BackgroundTenofovir disoproxil fumarate has been recommended for pre-exposure prophylaxis (PrEP) to prevent HIV infection. Several studies have shown short but potent intermittent PrEP could provide comparable protection to daily PrEP in men, suggesting such dosing strategy might be useful in Chinese as well. The objective of this study was to evaluate the impact of different dosing strategies on plasma concentrations of tenofovir.MethodsAn open label study in 40 Chinese healthy volunteers, randomized to receive the WHO-recommended dose of tenofovir (300mg) at four different dosing intervals: twice weekly for 4 weeks; once daily for 4 weeks with one missing dose in weeks 2–4; once daily for 4 weeks with two missing doses in weeks 2–4; and once every other day for 12 days. Plasma samples were collected at pre-dose, weekly trough and 24h post last dose and assayed using HPLC-UV.ResultsThe tenofovir trough concentrations were below the lower limit of quantification with the twice weekly regimen. The trough concentrations (24h dosing interval) at the steady state were 51.7±12.1ng/ml and 53.5±13.8ng/ml (mean±SD) in the once daily groups. Missing doses, once or twice weekly, had no significant impact on trough concentrations. Prolongation of dosing interval to 48h resulted with concentrations at 24h and 48h (trough) of ∼40 and 20ng/ml, respectively.ConclusionsIntermittent tenofovir regimens resulted with remarkably low plasma concentrations in Chinese participants. Missing doses did not affect trough concentrations significantly.

As a first-line tuberculostatic drug, isoniazid (INH) plays effective and irreplaceable role in prevention and treatment of tuberculosis. In this work, a rapid and simple signal-on fluorescence approach is established for INH assay by employing a platform composed of silver nanoclusters (AgNCs) and MnO2 nanosheets. In the proposed sensing system, strong red fluorescence of poly (methacrylic acid)-stabilized AgNCs can be greatly quenched after they attach to the surfaces of MnO2 nanosheets. With the addition of INH, MnO2 nanosheets are reduced to Mn2+ and subsequently release the AgNCs, which leads to obvious fluorescence recovery again. Based on this mechanism, highly sensitive detection of INH in the range of 0.8–200 μM is realized (detection limit: 476 nM). The present strategy shows remarkable advantages including simplicity, rapidness, high sensitivity and wide detectable range. This method is also practical and comparable to high-performance liquid chromatography, which can be applied to detect INH in human urine and serum samples as well as pharmaceutical products.

Aiming at the establishment of a sensitive and specific diagnostic method for early heart failure (HF), we developed a cost-effective fluorescence resonance energy transfer (FRET) platform for the detection of B-type natriuretic peptide (BNP), a characteristic biomarker of HF. Graphene oxide (GO) was selected as the FRET receptor in view of its advantages including commercial availability, low-cost and chemical stability, and dye-modified aptamer was used as the energy donor of FRET as well as in charge of the specific recognition of BNP. Based on the ON (strong emission) and OFF (quenching) states of FRET in the presence and absence of BNP, respectively, specific detection of BNP was achieved in the range 0.074–0.56 pg/mL with a limit of detection as low as 45 fg/mL (3σ). This FRET platform was applied to detect BNP in 45 blood samples to demonstrate its practicability in clinical diagnosis. Compared to the commonly used Siemens method (chemiluminescence immunoassay, CLIA) in hospital, our approach is more accurate and specific for HF diagnosis with areas under the receiver operating characteristic curves of 0.869 (95% CI 0.733–1.00, P < 0.05) vs 0.850 (95% CI 0.703–0.997, P < 0.05) and specificity of 68.8% vs 65.6%. This platform is promising in early diagnosis of HF through ultrasensitive and specific detection of BNP.

A sensitive and reliable method based on environment test chamber coupled with thermal desorption and gas chromatography-mass spectrometry (ETC-TD-GC/MS) was developed and validated for the determination of 103 volatile organic compounds (VOCs) emitted from mattresses. In the study, two commercial sorbent tubes were compared in terms of adsorption efficiency towards the target analytes. The result illustrated that the multisorbent tubes containing Carbopack C, Carbopack B and Carboxen 1000 had better performance than Tenax TA tubes owing to their large surface area, low capacity for water and high temperature stability, which allowed a wide range of VOCs to be absorbed, especially for VOCs with low boiling points and small molecules. To achieve the optimum conditions for the analysis, several thermal desportion parameters were accurately investigated. Under the optimal conditions, the method showed good linearities, with correlation coefficients ranging from 0.9982 to 0.9999 and the method detection limits and method quantification limitsfor target compounds in the range of 0.006 similar to 0.561 mu g/m(3) and 0.020 similar to 1.870 mu g/m(3), respectively. In order to evaluate the performance of the developed method on real samples, various mattresses from different manufacturers were analysed. All mattress samples were found to emit VOCs and the values of area-specific emission rate (SERs) for total target compounds were in the range of 90.25 similar to 288.63 mu g/m(2)center dot h. Moreover, the SERs of VOCs were influenced by the type of sponge materials and mattress fabric layers. The study demonstrated that the method is sensitive, accurate and well-suited for the determination of VOCs emitted from mattresses.

目的 探讨芪术润肠汤对习惯性便秘的临床疗效.方法 选取2017年11月至2018年11月符合习惯性便秘诊断标准的患者120例,按随机数表法分为对照组和观察组,每组各60例;对照组服用麻仁丸,观察组服用芪术润肠汤汤剂,观察两组用药后的临床疗效及不良反应.结果 治疗前,两组排便率比较,差异无统计学意义(P＞0.05);治疗后,观察组排便时间间隔总有效率为90.00％,对照组为63.33％,差异有统计学意义(P＜0.05);治疗后观察组粪便干结总有效率为93.33％,对照组为55.00％(P＜0.05);对照组与观察组治疗前排便费力程度比较,差异无统计学意义(P＞0.05),治疗后观察组治疗总有效率为91.67％,对照组58.33％,差异有统计学意义(P＜0.05);治疗后观察组口干、腹痛、腹胀及纳差控制率和总有效率均优于对照组,差异有统计学意义(P＜0.05).依据中医症候疗效评价标准:观察组痊愈19例、显效28例、有效11例,总有效率为96.67％,对照组痊愈3例、显效22例、有效26例,总有效率为85.00％,差异有统计学意义(P＜0.05).结论 中医辩证为脾虚气弱、阴虚肠燥证型的习惯性便秘采用芪术润肠汤治疗效果明显,值得临床推广使用.

Baicalin (BCL) is a flavonoid compound with demonstrated potential therapeutic benefits, but the clinical advancements are limited mainly due to its poor aqueous solubility. A guest-host supermolecular inclusion complex of mono-6-O-α-maltosyl-β-cyclodextrin (G2-β-CD) with BCL was developed to improve the aqueous solubility of BCL. The resultant inclusion complex was characterized by DSC, FT-IR, P-XRD, 1HNMR, 2D-ROESY and SEM analysis. Solubility test suggested that G2-β-CD markedly improved the solubility of BCL and showed AL type phase diagrams. The spectral shifts suggested that the phenyl moiety is buried deeper than the chromen moiety and protrudes from the 6-hydroxyl side of G2-β-CD. Molecular docking verified the experimental findings and supported the insertion of benzene ring of BCL into G2-β-CD cavity via hydrophobic interactions and possible hydrogen bonds. The enhanced bioavailability of the inclusion complex was reflected in earlier Tmax, higher Cmax and larger AUC0-∞ than that of BCL after its oral administration. Taken together, these findings suggested that the solid inclusion complex BCL-G2-β-CD may serve as valuable BCL solid dosage form with good solubility and dissolution rate.

为了促进学生毕业实习质量的提高,文章首先论述了药学专业毕业实习的现状,接着阐述了药学专业毕业实习实施策略,包括建立行之有效的组织与管理制度、完善教师的指导方法、建立有效的过程监控管理制度、建立有效的毕业实习信息反馈系统.

Objective:To establish an HPLC method for the determination of the concentration of targeted antitumor drugs luteolin in rat plasma,and to study the pharmacokinetics of luteolin and its sulfobutyl ether-β-cyclodextrin (SBE-β-CD) inclusion complex in rat.Methods:SD rats with luteolin and luteolin/SBE-β-CD inclusion complex were given by intragastric administration and intravenous injection in 2 ways,respectively.Plasma samples were pretreated by water bath and liquid-liquid extraction,detected by HPLC,diosmetin was employed as an internal standard.The separation was performed on a ZORBAX SB-C18 (4.6 mm × 250 mm,5 μm) column and the mobile phase consisted of 0.2％ H3PO4-methanol (48∶52) at a flow rate of 1.0 mL· min-1,and the detection wavelength was 348 nm.The DAS pharmacokinetic program was used to calculate the relevant pharmacokinetic parameters.Results:The average entrapment efficiency of luteolin/SBE-β-CD inclusion complex was 75.94％.Luteolin in rat plasma had a good liner relationship in concentration range in 0.06-13.00 μg· mL-1.The extraction recovery (n=5) and the RSD of luteolin were within 72.19％-86.62％ and 5.60％-12.77％,respectively.Conclusion:The method conforms to the basic requirements of methodology validation and is suitable for the determination of luteolin in rat plasma and can be used for pharmacokinetic studies.The elimination of luteolin in rats conformed to two compartment model elimination.Compared with luteolin,the Tmax advance and the AUC increase which resulted in an improved bioavailability in luteolin/SBE-β-CD inclusion complex.

OBJECTIVE:To investigate the anti-cancer effect of Polygonatum sibiricum polysaccharides (PSP) and the underlying mechanism.METHODS:Tumor-bearing mice were randomly divided into normal saline (NS) group, adriamycin (ADM) group, PSP group and lipopolysaccharide (LPS) group. RAW264.7 cells were pre-treated with or without TLR4 inhibitor or MyD88 inhibitor. Quantitative RT-PCR and Western blot were performed to detect the mRNA and protein expressions, respectively. ELISA and Griess reaction was used to measure cytokines and NO levels. Flow cytometry was employed to examine T-lymphocyte subset and CCK-8 assay was used for cell viability.RESULTS:The in vivo experiment found that PSP inhibited tumor growth and improved the spleen index, thymus index, the cytokines secretion and CD4+/CD8+ lymphocytes ratio. Compared with the NS group, the mRNA and protein expressions of the critical nodes inTLR4-MAPK/NF-κB signaling pathways (except TRAM) significantly increased in PSP group, as well as the NO and cytokines levels. Nevertheless, PSP had no obvious effects on TRAM. Further analysis showed that PSP effects on the critical nodes in TLR4-MAPK/NF-κB signaling pathways were suppressed by inhibitor in vitro.CONCLUSION:The immunoenhancement effect of PSP against lung cancer is mediated by TLR4-MAPK/NF-κB signaling pathways.

建立了同时检测软体家具面料中40种挥发性有机物的环境舱-热脱附-气质联用(ETC-ATD-GC/MS)检测方法.以Tenax TA吸附管吸附环境舱内不同面料中释放的挥发性有机物,经热脱附仪加热,将挥发性有机物脱附后随载气进入GC/MS进行定性和定量分析.考察了吸附管脱附温度、脱附时间,冷阱温度等不同参数对挥发性有机物的脱附效率的影响.结果表明,40种挥发性有机物在2～200 ng质量范围内呈良好的线性关系,相关系数在09949～0.9999之间,方法的检测限为0.011～0.277μg/m3.方法回收率为88.0％ ～109.9％,相对标准偏差在1.5％ ～9.5％之间.方法适用于不同软体家具面料中挥发性有机物的定量分析.

An analytical method for simultaneously determining 32 volatile organic compounds in mattress fabrics based on static headspace coupled to gas chromatography and mass spectrometry detection was established. Samples were cut into 5x5mm small pieces and placed in a 20mL headspace vial at 90 degrees for 30min. To achieve the optimum conditions for the analysis, several parameters including the heating temperature, heating time, sample weight, and injection time were investigated. The results demonstrated that the most important parameter influencing the sensitivity of the analysis was the heating temperature. The optimum method showed good linearities with correlation coefficients ranged from 0.9944 to 0.9998. The limits of detection and quantification for the target compounds were in the ranges of 0.004-0.032 and 0.013-0.099 mu g/g, respectively. The method was successfully applied to determine the volatile organic compounds in six categories of mattress fabrics. The results showed that some volatile organic compounds were found, such as naphthalene, hexadecane, and 1,4-diisopropylbenzene. Moreover, the concentrations of 32 volatile organic compounds decreased following the order of jute, terylene, polyester, velboa, nylon, and cotton samples in the study. These results indicated that the method is fast, accurate, and successful for determining volatile organic compounds in mattress fabrics.

Backgrounds: Diabetes mellitus (DM)-induced morphological and/or functional complications may alter the pharmacokinetic profiles of mangiferin. This study aims to compare pharmacokinetic profiles of mangiferin in normal and alloxan-induced diabetic rats after oral and intravenous administration. Methods: Mangiferin was administered orally (10 mg/kg) and intravenously (2 mg/kg) to normal and alloxan-induced diabetic Sprague-Dawley (SD) rats (n = 8). Blood samples were collected at different time points post-dose. Mangiferin and esculentoside (internal standard) were analyzed by Waters Acquity ultra-performance liquid chromatography system and TSQ Quantum Ultra triple quadrupole mass spectrometer (UPLC-MS/MS). Results: Mangiferin in normal and alloxan-induced diabetic rats experienced serious first-pass effect, which resulted in 1.71 and 0.80% of oral bioavailability respectively. Meanwhile, mangiferin was predominantly restricted to blood but not extensively distributed to organ tissues after intravenous administration. Compared with normal rats, the diabetic condition induced 53.26 and 50.90% decreases in Cmax and AUC0–t, respectively, for mangiferin after oral administration, and 63.08% decreases in Cmax after intravenous administration. Conclusions: Compared to normal rats, pharmacokinetic parameters of mangiferin were altered in diabetic condition induced by alloxan. The findings might help to provide useful evidence for modeling of diabetic rats and the clinical applications of mangiferin.

Alendronate sodium (ALDS) is an important and regularly used medicine in clinical therapy of osteoporosis. In this work, a new analytical method is developed for the detection of ALDS based on a fluorescent-platform of copper(II)-mediated silver nanoclusters (AgNCs). Specifically, Cu2+ can selectively bind with DNA-stabilized AgNCs and thus greatly quench their red fluorescence. In the presence of ALDS, their fluorescence can largely recover again owing to the stronger coordination of ALDS with Cu2+. On the basis of such a mechanism, fluorescence "on-off-on" mode of the nanoprobe is applied to detect ALDS in a wide linear range of 800 pM-200 mu M, with a detection limit of 100 pM. Compared with previously reported methods, the present approach has significant advantages regard to simplicity, high sensitivity, and a wide detectable concentration range. This method has been successfully applied in ALDS assay in tablets and human body fluids. (c) 2018 Elsevier B.V. All rights reserved.

Ni2+-agarose bead-wrapped multi-enzyme/inorganic hybrid sphere composed of the immobilized enzymes as organic component and NaH2PO4 and NaCl as inorganic component was developed by co-immobilizing extracellular His-tagged 3-quinuclidinone reductases and glucose dehydrogenase without pre-purification. The resulting biocatalysts has 3D porous architectures as confirmed by SEM and FESEM, and it enabled the continuous biotransformation of 3-quinuclidone to (R)-3-quinuclidinol with cofactor regeneration in situ. The 3D porous biocatalysts were formed via three steps: First, immobilization of the His-tagged enzymes directly from the cell lysates supernatant. Next, formation of enzyme aggregates, ribbons and gels. Finally, the enzymes, the formed aggregates/ribbons/gels and salt were incorporated to the foam and then covered the Ni2+-agarose bead. The technique made the immobilization of these enzymes effective such that specific enzyme loading of 60.8 mg/g support and enzyme loading efficiency of 92.3% were achieved. As a direct consequence, the biocatalyst catalyzed the conversion of 3-quinuclidinone (204 g/L) to (R)-3-quinuclidinol in 100% yield and 100% ee at 4.5 h, and the recyclability of the biocatalyst was excellent, retaining > 95% conversion yield and 100% ee even after the fifteenth runs. Overall, our strategy is demonstrated to be a promising method for developing efficient and robust biocatalyst for asymmetric synthesis.

ObjectivesBaicalin (BCL) has potential therapeutic benefits, but its clinical outcomes are restricted mainly because of low water solubility. This study sought to improve the water solubility of BCL by the formation of inclusion complex with -cyclodextrin (-CD).MethodsThe inclusion complex was studied by solubility test, differential scanning calorimeter (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), H-1 Nuclear magnetic resonance ((HNMR)-H-1) and scanning electron microscopy (SEM). Molecular docking was conducted to verify the experimental findings. The dissolution rate was determined by dialysis membrane method. In vivo absorption studies in rats were conducted and high-performance liquid chromatography (HPLC) was used to analyse the plasma level of BCL after oral administration.Key findingsThe DSC, FTIR, XRD, (HNMR)-H-1 and SEM findings suggested the formation of inclusion complex between BCL and -CD in 1 : 1 stoichiometry. Molecular docking demonstrated the insertion of benzene ring of BCL into -CD cavity by hydrophobic interactions and possible H-bond formation. Moreover, -CD markedly improved the solubility of BCL and displayed A(L)-type phase diagrams. The improvement in dissolution rate of the inclusion complex was reflected in the earlier T-max, higher C-max and larger AUC(0-t) than that of BCL after oral administration.Conclusions-cyclodextrin complex can be used as an effective formulation strategy for development of BCL-loaded delivery system with better therapeutic outcomes.

A simple and rapid high-performance liquid chromatography method with electrochemical detection employing boron-doped diamond electrode (BDD) was established for simultaneous determination of eleven bioamines with their precursor amino acids and metabolites, including two precursors (tyrosine and tryptophan), three catecholamines (dopamine, norepinephrine and epinephrine) and their four metabolites (3,4-dihydroxyphenylacetic acid, 3-methoxytyramine, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol), as well as serotonin and its metabolite (5-hydroxyindoleacetic acid), in a single run of 20 min using vanillic acid as internal standard. The separation was performed on an ODS2 column (250 mm × 4.6 mm, 5.0 μm) with column oven temperature of 30 °C. Quantification was accomplished at an oxidation potential of 700 mV vs Ag/AgCl reference electrode after a range of applied voltages were tested. Several parameters of this new chromatographic method were validated after optimizaton of the analytical conditions. The new method was successfully applied to test cortex and hippocampus samples from Sprague-Dawley rats with good separation. These eleven compounds in cortices and hippocampi were compared, which was used for monitoring their variations in neuroscience research.

Introduction: Combretastatins, which are excellent anticancer agents, are isolated from Combretum. A sensitive ultra-performance liquid chromatography tandem mass spectrometry method was developed and validated for the pharmacokinetic study of a combretastatin analog (C4NP) in rats. Methods: Sample pretreatment was finished by simple protein precipitation in which methanol was added to plasma containing an internal standard (buspirone hydrochloride). Liquid chromatograph separation was accomplished on a reverse-phase Kinetex XB-C18 column [50 × 4.6 mm; internal diameter: 2.6 μm (Phenomenex, Torrance, CA, U.S.A.)] with a gradient mobile phase of acetonitrile (0.05% formic acid, volume for volume) and water (0.05% formic acid) at a flow rate of 0.3 mL/min. The analytes were analyzed in the positive ion by electrospray ionization and quantified in the selective reaction monitoring mode. The entire procedure was validated following the U.S. Food and Drug Administration guidelines for bioanalytical methods validation. Results: Our study investigated, for the first time, the detection and pharmacokinetic characteristics of C4NP in Sprague–Dawley rat plasma. The pharmacokinetic results suggest that C4NP is predominantly restricted to blood or extracellular fluid and is not extensively distributed to most organ tissues. In addition, C4NP can be cleared by renal filtration and active tubular secretion in Sprague–Dawley rats. Toxicokinetics of C4NP in these rats indicate that no saturation of the metabolic or excretion process occurs for C4NP, and metabolic induction and accumulation of toxic injury from multiple dosing are both absent. Conclusions: For 100 μL of analyte, recovery plus high accuracy and reproducibility indicate that our new ultra-performance liquid chromatography tandem mass spectrometry method is a reliable and high-throughput analytical tool for the pharmacokinetic study of C4NP in rats. Those results should be useful for risk assessment.

专业学位教育是我国现阶段研究生培养的热点,探索适应社会需求的药学(药物分析方向)专业学位硕士研究生的培养模式是目前我校拯待解决的问题.本文通过查阅国内外各高校培养方案并结合我校实际情况形成了课程设置的内容及考核方式,确定了实践环节的培养方案及保障措施.对药学专业学位硕士研究生的培养需要从业务要求、培养方式及其保障措施等环节来保证培养质量.

Supramolecular assemblies generated from self-assembling β-cyclodextrin-modified montmorillonite nanosheets were evaluated as anticancer drug carriers in vitro. The results showed that the assemblies had a high loading capacity of 5-fluorouracil (5-FU) under the optimized conditions that included a temperature of 80 °C and a pH level of 11. Scanning electron microscopy (SEM) images showed no morphological changes in the assemblies even after 20 days of storage at room temperature. Moreover, SEM and atomic force microscopy (AFM) observations revealed that the incorporation of 5-FU hardly affected the morphology of the assemblies. Furthermore, the assemblies showed sustained release behavior in vitro, and SEM and AFM analyses indicated that the kinetics of 5-FU release were closely associated with morphological changes in the surface of the assemblies during drug release. Cell viability assays showed that the blank assemblies had low cytotoxicity against A549 cells, while the inhibitory effects of 5-FU-loaded assemblies against A549 cells increased significantly with an increased concentration. More importantly, fluorescence microscopy imaging and transmission electron microscopy (TEM) demonstrated that both blank assemblies and 5-FU-loaded assemblies can easily penetrate cultured human ovarian cancer SKOV3 cells. These results suggest that the supramolecular assemblies may potentially be used as building blocks for the development of new anti-cancer drug delivery systems.