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1.
Stress Health ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804001

RESUMO

Although outcomes of job insecurity have been extensively examined, researchers have paid significantly less attention to antecedents of job insecurity. However, in order to lessen and eliminate job insecurity, a deeper understanding of the sources of job insecurity is required. Among triggers of job insecurity, very few studies have examined workplace interpersonal relationships as predictors of job insecurity. To fill this research gap, we examine the relation between workplace mistreatment (i.e., workplace incivility, bullying, and abusive supervision) and job insecurity. Examining multiple forms of mistreatment also allows us to compare and contrast the relative impact of each workplace mistreatment on job insecurity. Further, we identify a group of individuals who are particularly vulnerable to the negative impact of workplace mistreatment - those who are high in work centrality. Across two lagged survey studies, we largely found that work centrality exacerbates the relations of workplace incivility, bullying, and abusive supervision with job insecurity. Thus, this research contributes to the occupational health literature by demonstrating the relative predictive power of multiple forms of workplace mistreatment on job insecurity and identifying a vulnerable group who might suffer more from workplace mistreatment (i.e., those high in work centrality).

2.
Surg Oncol ; 30: 117-121, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31500773

RESUMO

PURPOSE: Multimodality treatment of soft tissue sarcoma(STS) by expert teams reportedly affords a tremendous improvement in outcome of patients. Despite advances, treatment of local unresectable recurrence remains difficult and is not standardized. We performed this retrospective study in order to assess the efficacy and safety of high-intensity focused ultrasound (HIFU) ablation in treating STS patients with local unresectable recurrence. METHODS: Thirty-six STS patients with local unresectable recurrence from January 2015 to December 2016 were recruited according to the inclusion criteria. Pain rating, response rate, disease control rate, local disease progression-free survival(LPFS), progression-free survival (PFS) and overall survival(OS) were used to evaluate efficacy of HIFU treatment. RESULTS: HIFU resulted in a significant relief in pain rating, without severe side effects. According to magnetic resonance imaging(MRI), three months after HIFU treatment, response rate was 47.3% and the local disease control rate was 80.6%. Twelve months post HIFU treatment, response rate was 38.9% and the local disease control rate was 55.6%. The median LPFS, PFS and OS time for 36 patients was 13 months, 10 months and 20 months respectively. CONCLUSION: HIFU is a tolerated treatment modality with promising activity and safety in STS patients with local unresectable recurrence.

3.
Biomaterials ; 224: 119490, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31542515

RESUMO

Tumor ablation therapies provide a minimally invasive approach to treat cancer. However, inhibition of cancer metastasis and recurrence after ablation is still a challenge in clinical trials. Here, we propose a strategy using combinatorial thermal ablation, adjuvants and immune checkpoint blockade (ICB) to inhibit metastatic tumor and recurrence via antitumor immune responses post tumor thermal ablation, which are frequently used in the clinic. Furthermore, a strong immune memory against cancer was observed 80 days after the primary tumor was ablated. Considering that all components in our design are approved by Food and Drug Administration (FDA), we provide a strategy based on clinically used cancer treatment technique that is promising in clinical translation.

5.
BJU Int ; 124(6): 1028-1033, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31077518

RESUMO

OBJECTIVE: To examine the association of kidney stones with new-onset hypertension, diabetes and obesity. PARTICIPANTS AND METHODS: This prospective cohort study included participants in the Qingdao Port Cardiovascular Health Study who were aged ≥18 years and had abdominal ultrasonography results in 2013 that were negative for kidney stones. Multivariable Cox regression models with time-dependent covariates were used to estimate the effects of new-onset hypertension, diabetes and obesity on the incidence of kidney stones. RESULTS: There were 9667 participants without kidney stones in 2013 (mean age 46.2 years; 75.6% men). During a mean (range) follow-up of 33.5 (6-42) months, 676 (7.0%) incident cases of kidney stones were identified. Kidney stones were more frequent among those who had new-onset of a metabolic factor vs those who did not (hypertension: 7.7 vs 6.0%; diabetes: 8.4 vs 6.6%; obesity: 7.4 vs 6.8%). Adjusted Cox models identified that increased risk of kidney stones was associated with new-onset hypertension (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.25-2.27), new-onset diabetes (HR 1.78, 95% CI 1.07-2.96), and new-onset obesity (HR 1.78, 95% CI 1.15-2.74). CONCLUSIONS: New-onset of hypertension, diabetes and obesity were all strongly associated with an increased risk of kidney stones in this prospective cohort study. Results suggest that a substantial proportion of kidney stones are potentially preventable by appropriate control of these metabolic risk factors.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30974818

RESUMO

Although previous research has documented a host of negative consequences of job insecurity, workplace interpersonal relationships have rarely been considered. This omission might be caused by the application of broad stress theories to the job insecurity literature without taking a nuanced perspective to understand the nature of job insecurity. To address this issue, we conceptualized job insecurity as a threat to employee social acceptance by their employer. This conceptualization, therefore, allows us to apply the multimotive model of social rejection to investigate a previously-overlooked outcome of job insecurity-workplace friendships. Specifically, we investigated the relationship between both job feature insecurity and job loss insecurity with workplace friendships. Based on stress coping theory and the fundamental differences between job feature insecurity and job loss insecurity, we further proposed that employees' tendency to engage in positive gossip buffers the negative impact of job feature insecurity on workplace friendships, whereas employees' tendency to engage in negative gossip buffers the negative impact of job loss insecurity on workplace friendships. Data collected from 286 working adults from Mturk supported our hypotheses. Our study opens the door for future research to take a more nuanced approach when examining nontraditional consequences of job insecurity.


Assuntos
Comunicação , Amigos/psicologia , Satisfação no Emprego , Local de Trabalho/psicologia , Adulto , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade
7.
J Am Coll Cardiol ; 73(22): 2819-2828, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-30898608

RESUMO

BACKGROUND: The efficacy of ticagrelor in the long-term post-ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain. OBJECTIVES: The purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. METHODS: This international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months. RESULTS: The combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups. CONCLUSION: Among patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088).

8.
BMJ Open ; 9(2): e025144, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30782925

RESUMO

INTRODUCTION: China faces the prospect of a large growth in the prevalence of heart failure (HF). However, there is limited knowledge about outcomes in patients after HF hospitalisations, including patient-reported outcomes (PROs). This paper is to present the study goal, methodology and data collection of the China Patient-centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (China PEACE 5p-HF Study). METHODS AND ANALYSIS: The China PEACE 5p-HF Study, a prospective cohort study, will enrol 5000 patients with HF during 2016-2018 from 52 diverse hospitals throughout China and the follow-up period will be 12 months. Information on patients' medical history, in-hospital treatment and in-hospital outcomes are being abstracted from medical records. Details of patients' demographics, socioeconomic status, cardiovascular risk factors, access to healthcare services are being collected through comprehensive baseline interviews. Generic and disease-specific health status, depression, stress, anxiety and cognitive function are being administered using validated PRO instruments. Follow-up interviews will capture PROs and hospitalisation events at 1, 6 and 12 months follow-up. Standardised transthoracic echocardiograms and 6 min walk tests are being done in patients who enrolled in hospitals with these facilities at baseline and at 1 and 12 months after discharge. Collection of blood and urine samples are also being conducted at baseline, 1 and 12 months follow-up and stored for future analyses. ETHICS AND DISSEMINATION: The National Center for Cardiovascular Diseases/Fuwai Hospital ethics committee approved this study, and all collaborating hospitals received approval from their local ethics committee. Written informed consent will be obtained from all patients. Findings will be disseminated in future peer-reviewed papers and will help to support improvements in the quality of care for HF nationwide. TRIAL REGISTRATION NUMBER: NCT02878811.

9.
Heart ; 105(12): 946-952, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30661037

RESUMO

OBJECTIVE: To assess the association between educational attainment and acute myocardial infarction (AMI) outcomes in China to inform future healthcare interventions. METHODS: We used data from the China Patient-centred Evaluative Assessment of Cardiac Events-Prospective AMI study of 3369 consecutive patients hospitalised with AMI from 53 hospitals. Educational attainment was categorised as: high (senior high school, college or postgraduate degree), intermediate (junior high school) or low (primary school or illiterate). We used survival models to assess the relationship between education and 1-year major adverse cardiovascular events (MACE), all-cause mortality, both unadjusted and after adjustment for demographic characteristics and cardiovascular risk factors. RESULTS: The median participant age was 61 (52, 69) years, 23.2% were women, and 33.3% had high, 32.4% intermediate and 34.3% low educational attainment. In unadjusted analysis, compared with high educational attainment, low educational attainment was associated with a higher 1-year risk of MACE (HR 2.41, 95% CI 1.72 to 3.37) and death (HR for low vs high education 3.09, 95% CI 1.69 to 5.65). In risk-adjusted analyses, the association between education and death was attenuated and no longer statistically significant (adjusted HR 1.41, 95% CI 0.74 to 2.69, p=0.30). However, the risk of 1-year MACE (adjusted HR 1.68, 95% CI 1.18 to 2.41, p=0.004) remained significantly greaterin low educational attainment group. CONCLUSIONS: In a national Chinese cohort of patients hospitalised with AMI, low educational attainment was associated with a higher risk of adverse events in the year following discharge. This association highlights the need to consider interventions to improve AMI outcomes in adults with low levels of education. CLINICAL TRIAL REGISTRATION: NCT01624909; Results.

10.
Atherosclerosis ; 281: 1-8, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30583242

RESUMO

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a an autosomal dominant disorder characterized by very high levels of low-density lipoprotein cholesterol (LDL-C). It is estimated that >85% of all FH-causing mutations involve genetic variants in the LDL receptor (LDLR). To date, 795 single amino acid LDLR missense mutations have been reported in the Leiden Open Variation Database (LOVD). However, the functional impact of these variants on the LDLR pathway has received little attention and remains poorly understood. We aim to establish a systematic functional prediction model for LDLR single missense mutations. METHODS: Using a combined structural modeling and bioinformatics algorithm, we developed an in silico prediction model called "Structure-based Functional Impact Prediction for Mutation Identification" (SFIP-MutID) for FH with LDLR single missense mutations. We compared the pathogenicity and functional impact predictions of our model to those of other conventional tools with experimentally validated variants, as well as in vitro functional test results for patients with LDLR variants. RESULTS: Our SFIP-MutID model systematically predicted 13,167 potential LDLR single amino acid missense substitutions with biological effects. The functional impact of 52 out of 54 specific mutations with reported in vitro experimental data was predicted correctly. Further functional tests on LDLR variants from patients were also consistent with the prediction of our model. CONCLUSIONS: Our LDLR structure-based computational model predicted the pathogenicity of LDLR missense mutations by linking genotypes with LDLR functional phenotypes. Our model complements other prediction tools for variant interpretation and facilitates the precision diagnosis and treatment of FH and atherosclerotic cardiovascular diseases.

11.
Cardiology ; 141(2): 88-97, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30423567

RESUMO

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising target for lowering plasma low-density lipoprotein cholesterol and preventing cardiovascular (CV) disease. Whether plasma PCSK9 measured during the acute phase predicts recurrent CV events in patients with acute myocardial infarction (AMI) remains unresolved. METHODS AND RESULTS: Plasma PCSK9 levels were measured in 1,646 patients with AMI from the China PEACE-Prospective AMI Study at the acute phase. Additionally, 248 patients were resampled and measured at 1 month post-AMI. Associations of acute-phase PCSK9 tertiles with clinical characteristics and recurrent CV events within 1 year were assessed. Female gender (OR 1.94, 95% CI 1.24-3.03), premature coronary heart disease (CHD; OR 2.12, 95% CI 1.37-3.26), higher high-sensitivity C-reactive protein (OR 1.67, 95% CI 1.44-1.95), and higher triglycerides (OR 1.46, 95% CI 1.03-2.09) were associated with higher baseline PCSK9. Plasma PCSK9 levels in the highest tertile (versus lowest) did not have an increased risk of 1-year recurrent CV events in the AMI cohort (HR 0.78, 95% CI 0.52-1.16) or any subgroup. There was also no association between percentage changes in PCSK9 over the first month and 1-year recurrent events, although there was a trend of differences between patients in the upper versus lower tertiles. CONCLUSION: Plasma PCSK9 levels measured during the acute phase were associated with high-sensitivity C-reactive protein, triglycerides, premature CHD, and gender in patients with AMI but did not predict recurrent CV events within 1 year. Dynamic changes in PCSK9 suggested a trend yet no significance value in predicting recurrent CV events.

12.
Lancet ; 392(10155): 1306, 2018 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-30322574
13.
Onco Targets Ther ; 11: 6259-6269, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30288061

RESUMO

Objective: In this research, we explored the effect of long non-coding RNA (lncRNA) AOC4P on gastrointestinal stromal tumor (GIST) cells. Materials and methods: The expression of lncRNA AOC4P in tissues was detected by real-time PCR (RT-PCR). The epithelial-mesenchymal transition (EMT)-related proteins in tissues were analyzed by Western blot. The experiment included negative control group (CN), silence AOC4P group (si AOC4P), and silence negative control group (si CT). RT-PCR, MTT, Scratch, Transwell, and Annexin V-FITC methods were used to detect the expression of lncRNA AOC4P, cell proliferation, cell migration ability, cell invasion ability, and apoptosis, respectively. The EMT-related proteins including TGF-ß, ZEB1, Vimentin, Snail, and E-cadherin were analyzed by Western blot. Results: The expression of lncRNA AOC4P and the expression of EMT-related proteins in high-risk GISTs were higher than that in low- and intermediate-risk GISTs (P<0.05). It was revealed that cell proliferative migration and invasive ability in si AOC4P group was decreased than that in CN and si CT groups (P<0.05), and cell apoptosis in si AOC4P group was higher than that in si CT group. The results of Western blot demonstrated that the expression of TGF-ß1, ZEB1, Vimentin, and Snail in si AOC4P group were lower than that in si CT and CN group (P<0.05), and the expression of E-cadherin in si AOC4P group was higher than that in si CT and CN group (P<0.05).

14.
Eur Heart J Acute Cardiovasc Care ; : 2048872618803726, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30270637

RESUMO

BACKGROUND: We examined sex differences in long-term health outcomes following acute myocardial infarction in China, including mortality, major adverse cardiac events and health status (symptoms, functioning, quality of life). METHODS: A total of 3415 acute myocardial infarction patients (23.2% women) aged ⩾18 years were enrolled across 10 geographic regions in China (2012-2014) in the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) study. Clinical data was abstracted from medical records. Generic (Euro-Quality of Life Scale) and disease-specific (Seattle Angina Questionnaire) health status was obtained through interviews at baseline and one year. RESULTS: At one year, women with acute myocardial infarction had a higher risk of death from all causes ( p<0.001), but had similar rates of major adverse cardiac events ( p=0.2). Women had lower mean generic (Euro-Quality of Life Scale utility index score: 0.90±0.13 vs 0.94±0.11) and disease specific health scores indicating poorer functioning (Seattle Angina Questionnaire summary score: 75.3±11.4 vs 78.4±9.7) and higher rates of daily/weekly angina (Seattle Angina Questionnaire angina frequency score ⩽60 vs >60: 9.1% vs 4.7%; all p<0.001). In multivariable analysis, there was a significant association between female sex and mortality (ß=0.45, standard error=0.21, p=0.03) but not for major adverse cardiac events (ß=-0.02, standard error=0.14, p=0.89). The association between female sex and worse generic health status persisted (ß=-0.02, standard error=0.01, p=0.003), but was no longer significant between sexes for disease-specific health status (ß=-0.82, standard error=0.58, p=0.154) or daily/weekly angina (odds ratio=1.39; 95% confidence interval 0.88-2.21). CONCLUSION: Women in China have higher crude rates of all-cause/cardiovascular death versus men, as well as worse generic/disease specific health status at one-year post-acute myocardial infarction. The association between female sex and worse generic health status persisted following adjustment.

15.
Biochem Biophys Res Commun ; 505(1): 113-118, 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30241937

RESUMO

The transcription factor Gli2 plays crucial roles in the transduction of Hedgehog (Hh) signals, yet the mechanisms that control Gli2 degradation remain unclear. Here we have identified the eubiquitinating enzyme otubain2 (OTUB2) as a regulator of Gli2 protein degradation. We found that OTUB2 was coimmunoprecipitated with Gli2. Knockdown of OTUB2 decreased Gli2 protein level while the proteasome inhibitor MG-132 treatment restored Gli2 expression. Additionally, OTUB2 overexpression stabilized Gli2 protein in U2OS cells and extended the half-life of Gli2. We also found that knockdown of OTUB2 reduced deubiquitination of Gli2 in vivo. In vitro deubiquitination assay showed that ubiquitinated Gli2 was decreased by wild-type OTUB2 but not OTUB2 mutations. We also found that OTUB2 knockdown suppressed the ALP activity and the expression of the common markers BMP2 and RUNX2 during osteogenesis of MSCs in response to Shh and Smo agonists, which indicated OTUB2 may have effect on osteogenic differentiation by regulating Hh signaling.

17.
BMJ ; 362: k2357, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29997129

RESUMO

OBJECTIVE: To examine the effect of the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guidelines on the prevalence of hypertension and eligibility for initiation and intensification of treatment in nationally representative populations from the United States and China. DESIGN: Observational assessment of nationally representative data. SETTING: US National Health and Nutrition Examination Survey (NHANES) for the most recent two cycles (2013-14, 2015-16) and China Health and Retirement Longitudinal Study (CHARLS) (2011-12). PARTICIPANTS: All 45-75 year old adults who would have a diagnosis of hypertension and be candidates for treatment on the basis of the ACC/AHA guidelines, compared with current guidelines. MAIN OUTCOME MEASURES: Diagnosis of hypertension and candidacy for initiation and intensification of antihypertensive treatment. RESULTS: Adoption of the 2017 ACC/AHA hypertension guidelines in the US would label 70.1 (95% confidence interval 64.9 to 75.3) million people in the 45-75 year age group as having hypertension, representing 63% (60.6% to 65.4%) of the population in this age group. Their adoption in China would lead to labeling of 266.9 (252.9 to 280.8) million people or 55% (53.4% to 56.7%) of the same age group as having hypertension. This would represent an increase in prevalence of 26.8% (23.2% to 30.9%) in the US and 45.1% (41.3% to 48.9%) in China. Furthermore, on the basis of treatment patterns and current guidelines, 8.1 (6.5 to 9.7) million Americans with hypertension are untreated, which would be expected to increase to 15.6 (13.6 to 17.7) million after the implementation of the ACC/AHA guidelines. In China, on the basis of current treatment patterns, 74.5 (64.1 to 84.8) million patients with hypertension are untreated, estimated to increase to 129.8 (118.7 to 140.9 million. In addition, the ACC/AHA guidelines would label 8.7 (6.0 to 11.5) million adults in the US and 51 (40.3 to 61.6) million in China as having hypertension that would not require antihypertensive treatment, compared with 1.5 (1.2 to 2.1) million and 23.4 (12.1 to 35.1) million with the current guidelines. Finally, even among people receiving treatment, the proportion that are candidates for intensification of treatment is estimated to increase by 13.9 (12.2 to 15.6) million (from 24.0% to 54.4% of treated patients) in the US, and 30 (24.3 to 35.7) million (41.4% to 76.2% of treated patients) in China, if the ACC/AHA treatment targets are adopted. CONCLUSIONS: If adopted, the 2017 ACC/AHA hypertension guidelines will markedly increase the number of people labeled as having hypertension and treated with drugs in both the US and China, leading to more than half of those aged 45-75 years in both countries being considered hypertensive.

18.
Sci Rep ; 8(1): 10234, 2018 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-29980694

RESUMO

The pathological status of axillary lymph nodes (ALN) plays a critical role in the staging and treatment of patients with breast cancer. Therefore, differential diagnosis of metastatic ALN is highly desirable in the clinic. We used real-time elastography (RTE) and gray-scale ultrasound to generate a new scoring system for determining ALN status and estimate their performance of this system. Ninety-seven ALNs were examined by both gray-scale ultrasound and RTE. The performance of gray-scale ultrasound was evaluated by the sum of scores according to its features. RTE images were determined by a modulated scoring system based on the percentage and distribution of hypoechoic cortex regions in the ALNs. Strain ratio was also calculated. Diagnostic performance was obtained by receiver operating characteristic curve analysis with pathologic findings used as the reference standard. The sensitivity, specificity and accuracy were 92%, 73% and 83%, respectively, for gray-scale ultrasound; 78%, 93%, 86%, respectively, for RTE; 88%, 96% and 92%, respectively, for the combined evaluation (AUC = 0.963), and 87%, 76% and 81%, respectively, for strain ratio. Gray-scale ultrasonography had a better sensitivity than RTE (92% vs 78%, P = 0.039), while the specificity for RTE was superior to that of gray-scale ultrasonography (93% vs 73%, P = 0.012). In conclusion, RTE showed a high specificity for evaluating the ALN status and may improve the diagnostic accuracy when combined with gray-scale ultrasound.

19.
Oncol Lett ; 16(2): 2009-2015, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30034553

RESUMO

Papillary thyroid carcinoma (PTC) is the most common form of non-medullary thyroid cancer, accounting for ~80% of all cases of thyroid cancer. The aim of the present study was to explore the role of BRAF-activated long noncoding RNA (BANCR) in the development of PTC. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the mRNA expression levels of BANCR, thyroid-stimulating hormone receptor (TSHR) and cyclin D1 between PTC and benign control thyroid nodule tissue samples from 60 patients were determined. Using RT-qPCR and western blot analysis, the expression levels of TSHR and cyclin D1 mRNA and protein were determined in cells transfected with BANCR-small interfering (si)RNA. An MTT assay and flow cytometry were used to analyze the effect of BANCR knockdown on the proliferation and cell cycle distribution of IHH-4 PTC cells. The expression of BANCR, TSHR and cyclin D1 was increased in the PTC group compared with the control group based on the RT-qPCR data. The transfection of IHH-4 cells with BANCR-siRNA induced the inhibition of TSHR and cyclin D1 expression compared with a transfection control. In addition, the proliferation of the IHH-4 cells transfected with BANCR-siRNA was suppressed, relative to the transfection control, and cells arrested in the G0/G1 phase, potentially due to the inhibition of the expression of cyclin D1. The data suggested that the expression of BANCR may promote the development of malignant thyroid nodules via the modulation of TSHR expression and its downstream effector, cyclin D1.

20.
Am Heart J ; 202: 89-96, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29908420

RESUMO

BACKGROUND: The safety and efficacy of ticagrelor in patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remain uncertain. OBJECTIVES: The primary objective of the TicagRElor in pAtients with ST elevation myocardial infarction treated with Thrombolysis (TREAT) trial is to evaluate the short-term safety of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. Key secondary objectives are to assess the safety and efficacy of ticagrelor compared with clopidogrel at 12-months. DESIGN: The TREAT trial is a multicenter, randomized, phase III, Prospective randomized open blinded end-point (PROBE) study that enrolled 3,799 patients in 152 sites from 10 countries. Following administration of fibrinolytic therapy patients were randomized to a loading dose of ticagrelor 180 mg or clopidogrel 300 mg followed by a maintenance dose of ticagrelor 90 mg twice daily or clopidogrel 75 mg/day for 12-months. The primary outcome is the rate of TIMI major bleeding at 30-days and will be assessed for non-inferiority using an intention-to-treat analysis. Co-treatments include aspirin and anticoagulants. Other evidence based therapies are also recommended. Secondary efficacy outcome include a composite of death from vascular causes, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack or other arterial thrombotic event. All-cause mortality as well as individual components of the combined efficacy endpoint will also be ascertained. SUMMARY: TREAT is an international randomized controlled trial comparing ticagrelor with clopidogrel in STEMI patients treated with fibrinolytic therapy. The results of this trial will inform clinical practice and international guidelines.

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