Objective　To study the role of hypertension-related gene (HRG-1) in cardiovascular disease. Methods　The expression of HRG-1 was analyzed with RT-PCR and Northern blotting. Vascular smooth muscle cell (VSMC) proliferation was measured with 3 H-TdR incorporation and was confirmed with histological analysis. Results　Northern blot analysis showed that HRG-1 mRNA was expressed not only in VSMC, but also in various rat tissues (heart, brain, lung, kidney, and liver). In addition, the expression of HRG-1 mRNA in heart, brain, kidney and liver of spontaneously hypertensive rat (SHR) was lower than that in the same tissues of Wistar-Kyotorat (WKY). Semi-quantitative RT-PCR and histological analysis showed that the expression of HRG-1 mRNA in ApoE-knockout mice and in animal models of restenosis was decreased and neointimal formation was observed in both models. ET, AII, and IL-1 stimulating VSMC proliferation reduced the expression of HRG-1 mRNA of VSMC. Atrial natriuretic factor (ANF), calcitonin gene-related peptide and adrenomedullin, inhibited VSMC proliferation and elevated the expression of HRG-1 mRNA. These effects could be blocked or attenuated by their corresponding antagonists or antibodies. Conclusion　HRG-1 is a gene related to VSMC proliferation. It may play an important role in several occlusive cardiovascular diseases including atherosclerosis, restenosis and hypertension.

OBJECTIVETo evaluate the therapeutic effect of clarithromycin combined with tanshinone in the treatment of rhinosinusal and laryngeal radiation injury induced by radiotherapy in patients with nasopharyngeal carcinoma (NPC).

METHODSA total of 255 NPC patients with rhinosinusal and laryngeal radiation injury following radiotherapy were randomized into 3 groups for treatment with clarithromycin (group A, n=69), tanshinone (group B, n=69), and clarithromycin + tanshinone (group C, n=69), and the clinical outcomes of the patients were evaluated.

RESULTSIn all the 3 groups the patients responded favorably to the treatments and showed obvious improvements (P<0.05). The therapeutic effects were similar between groups A and B (P>0.05), but the patients in group C showed the most obvious improvements (P<0.05).

CONCLUSIONSClarithromycin combined with tanshinone can be an effective regimen for treatment of rhinosinusal and laryngeal radiation injury induced by radiotherapy in NPC patients.

Adult ; Aged ; Carcinoma ; Clarithromycin ; therapeutic use ; Combined Modality Therapy ; Diterpenes, Abietane ; therapeutic use ; Female ; Humans ; Larynx ; pathology ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; radiotherapy ; Nose ; pathology ; Paranasal Sinuses ; pathology ; Pharynx ; pathology ; Radiation Injuries ; drug therapy ; Young Adult

Objectives To establish a new transgenic mouse model for determining the function and role of human scavenger receptor A (SR-A) in atherosclerosis in vivo. Methods Human scavenger receptor minigene-driven mouse tie-1 promoter was constructed and confirmed by endonuclease digestion and sequence analysis. Transgenic mice were generated via the microinjection method. PCR and Southern blot were used to screen the positive transgenic mice. RT-PCR and immunohistochemical analysis were used to detect the level and location of human SR-A Ⅰ expression in transgenic mice. The activity of human SR-A Ⅰ was determined by morphologic observation of aortic endothelial cells of transgenic mice under transmission electron microscopy. Results The electrophoresis assay showed the expected 4 fragments of 0.9 kb, 1.1 kb, 1.2 kb and 4.2 kb in the Sma Ⅰ digest and 2 fragments of 0.8 kb and 6.7 kb in Bgl Ⅱ digest of plasmids pTie-1/hSR-A. The fragment sequence of tie-1 promoter and human SR-A cDNA in plasmids pTie-1/hSR-A was correct and no ATG before the translation initiation sites of human SR-A was found by sequence analysis. 561 injected and surviving embryos with the purified human SR-A minigene were implanted into the oviducts of 19 ICR pseudopregnant mice. Among the 54 surviving pups from 13 foster mothers, 7 were identified by PCR and Southern blot analysis. The results of RT-PCR and imrnunohistochemical analysis showed human SR-A was specifically expressed on vascular endothelial cells of the aorta and renal artery, as well as hepatic sinusoidal endothelial cells in transgenic mice. Transmmion electron microscope (TEM) of aorta of transgenic mice showed that a large number of vesicles, multivesicle bodies and swollen mitochondria filled the plasma of endothelial cells. Conclusions A transgenic mouse model with overexpression of human SR-A in endothelial cells was successfully established. The transgene was integrated and transmitted into the chromosome of transgenic mice. Tie-1 promoter controlled the transgene to express in endothelial cells in mice. Pinocytic activity of aortic endothelial cells in transgenic mice was higher than that of C57BL/6J mice. Our studies will provide a new transcgenic model for investigation of atherosclerosis and functions of human SR-A.