Enhancer RNAs (eRNAs) are a group of lncRNAs transcribed from enhancers, whose regulatory effects on gene expression are an emerging area of interest. However, the role of eRNAs in regulating trophoblast cells and unexplained recurrent pregnancy loss (URPL) remains elusive. We profiled eRNAs in villi from URPL patients and matched controls by RNA-seq. Functions of URPL-related eRNAs were further investigated in vitro. We identified lnc-SLC4A1-1, which was transcribed from an active enhancer marked with H3K27ac and H3K4me1 and so-called eRNA, highly expressed in URPL patients. Gain-of-function experiments indicated that lnc-SLC4A1-1 facilitated trophoblast cell migration and apoptosis. Mechanistically, as an eRNA, lnc-SLC4A1-1 was retained in the nuclei and recruited transcription factor NF-κB to bind to CXCL8, resulting in increased H3K27ac in the CXCL8 promoter and subsequent elevation of CXCL8 expression. Activation of CXCL8 exacerbated inflammatory reactions in trophoblast cells by inducing TNF-α and IL-1β, which could be blocked by an antagonist of lnc-SLC4A1-1. These findings indicate that an eRNA, lnc-SLC4A1-1, alters trophoblast function via activation of immune responses and by regulating the NF-κB/CXCL8 axis. Our study provides new insights in understanding lncRNA/eRNA function in pathological pregnancy, potentially informing on therapeutic strategies for URPL. FUND: National Natural Science Foundation of China, Natural Science Foundation of Jiangsu Province, National Key Research and Development Program, the Priority Academic Program for the Development of Jiangsu Higher Education Institutions.

Team-based learning (TBL) has been adopted as a new medical pedagogical approach in China. However, there are no studies or reviews summarizing the effectiveness of TBL on medical education. This study aims to obtain an overall estimation of the effectiveness of TBL on outcomes of theoretical teaching of medical education in China. We retrieved the studies from inception through December, 2015. Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Wanfang Database, Chinese Scientific Journal Database, PubMed, EMBASE and Cochrane Database were searched. The quality of included studies was assessed by the Newcastle-Ottawa scale. Standardized mean difference (SMD) was applied for the estimation of the pooled effects. Heterogeneity assumption was detected by I2 statistics, and was further explored by meta-regression analysis. A total of 13 articles including 1545 participants eventually entered into the meta-analysis. The quality scores of these studies ranged from 6 to 10. Altogether, TBL significantly increased students’ theoretical examination scores when compared with lecture-based learning (LBL) (SMD = 2.46, 95% CI: 1.53–3.40). Additionally, TBL significantly increased students’ learning attitude (SMD = 3.23, 95% CI: 2.27–4.20), and learning skill (SMD = 2.70, 95% CI: 1.33–4.07). The meta-regression results showed that randomization, education classification and gender diversity were the factors that caused heterogeneity. TBL in theoretical teaching of medical education seems to be more effective than LBL in improving the knowledge, attitude and skill of students in China, providing evidence for the implement of TBL in medical education in China. The medical schools should implement TBL with the consideration on the practical teaching situations such as students’ education level.

Aberrant DNA methylation is considered to be a potential cause of recurrent pregnancy loss (RPL), while potential mechanism has not yet been elucidated. In order to uncover the contribution of the perturbation of DNA methylation in RPL, we performed genome-wide DNA methylation analysis combined with genome-wide gene expression in decidua tissue. Totally, 539 differentially methylated regions (DMRs) were identified and significantly correlated with gene expressions. We observed that hypo-methylated DMR near CREB5 recruited transcription factors binding, such as P53 and SP1, and in turn upregulated CREB5. Compromised cell migration and apoptosis were observed in human CREB5 overexpression trophoblast cell lines, indicating dysfunctional trophoblast cells might contribute to RPL after hypo-methylation of CREB5. In addition, overexpression of CREB5 altered cell cycle. Our data highlights a role of CREB5 involved in the pathogenesis of RPL, and CREB5 maybe a potential diagnostic biomarker for RPL.