The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

Tet (ten-eleven translocation) proteins belong to α-ketoglutaric acid (α-KG or 2-OG) and Fe2+ dependent dioxygenases. Tets are found to be involved in the unique mammalian DNA active demethylation process by specifically oxidizing the methyl group of 5-methylcytosine (5mC) in mammalian genome, and play critical roles in gene regulation in early embryonic development and stem cell differentiation via regulating the dynamic balance distribution of 5mC. Abnormal expression and function of Tets are closely associated with various hematological malignances, including myelodysplastic syndrome, chronic myelomonocytic leukemia, and acute lymphoblastic leukemia, as well as solid tumors. Hence, Tets and Tets-mediated DNA demethylation are novel anti-tumor drug targets. Investigation of biological function and catalytic mechanism of Tets is helpful for further understanding mechanisms of tumor incidence and development relevant to DNA demethylation pathway and can provide reference for developing new anti-tumor targeted drugs.

Objective To explore the diagnostic performance of susceptibility weighted imaging (SWI) in distinguishing malignant from benign parotid lesions.Methods We prospectively evaluated preoperative SWI findings of 41 patients with 12 malignant and 29 benign parotid lesions by surgical pathology, and explore the intravenous distribution, the largest diameter of veins (dv-max), the number of veins per unit area (N/Svein) and the graduation of intratumoral susceptibility signal intensity (ITSS).The parameters was analyzed by Chi-square test, Independent t-test, Mann-Whitney U rank test and receiver operating characteristics (ROC) curves with SPSS 16.0 software.Results (1) For intravenous distribution, the benign ones mainly distributed around peripheral areas, accounting for 89.7％ (26/29), while the malignant ones were centrally distributed, making up 10/12.There were significant difference (x2=20.882, P=0.000) between benign and malignant ones.(2) The largest diameter of veins (dv-max) of benign and malignant lesions were (1.1±0.5) mm and (2.5 ± 1.0)mm respectively.There were significant difference (t=4.633, P=0.000) between benign and malignant ones.(3) The N/Svein of benign lesions were (0.80±0.92) per cm2, while that of malignant ones are (1.07±0.69) per cm2.The N/Svein (t=0.9143, P=0.367) was statistically insignificant.(4) For the graduation of ITSS,among benign lesions, there were 3 cases of grade 0, 22 cases of grade 1, 2 cases of grade 2 and 2 cases of grade 3.Meanwhile, there were 2 cases of grade 1, 5 cases of grade 2 and 5 cases of grade 3 among malignant lesions.When the Youden index reached the highest point, the optimal diagnostic threshold of dv-max and ITSS values were 1.75 mm and 1.5 mm, the corresponding area under the ROC curve (AUC) were 0.924 and 0.856 respectively.The sensitivity of d and ITSS ondiagnosis were 10/12 and 10/12, and the specificity of that were 96.6％ and 86.2％ respectively.The table shows that the sensitivity and specificity of intravenous distribution in diagnosis of malignant lesions are 10/12 and 89.7％.Conclusions The results provided evidence that SWI may be helpful in distinguishing malignant from benign parotid lesions, and it is worth to be generalized in clinical medicine.

Objective Compare the efifcacy and safety of drug eluting stent (DES) for treatment of in stent restenosis (ISR) and coronary de novo lesions. Methods Patients treated with DES for ISR and de novo lesions in Beijing Anzhen Hospital between October 2008 and December 2011 were followed up for 1 year. All lesions were divided into ISR and de novo group. Major adverse cardiovascular events (MACE) including all-cause death, myocardial infarction (MI) and clinical target lesion revascularization (TLR) were the primary endpoints. Results The study population consisted of 204 patients in the ISR group and 494 patients in the de novo group. Baseline clinical and angiographic parameters were comparable between the two groups. The rate of diabetic was higher in the ISR group than that in the de novo group (36.6%to 27.1%, P < 0.05). The diameter of coronary artery was smaller in the ISR group than that in the de novo group (2.72±0.36 to 3.08±0.54, P<0.01). The rate of TLR in the ISR group was higher than that in the de novo group (10.7%to 17.2%, P<0.05;14.2%to 21.1%, P<0.05),contributing to higher MACE in ISR group. Conclusions DES implantation is safe and effective for treatment of ISR lesions, but the rate of TLR is higher compared to treatment of de novo lesions.