Hypoxia contributes significantly to the development of chemoresistance of many malignancies including esophageal cancer (EC). Accumulating studies have indicated that long non-coding RNAs play important roles in chemotherapy resistance. Here, we identified a novel lncRNA-EMS/miR-758-3p/WTAP axis that was involved in hypoxia-mediated chemoresistance to cisplatin in human EC. Hypoxia induced the expressions of lncRNA EMS and WTAP, and reduced the expression of miR-758-3p in EC cell line ECA-109. In addition, the expressions of EMS and WTAP were required for the hypoxia-induced drug resistance to cisplatin in EC cells, while overexpression of miR-758-3p reversed such chemoresistance. The targeting relationships between EMS and miR-758-3p, as well as miR-758-3p and WTAP, were verified by luciferase-based reporter assays and multiple quantitative assays after gene overexpression/knockdown. Moreover, we found significant correlations between tumor expressions of these molecules. Notably, higher levels of EMS/WTAP, or lower levels of miR-758-3p in tumors predicted worse survivals of EC patients. Furthermore, in a xenograft mouse model, targeted knockdown of EMS and WTAP in ECA-109 cells markedly attenuated the resistance of tumors to cisplatin treatments. Our study uncovers a critical lncRNA-EMS/miR-758-3p/WTAP axis in regulating hypoxia-mediated drug resistance to cisplatin in EC.

Background: Combination therapy with immune checkpoint inhibitors (ICIs) has been applied in the clinic to achieve synergistic effects and to improve clinical efficacy. Compared with monotherapy, combination therapy has promising efficacy against various advanced cancers. To further verify the effectiveness of combination therapy, we conducted a meta-analysis of the efficacy and safety of nivolumab (NIVO) and NIVO plus ipilimumab (IPI) in advanced cancer. Methods: Electronic databases (PubMed, EMbase, and The Cochrane Library) were systematically searched for applicable studies published in English between January 1990 and June 2019. Relevant outcomes included objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and grade 3-4 adverse events (AEs).

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Background: Individuals with heart failure (HF), a debilitating disease with ongoing adaptation and management, are often cared for by partner caregivers whose needs and voices are overshadowed by the demands of HF management. With multidimensional needs and complex challenges for individuals with HF, partner caregivers have to deal with uncertainty and need guidance. Given the vital role of partners, attention should be drawn toward understanding the experience of HF partner caregivers. Objective: The aim of this study was to synthesize existing qualitative evidence related to caregivers' views and experiences of caring for their partners with HF. This knowledge would assist healthcare providers to better meet the demand of partners and provide them with effective guidance. Methods: A metaethnography of qualitative evidence was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations for reporting systematic reviews. A comprehensive search of PubMed, Scopus, ISI Web of Science, CINAHL, PsycINFO, and EMBASE, as well as hand searches of the reference lists from included articles, was conducted. A combination of subject terms including MeSH and keywords related to HF, partner experience, and qualitative methods was used to identify studies. Studies were included if they were published in English between January 2000 and December 2020 and examined caregivers' experiences in providing care for their partner with HF by using qualitative methods. Results: Ten articles were included, with 178 participants, and most partners were female. Five studies were conducted in the United States, and 4 studies were conducted in Sweden. Five studies reported partners' health problems; 8 of the studies delineated the inclusion and exclusion criteria for partners. Five overarching themes emerged: shouldering the responsibility, being overloaded, bearing emotional burdens, staying positive, and "left in the dark," craving support from others. Conclusions and Clinical Implications: Given the complex roles in caring for individuals with HF, more qualitative research is strongly warranted to enhance caregivers' support and education. A deeper and more comprehensive understanding of the experiences of caregivers for partners with HF is essential for developing tailored interventions. Healthcare providers should be aware of the importance of ongoing assessment and evaluate partner caregivers' needs and assist them in providing more information and formulating coping strategies as required.