Acetylcholine ; metabolism ; Acetylcholinesterase ; metabolism ; Animals ; Brain ; enzymology ; metabolism ; Female ; Hypoxia, Brain ; physiopathology ; Ischemic Preconditioning ; methods ; Male ; Memory ; physiology ; Mice ; Random Allocation ; Reperfusion Injury ; prevention & control

Objective:To study how to guide the individual dose of clopidogrel in line with the genetic testing results. Methods:Clinical pharmacists decided how to optimize the prescription of clopidogrel according to the genotype combined with the drug metabolism and drug interactions for three patients respectively with slow clopidogrel metabolism,intermediary metabolism and super fast metabolism. Results:The slow clopidogrel metabolism patient with subacute stent thrombosis after half a month of coronary stenting was switched to orally administrate with ticagrelor. The super fast metabolism patient suffered from repeatedly subcutaneous hemorrhage with antiplatelet therapy was suggested to lower the dose of clopidogrel,temporarily withdraw Maixuekang capsules and conventionally administrate with vitamin C tablets orally. The intermediary metabolism patient with late stent thrombosis co-treated with lansoprazole was suggested to increase the dose of clopidogrel or use ticagrelor instead,and when it was necessary,panxitorazole,ray Bella or the other ranitidine acid suppression drugs such as ranitidine could be considered. Conclusion:Through genetic testing and drug interactions,clinical pharmacists guide the clinical use of clopidogrel and the optimization of antiplatelet therapy.

Objective To explore the relationships between the serum and urinary levels of procollagen Ⅲ and renal injury at the early stage of hypertension in sponantously hypertensive rats. Methods 16 sponantously hypertensive rats (SHR) were divided into treated group (losartan 30mg?kg -1?d -1) and untreated group, each group containing 8 animals, and 8 Wistar-kyoto rats served as normotensive control group(WKY). The serum and urinary levels of procollagen Ⅲ and ? 2-microglobin, and urinary microalbumin level were measured by radioimmunoassay 16 weeks after treatment. Results Blood pressure, serum ? 2-microglobin level, and the urinary levels of procollgen Ⅲ, ? 2-microglobin and microalbumin in SHR were significantly higher than those in wistar-kyoto rats. Losartan could decease the levels of the indices above in SHR. Serum procollagen Ⅲ level had not significant difference among the three groups of rats, and was not correlated with urinary procollagen Ⅲ level. There were positive correlation between serum and urinary ? 2-microglobin levels, and urinary procollgen Ⅲ level was positively retated to urinary ? 2-microglobin, urinary microalbumin and systalic pressure. Conclusion The levels of urinary procollgen Ⅲ,? 2-microglobin and microalbumin could reflect the lesion of glomerulus and tubulointerstitum at the early stage of essential hypertension in SHR.

To study the pharmacokinetics characteristic of loganin, ferulic acid and stilbene glucoside in rat plasma after oral administration of Bushen Tongluo formula. The plasma samples were treated by using liquid-liquid extraction technique, the concentrations were determined by HPLC-UV. Johnson spherigel C18 column (4.6 mm x 250 mm, 5 μm) was adopted and eluted with the of mobile phase of methanol-water containing 0.01% glacial acetic acid in a gradient mode, with the flow rate at 1.0 mL x min(-1), column temperature at 30 degrees C and injection volume of 10 μL. According to the findings, loganin was determined at 235 nm, ferulic acid and stilbene glucoside were determined at 320 nm, with the sample size of 10 μL. The pharmacokinetic parameters of loganin, ferulic acid and stilbene glucoside were calculated by DAS 2. 0 software as follows: C(max) was (0.369 ± 0.042), (0.387 ± 0.071), (0.233 ± 0.044) mg x L(-1); t(max) was (0.226 ± 0.022), (0.282 ± 0.031), (0.233 ± 0.044) h; t(½β) was (6.89 ± 0.20), (10.73 ± 0.11), (6.93 ± 0.09) h; AUC(0-∞) was (1.91 ± 0.36), (3.22 ± 0.52), (1.52 ± 0.33) mg x h x L(-1); AUCO(0-t) was (1.62 ± 0.33), (2.58 ± 0.43), (1.30 ± 0.30) mg x h x L(-1); CL was (20.2 ± 4.0), (1.39 ± 0.23), (31.7 ± 6.9) L x h(-1) x kg(-1), respectively. The results showed that after the oral administration with Bushen Tongluo formula, loganin, ferulic acid and stilbene glucoside showed concentration-time curves in conformity with the two compartment model, with a rapid absorption, loganin and stilbene glucoside was excreted at a moderate speed, and ferulic acid was excreted slowly (but with the highest bioavailability). Bushen Tongluo formula can main maintain plasma concentration with three administrations everyday and so is suitable to be made into common oral preparation.
Administration, Oral ; Animals ; Biological Availability ; Coumaric Acids ; administration & dosage ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; pharmacokinetics ; Glucosides ; administration & dosage ; blood ; pharmacokinetics ; Iridoids ; administration & dosage ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; administration & dosage ; blood ; pharmacokinetics

In this study, we explored the mechanism of Huganning tablet (HGNP) in the treatment of nonalcoholic fatty liver disease (NAFLD) based on network pharmacology and computer-aided drug design. Firstly, the potential ingredients and targets of HGNP were identified from TCMSP database, Swiss Target Prediction database, Chinese pharmacopoeia (2015) and literatures, and then the targets of HGNP intersected with NAFLD disease targets that obtained in GeneCards database to acquired potential targets. The bioconductor bioinformatics package of R software was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. The network of “potential ingredient-key target-pathway” was formed in Cytoscape software to study the interactions between potential ingredients of HGNP, key targets, pathways and NAFLD. Based on the results of network pharmacology, the molecular docking analysis of the key targets and potential active ingredients in HGNP tablets with top degree in the network was conducted using Discovery Studio 2020 software, followed by molecular dynamics simulations, binding free energy calculation, drug-likeness properties analysis and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties prediction. In vitro, HepG2 cells were used to establish steatosis model, and the effects of five key compounds on hepatocyte steatosis were analyzed by oil red O staining and triglyceride (TG) content determination. The results showed that 141 ingredients and 151 potential targets were obtained. A total of 2 526 items and 151 pathways were identified by GO and KEGG enrichment analysis. The molecular docking suggested that five components, isorhamnetin, salvianolic acid B, emodin, resveratrol and rhein, exhibited strong binding ability with key targets [retinoic acid receptor RXR-alpha (RXRA), tumor necrosis factor (TNF), glycogen synthase kinase-3 beta (GSK3B), serine/threonine-protein kinase 1 (AKT1)]. It was further verified that isorhamnetin and salvianolic acid B bind to key targets with good structural stability and binding affinity based on molecular dynamics simulations and binding free energy calculations. The drug-likeness properties, pharmacokinetic properties and toxicity of five key compounds were more comprehensively analyzed through drug-likeness properties analysis and ADMET properties prediction. In vitro, all five compounds, isorhamnetin, salvianolic acid B, emodin, resveratrol, and rhein, improved hepatocyte steatosis of HepG2 cells, confirming the reliability of the present study. In conclusion, based on network pharmacology, computer-aided drug design and in vitro validation, this study investigated the mechanism of HGNP for the treatment of NAFLD at multiple levels and provided a basis for its clinical application.

We applied Lempel-Ziv complexity (LZC) combined with brain electrical activity mapping (BEAM) to study the change of alertness under sleep deprivation in our research. Ten subjects were involved in 36 hours sleep deprivation (SD), during which spontaneous electroencephalogram (EEG) experiments and auditory evoked EEG experiments-Oddball were recorded once every 6 hours. Spontaneous and evoked EEG data were calculated and BEAMs were structured. Results showed that during the 36 hours of SD, alertness could be divided into three stages, i. e. the first 12 hours as the high stage, the middle 12 hours as the rapid decline stage and the last 12 hours as the low stage. During the period SD, LZC of Spontaneous EEG decreased over the whole brain to some extent, but remained consistent with the subjective scales. By BEAMs of event related potential, LZC on frontal cortex decreased, but kept consistent with the behavioral responses. Therefore, LZC can be effective to reflect the change of brain alertness. At the same time LZC could be used as a practical index to monitor real-time alertness because of its simple computation and fast calculation.
Attention ; physiology ; Brain Mapping ; Electroencephalography ; Evoked Potentials ; Humans ; Nonlinear Dynamics ; Sleep Deprivation

Objective To explore the methods and mid-term results of interventional therapy for atherosclerotic occlusive disease of the superficial femoral artery(SFA).Methods From January 2005 to August 2008,Nineteen cases with 22 diseased lower limbs were admitted.According to Fontaine stage system,there were 6 stage Ⅱb limbs(moderate to severe intermittent claudication),8 stage Ⅲ limbs(rest pain),and 8 stage Ⅳ limbs(6 with ulcer and 2 with gangrene).The mean lesion length was 8.8 cm(5～13 cm).On the basis of the TransAtlantic Inter-Society Consensus(TASC)femoropopliteal classification,the lesions were classified as type B in 4 limbs,type C in 17,and D in 1.Follow up examinations with color duplex ultrasound and/or arteriography were carried out to determine the patency.The improvement of clinical symptoms after operation was analyzed.Results 17 limbs were revascularization successfully,2 limbs were turned to bypass operation,3 limbs were judged untreatable.The technical success rate is 77.3%,and the clinical improvement of symptoms was achieved in 100% of the 17 limbs on which the procedure was successful.The 17 limbs were followed up for a mean of 12.5 months(range 3-33 months).One patient died of cardia infarction one month postoperatively.SFA occlusion happened in 4 limbs.At one year postoperatively,the patency rate was 75%(13/17)after primary operation.Conclusions Primary endovascular treatment of SFA occlusion diseases is a safe,minimally invasive,and effective method.

Objective To investigate the adverse effects of taurine on rabbit corneal endothelial cells. Methods Six rabbits (12 eyes) were selected, and 6 histologic sections were prepared from each of the eyes. Rabbit corneal endothelial cells were cultured by explant culture method. Cells were innoculated on a 12-well tissue culture plate, 2%, 4%, 6%, 8% and 10% taurine solutions were added respectively (cells from the right and left eyes of the same rabbit were added the same concentration of taurine solution), and blank control was established. The growth of corneal endothelial cells was observed by inverted microscopy, and cell morphology on the 1st, 2nd, 4th, 6th and 8th day of culture was observed with Wright staining. Results Corneal endothelial cells cultured with 2%, 4% and 6% taurine solutions and those of blank control formed endothelial cell layers after culture for one week, and the cells exhibited hexagonal or round-like morphology. Corneal endothelial cells cultured with 8% taurine solution appeared to be undergrowth with small cell body on the 4th day, and cell death occurred on the 8th day. Corneal endothelial cells cultured with 10% taurine solution turned out to be undergrowth with small cell body on the 2nd day, and cell death had occurred. The same growth velocity and cell morphology were observed in the corneal endothelial cells from the right and left eyes of the same rabbit. Conclusion Taurine with concentration between 2% and 6% has no adverse effects on the growth of rabbit corneal endothelial cells.

Objective To investigate the association of platelet activating factor acetylhydrolase(PAF-AH) activity in children with primary nephrotic syndrome(PNS).Methods The plasma PAF-AH activity was measured in 78 children with PNS who were divided into 3 groups:steroid-responsive nephritic,steroid-dependent nephritic,steroid-resistent nephritic,after they had been given steroid for 6 months.The plasma PAF-AH activity were also measured in 60 healthy children at the same age,with spectrophotometric assay,at the ame time,the blood cholesterol was measured.Results The blood cholesterol has positive correlation with the plasma PAF-AH activity,there was no significant difference of the blood cholesterol among 3 groups in nephrotic syndrome children,there was a significant difference in the plasma PAF-AH activity among 3 groups in PNS children,but there was no significant difference in the plasma PAF-AH activity between the groups of steroid-responsive nephritic and healthy children.Conclusion Plasma PAF-AH activity is related to the sensibility to steroid treatment in children′s PNS,and the plasma PAF-AH activity in steroid-resistent nephritic is higher than steroid-dependent nephritic.It is a question that if gene mutation is related with PAF-AH activity.

Objective To release the correlation of point mutation of platelet activating factor acetylhydrolase(PAF-AH)gene and primary nephritic syndrome (PNS).Method According to the effect of hormonal therapy,94 children with PNS were divided into three groups:steroid-sensitive nephritic syndrome(SSNS),steroid-resistent nephritic syndrome(SRNS),steroid-dependent nephritic syndrome(SDNS).The point mutation of PAF-AH gene (G994T) were identified by molecular biology technique in children with PNS and 239 healthy children were set as control group.Results No statistics differences were found relating to the genotype and allele frequencies between patients with PNS,SSNS,SRNS and normal controls.But it is confirmed that the genotype and allele frequencies among patients with nephritic type nephritic syndrome (NTNS)was higher than patients with simple type nephritic syndrome(STNS) and normal controls.SDNS was higher than both SSNS and normal controls.The number of relapses during the first year after onset was significantly higher in the patients who were heterozygous for the mutant allele (GT) or homozygotes (TT) than in those of the GG homozygotes.Conclusion Most PNS children with PAF-AH gene mutation occurred at position 994 were NTNS.The risk of relapse during the treatment period was higher in patients with PAF-AH gene mutation occurred at position 994.