The study aims to develop a rapid, sensitive and specified method of liquid chromatography with heated electrospray ionization tandem mass spectrometry (LC-HESI/MS/MS) for simultaneous determination of amlodipine, benazepril and benazeprilat in human plasma using amlodipine-d4 and ubenimex as internal standards (ISs). Selected reaction monitoring (SRM) with heated electrospray ionization (HESI) was used in the positive mode for mass spectrometric detection. Analytes and ISs were extracted from plasma by simple protein precipitation. The reconstituted samples were chromatographed on a C18 (100 mm x 4.6 mm, 5 microm) column with mixture of methanol-acetonitrile-5 mmol.L- ammonium acetate-formic acid (30 : 30 : 40 : 0.1) as mobile phase at a flow rate of 0.6 mL.min-1. The standard curves were demonstrated to be linear in the range of 0.02 to 6.00 ng.mL-1 for amlodipine, 0.2 to 1,500 ng.mL-1 for benazepril and benazeprilat with r2>0.99 for each analyte. The lower limit of quantitation was identifiable and reproducible at 0.02, 0.2 and 0.2 ng mL-1 for amlodipine, benazepril and benazeprilat, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limit across all concentrations. The plasma samples were stable after four freeze-thaw cycles and being stored for 93 days at -20 degrees C. The method was applied to a pharmacokinetic study of a fixed-dose combination of amlodipine and benazepril on Chinese healthy volunteers.
Administration, Oral ; Amlodipine ; administration & dosage ; blood ; Benzazepines ; administration & dosage ; blood ; Chromatography, Liquid ; Humans ; Sensitivity and Specificity ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

OBJECTIVETo evaluate the effect and safety of L-carnitine in the treatment of idiopathic oligoasthenozoospermia based on current clinical evidence.

METHODSWe searched the Cochrane Library, PubMed, MEDLINE, EMBASE, CNKI, VIP, CBM and Wanfang Database from the establishment to April 2014 for the published literature on the treatment of idiopathic oligoasthenozoospermia with L-carnitine. We conducted literature screening, data extraction, and assessment of the methodological quality of the included trials according to the inclusion and exclusion criteria, followed by statistical analysis with the RevMan 5. 2 software.

RESULTSSeven randomized controlled trials involving 751 patients with idiopathic oligoasthenozoospermia met the inclusion criteria, and 678 of them were included in the meta-analysis. L-carnitine treatment achieved a significantly increased rate of spontaneous pregnancy as compared with the control group (RR = 3.2, 95% CI 1.74 to 5.87, P = 0.0002). After 12-16 and 24-26 weeks of medication, total sperm motility (WMD = 5.21, 95% CI 2.78 to 7.64, P < 0.0001 and WMD = 9.29, 95% CI 1.28 to 17.29, P = 0.02) and the percentage of progressively motile sperm (WMD = 12.44, 95% CI 4.58 to 20.31, P = 0.002 and WMD = 9.76, 95% CI 3.56 to 15.97, P = 0.002) were remarkably higher than those in the control group, but no statistically significant differences were observed in sperm concentration between the two groups (WMD = 4.91, 95% CI -2.63 to 12.45, P = 0.2 and WMD = 0.93, 95% CI -3.48 to 5.34, P = 0.68). After 12-16 weeks of treatment, the percentage of morphologically abnormal sperm was markedly decreased in the L-carnitine group as compared with the control (WMD = -2.48, 95% CI -4.35 to -0.61, P = 0.009), but showed no significant difference from the latter group after 24-26 weeks (WMD = -4.38, 95% CI -9.66 to 0.89, P = 0.1). No statistically significant difference was found in the semen volume between the two groups after 12-16 or 24-26 weeks of medication (WMD = -0.13, 95% CI -0.43 to 0.18, P = 0.42 and WMD = 0.28, 95% CI -0.02 to 0.58, P = 0.07). No serious L-carnitine-related adverse events were reported in 4 of the randomniized controlled trials.

CONCLUSIONThe current evidence indicates that L-carnitine can improve spontaneous pregnancy and semen parameters in the treatment of idiopathic oligoasthenozoospermia, with no serious adverse reactions.

Asthenozoospermia ; drug therapy ; Carnitine ; adverse effects ; pharmacology ; Female ; Humans ; Male ; Pregnancy ; Pregnancy Rate ; Randomized Controlled Trials as Topic ; Semen Analysis ; Sperm Count ; Sperm Motility

This study aims to develop a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of ivabradine and N-demethylivabradine in human plasma, and investigate effects of stable isotope labeled (SIL) internal standard (IS) on ivabradine. The analytes and IS were extracted from plasma by protein precipitation with acetonitrile, and chromatographied on a Capcell PAK C18 (100 mm x 4.6 mm, 5 μm) column using a mobile phase of methanol and 5 mmol x L(-1) ammonium acetate. Multiple reaction monitoring with electrospray ionization (ESI) was used in the positive mode for mass spectrometric detection. The effect of ivabradine isotope peak [M+H+3] + on IS and the effect of SIL IS purity on ivabradine were evaluated. An appropriate concentration of SIL IS was chosen to permit method selectivity and linearity of the assay over the required range. The standard curves were demonstrated to be linear in the range of 0.100 to 60.0 ng x mL(-1) for ivabradine, and 0.050 0 to 20.0 ng x mL(-1) for N-demethylivabradine. The intra and inter day precision and accuracy were within the acceptable limits for all concentrations. Besides, the interaction between IS and ivabradine did not impact the determination of analytes. This method was successfully applied to a pharmacokinetic study of hydrogen sulfate ivabradine sustained release tablets on Chinese healthy volunteers.
Benzazepines ; blood ; Chromatography, High Pressure Liquid ; Delayed-Action Preparations ; Humans ; Isotope Labeling ; standards ; Reference Standards ; Reproducibility of Results ; Sensitivity and Specificity ; Spectrometry, Mass, Electrospray Ionization ; Tablets ; Tandem Mass Spectrometry

Objective:To investigate the specific killing effect of magnetic nanoparticles Fe3O4@PEI induced targeted suicide gene therapycombinedwithmagneticfluidhyperthermiaonhepatomaxenograft.Methods:Thesuicidegenetargetinghepatomap[HRE]AFP-HSVTK and tumor cell imaging reporter gene vector p[HRE]AFP-Luc were constructed by sub-cloning gene recombination method, and tested by restriction endonuclease gel electrophoresis. Fe3O4 nano-particles were prepared by co-precipitation method and modified by Polyethyleneimine (PEI) to obtain the magnetic nano-particles Fe3O4@PEI,which could be used as carrier for tumor gene therapy and a medium for magnetic fluid hyperthermia treatment; and the characterization of Fe3O4@PEI was identified by transmission electron microscopy, particle size analyzer and Fourier transform infrared spectroscopy. The reporter genes p[HRE]AFP-Luc were delivered into the nude mice bearing xenografts via tail vein by Fe3O4@PEI, then the bioluminescence signals of mice were observed in an IVIS system.After the treatment of p[HRE]AFP-HSVTK/Fe3O4@PEI, the tumor cell inhibition rate was examined by MTT assay, the cell apoptosis was tested by Flow cytometry, the in vivo tumor development rate and tumor inhibition rate was tested by animal experiment, and the sub-cellular construction of tumor cells was observed by Transmission electron microscopy. Results: Nano-particles Fe3O4@PEI and recombinant vectors p[HRE]AFP-HSVTK and p[HRE]AFP-Luc were successfully constructed; after tale vein injection, image signals were detected only in tumor tissues via IVIS system, but no obvious pathologic damage in other major organs. In the in vitro cell killing test, the cell proliferation inhibition rate and the cell apoptosis rate in combination group was higher than that in hyperthermia treatment group and gene treatment group [inhibition rate: (76.02±7.33)% vs (42.31±4.28)%， (47.76±4.81)%, all P<0.05; apoptosis rate: (34.05±3.41)% vs (14.41±1.55)%， (11.64±1.20)%， all P<0.01]. The in vivo treatment showed that tumor volume development significantly slowed-down and even decreased in combination treatment group, and the tumor mass were significantly smaller than those of the single treatment groups (all P<0.05); and the tumor cell sub- cellular structure showed obvious apoptotic morphology. Conclusion: the suicide gene p [HRE]AFP-HSVTK has specifickillingeffecton hepatomacells,Fe3O4@PEI can be used as effectivegene treatmentcarrierand mediaof magnetic heperthermia treatment; Fe3O4@PEI mediated target treatment combined with magnetic fluid hyperthermia treatment could specificallyinhibitthehepatomaxenograft.

OBJECTIVETo prepare shuxiong micropellets.

METHODShuxiong micropellets were prepared by using a centrifugal granulator. The formulation composition and process factors were optimized investigated by adopting several indices such as size distribution, repose angle, bulk density and friability as indexes.

RESULTThe optimal process parameters were as follows. The ratio of fine intermediate product and MCC was 3:1 (w/w), the adhesive agent was 3% HMPC solution, the rotating rate of plate was 200 r x min(-1), the blower rate was 15 x 20 L x min(-1), the rate of air flow was 15 L x min(-1), the spray air pressure was 0.5 MPa, the rotating of spray solution pump was 5-25 r x min(-1) and the rotating rate of powder feed machine was 5-25 r x min(-1).

CONCLUSIONUnder the optimal conditions, micropellets prepared by using centrifugal granulator hadpossessed prefect shape and surface characteristics and the yield of shuxiong pellets was 90.5%.

Carthamus tinctorius ; chemistry ; Cellulose ; Centrifugation ; methods ; Chalcone ; administration & dosage ; analogs & derivatives ; isolation & purification ; Drug Combinations ; Excipients ; Ginsenosides ; administration & dosage ; isolation & purification ; Hypromellose Derivatives ; Ligusticum ; chemistry ; Methylcellulose ; analogs & derivatives ; Microspheres ; Panax notoginseng ; chemistry ; Particle Size ; Phenols ; administration & dosage ; isolation & purification ; Plants, Medicinal ; chemistry ; Quinones ; administration & dosage ; isolation & purification ; Technology, Pharmaceutical ; methods

Objective To investigate the high-risk behaviors related to acquared immune deficiency syndrome/sexually transmitted disease (AIDS/STDs) infection among fishermen in Lv-si harbor,Jiangsu province.Methods A cross-sectional study was designed to investigate the research participants' demographic characteristics,high-risk behaviors that related to AIDS/STDs.Logistic regression was performed to measure the associations between potential risk factors and reported potential high-risk sexual behavior.Results 817 fishermen participated in the study and casual or commercial sex activities appeared to be the main high-risk behavior for AIDS/STDs infection in the target population.The rates of casual and commercial sex reported were 18.1％ and 28.9％ among fishermen.Risk factors associated with AIDS/STDs related high-risk behaviors among fishermen were high mobility (OR=1.516,P=0.038),higher lifetime sex frequency (OR=1.422,P=0.002)and unmarried status ( OR =7.527,P=0.014).Protective factors against high-risk behaviors were low intake of alcohol (OR=0.803,P=0.053),negative STD history (OR=0.268,P=0.001 ),age of initial sexual intercourse at or older than 22 years (OR =0.440,P=0.000) of age,as well as negative attitude toward multiple sexual parmers (OR=0.662,P=0.023 ) and legitimation for commercial sex (OR=0.612,P=0.007).Conclusion There were risk behaviors of AIDS/STDs in those infected fishmen.Casual and commercial sex were common high-risk behaviors.

OBJECTIVETo evaluate the effectiveness of free graft transplantation two-stage urethroplasty for hypospadias repair.

METHODSFifty-eight cases with different types of hypospadias including 10 subcoronal, 36 penile shaft, 9 scrotal, and 3 perineal were treated with free full-thickness skin graft or (and) buccal mucosal graft transplantation two-stage urethroplasty. Of 58 cases, 45 were new cases, 13 had history of previous failed surgeries. Operative procedure included two stages: the first stage is to correct penile curvature (chordee), prepare transplanting bed, harvest and prepare full-thickness skin graft, buccal mucosal graft, and perform graft transplantation. The second stage is to complete urethroplasty and glanuloplasty.

RESULTSAfter the first stage operation, 56 of 58 cases (96.6%) were successful with grafts healing well, another 2 foreskin grafts got gangrened. After the second stage operation on 56 cases, 5 cases failed with newly formed urethras opened due to infection, 8 cases had fistulas, 43 (76.8%) cases healed well.

CONCLUSIONSFree graft transplantation two-stage urethroplasty for hypospadias repair is a kind of effective treatment with broad indication, comparatively high success rate, less complications and good cosmatic results, indicative of various types of hypospadias repair.

Adolescent ; Adult ; Child ; Child, Preschool ; Humans ; Hypospadias ; surgery ; Male ; Mouth Mucosa ; transplantation ; Penis ; abnormalities ; surgery ; Retrospective Studies ; Scrotum ; abnormalities ; surgery ; Skin Transplantation ; Treatment Outcome ; Urethra ; surgery ; Urologic Surgical Procedures, Male ; methods

OBJECTIVETo investigate the incidence of HBV reactivation and its clinical characteristics in the non-active HBsAg carriers receiving chemotherapy or immunosuppressant treatment, and to evaluate the role of nucleos(t)ide analogues against HBV reactivation.

METHODSNon-active HBsAg carriers suffering from cancer, autoimmune diseases recieving immunosuppression therapy or cytotoxic chemotherapy were enrolled in the study. The in-patients from June 2002 to April 2007 in the Second Affiliated Hospital of Chongqing Medical University were assigned in the control group. The outpatients or in-patients with the similar disease condition from April 2007 to July 2008 were enrolled in the preventive group. The characteristics of HBV replication, liver damage, clinical symptoms and effectiveness of nucleos(t)ide analogues as prophylaxis for HBV reactivation were observed. The nucleos(t)ide analogues were used before chemotheraphy or immunosuppressive agents. The characheristics and clinical manifestations about HBV reactivation were investigated.

RESULTSOf the 32 patients in preventive group, the amount of HBV DNA was detected in the 1rst, 3rd, 6th and 12th month after nucleos(t)ide analogues treatment. After chemotherapy or immunosuppressant treatment, only 9.4% (3/32) of them suffered from HBV reactivation, as indicated by positive HBV DNA in the serum and abnormal liver function. Ot the 77 patients in control group without nucleos(t)ide analogues treatment before chemotherapy or immunosuppression therapy, 58.4% (45/77) shown HBV reactivation, 4 patients in the control group died of liver failure, and one liver failure patient recieved liver transplantation.

CONCLUSIONHBV can be activated in immunosuppressed patients, nucleos(t)ide analogues should be used in early phase to prevent HBV reactivation.

Adult ; Antineoplastic Agents ; adverse effects ; Antiviral Agents ; therapeutic use ; Carrier State ; DNA, Viral ; blood ; Female ; Hepatitis B ; drug therapy ; prevention & control ; virology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; drug effects ; Humans ; Immunosuppressive Agents ; adverse effects ; Lamivudine ; adverse effects ; therapeutic use ; Liver Function Tests ; Male ; Middle Aged ; Nucleosides ; therapeutic use ; Retrospective Studies ; Virus Activation ; drug effects

Objective: To investigate the effects of psycholog ical factors on treatment and outcome of patients with high altitude pulmonary e dema(HAPE). Methods: In the present study, one hundred and fifty -two patients with HAPE were tested by hospital anxiety and depression scale. Results: The results showed that there were 61 patients (40.13%) with anxiety and 29 patients (19.08%) with depression. The important factors on mental state of patients were preventive education, the first time suffering HA PE, characters of patients, degree of the disease and the medical fee, the less w ere age, sex, occupation and education of patients. Duration of rales of lung an d course of illness were significantly prolonged in HAPE patients with mental di sorders compared to the patients without mental disorder. Conclusion:The study suggests that anxiety and depression might aggravate the state of HAPE.

Objective To evaluate the feasibility,reliability,validity and responsiveness of a Chinese Menopause Rating Scale (CMRS).Methods Cross-sectional survey and convenience sampling were adopted. Participants:women with menopause syndrome and those in menopause but without menopause syndrome were recruited.All participants were asked to complete the CMRS,Kupperman Index,WHOQOL-BREF and MENQOL.The Self-control observation design was adopted when the responsiveness was evaluated.Patients were treated with TCM for weeks.MRSTCM was evaluated before and after the treatment.Results (1) Feasibility:3343 participants including 2320 patients and 1023 menopause women,were surveyed in 8 different settings.The recovery rate of CMRS was 100%,with a response rate as 99.7%.The completion of the CMRS took 10.30 minutes on average.(2)Reliability:Cronbach's alpha of CMRS,soma dimension,psychology dimension and community dimension of CMRS were 0.93,0.87,0.89 and 0.73 respectively,with the correlation coefficient of split half of the CMRS.Soma dimension,psychology dimension and community dimension were 0.92,0.89,0.86 and 0.73 respectively and the test-retest correlation coefficient of MRSTCM,the soma dimension,psychology dimension and community dimension were as 0.88,0.91,0.85 and 0.77 respectively.(3) Validity:CMRS was established on the basis of connotation of menopause syndrome,and a series of steps were adopted to modify the scale.CMRS was applicable for patients with menopause syndrome.CMRS seemed to have had good content-related validity.The result of exploratory factor analysis was accorded with the theory frame of CMRS by and large.The correlations between CMRS and KI,CMRS and WHOQOLBREF,CMRS and MENQOL seemed good.The CMRS was able to discriminate between groups of people with or without menopausal syndrome and bad good discriminative validity.(4) Responsibility:The CMRS was measured based on 174 patients with menopausal syndrome before and after the TCM therapy.Our result showed that the CMRS having the ability to measure the clinically important differences.Conclusion CMRS was suitable for outcome assessment of menopausal syndrome.This primary research proved that the CMRS had good feasibility,reliability,validity as well as responsiveness.