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Abstract:The elderly are more likely to develop diabetes mellitus. More than half of the diabetic patients are elderly individuals. The outcome of these patients differs greatly due to the complex of the condition, the variety of complicated diseases, and multiplicity of the influencing factors. So, it is very important to evaluate their accommodation ability, the function of the major organs, and the level of self-management to establish the individualized treatment strategy and blood glucose control target for different patients. The modification of life style is the basic treatment option for metabolic disorder. Early diagnosis and treatment are decisive to the patients? prognosis. Metformin, glycosidase inhibitors and dipeptidyl aminopeptidase inhibitors are the first-line oral antidiabetic drugs. The timely use of insulin is beneficial for the control of blood glucose. The comprehensive control of multiple cardio-vascular risk factors, especially the blood pressure and body weight control, should be emphasized.

Abstract:Stress hyperglycemia is very common among critically ill patients, and seriously affects its prognosis. Currently, it attracts increasing attention. Its mechanism has been elucidated. The treatment of stress hyperglycemia mainly depends on insulin therapy. It is reported that insulin therapy can reduce the mortality of critically ill patients and improve their prognosis. However, because insulin therapy has been applied for a relatively short duration in critically ill patients, the target glycemic control level is still controversial. At present, there is no unified standard yet for glycemic control level in the clinical practice. In this paper, we introduced briefly the epidemiological characteristics of stress hyperglycemia. Additionally, we also discussed its mechanism and clinical significance. We reviewed the progress of research on insulin therapy and analyzed the good and bad points of intensive insulin therapy. We also proposed the principles of insulin therapy and target level of glycemic control for different patients.

Abstract:Objective To analyze the function of islet β cells in population who had normal glucose tolerance (NGT) or impaired glucose regulation (IGR) with hyperinsulinemia(HINS). Methods A total of 634 adults diagnosed as NGT or IGR with HINS by 75g oral glucose tolerance test(OGTT) were included for the analysis of the islet β cells function. Results In HINS group, homeostasis model insulin resistance index(HOMA-IR), ?I120/?G120, the first and second phase insulin secretion index were significantly higher than those in non-HINS group of non-diabetic population(P＜0.05), but insulin sensitive index(ISI)-Stumvoll and HOMA beta cells function index/insulin resistance(HBCI/IR) were significantly lower(P＜0.05). There was no significant difference in ?I120/?G120/IR between the two groups(P＞0.05). In IGR with HINS group, HBCI, HBCI/IR, and the first and second phase insulin secretion index were significantly lower than those in NGT with HINS group(P＜0.05). There was no significant difference in HOMA-IR and ISI-Stumvoll between the two groups(P＞0.05). Conclusions Although the absolute insulin secretion is increasing in the NGT or IGR population with HINS, the islet ? cells function decreases gradually. NGT or IGR with HINS are the transition state in the progress of diabetes mellitus, and the early detection and interference are strongly recommended.

Abstract:Objective To investigate the relationship between the prolonged QTc interval and the multi-cardiovascular risk factors in patients with type 2 diabetes mellitus(T2DM). Methods Medical data of 3940 T2DM patients were analyzed. After patients who had coronary heart diseases, arrhythmia, myocardial infarction, which may cause abnormal QTc, were excluded, a total of 3426 T2DM patients who had underwent diabetic complication assessment and 12 standard electrocardiogram(ECG) recording were enrolled. They were divided into normal QTc interval group(QTc＜0.44 s, n = 2157) and prolonged QTc interval group(QTc≥0.44s, n = 1269). The multi-cardiovascular risk factors were compared between the two groups and further analyzed. Results Compared with normal QTc interval group, the patients in prolonged QTc interval group were older[(55.6±11.0) vs (54.6±10.9) years], had longer diabetes duration[36(12, 96) vs 36(6, 84)months, median(P25, P75)], more females (51.5% vs 41.5%), shorter body height[ (1.64±0.08) vs (1.65±0.08) m], bigger body mass index(BMI)[(26.2±3.6) vs (25.8±3.2) kg/m2], bigger waist circumference[(89.7±9.6) vs (88.2±9.5) cm], bigger hip circumference[(95.4±7.3) vs (94.4±6.6)cm], higher waist hip ratio(WHR)[(0.94±0.07) vs (0.93±0.08)], higher blood pressure [(134.8±20.3) /(76.9±10.2) vs (130.1±19.1) /(74.5±9.6) mmHg], increased heart rate [(82.9±10.2) vs (70.7±10.1)beats/min], higher HbA1c [(8.0±2.0)% vs (7.7±1.9)%], higher post-meal glucose[(13.7±5.1) vs (12.8±4.8) mmol/L], higher fasting insulin[(9.4±8.6) vs (8.2±7.5)IU/ml], increased total cholesterol[(5.1±1.1) vs (5.0±1.1) mmol/L], higher triglyceride [(2.4±2.6) vs (2.2±2.5) mmol/L], and higher urine albumin/creatinine(Alb/Cr)[15(8, 36) vs 12 (7, 27) mg/g, median(P25, P75)]. All these indices were significantly different between the two groups(P＜0.05). Logistic regression analysis showed that factors including age, sex, BMI, waist circumference, WHR, heart rate and Cr, were significantly associated with prolonged QTc interval. Conclusions More than one third of T2DM patients present with prolonged QTc interval and more severe multi-cardiovascular risk factors.

Abstract:Objective To examine the prevalence of normal, low and high ankle-brachial index(ABI) in patients with type 2 diabetes and the relative risk factors. Methods A total of 3924 patients, who underwent ABI examination in our center between September 2003 and June 2010 , were enrolled. Their medical profiles and laboratory data were analyzed retrospectively. The risk factors for abnormal ABI were determined using univariate and stepwise Logistic regression analysis. Results ABI was normal in 3653 patients(93.1%), ＜0.9 in 206 patients(5.2%), and ≥ 1.3 in 65 patients(1.7%). Elderly patients (≥65 years) had a higher prevalence of low ABI than non-elderly patients(＜65years)( (12.2% vs 3.6%). Using normal ABI as referent, low ABI in non-elderly patients was independently associated with HbA1c, urine albumin to creatinine ratio, diabetic peripheral neuropathy, diabetic retinopathy and cerebral vascular disease. Low ABI in elderly patients was independently associated with age, smoking, HbA1c, uric acid, total cholesterol, diabetic peripheral neuropathy, diabetic retinopathy, diabetic nephropathy and cerebral vascular disease. High ABI in non-elderly patients was associated with male gender. Conclusions The prevalence of abnormal ABI is high in patients with type 2 diabetes, especially in elderly patients. Early identification and intensive treatment are strongly recommended to improve the patients? life quality and overall prognosis.

Abstract:Objective To evaluate the effect of aging on the insulin receptor in islet beta-cells of Wistar rats, so as to investigate the mechanism of impaired glucose tolerance in elderly population. Methods Thirty healthy male Wistar rats were divided into young group(4-month old, n = 15) and elderly group(24-month old, n = 15). The fasting blood glucose, blood insulin, free fatty acid, and blood lipid were observed. Insulin sensitivity and the function of islet cells were assessed by the euglycaemic-hyperinsulinaemic clamp technique. The insulin receptor in islet beta-cells was observed using immunofluorescence staining, and the fluorescence intensity was analyzed using software. Results The body mass of rats in young group and elderly group was (490.60±7.72)g and (728.90±7.57) g respectively(P＜0.01). There was no significant difference in fasting blood glucose between the two groups(P>0.05). The fasting blood insulin was (0.59±0.14)ng/ml and (2.37±0.04)ng/ml in young group and elderly group respectively (P＜0.01). The blood free fatty acid was significantly lower in young group than in elderly group[(0.76±0.14) vs (1.51±0.04) mmol/L,P＜0.01]. The euglycaemic-hyperinsulinaemic clamp test displayed that the glucose infusion rate was significantly higher in young group than in elderly group[( 26.02±2.83) vs (10.73±0.72)mg/(kg?min),P＜0.01]. Homeostasis model insulin resistance index(HOMA-IR) was (3.09±0.80) and (13.14±l.59) in young group and elderly group(P＜0.01). The fluorescence intensity was (63.55±5.20) and (23.26±2.50) respectively in young group and elderly group respectively(P＜0.01). Conclusion The elderly rats present with insulin resistance and compensatory high level insulin secretion. Meanwhile, insulin receptor in islet beta-cells is decreased. It is possible that the peripheral insulin resistance and the insulin resistance in islet beta-cells itself coexist in elderly rats.

Abstract:Objective To investigate age-related changes in the expression of human leukocyte antigen-DR (HLA-DR) in peripheral blood mononuclear cells (PBMCs) and levels of cytokines secreted by PBMCs. Methods A total of 352 individuals who underwent physical examinations in our hospital were stratified into four groups based on age: group A, n = 120, age 20-69 years; group B, n = 85, age 70-79 years; group C, n = 98, age 80-89 years; group D, n = 49, age 90-102 years. Expression of HLA-DR in PBMCs was detected with flow cytometry. In addition, 10 individuals from each group were randomly selected, and their PBMCs were isolated and subsequently used for determining the levels of TNF-α, IL-6 and IL-10 by ELISA before and after LPS stimulation. HLA-DR expression and cytokine levels were compared between the different age groups. Results HLA-DR expression was significantly different between A, B, C, and D groups (F = 159.712, P = 0.000), and it increased in an age dependent manner (r = 0.744, P = 0.000). No significant difference was found in TNF-α, IL-6 and IL-10 levels in PBMCs before LPS stimulation between group A, B, C and D (P＞0.05), while, their levels increased significantly after LPS stimulation (P＜0.05). Compared with group A, TNF-α and IL-6 levels decreased, and the IL-10 level increased significantly(P ＜0.05) in group B, C and D after LPS stimulation. Conclusion Expression of HLA-DR increases in an age-dependent manner in human PBMCs, indicating an age-related change of immunological function. There is no significant difference in the levels of TNF-α, IL-6 and IL-10 secreted by PBMCs before LPS stimulation, while after LPS stimulation, the TNF-α and IL-6 levels decrease and IL-10 level increases significantly in individuals more than 70 years old.

Abstract:Objective To determine the roles of heart rate variability(HRV) in evaluating cardiac autonomic nerve function of patients with vascular dementia. Methods Totally 124 patients with vascular dementia and 102 control subjects received 24h dynamic Holter monitoring to perform frequency domain measures, time domain measures and non-linear analysis of HRV. The following HRV spectral parameters were considered: total frequency power(TF), low frequency power(LF), high frequency power(HF), standard diviation of normal-to-normal intervals(SDNN), square-root of mean squared differences of successive NN intervals(RMSS), and standard deviation of SDNN(SDSD). Poincare plot descriptors included vector angle index(VAI) and vector length index(VLI). Results The time domain measures (SDNN,RMSS,SDSD), frequency domain measures(TF,LF,HF), VAI and VLI were significantly lower in patients with vascular dementia than in control subjects[SDNN:(78±28) vs (129±30) ms, RMSS: (20±8) vs (24±8) ms, SDSD:(17±7) vs (22±8) ms, P＜0.01; TF:(1432±621) vs (1962±583) ms2/Hz, LF:(934±347) vs(1309±371) ms2/Hz, HF:(473±174) vs (601±247) ms2/Hz, P＜0.01; VAI:(0.54±0.14) vs (0.67±0.13) ms, VLI:(154±19) vs (194±25) ms, P＜0.01]. There were less patients who had Poincare scatter grams in shape of comet in patients with vascular dementia than in control subjects. Conclusion We recommend to perform HRV analysis, a noninvasive mehtod, for patients with vascular dementia to evaluate the cardiac autonomic nerve function.

Abstract:Objective To assess the efficacy and safety of memantine for domestic patients with Alzheimer?s disease (AD). Methods Randomized controlled trials carried in China, which compared memantine with placebo or other medicines in patients with AD, were searched from the electronic bibliographic databases, references listed in articles and journals. A systematic review was conducted based on the methods recommended by the Cochrane Collaboration. Results Nine trials involving 1273 patients were included, of which two were placebo-controlled trials and seven non-placebo-controlled trials (piacetam and donepezil). Two placebo-controlled trials, in which neurological changes were assessed by some neuropsychometric questionnaires, showed that there were significant differences in mini-mental state examination(MMSE), Severe Impairment Battery(SIB), Alzheimer?s Disease Cooperative Study-Activities of Daily Living Inventory(ADCS-ADL19) and Alzheimer?s Disease Assessment Scale-Cognitive Subscale(ADAS-Cog) scores between two groups (P＜0.05), and there was no significant difference in Neuropsychiatric Inventory(NPI) score (P＞0.05) although memantine group had better score than placebo group. Six donepezil-controlled trials showed that there was no significant difference in MMSE, ADAS-Cog, Activities of Daily Living Scale(ADL), Blessed-Roth, NPI and Clinician?s Interview Based Impression of Change-Plus Caregiver Input(CIBIC-Plus) scores between two groups (P＞0.05). One piacetam-controlled trial showed that there were significant differences in MMSE and Barthel Index(BI) scores between two groups (P＜0.05). One blank-controlled trial showed that there were significant differences in MMSE and ADL scores between the two groups (P＜0.05). Adverse reactions associated with medicines were reported in seven trials, including doze, fatigue, dizziness, confusion, deliria, agitation, anorexia, nausea, etc. However, no severe adverse reaction was reported. Conclusions Memantine can improve the general condition of patients with AD, including the cognitive function, daily life ability, mental behavior and global function. It has better therapeutic effects than piacetam, and at least equal tharapeutic effects to donepezil. It is safe for patients with AD.

Abstract:Objective To evaluate the effects of interventional therapy for 1eft iliac vein compressed syndrome in elderly patients. Methods Fifty cases of 1eft iliac vein compressed syndrome underwent stent placement and balloon angioplasty through the femoral vein. For patients who had thrombosis, an inferior vena cava (IVC) filter device was placed firstly and transcatheter thrombolysis via the popliteal vein was performed, then 1eft iliac vein compressed syndrome was treated sequentially. For patients with varices, staged saphenous vein high ligation and stripping was carried out. Results The stenosis or occlusive segments of left iliac vein were suc-cessfully dilated in 39 cases, of which 30 cases received stent implantation, and no in-hospital death or pulmonary embolism was reported. The leg swelling was greatly relieved at discharge. Thrombus disappeared completely in 15 cases and partly in 2 cases. Post-thrombosis syndrome was reported in 4 cases. The symptoms of varicose vein were dramatically lessened. Leg ulcers healed completely in 7 cases. Among 41 cases who had follow-up results, in-stent thrombus formation was observed in 2 case, and in-stent restenosis and stent displacement in 1 case. Conclusion Interventional therapy for 1eft iliac vein compressed syndrome in elderly patients has the advantages of less trauma, quick recovery, and less complications. The short-term efficacy is satisfactory, and long-term efficacy still needs further study.

Abstract:Objective To evaluate the effect of tirofiban on short-term prognosis of elderly patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention(PCI). Methods Totally 325 ACS patients were divided into two groups: Tirofiban group (n = 210) and control group (n = 115). All subjects underwent PCI with drug-eluting stents. Patients in tirofiban group received tirofiban, in addition to aspirin and clopidogrel. Patients in control group received oral administration of aspirin and clopidogrel only. The general data, the rate of thrombolysis in myocardial infarction (TIMI) grade 3 flow immediately after PCI, the in-stent thrombosis incidence, mild and severe bleeding rate, platelet decrease rate, mortality, and incidences of myocardial infarction (MI) and target vessel revascularization(TVR) at 30 days after PCI were compared between the two groups. Results The rate of TIMI grade 3 flow immediately after PCI was significantly higher in Tirofiban group than in control group (99.05% vs 94.78%, P＜0.05). The in-stent thrombosis incidence was lower in Tirofiban group than in control group(0.47% vs 3.47%, P＜0.01). The mortality and incidences of MI and TVR at 30 days after PCI were lower in Tirofiban group than in control group(0.00% vs 2.61%, 0.47% vs 3.47%, and 0.47% vs 1.73%, P＜0.01). The mild bleeding rate was higher in Tirofiban group than in control group, with no significant difference (7.14% vs 4.35%, P＞0.05).The rates of severe bleeding and platelets decrease were not significantly different between the two groups (0.00% vs 0.00%, and 0.95% vs 0.87%, P＞0.05). Conclusion Tirofiban can improve the TIMI grade flow in elderly patients with ACS after PCI. It can also decrease the in-stent thrombosis incidence, mortality, and incidences of MI and TVR at 30 days after PCI, but do not increase the rates of severe bleeding and platelets decrease in these patients. So it can improve the short-term prognosis in elderly patients with ACS undergoing PCI.

Abstract:Objective To investigate the association of oral chlorhexidine rinse with incidence of ventilator-associated pneumonia (VAP). Methods We searched PubMed as well as references lists from publications to collect randomized controlled trials comparing oral chlorhexidine with placebo in their effects on incidence of VAP. Meta analysis was performed using software Review Manager 5.0. Results Nine randomized controlled trials were included. Oral chlorhexidine rinse resulted in a reduced incidence of VAP (OR=0.44, 95%CI 0.32－0.62). There was no difference in mortality rate between patients receiving oral chlorhexidine rinse and placebo (OR=1.04, 95%CI 0.79-1.83). Conclusion The available evidence indicates that oral chlorhexidine rinse can reduce incidence of VAP.

Abstract:Objective To assess the safety of esophageal and gastric endoscopy for elderly patients with coronary heart disease(CHD) by monitoring the changes of their vital signs during operation process. Methods A total of 60 patients over 60 years old accepting esophageal and gastric endoscopy were divided into CHD group(with mild ST-T change or history of angina or old myocardial infarction but without respiratory diseases) and control group(without heart diseases), with 30 in each group. The heart rate, blood pressure, oxygen saturation(SpO2) and electrocardiogram during performance of esophageal and gastric endoscopy were compared between the two groups. Results Heart rate was significantly increased during operation in both groups(P＜0.05), and the variation in CHD group was greater than that in control group(P＜0.05). Blood pressure was also increased in both groups(P＜0.05) and there was no significant difference between two groups(P＞0.05). SpO2 was significantly decreased in CHD group(P＜0.05) during operation but with no significant difference compared with control group(P＞0.05). Arrhythmia, but no dangerous arrhythmia, oc-curred in both groups during operation. In addition, there were 6 cases with ST-T changes in CHD group and all cases recovered to normal after operation. Conclusion With full preparation before operation and electrocardiographic monitoring if necessary during operation, esophageal and gastric endoscopy is safe for elderly patients with CHD.

Abstract:Objective To construct the Saccharomyces cerevisiae cell strains expressing aldose reductase(AR) and AR-green fluorescent protein(AR-GFP) fusion protein, and to detect the target gene expression and the AR enzyme activity. Methods The yeast expression plasmids pYEX-BX inserted with AR and AR::GFP fusion gene were transformed into the yeast strain INVSc1, which were named as XAR and XAG strains respectively. The blank pYEX-BX strain was used as the normal control. The growth curves and the fluorescence were determined in all strains. Northern blot, Western blot and the fluorescent method were used to detect the AR mRNA transcription, AR protein expression, and the AR activity respectively. Results There was no significant difference in the growth rates among three strains. There was a linear relationship between relative fluorescence of the XAG and the growth time. The mRNA transcription and protein expression of AR and AR::GFP were sustainable and stable in XAR and XAG strains. The AR activities in the two strains were both proved by the fluorescent method. Conclusion The yeast expression strain of AR was constructed successfully, which lays basis for its application in the researches on pathogenic mechanism of AR and preliminary screening of new AR inhibitors.

Abstract:Objective To investigate the protective efficacy of anisodamine against lung edema after ischemia-reperfusion in rabbits, and to explore the possible mechanism. Methods In vivo lung ischemia-reperfusion model of rabbit was developed. Twenty-four Chinese rabbits of either gender, aged 10-12 weeks, weighing 2200?2600 g, were divided into 3 groups randomly: anisodamine group, control group and sham group, with 8 rabbits in each group. In anisodamine group, the left pulmonary hilum was occluded for 1 hour and then released for 3 hours, and anisodamine (3 mg/kg) was given by intravenously injection before occlusion. In control group, only ischemia-reperfusion was performed. In sham group, left lung received no ischemia-reperfusion. Left lung tissue in each group was harvested for histopathological analysis, lung water content determination and myeloperoxidase (MPO) level detection. Also, 2% Evens blue (1.5 ml/kg) was injected into femoral venous to measure lung vascular permeability. Results After ischemia-reperfusion, the lung tissue water content, MPO level and Evens blue level in control group were (6.6±0.5) g/g dry tissue, (1.16±0.14) U/g protein and (173±16) μg/g wet tissue respectively, significantly higher than those in sham group [(4.3±0.4) g/g dry tissue, (0.53±0.09) U/g protein and (103±11) μg/g wet tissue, P＜0.05]. These indices in anisodamine group were (5.6±0.4) g/g dry tissue, (0.82±0.11) U/g protein and (124±18) μg/g wet tissue, obviously lower than those in control group (P＜0.05). Left lung displayed prominent edema, septal swelling, hemorrhage and neutrophil infiltration in control group, while which was significantly improved in anisodamine group. Conclusion Anisodamine can significantly prevent lung edema after ischemia-reperfusion in rabbits. The mechanism may be ascribed to inhibition of neutrophil infiltration and decrease in vascular permeability.

Abstract:Objective To investigate the effects of valsartan on sarcoplasmic reticulum calcium adenodine triphosphatase expression and function in a rabbit model of heart failure. Methods Twenty-seven rabbits were divided into sham-operated, heart failure and valsartan groups, with 9 in each group. The rabbit model of heart failure was prepared by volume overload plus pressure overload. After 7 weeks, left ventricular function, hemodynamic parameters, and expression and function of SERCA2 were observed. Results Compared with sham-operated rabbits, left ventricular mass index (LVMI)and left ventricular end diastolic pressure (LVEDP)were significantly increased in heart failure rabbits [(1.32±0.06)vs (3.61±0.09)g/kg and (?0.50±1.05)vs (23.00±2.37)mmHg respectively, P＜0.05], but the left ventricular shortening fraction and left ventricular ejection fraction (LVEF)were significantly decreased in heart failure rabbits [(37.83±3.58)% vs (17.38±3.13)%; (72±5)% vs (38±6)%, P＜0.05]. Compared with heart failure rabbits, LVMI and LVEDP were significantly decreased in valsartan rabbits [(2.07±0.14)g/kg and (2.17±0.72)mmHg respectively, P＜0.05], but their left ventricular shortening fraction and LVEF were increased [(33.8±2.9)% and (65±4)% respectively, P＜0.05]. Expression and function of SERCA2 were remarkably lower in heart failure rabbits than in sham-operated rabbits [(0.69±0.04)vs (1.02±0.02)and (54.4±7.9)% vs (95.5±2.1)% respectively, P＜0.05], while compared with heart failure rabbits, they were significantly higher in valsartan rabbits [(0.91±0.02)and (81.7±4.9)% respectively, P＜0.05)]. Conclusion Valsartan can improve cardiac function, probably owing to its roles in upregulating expression and function of SERCA2 in the prevention of heart failure.

Abstract:Objective To evaluate whether hyperglycemia and ageing influence myocardial microvessels and the expression of myocardial PAI-1 mRNA by observing changes in the number of myocardial microvessels and the expression of myocardial PAI-1 mRNA in aged and young diabetic rats. Methods Aged and young SD rats were randomized to diabetes mellitus (DM) group and control group. The DM model was established by intraperitoneal STZ injection. The rats were raised for 8 weeks and sacrificed. Part of the left ventricular tissue was used for immunohistochemical evaluation, and the remaining part was used for detection of PAI-1 mRNA exprerssion. Myocardial microvascular endothelial specific antigen CD34 was detected by using CD34 antibody and EnVision immunohistochemistry. The number of myocardial microvessels was counted by Medical Image Analysis Software. The expression of myocardial PAI-1 mRNA was detected by real-time fluorescence quantitative PCR. Results The number of myocardial microvessels of DM group was significantly smaller than that of the control in all age groups 8 weeks after modeling (P＜0.01), and the number of myocardial microvessels of the aged DM group was significantly smaller than that of the young DM group and young control group (P＜0.01), while there was no significant difference between the aged and young control groups (P＞0.05). The expression of myocardial PAI-1 mRNA in DM rats of all age groups was significantly increased as compared with the control group at corresponding ages (P＜0.01). In addition, the expression of myocardial PAI-1 mRNA in the aged control rats was higher than that in the young control rats (P＜0.05). Conclusion Ageing has a significant influence on the number of myocardial microvessels in diabetic rats but not in non-diabetic rats. Ageing enhances the expression of myocardial AI-1 mRNA in rats. The number of myocardial microvessels is decreased and the expression of myocardial PAI-1 mRNA is enhanced in diabetic rats at all ages.

Abstract:Objective To study the effects of telmisartan on matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) expressions and insulin resistance in rat model of nonalcoholic steatohepatitis (NASH). Methods Thirty male SD rats were randomized into normal control group, NASH model group and telmisartan intervention group. The rats were given standard food in normal control group, while high fat diet for 16 weeks in the other two groups to induce NASH. In telmisartan intervention group, telmisartan[5 mg/(kg?d) ] was adminstrated intragastrically for 4 weeks since the 12th week. All animals were sacrificed at 16 weeks. Serum levels of alanine aminotransferase(ALT), aspartate transaminase(AST), fasting blood glucose (FBG) and fasting insulin (FINS) were detected. Insulin sensitivity was evaluated by homeostasis model assessment of insulin resistance(HOMA-IR). Western blot and RT-PCR were used to measure TIMP-1 and MMP-13 expressions in hepatic tissue. Histological observation and immunohistochemical staining of α-smooth muscle actin(α-SMA) were also performed. Results Serum levels of ALT, AST, FPG, FINS and HOMA-IR were significantly higher in NASH group than in normal control group (P＜0.01). Compared with NASH group, serum levels of ALT, FPG, FINS and HOMA-IR decreased significantly(P＜0.01), and AST level also decreased, but with no significance(P＞0.05). Telmisartan improved significantly hepatic inflammation and fibrosis(P＜0.01), decreased HOMA-IR significantly(P＜0.01), reduced expresseions of α-SMA and TIMP-1, and increased expressions of MMP-13 in hepatic tissue(P＜0.01). Conclusion Telmisartan can improve insulin resistance and prevent hepatic fibrosis in NASH rats.

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Abstract:Approximately 20% of human tumors are associated with mutations of ras genes. Ras proteins control cellular signaling pathways responsible for cell proliferation, differentiation, survival and apoptosis. Ras proteins belong to the large family of small GTPases, which are activated in response to various extracellular stimuli. RASAL1, as a ras GTPase activating protein, inhibits ras activation. Regulation of ras and RASAL1 activities may lead the direction of target treatment of tumors. Detection of ras and RASAL1 activities can provide more relevant information about diagnosis and prognosis of gastrointestinal tumors. In this paper, we reviewed the structure, the biochemical properties of ras proteins, and the role of its mutations in tumors. We further discussed the inhibitive effects of RASAL1 on ras activities. Finally, we commented the correlation of ras and RASAL1 with gastrointestinal tumors.

Abstract:Interstitial lung disease(ILD) is one of the common extra-articular manifestations of rheumatoid arthritis(RA). Its incidence in RA is 7.7%, and the prognosis is poor. Leflunomide is one of the commonly used drugs for RA, but there are more and more reports about leflunomide caused interstitial pneumonia. Then, should leflunomide be used when RA is complicated with ILD? However, It has been reported that leflunomide can be an effective treatment for RA patient who already sufferred from lung disease [including ILD caused by methotrexate (MTX)], and no adverse drug reaction or pulmonary exacerbation was observed. So, leflunomide could be used as a replacement therapy in patients with MTX related ILD. The safety of leflunomide in treatment of RA was relatively approved in China, but the reports on leflunomide induced ILD were not rare recently outside of China. A cohort study performed in Canada reported that the risk of ILD was increased in RA patients treated with leflunomide (adjusted RR 1.9), but it was not elevated in patients with no previous history of MTX use or ILD(adjusted RR1.2). Japanese scholars proposed that leflunomide application should be prohibited or require careful consideration in elderly male RA patients with history of ILD or smoking. Pulmonary function responsed to leflunomide adversely in an ethnic group dependent manner. Genetics testing might be the key to find the answer. Although leflunomide had a potential risk of causing ILD, meta-analysis indicated satisfactory therapeutic effects and safety of leflunomide for RA. For RA patients with preexisting pulmonary disorders, leflunomide application requires careful consdideration and CT scanning should be monitored regularly.

Abstract:Pulmonary hypertension(PH) is a heterogeneous group of disorders characterized by increased pulmonary vascular resistance(PVR). The term PH pertains to the hemodynamic profile. PH can be found in different clinical conditions. The non-pulmonary arterial hypertension pulmonary hypertension(non-PAH PH) refers to those forms of PH that are found in group 2 to 5 of the current classification of PH. They included pulmonary hypertension due to left heart disease, pulmonary hypertension due to lung diseases and hypoxemia, chronic thromboembolic pulmonary hypertension, and other diseases. Some advances has been made for the diagnosis and medical therapy of pulmonary arterial hypertension(PAH), but PAH is usually severe and overall quite rare. Non-PAH PH is much more common than PAH, and has been less well studied, especially in terms of diagnosis and medical therapy. The di-agnosis and medical therapy of non-PAH PH would be the hot topics and it is important to conduct further studies.

Abstract:Genetic factors play important roles in the development of Alzheimer?s disease(AD). We mainly introduced some genes, which has been reported in recent years, predisposing to different aspects of AD. Besides, from the aspects of epigenetics, gene or drug therapy, we also discussed how to block the expression pathway of some predisposing genes, so as to inhibit or delay the development of AD. Except several genes related to familial AD and apolipoprotein E, some other predisposing genes related to sporadic AD remains controversal. Racial diversity and sample size might explain the disagreement of various researches. Therefore, further studies are needed for better diagnosis and gene therapy of AD.