The human leukocyte antigen (HLA)-DR expression on monocytes and plasma Interleukin (IL)-10 levels are key indicators of immune response during the acute phase of severe acute pancreatitis (SAP). We designed a pilot study to investigate whether omega-3 fatty acids (FAs) supplemented parenteral nutrition (PN) could improve immune response in SAP patients. Fifty-six SAP patients were enrolled (28 patients in each group) and received isocaloric and isonitrogenous parenteral nutrition, providing 1.0 g/kg/day standard soybean-oil based fat (omega-6 FAs group) or 0.8 g/kg/day soybean oil +0.2 g/kg/day omega-3 FAs based fat (omega-3 FAs group). IL-10, HLA-DR and the ratio of CD4(+) to CD8(+) were determined before PN treatment and on day 6 after starting PN. The infection and surgery rates were recorded until hospital discharge. A significant IL-10 increase was associated with the administration of omega-3 FAs (p = 0.04, vs omega-6 FAs group). Monocyte HLA-DR expression improved in both groups after 5 days of PN treatment. This increase was significantly higher in the omega-3 FAs group compared to omega-6 FAs (p = 0.01). There was no significant difference of CD4(+)/CD8(+), infection and surgery rates between the two groups. In conclusion, omega-3 FAs supplemented PN can elevate the IL-10 level and HLA-DR expression in SAP patients. A larger trial is required to see whether omega-3 FAs supplemented PN treatment in SAP patients would result in better clinical outcomes than omega-6 FAs.

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Hirschsprung-associated enterocolitis (HAEC) is a life-threatening complication of Hirschsprung’s disease (HD). Although the pathological mechanisms are still unclear, studies have shown that HAEC has a close relationship with the disturbance of intestinal microbiota. This study aimed to investigate the characteristics of the intestinal microbiome of HD patients with or without enterocolitis. During routine or emergency surgery, we collected 35 intestinal content samples from five patients with HAEC and eight HD patients, including three HD patients with a history of enterocolitis who were in a HAEC remission (HAEC-R) phase. Using Illumina-MiSeq high-throughput sequencing, we sequenced the V4 region of bacterial 16S rRNA, and operational taxonomic units (OTUs) were defined by 97% sequence similarity. Principal coordinate analysis (PCoA) of weighted UniFrac distances was performed to evaluate the diversity of each intestinal microbiome sample. The microbiota differed significantly between the HD patients (characterized by the prevalence of Bacteroidetes) and HAEC patients (characterized by the prevalence of Proteobacteria), while the microbiota of the HAEC-R patients was more similar to that of the HAEC patients. We also observed that the specimens from different intestinal sites of each HD patient differed significantly, while the specimens from different intestinal sites of each HAEC and HAEC-R patient were more similar. In conclusion, the microbiome pattern of the HAEC-R patients was more similar to that of the HAEC patients than to that of the HD patients. The HD patients had a relatively distinct, more stable community than the HAEC and HAEC-R patients, suggesting that enterocolitis may either be caused by or result in a disruption of the patient’s uniquely adapted intestinal flora. The intestinal microbiota associated with enterocolitis may persist following symptom resolution and can be implicated in the symptom recurrence.

Excessive production of reactive oxygen species (ROS) and P2X7R activation induced by high glucose increases NLRP3 inflammasome activation, which contributes to the pathogenesis of diabetic cardiomyopathy. Although H3 relaxin has been shown to inhibit cardiac fibrosis induced by isoproterenol, the mechanism has not been well studied. Here, we demonstrated that high glucose (HG) induced the collagen synthesis by activation of the NLRP3 inflammasome, leading to caspase‐1 activation, interleukin‐1β (IL‐1β) and IL‐18 secretion in neonatal rat cardiac fibroblasts. Moreover, we used a high‐glucose model with neonatal rat cardiac fibroblasts and showed that the activation of ROS and P2X7R was augmented and that ROS‐ and P2X7R‐mediated NLRP3 inflammasome activation was critical for the collagen synthesis. Inhibition of ROS and P2X7R decreased NLRP3 inflammasome‐mediated collagen synthesis, similar to the effects of H3 relaxin. Furthermore, H3 relaxin reduced the collagen synthesis via ROS‐ and P2X7R‐mediated NLRP3 inflammasome activation in response to HG. These results provide a mechanism by which H3 relaxin alleviates NLRP3 inflammasome‐mediated collagen synthesis through the inhibition of ROS and P2X7R under HG conditions and suggest that H3 relaxin represents a potential drug for alleviating cardiac fibrosis in diabetic cardiomyopathy.