Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. In order to explore the effects of comorbid chronic diseases on clinical outcomes of COVID-19, a search was conducted in PubMed, Ovid MEDLINE, EMBASE, CDC, and NIH databases to April 25, 2020. A total of 24 peer-reviewed articles, including 10948 COVID-19 cases were selected. We found diabetes was present in 10.0%, coronary artery disease/cardiovascular disease (CAD/CVD) was in 8.0%, and hypertension was in 20.0%, which were much higher than that of chronic pulmonary disease (3.0%). Specifically, preexisting chronic conditions are strongly correlated with disease severity [Odds rati o (OR) 3.50, 95% CI 1.78 to 6.90], and being admitted to intensive care unit (ICU) (OR 3.36, 95% CI 1.67 to 6.76); in addition, compared to COVID-19 patients with no preexisting chronic diseases, COVID-19 patients who present with either diabetes, hypertension, CAD/CVD, or chronic pulmonary disease have a higher risk of developing severe disease, with an OR of 2.61 (95% CI 1.93 to 3.52), 2.84 (95% CI 2.22 to 3.63), 4.18 (95% CI 2.87 to 6.09) and 3.83 (95% CI 2.15 to 6.80), respectively. Surprisingly, we found no correlation between chronic conditions and increased risk of mortality (OR 2.09, 95% CI 0.26 to16.67). Taken together, cardio-metabolic diseases, such as diabetes, hypertension and CAD/CVD were more common than chronic pulmonary disease in COVID-19 patients, however, each comorbid disease was correlated with increased disease severity. After active treatment, increased risk of mortality in patients with preexisting chronic diseases may reduce.

The aim of this study was to investigate the effects of age on hemispheric asymmetry in the auditory cortex after pure tone stimulation. Ten young and 8 older healthy volunteers took part in this study. Two-dimensional multivoxel 1H-magnetic resonance spectroscopy scans were performed before and after stimulation. The ratios of N-acetylaspartate (NAA), glutamate/glutamine (Glx), and γ-amino butyric acid (GABA) to creatine (Cr) were determined and compared between the two groups. The distribution of metabolites between the left and right auditory cortex was also determined. Before stimulation, left and right side NAA/Cr and right side GABA/Cr were significantly lower, whereas right side Glx/Cr was significantly higher in the older group compared with the young group. After stimulation, left and right side NAA/Cr and GABA/Cr were significantly lower, whereas left side Glx/Cr was significantly higher in the older group compared with the young group. There was obvious asymmetry in right side Glx/Cr and left side GABA/Cr after stimulation in young group, but not in older group. In summary, there is marked hemispheric asymmetry in auditory cortical metabolites following pure tone stimulation in young, but not older adults. This reduced asymmetry in older adults may at least in part underlie the speech perception difficulties/presbycusis experienced by aging adults.

Salmonella Typhimurium (S. Typhimurium) is an aggressive zoonotic pathogen that causes enteritis and diarrhea. Antibiotic therapy is still the primary method at present. However, the increasing emergence of multi-drug resistant bacteria weakens the therapeutic efficacy of antibiotics. Probiotics have been widely studied as an alternative antibiotic therapy. In this study, we established an IPEC-J2 cell model of S. Typhimurium infection, aiming to determine the protective effect of Lactobacillus johnsonii L531 (L. johnsonii L531) on S. Typhimurium infection. As our data showed, S. Typhimurium infection resulted in a robust inflammatory response demonstrated by promoted protein levels of the inflammatory-related pathway (TLR4, MyD88, p-IκBα, and p-p65), increased cytokine levels of IL-6, IL-1β, IL-18, and TNF-α, and activated the NLRP3 inflammasome via promoting its assembly. However, L. johnsonii L531 pre-incubation inhibited the activation of the above inflammatory signaling pathways and reduced the expression levels of pro-inflammatory cytokines. In addition, L. johnsonii L531 alleviated the damage of S. Typhimurium to tight junctions ZO-1, Occludin, and Claudin-1. In summary, our findings suggested that L. johnsonii L531 alleviated S. Typhimurium-induced tight junction injury by inhibiting the TLR4/NF-κB/NLRP3 inflammasome signaling pathway.

Tumor residue or recurrence is common after radiation therapy for nasopharyngeal cancer (NPC) since the tumor cells can repair irradiation-induced DNA damage. The ubiquitination cascade mediates the assembly of repair and signaling proteins at sites of DNA double-strand breaks (DSBs). Ring finger protein 8 (RNF8) is an E3 ubiquitin ligase that triggers ubiquitination at the site of DSBs. The present study aimed to identify whether and how RNF8 small interfering RNA (siRNA) treatment enhances the radiosensitivity of irradiated human NPC cell lines. The CNE1, CNE2, and SUNE human NPC cell lines were stably transfected with a constructed RNF8-targeting siRNA expression vector. Western blotting was used to detect the effectiveness of RNF8 downregulation by RNF8 siRNA. The siRNA-transfected (RNF8-) and non-transfected (RNF8+) cells were irradiated at different doses by a linear accelerator. The growth inhibition ratio and apoptosis rate were detected by the methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. The ataxia-telangiectasia mutated (ATM), DNA-PKcs, Chk1, Chk2, Nbs1 and Ku80 protein levels in each group were determined. The growth inhibition ratio and apoptotic percentage of RNF8- cells were higher than those of the RNF8+ cells in each of the three cell lines. Lower protein expression levels of Chk1, Chk2, ATM, and Nbs1 were observed in the irradiated RNF8- cells compared to the irradiated RNF8+ cells in each of the three cell lines (P<0.01). As a result, a conclusion could be drawn that RNF8 recruits and ubiquitinates many factors to repair DNA damage, including DSBs, thereby conferring radioresistance to NPC cells.