Aged ; Aged, 80 and over ; Anthracosis ; complications ; microbiology ; Drug Resistance, Bacterial ; Gram-Negative Bacteria ; isolation & purification ; Gram-Negative Bacterial Infections ; complications ; Humans ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; etiology ; microbiology

Objective To establish a method for studying molecular mechanism of Rhubarb inhibiting anti-Yersinia pesti based on DNA microarray.Methods A whole genome DN A microarray containing 4005 annotated genes of Yersiniapesti Was used.The minimal inhibitory concentration(MIC)of Rhubarb to Yersiniapestiwas determined by liquid dilution method.The gene expression profile of Yersinia pesti was performed after the exposure to Rhubarb at a concentration of 10×MIC for 30 minutes.The total RNA extracted and purified from Yersinia pesti Was reversely transfected to cDNA and labeled by Cy3-Cy5 dye.The labeled probes were hybridized to the microarray anti the results were obtained by a laser scanner and the microarray data was confirmed by real-time quantitative RT-PCR.Results The platform of the DNA microarray-based bacteria transcriptional profile was established.A total of 498 genes of Yersinia pesti changed significantly in response to Rhubarb.Among them.358 genes were up-regulated,140 down-reguated.Conclusions The whole genome DNA microarray can be used in the studying of molecular anti-Yersinia pesti mechanism of Rhubarb.

Objective To investigate the antibacterial molecular mechanism of Traditional Chinese Medicine Coptis rhizome against Yersinia pestis(Y.pestis).Methods The method based on whole genome DNA micrnarray of Y.pestis was used.The minimal inhibition concentration(MIC)of berberine to Y.pestis was determined with liquid dilution method.Then gene expression profile of Y.pestis was performed after exposed to berberine at the concentration of 10×MIC for 30 minutes.Total RNA extracted and purified from Y.pestis and reverse-transcribed to cDNA,then labeled by Cy-dye.Finally,the labeled probes were hybridized to the microarray and the results were obtained by a laser scanner and analyzed by the SAM software.Results The gene expression profile data revealed that the response of Y.pestis to berberine was a global phenomenon.A total of 360 genes changed significantly.Among them,333 genes were up-regulated,27 down-regulated.These differentially expressed genes were further classified into 24 different functional categories based on the genomie annotation of Y.pestis CO92,in which the number of mainly related genes were 83,75 and 48,including cell envelop,unkown,transport/binding proteins functions.The 40 genes related to the metabolism were upregulated,which was a remarkable change.Conclusion Our results have revealed the general gene expression changes of Y.pestis in response to berberine and demonstrated the antibacterial molecular mechanism of the Coptis rhizome.The major mechanism of Y.pestis in response to berberine is the upregulation of genes related to the metabolism.

Objective To investigate drug resistance genes and epidemic characteristics of β-lactamase carried by carbapenem-resistant Acinetobacter baumannii (CRAB) in the respiratory intensive care unit(RICU) in a hospital.Methods Clinically isolated CRAB from RICU patients in October-December 2015 were collected.Five drug resistance genes (KPC-2,IMP,VIM,NDM-1,OXA-23) were specifically amplified by polymerase chain reaction (PCR),amplified products were performed agarose gel electrophoresis and sequencing analysis,the homology was analyzed with pulsed-field gel electrophoresis (PFGE).Results A total of 22 CRAB strains were isolated in October-December 2015,19 (86.36％) of which were isolated from sputum.The resistance rate of 22 CRAB strains to compound sulfamethoxazole was 59.09 ％,resistance rate to minocycline was 9.09 ％,all were sensitive to polymyxin B,resistance rates to other antimicrobial agents were more than 80％.Three kinds of resistance genes KPC-2,IMP and NDM-1 were not found by PCR amplification,positive rates of VIM and OXA-23 were both 100％.PFGE homology analysis revealed that 22 strains were divided into 13 different types,each type contained 1-5 strains,9 types(69.23％) contained only 1 strain respectively,the other 4 types (30.77％) contained 2-5 strains.A5,A7,and A8;A9,A11,A14,A19 and A22;A4,A10 and A12;A16 and A18 were of the same type respectively.Conclusion The main types of β-lactamase-resistant genes of CRAB in RICU are VIM and OXA-23.Homology analysis shows a small parts are of the same clone strains,which reveals epidemic of a small scale.

OBJECTIVETo develop a colon-specific prodrug of Indomethacin microbially triggered, carry out in vitro/in vivo evaluation of drug release, and appraise its inhibitory effect on liver metastasis from colon cancer.

METHODSIndomethacin prodrugs were synthesized and characterized by FTIR and NMR, and dissolution test simulating gastrointestinal tract was employed to screen the colon-specific prodrug. Then, the pharmacokinetic profile of portal vein and peripheral blood in Sprague-Dawley rats was studied. Lastly, the inhibitory effect on liver metastasis from colon cancer in nude mice was observed.

RESULTSThe chemical structure characterized by FTIR and NMR demonstrated that six kinds of indomethacin-block-amylose with different drug loading (IDM-AM-1-6) were synthesized, among which IDM-AM-3 was degraded 1.3%, 9.3% and 95.3%, respectively, in simulated gastric fluid for 4 h, small intestine for 6 h, and colon for 36 h. The pharmacokinetic test of IDM-AM-3 showed that absorption was delayed significantly (P < 0.01), peak time [(11.35 + or - 2.45) h], elimination half-life [(16.74 + or - 4.04) h] and mean residence time [(22.27 + or - 0.52) h] were significantly prolonged (P < 0.01), as well as peak serum concentrations [(9.69 + or - 2.40) mg/L] and AUC(0-t) [(236.7 + or - 13.1) mg x L(-1) x h] were decreased markedly (P < 0.01) as compared with those of IDM regarding to portal vein. Additionally, its AUC(0-t) in peripheral blood was remarkably lower than that in Portal vein (P < 0.01). The tumor suppression observation showed that it could remarkably reduce the number of liver metastases in contrast to IDM (P < 0.05).

CONCLUSIONColon-specific IDM-AM-3 possesses advantage of sustained release in portal vein providing some experimental basis for colon-specific delivery system applied to sustained release in the portal vein.

Amylose ; administration & dosage ; chemical synthesis ; pharmacokinetics ; therapeutic use ; Animals ; Colon ; metabolism ; Colonic Neoplasms ; pathology ; Delayed-Action Preparations ; Drug Delivery Systems ; HT29 Cells ; Humans ; Indomethacin ; administration & dosage ; chemical synthesis ; pharmacokinetics ; therapeutic use ; Liver Neoplasms ; prevention & control ; secondary ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Prodrugs ; administration & dosage ; chemical synthesis ; pharmacokinetics ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the mechanism of clinical haemorrhage in an inherited coagulation factor VII (FVII) deficiency and tissue factor abnormality pedigree.

METHODSAll exons, exon-intron boundaries and the 3', 5' untranslated sequences of FVII and tissue factor (TF) genes were amplified by PCR and sequenced directly. Any mutation identified by direct sequencing was confirmed by reverse sequencing. FVII cDNA of the proband was synthesized with random primers and amplified by nest PCR.

RESULTS55C-->T heterozygous mutation located in promoter of FVII gene was identified in the proband. The heterozygous mutation was derived from his mother. Tracing the other pedigree members found that his sister had the same heterozygous mutation and the others had wild-type FVII genes. A 9363 C-->T (Arg131Trp) heterozygous polymorphism in TF gene, which was 2.63% frequency of T allele polymorphism, was found in all of the pedigree members.

CONCLUSIONIt was the first report that the -55C-->T heterozygous mutation in FVII gene and the Arg131Trp heterozygous polymorphism in TF gene explained the clinical symptom of the proband.

Adult ; DNA Mutational Analysis ; Factor VII ; genetics ; Factor VII Deficiency ; genetics ; Heterozygote ; Humans ; Male ; Pedigree ; Polymorphism, Genetic ; Thromboplastin ; genetics

OBJECTIVETo investigate the effect and the possible mechanism underlying the promotional effect of Astragalus membranaceus and Panax notoginseng on the transformation of bone narrow stem cells and proliferation of EPC.

METHODThe marrow blood was collected in the patients with ischemia of lower limbs and BM-MNCs were separated and proliferated under different conditions. A. morphologic observation was performed and the ratio of CD34+ cells was measured.

RESULTThe shuttle shaped cells lined up as bunches with several round cells scattered. The ratio of CD34+ cells was significantly increased in groups treated with medium (P < 0.01) and lower (P < 0.05) dosages of A. membranaceus and medium (P < 0.01) and high dosages (P < 0.01) of P. notoginseng respectively as compared with control group.

CONCLUSIONA. membranaceus and P. notoginseng can promote the transformation and proliferation of EPC.

Antigens, CD34 ; metabolism ; Astragalus membranaceus ; chemistry ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Endothelial Cells ; cytology ; drug effects ; metabolism ; Ginsenosides ; administration & dosage ; isolation & purification ; pharmacology ; Hematopoietic Stem Cells ; cytology ; drug effects ; metabolism ; Humans ; Panax notoginseng ; chemistry ; Plants, Medicinal ; chemistry

To search for potential antitumor drugs with potent efficiency and low toxicity, a novel 1,4,7-triazacyclodecane and its platinum (II) complex were synthesized. These compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, MS spectra, thermoanalysis and conductivity measurement. Antitumor activity study indicated these compounds had strong antitumor activity in vitro to some extent. Inhibition of human liver tumor of CA was examined by antitumor rate and growth rate, complex C showed inhibition activity on transplanting-tumor growth of CA, 12 mg x kg(-1) was as potent as cisplatin, its ID50 was 853.6 mg x kg(-1).
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Screening Assays, Antitumor ; Female ; Humans ; Inhibitory Concentration 50 ; Liver Neoplasms ; pathology ; Male ; Mice ; Neoplasm Transplantation ; Organoplatinum Compounds ; chemical synthesis ; chemistry ; pharmacology ; Random Allocation

OBJECTIVETo compare brain lead accumulation and neurotoxicity induced by lead under drinking purified water and tap water on rat.

METHODSAll 104 male weaning SD rats were randomly divided into eight groups, matched-four pairs according to drinking water: tap water, purified water, tap water with lead 50 mg/L(lead acetate water-solution), purified water with lead 50 mg/L, tap water with lead 200 mg/L, purified water with lead 200 mg/L, tap water with lead 800 mg/L. All were fed with normal food and environmental cognitions kept consistent Morris water maze(including Place Navigation, Spatial Probe Test, Visible Platform Trial) was measured to test rat spatial learning at the 12 and 24 week. At the end of the experiment (28 week), rats were killed and the lead of brain and blood was measured by Graphite furnace atomic absorption spectrometric method; the NR1, NR2A, NR2B of NMDAR (N-methyl-D-aspartame receptor) in hippocampus were analyzed by RT-PCR.

RESULTSUnder the same lead exposure, no significant differences were observed in blood lead, however, brain lead level showed higher in drinking purified water group than that in tap water group. Expression of NR1, NR2A and NR2B in hippocampus of the rats drinking purified water was lower than those drinking tap water, especially at low lead exposure (50 mg/L) (P < 0.05). In the 24 week Morris water maze, place navigation test's escape latency showed significantly prolonged at the rats drinking purified water as compared with those drinking tap water on the pairs of 50 mg/L and 200 mg/L pb2+ groups (P < 0.05), and the differences occurred in early 1-2 days.

CONCLUSIONCompared with drinking tap water, drinking purified water might increase the accumulation of brain lead, lower NR1, NR2A, NR2B expression and delay the spatial learning and memory ability under chronic lead exposure in water.

Animals ; Drinking ; Intelligence ; drug effects ; Lead ; toxicity ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; N-Methylaspartate ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; drug effects

OBJECTIVETo explore the regulatory effect of clearing-Heat secreting-bile regulating-Qi flow and activating blood circulation (CSRA) principle on cholecystokinin receptor (CCK-R) and its mechanism.

METHODSCholecystokinin (CCK) in serum of portal venous blood, maximum binding capacity (Bmax) and affinity (Kd) of CCK-R levels in gallbladder of guinea pigs allocated in four groups (control, high cholesterol, natural recovery and treated groups) were determined using radioimmunoassay and radioligand receptor assay (RRA). At the same time, changes of fasting volume (FV) and postprandial volume (PV) of gallbladder, fasting and postprandial bile (FB and PB) in gallbladder, gallbladder contraction rate (GCR) and cholesterol concentration (CC) in bile were observed.

RESULTSCompared with the control group, after two weeks of high cholesterol feeding, increase of FV, FB, PV, PB and CC (P < 0.05), and decrease of GCR (P < 0.01) and Bmax were found in cholesterol group, but with no significant change in Kd and CCK level. The above-mentioned criteria were restored to normal range in the treated group.

CONCLUSIONCSRA principle could promote the recovery of gallbladder contraction by regulating CCK-R expression in it, its mechanism is possibly correlated with reduction of cholesterol concentration in bile.

Animals ; Bile ; metabolism ; Cholecystokinin ; metabolism ; Cholesterol ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Gallbladder ; physiopathology ; Guinea Pigs ; Hypercholesterolemia ; metabolism ; Male ; Medicine, Chinese Traditional ; Random Allocation ; Receptors, Cholecystokinin ; metabolism