Objective To investigate the clinical significance of PiCCO monitoring in critically ill patients' capacity management. Methods Selected 40 cases critically ill patients from January 2012 to January 2014 in our ICU,22 cases were treated with PiCCO monitoring,established the observation group,18 cases were treated with superior vena cava catheterization monitoring,established the control group,the APACHEⅡ score, HR, MAP, CVP,EVLWI GEDVI,me-chanical ventilation time,ICU stay time were compared. Results GEDVI in the observation group at third day after treatment significantly increased than the first day,and the second day(P<0.01﹚. The EVLWI in the observation group at third day after treatment obviously decreased than before treatment, the first day,the second day after treatment re-spectively(P<0.05﹚. The APACHEⅡ score, HR, MAP, CVP in observation group respectively compared with the control group, there was significant difference (P<0.05﹚. The mechanical ventilation time, ICU stay time in the ob-servation group were significantly shorter than that the control group(P<0.05﹚. Conclusion The capacity index applica-tion of PiCCO monitoring in critically ill patients to guide capacity management is superior to CVP monitoring,facili-tates the assessment the treatment and prognosis in critically ill patients.

Objective:To evaluate the effect of down-regulation of Sp1 expression on the radiosensitivity of glioma cells.Methods:The oligonucleotide sequence encoding shRNA was designed and synthesized, and cloned into LV3 (H1/GFP & Puro) vector to construct the recombinant. U251 and U87 cells were infected with recombinant lentivirus, then the stably-transfected cell lines were obtained by puromycin screening. The expression levels of Sp1 mRNA and protein were detected by RT-PCR and Western blot. Cell survival was detected by clonal survival assay, cell cycle was determined by flow cytometry, and DNA damage was measured by immunofluorescence assay, respectively.Results:At 72 h after infection, high expression of Sp1 lentiviral vector was observed in two cell lines under fluorescence microscope. RT-PCR and Western blot confirmed that the expression levels of Sp1 mRNA and protein were significantly down-regulated in both transfected cells (both P<0.01) and the silencing rates of Sp1 were above 90%. The sensitization enhancement ratio (SER) of shRNA-U251 and shRNA-U87 cells at 10% cell survival level were 1.39 and 1.18, respectively. After irradiation, the G 2/M phase ratio and the number of γ-H2AX foci in two Sp1 knockout groups were significantly increased. Conclusion:shRNA silencing of Sp1 increases the G 2/M phase arrest induced by X-ray, aggravates the degree of DNA double-strand breaks, and improves the radiosensitivity of glioma cells.

KRAS‒PDEδ interaction is revealed as a promising target for suppressing the function of mutant KRAS. The bottleneck in clinical development of PDEδ inhibitors is the poor antitumor activity of known chemotypes. Here, we identified novel spiro-cyclic PDEδ inhibitors with potent antitumor activity both in vitro and in vivo. In particular, compound 36l (K _D = 127 ± 16 nmol/L) effectively bound to PDEδ and interfered with KRAS-PDEδ interaction. It influenced the distribution of KRAS in Mia PaCa-2 cells, downregulated the phosphorylation of t-ERK and t-AKT and promoted apoptosis of the cells. The novel inhibitor 36l exhibited significant in vivo antitumor potency in pancreatic cancer patient-derived xenograft (PDX) models. It represents a promising lead compound for investigating the druggability of KRAS‒PDEδ interaction.