Changes in expression of circRNAs in the intestinal mucosa in septic mice and patients with critical illnesses. (A) Heat map (a) and scatter plot (b) depictions of circRNAs differentially expressed in the small intestinal mucosa in mice exposed to CLP for 48 h as measured by circRNA microarray. (B) Differential expression analysis of circRNAs in results described in A. Values are the means from three animals. (C) Levels of mucosal circHIPK3 and other circRNAs in the small intestine as examined by Q-PCR analysis. Values are the means ± SEM (n = 5). * P < 0.05 compared with sham mice. (D) Total levels and quantification of copy numbers of circHIPK3 in the intestinal mucosa from patients with active CD and UC as measured by Q-PCR and droplet digital Q-PCR analyses, respectively. Values are the means ± SEM (n = 6). * P < 0.05 compared with controls. (E) RNA-FISH analysis of circHIPK3 with fluorescent LNA-RNA detection probe in the mucosa from patients with CD, UC, and sepsis, as shown in yellow-green. Scale bars: 25 μm. All these experiments were repeated in tissue samples obtained from 4 control individuals, 4 patients with CD, 4 patients with UC 4 or 4 patients with sepsis and showed similar results.