Dyslipidemia is one of the major risk factors for cardiovascular disease in elderly,but clinical practices in the management of elderly dyslipidemia are still not satisfactory.The cornerstone of treatment for elderly dyslipidemia consists of therapeutic lifestyle change and statins.Recent guidelines emphasize aggressive low density lipoprotein-cholesterol control with statins.However,intensive statin therapy may increase the risk of myopathy and diabetes.Therefore,it is important to consider risk benefit ratio in individual patients.The additional benefit of statins in combination with other hypolipidemic drugs on cardiovascular risk still needs verifying by further investigation.

Dyslipidemia is one of the major risk factors for cardiovascular disease in diabetes mellitus,but clinical practices in the management of diabetic dyslipidemia are still not satisfactory in China.The cornerstone of treatment for diabetic dyslipidemia consists of therapeutic lifestyle change and statins.Recent guidelines emphasize aggressive low density lipoprotein-cholesterol control with statins.However,intensive statin therapy may increase the risk of myopathy and diabetes.Therefore,it is important to consider its risk benefit ratio in individual patients.The additional benefit of statins in combination with other hypolipidemic drugs on cardiovascular risk needs verifying by further investigation.

Cytokines play an important role in the genesis and development of tumor.Antitumor mechanisms of some cytokines are clearly testified.Currently,the main cytokines used in tumor clinical treatments are interferons,interleukins and tumor necrosis factors.For the lack of specificity,there are too many side effects for some patients to continue.So the application range of cytokines in tumor clinical treatment is limited.The most important measures to develop cytokines therapy are improving the stability of curative effect and reducing side effects.

Objective To determine the involvement of DNA demethylation in tumor necrosis factor-α(TNF-α)-induced matrix metalloproteinase 9 ( MMP9) expression in human epidermal keratinocytes. Methods Real-time RT-PCR, Western blot, and enzyme-linked immuno sorbent assay (ELISA) were performed to determine the mRNA and protein levels of MMP9 after human keratinocyte cell line (HaCaT) cells were treated with 10 ng/ ml TNF-α or 2. 5 μmol/ L DAC/ 300 nmol/ L TSA. Bisulfite sequencing PCR ( BSP) and Methylation-sensitive high-resolution melt analysis ( Ms-HRM) were used to detect significantly differentially demethylated CpG sites in the human MMP9 promoter region in cells exposed to TNF-α. Different sites methylation constructs of promoter-luciferase reporter gene were made to detect the influences of site-specific DNA demethylation on transcription activity of MMP9 promoter. Results Compared with PBS-treated control, TNF-α significantly increased the expression of MMP9 in HaCaT cells for indicated culture duration ( P < 0. 05 ). Real time PCR, Western blot, and ELISA analysis demonstrated that the mRNA and protein levels of MMP9 were increased initially, followed by a decline with prolonged incubation time. After TNF-α treatment, varied degrees of DNA demethylation occurred at 10 CpG sites in the promoter of MMP9, and the changes at the -36 bp site were statistically significant (P<0. 05). The demethylation at the -36 bp site greatly increased the transcription activity of MMP9. Conclusion TNF-α promotes MMP9 expression in HaCaT cells through inducing -36 bp site DNA demethylation on the promoter of MMP9.

Objective To study the effects of high matrix metalloproteinase 9 (MMP 9 ) on the biological behaviors of fibroblasts,in order to clarify the possible mechanisms in the wound healing of diabetic foot.Methods Establish the cell model of skin fibroblast with high expression of MMP 9 by high glucose (22.0 mmol/L) and high homocysteine (100 μmol/L) co-culture.Control group was incubated with normal glucose (5.5 mmol/L).Realtime PCR,ELISA and gelatin zymography were used to detect the MMP 9 mRNA,protein expression and activity of MMP 9.Flow cytometry,CCK-8,ELISA assay,scratch test and transwell were used to detect cell proliferation,viability,collagen (hydroxyproline) secretion,horizontal migration and vertical migration of cells.Results Data were expressed as (x- ± s).Differences were considered significant if their P value was ＜ 0.05.Results The expression of MMP 9 mRNA,protein levels and the activity of MMP 9 in high MMP 9 group were 6.05 folds,4.12 folds and 1.58 folds higher than those in control group (P ＜ 0.01,respectively).The proportion of S phase cells,proliferation index,cell viability,collagen (hydroxyproline) secretion,6 h horizontal migration rate and the number of vertical migration cells in high MMP9 group decreased by 29.8 ％,18.1％,23.3 ％,68.7 ％,45.0 ％ and 21.4 ％ than those in control group (P ＜ 0.01,respectively ). Conclusions Fibroblast with high expression of MMP 9 have decreased proliferation,activity,collagen secretion and reduced migration,which suggests that MMP 9 may inhibit the biological behaviors of fibroblasts.

Objective To investigate relationship between adiponectin and cardiac damage induced by aldosterone in SD rats. Methods Male SD rats were treated with aldosterone infusion for 4 weeks, systolic blood pressure (SBP) was measured every week. At the end of experiment, the myocardial structure was observed, the levels of adiponectin in plasma and adiponectin mRNA expression of adipose tissue in epididymal fat pad were measured. 3T3-L1 adipocytes treated with 10-8 and 10-6 moL/L aldosterone for 24 and 48 h, adiponectin mRNA expressions and adiponectin concentrations in culture medium were measured. Results Aldosterone induced only a slight increase in the SBP of SD rats[(123±7)mm Hg, P<0.05]. However, aldosterone significantly induced cardiac ultrastructure changes, such as mitochondrial swelling and disordered internal structures. Furthermore, the level of plasma adiponectin decreased 22.8% after aldosterone treatment for 4 weeks ( P<0. 05 ). When 3T3-L1 adipocytes were treated with 10-8 and 10-6 mol/L aldosterone for 24 h, adiponectin concentrations in culture medium decreased 21.8% and 27. 2%, respectively (P < 0. 05); for 48 h, adiponctin mRNA expressions decreased 22.1% and 37.4%, respectively ( P<0. 05 ). The effect of aldosterone was reversed by spironolactone,which was partly independent of SBP. Conclusions Low level of adiponectin may be involved in cardiac damage induced by aldosterone in SD rats.

AIM:To explore the effect of aldosterone on visfatin gene expression and secretion in 3T3-L1 preadipocytes or adipocytes.METHODS:Aldosterone at concentration of 10-8 or 10-6 mol/L with or without 10-6 mol/L spironolactone was added to cultured 3T3-L1 preadipocytes or adipocytes for 24 h or 48 h.The mRNA levels of visfatin and mineralocorticoid receptor were measured using real time PCR.The concentration of visfatin in the culture medium was determined by ELISA.RESULTS:In 3T3-L1 preadipocytes treated with aldosterone,the mRNA expression of visfatin reduced and the mRNA expression of mineralocorticoid receptor(MR) increased,but the concentration of visfatin in culture medium was not regulated significantly by aldosterone.In adipocytes with aldosterone treatment,the mRNA expression of visfatin and visfatin concentration in culture medium reduced,and mRNA expression of MR increased.The effect of aldosterone was blocked by spironolactone to some extent.CONCLUSION:Aldosterone inhibits the gene expression and protein secretion of visfatin in 3T3-L1 adipocytes.

Objective To explore the clinical characteristics of Gitelman syndrome in children and the difference between Gitelman syndrome and Bartter syndrome.Methods Clinical date,biochemical tests and therapy of 6 patients diagnosed as Gitelman syndrome in Beijing children′s hospital from Mar.to Dec.2006 were retrospectively analyzed.At the same time,the relative articies of Gitelman syndrome and Bartter syndrome were reviewed.Results The symptoms of 6 patients appeared early.The age of onset of Gitelman syndrome at infancy stage,the main complains were growth delay,weakness,tetany.All patients had normal blood pressure.The biochemical tests showed hypocalemic,hypomagnesium,alkalosis and hyperreninemia.But the concentration of aldosterone was normal or little higher.The manifestations of all patients were relieved after taking both potassium and magnesium.Conclusion Gitelman syndrom and Bartter syndrome have differences at clinical syndrome and machanism of onset.

The effect of globular adiponectiin (gAd)on the function of NIT-1 cells under high glucose medium was investigated. The results showed that gad could completely block the increase of NADPH oxidase components p47phox expression and recover mRNA expression of pancreatic duodenal homeobox-I ,paired box gene 6,glucose transpoter 2,and glucokinase except neurogenic differentiation factor 1 (P<0.05 or P<0.01). Whereas,impaired insulin secretion and mRNA expression at high glucose concentration were not significantly improved by gAd.

[Objective]To explore the relationship between peripheral arterial disease(PAD)and diabetic retinopathy(DR)in type 2 diabetes patients.[Methods]A total of 99 patients diagnosed with PAD were classified into grade 1-3 by their total scores of peripheral arterial stenosis assessed by color doppler ultrasound examinations,where the degree of stenosis 30% ~ 49% scored 0, 50%~99%scored 1,lumen occlusion(i.e. degree of stenosis 100%)scored 2,and therefore the total score 0-2 was categorized into Grade 1 ,3~4 into Grade 2 ,5~12 into Grade 3. The bilateral anterior tibial artery ,posterior tibial artery and dorsalis pedis artery of these patients were analyzed. The presence of diabetic retinopathy(DR)was graded from retinal photographs using a standard protocol.[Results]Among 99 cases of type 2 diabetic patients with peripheral arterial disease ,58.6%of them were male with average age of 67.3 ± 7.9 years old. Patients of Grade 1,Grade2,Grade 3 lesion accounted for 45.4%,30.3%,24.2%,respectively. Age, gender,smoking history,SBP,DBP,BMI,FBG,TC,TG,LDL-C,HDL-C,HbA1C among 3 groups were not statistically signifi-cant. The associations of DM duration and HbA1C value were significantly larger in DR than in PAD. The proportion of DR patients increased with the severity degree of PAD(p for trend=0.004). Degree of stenosis Grade 2 and Grade 3 could be predictive for DR.[Conclusions]DR is associated with the severity degree of PAD in type 2 diabetes patients as evaluated by duplex ultrasonography.Degree of stenosis Grade 2 and 3 could be used for screening or finding DR. Strategies for optimum treatment and early prevention are needed.