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.

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 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.

Objective To investigate the expression and significance of calcyclin binding protein (CacyBP)in the brain of rat model of traumatic brain injury(TBI).Methods Sixty 60 male SD rats were divided randomly into normal control group (n=10) and TBI group (n=50).The TBI model was created by using lateral head rotation device and subdivided into 6 h,24 h,72 h,7 d and 14 d group (10 rats per group).The expression and distribution of CacyBP in the rat brain was investigated immunohistochemically.The presence of the brown stained particles was considered aspositiveand lack of the stained particles agnegative. Results CacyBP was mainly distributed in the hippocampus,dentate gyrus and cortical neuron cytoplasm.Compared with the high level expression of CacyBP in the normal control group,the expression of CacyBP was decreased to the lowest in the rat brain at 6 h post TBI (P<0.01),became stronger gradually at 24 hours and recovered to normal at day 14,with no statistical difference compared with normal control group (P>0.05). Conclusion The lowest level expression of CacyBP after TBI indicates that CacyBP may play an important role in development of brain injury under effect of difierent mechanisms.

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.

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

Objectives To explore the effects of aging on midgastric transverse band(MTB)and gastric emptying.Methods In our prospective study,57 healthy volunteer were divided into young, middle and old-age groups.After taking test meal labeled by 99mTc-iethylenetriaminepentaacetic acid(99mTc-DTPA), the pictures were collected using double probe single photon emission computed tomography(SPECT).Stomach in each frame of the pictures was divided into proximal, midgastric transverse band(MTB)and distal parts.And half gastric emptying time,gastric remnant rate at 90 min, areas of different gastric parts were tested and calculated respectively.Results Half gastric emptying time of whole stomach was(43.24± 11.87)min,(42.07 ± + 9.31)min and(45.81 ± 10.73)min in young,middle and old-age groups, respectively, with P＞0.05.Among young, middle and oldage groups, half gastric emptying time was(38.09 ± 10.26)min,(37.33 ± 9.28)min and(26.74 ± 12.07)min in proximal stomach, and it was(38.35 ± 12.96)min,(37.73 ± 7.46)min and(46.41 ± 10.74)min in distal stomach,respectively.The half gastric emptying time was significantly reduced in proximal stomach and increased in distal stomach in old-age group(both P＜0.05).The gastric nuclide remnant rate at 90min in total stomach was(30.38 ± 19.32)％,(29.03 ± 10.36)％ and(31.92 ± 13.47)％ ,in young, middle and old-age groups, respectively, with P＞0.05.This rate in proximal stomach was(25.01 ± 12.35)％,(26.36± 15.29)％ and(19.54±8.47)％ among three group, respectively.The rate in proximal stomach was(42.25 ± 12.36)％,(41.56 ±± 9.33)％ and(56.05 ± 11.72)％ among three group,respectively.The gastric remnant rate at 90min was reduced in proximal stomach and was increased in distal stomach significantly in old-age group(both P＜0.05).Compared with young and middle-age group,the old-age group showed no difference in areas of total stomach in all the time, while the areas were reduced in proximal stomach and increased in distal stomach significantly from 30 min to 90 min(all P＜0.05).Total stomach versus proximal and distal stomach showed no difference in count/pixel ratio in all time,while a count/pixel ratio was reduced in proximal stomach and increased in distal stomach significantly from 30 min to 90 min(both P＜ 0.05).Both areas and count/pixel ratio of MTB at 60 min and 90 min were significantly increased in old-age group(both P＜0.05).Conclusions The total gastric emptying is not delayed along with aging, while the gastric emptying is increased in proximal stomach and reduced in distal stomach in the elderly.This abnormity of intragastric distribution of food might be related with larger area of midgastric transverse band.

Vigilance is defined as the ability to maintain attention for prolonged periods of time. In order to explore the variation of brain vigilance in work process, we designed addition and subtraction experiment with numbers of three digits to induce the vigilance to change, combined it with psychomotor vigilance task (PVT) to measure this process of electroencephalogram (EEG), extracted and analyzed permutation entropy (PE) of 11 cases of subjects' EEG and made a brief comparison with nonlinear parameter sample entropy (SE). The experimental results showed that: PE could well reflect the dynamic changes of EEG when vigilance decreases, and has advantages of fast arithmetic speed, high noise immunity, and low requirements for EEG length. This can be used as a measure of the brain vigilance indicators.
Attention ; Brain ; physiology ; Electroencephalography ; Entropy ; Humans ; Mathematics