13 research outputs found

    Diagnostic Accuracy of Chest Computed Tomography Scans for Suspected Patients With COVID-19: Receiver Operating Characteristic Curve Analysis

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    BACKGROUND: Computed tomography (CT) scans are increasingly available in clinical care globally. They enable a rapid and detailed assessment of tissue and organ involvement in disease processes that are relevant to diagnosis and management, particularly in the context of the COVID-19 pandemic. OBJECTIVE: The aim of this paper is to identify differences in the CT scan findings of patients who were COVID-19 positive (confirmed via nucleic acid testing) to patients who were confirmed COVID-19 negative. METHODS: A retrospective cohort study was proposed to compare patient clinical characteristics and CT scan findings in suspected COVID-19 cases. A multivariable logistic model with LASSO (least absolute shrinkage and selection operator) selection for variables was used to identify the good predictors from all available predictors. The area under the curve (AUC) with 95% CI was calculated for each of the selected predictors and the combined selected key predictors based on receiver operating characteristic curve analysis. RESULTS: A total of 94 (56%) patients were confirmed positive for COVID-19 from the suspected 167 patients. We found that elderly people were more likely to be infected with COVID-19. Among the 94 confirmed positive patients, 2 (2%) patients were admitted to an intensive care unit. No patients died during the study period. We found that the presence, distribution, and location of CT lesions were associated with the presence of COVID-19. White blood cell count, cough, and a travel history to Wuhan were also the top predictors for COVID-19. The overall AUC of these selected predictors is 0.97 (95% CI 0.93-1.00). CONCLUSIONS: Taken together with nucleic acid testing, we found that CT scans can allow for the rapid diagnosis of COVID-19. This study suggests that chest CT scans should be more broadly adopted along with nucleic acid testing in the initial assessment of suspected COVID-19 cases, especially for patients with nonspecific symptoms

    Balloon Rupture during Pre-Dilation for Transcatheter Aortic Valve Replacement in Patients with a Bicuspid Aortic Valve: Classification, Treatment Strategies, and Prevention

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    Balloon rupture during transcatheter aortic valve replacement (TAVR) is a rare but serious complication. Here, we present two cases of balloon rupture in patients with severe aortic stenosis and type 0 bicuspid aortic valves. Three-dimensional models based on pre-procedure cardiac CT angiography were used to investigate these cases post hoc. The models revealed asymmetrical distribution of calcifications with sharply spiked features in the bicuspid aortic valves. The narrow calcified orifices resulted in uneven force distribution on the expanded balloon, thus leading to balloon rupture. We additionally review the classification and causes of balloon rupture, summarize methods for avoiding complications, and describe treatment options. Accurate pre-procedural anatomy evaluation and computer modeling are crucial for planning and managing TAVR procedures. Further investigation through computer simulation is necessary to determine the appropriate balloon size and inflation locations, to provide a reference for pre-procedural preparation

    Changes of N6-methyladenosine modulators promote breast cancer progression

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    Abstract Background Breast cancer (BC) displays striking genetic, epigenetic and phenotypic diversity. N6-methyladenosine (m6A) in mRNA has emerged as a crucial epitranscriptomic modification that controls cancer self-renewal and cell fate. However, the key enzymes of m6A expression and function in human breast carcinogenesis remain unclear. Methods The expression of m6A methylases (METTL3, METTL14 and WTAP) and demethylases (FTO and ALKBH5) were analyzed by using ONCOMINE and The Cancer Genome Atlas databases and in 36 pairs of BC and adjacent non-cancerous tissue. The level of m6A in BC patients was detected by ELISA, and the function of m6A was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay and transwell assay. The database of bc-GenExMiner v4.0, Kaplan-Meier Plotter and cBioPortal were queried for correlation, mutation and prognosis analysis of BC. Results The m6A methylases and demethylases were dysregulated in several major malignant tumors. Specifically, the expression of all m6A methylases was reduced in BC as compared with normal controls, but the demethylase ALKBH5 was induced in ONCOMINE databases and confirmed in clinical patients. METTL14 expression was positively correlated with METTL3 expression, and both showed high expression in normal breast-like and luminal-A and -B BC. Functionally, reducing m6A expression by overexpressing METTL14 and/or knockdown of ALKBH5 could inhibit breast cell viability, colony formation and cell migration. Furthermore, Kaplan-Meier, meta-analysis and univariate Cox assay showed that the expression of m6A members including METTL3, METTL14, WTAP and FTO but not their gene mutation and amplification, was tightly associated with cancer progression and poor survival. Conclusions Changes of m6A modulators reduced m6A may promote tumorigenesis and predict poor prognosis in BC

    FUN14 domain-containing 1 promotes breast cancer proliferation and migration by activating calcium-NFATC1-BMI1 axisResearch in context

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    Background: FUN14 domain-containing 1 (FUNDC1), as a novel member of mitochondria-associated endoplasmic reticulum (ER) membranes associates with mitochondrial division and mitophagy. However, the expression profile and functional roles of FUNDC1 remain largely unclear in human cancer biology, including breast cancer (BC). Methods: Immunohistochemistry and western blot analysis were used to determine the expression of FUNDC1 and BMI1 polycomb ring finger oncogene (BMI1). CCK8, cell counting and transwell assays were used to analyze cell proliferation, migration and invasion, respectively. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were used to detect the transcriptional regulation of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1). The prognostic merit of NFATC1 expression was assessed by Kaplan-Meier assay. Findings: Immunohistochemistry revealed strong immunostaining for FUNDC1 in cytoplasmic and nuclear membrane distribution in BC tissues as compared with normal breast epithelium. Kaplan–Meier survival analysis showed worse outcome for BC patients with high FUNDC1 expression. In vitro assay of gain- and loss-of-function of FUNDC1 suggested that FUNDC1 could stimulate BC cell proliferation, migration and invasion. Furthermore, elevated FUNDC1 level promoted Ca2+ cytosol influx from ER and extracellular, as well as NFATC1 nuclear translocation and activity. Nuclear NFATC1 bound to the BMI1 gene promoter and transcriptionally upregulated its expression. Notably, BMI1 overexpression could rescue the loss of function of FUNDC1. Co-expression of FUNDC1 and BMI1 in BC patients predicted worse prognosis than without either expression. Interpretation: FUNDC1 might promote BC progression by activating the Ca2+–NFATC1–BMI1 axis. This pathway may be promising for developing multiple targets for BC therapy. Keywords: FUNDC1, Breast cancer, Calcium, NFATC1, BMI

    Plasma Cell-Free DNA as a Novel Biomarker for the Diagnosis and Monitoring of Atherosclerosis

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    Atherosclerosis (AS) is the leading cause of cardiovascular diseases (CVDs) with a high rate of mortality worldwide. Plasma cell-free DNA (cfDNA), mainly originating from apoptosis, necrosis, and active secretion, has been recognized as a promising biomarker for the diagnosis and prognosis of multiple cancers, whereas there are no reports about cfDNA in CVDs. Here, we found an increased quantity and decreased integrity of cfDNA (cfDI) in the serum from AS patients compared with normal controls. Moreover, the reduced cfDI is inversely correlated with serum LDL levels, carotid plaque size, and carotid plaque thickness in the progression of AS. Consistently, in vivo experiments confirmed that the release and cleavage of cfDNA were increased concomitantly with the development and progression of AS in ApoE−/− mice. Our study sheds light on the potential of cfDNA and cfDI as molecular biomarkers for detecting and monitoring AS

    A newly designed curcumin analog Y20 mitigates cardiac injury via anti-inflammatory and anti-oxidant actions in obese rats.

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    Obesity is strongly associated with the cause of structural and functional changes of the heart in both human and animal models. Oxidative stress and inflammation play a critical role in the development of obesity-induced cardiac disorders. Curcumin is a natural product from Curcuma Longa with multiple bioactivities. In our previous study, in order to reach better anti-inflammatory and anti-oxidant dual activities, we designed a new mono-carbonyl curcumin analog, Y20, via the structural modification with both trifluoromethyl and bromine. This study was designed to investigate the protective effects of Y20 on obesity-induced cardiac injury and its underlying mechanisms. In high fat diet-fed rats, oral administration of Y20 at 20 mg/kg or curcumin at 50 mg/kg significantly decreased the cardiac inflammation and oxidative stress and eventually improved the cardiac remodeling by mitigating cardiac disorganization, hypertrophy, fibrosis and apoptosis. Y20 at 20 mg/kg showed comparable and even stronger bioactivities than curcumin at 50 mg/kg. The beneficial actions of Y20 are closely associated with its ability to increase Nrf2 expression and inhibit NF-κB activation. Taken together, these results suggest that Y20 may have a great therapeutic potential in the treatment of obesity-induced cardiac injury using Nrf2 and NF-κB as the therapeutic targets for treating obesity-related disorders

    Y20 attenuates cardiac fibrosis in the hearts of HFD-fed rats.

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    <p>(A) Representative images for Sirius Red staining and masson staining in the formalin-fixed myocardial tissues indicating collagen deposition and implying the extent of cardiac fibrosis (400×magnification). (B) Western blot analysis for the protein expression of TGF-β in the myocardial tissues was performed. (C-F) The mRNA expression of fibrotic markers such as collagen 1, TGF-β, MMP-2 and MMP-9 in the myocardial tissues was detected by real-time qPCR. Four rats in each group were used for above analysis. * <i>P</i><0.05, ** <i>P</i><0.01 v.s. HFD group; # <i>P</i><0.05 v.s. vehicle control (Ctrl).</p

    Y20 attenuates cardiac histological abnormalities and hypertrophy in the hearts of HFD-fed rats.

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    <p>(A) Representative images for the Hematoxylin-Eosin (H&E) staining in the formalin-fixed myocardial tissues (400× magnification). (B) Qantitative data of myocyte cross-section lenth of 100 cells chosen from different visual scopes of 4 samples per group in myocardial transverse H&E staining were shown. (C) Western blot analysis for the protein expression of ANP in the myocardial tissues was performed. (D & E) The mRNA expression of the hypertrophic markers ANP and BNP in the myocardial tissues was detected by real-time qPCR. Four rats in each group were used for above analysis. *, <i>P</i><0.05, **, <i>P</i><0.01 v.s. HFD; # <i>P</i><0.05 v.s. vehicle control (Ctrl).</p

    The design and synthesis of compound Y20.

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    <p>(A) The chemical structure of curcumin, C66 and Y20. (B) The chemical synthesis of Y20. Reagents and conditions: (i) 4-Methylbenzenesulfonic acid, toluene, 110℃ reflux, 4h; (ii) EtOH, 78℃, reflux, 5h, saturate HCl; (iii) 20% NaOH, EtOH, r.t., 10h.</p
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