo fatty acid (FA) synthesis, positively associated with ccRCC progression and predicted poor patient survival. Mechanistically, ECHS1 downregulation induced FA and branched-chain amino acid (BCAA) accumulation which inhibited AMPK-promoted expression of GATA3, a transcriptional activator of ECHS1. BCAA accumulation induced activation of mTORC1, de novo FA synthesis, and promoted cell proliferation. Furthermore, GATA3 expression phenocopied ECHS1 in predicting ccRCC progression and patient survival. The AMPK-GATA3-ECHS1 pathway may offer new therapeutic approaches and prognostic assessment for ccRCC in the clinic.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31691079

RESUMO

PURPOSE: To determine the maximum tolerated dose (MTD) and recommended dose (RD) of modified FLOT regimen (fluorouracil plus leucovorin, oxaliplatin and docetaxel) for treating Chinese patients with metastatic adenocarcinoma of stomach. METHODS: Chinese patients with untreated advanced or metastatic stomach adenocarcinoma were enrolled. Docetaxel (D), oxaliplatin (O) and leucovorin were administrated intravenously on day 1. Fluorouracil (F) was administrated continuous intravenously on day 1 for 48 h. The treatment was repeated every 2 weeks. The start doses of docetaxel and oxaliplatin were 40 mg/m2 and 65 mg/m2, respectively. Dose escalation followed a 3 + 3 design. Total 6 dose levels were set to determine the MTD and RD. Fluorouracil and leucovorin were given as fix doses at 2200 mg/m2 and 200 mg/m2, respectively. Adverse events that occurred in the first 2 cycles were recorded to determine dose-limiting toxicity (DLT). The primary endpoints were MTD and RD determination. RESULTS: A total of 18 patients were treated in 5 dose levels. DTL occurred in one patient of level 4 (grade 3 hypophosphatemia). Other 3 patients were enrolled in level 4 and no DLTs were observed. In level 5, 2 patients suffered grade 4 neutropenia after first cycle of treatment and were defined as DLTs. Therefore, level 5 (D/O/F: 50/75/2200 mg/m2) was defined as MTD and level 4 (D/O/F: 45/75/2200 mg/m2) was defined as RD. Common adverse events in first two cycles were nausea, anorexia, leukopenia, neutropenia and anemia. For 16 patients assessable for tumor response, 7 patients had partial response (43.7%) and 5 experienced stable disease. Disease control rate were 75% (12/16). Two patients underwent conversion operation after 6 cycles of treatment. One pathological complete response (case in level 3) and one pathological partial response (case in level 2) were observed. Median progression-free survival was 4.4 months (95% CI 2.9-5.9 months) in 14 patients. CONCLUSIONS: The RD of modified FLOT regimen in Chinese patients with advanced gastric cancer was docetaxel 45 mg/m2, oxaliplatin 75 mg/m2, leucovorin 200 mg/m2 and fluorouracil 2200 mg/m2 on day 1 of every 14-day cycle. Its efficacy will be assessed by further phase II study.

9.
Gastrointest Endosc ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31738926

RESUMO

BACKGROUND AND AIMS: The studies comparing the diagnostic efficacy of liquid-based cytology (LBC) and smear cytology (SC) of pancreatic tissue sampling obtained via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are still insufficient. Results were controversial. We compared the diagnostic efficiency of LBC and SC of EUS-FNA of pancreatic lesions in one of the largest tertiary hospitals in China. METHODS: A retrospective database search (Jan 2015 to Jan 2019) was performed for patients who underwent EUS-FNA with both LBC and SC. Demographic, cytological and endosonographic data were collected from 819 patients. 514 cases met the inclusion criteria. Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) were compared. Rapid on-site evaluation (ROSE) was not available in all cases. RESULTS: Three hundred eighty-five cases (74.90%) confirmed with malignancy, 40 cases (7.78%) confirmed benign neoplasm. Adequate tissue sampling rates showed no significant difference between the 2 groups. The sensitivity, accuracy, and NPV of LBC were higher than those of SC with statistical significance (71.4% versus 55.1%, 76.1% versus 61.6%, 40.6% versus 27.7%, respectively).The sensitivity, accuracy and NPV of combined SC and LBC were higher than those of LBC alone with statistical significance (83.9% versus 71.4%, 86.5% versus 76.1%, 56.8% versus 40.6%, respectively). Multivariate analysis revealed that pancreatic neck/body/tail lesions(P=0.003), solid lesions(P<0.001), needle size of 22-gauge (P<0.001), and number of needle passage>3(P=0.041) were associated with higher diagnostic sensitivity in all participants using LBC, whereas number of needle passage>3(P=0.017)was associated with higher diagnostic sensitivity using SC. CONCLUSIONS: LBC was more accurate and sensitive than SC in EUS-FNA of pancreatic lesion with higher NPV, when ROSE is unavailable. Pancreatic neck/body/tail lesions, solid lesions, 22-gauge needle and more than 3 passes are associated with higher sensitivity when using LBC. Doing more than 3 passes is associated with higher sensitivity when using SC.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31766186

RESUMO

High-speed railways have strict standards of infrastructure deformation and post-construction settlement. The interferometric synthetic aperture radar (InSAR) has the ability to detect ground deformation with a high accuracy and wide coverage and is becoming a useful tool for monitoring railway health. In this study, we analyzed the Beijing-Tianjin Intercity Railway (BTIR) track using InSAR time-series analysis with different data sets. First, by using RADARSAT-2 images, we examined the areas along the BTIR with significant subsidence. Then, we characterized these areas by means of X-band TerraSAR-X data. We adopted the expectation (Ex) and entropy (En) method, combined with GIS spatial analysis, to analyze the ground settlement differences on both sides of the railway. The results show that the area with the most severe differential settlement occurs between 12 and 20 km along the railway and within 120 to 20 m on both sides of the Chaoyang-Tongzhou section (CTS). Thereafter, we analyzed the reasons for the large difference in this area by considering different factors, e.g., regional land subsidence, groundwater level changes, and the dynamic load. In addition, we studied the impact of regional subsidence on the safe operation of the BTIR. The results show that the maximum different settlement along the BTIR is within the safe range, according to the high-speed railway design standard between 2010 and 2015. This study aims to provide technical support for assessing the impact of subsidence on the safety of railway operations.

11.
Leukemia ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776466

RESUMO

Recurrent oncogenic mutations of MyD88 have been identified in a variety of lymphoid malignancies. Gain-of-function mutations of MyD88 constitutively activate downstream NF-κB signaling pathways, resulting in increased cellular proliferation and survival. However, whether MyD88 activity can be aberrantly regulated in MyD88-wild-type lymphoid malignancies remains poorly understood. SPOP is an adaptor protein of CUL3-based E3 ubiquitin ligase complex and frequently mutated genes in prostate and endometrial cancers. In this study, we reveal that SPOP binds to and induces the nondegradative ubiquitination of MyD88 by recognizing an atypical SPOP-binding motif in MyD88. This modification blocks Myddosome assembly and downstream NF-κB activation. SPOP is mutated in a subset of lymphoid malignancies, including diffuse large B-cell lymphoma (DLBCL). Lymphoid malignancies-associated SPOP mutants exhibited impaired binding to MyD88 and suppression of NF-κB activation. The DLBCL-associated, SPOP-binding defective mutants of MyD88 escaped from SPOP-mediated ubiquitination, and their effect on NF-κB activation is stronger than that of wild-type MyD88. Moreover, SPOP suppresses DLBCL cell growth in vitro and tumor xenograft in vivo by inhibiting the MyD88/NF-κB signaling. Therefore, SPOP acts as a tumor suppressor in DLBCL. Mutations in the SPOP-MyD88 binding interface may disrupt the SPOP-MyD88 regulatory axis and promote aberrant MyD88/NF-κB activation and cell growth in DLCBL.

12.
BMC Genomics ; 20(1): 893, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752718

RESUMO

BACKGROUND: Parasitic insects are well-known biological control agents for arthropod pests worldwide. They are capable of regulating their host's physiology, development and behaviour. However, many of the molecular mechanisms involved in host-parasitoid interaction remain unknown. RESULTS: We sequenced the genomes of two parasitic wasps (Cotesia vestalis, and Diadromus collaris) that parasitize the diamondback moth Plutella xylostella using Illumina and Pacbio sequencing platforms. Genome assembly using SOAPdenovo produced a 178 Mb draft genome for C. vestalis and a 399 Mb draft genome for D. collaris. A total set that contained 11,278 and 15,328 protein-coding genes for C. vestalis and D. collaris, respectively, were predicted using evidence (homology-based and transcriptome-based) and de novo prediction methodology. Phylogenetic analysis showed that the braconid C. vestalis and the ichneumonid D. collaris diverged approximately 124 million years ago. These two wasps exhibit gene gains and losses that in some cases reflect their shared life history as parasitic wasps and in other cases are unique to particular species. Gene families with functions in development, nutrient acquisition from hosts, and metabolism have expanded in each wasp species, while genes required for biosynthesis of some amino acids and steroids have been lost, since these nutrients can be directly obtained from the host. Both wasp species encode a relative higher number of neprilysins (NEPs) thus far reported in arthropod genomes while several genes encoding immune-related proteins and detoxification enzymes were lost in both wasp genomes. CONCLUSIONS: We present the annotated genome sequence of two parasitic wasps C. vestalis and D. collaris, which parasitize a common host, the diamondback moth, P. xylostella. These data will provide a fundamental source for studying the mechanism of host control and will be used in parasitoid comparative genomics to study the origin and diversification of the parasitic lifestyle.

13.
Mol Cancer ; 18(1): 170, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771591

RESUMO

BACKGROUND: The gene encoding the E3 ubiquitin ligase substrate-binding adaptor SPOP is frequently mutated in primary prostate cancer, but how SPOP mutations contribute to prostate cancer pathogenesis remains poorly understood. Stress granules (SG) assembly is an evolutionarily conserved strategy for survival of cells under stress, and often upregulated in human cancers. We investigated the role of SPOP mutations in aberrant activation of the SG in prostate cancer and explored the relevanve of the mechanism in therapy resistance. METHODS: We identified SG nucleating protein Caprin1 as a SPOP interactor by using the yeast two hybrid methods. A series of functional analyses in cell lines, patient samples, and xenograft models were performed to investigate the biological significance and clinical relevance of SPOP regulation of SG signaling in prostate cancer. RESULTS: The cytoplasmic form of wild-type (WT) SPOP recognizes and triggers ubiquitin-dependent degradation of Caprin1. Caprin1 abundance is elevated in SPOP-mutant expressing prostate cancer cell lines and patient specimens. SPOP WT suppresses SG assembly, while the prostate cancer-associated mutants enhance SG assembly in a Caprin1-dependent manner. Knockout of SPOP or expression of prostate cancer-associated SPOP mutants conferred resistance to death caused by SG inducers (e.g. docetaxel, sodium arsenite and H2O2) in prostate cancer cells. CONCLUSIONS: SG assembly is aberrantly elevated in SPOP-mutated prostate cancer. SPOP mutations cause resistance to cellular stress induced by chemtherapeutic drug such as docetaxel in prostate cancer.

14.
Medicine (Baltimore) ; 98(48): e18147, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770254

RESUMO

INTRODUCTION: Neurosyphilis is a chronic infection of the central nervous system that is commonly found in adult with long latency periods. Neurosyphilis-attributed deaths in young patients have grown exponentially in the past decade, yet there have been few studies on the early stages of neurosyphilis. PATIENT CONCERNS: A young male patient with syphilitic cerebral arteritis was evaluated in our clinic for the clinical signs of progressive ischemic stroke. DIAGNOSIS: The progression of syphilitic cerebral arteritis was observed through computed tomography imaging, magnetic resonance imaging, magnetic resonance angiogram, and transcranial color Doppler. The pathological changes and clinical outcomes were reviewed. In this specific case, the development of syphilitic cerebral arteritis was dynamic, continuous, and rapid. The pathogenesis was related to Heubner arteritis, in which the formation of a mural thrombus (MT) causes the severe obstruction of blood flow without complete occlusion, leading to an increased risk of infarction. In this patient, formation of the MT resulted in the infarction of the smaller vessels and narrowing of the larger vessels. The partial dislodgment of the MT from the arterial wall of the larger vessels occluded the smaller vessels, leading to infarction. INTERVENTIONS: Standard pharmacotherapy for the treatment of the cerebral infarction and a single course of penicillin were applied. OUTCOMES: Muscle strength was recovered. The Glasgow Coma Scale score was 15, whereas the NIH Stroke Scale score was 0. The increase in blood flow of the right MCA was accompanied by severe stenosis with compensation of the anterior communicating artery. In addition, moderate to severe stenosis of the right vertebral artery and the basilar artery was suspected. There was a possibility that the right posterior communicating artery was recruited for compensation. CONCLUSION: Progressive stroke was the initial symptom of the neurosyphilis. Disease progression is rapid and difficult to control with a single course of penicillin.

15.
Org Biomol Chem ; 17(47): 9990-9993, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31746922

RESUMO

A facile synthetic method for the formation of dihydroquinoline-azide from alkylidenecyclopropanes and TMSN3 under the catalysis of a Lewis acid has been developed, and a number of azide-containing compounds can be instantly accessed in moderate to good yields. A click reaction with these azido compounds was also realized along with a mechanistic investigation.

16.
Gene ; : 144197, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31669636

RESUMO

Enterococcus faecalis is one of the main components of symbiotic bacteria in the intestine of silkworm (Bombyx mori L.). The abundance of E. faecalis in the intestine of silkworm is affected by fluoride exposure. However, the response mechanism of E. faecalis toward fluoride remains largely unknown. In this study, a strain of E. faecalis (named TV4), which is a symbiotic bacteria of silkworm, was isolated and characterized. Inhibition assay showed that fluoride can significantly inhibit the growth of the TV4 strain (P < 0.05) after culture for 4 h. Finally, Illumina X-Ten platform was used to investigate the response mechanism of E. faecalis TV4 under fluoride exposure. We found that the TV4 strain demonstrated significant changes in its carbohydrate transport and metabolism and energy metabolism. The transcriptome sequencing results revealed that 237 genes were differentially expressed for TV4 grown after fluoride exposure, i.e., 92 genes were differentially up-regulated and 145 genes were differentially down-regulated. Many of the down-regulated genes were involved in cell carbohydrate transport and metabolism and energy production, whereas the up-regulated genes were mostly related to ethanolamine utilization and amino acid synthesis and metabolism. Our results revealed that strain TV4 reduced its carbohydrate metabolism and energy metabolism and increased ethanolamine utilization and amino acid metabolism to adapt and survive under fluoride exposure. This study enhances our understanding about the response mechanism of E. faecalis after fluoride exposure and has important implications for investigations on the three-way interaction among fluoride, symbiotic bacteria and silkworm.

17.
Ann Diagn Pathol ; 44: 151412, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31778950

RESUMO

Hypereosinophilia (HE) is defined as persistently elevated absolute eosinophil count (AEC) ≥ 1.5 × 109/L, which can be due to a variety of underlying causes. In this study, we investigated the prevalence and spectrum of T-cell lymphoproliferative disorders in 124 consecutive patients with HE by flow cytometric immunophenotyping. Available medical records, pathology reports and T-cell receptor (TCR) gene rearrangement were reviewed. Fifteen patients (12%) with HE had abnormal T-cell populations that were initially detected by flow cytometry. The presence of immunophenotypically abnormal T cells was not associated with higher AEC or higher absolute lymphocyte count levels, in comparison to those without abnormal T cells. Molecular studies concordantly identified a clonal TCR gene rearrangement in 8 of 10 cases tested. Based on the combination of clinical presentation, morphologic findings and laboratory studies, seven patients were diagnosed with the lymphocytic variant of hypereosinophilic syndrome and five with overt T-cell lymphoma (4 peripheral T-cell lymphoma NOS, 1 primary cutaneous T-cell lymphoma). The remaining three had an unknown diagnosis due to lack of information and additional workup would be warranted. These findings underscore the importance of flow cytometry as a screening tool to identify T-cell lymphoproliferative disorders in patients with HE.

18.
Rev. bras. cir. cardiovasc ; 34(5): 596-604, Sept.-Oct. 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1042043

RESUMO

Abstract Aortic dissection (AD) has been recognized to be associated with an inflammatory process. Clinical observations demonstrated that patients with AD had an elevated interleukin (IL)-6 level in comparison to hypertensive or healthy controls. Adverse events such as acute lung injury, postimplantation syndrome, and death are associated with an elevated IL-6 level. Thus, circulating IL-6 could be a reliable biomarker for the diagnosis of AD and for the eveluation of the therapeutic outcomes and the prognosis of AD patients. Therapeutic interventions aiming at attenuating the inflammatory status by IL-6 neutralization could effectively decrease the IL-6 level and thus reverse the progression of the disorder of AD patient. Endovascular aortic repair can effectively control the inflammatory cytokines. Selective antegrade cerebral perfusion with deep hypothermic circulatory arrest during aortic arch replacement shows better neuroprotectve effect with an improved IL-6 level of the cerebrospinal fluid. These results facilitate the understanding of the etiology of AD and guide the directions for the treatment of acute AD in the future. More effective therapeutic agents developed based on the theories of IL-6 signaling involved in the mechasims of AD are anticipated.

19.
J Org Chem ; 84(22): 14487-14497, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31599586

RESUMO

We reported herein an unexpected cinchona alkaloid-derived squaramide-catalyzed asymmetric two-component Ugi-type reaction of α-aryl-substituted isocyanoacetates with C,N-cyclic azomethine imines, which provides concise access to optically active C1-oxazole-substituted tetrahydroisoquinolines in good yields (86-93%) and high enantioselectivities (up to 98% enantiomeric excess) under mild conditions.

20.
Epidemiology ; 30(6): 845-852, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31584892

RESUMO

BACKGROUND: Perineal talc use and douching could affect the risk of uterine cancer through several possible pathways, including inflammation response, microbiota changes, or endocrine disruption. Two previous cohort studies of the association between talc use and uterine cancer have reported weak positive associations, but we know of no previous evaluations of the relationship between douching and uterine cancer. METHODS: Using a large prospective cohort, we examined the relationship between incident uterine cancer and self-reported use of talc or douche using Cox proportional hazards models. RESULTS: After excluding those with prior hysterectomy, 271 of 33,609 women reported incident uterine cancer (mean follow-up = 8.3 years in noncases; maximum 12.6 years). Overall, 26% of women reported ever using talc and 15% reported ever having douched. Ever talc use was associated with an increase in risk of uterine cancer (adjusted hazard ratio [HR] = 1.2; 95% confidence interval [CI] = 0.94, 1.6), with some evidence of a dose-response for frequency of talc use (P-for-trend = 0.07). Ever douching was not associated with uterine cancer risk (HR = 1.0; 95% CI = 0.72, 1.5), with no evidence of a frequency dose-response (P = 0.96). The estimates were similar when we restricted to invasive endometrial cancers, but not when we further restricted to endometroid adenocarcinomas. CONCLUSION: The positive association we observed between talc use and uterine cancer risk is consistent with findings from previous prospective cohort studies of endometrial cancer. The relationships between uterine cancer and both douching and talc use merit further consideration, particularly as both exposures are preventable.

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