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Atrial fibrillation (AF) is the most common cardiac arrhythmia with a high incidence of stroke. Many circular RNAs (circRNAs) have been demonstrated they are elated to various heart diseases and may play important roles in diagnostics or many pathophysiological processes. Nevertheless, there is Few studies on circRNAs functions in persistent AF. To identify AF-related circRNAs and construct the integrative regulatory network of circular RNAs, miRNAs, and mRNAs, we collected human right atrial appendage tissues from 5 patients suffering persistent AF (AF group) and 5 patients with normal sinus rhythm (NSR group) and characterized the global changes in circRNA expression with high-throughput sequencing technology. The differential expression of circRNAs and the interactions between circRNAs and microRNAs were analyzed. The microRNA expression file GSE68475 dataset was downloaded from the Gene Expression Omnibus (GEO) database to explore the differentially expressed microRNAs. The target genes of overlapped miRNAs were predicted by using DIANA-TarBase v8. We constructed the circRNA- miRNA-mRNA network using Cytoscape (version 3.4.0) and the network topology was analyzed by utilizing CentiScaPe app. Results showed that all of 600 differentially expressed circRNAs related to AF were screened, including 340 up-regulated and 260 down-regulated circRNAs. An integrative regulatory network was constructed, which included 30 circRNAs, 9 miRNAs and 130 target mRNAs of these miRNAs. It was concluded that that 30 circRNAs, including 8 upregulated circRNAs and 22 downregulated circRNAs, were predicted to highly possibly function as sponges of 9 miRNAs to regulate gene expression by using bioinformatics analysis. Moreover, the interactions of hsa-miR-339-5p with its related circRNAs and target mRNAs constructed the hub regulatory network in persistent AF by utilizing topology analysis. Our proposed regulatory network of circRNAs-miRNAs-mRNAs may provide new insight into the potential mechanism underlying persistent AF. Additionally, these important molecular may become novel biomarkers providing a new strategy in diagnosis and therapy of AF.

Nifekalant has been used in the treatment of atrial arrhythmia recently. However, there is no consensus on the preferable nifekalant dose to treat atrial fibrillation (AF). The purpose of this study was to explore efficacy and safety of different doses of nifekalant in the cardioversion of persistent AF. The study was a single-centre, randomized controlled trial. All subjects received nifekalant or placebo intravenously, and the nifekalant was given at the dosage of 0.3, 0.4 or 0.5 mg/kg. Primary efficacy end-point: compared with 0.3 mg group, the rate of cardioversion to sinus rhythm from AF in 0.4 and 0.5 mg group was higher. The 0.4 and 0.5 mg/kg doses were associated with a similar magnitude of efficacy (P > .05). Secondary efficacy end-point: termination rates of AF in the group of 0.4 mg and 0.5 mg were higher than 0.3 mg. Primary safety end-point: the rate of Torsades de Pointes or ventricular fibrillation was numerically lower in the 0.4 mg group than 0.5 mg group (P = .02). Secondary safety end-point: The rates of the majority of other common drug-related adverse events in the group of 0.5 and 0.4 mg were higher than the 0.3 mg group. A 0.4 mg/kg dose of intravenous nifekalant may be recommended during the radiofrequency ablation for persistent AF considering the benefit-risk profile.

Background: Quiescin Q6-Sulfydryl Oxidase 2 (QSOX2), an enzyme that can be directly secreted into the extracellular space, is known to be associated with oxidative protein folding. However, whether QSOX2 is abnormally expressed in non-small cell lung cancer (NSCLC) and its role in tumor growth remains unclear. Methods: Real-time quantitative PCR (qPCR), immunohistochemistry (IHC), bioinformatics analyses were applied to analyze the expression pattern and prognostic significance of QSOX2 in NSCLC. Xenografts model, enzyme-linked immunosorbent assays (ELISA), western blot analysis (WB), and IHC were preformed to examine in vivo tumor suppression and intracellular and extracellular expression of QSOX2. Flow cytometry, WB and qPCR analyses were used to elucidate the role of QSOX2 in cell cycle regulation. Chromatin immunoprecipitation assay (ChIP) assay and Dual-Luciferase reporter assay were employed to investigate transcriptional regulation of QSOX2 by E2F Transcription Factor 1 (E2F1) Results: QSOX2 was significantly overexpressed in NSCLC and associated with poor survival in advanced-stage patients. The intracellular and extracellular expression of QSOX2 by tumor cells markedly decreased after anti-cancer therapy in vitro, in vivo and in the clinic. Moreover, QSOX2 silencing in NSCLC cell lines resulted in inhibition of cancer cell proliferation, induction of apoptosis, and decreased expression of cell division-related genes ( CENPF and NUSAP1) and Wnt pathway activators (PRRX2 and Nuc-β-catenin). Mechanically, QSOX2 was expressed periodically during cell cycle and directly regulated by E2F1. Conclusions: Our findings demonstrate that QSOX2 is directly regulated by E2F1 in the cell cycle is essential for the proliferation of NSCLC cells. Furthermore, QSOX2 is an inferior prognostic indicator for NSCLC and may be developed into a biomarker for monitoring tumor burden and therapeutic progress. Funding Statement: This work was supported by the National Natural Science Foundation of China (81660467 to Chao Shi, and 81860427 to Jianping Xiong) and the Youth Science Foundation of Jiangxi Province ( 20171BAB215081 to Chao Shi). Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: This work was approved by the Ethics Committee of the First Affiliated Hospital of Nanchang University (no. MR2018-83).

Cardiomyocyte death is a fundamental progress in cardiomyopathy. However, the mechanism of triggering the death of myocardial cells remains unclear. Ferroptosis, which is the nonapoptotic, iron-dependent, and peroxidation-driven programmed cell death pathway, that is abundant and readily accessible, was not discovered until recently with a pharmacological approach. New researches have demonstrated the close relationship between ferroptosis and the development of many cardiovascular diseases, and several ferroptosis inhibitors, iron chelators, and small antioxidant molecules can relieve myocardial injury by blocking the ferroptosis pathways. Notably, ferroptosis is gradually being considered as an important cell death mechanism in the animal models with multiple cardiomyopathies. In this review, we will discuss the mechanism of ferroptosis and the important role of ferroptosis in cardiomyopathy with a special emphasis on the value of ferroptosis as a potential novel diagnostic and therapeutic target for patients suffering from cardiomyopathy in the future.

Background. Respiratory motion may compromise the dose delivery accuracy in liver stereotactic body radiation therapy (SBRT). Motion management can improve treatment delivery. However, external surrogate signal may be unstable and inaccurate. This study reports the first case of liver SBRT based on internal electromagnetic motion monitoring in China.Materials and Methods. The patient with a primary liver cancer was treated with respiratory-gated SBRT guided by three implanted electromagnetic transponders. The treatment was carried out in breath-hold end-exhale with beam-on when the centroid of the three transponders drifted within 5 mm (left-right (LR), anterior-posterior (AP) and cranio-caudal (CC) directions) from the planned position. The motion monitoring treatments were delivered in breath-hold end-exhale mode with the energy of 6 MV in FFF mode with 1200 monitor units (MU) per minute. For each fraction, QA results, intertransponder distances, geometric checks as well as tumor motion logs were explicitly recorded.Results. Comparing with the plan data, distance variances between each two transponders were -0.056±0.032 cm, 0.017±0.033 cm and -0.082±0.068 cm. Geometric residual, the pitch, roll and yaw angles were 0.048±0.021 cm (threshold 0.2 cm), 2.17°±1.85°(threshold 10°), -2.42°±1.51° (threshold 10°) and 1.67°±1.07° (threshold 10°), respectively. The delivery time of the five fields were 13.8 s, 13.1 s, 11.18 s, 11.57 s, 11.62 s with the average value of 12.254±1.13 s. Treatment duration of each fraction ranged from 6.22 minutes to 21.43 minutes, with the average value of 11.25±5.03 minutes.Conclusions. The first case of liver SBRT patient of China based on internal electromagnetic motion monitoring was performed. The system had a high tracking accuracy, and it did not delay the treatment time. In addition, the patient did not show any severe side effects except for I°myelotoxicity. The internal electromagnetic motion monitoring system provides a real-time and direct way to track liver tumor targets.

Long QT syndrome (LQTS) is an arrhythmic heart disease caused by congenital genetic mutations, and results in increased occurrence rates of polymorphic ventricular tachyarrhythmias and sudden cardiac death (SCD). Clinical evidence from numerous previous studies suggested that beta blockers (BBs), including atenolol, propranolol, metoprolol, and nadolol, exhibit different efficacies for reducing the risk of cardiac events (CEs), such as syncope, arrest cardiac arrest (ACA), and SCD, in patients with LQTS. In this study, we identified relevant studies in MEDLINE, PubMed, embase, and Cochrane databases and performed a meta-analysis to assess the relationship between the rate of CEs and LQTS individuals with confounding variables, including different gender, age, and QTc intervals. Moreover, a network meta-analysis was not only established to evaluate the effectiveness of different BBs, but also to provide the ranked efficacies of BBs treatment for preventing the recurrence of CEs in LQT1 and LQT2 patients. In conclusion, nadolol was recommended as a relatively effective strategy for LQT2 in order to improve the prognosis of patients during a long follow-up period.

Evidence regarding the association between blood lead levels (BLL) and hyperhomocysteinemia (HHcy) in US adults was limited. We aimed to investigate the association of BLL with the risk of HHcy, and to examine possible effect modifiers using US National Health and Nutrition Examination Survey (NHANES) database. We performed a cross-sectional study using data from up to 9,331 participants aged ≥ 20 years of NHANES from 2001 to 2006. BLL was measured by atomic absorption spectrometry. HHcy was defined as plasma homocysteine level > 15 µmol/L. The weighted prevalence of HHcy was 6.87%. The overall mean BLL was 1.9 μg/dL. Overall, there was a nonlinear positive association between Ln-transformed BLL (LnBLL) and the risk of HHcy. The Odds ratios (95% CI) for participants in the second (0.04–0.49 μg/dL), third (0.5–0.95 μg/dL) and fourth quartiles (> 0.95 μg/dL) were 1.12 (95% CI: 0.71, 1.76), 1.13 (95% CI: 0.73, 1.77), and 1.67 (95% CI: 1.07, 2.61), respectively, compared with those in quartile 1. Consistently, a significantly higher risk of HHcy (OR: 1.49; 95% CI: 1.19, 1.88) was found in participants in quartile 4 compared with those in quartiles 1–3. Furthermore, a strongly positive association between LnBLL and HHcy was observed in participants with estimated glomerular filtration rate (eGFR) −1/1.73 m−2. Our results suggested that a higher level of BLL (LnBLL > 0.95 μg/dL) was associated with increased risk of HHcy compared with a lower level of BLL (LnBLL ≤ 0.95 μg/dL) among U.S. adults, and the association was modified by the eGFR.

ARHGEF16 is a recently identified Rho-family guanine nucleotide exchange factor (GEF) that has been implicated in the activation of Rho-family GTPases such as Rho G, Rac, and Cdc42. However, its functions in colon cancer cell proliferation and migration are not well understood. In this study, we showed that ARHGEF16 was highly expressed in clinical specimens of colon cancer. In colon cancer cells, ARHGEF16-stimulated proliferation and migration in vitro and in vivo. Furthermore, we identified a nonreceptor tyrosine kinase, FYN, as a novel partner of ARHGEF16. Knocking down FYN expression decreased ARHGEF16 protein level in colon cancer cells. We further demonstrated that ARHGEF16-induced colon cancer cell proliferation and migration were dependent on FYN since knockdown FYN abolished the ARHGEF16-induced proliferation and migration of colon cancer cells. The FYN-ARHGEF16 axis mediates colon cancer progression and is a potential therapeutic target for colon cancer treatment.

DNAJC5 (DnaJ heat shock protein family (Hsp40) member C5), also known as cysteine tandem protein (CSPα), is important for maintaining the normal function of nerve tissues, but its oncogenic function remains unknown. Here, we report a unique mechanism underlying the oncogenic function of DNAJC5. DNAJC5 protein expression is highly detectable in human hepatocellular carcinoma (HCC) tissues and is strongly related to a poor prognosis among HCC patients. DNAJC5 overexpression promotes HCC cell proliferation and reduced the ratio of cells in G1 phase of the cell cycle. Furthermore, DNAJC5 interacts with SKP2 and enhances the degradation of p27 (a cyclin-dependent kinase inhibitor1B) by promoting formation of the SKP2-p27 complex. In contrast, DNAJC5 knockdown rescues the SKP2-mediated decrease in p27 protein levels. These results reveal that the DNAJC5-SKP2-p27 pathway is a novel mechanism for the oncogenic function of DNAJC5 in HCC.