OBJECTIVE:To study pharmacokinetics of cyclosporine in healthy volunteers, and to investigate the relationship of drug exposure with blood sampling time after treatment. METHODS: The data of trial at the first 12 blood sampling time points after medication were collected from bioequivalence test in 24 healthy volunteers (trial preparation vs. reference preparation). Multiple linear regression analysis was used to study the blood concentrations of cyclosporine at different sampling time points and the area under the blood concentration-time curve (AUC). RESULTS: The concentrations at two points were adopted to estimate AUC. The correlation coefficient of different cyclosporines could reach 0.9 with estimation deviations less than 15%. The AUC of cyclosporine of trial preparation could be estimated by C8 and C12, and that of reference preparation by C2.5 and C12. CONCLUSION: The AUC estimated by concentrations at two points can meet clinical demand. There is great difference in estimate point among different preparations.

Objective To evaluate left ventricular rotation and torsion and its early recovery after percutaneous coronary intervention (PCI) in patients with coronary heart disease and normal left ventricular ejection fraction (LVEF) using two dimensional speckle tracking echocardiography.Methods Twenty three consecutive patients with coronary heart disease and normal LVEF were divided into group B (with coronary stenosis ＜70％) and group C (with coronary stenosis ＞70％ and with PCI).Along with 11 healthy controls(group A),indices including basal rotation (BR),apical rotation (AR),left ventricular torsion (LVT) and normalized time to peak were compared among groups,correlative analysis was made between LVT and each indices mentioned above,indices of group C before and 24 hours after PCI were compared.Results AR,LVT in group B and C reduced relative to group A (P ＜0.05),meanwhile time to peak of BR in group C shortened relative to other groups.BR,AR and normalized time to peak of BR were correlated to LVT respectively.BR and LVT in group C increased after PCI(P ＜0.05).Conclusions AR was sensitive to ischemia,the reduction of time to peak of BR in group C might be restriction and compensation.Sensitive to early recovery of left ventricular function after reperfusion,BR could be a predictive index of early effect of percutaneous coronary intervention.

OBJECTIVE Tostudythehepatotoxicityofveratrinehydrochloride(VH)anditsmecha-nismoninductionofapoptosisinvitro.METHODS HepG2cellswereexposedtoVH0.1-0.6g·L-1 for 24 h,cell viability was examined by CCK-8 assay,and the morphologic changes in HepG2 cells were quantified.After the treatment with VH 0.1 -0.5 g·L-1 for 24 h,cell membrane injury was examined by detecting the release rate of lactate dehydrogenase (LDH).The effect on reactive oxygen species (ROS),mitochondrial membrane potential and apoptosis was detected by flow cytometry.The mRNA expression of p53,Bax,cytochrome c,caspase 9,caspase 3 was evaluated by real-time PCR. RESULTS HepG2cellviabilitywassignificantlyreducedfollowingexposuretoVH0.1-0.5g·L-1. The IC50 value was 0.4 g·L-1 .The 95%confidence limit was 0.2558-0.6965 g·L-1 .The LDH release rate,ROS and apoptosis rate of HepG2 cells were significantly increased after exposure to VH 0.1 -0.5 g·L-1 for 24 h (P<0.05,P<0.01 ),and the mitochondrial membrane potential markedly declined (P<0.05,P<0.01 ).The expression of p53,Bax,cytochrome c,caspase 9 and caspase 3 was increased(P<0.05,P<0.01).CONCLUSION VHhascytotoxicpotential.Damagetocell me mbrane and mitochondria and initiation of apoptosis-related genes of caspase 9 and caspase 3 mRNA expression may be the mechanis m of apoptosis.

Aim To investigate the induction effect of ginsenoside Rc, Re, Rf and Rg1 on CYP1A1, and further validate the role of aryl hydrocarbon receptor in CYP1A1 expression. Methods Dual luciferase re-porter gene system was performed. Four kinds of gin-senoside were screened for aryl hydrocarbon receptor activation by reporter assays, and TCDD as the positive control. Further with different concentrations of ginsen-oside Rc, Re, Rf and Rg1 treated on LS174T cells, RNA and total protein were extracted to detect the reg-ulating effect of ginsenosides on CYP1 A1 mRNA and protein expression with Real-time PCR and Western blot technology respectively. Results Reporter gene screening showed that the ginsenoside Rc, Re, Rf and Rg1 could activate AhR and had potential effects on the induction of CYP1A1 enzyme. Meanwhile, dose-de-pendent induction of the gene expression were observed in response to ginsenoside Rc, Re, Rf and Rg1 and the levels of CYP1 A1 protein expression were increased by ginsenoside Rc, Re, Rf and Rg1 in varying de-grees. Conclusion Ginsenoside Rc, Re, Rf and Rg1 can up-regulate the gene and protein expression of CYP1 A1 possibly via the AhR-mediated CYP1 A1 path-way.

We have done a research on mathematical morphology filter in order to eliminate baseline drift in the wave of electrocardiograph (ECG). Marago morphology filter type was chosen and flat structuring element filtering was found to be the best morphology filter modality for eliminating baseline drift, and the ratio of "signal numerical frequency to length of structuring element" determined the attenuation magnitude of the signal eliminated. We have come to the conclusion that the length of flat structuring element ought to be greater than or equal to the width of the signal component to be eliminated. The arithmetical algorithm was simulated with Matlab software, and was transplanted to DSP hardware platform. The result of experiment has shown that the arithmetic operation is simple and the method spends a short time (less than 1 ms) in eliminating the baseline drift of ECG effectively and instantly.
Algorithms ; Artifacts ; Electrocardiography ; instrumentation ; methods ; Equipment Design ; Humans ; Signal Processing, Computer-Assisted

OBJECTIVE To study the mitochondrial toxicity effect of Radix Aconiti Lateralis Praepa?rata(Fuzi)on H9c2 cardiomyocytes. METHODS H9c2 cells were exposed to Fuzi decoction 6.25, 12.5,25,50 and 100 g·L-1 for 24 h. Fluorescence staining and CCK-8 assay were used to detect cell viability. H9c2 cells were exposed to Fuzi decoction 6.25,12.5 and 25 g · L-1 for 24 h,while the effect on mitochondrial membrane potential and reactive oxygen species(ROS)was detected by flow cytometry. The fluorescence molecular probe and laser scanning confocal microscope were used to observe the effect on Ca2+ in cells,Ca2+ and superoxide in mitochondria. The effect on ATP concentration in cells was detected via firefly luciferin and the expression of Pgc-1α,Bcl-2 and Bax mRNA evaluated by real-time PCR,while the expression of Pgc-1α protein was measured by Western blotting. RESULTS H9c2 cell viability was significantly inhibited by Fuzi decoction 12.5-100 g · L-1(P<0.05,P<0.01). The IC50 value was 47.4669 g · L-1,while the 95%confidence limit was 32.5997-69.1145 g · L-1. After treatment with Fuzi decoction 25 g · L-1 ,the fluorescence intensity of ROS in the normal control group increased from 204±67 to 454±78(P<0.05),that of mitochondrial superoxide increased from 5.4±1.8 to 26.8±8.5 (P<0.01),mitochondrial membrane potential decreased from 1.7±0.5 to 0.8±0.4(P<0.05),the fluores?cence intensity of intracellular Ca2+increased from 7.8±0.8 to 22.1±0.5(P<0.05)while that of mitochon?drial Ca2+decreased from 38.0±4.3 to 9.2±1.6(P<0.01),and intracellular ATP concentration decreased from (10.6 ± 0.4)μmol · g-1 to (5.3 ± 1.1)μmol · g-1 protein (P<0.05). qPCR and Western blotting test results showed that compared with the normal control group ,Pgc-1αand Bcl-2 mRNA relative expression level in Fuzi decoction 25 g·L-1 group was decreased from 1.00±0.10 and 1.00±0.10 to 0.09±0.06(P<0.01)and 0.43±0.06(P<0.01),respectively, while the relative expression of Bax mRNA was increased from 1.00 ± 0.03 to 1.17 ± 0.06 (P<0.05),and the expression of Pgc-1α protein was decreased from 0.906±0.034 to 0.541±0.003(P<0.01). CONCLUSION Fuzi has some mitochondrial toxicity to cardiomy?opathy. This effect arises from the combined action of different mechanisms. Mitochondrial toxicity of myocytes may account for the cardiac toxicity of Fuzi.

Objective: To observe the characteristics of dynamic changes of lysophosphatidic acid (LPA) levels in cerebrospinal fluid (CSF) in patients with subarachnoid hemorrhage (SAH) and its relationship with cerebral vasospasm (CVS) and to explore the pathogenesis of CVS. Methods: Sixty-seven patients with SAH diagnozed by clinical and accessory examinations were selected. The LPA levels in CSF were measured at 24 hours, day 7,14, and 28 respectively after the onset of symptoms,and they were compared with a control group. The correlation between LPA levels and CVS on the time course was also observed at the same time. Results: Of the 67 patients with SAH, a total of 29 patients (43.3%) occurred CVS, the average time of occurrence was 6. 6 days. There was no significant difference between the LPA levels in CSF in patients with SAH and the control group at 24 hours after the onset of symptoms; they were significantly higher than the control group at day 7 (P ＜0. 001); they were significantly higher than the control group at day 14 (P ＜ 0. 001), but they were significantly lower than those at day 7 (P ＜ 0. 01); they decreased to baseline at day 28, and there was significant difference compared with the control group. There was no significant difference between the LPA levels in the CVS group and those in the non-CVS group at 24 hours, they were significantly higher than those in the non-CVS group at day 7 (P ＜0. 001), they were still significantly higher than those in the non-CVS group at day 14 (P ＜0. 01); and there was no significant difference between the 2 groups at day 28. Conclusions: The LPA levels in CSF in patients with SAH increased significantly from day 7 to day 14 after the onset of symptoms, and they had obvious association with CVS on the time course. The detection of the LPA levels in CSF may have important significance in predicting the occurrence of CVS.

Aim With metabolomics method, to study Shen-Mai decoction’ s function on protecting the myo-cardial injured rats caused by doxorubicin for probing into the functioning mechanism of Shen-Mai decoction’ s medical effect. Methods By means of UPLC-TOF-MS, the metabolites of urine of the rats treated by Shen-Mai decoction were analyzed. Then, the differ-ences between each group of the metabolites were sought with PLS-DA ( the partial least square discrimi-nant analysis ) and OPLS-DA ( the orthogonal partial least squares discriminant analysis ) . VIP ( variable importance in projection ) and t test were used to screen out potential biomarkers. Results Fourteen endogenous metabolites such as succinyladenosine, a-denosine 2′, 3′-cyclic phosphate, S-( 3-methylbu-tanoyl )-dihydrolipoamide-E, cis-4-hydroxycyclohexy-lacetic acid, phenylbutyrylglutamine, 3-butyn-1-al, 3-hydroxytetradecanedioic acid, dihydrolipoamide and pyruvic acid, etc. were characterized. Conclusions The results indicate that Shen-Mai decoction can pro-tect the body from myocardial injury by regulating pu-rine metabolism, some acid metabolism, fat metabo-lism and energy metabolism, etc. The study expounds the functioning mechanism for Shen-Mai decoction ’ s medical effect in the body and provides theoretical grounds for the rationality of the two medical herbs ’ compatibility and their combination in clinical treat-ment of diseases.

Aim To study the effect of emodin in Po-lygonum multiflorum on the expression of CYP450 isoenzymes in L02 hepatocytes and explore its mecha-nism of cytotoxicity. Methods L02 cells were treated with different concentrations of emodin. Cell viability was examined by MTS assay kit, and cell membrane injury was examined by detecting the release rate of lactate dehydrogenase( LDH) . The expression of cyto-chrome P450 mRNA was detected by real time PCR. Results The result of MTS assay showed that L02 cells viability was significantly reduced following expo-sure to emodin in a concentration and time dependent manner. The LDH release rate of L02 cells significant-ly increased after exposure to emodin for 48 h com-pared with the control group. On the mRNA level, compared with the control group,emodin had inductive effects on mRNA of each CYP450 enzyme, while had significant inductive effects on mRNA of CYP1 A1 and CYP1 B1 in a concentration and time dependent man-ner. Conclusion Emodin in Polygonum multiflorum may generate significant liver injury in L02 cells and has inductive effects on CYP450 enzyme activity.

Aim To study the effect of ginsenoside F1 on the enzyme activity and expression of gene of CYP3 A4 through activation of pregnane X receptor ( PXR ) . Methods With different concentrations of ginsenoside F1 treated on LS174T cells, the expression of CYP3A4 mRNA was determined by Q-PCR, and the enzyme activity was measured by P450-GloTM CYP3A4 assay according to the manufacturer′s instructions, fur-ther PXR-CYP3 A4 stable translation HepG2 cell lines were used to test ginsenoside F1 activates PXR by re-porter gene screening assay. Results The results re-vealed that the levels of CYP3 A4 gene and protein ex-pression were significantly increased by ginsenoside F1 in a concentration-dependent manner. At the same time, reporter gene screening showed that ginsenoside F1 could also enhance the transcriptional activity of PXR. Conclusion Ginsenoside F1 can significantly up-regulate the gene expression and enzyme activity of CYP3A4 via the PXR-CYP3A4 pathway.