Background and objectives:Diarrhea is a common complication of enteral nutrition (EN), which affects recovery and prolongs the length of hospital stay (LOHS). To investigate the effect of fiber and probiotics in reducing diarrhea associated with EN in postoperative patients with gastric cancer (GC), the authors designed this prospective randomized-controlled trial.Methods and study design:This study included 120 patients with GC, and the patients were classified into 3 groups via random picking of envelopes: fiber-free nutrition formula (FF group, n = 40), fiber-enriched nutrition formula (FE group, n = 40), and fiber- and probiotic-enriched nutrition formula (FEP group, n = 40). All patients were given EN formulas for 7 consecutive days after surgery.Results:The number of diarrhea cases was higher in the FF group than in the FE group (P = .007). The FEP group had a lower number of diarrhea cases compared with the FE group (P = .003). Patients in the FE group had a significantly shorter first flatus time than the FF group (P = .002). However, no significant difference was observed between the FE group and FEP group (P = .30). Intestinal disorders were similar between the FE group and FF group (P = .38). The FEP group had a lower number of intestinal disorder cases than the FF group (P = .03). LOHS in the FE and FEP groups was shorter than that in the FF group (P = .004; P < .001). However, no significant difference was observed between the FE and FEP groups (P = .28). In addition, no significant difference was observed between the 3 groups in terms of total lymphocyte count, albumin, prealbumin, and transferrin levels on day 7 of enteral feeding.Conclusions:The combination of fiber and probiotics was significantly effective in treating diarrhea that is associated with EN in postoperative patients with GC.

Agomelatine (S20098) is a novel antidepressant drug with melatonergic agonist and 5-HT2C receptor antagonist properties, displaying antidepressant/anxiolytic-like properties in animal models and in humans. In a depression/anxiety-like mouse model in which the response of the HPA axis is blunted, we investigated whether agomelatine could reverse behavioural deficits related to depression/anxiety compared to the classical selective serotonin reuptake inhibitor, fluoxetine. Adult mice were treated for 8 wk with either vehicle or corticosterone (35 μg/ml.d) via drinking water. During the final 4 wk, animals were treated with vehicle, agomelatine (10 or 40 mg/kg i.p.) or fluoxetine (18 mg/kg i.p.) and tested in several behavioural paradigms and also evaluated for home-cage activity. Our results showed that the depressive/anxiety-like phenotype induced by corticosterone treatment is reversed by either chronic agomelatine or fluoxetine treatment. Moreover, agomelatine increased the dark/light ratio of home-cage activity in vehicle-treated mice and reversed the alterations in this ratio induced by chronic corticosterone, suggesting a normalization of disturbed circadian rhythms. Finally, we investigated the effects of this new antidepressant on neurogenesis. Agomelatine reversed the decreased cell proliferation in the whole hippocampus in corticosterone-treated mice and increased maturation of newborn neurons in both vehicle- and corticosterone-treated mice. Overall, the present study suggests that agomelatine, with its distinct mechanism of action based on the synergy between the melatonergic agonist and 5-HT2C antagonist properties, provides a distinct antidepressant/anxiolytic spectrum including circadian rhythm normalization.

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The severity of acute liver failure (ALF) induced by bacterial lipopolysaccharide (LPS) is associated with the hepatic innate immune response. The core circadian molecular clock modulates the innate immune response by controlling rhythmic pathogen recognition by the innate immune system and daily variations in cytokine gene expression. However, the molecular link between circadian genes and the innate immune system has remained unclear. Here, we showed that mice lacking the clock gene Per1 (Period1) are more susceptible to LPS/d-galactosamine (LPS/GalN)-induced macrophage-dependent ALF compared with wild-type (WT) mice. Per1 deletion caused a remarkable increase in the number of Kupffer cells (KCs) in the liver, resulting in an elevation of the levels of pro-inflammatory cytokines after LPS treatment. Loss of Per1 had no effect on the proliferation or apoptosis of macrophages; however, it enhanced the recruitment of macrophages, which was associated with an increase in CC chemokine receptor 2 (Ccr2) expression levels in monocytes/macrophages. Deletion of Ccr2 rescued d-GalN/LPS-induced liver injury in Per1−/− mice. We demonstrated that the upregulation of Ccr2 expression by Per1 deletion could be reversed by the synthetic peroxisome proliferator-activated receptor gamma (PPAR-γ) antagonist GW9662. Further analysis indicated that PER1 binds to PPAR-γ on the Ccr2 promoter and enhanced the inhibitory effect of PPAR-γ on Ccr2 expression. These results reveal that Per1 reduces hepatic macrophage recruitment through interaction with PPAR-γ and prevents an excessive innate immune response in endotoxin-induced liver injury.