Exosomes,ubiquitously present in body fluids,serve as non-invasive biomarkers for disease diagnosis,monitoring,and treatment.As intercellular messengers,exosomes encapsulate a rich array of proteins,nucleic acids,and ...Exosomes,ubiquitously present in body fluids,serve as non-invasive biomarkers for disease diagnosis,monitoring,and treatment.As intercellular messengers,exosomes encapsulate a rich array of proteins,nucleic acids,and metabolites,although most studies have primarily focused on proteins and RNA.Recently,exosome metabolomics has demonstrated clinical value and potential advantages in disease detection and pathophysiology,despite significant challenges,particularly in exosome isolation and metabolite detection.This review discusses the significant technical challenges in exosome isolation and metabolite detection,highlighting the advancements in these areas that support the clinical application of exosome metabolomics,and illustrates the potential of exosomal metabolites from various body fluids as biomarkers for early disease diagnosis and treatment.展开更多
The as-cast Mg2Ni-type Mg20–xYxNi10 (x=0, 1, 2, 3 and 4) electrode alloys were prepared by vacuum induction melting. Subsequently, the as-cast alloys were mechanically milled in a planetary-type ball mill. The analys...The as-cast Mg2Ni-type Mg20–xYxNi10 (x=0, 1, 2, 3 and 4) electrode alloys were prepared by vacuum induction melting. Subsequently, the as-cast alloys were mechanically milled in a planetary-type ball mill. The analyses of scanning electron microscopy (SEM), X-ray diffraction (XRD) and transmission electron microscopy (TEM) reveal that nanocrystalline and amorphous structure can be obtained by mechanical milling, and the amount of amorphous phase increases with milling time prolonging. The electrochemical measurements show that the discharge capacity of Y0 alloy increases with milling time prolonging, while that of the Y-substituted alloys has a maximum value in the same condition. The cycle stabilities of the alloys decrease with milling time prolonging. The effect of milling time on the electrochemical kinetics of the alloys is related to Y content. Whenx=0, the high rate discharge ability, diffusion coefficient of hydrogen atom, limiting current density and charge transfer rate all increase with milling time prolonging, but the results are exactly opposite whenx=3.展开更多
Aim To investigate novel bioactive and structural metabolites from marineorganisms. Methods Column chromatography in association with semi-preparative HPLC were used for theisolation of compounds. 1D and 2D NMR, IR, U...Aim To investigate novel bioactive and structural metabolites from marineorganisms. Methods Column chromatography in association with semi-preparative HPLC were used for theisolation of compounds. 1D and 2D NMR, IR, UV, and MS were employed for structure elucidation.Results From the butanol fraction of the 95% EtOH extract of the starfish Asterias rollestoni, a newcompound N^7 -2'-deoxypseudoxanthosine (1), along with sixteen known compounds, 2'-0-methyl-inosine(2), 2'-deoxyinosine (3), 2'-0-methylguanosine (4), inosine (5); thymine (6), uracil (7), thymidine(8), deoxyuridine (9), 2'-0-methyluridine (10), ( ― )-(1S, 3S)-1-methyl-1, 2, 3,4-terrahydro-β-carboline-3-carboxyl-ic acid (11), ( ― )-(1R, 3S)-1-methyl-1, 2, 3,4-tetrahydro-β-carboline-3-carboxylic acid (12) , ( ― )-(3S)- 1, 2, 3,4-tetrahydro-β-carboline-3-carboxylic acid (13), L-tryptophan (14), L-phenylalanine (15), 3-carboxyindole (16), and p-hydroxybenzoic acid (17) , have been isolated. Conclusion Compound 1 is a newnatural product, and compounds 8, 9 and 10 are isolated from natural sources for the first time, andthe known compounds except 14 and 15 are first reported from starfish Asterias rollestoni.展开更多
The La-Mg-Ni-based A2B7-type La0.8-xNdxMg0.2Ni3.15Co0.2Al0.15 (x=0, 0.1, 0.2, 0.3, 0.4) electrode alloys were prepared by casting and annealing. The influences of partial substitution of Nd for La on the structure a...The La-Mg-Ni-based A2B7-type La0.8-xNdxMg0.2Ni3.15Co0.2Al0.15 (x=0, 0.1, 0.2, 0.3, 0.4) electrode alloys were prepared by casting and annealing. The influences of partial substitution of Nd for La on the structure and electrochemical performance of the as-cast and annealed alloys were investigated. It was found that the experimental alloys consist of two major phases, (La, Mg)2Ni7 phase with the hexagonal Ce2Ni7-type structure and LaNi5 phase with the hexagonal CaCu5-type structure, as well as some residual phase LaNi3 and NdNi5. The discharge capacity and high rate discharge ability (HRD) of the as-cast and annealed alloys first increase and then decrease with Nd content growing. The as-cast and annealed alloys (x=0.3) yield the largest discharge capacities of 380.3 and 384.3 mA·h/g, respectively. The electrochemical cycle stability of the as-cast and annealed alloys markedly grows with Nd content rising. As the Nd content increase from 0 to 0.4. The capacity retaining rate (S100) at the 100th charging and discharging cycle increases from 64.98% to 85.17% for the as-cast alloy, and from 76.60% to 96.84% for the as-annealed alloy.展开更多
To evaluate the effect of components in Guanxin Ⅱ prescription on the pharmacokinetic profiles of paeoniflorin. Plasma concentration of Paeoniflorin in rats after intravenous injection of Paronia Pall Extract (PPE)...To evaluate the effect of components in Guanxin Ⅱ prescription on the pharmacokinetic profiles of paeoniflorin. Plasma concentration of Paeoniflorin in rats after intravenous injection of Paronia Pall Extract (PPE) and oral administration of PPE and three types of decoctions in Guanxin Ⅱ prescription, respectively, were determined by HPLC analyses. NONMEM (nonlinear mixed-effect modeling) method was used to analyze full set of pharmacokinetic data directly. A two-compartment model with first-order degradation in absorption compartment was employed for the data analysis. The mean of population parameters, CL1, V1, CL2, V2, Ka0, and Kal, were measured to be 0.509 L/h, 0.104 L, 0.113 L/h, 0.123 L, 0.135/h, and 0.0135/h, respectively. Inter-individual variabilities were estimated and dose formulation (DF) was identified as a significant covariate of Ka 1, Ka0, and V1. It is concluded that the pharmacokinetic behaviors of paeoniflorin in rats can alter with different dose formulations.展开更多
Aim To study the pharmacokinetics of oxiracetam after single and multipleintravenous administrations in healthy volunteers. Method A HPLC method was used to determine theserum concentration of oxiracetam after intrave...Aim To study the pharmacokinetics of oxiracetam after single and multipleintravenous administrations in healthy volunteers. Method A HPLC method was used to determine theserum concentration of oxiracetam after intravenous single dose and daily dose of 2 000 mg for 7 din ten Chinese healthy volunteers. Pharmacokinetic analysis was carried out using Drug And Statisticsoftware. Results The AUC_(0-12), AUC_(0-∞), K_e, t_(1/2), MRT after a single dose of 2 000 mgoxiracetam were 256.26 ± 16.84 μg·mL^(-1)·h, 276.74 ±18.11 μg·mL^(-1)·h, 0.18 ±0.03 h^(-1),3.84±0.64 h, and 4.39 10.39 h, and after multiple doses of oxiracetam were 259.36 ±25.43μg·mL^(-1)·h, 285.59 ±27.38 μg·mL^(-1)·h, 0.17 ±0.04 h^(-1), 4.14 ± 0.82 h, and 4.87 ±0.69 h, respectively. Conclusion The pharmacokinetic parameters of oxiracetam do not differremarkably after single and multiple intravenous administration and there is accumulation in serumafter 2 000 mg multiple intravenous administration once a day fof 7 d.展开更多
To deal with the data mining problem of asymmetry misclassification cost, an innovative churn prediction method is proposed based on existing churn prediction research. This method adjusts the misclassification cost b...To deal with the data mining problem of asymmetry misclassification cost, an innovative churn prediction method is proposed based on existing churn prediction research. This method adjusts the misclassification cost based on the C4. 5 decision tree as a baseline classifier, which can obtain the prediction model with a minimum error rate based on the assumption that all misclassifications have the same cost, to realize cost-sensitive learning. Results from customer data of a certain Chinese telecommunication company and the fact that the churners and the non-churners have different misclassification costs demonstrate that by altering the sampling ratio of churners and non-churners, this cost-sensitive learning method can considerably reduce the total misclassification cost produced by traditional classification methods. This method can also play an important role in promoting core competence of Chinese telecommunication industry.展开更多
Aim To study the pharmacokinetics of remifentanil in Chinese aduh patients undergoing elective surgery and compare the results with the data already published. Methods The pharmacokinetics of remifentanil was determin...Aim To study the pharmacokinetics of remifentanil in Chinese aduh patients undergoing elective surgery and compare the results with the data already published. Methods The pharmacokinetics of remifentanil was determined in 10 aduh patients undergoing elective surgery. Remifentanil 5 - 6 μg·kg^-1 was administered within 1 min after the induction of anesthesia. One point five millilitre of arterial blood samples were collected at 0 (baseline), 1,2, 3, 5,7, 10, 15, 20, 25, 30, 45, 60, and 90 min after drug administration. Remifentanil concentration was assayed by HPLC/MS/MS. Resuits The concentration-time course of remifentanil was best described by a two-compartment model. Total clearance (CL = 2. 149 ± 0. 431 L·min^-1) of remifentanil was greater than the normal hepatic blood flow. The distribution half-life (t1/2α) [ 1.56 ± 0. 52 min (0.73 - 2.31 ) ] and the elimination half-life (t1/2β) [22.07 ± 10.30 min (9, 71 -36.07)] were similar with those in previous reports. Volume of distribution ( Vd = 65. 766 ± 29. 100 L) was about two times greater than that reported in previous studies of other ethnics. Conclusion In the present study, the volume of distribution is significantly greater than thai reported in previous studies of other ethnics, indicating that there are some differences in the pharmacokinetics of remifentanil among different ethnics.展开更多
Aim To establish a new and sensitive HPLC-MS method for the determination ofzolmitriptan in human plasma and study the pharmacokinetics of zolmitriptan in healthy volunteers.Methods A single oral dose of 5 mg of zolmi...Aim To establish a new and sensitive HPLC-MS method for the determination ofzolmitriptan in human plasma and study the pharmacokinetics of zolmitriptan in healthy volunteers.Methods A single oral dose of 5 mg of zolmitriptan tablet was given to 20 healthy male volunteers.After dosing, blood samples were collected for a period of 24 h, and zolmitriptan concentration inplasma was analyzed by HPLC-MS. Results The plasma concentration-time course fitted well atwo-compartment open model with a lag time, giving the following pharmacokinetic parameters: T_(max)1.60 ± 0.24 h, C_(max) 9.73 ± 1.43 ng·mL^(-1). T_(1/2α)1.72±0.46 h, T_(1/2β) 4.52 + 0.97 h,and AUC_(0-t) 55.59 ± 5.12 ng·mL^(-1)·h. Conclusion The improved analytical method forzolmitriptan is rapid, sensitive and suitable for application to pharmacokinetic studies and routinedetermination of numerous samples.展开更多
Puts forward an algebraic structure of the Chaplygin's equations of nonholonomic systems, establish the Poisson's theory of the integration equations and gives an example for illustrating the application of th...Puts forward an algebraic structure of the Chaplygin's equations of nonholonomic systems, establish the Poisson's theory of the integration equations and gives an example for illustrating the application of the result.展开更多
To test and study the Syndrome and Treatment Pharmacokinetics (S & TRK),we studied the pharmacokinetics of ferulic acid in healthy and blood stasis (microcirculation dysfunction)rabbits by RP-HPLC. After a single ...To test and study the Syndrome and Treatment Pharmacokinetics (S & TRK),we studied the pharmacokinetics of ferulic acid in healthy and blood stasis (microcirculation dysfunction)rabbits by RP-HPLC. After a single intravenous injection offenilic acid(5mg/kg)to healthy and blood stasis rabbits, compartment model of ferulic acid serum concentration was fitted and then pharmacokinetic parameters were calculated with a MCPKP program on a COMPAQ 386 compute Important parameters are as follows: In healthy rabbits V_B=0.9525±0.0211 L/kg,V_1=0.2462±0.0381 L/kg, CL_B=1.8133±0.9512 L/h·kg, T_(1/2β)=0.3639±0913, AUC=2.7566±0.8232 μg·h/ml; In blood stasis rabbits V_B=0.7882±0.0321 L/kg,V_1=0.1966±0.0537 L/kg,CL_B=0.8820±0.5481 L/h·kg,T_(1/2β)=0.6193±0.1216 h, AUC=5.6690±2.3541μg·h/ml.Through this experiment we found the sig-nificant differences in the FA's pharmacokinetic parameters between healthy and blood stasis rabbits.The results obtained correspond with S & TPK.展开更多
Ahn To develop a high resolution HPLC method for the determination of ondansetron in human plasma and to study the pharmacokinetics of ondansetron in orally disintegrating tablets. Methods HPLC determination involved ...Ahn To develop a high resolution HPLC method for the determination of ondansetron in human plasma and to study the pharmacokinetics of ondansetron in orally disintegrating tablets. Methods HPLC determination involved liquid-liquid extraction, separation on a CN column and ultraviolet detection at 310 ran with granisetron as an internal standard. Pharmacokinetics and bioequivalence of ondansetron in orally disintegrating tablets by direct compression and conventional 8 mg tablets were evaluated and compared in 20 healthy human male volunteers after a single oral dose in a randomized cross-over study. Results The limit of quantification was 0.25 ng· mL^-1. The recovery was about 85 % or over for ondan setron and about 90% for internal standard. Linearity was good within the concentration range of 0.5 - 50 ng·mL^-1 with r^2 ranging from 0.997 1 to 0.999 9. Intra- and inter-assay coefficients of variation ranged from 1.78% to 2.38% and 3.88% -5.19%, respectively. Accuracies for spiked concentrations of 2.0, 10.0, and 30.0 ng·mL^-1 were 104.7% ±4.4%, 102.2% ± 1.1%, and99.51% ±2.34%, respectively. Pharmacokinetic parameters of AUCo-t, AUCo-∞ , Cmax, Tmax, and T1/2 were 230.2 ± 78.0 ng·h·L^-1 , 265.2± 101.5 ng·h·mL^-1, 35.67 ± 8.94 ng·mL^-l, 1.51 ±0.79 h, and 5.00± 1.41 h for orally disintegrating tablets, respectively. The analysis of variance did not show any significant difference between orally disintegrating tablets and conventional tablets, and 90% confidence intervals fell within the acceptable range for bioequivalence. Conclusion High resolution HPLC method has been set up and applied in pharmacokinetic evaluation of ondansetron in orally disintegrating tablets.展开更多
Aim To develop pluronic F127 (PF127) based formulations of penciclovir (PCV) aimed at enhancing its ocular bioavailability. Methods Thermosensitive in situ gels of penciclovir were prepared through combination of ...Aim To develop pluronic F127 (PF127) based formulations of penciclovir (PCV) aimed at enhancing its ocular bioavailability. Methods Thermosensitive in situ gels of penciclovir were prepared through combination of HPMC K4M or carbopol 934P and pluronic F127. Optimized formulations were examined through measuring gelation temperature, rheology speciality, drug release behavior, pharmacokinetics and ocular irritation. Results The gelation temperature was reduced by adding HPMC K4M or carbopol 934P, and the viscosity was enhanced slightly. Either HPMC K4M or carbopol 934P delayed the release of PCV from in situ gel. PCV was released by non-Fickian diffusion. The study of ocular irritation for different PCV formulations did not show any irritation or damage for the cornea. PCV bioavailability from combination of carbopol 934P and pluronic F127 gels was higher than that obtained from any other gels. Conclusion Pluronic F127 formulations of PCV can be used as liquid for administration by instilling into the eye. Facilitated by the appropriate eye temperature, the formulations were transformed to gel phase. On the basis of in vitro and in vivo results, PCV formulations containing HPMC K4M or carbopol 934P and low concentration of pluronic F127 (12%) showed potential for use as a drug delivery system with improved ocular bioavailability.展开更多
Aim To establish an RP-HPLC method for the determination of scutellarin in plasma and study its pharmacokinetics in dogs. Methods Scutellarin was given to dogs by intravenous injection and determined by RP-HPLC, the m...Aim To establish an RP-HPLC method for the determination of scutellarin in plasma and study its pharmacokinetics in dogs. Methods Scutellarin was given to dogs by intravenous injection and determined by RP-HPLC, the mean plasma concentration-time curve was plotted and pharmacokinetic parameters were calculated by program 3p87. Resu;ts The concentration-time curve of scutellarin could be fitted to three-compartment model with T1/2 pi, T1/2 α and T1/2 β being 1.05 ± 0.80 min, 6.99 + 2.76 min and 51.61 + 28.78 min, respectively, Vc being 880.1 + 508.3 mL, CL being 189.6 + 53.8 mL@ min- 1, and AUC0-90 and AUC0-∞ being 574.43 + 133.95 μg@ min@ mL - 1 and 599.34 ± 132.00μg@ min@mL- 1, respectively. Conclusion The fact that the concentrations of scutellarin in plasma declined rapidly after the medication suggested that the T1/2 of scutellarin should be taken into account in drug administration and preparation development.展开更多
In order to improve the hydrogen storage kinetics of the Mg2Ni-type alloys, Ni in the alloy was partially substituted with element Co. The Mg2Ni-type Mg2Ni1-xCox (x=0, 0.1, 0.2, 0.3, 0.4) alloys were fabricated by m...In order to improve the hydrogen storage kinetics of the Mg2Ni-type alloys, Ni in the alloy was partially substituted with element Co. The Mg2Ni-type Mg2Ni1-xCox (x=0, 0.1, 0.2, 0.3, 0.4) alloys were fabricated by melt-spinning technique. The structures of the as-spun alloys were characterized by XRD and TEM. The gaseous and electrochemical hydrogen storage kinetics of the alloys was measured. The results show that the substitution of Co for Ni notably enhances the glass forming ability of the Mg2Ni-type alloy. The amorphization degree of the alloys visibly increases with rising of Co content. Furthermore, the substitution of Co for Ni significantly improves the hydrogen storage kinetics of the alloys. With an increase in the amount of Co substitution from 0 to 0.4, the hydrogen absorption saturation ratio of the as-spun (15 m/s) alloy increases from 81.2% to 84.9%, the hydrogen desorption ratio from 17.60% to 64.79%, the hydrogen diffusion coefficient increases from 1.07×10-11 to 2.79×10-11 cm2/s and the limiting current density increases from 46.7 to 191.7 mA/g, respectively.展开更多
Aim To prepare the sustained release melatonin tablet with HPMC matrix and study its pharmacokinetics and bioavailatility. Methods HPMC was used as matrix to formulate the sustained release tablet. The influences of t...Aim To prepare the sustained release melatonin tablet with HPMC matrix and study its pharmacokinetics and bioavailatility. Methods HPMC was used as matrix to formulate the sustained release tablet. The influences of the size of melatonin, type and amount of HPMC, drug loading, type and amount of additives, and compressing pressure were investigated. Plasma concentration of melatonin in dogs after intravenous injection of two doses and oral administration of sustained release tablets and unmodified release capsules was detected by HPLC using fluorescence detector. Results The drug release from sustained release tablets was influenced by the size of melatonin, type and amount of HPMC, drug loading, and type and amount of additives. Melatonin was found to fit two compartment model after intravenous injection, AUC was proportional to doses, and t(1/2β) of two doses has no significant difference. Relative bioavailability of melatonin sustained release tablet to normal capsule was 83.8%, and absolute bioavailability was 3.75% for sustained release tablet and 4.49% for capsule. Conclusion The melatonin sustained release tablet was well formulated. The absolute bioavilability for oral administration of either sustained release tablet or unmodified release capsule of melatonin was less than 5%. The bioavailability of melatonin sustained release tablet was lower than that of unmodified release capsule, but MRT of sustained release tablet was significantly longer than that of capsule.展开更多
Aim To develop and validate a sensitive and specific liquid chromatography electrospray ionization ion-trap mass spectrometry (LC-ESI-MS/MS) method for the identification and concentration of rupatadine in human pla...Aim To develop and validate a sensitive and specific liquid chromatography electrospray ionization ion-trap mass spectrometry (LC-ESI-MS/MS) method for the identification and concentration of rupatadine in human plasma. Methods After the addition of the internal standard (IS, loratadine) and 0.01 mol·L^-1 sodium hydroxide solution, plasma samples were extracted with methylene chloride: ethyl acetate mixture (20:80, V/V). The organic layer was evaporated under vacuum drying at 37 ℃. The residue was reconstituted with 200 μL mobile phase. Chromatography was performed on an Agilent Eclipse XDB-C18 (4.6 mm × 150 mm, 5 μm) column with a mobile phase consisting of acetonitrile (1% formic acid) -20 mmol·L^-1 ammonium acetate (76:24, V/V) at a flow-rate of 0.6 mL·min^-1. Detection was performed on Agilent MSD Trap XCT ion-trap mass spectrometry connected to a Agilent 1100 high performance liquid chromatography (HPLC) by selected reaction monitoring (SRM) mode via electrospray ionization (ESI) source. Rupatadine (MRM m/z 416 → 309) and loratadine (MRM m/z 383 → 337) were detected by Agilent MSD Trap XCT ion-trap mass analyser. Results The method was proved to be sensitive and specific by testing 20 different plasma batches. Linearity was established for the range of concentrations 0.05 - 14.0 ng·mL^ -1 with a coefficient of determination (r) of 0.998. The intra-and inter-day precision (RSD %) were lower than 15% and accuracy ranged from 85.1% to 114.0%. The lower limit of quantitation (LLOQ) was identifiable and reproducible at 0.05 ng·mL^-1 with a precision of 9.22% (n =5). Conclusion The proposed method is sensitive and reproducible enough to be used in pharmacokinetic, bioavailability or bioequivalence studies of rupatadine.展开更多
The nanocrystalline and amorphous Mg2Ni-type alloys with nominal compositions of Mg2Ni1-xMnx (x=0, 0.1, 0.2, 0.3, 0.4) were synthesized by melt-spinning technique. The spun alloy ribbons with a continuous length, a ...The nanocrystalline and amorphous Mg2Ni-type alloys with nominal compositions of Mg2Ni1-xMnx (x=0, 0.1, 0.2, 0.3, 0.4) were synthesized by melt-spinning technique. The spun alloy ribbons with a continuous length, a thickness of about 30 μm and a width of about 25 mm are obtained. The structures of the as-spun alloy ribbons were characterized by XRD and HRTEM. The electrochemical hydrogen storage characteristics of the as-spun alloy ribbons were measured by an automatic galvanostatic system. The electrochemical impedance spectrums (EIS) were plotted by an electrochemical workstation. The hydrogen diffusion coefficients (D) in the alloys were calculated by virtue of potential-step measurement. The results show that all the as-spun (x=0) alloys hold a typical nanocrystalline structure, whereas the as-spun (x=0.4) alloy displays a nanocrystalline and amorphous structure, confirming that the substitution of Mn for Ni facilitates the glass formation in the Mg2Ni-type alloy. The substitution of Mn for Ni significantly improves the electrochemical hydrogen storage performances of the alloys, involving the discharge capacity and the electrochemical cycle stability. With an increase in the amount of Mn substitution from 0 to 0.4, the discharge capacity of the as-spun (20 m/s) alloy increases from 96.5 to 265.3 mA·h/g, and its capacity retaining rate (S20) at the 20th cycle increases from 31.3% to 70.2%. Furthermore, the high rate dischargeability (HRD), electrochemical impedance spectrum and potential-step measurements all indicate that the electrochemical kinetics of the alloy electrodes first increases then decreases with raising the amount of Mn substitution.展开更多
Aim To investigate the pharmacokinetics of NM394 (an active metabolite of prulifloxacin) and evaluate the dose relationship and accumulation characteristics after single and multiple doses of prulifloxacin. Methods ...Aim To investigate the pharmacokinetics of NM394 (an active metabolite of prulifloxacin) and evaluate the dose relationship and accumulation characteristics after single and multiple doses of prulifloxacin. Methods Twelve healthy volunteers were given 132.1 mg, 264.2 mg, and 396.3 mg of prulifloxacin tablets in a randomized 3 × 3 crossover design test for single doses trial. With one-week washout period, 264.2 mg of prulifloxacin tablets were given for multiple doses trial. NM394 in plasma was determined by a sensitive HPLC method and its pharmacokinetic parameters were analyzed and evaluated by Drug and Statistics saftware (version 1.0). Results The Cmax, Tmax, t 1/2, AUC0-24, and AUC0-∞ of NM394 after single doses of 132.1 mg, 264.2 mg, and 396.3 mg of prulifloxacin tablets were 0.64 ± 0.25 μg· mL^-1, 1.06 ± 0.35 μg· mL^-1, and 1.45 ± 0.44 μg· mL^-1 , respectively; Tmax 0.94±0.22 h, 1.02±0.17 h, and 0.98±0.23 h, respectively; t 1/2 8.37±0.70 h, 7.70±0.82 h, and 7.78 ± 0.77 h, respectively; AUC0-24 2.93 ± 0.78 μg· mL^-1· h, 4.39 ± 1.05 μg· mL^-1· h, and 5.55± 1.32 μg·mL^-1 ·h, respectively; AUC0-∞ 3.32±0.84 μg·mL^-1 ·h, 4.82± 1.06 μg·mL^-1 ·h, and 6.10 ± 1.38 μg·mL^-1· h, respectively. And the Cmax, Tmax, t,1/2, AUC0- 24, and AUC0-∞ after multiple doses of 264.4 mg prulifloxacin tablets were 1.20 ± 0.33 μg· mL^- 1, 0.67 ± 0.12 h, 7.38 ± 1.03 h, 5.58 ± 1.25 μg· mL^-1·h, and 6.09 ± 1.24 μg· mL^-1· h, respectively. Conclusion The Cmax and AUC of NM394 are in high correlation with given prulifloxacin doses. There are no differences in pharnacokinetic characteristics of NM394 between single and multiple doses. No accumulation in plasma is observed after multiple doses of 264.2 mg per day for 7 d.展开更多
文摘Exosomes,ubiquitously present in body fluids,serve as non-invasive biomarkers for disease diagnosis,monitoring,and treatment.As intercellular messengers,exosomes encapsulate a rich array of proteins,nucleic acids,and metabolites,although most studies have primarily focused on proteins and RNA.Recently,exosome metabolomics has demonstrated clinical value and potential advantages in disease detection and pathophysiology,despite significant challenges,particularly in exosome isolation and metabolite detection.This review discusses the significant technical challenges in exosome isolation and metabolite detection,highlighting the advancements in these areas that support the clinical application of exosome metabolomics,and illustrates the potential of exosomal metabolites from various body fluids as biomarkers for early disease diagnosis and treatment.
基金Projects(51161015,51371094)supported by the National Natural Science Foundation of China
文摘The as-cast Mg2Ni-type Mg20–xYxNi10 (x=0, 1, 2, 3 and 4) electrode alloys were prepared by vacuum induction melting. Subsequently, the as-cast alloys were mechanically milled in a planetary-type ball mill. The analyses of scanning electron microscopy (SEM), X-ray diffraction (XRD) and transmission electron microscopy (TEM) reveal that nanocrystalline and amorphous structure can be obtained by mechanical milling, and the amount of amorphous phase increases with milling time prolonging. The electrochemical measurements show that the discharge capacity of Y0 alloy increases with milling time prolonging, while that of the Y-substituted alloys has a maximum value in the same condition. The cycle stabilities of the alloys decrease with milling time prolonging. The effect of milling time on the electrochemical kinetics of the alloys is related to Y content. Whenx=0, the high rate discharge ability, diffusion coefficient of hydrogen atom, limiting current density and charge transfer rate all increase with milling time prolonging, but the results are exactly opposite whenx=3.
文摘Aim To investigate novel bioactive and structural metabolites from marineorganisms. Methods Column chromatography in association with semi-preparative HPLC were used for theisolation of compounds. 1D and 2D NMR, IR, UV, and MS were employed for structure elucidation.Results From the butanol fraction of the 95% EtOH extract of the starfish Asterias rollestoni, a newcompound N^7 -2'-deoxypseudoxanthosine (1), along with sixteen known compounds, 2'-0-methyl-inosine(2), 2'-deoxyinosine (3), 2'-0-methylguanosine (4), inosine (5); thymine (6), uracil (7), thymidine(8), deoxyuridine (9), 2'-0-methyluridine (10), ( ― )-(1S, 3S)-1-methyl-1, 2, 3,4-terrahydro-β-carboline-3-carboxyl-ic acid (11), ( ― )-(1R, 3S)-1-methyl-1, 2, 3,4-tetrahydro-β-carboline-3-carboxylic acid (12) , ( ― )-(3S)- 1, 2, 3,4-tetrahydro-β-carboline-3-carboxylic acid (13), L-tryptophan (14), L-phenylalanine (15), 3-carboxyindole (16), and p-hydroxybenzoic acid (17) , have been isolated. Conclusion Compound 1 is a newnatural product, and compounds 8, 9 and 10 are isolated from natural sources for the first time, andthe known compounds except 14 and 15 are first reported from starfish Asterias rollestoni.
基金Projects(51161015,50961009)supported by the National Natural Science Foundations of ChinaProject(2011AA03A408)supported by the National Hi-tech Research and Development Program of ChinaProjects(2011ZD10,2010ZD05)supported by the Natural Science Foundation of Inner Mongolia,China
文摘The La-Mg-Ni-based A2B7-type La0.8-xNdxMg0.2Ni3.15Co0.2Al0.15 (x=0, 0.1, 0.2, 0.3, 0.4) electrode alloys were prepared by casting and annealing. The influences of partial substitution of Nd for La on the structure and electrochemical performance of the as-cast and annealed alloys were investigated. It was found that the experimental alloys consist of two major phases, (La, Mg)2Ni7 phase with the hexagonal Ce2Ni7-type structure and LaNi5 phase with the hexagonal CaCu5-type structure, as well as some residual phase LaNi3 and NdNi5. The discharge capacity and high rate discharge ability (HRD) of the as-cast and annealed alloys first increase and then decrease with Nd content growing. The as-cast and annealed alloys (x=0.3) yield the largest discharge capacities of 380.3 and 384.3 mA·h/g, respectively. The electrochemical cycle stability of the as-cast and annealed alloys markedly grows with Nd content rising. As the Nd content increase from 0 to 0.4. The capacity retaining rate (S100) at the 100th charging and discharging cycle increases from 64.98% to 85.17% for the as-cast alloy, and from 76.60% to 96.84% for the as-annealed alloy.
基金National Natural Science Foundation (Grant No. 30472165)
文摘To evaluate the effect of components in Guanxin Ⅱ prescription on the pharmacokinetic profiles of paeoniflorin. Plasma concentration of Paeoniflorin in rats after intravenous injection of Paronia Pall Extract (PPE) and oral administration of PPE and three types of decoctions in Guanxin Ⅱ prescription, respectively, were determined by HPLC analyses. NONMEM (nonlinear mixed-effect modeling) method was used to analyze full set of pharmacokinetic data directly. A two-compartment model with first-order degradation in absorption compartment was employed for the data analysis. The mean of population parameters, CL1, V1, CL2, V2, Ka0, and Kal, were measured to be 0.509 L/h, 0.104 L, 0.113 L/h, 0.123 L, 0.135/h, and 0.0135/h, respectively. Inter-individual variabilities were estimated and dose formulation (DF) was identified as a significant covariate of Ka 1, Ka0, and V1. It is concluded that the pharmacokinetic behaviors of paeoniflorin in rats can alter with different dose formulations.
文摘Aim To study the pharmacokinetics of oxiracetam after single and multipleintravenous administrations in healthy volunteers. Method A HPLC method was used to determine theserum concentration of oxiracetam after intravenous single dose and daily dose of 2 000 mg for 7 din ten Chinese healthy volunteers. Pharmacokinetic analysis was carried out using Drug And Statisticsoftware. Results The AUC_(0-12), AUC_(0-∞), K_e, t_(1/2), MRT after a single dose of 2 000 mgoxiracetam were 256.26 ± 16.84 μg·mL^(-1)·h, 276.74 ±18.11 μg·mL^(-1)·h, 0.18 ±0.03 h^(-1),3.84±0.64 h, and 4.39 10.39 h, and after multiple doses of oxiracetam were 259.36 ±25.43μg·mL^(-1)·h, 285.59 ±27.38 μg·mL^(-1)·h, 0.17 ±0.04 h^(-1), 4.14 ± 0.82 h, and 4.87 ±0.69 h, respectively. Conclusion The pharmacokinetic parameters of oxiracetam do not differremarkably after single and multiple intravenous administration and there is accumulation in serumafter 2 000 mg multiple intravenous administration once a day fof 7 d.
文摘To deal with the data mining problem of asymmetry misclassification cost, an innovative churn prediction method is proposed based on existing churn prediction research. This method adjusts the misclassification cost based on the C4. 5 decision tree as a baseline classifier, which can obtain the prediction model with a minimum error rate based on the assumption that all misclassifications have the same cost, to realize cost-sensitive learning. Results from customer data of a certain Chinese telecommunication company and the fact that the churners and the non-churners have different misclassification costs demonstrate that by altering the sampling ratio of churners and non-churners, this cost-sensitive learning method can considerably reduce the total misclassification cost produced by traditional classification methods. This method can also play an important role in promoting core competence of Chinese telecommunication industry.
文摘Aim To study the pharmacokinetics of remifentanil in Chinese aduh patients undergoing elective surgery and compare the results with the data already published. Methods The pharmacokinetics of remifentanil was determined in 10 aduh patients undergoing elective surgery. Remifentanil 5 - 6 μg·kg^-1 was administered within 1 min after the induction of anesthesia. One point five millilitre of arterial blood samples were collected at 0 (baseline), 1,2, 3, 5,7, 10, 15, 20, 25, 30, 45, 60, and 90 min after drug administration. Remifentanil concentration was assayed by HPLC/MS/MS. Resuits The concentration-time course of remifentanil was best described by a two-compartment model. Total clearance (CL = 2. 149 ± 0. 431 L·min^-1) of remifentanil was greater than the normal hepatic blood flow. The distribution half-life (t1/2α) [ 1.56 ± 0. 52 min (0.73 - 2.31 ) ] and the elimination half-life (t1/2β) [22.07 ± 10.30 min (9, 71 -36.07)] were similar with those in previous reports. Volume of distribution ( Vd = 65. 766 ± 29. 100 L) was about two times greater than that reported in previous studies of other ethnics. Conclusion In the present study, the volume of distribution is significantly greater than thai reported in previous studies of other ethnics, indicating that there are some differences in the pharmacokinetics of remifentanil among different ethnics.
文摘Aim To establish a new and sensitive HPLC-MS method for the determination ofzolmitriptan in human plasma and study the pharmacokinetics of zolmitriptan in healthy volunteers.Methods A single oral dose of 5 mg of zolmitriptan tablet was given to 20 healthy male volunteers.After dosing, blood samples were collected for a period of 24 h, and zolmitriptan concentration inplasma was analyzed by HPLC-MS. Results The plasma concentration-time course fitted well atwo-compartment open model with a lag time, giving the following pharmacokinetic parameters: T_(max)1.60 ± 0.24 h, C_(max) 9.73 ± 1.43 ng·mL^(-1). T_(1/2α)1.72±0.46 h, T_(1/2β) 4.52 + 0.97 h,and AUC_(0-t) 55.59 ± 5.12 ng·mL^(-1)·h. Conclusion The improved analytical method forzolmitriptan is rapid, sensitive and suitable for application to pharmacokinetic studies and routinedetermination of numerous samples.
文摘Puts forward an algebraic structure of the Chaplygin's equations of nonholonomic systems, establish the Poisson's theory of the integration equations and gives an example for illustrating the application of the result.
文摘To test and study the Syndrome and Treatment Pharmacokinetics (S & TRK),we studied the pharmacokinetics of ferulic acid in healthy and blood stasis (microcirculation dysfunction)rabbits by RP-HPLC. After a single intravenous injection offenilic acid(5mg/kg)to healthy and blood stasis rabbits, compartment model of ferulic acid serum concentration was fitted and then pharmacokinetic parameters were calculated with a MCPKP program on a COMPAQ 386 compute Important parameters are as follows: In healthy rabbits V_B=0.9525±0.0211 L/kg,V_1=0.2462±0.0381 L/kg, CL_B=1.8133±0.9512 L/h·kg, T_(1/2β)=0.3639±0913, AUC=2.7566±0.8232 μg·h/ml; In blood stasis rabbits V_B=0.7882±0.0321 L/kg,V_1=0.1966±0.0537 L/kg,CL_B=0.8820±0.5481 L/h·kg,T_(1/2β)=0.6193±0.1216 h, AUC=5.6690±2.3541μg·h/ml.Through this experiment we found the sig-nificant differences in the FA's pharmacokinetic parameters between healthy and blood stasis rabbits.The results obtained correspond with S & TPK.
文摘Ahn To develop a high resolution HPLC method for the determination of ondansetron in human plasma and to study the pharmacokinetics of ondansetron in orally disintegrating tablets. Methods HPLC determination involved liquid-liquid extraction, separation on a CN column and ultraviolet detection at 310 ran with granisetron as an internal standard. Pharmacokinetics and bioequivalence of ondansetron in orally disintegrating tablets by direct compression and conventional 8 mg tablets were evaluated and compared in 20 healthy human male volunteers after a single oral dose in a randomized cross-over study. Results The limit of quantification was 0.25 ng· mL^-1. The recovery was about 85 % or over for ondan setron and about 90% for internal standard. Linearity was good within the concentration range of 0.5 - 50 ng·mL^-1 with r^2 ranging from 0.997 1 to 0.999 9. Intra- and inter-assay coefficients of variation ranged from 1.78% to 2.38% and 3.88% -5.19%, respectively. Accuracies for spiked concentrations of 2.0, 10.0, and 30.0 ng·mL^-1 were 104.7% ±4.4%, 102.2% ± 1.1%, and99.51% ±2.34%, respectively. Pharmacokinetic parameters of AUCo-t, AUCo-∞ , Cmax, Tmax, and T1/2 were 230.2 ± 78.0 ng·h·L^-1 , 265.2± 101.5 ng·h·mL^-1, 35.67 ± 8.94 ng·mL^-l, 1.51 ±0.79 h, and 5.00± 1.41 h for orally disintegrating tablets, respectively. The analysis of variance did not show any significant difference between orally disintegrating tablets and conventional tablets, and 90% confidence intervals fell within the acceptable range for bioequivalence. Conclusion High resolution HPLC method has been set up and applied in pharmacokinetic evaluation of ondansetron in orally disintegrating tablets.
文摘Aim To develop pluronic F127 (PF127) based formulations of penciclovir (PCV) aimed at enhancing its ocular bioavailability. Methods Thermosensitive in situ gels of penciclovir were prepared through combination of HPMC K4M or carbopol 934P and pluronic F127. Optimized formulations were examined through measuring gelation temperature, rheology speciality, drug release behavior, pharmacokinetics and ocular irritation. Results The gelation temperature was reduced by adding HPMC K4M or carbopol 934P, and the viscosity was enhanced slightly. Either HPMC K4M or carbopol 934P delayed the release of PCV from in situ gel. PCV was released by non-Fickian diffusion. The study of ocular irritation for different PCV formulations did not show any irritation or damage for the cornea. PCV bioavailability from combination of carbopol 934P and pluronic F127 gels was higher than that obtained from any other gels. Conclusion Pluronic F127 formulations of PCV can be used as liquid for administration by instilling into the eye. Facilitated by the appropriate eye temperature, the formulations were transformed to gel phase. On the basis of in vitro and in vivo results, PCV formulations containing HPMC K4M or carbopol 934P and low concentration of pluronic F127 (12%) showed potential for use as a drug delivery system with improved ocular bioavailability.
文摘Aim To establish an RP-HPLC method for the determination of scutellarin in plasma and study its pharmacokinetics in dogs. Methods Scutellarin was given to dogs by intravenous injection and determined by RP-HPLC, the mean plasma concentration-time curve was plotted and pharmacokinetic parameters were calculated by program 3p87. Resu;ts The concentration-time curve of scutellarin could be fitted to three-compartment model with T1/2 pi, T1/2 α and T1/2 β being 1.05 ± 0.80 min, 6.99 + 2.76 min and 51.61 + 28.78 min, respectively, Vc being 880.1 + 508.3 mL, CL being 189.6 + 53.8 mL@ min- 1, and AUC0-90 and AUC0-∞ being 574.43 + 133.95 μg@ min@ mL - 1 and 599.34 ± 132.00μg@ min@mL- 1, respectively. Conclusion The fact that the concentrations of scutellarin in plasma declined rapidly after the medication suggested that the T1/2 of scutellarin should be taken into account in drug administration and preparation development.
基金Projects(50871050,50961009)supported by the National Natural Science Foundation of ChinaProjects(2010ZD05,2011ZD10)supported by Natural Science Foundation of Inner Mongolia,ChinaProject(NJzy08071)supported by High Education Science Research Project of Inner Mongolia,China
文摘In order to improve the hydrogen storage kinetics of the Mg2Ni-type alloys, Ni in the alloy was partially substituted with element Co. The Mg2Ni-type Mg2Ni1-xCox (x=0, 0.1, 0.2, 0.3, 0.4) alloys were fabricated by melt-spinning technique. The structures of the as-spun alloys were characterized by XRD and TEM. The gaseous and electrochemical hydrogen storage kinetics of the alloys was measured. The results show that the substitution of Co for Ni notably enhances the glass forming ability of the Mg2Ni-type alloy. The amorphization degree of the alloys visibly increases with rising of Co content. Furthermore, the substitution of Co for Ni significantly improves the hydrogen storage kinetics of the alloys. With an increase in the amount of Co substitution from 0 to 0.4, the hydrogen absorption saturation ratio of the as-spun (15 m/s) alloy increases from 81.2% to 84.9%, the hydrogen desorption ratio from 17.60% to 64.79%, the hydrogen diffusion coefficient increases from 1.07×10-11 to 2.79×10-11 cm2/s and the limiting current density increases from 46.7 to 191.7 mA/g, respectively.
文摘Aim To prepare the sustained release melatonin tablet with HPMC matrix and study its pharmacokinetics and bioavailatility. Methods HPMC was used as matrix to formulate the sustained release tablet. The influences of the size of melatonin, type and amount of HPMC, drug loading, type and amount of additives, and compressing pressure were investigated. Plasma concentration of melatonin in dogs after intravenous injection of two doses and oral administration of sustained release tablets and unmodified release capsules was detected by HPLC using fluorescence detector. Results The drug release from sustained release tablets was influenced by the size of melatonin, type and amount of HPMC, drug loading, and type and amount of additives. Melatonin was found to fit two compartment model after intravenous injection, AUC was proportional to doses, and t(1/2β) of two doses has no significant difference. Relative bioavailability of melatonin sustained release tablet to normal capsule was 83.8%, and absolute bioavailability was 3.75% for sustained release tablet and 4.49% for capsule. Conclusion The melatonin sustained release tablet was well formulated. The absolute bioavilability for oral administration of either sustained release tablet or unmodified release capsule of melatonin was less than 5%. The bioavailability of melatonin sustained release tablet was lower than that of unmodified release capsule, but MRT of sustained release tablet was significantly longer than that of capsule.
文摘Aim To develop and validate a sensitive and specific liquid chromatography electrospray ionization ion-trap mass spectrometry (LC-ESI-MS/MS) method for the identification and concentration of rupatadine in human plasma. Methods After the addition of the internal standard (IS, loratadine) and 0.01 mol·L^-1 sodium hydroxide solution, plasma samples were extracted with methylene chloride: ethyl acetate mixture (20:80, V/V). The organic layer was evaporated under vacuum drying at 37 ℃. The residue was reconstituted with 200 μL mobile phase. Chromatography was performed on an Agilent Eclipse XDB-C18 (4.6 mm × 150 mm, 5 μm) column with a mobile phase consisting of acetonitrile (1% formic acid) -20 mmol·L^-1 ammonium acetate (76:24, V/V) at a flow-rate of 0.6 mL·min^-1. Detection was performed on Agilent MSD Trap XCT ion-trap mass spectrometry connected to a Agilent 1100 high performance liquid chromatography (HPLC) by selected reaction monitoring (SRM) mode via electrospray ionization (ESI) source. Rupatadine (MRM m/z 416 → 309) and loratadine (MRM m/z 383 → 337) were detected by Agilent MSD Trap XCT ion-trap mass analyser. Results The method was proved to be sensitive and specific by testing 20 different plasma batches. Linearity was established for the range of concentrations 0.05 - 14.0 ng·mL^ -1 with a coefficient of determination (r) of 0.998. The intra-and inter-day precision (RSD %) were lower than 15% and accuracy ranged from 85.1% to 114.0%. The lower limit of quantitation (LLOQ) was identifiable and reproducible at 0.05 ng·mL^-1 with a precision of 9.22% (n =5). Conclusion The proposed method is sensitive and reproducible enough to be used in pharmacokinetic, bioavailability or bioequivalence studies of rupatadine.
基金Project (2007AA03Z227) supported by the High-tech Research and Development Program of ChinaProjects (50871050, 50701011) supported by the National Natural Science Foundation of China+1 种基金Project (200711020703) supported by Natural Science Foundation of Inner Mongolia, ChinaProject (NJzy08071) supported by Higher Education Science Research Project of Inner Mongolia, China
文摘The nanocrystalline and amorphous Mg2Ni-type alloys with nominal compositions of Mg2Ni1-xMnx (x=0, 0.1, 0.2, 0.3, 0.4) were synthesized by melt-spinning technique. The spun alloy ribbons with a continuous length, a thickness of about 30 μm and a width of about 25 mm are obtained. The structures of the as-spun alloy ribbons were characterized by XRD and HRTEM. The electrochemical hydrogen storage characteristics of the as-spun alloy ribbons were measured by an automatic galvanostatic system. The electrochemical impedance spectrums (EIS) were plotted by an electrochemical workstation. The hydrogen diffusion coefficients (D) in the alloys were calculated by virtue of potential-step measurement. The results show that all the as-spun (x=0) alloys hold a typical nanocrystalline structure, whereas the as-spun (x=0.4) alloy displays a nanocrystalline and amorphous structure, confirming that the substitution of Mn for Ni facilitates the glass formation in the Mg2Ni-type alloy. The substitution of Mn for Ni significantly improves the electrochemical hydrogen storage performances of the alloys, involving the discharge capacity and the electrochemical cycle stability. With an increase in the amount of Mn substitution from 0 to 0.4, the discharge capacity of the as-spun (20 m/s) alloy increases from 96.5 to 265.3 mA·h/g, and its capacity retaining rate (S20) at the 20th cycle increases from 31.3% to 70.2%. Furthermore, the high rate dischargeability (HRD), electrochemical impedance spectrum and potential-step measurements all indicate that the electrochemical kinetics of the alloy electrodes first increases then decreases with raising the amount of Mn substitution.
文摘Aim To investigate the pharmacokinetics of NM394 (an active metabolite of prulifloxacin) and evaluate the dose relationship and accumulation characteristics after single and multiple doses of prulifloxacin. Methods Twelve healthy volunteers were given 132.1 mg, 264.2 mg, and 396.3 mg of prulifloxacin tablets in a randomized 3 × 3 crossover design test for single doses trial. With one-week washout period, 264.2 mg of prulifloxacin tablets were given for multiple doses trial. NM394 in plasma was determined by a sensitive HPLC method and its pharmacokinetic parameters were analyzed and evaluated by Drug and Statistics saftware (version 1.0). Results The Cmax, Tmax, t 1/2, AUC0-24, and AUC0-∞ of NM394 after single doses of 132.1 mg, 264.2 mg, and 396.3 mg of prulifloxacin tablets were 0.64 ± 0.25 μg· mL^-1, 1.06 ± 0.35 μg· mL^-1, and 1.45 ± 0.44 μg· mL^-1 , respectively; Tmax 0.94±0.22 h, 1.02±0.17 h, and 0.98±0.23 h, respectively; t 1/2 8.37±0.70 h, 7.70±0.82 h, and 7.78 ± 0.77 h, respectively; AUC0-24 2.93 ± 0.78 μg· mL^-1· h, 4.39 ± 1.05 μg· mL^-1· h, and 5.55± 1.32 μg·mL^-1 ·h, respectively; AUC0-∞ 3.32±0.84 μg·mL^-1 ·h, 4.82± 1.06 μg·mL^-1 ·h, and 6.10 ± 1.38 μg·mL^-1· h, respectively. And the Cmax, Tmax, t,1/2, AUC0- 24, and AUC0-∞ after multiple doses of 264.4 mg prulifloxacin tablets were 1.20 ± 0.33 μg· mL^- 1, 0.67 ± 0.12 h, 7.38 ± 1.03 h, 5.58 ± 1.25 μg· mL^-1·h, and 6.09 ± 1.24 μg· mL^-1· h, respectively. Conclusion The Cmax and AUC of NM394 are in high correlation with given prulifloxacin doses. There are no differences in pharnacokinetic characteristics of NM394 between single and multiple doses. No accumulation in plasma is observed after multiple doses of 264.2 mg per day for 7 d.