A cohort study to investigate the potential indicators for prenatal echocardiographic detection of suspected coarctation of the aorta

ObjectivesSuspected coarctation of the aorta (CoA) is a common fetal echocardiographic presentation. However, the prenatal findings did not indicate a satisfied accuracy in determining the truly CoA after birth, which made the prenatal diagnosis of CoA still as a critical challenge with high false positive rate. Thus, this research is aimed to distinguish the potential prenatal parameters influencing the fetal echocardiographic images and enhance the true positive diagnostic rate of CoA fetuses which require early clinical intervention in postnatal life.MethodsA retrospective study had been designed and fetuses with suspected with CoA had been included from Jan 2016 to Dec 2021 in our center. The fetal echocardiography and related clinical information had been collected. And the postnatal diagnosis had been reached by echocardiography or CTA. Then, all the parameters had been analyzed by univariate analysis, and a multivariate logistic regression analysis was further involved to determine the independent parameters influencing the accuracy of diagnosis CoA fetuses. Moreover, such results had been validated by nomogram analysis and ROC curve.ResultsAmong the included 44 liveborn infants who presented suspected CoA in fetal cardiac screening, 18 cases had been proved to be CoA postnatally (Group P). The true positive rate for this study was 40.9% (18/44). The abnormal atrial hemodynamic status (AAHs) and the gestational week of delivery (GWoD) were associated with the postnatal CoA confirmation among prenatal suspected fetuses. The ROC curve of predicting probability of the mode combined with two independent factors of absence of AAH and GWoD (AUC = 0.880, 95% CI 0.763–0.997) presented a satisfied efficacy in distinguishing postnatal positive CoA diagnosis. The nomogram plot had been be utilized in CoA prediction (model likelihood ratio test, p < 0.0001).ConclusionsAAH and GWoD had been identified as independent factors of predictive accuracy in detecting postnatal CoA among prenatal suspected fetuses. The prediction mode based on nomogram scores could be used to predict the risk of occurring CoA fetuses

Quantifying concordant genetic effects of de novo mutations on multiple disorders

Exome sequencing on tens of thousands of parent-proband trios has identified numerous deleterious de novo mutations (DNMs) and implicated risk genes for many disorders. Recent studies have suggested shared genes and pathways are enriched for DNMs across multiple disorders. However, existing analytic strategies only focus on genes that reach statistical significance for multiple disorders and require large trio samples in each study. As a result, these methods are not able to characterize the full landscape of genetic sharing due to polygenicity and incomplete penetrance. In this work, we introduce EncoreDNM, a novel statistical framework to quantify shared genetic effects between two disorders characterized by concordant enrichment of DNMs in the exome. EncoreDNM makes use of exome-wide, summary-level DNM data, including genes that do not reach statistical significance in single-disorder analysis, to evaluate the overall and annotation-partitioned genetic sharing between two disorders. Applying EncoreDNM to DNM data of nine disorders, we identified abundant pairwise enrichment correlations, especially in genes intolerant to pathogenic mutations and genes highly expressed in fetal tissues. These results suggest that EncoreDNM improves current analytic approaches and may have broad applications in DNM studies

RUNX3 Mediates Suppression of Tumor Growth and Metastasis of Human CCRCC by Regulating Cyclin Related Proteins and TIMP-1

Here we presented that the expression of RUNX3 was significantly decreased in 75 cases of clear cell renal cell carcinoma (CCRCC) tissues (p<0.05). Enforced RUNX3 expression mediated 786-O cells to exhibit inhibition of growth, G1 cell-cycle arrest and metastasis in vitro, and to lost tumorigenicity in nude mouse model in vivo. RUNX3-induced growth suppression was found partially to regulate various proteins, including inhibition of cyclinD1, cyclinE, cdk2, cdk4 and p-Rb, but increase of p27Kip1, Rb and TIMP-1. Therefore, RUNX3 had the function of inhibiting the proliferative and metastatic abilities of CCRCC cells by regulating cyclins and TIMP1

Calculation of thermodynamic properties of water by the CPA equation of state

An appreciable amount of formation water exists inevitably in the porous media of reservoirs, but the existence of water is often neglected in the usual calculation of phase equilibrium. The commonly used equation of state is simple, but may have large deviations in estimating some thermodynamic properties. The existing equation of state, which has been modified, is not very suitable for the system containing polar substances (e.g. hydrocarbons, water, and alcohols). In this paper, the CPA (Cubic-Plus-Association) equation of state which considers both physical and association interactions between molecules was used to calculate the thermodynamic properties of water under the saturated and unsaturated states. Moreover, the disadvantages of the commonly used equation of state in the calculation were analyzed. The following results were obtained. First, the commonly used equation of state can be used to effectively calculate the saturated vapor pressure of water, but it presents certain differences in calculating water density and enthalpy, and the enthalpy calculation is not affected by volume modification. Second, the average absolute/relative deviations between the thermodynamic properties of water calculated by the CPA equation of state and the experimental data are approximately 1%. For the system containing polar substances, the CPA equation of state is preferred in calculating the thermodynamic properties. The accurate estimation of the thermodynamic properties of water is fundamental in identifying the fluid state in the water-bearing gas reservoirs, and it is of great significance in the development and production of such gas reservoirs

Multiomics Analysis of a DNAH5-Mutated PCD Organoid Model Revealed the Key Role of the TGF-&beta;/BMP and Notch Pathways in Epithelial Differentiation and the Immune Response in DNAH5-Mutated Patients

Dynein axonemal heavy chain 5 (DNAH5) is the most mutated gene in primary ciliary dyskinesia (PCD), leading to abnormal cilia ultrastructure and function. Few studies have revealed the genetic characteristics and pathogenetic mechanisms of PCD caused by DNAH5 mutation. Here, we established a child PCD airway organoid directly from the bronchoscopic biopsy of a patient with the DNAH5 mutation. The motile cilia in the organoid were observed and could be stably maintained for an extended time. We further found abnormal ciliary function and a decreased immune response caused by the DNAH5 mutation through single-cell RNA sequencing (scRNA-Seq) and proteomic analyses. Additionally, the directed induction of the ciliated cells, regulated by TGF-&beta;/BMP and the Notch pathway, also increased the expression of inflammatory cytokines. Taken together, these results demonstrated that the combination of multiomics analysis and organoid modelling could reveal the close connection between the immune response and the DNAH5 gene

Target genes regulated by RUNX3.

<p>a. The expression of cyclin D1, cyclin E, cdk2, cdk4, p-Rb, Rb, p27, MMP2, MMP9, TIMP-1 and TIMP-2 proteins were evaluated in 786-O-Ctrl and 786-O-RUNX3 cells by Western blot. b. The expression of cyclin D1, cyclin E, cdk2, cdk4, p-Rb, Rb, p27, MMP2, MMP9, TIMP-1 and TIMP-2 proteins were evaluated in HKC-Ctrl and HKC-siRUNX3 by Western blot. All examined gene expression levels quantitatively analyzed and expressed as the ratios over β-actin.</p

Safety of an Escherichia coli-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine An open-label phase I clinical trial

National Major Scientific and Technological Special Project [2012ZX09101316]; National High-tech R&D Program (863 Program) [2012AA02A408]; International Science and Technology Cooperation Program of China [2011DFG33050]; Xiamen Scientific Project [3502Z20127027]An Escherichia coli-expressed recombinant bivalent human papillomavirus (types 16 and 18) vaccine candidate has been shown to be safe and immunogenic in preclinical trials. The safety of this vaccine was analyzed in an open-label phase I clinical trial in Jiangsu province, China. Thirty-eight healthy women from 18 to 55 y of age were enrolled and vaccinated at 0, 1, and 6 mo. Adverse events that occurred within 30 d after each injection and serious adverse events that occurred throughout the study were recorded. In addition, blood parameters were tested before and after each injection. All but one woman received all 3 doses. Thirty-two (84.2%) of the participants reported adverse events, all adverse events of which were mild, of short duration and resolved spontaneously. No serious adverse events occurred during the study. Changes in blood parameters after each injection were random, mild, and not clinically significant. These preliminary results show that a new Escherichia coli-expressed recombinant HPV 16/18 bivalent vaccine is well tolerated in healthy women and support further immunogenicity and efficacy studies for this HPV vaccine candidate