Contrast-enhanced ultrasound is a promising noninvasive technique for the differential diagnosis of benign and malignant thyroid nodules and could be a valuable supplemental method to fine-needle aspiration.

Background: Conflicting results have been reported on the prognostic significance of serum uric acid (SUA) in patients with acute heart failure (AHF). This meta-analysis aimed to determine the prognostic significance of SUA level in patients with AHF. Methods: We made a comprehensive literature search in Pubmed and Embase databases from inception to April 6, 2018. All available observational studies or post hoc analysis of randomized controlled trial that evaluated the prognostic value of SUA level in patients with AHF were eligible. Outcome of interests were all-cause mortality and the combined endpoint of death or readmission. Prognostic values of SUA level were summarized as higher vs lower SUA category or per 1 mg/ml SUA rise. Results: Ten studies involving 12,854 AHF patients were identified and analyzed. AHF patients with the highest SUA level had an increased risk of all-cause mortality (risk ratio [RR] 1.43; 95% confidence intervals [CI] 1.31–1.56) and combined endpoint of death or readmission (RR 1.68; 95% CI 1.33–2.13) after adjusting potential variables. In addition, per 1 mg/ml SUA rise significantly increased by 11% and 12% higher risk all-cause mortality and combined endpoint of death or readmission, respectively. A leave out 1 study sensitivity analysis confirmed the reliability of the pooling effect sizes. Conclusion: This meta-analysis indicates that elevated SUA level independently predicts all-cause mortality and the combined endpoint of death or readmission in AHF patients. Measurement of SUA level may improve risk stratification of adverse outcomes in these patients.

Pancreatic cancer (Pa) is a malignant tumor of the digestive tract with high degree of malignancy, this study aimed to obtain the hub genes in the tumorigenesis of Pa.Microarray datasets GSE15471, GSE16515, and GSE62452 were downloaded from Gene Expression Omnibus (GEO) database, GEO2R was conducted to screen the differentially expressed genes (DEGs), and functional enrichment analyses were carried out by Database for Annotation, Visualization and Integrated Discovery (DAVID). The protein-protein interaction (PPI) network was constructed with the Search Tool for the Retrieval of Interacting Genes (STRING), and the hub genes were identified by Cytoscape. Totally 205 DEGs were identified, consisting of 51 downregulated genes and 154 upregulated genes enriched in Gene Ontology terms including extracellular matrix (ECM) organization, collagen binding, cell adhesion, and pathways associated with ECM-receptor interaction, focal adhesion, and protein digestion. Two modules in the PPI were chosen and biological process analyses showed that the module genes were mainly enriched in ECM and cell adhesion.Twenty-four hub genes were confirmed, the survival analyses from the cBioPortal online platform revealed that topoisomerase (DNA) II α (TOP2A), periostin (POSTN), plasminogen activator, urokinase (PLAU), and versican (VCAN) may be involved in the carcinogenesis and progression of Pa, and the receiver-operating characteristic curves indicated their diagnostic value for Pa. Among them, TOP2A, POSTN, and PLAU have been previously reported as biomarkers for Pa, and far too little attention has been paid to VCAN. Analysis from R2 online platform showed that Pa patients with high VCAN expression were more sensitive to gemcitabine than those with low level, suggesting that VCAN may be an indicator to guide the use of the chemotherapeutic drug. In vitro experiments also showed that the sensitivity of the VCAN siRNA group to gemcitabine was lower than that of the control group. In conclusion, this study discerned hub genes and pathways related to the development of Pa, and VCAN was identified as a novel biomarker for the diagnose and therapy of Pa.Qing Chen and Dongmei Yu contributed equally to this work. K E Y W O R D S differentially expressed genes, functional enrichment analysis, pancreatic cancer, protein-protein interaction

Objectives Early fetal echocardiography is becoming increasing common during the nuchal translucency scan period. The aim of this meta‐analysis was to assess the accuracy of first‐trimester fetal echocardiography in diagnosing congenital heart defects (CHDs). Methods The databases of PubMed, Embase, the Cochrane Library, and the Cumulative Index to Nursing and Allied Health Literature were systematically searched for the candidate articles, and the references of included studies were also examined. We recorded the characteristics of the included studies and assessed the quality of each study by the Quality Assessment of Diagnostic Accuracy Studies tool. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated with Meta‐Disc version 1.4 software (Ramón y Cajal Hospital, Madrid, Spain). We also evaluated the publication bias by using Stata version 12.0 software (StataCorp, College Station, TX). Results This meta‐analysis included 18 studies with 26,201 fetal hearts. The overall pooled sensitivity, specificity, PLR, and NLR were 0.750, 0.999, 392.95, and 0.277, respectively. The DOR and AUC were 1736.0 and 0.9331. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC for major CHDs were 0.838, 1.000, 725.69, 0.203, 5084.8, and 0.9617. Conclusions First‐trimester fetal echocardiography had high value in diagnosing CHDs, especially major CHDs.

Background: Tumor necrosis factor-α-induced protein 8-like 3 (TNFAIP8L3, also called TIPE3) has been shown to activate PI3K-AKT and MEK-ERK pathways. However, the roles of TIPE3 in progression of lung cancer are largely unknown. Methods: Immunohistochemistry and western blotting were carried out to analyze the expression of TIPE3 in lung cancer clinical tissues and cells. TIPE3-overexpressing and knock-down NSCLC cell lines were established by transfer of TIPE3 coding sequence and shRNA, respectively. In vitro functional assays were performed to assess the effects of TIPE3 on proliferation and metastasis of NSCLC cells. Tumor xenograft mouse model was used to examine the roles of TIPE3 in growth of NSCLC cells in vivo. Western blotting, immunofluorescence, and immunohistochemistry were conducted to evaluate the association of TIPE3 and molecules related to AKT/ERK1/2-GSK3β-β-catenin/Snail pathway. PI3K, MEK, or GSK3β kinase and proteasome inhibition assays as well as β-Trcp and STUB1 siRNA assays were employed to determine the contribution of AKT/ERK1/2-GSK3β signaling and ubiquitin-proteasome pathway to the regulatory effects of TIPE3 on expression of β-catenin, Snail1, and Slug. Results: We demonstrated that TIPE3 was elevated in lung cancer tissues and cells. The expression level of TIPE3 was positively correlated with malignant clinicopathological characteristics of lung cancer patients, such as tumor size, pathologic stage, and lymph node metastasis. Knockdown of TIPE3 suppressed the proliferation and growth of NSCLC cells as well as their migration and invasion ability, whereas TIPE3 overexpression facilitated these biological processes. Mechanistic data showed that TIPE3 promoted AKT and ERK1/2 signaling, inactivated GSK3β activity, and enhanced the expression and transcriptional activity of β-catenin, Snail1, and Slug in NSCLC cells. Kinase or proteasome inhibition and β-Trcp or STUB1 knockdown assays further revealed that TIPE3 upregulated β-catenin, Snail1, and Slug via the AKT/ ERK1/2-GSK3β pathway, in an ubiquitin-proteasome-dependent manner. More importantly, clinical data demonstrated that the expression level of TIPE3 was positively associated with the activation of AKT/ ^ ORCID: 0000-0003-0171-9458. ERK1/2-GSK3β-β-catenin/Snail pathway in lung cancer. Conclusions: Our findings indicate that upregulation of TIPE3 promotes the progression of human NSCLC considerably by activating β-catenin, Snail1, and Slug transcriptional signaling via the AKT/ ERK1/2-GSK3β axis. Therefore, TIPE3 may represent a potential therapeutic target for NSCLC. Keywords: Non-small cell lung cancer (NSCLC); tumor necrosis factor-α-induced protein 8-like 3 (TNFAIP8L3, also called TIPE3); proliferation and growth; metastasis; protein kinase B (AKT)/extracellular signal-regulated kinase 1/2 (ERK1/2)-glycogen synthase kinase 3β (GSK3β)-β-catenin/Snail axis