OBJECTIVE:To study inhibitory effects in vivo and in vitro of gemcitabine on liver cancer. METHODS:MCF-7 cells and HepG2 cells were treated with different concentrations of gemcitabine solutions(5,10,20,30,50,70 and 90 μmol/L). The absorbance of cells was determined by MTT assay after treated for 24,48 and 72 h. The inhibition ratio and 50% inhibiting concentration(IC50) of cells were calculated. Tumor-bearing mice were established by inoculating 0.2 ml liver cancer H22 cell line via right anterior axillary,and then randomly divided into control group(normal saline)and gemcitabine group(40 mg/kg)with 5 mice in each group. They were given relevant medicine intravenously every 2 days,for 3 times. The changes of body weight and in-hibition ratios were recorded. RESULTS:Gemcitabine can inhibit MCF-7 cells and HepG2 cells,and IC50 of gemcitabine to them were 30 and >90 μmol/L within 24 h respectively,and those of gemcitabine to them were all lower than 5 μmol/L after 48 h and 72 h. There was no statistical significance in body weight of tumor-bearing mice between 2 groups,and inhibitory rate of gemcitabi-ne to H22 cell line was 75.76%. CONCLUSIONS:Gemcitabine can inhibit liver cancer in vivo and in vitro.

ObjectiveTo evaluate the safety and efficacy of tirofiba in the treatment of patients with acute ST-elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI). MethodsA total of 158 patients with acute STEMI were randomly divided into tirofiban group 1 (59 cases, received tirofiban before PCI), tirofiban group 2 (56 cases, received tirofiban when PCI) and control group(43 cases, only received PCI). The coronary reperfusion flow(TIMI grade) of infarct related artery (IRA) after PCI, the resolution of the sum of ST segment elevation(sum STR) at 90 min after the procedure, the changes of myocardial enzyme at 6 h and 12 h afterwards, the left ventricular ejection fraction (LVEF) 1 week later, the major adverse cardiac events(MACE) within 30 d, bleeding and thrombocytopenia complications were analyzed and compared among the three groups. ResultsTIMI reperfusion grades in tirofiban group 1[98.3％(58/59 )]and tirofiban group 2[92.9％(52/56)]were higher than those in control group[60.5％(26/43)](P ＜0.05). The resolution of sum STR at 90 min after PCI in tirofiban group 1 [(89.3 ± 6.9)％]and tirofiban group 2[(82.4 + 7.3)％]was higher than that in control group[(65.6 +8.1 )％](P＜ 0.01 ),and there was significant difference between tirofiban group I and tirofiban group 2 (P＜0.05 ). The occurrence of MACE within 30 d was lower in tirofiban group 1 and tirofiban group 2 than that in control group (P＜ 0.05). The level of CK-MB at 6 h and 12 h afterwards was lower in tirofiban group 1 than that in tirofiban group 2,and tirofiban group 2 was lower than control group (P＜ 0.05). LVEF 1 week later in tirofiban group 1[(56.2 + 6.4)％]was higher than that in tirofiban group 2[(51.1 + 4.9)％]and control group[(49.8 + 5.7)％](P ＜ 0.05),but there was no significant difference between tirofiban group 2 and control group (P ＞ 0.05). Although bleeding incidence in tirofiban group 1 and tirofiban group 2 was higher than that in control group, no severe bleeding and thrombocytopenia was observed. Conclusion Tirofiban can safely and effectively reduce the incidence of the ischemic events in the patients with acute STEM1 during preoperative of emergency PCI.

s To compare the clinical effects of intravenously and orally administered aspirin in the treatment for acute coronary syndrome (ACS),and to evaluate the adverse effects of intravenous administration of aspirin.Methods One hundred and twenty-five patients with unstable angina pectoris or acute myocardial infarction were randomized into three groups:group 1 received intravenous aspirin (300mg/d,n =40),while groups 2 (n =42) and 3 (n =43) received orally administered aspirin (100mg/d and 300mg/ d,respectively).The control group included 30 patients with no heart disease or blood disease,and they had never taken aspirin and clopidogrel.Blood samples were taken at 2nd and 7th day of hospitalization.Platelet aggregation and the level ofplatelet activation marker CD62p were measured and compared among the groups.Patients were followed up for 6 months for the occurrence of major adverse cardiovascular events.Results There were no statistically significant differences in the decrease in adenosine diphosphate (ADP)-induced platelet aggregation rate (12.01±10.45%,6.76±14.62% and 9.73±16.72% for group 1,group2 and group 3,respectively),the decrease in arachidonic acid (AA)-induced platelet aggregation rate (6.73±11.34%,6.95±12.45% and 7.57±13.11%,respectively),and the decrease in CD62p level (10.89±18.62%,8.92±11.57% and 7.05±15.67%,respectively).At six months,there were 4 deaths (10%) in group 1,4 deaths (9.5%) in group 2 and 5 deaths (11.6%) in group 3 (P＞0.05).Conclusions Intravenous administration of aspirin provides a new approach as an anti-platelet treatment for ACS patients,especially those who can not tolerate oral administration of aspirin.(J Geriatr Cardiol 2008;5:212-216)

The methylation status of GNAS1 gene in pseudohypoparathyroidism type Ib patients was detected by methylation-specific PGR technique. There was an abnormal methylation of 1A region in all seven PHPIb patients. Loss of exon 1A methylation (imprinting defect) seems to be the cause of PHPIb.

Up to 2015, almost all of the Third-grade class-A TCM hospitals in Beijing set up multiple sub-hospitals, under the regional integrating of Beijing-Tianjin-Hebei region, in order to meet regional homogenization of medical and health care demand, to provide high-quality medical service for the patients, and to improve the hospital development in a certain stage. Taking Beijing university of traditional Chinese medicine affiliated Dongfang hospital for example, it creates "two sub-hospitals " a court layout of mode of "one hospital with multiple branches". This article analyzed the sub-hospitals organization structure reform, cost budget control, performance management & personnel training, information system construction, to draw lessons from practical manage experience, and explored the "multiple sub-hospitals " superior management mode for our hospital.

Geldanamycin (Gdm), an inhibitor of heat shock protein 90 (Hsp90), shows antitumor and antivirus bioactivity. Most Geldanamycin biosynthetic genes have been cloned from the genome library of Streptomyces hygroscopicus 17997. In this report, polyketide synthase (pks) gene, mono-oxygenase (gdmM) gene and carbamoyltransferase gene (gdmN) were subjected to inactivation. Three gene disrupted mutants (deltapks, deltagdmM and deltagdmN) were obtained by double crossover. No Geldanamycin production was detected in three mutant strains cultured in fermentation broth. Gene complementation experiments excluded the possible polar effect of gene disruption on other genes. These results confirmed that pks, gdmM and gdmN genes were essential for Geldanamycin biosynthesis.
Benzoquinones ; metabolism ; Carboxyl and Carbamoyl Transferases ; genetics ; Lactams, Macrocyclic ; metabolism ; Mixed Function Oxygenases ; genetics ; Polyketide Synthases ; genetics ; Streptomyces ; genetics ; metabolism

Spiramycin and midecamycin are 16-membered macrolide antibiotics with very similar chemical structures. Spiramycin has three components, namely spiramycin I, II and III. Spiramycin II and III are, respectively, the O-acetyl and propionyl derivatives at C3-hydroxyl group of spiramycin I. Midecamycin has four components, and the C3-hydroxyl group of midecamycin is all O-propionylated. The enzyme adding acyl group(s) at the C3-hydroxyl group during the biosynthesis of spiramycin and midecamycin is 3-O-acyltransferase. The 3-O-acyltransferases for spiramycin and midecamycin are also very similar, and presume to function when exchanged. To explore whether the 3-O-acyltransferase for midecamycin biosynthesis hold still the character of selective and efficient propionylation for spiramycin I at its C3-hydroxyl group, we inserted mdmB, the 3-O-acyltransferase gene from Streptomyces mycarofaciens ATCC 21454 for midecamycin biosynthesis, into a mutant strain of S. spiramyceticus F21, in which the 3-O-acyltransferase gene for spiramycin biosynthesis, sspA, was deleted; and the mdmB was integrated exactly into the chromosomal site where the sspA was deleted. We name this "hybrid" strain as SP-mdmB. HPLC analysis of the spiramycin produced by SP-mdmB showed that spiramycin I was still the major component, although the relative proportions of both spiramycin II and III increased significantly. We thus conclude that MdmB from Streptomyces mycarofaciens ATCC 21454 for midecamyicn biosynthesis do not hold the character of selective and efficient propionylation for spiramycin I within S. spiramyceticus F21, and this character is possibly limited in Streptomyces mycarofaciens ATCC 21454 for midecamycin biosynthesis.
Acylation ; Acyltransferases ; genetics ; metabolism ; Culture Media ; Genes, Bacterial ; Genetic Engineering ; methods ; Leucomycins ; biosynthesis ; Spiramycin ; biosynthesis ; Streptomyces ; enzymology ; genetics ; Substrate Specificity

To identify the anti-bacterial compound(s) from Streptomyces hygroscopicus 17997, a geldanamycin producer, silica gel thin layer chromatography (TLC) TLC was used to separate the secondary metabolites of S. hygroscopicus 17997. Compound(s) from the silica gel TLC with anti-Gram positive bacteria activity and becoming red upon color reaction by 2.0 mol/L NaOH was analyzed by HPLC. The UV absorption profile and the retention time of a peak of HPLC were identical to those of authentic elaiophylin. A conserved region of dTDP-glucose-4,6-dehydratase (Tgd) gene was amplified by PCR from the genomic DNA of Streptomyces hygroscopicus 17997. DNA sequence analysis of the amplified DNA fragment indicated that it should be the tgd gene of elaiophylin biosynthetic gene cluster. These results implied that the compound in the peak of HPLC was elaiophylin, a macrodiolide antibiotic. The compound was then confirmed to be elaiophylin by LC-(+)-ESI-MS, which revealed that Streptomyces hygroscopicus 17997 was an elaiophylin producer. At the same time, a fast procedure, which consisted of silica gel TLC, color reaction, HPLC, PCR detection and DNA sequence analysis of tgd gene, and LC-(+)-ESI-MS, was established for rapid identification of elaiophylin and its producer.
Benzoquinones ; metabolism ; Chromatography, Liquid ; methods ; DNA, Bacterial ; genetics ; Hydro-Lyases ; genetics ; Lactams, Macrocyclic ; metabolism ; Macrolides ; analysis ; isolation & purification ; metabolism ; Mass Spectrometry ; methods ; Sequence Analysis, DNA ; Streptomyces ; genetics ; isolation & purification ; metabolism

Drug delivery systems (DDS) are defined as methods by which drugs are delivered to desired tissues, organs, cells and subcellular organs for drug release and absorption through a variety of drug carriers. Its usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility, drug aggregation, low bioavailability, poor biodistribution, lack of selectivity, or to reduce the side effects of therapeutic drugs. During 2015-2018, significant progress in the research on drug delivery systems has been achieved along with advances in related fields, such as pharmaceutical sciences, material sciences and biomedical sciences. This review provides a concise overview of current progress in this research area through its focus on the delivery strategies, construction techniques and specific examples. It is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.