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.

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.

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

Objective:To observe the effect of electroacupuncture (EA) at Jiaji (EX-B 2) points plus hydro-acupuncture with sinomenine hydrochloride for low back pain caused by compression fractures in the elderly.Methods:Ninety-five elderly in-patients with low back pain caused by compression fractures were randomly divided into an observation group and an EA group according to the visit sequence.Both groups received the same basic treatment.In the EA group,48 cases were treated with EA at Jiaji (EX-B 2) points plus the basic therapy;47 cases in the observation group received the basic treatment plus EA and hydro-acupuncture with sinomenine hydroch｜oride at Jiaji (EX-B 2) points.The levels of osteoprotegerin (OPG) and interleukin-1β (IL-1β) in peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA) before and at the 21st day of treatment in both groups.Oswestry disability index (ODI) and visual analog scale (VAS) scores were used to analyze the clinical efficacy.Results:After treatment,the OPG content in the observation group was higher with statistical significance compared with that before treatment in the observation group and after the treatment in the EA group,respectively (both P＜0.05);the content of IL-1β,ODI and VAS scores were lower than those before treatment in the observation group and after treatment in the EA group with statistical significances (all P＜0.05).Conclusion:The combination of EA and hydro-acupuncture with sinomenine hydrochloride at Jiaji (EX-B 2) points is effective for low back pain caused by compression fractures in the elderly,and is superior to EA at Jiaji (EX-B 2) points alone.

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

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.

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.