Objective:To establish a rapid, sensitive and accurate HPLC-QTOF/MS determination method for the illegally added antihypertensive drugs in traditional Chinese medicines and healthy care products .Methods:An Agilent Eclipse plus C 18 column ( 50 mm ×2.1 mm,1.8 μm) was adopted with the mobile phase of 0.5%formic acid and acetonitrile with gradient elution .The flow rate was 0.2 ml· min-1 .The electrospray ionization source was applied and operated in a positive ion mode .Results:The detection limit of 18 antihypertensive drugs was within the range of 0.2-2.5 ng· ml-1 .Reserpine was found in one sample .Conclusion:The method is selective and sensitive , which can be used for the detection of 18 chemical medicines illegally added in antihypertensive traditional Chinese medicines and health care products .

Objective:To improve the determination method for the residual solvents in olsalazine sodium. Methods:1,2-Dichlo-roethane and chloroform were determined by headspace GC with a DB-624 capillary column and an FID detector. The column tempera-ture was 110℃. The temperature of the injector and the detector was 200℃ and 250℃, respectively. The carrier gas was nitrogen with a flow of 3. 0 ml·min-1 . The split ratio was 1∶1. Water was used as the solvent. Results:1,2-Dichloroethane and chloroform were completely separated with good linearity within the respective range of 0. 25-2. 52 ( r =0. 999 5 ) and 2. 28-22. 84 μg · ml-1 ( r =0. 999 5). The average recoveries were 98. 4% and 99. 5% with RSD of 1. 14% and 0. 98%(n=9), respectively. The detection lim-it were 0. 02 and 0. 06 μg·ml-1 , respectively. Conclusion:The method is rapid, sensitive and accurate, which can be used in the determination of residual organic solvents in olsalazine sodium.

It is the objective of this paper to study pharmacokinetics-pharmacodynamics (PK-PD) characteristics of ginsenoside Rg1 and Rb1 on the effect of inducing nitric oxide (NO) release after intravenous administration of Shengmai injection to rats with myocardial ischemia. The model of myocardial ischemia rats was produced by subcutaneous injection of isoproterenol. The serum samples were collected at different time points after intravenous administration of Shengmai injection to rats with the dose of 10.8 mL x kg(-1). The concentrations of ginsenoside Rg1 and Rb1 in serum were determined, and then the concentration-time curves were drawn. Pharmacokinetic parameters of ginsenoside Rg1 and Rb1 were calculated after the construction of pharmacokinetic models. Meanwhile, NO2- and NO3-, the metabolites of NO, in serum were determined, and then the effect-time curve was drawn. The combined PK-PD model was established based on the theory of effect compartment by Sheiner et al. Then pharmacodynamic parameters were calculated. The results indicated that the pharmacokinetics of ginsenoside Rg1 and Rb1 conformed to a two-compartment model. Ginsenoside Rg1 and Rb1 exhibited quick and slow elimination in rats respectively. The effect of Shengmai injection on inducing NO release did not relate directly with and lagged behind the concentrations of ginsenoside Rg1 and Rb1 in serum. The effect exhibited good correlation with ginsenoside Rg1 and Rb1 levels in effect compartment. The relationship between effect and serum concentration fits Sigmoid-E(max) model. This study successfully established the combined PK-PD model of ginsenoside Rg1 and Rb1 after intravenous administration of Shengmai injection to rats. The model can efficiently predict the concentration and effect of Shengmai injection in vivo.
Administration, Intravenous ; Animals ; Ginsenosides ; administration & dosage ; pharmacokinetics ; Humans ; Male ; Myocardial Ischemia ; drug therapy ; metabolism ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the prognostic factors of young, middle-age and old-age colorectal cancer patients in order to improve the treatment in the future.

METHODSColorectal cancer patients (n = 842) who had undergon curative resection were divided into three groups according their age: young group (< or = 40 years), middle-age group (41 to 64 years) and old group (> o = 65 years). Thirty-five clinical factors in the three groups were analyzed and compared by univariate survival and multivariate analysis. Cox proportional hazards regression model was used with SPSS statistic software.

RESULTSThe overall 5-, 10- and 15-year survival rates were 66.3%, 54.2% and 48.5% respectively. The 5- and 10-year survival rates were 53.0% and 42.7% in the young group, which were lower than those in the other two groups. Cox proportional hazards regression model demonstrated that Dukes stage and family history of cancer were common prognostic factors in both young and middle-age groups; chronic constipation was an independent prognostic factor in middle-age group; bowel obstruction, length of operating time and number of metastatic lymph nodes were prognostic factors in the older group. In the young group, the symptomatic duration was not demonstrated as a prognostic factor. The 5- and 10-year survival rates were 82.6% and 64.5% in Dukes A stage; 73.3% and 67.4% in B stage; 37.3% and 27.0% in C stage; 33.3% and 22.2% in D stage. The survival rates in Dukes A and B stages were similar, but in Dukes C and D stages they were lower than those of the middle-age and older groups if the patient had the same stage of disease. In the young colorectal cancer patients with family cancer history, the 5- and 10-year survival rates were 73.1% and 64.5%, which were better than those of patients without it (48.1% and 37.3%).

CONCLUSIONIn young colorectal cancer patients, the survival rate is lower than those in the middle-age and old patients. Family cancer history and/or advanced Dukes stage are poor prognostic factors, whereas the symptomatic duration is not demonstrated as a poor prognostic factor. The prognostic factors affecting the survival after surgical treatment may be different in different age groups of colorectal cancer patients.

Adult ; Age Factors ; Aged ; China ; epidemiology ; Colorectal Neoplasms ; epidemiology ; mortality ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Survival Rate

Animals ; Bacterial Toxins ; chemistry ; pharmacology ; therapeutic use ; Humans ; Neoplasms ; therapy ; Neurotoxins ; chemistry ; pharmacology ; therapeutic use ; Proteins ; chemistry ; pharmacology ; therapeutic use ; Toxins, Biological ; chemistry ; pharmacology ; therapeutic use

Acute Disease ; Adult ; CD56 Antigen ; immunology ; Female ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; complications ; immunology ; surgery ; Recurrence ; Stem Cell Transplantation

OBJECTIVETo analyze the mutational features of adenomatous polyposis coli (APC) gene and to explore the effect of mismatch repair (MMR) deficiency on its mutations in hereditary non-polyposis colorectal cancers (HNPCC).

METHODSPCR-based in vitro synthesized protein test (IVSP) assay and sequencing analysis were used to confirm somatic mutations of whole APC gene in 19 HNPCC patients.

RESULTSEleven cases with thirteen mutations were determined. The frequency of APC mutation was 58%(11/19). The exhibiting mutations consisted of 9 frameshift mutations and 4 nonsense ones, indicating the existence of more frameshift mutations (69%). All of frameshift mutations were deletion or insertion of 1-2 bp and most of them (7/9) happened at simple nucleotide repeat sequences, particularly within (A) n tracts (5/9). All of four nonsense mutations resulted from C to T transitions at CpG sites.

CONCLUSIONMutational inactivations of APC gene were detected in more than half of HNPCC patients in this study, indicating that APC mutation is a common molecular event in the tumorigenesis of HNPCC. According to the location of frameshift mutations at simple nucleotide repeat sequences and point mutations at CpG sites, it was suggested that endogenous mechanisms like MMR deficiency might exert an effect on the nature of APC mutations in most HNPCC.

Adenomatous Polyposis Coli ; genetics ; Adenomatous Polyposis Coli Protein ; genetics ; metabolism ; Carcinoma ; genetics ; Colorectal Neoplasms ; genetics ; pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; Genes, APC ; physiology ; Humans

OBJECTIVETo investigate the effect of microRNA143 on cell proliferation and K-ras expression in colorectal carcinoma.

METHODSNorthern blot was used to examine the expression of miR-143 in colorectal carcinoma and adjacent normal tissues. A miR-143 expression vector was constructed and transfected into a human colon adenocarcinoma cell line SW480. Cell proliferation was evaluated by MTT assay. RT-PCR and Western blot were used to examine the expression of K-ras oncogene in transfected cells.

RESULTSThe level of mature miR-143 was lower in tumors compared with adjacent normal tissues in 81% of colorectal carcinoma specimens. In transfected cells, the increased accumulation of miR-143 inhibited the cell proliferation, and resulted in approximately 40.3% decrease of K-ras protein levels, but had no effect on level of K-ras mRNA.

CONCLUSIONThe increased accumulation of miR-143 inhibits the proliferation of transfected cells, and results in down-regulation of K-ras protein in colorectal carcinoma.

Adenocarcinoma ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Colonic Neoplasms ; genetics ; metabolism ; pathology ; Down-Regulation ; Genes, ras ; Genetic Vectors ; Humans ; MicroRNAs ; genetics ; metabolism ; Plasmids ; RNA, Messenger ; metabolism ; Transfection ; ras Proteins ; metabolism

OBJECTIVETo screen and evaluate the active constituents of Chinese medicinal herbs as potent inhibitors of Cdc25 phosphatase.

METHODSThe affinity chromatography purified glutashione-S-transferase/Cdc25A phosphatase fusion protein and Cdc2/cyclin B from the extracts of starfish M phase oocytes are used as the cell cycle-specific targets for screening the antimitotic constituents. We tested 9 extracts isolated from the Chinese medicinal herbs and vegetables including the agents currently used in cancer treatment by measuring the inhibition of Cdc25A phosphatase and Cdc2 kinase activity. The antitumor activity of the extracts was also evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry.

RESULTSCdc25A inhibitory activity and antitumor activity are detected in the extracts isolated from three Chinese medicinal herbs Agrimona pilosa; Herba solani lyrati; Galla chinesis.

CONCLUSIONWe found three extracts isolated from Chinese medicinal herbs have potential inhibitory activity of Cdc25 phosphatase using a highly specific mechanism-based screen assay for antimitotic drug discovery.

Apoptosis ; drug effects ; Cell Cycle Proteins ; antagonists & inhibitors ; metabolism ; Cell Line, Tumor ; Cyclin-Dependent Kinases ; metabolism ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; analysis ; chemistry ; pharmacology ; Humans ; Lethal Dose 50 ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; enzymology ; pathology ; Medicine, Chinese Traditional ; methods ; Mitosis ; drug effects ; Phytotherapy ; methods ; Plants, Medicinal ; chemistry ; cdc25 Phosphatases ; antagonists & inhibitors ; metabolism

OBJECTIVETo gain an insight into large genomic deletions in mismatch repair genes MSH2 and MLH1 in Chinese hereditary nonpolyposis colorectal cancer (HNPCC) patients in order to improve genetic detections of HNPCC kindreds.

METHODSFourteen peripheral blood DNA samples were obtained from 14 unrelated HNPCC patients, and fluorescent labeled quantitative multiplex PCR was used to detect large genomic deletions in MSH2 and MLH1 genes.

RESULTSOne of the fourteen probands, a man, was found to have MSH2 exon 1-7 deletions. His cancer-distressed son was also found to have the mutations. Additionally, three normal members of the family had the same mutations.

CONCLUSIONLarge genomic deletions which mainly present to MSH2 account for 20% of general pathological sequence changes of MSH2 and MLH1 genes in Chinese HNPCC patients, and large genomic detections of mismatch repair genes should be included in the regular genetic detections of Chinese HNPCC kindreds.

Adaptor Proteins, Signal Transducing ; genetics ; Asian Continental Ancestry Group ; genetics ; China ; Colorectal Neoplasms, Hereditary Nonpolyposis ; ethnology ; genetics ; pathology ; Female ; Humans ; Male ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; genetics ; Nuclear Proteins ; genetics ; Pedigree ; Polymerase Chain Reaction ; Sequence Deletion