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Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer (GC) distinguished by the presence of the EBV genome and limited viral gene expression within malignant epithelial cells. EBV infection is generally thought to be a relatively late event following atrophic gastritis in carcinogenesis, which implies the heterogeneity of EBVaGC. To facilitate the study of the role of EBV in EBVaGC, we established two EBV-positive GC cell lines (AGS-EBV and HGC27-EBV) with an epitheliotropic EBV strain M81 and characterized viral and cellular gene expression profiles in comparison to SNU719, a naturally derived EBV-positive GC cell line. Like SNU719, AGS-EBV and HGC27-EBV stably maintained their EBV genomes and expressed EBV-encoded small RNAs and nuclear antigen EBNA1. Comprehensive analysis of the expression of EBV-encoded miRNAs within the BamHI-A region rightward transcript region, and the transcripts of EBV latent and lytic genes in cell lines, as well as xenografts, reveals that AGS-EBV and HGC27-EBV cells undergo distinct viral expression profiles. A very small fraction of AGS-EBV and SNU719 cells can spontaneously produce infectious progeny virions, while HGC27-EBV does not. AGS-EBV (both M81 and Akata) cells largely mimic SNU719 cells in viral gene expression profiles, and altered cellular functions and pathways perturbed by EBV infection. Phylogenetic analysis of the EBV genome shows both M81 and Akata EBV strains are closely related to clinical EBVaGC isolates. Taken together, these two newly established EBV-positive GC cell lines can serve as models to further investigate the role of EBV in different contexts of gastric carcinogenesis and identify novel therapeutics against EBVaGC.

Renin-angiotensin-aldosterone system (RAAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are one of the most prescribed antihypertensive medications. Previous studies showed RAAS inhibitors increase the expression of ACE2, a cellular receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which provokes a concern that the use of ACEI and ARB in hypertensive individuals might lead to increased mortality and severity of coronavirus disease 2019 (COVID-19). To further investigate the effects of ACEI/ARB on COVID-19 patients, we systematically reviewed relevant studies that met predetermined inclusion criteria in search of PubMed, Embase, Cochrane Library databases, medRxiv, and bioRxiv. The search strategy included clinical data published through October 12, 2020. Twenty-six studies involving 8104 hypertensive patients in ACEI/ARB-treated group and 8203 hypertensive patients in non-ACEI/ARB-treated group were analyzed. Random-effects meta-analysis showed ACEI/ARB treatment was significantly associated with a lower risk of mortality in hypertensive COVID-19 patients (odds ratio [OR] = 0.624, 95% confidence interval [CI] = 0.457-0.852, p = .003, I2 = 74.3%). Meta-regression analysis showed that age, gender, study site, Newcastle-Ottawa Scale scores, comorbidities of diabetes, coronary artery disease, chronic kidney disease, or cancer has no significant modulating effect of ACEI/ARB treatment on the mortality of hypertensive COVID-19 patients (all p > .1). In addition, the ACEI/ARB treatment was associated with a lower risk of ventilatory support (OR = 0.682, 95% CI = 0.475-1.978, p = .037, I2 = 0.0%). In conclusion, these results suggest that ACEI/ARB medications should not be discontinued for hypertensive patients in the context of COVID-19 pandemic.