BackgroundA liver-derived protein, fetuin-A, was first purified from calf fetal serum in 1944, but its potential role in lethal systemic inflammation was previously unknown. This study aims to delineate the molecular mechanisms underlying the regulation of hepatic fetuin-A expression during lethal systemic inflammation (LSI), and investigated whether alterations of fetuin-A levels affect animal survival, and influence systemic accumulation of a late mediator, HMGB1.Methods and FindingsLSI was induced by endotoxemia or cecal ligation and puncture (CLP) in fetuin-A knock-out or wild-type mice, and animal survival rates were compared. Murine peritoneal macrophages were challenged with exogenous (endotoxin) or endogenous (IFN-γ) stimuli in the absence or presence of fetuin-A, and HMGB1 expression and release was assessed. Circulating fetuin-A levels were decreased in a time-dependent manner, starting between 26 h, reaching a nadir around 24–48 h, and returning towards base-line approximately 72 h post onset of endotoxemia or sepsis. These dynamic changes were mirrored by an early cytokine IFN-γ-mediated inhibition (up to 50–70%) of hepatic fetuin-A expression. Disruption of fetuin-A expression rendered animals more susceptible to LSI, whereas supplementation of fetuin-A (20–100 mg/kg) dose-dependently increased animal survival rates. The protection was associated with a significant reduction in systemic HMGB1 accumulation in vivo, and parallel inhibition of IFN-γ- or LPS-induced HMGB1 release in vitro.ConclusionsThese experimental data suggest that fetuin-A is protective against lethal systemic inflammation partly by inhibiting active HMGB1 release.

BackgroundBronchoalveolar lavage (BAL) galactomannan (GM) assay has been used for diagnosing invasive aspergillosis (IA). We aimed to derive a definitive estimate of the overall accuracy of BAL-GM for diagnosing IA.Methods and ResultsWe undertook a systematic review of thirty diagnostic studies that evaluated the BAL-GM assay for diagnosing IA. PubMed and CBM (China Biological Medicine Database) databasees were searched for relevant studies published in all languages up until Feb 2012. The pooled diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC) were constructed for each cutoff value. Additionally, pooled sensitivity (SEN), specificity (SPE), and positive and negative likelihood ratios (PLR and NLR, respectively) were calculated for summarizing overall test performance. Thirty studies were included in this meta-analysis. The summary estimates of pooled DOR, SEN, SPE, PLR, and NLR of the BAL-GM assay (cutoff value 0.5) for proven or probable IA were 52.7 (95% confidence interval (CI) 31.8–87.3), 0.87 (95% CI 0.79–0.92), 0.89 (95% CI 0.85–0.92), 8.0 (95% CI 5.7–11.1) and 0.15 (95% CI 0.10–0.23) respectively. The SROC was 0.94 (95% CI 0.92–0.96). Compared with cutoff value of 0.5, it has higher DOR, SPE and PLR, and similar SEN and NLR with cutoff value of 1.0, which indicated the optimal cutoff value might be 1.0. Compared with BAL-GM, serum GM has a lower SEN and higher SPE, while PCR displays a lower SEN and a similar SPE.ConclusionWith the optimal cutoff value of 1.0, the BAL-GM assay has higher SEN compared to PCR and serum GM test. It is a useful adjunct in the diagnosis of proven and probable IA.

(J7 Clin Pathol 1995;48:133-136)

The direct and indirect effects of Helicobacter pylori on cell kinetics of gastric epithelial cell line AGS were investigated by flow cytometric analysis of