Hypofibrinogenemia is an independent predictor of hemophagocytic lymphohistiocytosis in children with sepsis.

Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening condition in children with sepsis. We herein aimed to identify clinical and laboratory predictors of HLH in children with sepsis. We conducted a retrospective study of 568 children with sepsis admitted to Guangdong Women and Children Hospital from January 2019 to June 2022. HLH, while rare (6.34%), proved to be a highly fatal complication (37.14%) in children with sepsis. Children with HLH had higher levels of aspartate aminotransferase, lactate dehydrogenase, triglycerides, and ferritin than children without HLH; conversely, they displayed decreased levels of neutrophils, hemoglobin, platelets, fibrinogen, and albumin. Additionally, the HLH group showed higher rates of prolonged fever (> 10 days), hepatomegaly, and splenomegaly than the non-HLH group. Our retrospective analysis identified hypofibrinogenemia (OR = 0.440, P = 0.024) as an independent predictor for the development of HLH in patients with sepsis. The optimal cutoff value for fibrinogen was found to be < 2.43 g/L. The area under the curve for diagnosing HLH was 0.80 (95% confidence interval: 0.73-0.87, P < 0.0001), with a sensitivity of 72.41% and specificity of 76.27%. Thus, hypofibrinogenemia emerges as a potentially valuable predictor for HLH in children with sepsis.

Xylanase improves the intestinal barrier function of Nile tilapia (Oreochromis niloticus) fed with soybean (Glycine max) meal.

BACKGROUND: Soybean (Glycine max) meal is one of the important protein sources for fish, but the non-starch polysaccharides (NSP) in soybean meal impair the intestinal barrier function. Here we aimed to investigate whether xylanase can alleviate the adverse effects on the gut barrier induced by soybean meal in Nile tilapia and to explore the possible mechanism. RESULTS: Nile tilapia (Oreochromis niloticus) (4.09 ± 0.02 g) were fed with two diets including SM (soybean meal) and SMC (soybean meal + 3,000 U/kg xylanase) for 8 weeks. We characterized the effects of xylanase on the gut barrier, and the transcriptome analysis was performed to investigate the underlying mechanism. Dietary xylanase improved intestinal morphology and decreased the concentration of lipopolysaccharide (LPS) in serum. The results of transcriptome and Western blotting showed that dietary xylanase up-regulated the expression level of mucin2 (MUC2) which may be related to the inhibition of protein kinase RNA-like endoplasmic reticulum kinase (perk)/activating transcription factor 4 (atf4) signaling pathways. Microbiome analysis showed that addition of xylanase in soybean meal altered the intestinal microbiota composition and increased the concentration of butyric acid in the gut. Notably, dietary sodium butyrate was supplemented into the soybean meal diet to feed Nile tilapia, and the data verified that sodium butyrate mirrored the beneficial effects of xylanase. CONCLUSIONS: Collectively, supplementation of xylanase in soybean meal altered the intestinal microbiota composition and increased the content of butyric acid which can repress the perk/atf4 signaling pathway and increase the expression of muc2 to enhance the gut barrier function of Nile tilapia. The present study reveals the mechanism by which xylanase improves the intestinal barrier, and it also provides a theoretical basis for the application of xylanase in aquaculture.

Non-coding RNAs and colitis-associated cancer: Mechanisms and clinical applications.

BACKGROUND: Colitis-associated cancer (CAC) is one of the most severe complications of inflammatory bowel disease (IBD), which has caused a worse survival rate in IBD patients. Although the exact aetiology and pathogenesis of CAC are not completely elucidated, evidence indicates that non-coding RNAs are closely involved and play a key role. METHODS: This review aims to summarise the major findings of non-coding RNAs in the development of CAC and present the potential mechanistic links between non-coding RNAs and CAC pathogenesis. The results show that non-coding RNAs can hinder DNA mismatch repair proteins and obstruct chromosome passenger complexes to increase microsatellite instability and accumulate chromosomal instability, respectively. The data also suggest that DNA promoter methylation or RNA methylation modifications of non-coding RNA are the main mechanisms to regulate oncogene or tumour suppressor expression during the CAC progression. Other factors, including gut microbiota perturbations, immune dysregulation and barrier dysfunction, are also regulated and influenced by non-coding RNAs. Besides, non-coding RNAs as molecular managers are associated with multiple critical signalling pathways governing the initiation, progression and metastasis of CAC, including the janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinase (ERK), Toll-like receptor 4 (TLR4), Wnt/ß-catenin and phosphatidylinositol 3-Kinase/Protein Kinase B (PI3K/AKT) pathways. In addition, non-coding RNAs can be detected in colon tissues or blood, and their aberrant expressions and diagnostic and prognostic roles are also discussed and confirmed in CAC patients. CONCLUSIONS: It is believed that a deepening understanding of non-coding RNAs in CAC pathogenesis may prevent the progression to carcinogenesis, and will offer new effective therapies for CAC patients.