AIM:To explore the effects of atorvastatin (Atorv) on atherosclerosis in streptozotocin (STZ)-in-duced diabetic apolipoprotein E knockout ( ApoE-/-) mice with fat-rich diet and the possible mechanism .METHODS:C57 mice served as control.ApoE-/-mice (n=34) fed with high-fat diet were randomly divided into ApoE-/-group, STZ-ApoE-/-group and STZ-ApoE-/-+Atorv group.Intraperitoneal injection of streptozotocin was performed to create di-abetic animal model .Blood glucose was determined by glucose oxidase method .Blood lipid levels were detected by enzymic method or selective homogeneous method .The plaque area in the thoracic aorta was measured by HE staining .The protein level of nicotinamide-adenine dinucleotide phosphate ( NADPH) oxidase subunit gp91phox in the thoracic aorta was deter-mined by Western blotting .The levels of reactive oxygen species ( ROS) in blood and thoracic aorta homogenates were de-tected by Fenton reaction and Griess reagent .Human umbilical vein endothelial cells ( HUVECs ) were isolated from healthy umbilical cords by collagenase I and cultured .ROS production was detected by flow cytometry .NADPH oxidase ac-tivity was measured using lucigenin assay .Effects of retinoid X receptor α( RXRα) on inhibition of oxidative stress by ator-vastatin were evaluated by RNA interference and plasmid transfection .RESULTS: (1) Compared with C57 group, the plaque areas of the thoracic aorta in ApoE-/-group were increased .No difference of the fasting glucose between the 2 groups was observed.The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), thoracic aorta gp91phox protein and ROS in blood and thoracic aorta homogenates were higher in ApoE-/-group than those in C57 group.(2) Compared with ApoE-/-group, the plaque areas of the thoracic aorta in STZ-ApoE-/-group were further enlarged [(314.13 ±35.72) μm2 vs (215.88 ±34.19) μm2, P<0.05].The levels of blood glucose, TG, TC and LDL-C, thoracic aorta gp91phox protein and ROS in blood and thoracic aorta homogenates were higher in STZ-ApoE-/-group than those in ApoE-/-group (P<0.05).(3) Compared with STZ-ApoE-/-group, the plaque areas of the thoracic aorta in STZ-ApoE-/-+Atorv group were reduced [(217.47 ±24.56) μm2 vs (314.13 ±35.72) μm2, P<0.05].The levels of blood glucose , LDL-C, TC, HDL-C and TG showed no significant difference between the 2 groups.Thoracic aorta gp91phox protein level and ROS production in blood and thoracic aorta homogenates were lower in STZ -ApoE-/-+Atorv group than those in STZ-ApoE-/-group (P<0.05).(4) High glucose-induced increases in NADPH oxidase activity and gp91phox expression were significantly inhibited by atorvastatin (10-6 mol/L) in HUVECs.The inhibitory effects of atorvasta-tin on high glucose-induced ROS production and NADPH oxidase activation were largely impaired when the cells were trans -fected with RXRαsiRNA.However , the effect of atorvastatin was significantly strengthened when RXRαwas over-expressed in the HUVECs transfected with RXRαplasmid.CONCLUSION: Atorvastatin inhibits atherogenesis by depressing high glucose-induced oxidative stress in diabetic ApoE-/-mice with fat-rich diet.The anti-oxidative stress effect of atorvastatin is mediated by RXRα.

Objective To explore the effect of retinoid X receptor (RXR) agonist bexarotene on atherosclerosis and the potential mechanism in streptozotocin (STZ) induced diabetic apolipoprotein E knockout (apoE-/-) mice.Methods Eight C57BL/6 mice served as control,46 apoE-/-mice were randomized into 4 groups:apoE-/-group (n =10),STZ + apoE-/-group (n =12),STZ + apoE-/-+ Bex 10 (10 mg · kg-1 · d-1)group (n=12),STZ+ apoE-/-+Bex 30 (30 mg · kg-1 · d-1)group (n=12).Diabetic apoE-/-animal model was established by intraperitoneal injection of STZ.Blood glucose was determined by glucose oxidase method.Patch area in thoracic aorta was measured by HE staining.Western blotting was used to determine the RXR and gp91 phox protein level in thoracic aorta.Reactive oxygen species (ROS) level in blood and thoracic aorta homogenates was detected by Fenton and Griess method.Results (1) Patch areas of thoracic aorta were larger in apoE-/-group than in C57BL/6 group[(38.40 ± 8.95) μm2 vs.(0.10 ±0.01) μm2,P ＜0.01],further increased in STZ + apoE-/-group [(94.06 ± 8.04) μm2,P ＜0.05 vs.apoE-/-group] and significantly reduced in STZ + apoE-/-+ Bex 10 group [(78.72 ± 4.62)μm2,P ＜0.05 vs.STZ + apoE-/-group] and further educed in STZ + apoE-/-+ Bex 30 group[(46.13 ±7.56) μm2,P ＜ 0.05 vs.STZ + apoE-/-+ Bex 10 group].(2) Blood glucose level,TG,TC,LDL-C,thoracic aorta gp91 phox protein level and ROS level in blood and thoracic aorta homogenates were significantly higher in STZ + apoE-/-group than in apoE-/-group (all P ＜ 0.05).Blood glucose level and TG,TC,LDL-C levels were similar between STZ + apoE-/-+ Bex10 and STZ + apoE-/-group.Thoracic aorta gp91 phox protein level and ROS level in blood and thoracic aorta homogenates were lower in STZ + apoE-/-+ Bex 10 group than in STZ + apoE-/-group (P ＜ 0.05).Blood glucose level,TG,TC,LDL-C levels,gp91 phox expression in thoracic aorta,ROS level in blood and thoracic in STZ + apoE-/-+ Bex 30 group were lower than in STZ + apoE-/-group (all P ＜ 0.05).Conclusion Bexarotene treatment could attenuate arteriosclerosis progression in STZ induced diabetic apoE-/-mice,the underlying mechanism might be related to suppressing oxidative stress and decreasing blood glucose level and improving lipids metabolism.

Objective:To investigate the high resolution CT (HRCT) features of lung adenocarcinoma for differentiating synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis.Methods:The clinical and imaging features of 131 lesions from 62 patients of synchronous multiple primary lung adenocarcinoma (primary group) and 67 lesions from 31 patients of lung adenocarcinoma with intrapulmonary metastases (metastasis group) were retrospectively analyzed. According to the types of lesion, including pure ground glass nodule (pGGN), mixed ground glass nodule (mGGN) and solid nodule (SN), the image feature matching types of patients were divided into 7 types. The differences of image feature matching types between the primary group and the metastasis group were compared. Multiple lesions in the lung of patients were classified into the main lesion and the concomitant lesions according to their size. The differences including the size of the main lesion and the concomitant lesion (long diameter of nodule, long diameter of solid component in nodule), whether it contains ground glass components in nodule, shape, lobulation, margin, spiculation, bubble-like lucency, pleural retraction and pleural attachment were recorded and analyzed. The differences of image features of main lesion and the concomitant lesion in the primary group and the metastasis group were compared.Results:The image feature matching types of pGGN + mGGN and mGGN + mGGN were more common in the primary group, and the ground glass component contained pGGN or mGGN was accounted for 62.9%(39/62). At least one lesion containing the ground glass component was accounted for 96.8% (60/62). There were two types in metastatic groups, mGGN+ SN and SN+ SN accounting for 6.5% (2/31) and 93.5% (29/31), respectively. There were significant differences in image feature matching types between the primary group and metastatic group ( P<0.01). Univariate analysis of the main lesions between the two groups showed that the gender, smoking history, long diameter of the main lesion, long diameter of the solid component, the ground glass component and pleural attachment were statistically different ( P<0.05). Further analysis by multivariate logistic regression showed that the male ( OR=5.742, P=0.010), SN ( OR=41.291, P<0.01) and pleural attachment ( OR=9.288, P=0.001) were the three significant risk factors associated with the main lesions in metastasis group.The most common concomitant lesions in primary group were pGGN, containing the ground glass component. However, all of the concomitant lesions in the metastatic group were SN ( P<0.01), showing round lesions with well-defined margin, attaching the pleura ( P<0.05). Conclusions:The HRCT features of lung adenocarcinoma can differentiate synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis. At least one lesion contains ground glass components (pGGN or mGGN) in synchronous multiple primary lung adenocarcinoma, while SN is more common in lung adenocarcinoma with lung metastasis. Lung cancer with intrapulmonary metastasis can be considered when the main lesion is SN with pleural attachment and the intrapulmonary accompanying lesion is also solid nodules without lobular, speculation and bubble-like lucency.

Objective:To investigate the high resolution CT (HRCT) features of lung adenocarcinoma for differentiating synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis.Methods:The clinical and imaging features of 131 lesions from 62 patients of synchronous multiple primary lung adenocarcinoma (primary group) and 67 lesions from 31 patients of lung adenocarcinoma with intrapulmonary metastases (metastasis group) were retrospectively analyzed. According to the types of lesion, including pure ground glass nodule (pGGN), mixed ground glass nodule (mGGN) and solid nodule (SN), the image feature matching types of patients were divided into 7 types. The differences of image feature matching types between the primary group and the metastasis group were compared. Multiple lesions in the lung of patients were classified into the main lesion and the concomitant lesions according to their size. The differences including the size of the main lesion and the concomitant lesion (long diameter of nodule, long diameter of solid component in nodule), whether it contains ground glass components in nodule, shape, lobulation, margin, spiculation, bubble-like lucency, pleural retraction and pleural attachment were recorded and analyzed. The differences of image features of main lesion and the concomitant lesion in the primary group and the metastasis group were compared.Results:The image feature matching types of pGGN + mGGN and mGGN + mGGN were more common in the primary group, and the ground glass component contained pGGN or mGGN was accounted for 62.9%(39/62). At least one lesion containing the ground glass component was accounted for 96.8% (60/62). There were two types in metastatic groups, mGGN+ SN and SN+ SN accounting for 6.5% (2/31) and 93.5% (29/31), respectively. There were significant differences in image feature matching types between the primary group and metastatic group ( P<0.01). Univariate analysis of the main lesions between the two groups showed that the gender, smoking history, long diameter of the main lesion, long diameter of the solid component, the ground glass component and pleural attachment were statistically different ( P<0.05). Further analysis by multivariate logistic regression showed that the male ( OR=5.742, P=0.010), SN ( OR=41.291, P<0.01) and pleural attachment ( OR=9.288, P=0.001) were the three significant risk factors associated with the main lesions in metastasis group.The most common concomitant lesions in primary group were pGGN, containing the ground glass component. However, all of the concomitant lesions in the metastatic group were SN ( P<0.01), showing round lesions with well-defined margin, attaching the pleura ( P<0.05). Conclusions:The HRCT features of lung adenocarcinoma can differentiate synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis. At least one lesion contains ground glass components (pGGN or mGGN) in synchronous multiple primary lung adenocarcinoma, while SN is more common in lung adenocarcinoma with lung metastasis. Lung cancer with intrapulmonary metastasis can be considered when the main lesion is SN with pleural attachment and the intrapulmonary accompanying lesion is also solid nodules without lobular, speculation and bubble-like lucency.

The unique advantages of traditional Chinese medicine (TCM) in treating late onset hypogonadism in male have gradually emerged with the continuous deepening of the understanding and research on late onset hypogonadism in male. Time sequence is a general summary of the natural growth and operational laws. Tian gui and testosterone have their normal time sequences, and they may be associated with each other. A man′s tian gui follows the regular time sequence from " inception" to " exhaustion" throughout " eight" under normal physiological conditions. " Tian gui out of time sequence" includes the loss of tian gui exuberance (dysfunction of viscera dominated by the liver) and exhaustion in the time sequence (pathological deficiency of viscera dominated by the kidney), resulting in " tian gui exhaustion" in advance of " eight eight". Tian gui and testosterone are key concepts in Chinese and Western medicine for understanding late onset hypogonadism in male. The theory of " tian gui out of time sequence" may be closely related to the core pathogenesis of this condition, particularly in cases of liver depression and kidney deficiency. This study suggests that restoring the normal time sequence of tian gui while treating the liver and kidney simultaneously through time-sharing treatment should be effective. The use of Xiongcan Yishen Formula has shown promising therapeutic result, offering new insights and references for treating late onset hypogonadism in male using TCM.