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Subset heterogeneity of the mononuclear phagocyte system (MPS) is controlled by defined transcriptional networks and programs; however, the dynamic establishment of programs that control broad, orchestrated expression of transcription factors (TFs) during the progression of monocyte-into-phagocyte (MP) differentiation remains largely unexplored. By using chromatin immunoprecipitation assays, we show the extensive trimethylation of histone H3 lysine 4 (H3K4me3) as well as histone H3 lysine 27 (H3K27me3) occupancy with broad footprints at the promoters of MP differentiation-related TFs, such as HOXA and FOXO genes, KLF4, IRF8 and others. The rapid repression of HOXA genes was closely associated with the MP differentiation program. H3K4me3 participates in regulating HOXA genes at mild and terminal differentiation periods, while H3K27me3 maintains low-level expression of HOXA genes at phagocytic maintenance periods. Furthermore, the reprogramming of H3K27me3 plays a major role in the up-regulation of KLF4 and FOXO genes during MP differentiation. Importantly, the pharmacological inhibition of H3K4me3 and/or H3K27me3 strikingly promotes the differentiation programs of THP-1 and K562 cells. Together, these findings elucidate mechanisms crucial to the dynamic establishment of epigenetic memory, which is central to the maintenance of the MP differentiation blockade.

BACKGROUND: This study aimed to observe the effect of early goal directed therapy (EGDT) on tissue perfusion, microcirculation and tissue oxygenation in patients with septic shock. METHODS: Patients with early septic shock (0.05). PtcO2, PtcO2/FiO2, and PtcCO2 were not linearly related to central venous saturation, lactate, oxygen delivery, and oxygen consumption (P>0.05). CONCLUSION: Peripheral perfusion was improved after EGDT in patients with septic shock, and it was not exactly reflected by the index of systemic perfusion.

To evaluate the hemodynamic response to passive leg raising (PLR) indicates fluid responsiveness in patients with septic shock.Twenty patients with septic shock, considered for fluid challenge (FC), were enrolled in the study from June 2009 to May 2010. Hemodynamic changes were determined by pulse-contour derived cardiac index at baseline, before and after PLR, return to baseline for 10 min, before and after fluid challenge (250 ml saline for 10 min). An increase of SV after fluid challenge (FC-ΔSV) ≥ 10% were defined responders.Twenty patients with septic shock were included in the study. PLR and fluid challenge were performed 46 instances, among which 15 instances were defined as response group. SV and pulse pressure induced by PLR (PLR-ΔSV and PLR-ΔPP) were increased significantly in response group [(76 ± 19) ml vs. (65 ± 18) ml, (73 ± 20) mmHg vs. (62 ± 20) mmHg (1 mmHg = 0.133 kPa), P0.05], while in nonresponse group there were no significant change. PLR-ΔSV and PLR-ΔPP were correlated with FC-ΔSV (r = 0.51, P = 0.001; r = 0.45, P = 0.006), central venous pressure (CVP) were unrelated with FC-ΔSV. Area under curve (AUC) for PLR-ΔSV, PLR-ΔPP and stroke volume variation (SVV) were 0.846, 0.791 and 0.708. PLR-ΔSV ≥ 12.5% predicted fluid responsiveness with sensitivity of 80% and specificity of 93.5%. PLR-ΔPP ≥ 9.5% predicted fluid responsiveness with sensitivity of 73.3% and specificity of 83.9%.PLR-ΔSV and PLR-ΔPP can predict fluid responsiveness in patients with septic shock. PLR-ΔSV and PLR-ΔPP have a greater ability in predicting volume responsiveness than CVP and SVV.