ABSTRACT
【Objective】 To study the effect of macrophage mediator 1 (MED1) deficiency on atherosclerosis in female mice. 【Methods】 ApoE knockout (ApoE-/-), LDLR knockout (LDLR-/-), MED1fl/fl, and macrophage MED1 knockout (MED1△Mac) mice were recruited in the study. Two types of mouse model were constructed:ApoE and macrophage MED1 double knockout (MED1△Mac/ApoE-/-) mice and their littermate controls (MED1fl/fl/ApoE-/-). ② LDLR knockout (LDLR-/-) mice receiving bone marrow from MED1△Mac (MED1△Mac→LDLR-/-) or MED1fl/fl (MED1fl/fl→LDLR-/-) mice. Female mice from these two models were fed a Western diet (21% fat and 0.15% cholesterol) for 12 weeks to promote the development of atherosclerosis. Body weight, total cholesterol (TC), and total triglyceride (TG) content in plasma were measured dynamically. After Western diet feeding for 12 weeks, aortic tree and aortic root were collected and hematoxylin-eosin (H&E) and oil red O staining were performed. 【Results】 Plasma TC and TG did not significantly differ between MED1fl/fl/ApoE-/- control group and MED1△Mac/ApoE-/-experimental group. However, the plaque area in aortic tree and aortic root was significantly increased in MED1△Mac/ApoE-/-mice. Moreover, compared with that in MED1fl/fl→LDLR-/- control group, the plaque area of aortic tree and aortic root had an increasing trend in MED1△Mac→LDLR-/- mice group. 【Conclusion】 MED1 deficiency in macrophages promotes the development of atherosclerosis in female ApoE or LDLR knockout mice.
ABSTRACT
Objective@#To explore the prognostic value of the international prognostic index (IPI), the national comprehensive cancer network IPI(NCCN-IPI)and the age-adjusted IPI (aa-IPI) in diffuse large B cell lymphoma.@*Methods@#A total of 311 patients with de novo diffuse large B-cell lymphoma (DLBCL) diagnosed from 2003 to 2012 in Nanfang hospital were included. All patients were divided into CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) and R-CHOP (rituximab, CHOP) groups. Survival analysis was compared among IPI, NCCN-IPI and aa-IPI models. Discrimination of three different prognostic models was assessed using the Harrell’s C statistic.@*Results@#A total of 311 patients were analyzed. Among them, 128 patients were treated with CHOP regimen and other 183 patients were treated with R-CHOP regimen. In CHOP groups, both NCCN-IPI (5-year OS: 59.7% vs 26.8%, P<0.001) and aa-IPI (5-year OS: 71.0% vs 25.0%, P<0.001) showed better risk stratification for low-intermediate and high-intermediate group than the IPI (5-year OS: 47.6% vs 36.6%, P=0.003). However, in the patients treated with R-CHOP, NCCN-IPI showed better risk stratification in low, low-intermediate, high-intermediate groups (5-year OS: 96.0% vs 83.0% vs 66.5%, P=0.009). According to the Harrell’s C statistic, C-index of IPI, NCCN-IPI and aa-IPI for overall survival (OS) were 0.546, 0.667, 0.698 in CHOP group and 0.611,0.654, 0.695 in R-CHOP group respectively. In patients younger than 60 years old, C-index of IPI, NCCN-IPI and aa-IPI for OS were 0.534, 0.675, 0.698 in CHOP group and 0.584, 0.648, 0.695 in R-CHOP respectively.@*Conclusion@#The NCCN-IPI is more powerful than IPI and aa-IPI in DLBCL patients receiving R-CHOP. aa-IPI is a preferable model in predicting prognosis than IPI and NCCN-IPI in anthracycline-based chemotherapy without rituximab.