ABSTRACT
Herein, we define the role of ferroptosis in the pathogenesis of diabetic cardiomyopathy (DCM) by examining the expression of key regulators of ferroptosis in mice with DCM and a new ex vivo DCM model. Advanced glycation end-products (AGEs), an important pathogenic factor of DCM, were found to induce ferroptosis in engineered cardiac tissues (ECTs), as reflected through increased levels of Ptgs2 and lipid peroxides and decreased ferritin and SLC7A11 levels. Typical morphological changes of ferroptosis in cardiomyocytes were observed using transmission electron microscopy. Inhibition of ferroptosis with ferrostatin-1 and deferoxamine prevented AGE-induced ECT remodeling and dysfunction. Ferroptosis was also evidenced in the heart of type 2 diabetic mice with DCM. Inhibition of ferroptosis by liproxstatin-1 prevented the development of diastolic dysfunction at 3 months after the onset of diabetes. Nuclear factor erythroid 2-related factor 2 (NRF2) activated by sulforaphane inhibited cardiac cell ferroptosis in both AGE-treated ECTs and hearts of DCM mice by upregulating ferritin and SLC7A11 levels. The protective effect of sulforaphane on ferroptosis was AMP-activated protein kinase (AMPK)-dependent. These findings suggest that ferroptosis plays an essential role in the pathogenesis of DCM; sulforaphane prevents ferroptosis and associated pathogenesis via AMPK-mediated NRF2 activation. This suggests a feasible therapeutic approach with sulforaphane to clinically prevent ferroptosis and DCM.
ABSTRACT
Objective To discuss the detail design of medical linear accelerator room to optimize the layout of radiation shield.Methods According to the optimization principle for medical exposure protection and national radiation protection related documents,the influence of detail design on room quality was analyzed.Optimization design was executed from theaspects of spatial layout,protection,shielding wall,decorating materials,labyrinth,control cabin,protective door,occupancy factor,purification ventilation,tennperature humidity control and etc.Results The design and layout of the roomwere optimized to eliminate hidden risksand reduce the design flaws to prevent adverse consequences due to design errors.Conclusion Detail design contributes to stable operation,enhanced quality and efficiency of medical linear accelerator room.
ABSTRACT
Objective To investigate the significance of monitoring P(c-a)CO2 (the gradients between transcutaneous PCO2 and arterial PCO2) in patients with septic shock.Method 31 patients with early septic shock were enrolled as the study group and 20 patients with stable hemodynamics as the control group from Fab.2013 to Sept.2014 in our Intensive Care Unit (ICU).The patients with septic shock were treated guided by early goal directed therapy (EGDT) within 6 hours since hospitalization.The differences of baseline P(c-a) CO2 levels and other index as arterial lactate (LAC) concentration between two groups and the variations of these indexes after EGDT in the study group were compared respectively.Results The baseline levels of P(c-a)CO2 and LAC in patients with septic shock were significantly higher than in patients of control group: (21.2 ± 10.1) mmHg vs.(7.5 ±4.6), P =0.000, and (4.0±2.4) mmol/ Lvs.(1.6 ± 0.5), P =0.000.The areas under receiver operator characteristic (ROC) curve (AUC) for baselineP(c-a)CO2 and LAC were 0.918 (95％ CI: 0.843-0.992) and 0.840 (95％ CI: 0.719-0.962) respectively.A threshold of 14.0 mmHg for P(c-a)CO2 and 2.1 mmol/L for LAC discriminated patients with septic shock from without shock with the same sensibility of 83.9％ and the same specificity of 90.0％, respectively.With regard to prognosis (Day 28), AUC for baseline P(c-a)CO2 and LAC were 0.739 (95％ CI: 0.562-0.917) and0.702 (95％ CI: 0.514-0.889) respectively.A threshold of 21.5 mmHg for P(c-a) CO2 and 3.9 mmol/L for LAC discriminated survivors from nonsurvivors with the same sensibility of 71.4％ and the same specificity of 70.6％ respectively.31 patients in the study group completed EGDT within 6 hours after the admission, 16 (51.6％) passed EGDT and 13 (81.3％) survived, 15 (48.4％) failed EGDT and 4 (26.7％) survived, and survival rates were significantly different, F =9.314, P =0.004.After EGDT, P(c-a) CO2 (18.8 ± 9.4) mmHg and LAC (3.3 ± 2.4) mmol/Lreduced significantly compared with the baselines, all P =0.000.AUC then for P(c-a) CO2 and LAC were 0.742 (95％ CI: 0.562-0.921) and 0.769 (95％ CI: 0.593-0.945), respectively.A threshold of 18.3 mmHg for P(c-a)CO2 and 3.1 mmol/L for LAC discriminated survivors from nonsurvivors with the same sensibility of 71.4％ and the specificity of 71.4％ and of 76.5％ respectively.P(c-a) CO2 and LAC of patients passed EGDT reduced significantly compared with those failed EGDT: (14.8 ± 7.5) mmHgvs.(23.6±9.6) mmHg (P=0.012)、 (2.5±1.5) mmol/L vs.(4.3±2.9) mmol/L (P=0.038), and so did with their baseline : (14.8±7.5) mmHgvs.(18.0±8.1) mmHg, (P=0.042)、 (2.5±1.5) mmol/Lvs.(3.2±1.8) mmol/L, P=0.043.In patients failed EGDT, P(c-a)CO2 and LAC changed little after EGDT, from (24.6 ± 9.2) to (23.6 ± 9.6) mmHg (P =0.238) and from (4.8 ± 2.5) mmol/L to (4.3 ± 2.9) mmol/L (P =0.629).When baseline levels were compared between patients passed EGDT with those failed EGDT, P(c-a) CO2 was (18.0 ±8.1) mmHg vs.(24.6 ± 9.2) mmHg (P =0.042), LAC was (3.2 ± 1.8) mmol/L vs.(4.8 ± 2.5) mmol/L (P =0.050).Conclusions P(c-a) CO2 ＞ 14.0 mmHg could play a role in recognizing early septic shock.EGDT was an effective therapy for the disease and P(c-a)CO2 level could reflect the efficacy of EGDT.P(c-a)CO2 ＞ 21.5mmHg before EGDT and P(c-a) CO2 ＞ 19.3 mmHg after EGDT both could predict the prognosis of patients with septic shock.All above correlated well with LAC and represented a new efficient technique to assess tissue microperfusion.