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.

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

Mental fatigue is an important factor of human health and safety. It is important to achieve dynamic mental fatigue detection by using electroencephalogram (EEG) signals for fatigue prevention and job performance improvement. We in our study induced subjects' mental fatigue with 30 h sleep deprivation (SD) in the experiment. We extracted EEG features, including relative power, power ratio, center of gravity frequency (CGF), and basic relative power ratio. Then we built mental fatigue prediction model by using regression analysis. And we conducted lead optimization for prediction model. Result showed that R2 of prediction model could reach to 0.932. After lead optimization, 4 leads were used to build prediction model, in which R' could reach to 0.811. It can meet the daily applicatioi accuracy of mental fatigue prediction.
Electroencephalography ; Humans ; Mental Fatigue ; Models, Biological ; Sleep Deprivation

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 analyze the distribution and subcellular localization of NOR1 alternative splice isoforms in human tissues and cell lines. Methods NOR1 open reading frame(ORF) was amplified from human fetal brain cDNA library and subcloned into pCMV/myc vector. The level of NOR1 mRNA in human tissues was determined by real-time RT-PCR. Region spanning exon 2 was amplified from cDNA or genomic DNA by specific primers and sequenced. The expression plasmids of NOR1 were transfected into cells and immunofluoresence assay was performed to determine the subcellular localization of NOR1 protein isoforms in human cells. Results The expression of NOR1 mRNA was high in human adult testis, moderate in human fetus nasopharynx, trachea, brain, and kidney tissues, and weak or undetectable in other tissues. Two splice variants of human NOR1 gene resulted from alternative splicing at exon 2 were identified. Both of isoform 1 and isoform 2 mRNA were detected in human fetus brain. Isoform 2 was the sole isoform in other tissues but brain. Only isoform 2 mRNA was detected in cell lines used in this study, though no genomic deletion of exon 2 could be found in all these cell lines. Immunofluoresence assay showed both isoform 1 and isoform 2 proteins were distributed in cytoplasm. Conclusion Alternative splice isoforms of tumor suppressor gene NOR1 are identified. NOR1 isoform 1 and isoform 2 are both detected in fetus brain. NOR1 isoform 2 lacking of exon 2 is the sole isoform in multiple tissues except for brain. The exon 2 encoded peptide does not affect the subcellular location of NOR1 protein.

Clinical practice is a key step that seven-year clinic student take to become doctors.Take the First Affiliated Hospital of Xi'an Jiaotong University as an example,in the medical practice of seven-year clinic students,there still exist some problems such as students' being unable to transform from probationers to doctors,not good at treating with interpersonal relationship in the department and having no perseverant practice attitude.So training before practice should be perfected and supervision should be strengthened to make the seven-year clinic students better.