Atherosclerosis (AS) is pathologically important basis of many kinds of coronary atherosclerosis disease (CAD). It can be substantially protected by raising high-density lipoprotein (HDL).In view of mechanism, drugs for raising HDL include: cholesterol ester transfer protein inhibitors, peroxisomal proliferator-activated receptor agonists, liver X-activated receptor agonists, farnesoid X receptor antagonists or agonists, lipoprotein lipase activators, niacin, and phenytoin and lecin : cholesterol acyltransferase activators, etc. This review aimed to the progress of drugs for regulating high-density lipoprotein and their mechanism, in view of clinical and preclinical aspects.

BACKGROUND: Researches on the diagnosis and detection methods of diabetic autonomic neuropathy(DAN) is very weak at present.OBJECTIVE: To get the data about the degree of autonomic neuropathy by using the nonlinear heart rate variability(HRV) so as to provide clinical evidence for the early diagnosis of DAN.DESIGN: A single sample study.SETTINGS: Computer department in a university; Staff room of medical physics of department of biomedical engineering in a university.PARTICIPANTS: The experiment was completed in the Staff Room of Medical Physics, Department of Biomedical Engineering in the First Military Medical University of Chinese PLA from March to May 2002. Thirty-four diabetic patients, including 22 with DAN complications, were selected from the inpatients of Department of Endocrinology in the Affiliated Nanfang Hospital of the First Military Medical University of PLA, and other 40 normal subjects, who were from the faculty in the First Military Medical University of Chinese PLA and students in the Department of Physical Education, Chinese PLA Institute of Physical Education, were taken as the controls. The R wave to R wave intervals(RRI) time series is sampled and corrected to 512 points for analysis.INTERVENTIONS: Based on the virtual instrumental workbench-LabVIEW, 74 standard adjacent RRI signals were selected from 34 diabetic patients and 40 normal cases, and then analyzed with the method of nonlinear predictability.MAIN OUTCOME MEASURES: Collective and analytical results of the 74 standard adjacent RRI signals.RESULTS: There was no significant difference between the diabetic patients without DAN and the controls by the analysis with normalized mean square error(NMSE) NMSE ( P = 0. 075 ), but the significant difference between the DAN patients and the controls( P = 0. 001) . While significant analysis between the diabetic patients without DAN complications and the controls was significant by the analysis of mean absolute error(MAE) (P = 0. 007 and P = 0. 000), there was also significant difference between the diabetic patients with and without DAN ( P = 0. 001 ).CONCLUSION: Different impaired degree of autonomic nerve system in diabetic patients can result in nonlinear reduction in HRV analysis, but nonlinear predictability analysis can prove the nonlinear model of HRV,. and can also provide important state information of sympathetic and parasympathetic systems so that it can provide reliable evidence for the earlier diagnosis and the prognosis evaluation of DAN.

Objective To analyze the risk factors for hypertension in patients with chronic kidney disease stage 5(CKD5) . Methods The basic information of 390 CKD5 patients complicated with hypertension was collected for univariate analysis ,in‐cluding gender ,age ,primary disease ,dialysis method ,body mass index(BMI) ,complications(hyperlipidemia ,high uric acid ,car‐diac insufficiency) ,level of education ,parathyroid hormone(PTH)level.Univariate variables that showed statistical significance were then subjected to the multivariate analysis(Logistic regression)to identify the risk factors for hypertension in CKD5 pa‐tients.The defined daily dose(DDD)that satisfied the criteria interms of different stages was evaluated.Results Overall hyper‐tension control rate was 22.8%.Univariate analysis showed that the following variables were significantly associated with hy‐pertension in CKD5 patients :>40 years old ,male ,diabetic nephropathy ,hypertensive nephropathy ,hemodialysis ,hyperlipemia , high uric acid level ,and high PTH level(P<0.05).Logistic multivariate analysis showed that diabetic nephropathy ,hyperlipi‐demia ,high PT H level were the independent risk factors for hypertension in patients with CKD5.In hypertension segmented standard ,there was no difference in the DDD between stage 0 and 1(P>0.05) ,and DDD at stage 2 and 3 was increased signifi‐cantly when compared with that at 0 and 1 standard(P<0.05).Conclusion Overall hypertension control rate is very low in pa‐tients with CKD5.Diabetics ,hyperlipidemia ,high PTH level are independent risk factors for hypertension in patients with CKD5.

Objective To evaluate the protective effects of mycophenolate mofetil (MMF) on the kidneys of diabetic rats and elucidate the associated mechanisms. Methods Wistar rats were divided into three groups: normal control rats, diabetic rats, and diabetic rats received and blood glucose were measured, and kidney pathology was observed. Inmmunohistochemistry and RT-PCR were used to analyze the expression of matrix metaUoproteinase-9 (MMP-9) and transforming growth factor 151 (TGF-β1). Results As compared with normal control rats, the 24 h urinary albumin excretion [(26.80±0.82) mg vs (6.64±1.42) mg], blood glucose[(22.18±3.36)mmol/L vs (6.40±0.87) mmol/L], Ccr [(0.220±0.380) ml/min vs (0.098±0.015) ml/min] of the diabetic rats were rised remarkbably. The 24 h urinary albumin excretion [(16.17±1.15) mg] and Ccr [(0.207±0.377) ml/min] of the diabetic rats received MMF were lower as compared to diabetic rats (P<0.05). MMP-9 in renal tissue of normal control rats was mainly expressed in glomerular mesangial ceils and renal tubular epithelial cells. Such MMP-9 expression was weak in diabetic rats and improved in the diabetic rats received MMF. There were significant differences among 3 groups. The expression of TGF-β1 was on the contrary. Conclusion Mycophenolate mofetil decreases 24 h urinary albumin, Cer and glomerular volume, which may be associated with the increase of MMP-9, the decrease of TGF-β1 expression and extracellular matrix deposition in renal tlssue.

Background: Studies showed that aberrant activation of JAK/STAT3 signaling pathway promoted the tumorigenesis and progression of hepatocellular carcinoma (HCC), and transforming growth factor-β1 (TGF-β1) has either tumor-suppressing or tumor-promoting effect in regulation of tumor progression.Aims: To investigate the effect of specific inhibition of JAK/STAT3 signaling pathway on HCC and whether TGF-β1 signaling pathway is involved in this process or not.Methods: Thirty Wistar rats were randomly divided into three groups: control group, HCC group, and HCC+AG490 group.In the latter two groups, diethylnitrosamine was administered in drinking water to induce HCC model, and in HCC+AG490 group, AG490, a specific inhibitor of JAK was injected intraperitoneally in the first week of model establishment.At the end of the 16th week, all rats were sacrificed.The maximum diameter of tumor nodules in the liver was recorded and the number of tumors with maximum diameter greater than 1 cm was counted.Expression and distribution of STAT3 and TGF-β1 in liver tissue were determined by real-time PCR, immunohistochemistry, and immunofluorescence.Results: Compared with the control group, expressions of STAT3 and TGF-β1 mRNA in liver tissue were significantly increased in HCC group (P<0.05).Phosphorylated STAT3 (p-STAT3) and TGF-β1 proteins were absent in liver tissue in control group, and both were up-regulated and co-expressed in HCC group.While in HCC+AG490 group, expressions of STAT3 and TGF-β1 mRNA were significantly lower than those in HCC group (P<0.05);the liver tissue was weakly positive for p-STAT3 and TGF-β1 proteins, and the number of tumor nodules greater than 1 cm and the maximum diameter were markedly reduced when compared with the HCC group [1.20±1.03 and (1.14±0.18) cm vs.4.30±1.06 and (1.78±0.27) cm, P all<0.05].Conclusions: Specific inhibition of JAK/STAT3 signaling pathway may restrain the tumorigenesis and progression of HCC partially by interfering TGF-β1 signaling pathway.

Objective To investigate the effect and mechanism of chitosan on vascular smooth muscle cell proliferation of uremia patients with arteriovenous fistula.Methods Primarily culturing the VSMCs of uremia patients with arteriovenous fistula and patients without uremia by explants adherent method,and taking the second generation.VSMCs from patients without uremia cultured with 20％ FBS medium were non-uremia group,VSMCs of uremia patients cultured with 20％ FBS medium were uremia group,VSMCs of uremia patients with 100 pg/ml chitosan were uremia+ chitosan group.The expression of α-SMA was detected by immunohistochemistry.The changes of migration and invasion of VSMCs were detected by scratches and transwell migration assays.The mRNA expressions of TLR4 and PCNA were measured by real-time PCR.VSMCs of uremia patients with arteriovenous fistula were intervened with different doses of chitosan (0,100 and 500 μg/ml),and the protein expressions of TLR4,MyD88 and NF-κB were detected by Western blotting.Results Compared with those in non-uremia group,in uremia group and uremia+chitosan group α-SMA was upregulated,migration and invasion of VSMCs were enhanced,and mRNA expressions of TLR4 and PCNA were increased (all P ＜ 0.05).Compared with those in uremia group,the level of α-SMA was significantly decreased,the ability of migration and invasion of VSMCs were decreased,and the mRNA expressions of TLR4 and PCNA were decreased (all P ＜ 0.05).TLR4,MyD88 and NF-κB protein expressions were reduced in concentration-dependent manner by 100 and 500 μg/ml chitosan.Conclusions (1) In vitro,chitosan decreases the ability of migration and invasion of VSMCs of uremia patients with arteriovenous fistula.(2) Chitosan inhibits the proliferation of VSMCs,which may be relevant in the decreased expressions of TLR4,MyD88 and NF-κB.

Objective To investigate the effects of lipoprotein lipase activator, NO-1886, on the mRNA and protein expression of glycogen synthase kinase-3β (GSK-3β) in the kidney of diet-induced diabetic minipigs. Methods Fifteen Guangxi Bama minipigs were randomized into three groups: C group (n=5, with the normal control diet), DM group (n=5, with the high-fat and high-sucrose diet), and NO-1886 group (n=5, with the high-fat and high-sucrose diet supplemented with 1.0% NO-1886). Plasma glucose, insulin, tfiglyceride (TG), oral glucose tolerant test, creatinine and blood urea nitrogen were measured monthly. Urinary samples in the morning were used for determination of microalbumin at month 0, 2, 4 and 5. The mRNA and protein expression of GSK-3β were measured by real time PCR, Western blot and immunohistochemistry in the kidneys obtained at the end of month 5. Results Compared with the C group, levels of plasma glucose, insulin, triglyceride and mieroalbuminuria were significantly increased in the DM group. The mRNA and protein expression of GSK-3β were increased in the kidneys of diabetic pigs (mRNA 0.0272±0.0052, protein 1.1600±0.0463, P<0.01) as compared with those of normal pigs (mRNA 0.0125±0.0045, protein 0.1385±0.0664). Compared with the DM group, the concentrations of plasma glucose, insulin, triglyceride and mieroalbuminuria obviously decreased in the NO-1886 group. The mRNA and protein expression of GSK-3β were decreased in the kidneys of the NO-1886 group (mRNA 0.0162±0.0019, protein 0.8429±0.0408, P<0.05) as compared with that of the DM group. Conclusion NO-1886 can improve disorders of glucose and TG metabolism and insulin resistance, and down-regulate the expression of GSK-3β in the kidneys, and protect renal function and morphologie damage in diet-induced diabetic minipigs.

Objective To investigate the effete of chitosan on rabbit carotid artery internal jugular vein fistula intimal hyperplasia and its regulation on TLR4/NF-κB signaling.Methods A total of 28 New Zealand white rabbits were randomly divided into the control group(n=4),the model group(n=12) and the chitosan group(n=12).Model group and chitosan group rabbits were established respectively carotid artery internal jugular vein fistula models.After AVF surgery,chitosan was smeared on venous blood vessels and anastomosis.After 4,6 and 8 weeks,the rabbits were separately sacrificed and the AVF venous vascular tissues were taken.The pathological changes of AVF venous vascular tissue in each group were observed.The changes of α-SMA were detected by immunohistochemistry method.The mRNA expressions of PCNA and TLR4 in the tissues were measured by Real-time PCR.At the same time,the protein expressions of PCNA,TLR4,MyD88 and NF-κB were detected by Western blotting.The experimental data were processed by two-factor analysis of variance in statistics.Results (1) After 4 weeks,vascular intimal was thicked in mdel group.In intimal hyperplasia,α-SMA was staining,and then proliferation of vascular smooth muscle cell was significant.As time increasing,more intimal hyperplasia shown obviously,the expression of α-SMA significantly increased.Compared with model group,chitosan group significantly reduced the degree of intimal hyperplasia,the level of α-SMA was significantly decreased,vascular smooth muscle cell proliferation was also extraordinarily decreased.(2) Compared with control group,the expression levels of PCNA,TLR4,MyD88 and NF-κB increased with time.The indices of Chitosan group were markedly higher than control group,but significantly lower than model groups.Conclusion Chitosan can inhibit the proliferation of rabbit VSMCs.The mechanism may be concerned in down regulating TLR4-mediated signaling pathway,reducing the possibility of intimal hyperplasia of rabbit AVF venous blood vessels.

In this paper a new technique, Empirical Mode Decomposition(EMD), for use in non-stationary and non-linear data processing, was introduced. Some simulated signal, real ECG and RRI signals combined with Hilbert Transform method were analyzed. The authors also put emphasis on the differences between EMD and Wavelet Transform.
Algorithms ; Computer Simulation ; Diagnosis, Computer-Assisted ; methods ; Electrocardiography ; Heart Rate

OBJECTIVETo assess mental fatigue by noninvasive monitoring of the physiological signals.

METHODSThe changes in the physiological parameters including the electrodermal activity, heart rate and heart rate variability were analyzed in 14 subjects performing the reaction-time tasks when fatigue and changes in the reaction time occurred.

RESULTSThe average skin conductance level, average heart rate, and heart rate variability parameters including the total power density, percentage of the very low power density, percentage of high power density all differed significantly between the sober state and the mental fatigue state.

CONCLUSIONMonitoring the physiological parameters including the electrodermal activity, heart rate and heart rate variability is a noninvasive, effective and practical approach to mental fatigue assessment.

Adult ; Galvanic Skin Response ; physiology ; Heart Rate ; physiology ; Humans ; Male ; Mental Fatigue ; physiopathology ; Reaction Time ; Young Adult