OBJECTIVETo investigate synergistically killing effect of histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) combined with imatinib on human chronic myeloid leukemia (CML) cell line.

METHODSK562 cells were co-treated with SAHA and imatinib. Cell growth was measured by MTT assay. Apoptosis was determined using Hoechst staining apoptosis detection kit and flow cytometric analysis. Activation of Caspase pathway, expression of Bcr-Abl and its downstream target genes, and expression of anti-apoptotic proteins were detected by Western blot.

RESULTSSAHA synergized the cytotoxicity of imatinib against leukemia K562 cells, concomitantly with increased apoptosis and enhanced activation of Caspase-3, -8 and PRAP. The combination therapy resulted in significantly lower levels of Bcr-Abl,phosphorylated Bcr-Abl compared to treatment with either SAHA or imatinib alone. Furthermore,the co-treatment resulted in down-regulation of anti-apoptotic protein Mcl-1 expression. Also,marked down-regulated expression of JAK2,STAT5,and phosphorylated STAT5 was detected in the combination therapy.

CONCLUSIONCombining HDAC inhibitor SAHA with imatinib can kill CML cells synergistically by inhibiting cell growth and inducing apoptosis, which is associated with activation of Caspase pathway and regulation of anti-apoptotic proteins.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Benzamides ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Drug Synergism ; Fusion Proteins, bcr-abl ; metabolism ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Hydroxamic Acids ; pharmacology ; Imatinib Mesylate ; Intracellular Signaling Peptides and Proteins ; metabolism ; Janus Kinase 2 ; metabolism ; K562 Cells ; Piperazines ; pharmacology ; Pyrimidines ; pharmacology ; STAT5 Transcription Factor ; metabolism

OBJECTIVETo demonstrate the myocardial lesion associated with long-term administration of methamphetamine in rats.

METHODSThe experimental models of intoxication of methamphetamine were established in Sprague-Dawley rats. Methamphetamine hydrochloride (3 mg x kg(-1) x d(-1)) was subcutaneously injected to rats in methamphetamine-treated group (n = 16), and normal saline at the same dose was injected to rats in control group (n = 16). After 1 week and 8 weeks of injection, 8 rats in each group were sacrificed and their hearts were examined with light microscopy and electron microscopy, respectively.

RESULTSAfter 1 week of methamphetamine exposure, foci of contraction band and cellular degeneration were present in subendocardial myocardium. Cellular degeneration, myocytolysis, and contraction band necrosis became prominent and extensive in methamphetamine-treated rats after 8 weeks. Hypertrophy, intracellular vacuolization, and fibrosis were also observed. The ultrastructural feature showed marked swelling and degeneration of mitochondria, enlargement of sarcoplasmic reticulum, and dissolution of myofilaments. No obvious cardiac myocyte lesions were observed in rats of control group.

CONCLUSIONMethamphetamine abuse daily for a long time may result in an increased risk of cardiovascular lesions similar to cardiomyopathy.

Adolescent ; Adult ; Animals ; Heart ; drug effects ; Humans ; Male ; Methamphetamine ; administration & dosage ; adverse effects ; Myocardium ; pathology ; ultrastructure ; Rats ; Rats, Sprague-Dawley

A new viral sampling concentration device was designed which was equipped with a new cationic filter membrane-Nanoceram suitable for field sampling. Norovirus Genegroup II was detected from environmental water with the aid of this device. The effects on virus recovery of prefiltration, various second-concentration methods, and different eluants were investigated through pre-experiment. The concentration optimized process, and the optimal concentration process were then determined. The results showed that the prefiltration had a profound effect on virus recovery, and two second-concentration method: PEG-NaC1 precipitation and celite adsorption, had almost the same concentration effects. The Na2 HPO4 solution of 0.15 mol/L was selected as the final eluant to elute the adsorbed Nuorovirus from the celite. The virus recovery of Nanoceram was determined to be 3.02%. Finally, successful detection of Norovirus GII in sewage from Yangqiao River, Fengtai District, Beijing was acheived. All these data had shown that the Naneceram filter concentration method could concentrate Norovirus from environmental water with a steady effects.
Filtration ; instrumentation ; methods ; Fractional Precipitation ; instrumentation ; methods ; Genotype ; Norovirus ; classification ; genetics ; isolation & purification ; Rivers ; virology ; Water Microbiology

OBJECTIVETo establish a stable high red fluorescent protein (RFP)-expressing orthotopic transplantation nude mice spontaneous metastasis model of pancreatic cancer.

METHODSStable high RFP-expressing cells SW1990-RFP were injected subcutaneously into mice to establish subcutaneous implantation model. Fluorescent tumor piece from subcutaneous was transplanted into the body of the pancreas to establish surgical orthotopic implantation model. The growth of primary tumor, metastasis and micrometastasis were assessed by whole-body fluorescence imaging system.

RESULTSTwelve RFP orthotopic transplantation nude mice metastasis models of pancreatic cancer were established successfully, the percentage of success rate was 100%. RFP-labeled pancreatic cancer growth could be monitored in real time way. The micrometastasis of primary lesions were detected in early stage with whole-body fluorescence imaging system.

CONCLUSIONSThe RFP orthotopic transplantation nude mice metastasis model of pancreatic cancer is stable and reliable, and can be observed dynamically in vitro in a noninvasive way, with much higher sensitivity and specificity.

Animals ; Disease Models, Animal ; Female ; Luminescent Proteins ; Male ; Mice ; Mice, Nude ; Neoplasm Metastasis ; Pancreas ; pathology ; Pancreatic Neoplasms ; pathology ; Xenograft Model Antitumor Assays

OBJECTIVETo analyze and evaluate the acceptability of mifepristone compatible with misoprostone versus conventional surgical abortion among women under unwanted early pregnancy, so as to help the unexpected pregnant women to choose the satisfactory abortion, and to provide the evidence for clinicians to make a proper clinical decision.

METHODSSix medical databases were searched, including MEDLINE, EMBASE, Cochrane library, CBMdisc, CNKI and VIP, together with twelve journals hand-searched, and references of included studies additionally searched. Two qualified reviewers reviewed the original articles, evaluating qualities of articles, and extracting data independently. After heterogeneity test, the data was pooled using Revman software if capable, or descriptive analysis was applied.

RESULTSIn total, nine original clinical controlled trials were included, containing 3565 cases. Before abortion, more unwanted pregnant women chose the medical abortion because they believed medical abortion was less painful than surgical abortion (OR = 466.51, 95% CI: 91.37 - 2381.88), but medical abortion was less time-consuming than surgical abortion (OR = 0.02, 95% CI: 0.01 - 0.06). After abortion, satisfaction with medical abortion was similar to that with surgical abortion, with insignificant difference (P = 0.89). However, second choice and recommendation rates of medical abortion were much higher than those of surgical abortion with OR and 95% CI as 2.72, 2.13 - 3.47 and 4.19, 2.16 - 11.16, respectively.

CONCLUSIONSMedical abortion was less painful than surgical abortion and the rate of second choice and recommendation to others were all also higher than those of surgical abortion. However, the process of medical abortion was not as quick as surgical abortion but the satifacation of both methods seemed similar. Therefore, the two artificial abortion methods were not recommended to replace each other at the present time.

Abortifacient Agents ; adverse effects ; Abortion, Induced ; adverse effects ; methods ; Choice Behavior ; Controlled Clinical Trials as Topic ; Female ; Humans ; Mifepristone ; Misoprostol ; Pain ; etiology ; Patient Satisfaction ; statistics & numerical data ; Pregnancy ; Pregnancy, Unwanted

OBJECTIVETo investigate the pathohistological characteristics of the prostate tissues in patients who receive a second TURP and to evaluate their clinical significance.

METHODSWe collected surgical specimens from 50 cases of TURP (the control group) and another 50 cases of re-TURP (the re-TURP group), detected the expressions of CD34, vascular endothelial growth factor (VEGF) and androgen receptor (AR) in the prostate tissues by immunohistochemistry (S-P), and determined microvessel density (MVD) and the expressions of VEGF and AR. We performed statistical analyses on the results obtained from the specimens of the control group as well as from those of the first and second operations of the re-TURP group.

RESULTSVEGF and AR expressed in all the specimens. The expressions of VEGF and AR and MVD were significantly higher in the re-TURP group than in the controls (P < 0.05), but showed no significant differences between the first and second operations in the re-TURP group (P > 0.05). Positive correlations were found between the expressions of AR and VEGF, VEGF and MVD, and AR and MVD (r = 0.650, 0.705 and 0.525, P < 0.05).

CONCLUSIONIncreased AR, VEGF and MVD in the prostatic tissues may be one of the important causes of recurrence of BPH after TURP, and could be considered as the risk factors for postoperative recurrence and targeted indicators for preventive measures.

Humans ; Male ; Prostatic Hyperplasia ; metabolism ; pathology ; surgery ; Receptors, Androgen ; metabolism ; Reoperation ; Transurethral Resection of Prostate ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo study the relationship between inflammation and neointimal proliferation after coronary stent implantation in porcine model.

METHODSTwenty normal minipigs were randomly divided into group A (implanted with 316L bare metal stents), group B (implanted with 605L bare metal stents), group C (implanted with PLGA coating 605L stents), and group D (implanted with rapamycin-loaded PLGA coating 605L stents). Each minipig was implanted with two same stents in left anterior descending artery and right coronary artery. Four weeks later, the animals were sacrificed and histomorphometric measurements on the stent-segment coronary arteries were made to calculate the correlation between inflammation area and neointimal area.

RESULTSGroup D had the smallest neointimal area [(0.64 +/- 0.38) mm2, P < 0. 001] and inflammation area (median 0.00 mm2, P = 0.009) among all the groups, while there were no statistical differences among group A, B, and C in neointimal area [(2.09 +/- 0.90), (2.11 +/- 1.07), and (1.42 +/- 0.35) mm2 respectively] and in inflammation area (0.22 , 0.21, and 0.09 mm2, respectively). Bivariate correlation analysis showed that the inflammation area was positively correlated with the neointimal area (P < 0.001, correlation coefficient = 0.719). When stent type, mean injury score, and EEL area were adjusted, partial correlations analysis showed that the inflammation area was still positively correlated with the neointimal area (P = 0.01, correlation coefficient = 0.498).

CONCLUSIONInflammation promotes the neointimal proliferation after coronary stent implantation. Sirolimus-eluting stent may reduce the inflammatory response.

Animals ; Coronary Vessels ; pathology ; Drug-Eluting Stents ; adverse effects ; Inflammation ; pathology ; Neointima ; pathology ; Stents ; adverse effects ; Swine ; Swine, Miniature ; Tunica Intima ; pathology

OBJECTIVEScreening and identification of differentially expressed genes in human primary hepatocellular carcinoma(HCC).

METHODSThe differentially expressed genes subtracted cDNA library of HCC constructed by suppression subtractive hybridization(SSH) technique was screened by colony in situ hybridization, then the positive clones were further screened with PCR amplification. The positive clones were sequenced and analyzed for homology in the Genbank databases with Basic Local Alignment Search Tool BLAST . The novel cDNA sequences were analyzed by Northern blot analysis.

RESULTSThirteen positive clones were obtained, and 11 cDNA sequences were identified. Sequences of 11 cDNA showed that 6 cDNA were homologous with the genes published in Genbank and 5 cDNA were unknown genes. Northern blot indicated that 3 novel cDNA(>300 bp) were only expressed in HCC.

CONCLUSIONThe subtracted cDNA library constructed by SSH technique contains differentially expressed genes of HCC. Three novel cDNA sequences might be differentially expressed genes of HCC. Further screening the library and gaining the whole gene sequence may lay a foundation for identifying differentially expressed genes in HCC.

Base Sequence ; Carcinoma, Hepatocellular ; genetics ; Cloning, Molecular ; DNA, Complementary ; chemistry ; genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Library ; Humans ; Liver Neoplasms ; genetics ; Molecular Sequence Data ; Sequence Analysis, DNA

OBJECTIVETo evaluate the safety and efficacy of sublingual immunotherapy with 'Dermatophagoides Farinae Drops' in D. farinae allergic asthma and/or rhinitis patients.

METHODSA 25-week double-blind, placebo-controlled, multi-centered trail was conducted in 278 children (aged 4 - 18 yr) with mite-induced asthma and/or rhinitis. Patients were randomly assigned to receive sublingual immunotherapy (SLIT) with 'Dermatophagoides Farinae Drops' (n = 139) or placebo (n = 139) for 25 weeks and the dosage and administration strictly followed the manufacturer's instructions. At the beginning of the 2nd, 3rd, 4th, 6th, 10th, 14th, 18th, 22nd week of the treatment, the patients were asked to accept follow-up visit, during the clinical trial all patients and parents were asked to keep a daily record of their asthma symptom scores, rescue medicine use, rhinitis symptom scores, morning and evening peak expiratory flow. Asthma symptom scores, reduction in use of rescue medicine, rhinitis symptom scores, lung function tests, skin sensitivity to mite, mite-specific immunoglobulin (Ig) E and IgG4, and quality of life and adverse effect were assessed during the study.

RESULT(1) Of the 278 children, 27 dropped out before the study completion. (2) After 25 weeks of treatment, the median variability of PEFR was -1.38 for SLIT group and -0.90 for the placebo (P < 0.05). (3) Besides, the mean variability of medicine score of asthma was -0.08 for SLIT group and 0.52 for the plcebo (P < 0.05). (4) The median variability of rhinitis symptom score was -1.96 for SLIT group and -1.03 for the placebo (P < 0.01). (5) The rescue medicine usage of SLIT reduced but did not show significant differences between SLIT and placebo. (6) After 25 weeks treatment, the increase of D. farinae specific IgE antibody of two groups were similar, while specific IgG4 increased significantly in SLIT compared to the patients in control one (P < 0.01); (7) No severe adverse events happened in the trial and the most-likely adverse events were mild asthma and local rash.

CONCLUSIONDermatophagoides Farinae Drops is safe and effective in treating allergic asthma and atopic rhinitis.

Adolescent ; Animals ; Asthma ; therapy ; Child ; Child, Preschool ; Dermatophagoides farinae ; chemistry ; metabolism ; Double-Blind Method ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mites ; chemistry ; Rhinitis ; therapy

BACKGROUNDThe traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo.

METHODSMiniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively.

RESULTSTongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA.

CONCLUSIONSTongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.

Animals ; Antigens, CD ; analysis ; Blood Pressure ; drug effects ; Cadherins ; analysis ; Drugs, Chinese Herbal ; therapeutic use ; Heart Rate ; drug effects ; Microscopy, Fluorescence ; Myocardial Infarction ; drug therapy ; physiopathology ; Myocardial Reperfusion Injury ; prevention & control ; Myocardium ; enzymology ; pathology ; Neutrophil Infiltration ; Nitric Oxide ; physiology ; Nitric Oxide Synthase ; metabolism ; Peroxidase ; metabolism ; Swine ; Swine, Miniature