An excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remain incompletely studied. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D. By performing BA-related metabolic and metagenomic analyses in 290 IBS-D patients and 89 healthy volunteers, we found that 24.5% of IBS-D patients exhibited excessive excretion of total BAs and alteration of BA-transforming bacteria in feces. Notably, the increase in Clostridia bacteria (e.g., C. scindens) was positively associated with the levels of fecal BAs and serum 7α-hydroxy-4-cholesten-3-one (C4), but negatively correlated with serum fibroblast growth factor 19 (FGF19) concentration. Furthermore, colonization with Clostridia-rich IBS-D fecal microbiota or C. scindens individually enhanced serum C4 and hepatic conjugated BAs but reduced ileal FGF19 expression in mice. Inhibition of Clostridium species with vancomycin yielded opposite results. Clostridia-derived BAs suppressed the intestinal FGF19 expression in vitro and in vivo. In conclusion, this study demonstrates that the Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients, which provides a mechanistic hypothesis with testable clinical implications.

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SummaryPropofol is used both for induction and maintenance of anaesthesia. Recent evidence shows that propofol has analgesic properties. This meta-analysis evaluated differences in postoperative analgesia between general anaesthetic maintenance with intravenous propofol and inhalational anaesthetics. Fourteen trials met inclusion criteria and were included. Our outcomes were pain scores 2 and 24 h after surgery. No significant difference in pain scores was found at 2 h after surgery (Hedge's g (95% CI) À0.120 (À0.415-0.175) (p = 0.425). Propofol was associated with a statistically significant, albeit marginal, reduction in pain scores 24 h after surgery (Hedge's g (95% CI) À0.134 (À0.248 to À0.021) (p = 0.021). Data were insufficient to allow a meaningful analysis regarding 24-h morphine-equivalent consumption. Propofol was associated with reduced postoperative nausea and vomiting (relative risk (95%CI) 0.446 (0.304-0.656) (p < 0.0001). In conclusion, this meta-analysis suggests that propofol improves postoperative analgesia compared with inhalational anaesthesia 24 h after surgery, with a lower incidence of nausea and vomiting.

SummaryIntranasal dexmedetomidine has been used successfully for sedation in children. A mucosal atomisation device delivers an atomised solution to the nasal mucosa which facilitates rapid and effective delivery of medication to the systemic circulation. We compared intranasal delivery of dexmedetomidine in a dose of 3 lg.kg À1 by either atomiser or drops from a syringe in children < 3 years old undergoing transthoracic echocardiography. Two hundred and seventy-nine children were randomly assigned to one or other group. One hundred and thirty-seven children received dexmedetomidine by atomiser and 142 by drops. The successful sedation rate was 82.5% (95% CI 75.3-87.9%) and 84.5% (95% CI 77.7-89.5%) for atomiser and drops, respectively (p = 0.569). Sedation tended to be less successful in older children (p = 0.028, OR 0.949, 95% CI 0.916-0.983). There were no significant complications. We conclude that both modes of dexmedetomidine administration are equally effective, although increasing age of the child was associated with a decreased likelihood of successful sedation.

Patients with triple-negative breast cancers (TNBC) are at a high risk for a recurrent or metastatic disease, and the molecular mechanisms associated with this risk are unclear. Proteoglycan serglycin (SRGN) proteins are involved in tumor metastasis, but their role in TNBC has not yet been elucidated. This study investigates the SRGN gene expression and how it regulates TGFβ2 and the downstream signaling of TGFβ2 in TNBC cells and tissues. Our results show that SRGN mRNA and protein expression levels were significantly higher in TNBC cell lines and tumor tissues than that in non-TNBC cells and tissues. We inhibited SRGN expression and protein secretion using shRNA and we observed this inhibited the invasive motility of TNBC cancer cells in vitro and metastasis of TNBC cancer cells in vivo. SRGN protein treatment increased the expression and secretion of transforming growth factor-β2 (TGFβ2) by activating CD44/CREB1 signaling and promoted epithelial-to-mesenchymal transition in TNBC cells. Moreover, TGFβ2 treatment increased the mRNA and protein expression of the SRGN gene by activating Smad3 to target the SRGN relative promoter domain in TNBC cells. Our findings demonstrate that SRGN interacts with TGFβ2 which regulates TNBC metastasis via the autocrine and paracrine routes. SRGN could serve as a potential target for development of agents or therapeutics for the TNBC.