ObjectiveTo explore the multidrug resistance(MDR) reversal activity of a novel compound liposome doxorubicin(PLD) and its mechanism.MethodsMTT assay was used to evaluate MDR reversal activity of PLD in P-gp expressing tumor cell lines,KBv200 and MCF-7/ADR.ResultsPLD had a strong reversal in vivo activity,recognized the strong reversal activity than verapamil reversal activity,in 5.0μmol/L concentration of multi-drug resistant cell KBv200 increased sensitivity to vincristine of 45 times.KBv200 PLD-dependent increased in intracellular concentration of rhodamine accumulation(0,2.5,5.0,10μmol/L).Mainly to its cardiac toxicity,bone marrow suppression and hair loss and other side effects were significantly reduced.ConclusionPLD was an efficient modulator,mainly through the continuous accumulation to tumor tissue,tumor local drug concentration,enhanced anti-tumor activity,

OBJECTIVE To investigate the effect and mechanisms of chrysophanol on the expression of c-fos and c-jun mRNA induced by ammonia chloride(NH4Cl) in mouse astrocytes. METHODS Primary mouse astrocytes were cultured with NH4Cl 5 mmol·L-1+chrysophanol 0.1,1.0 or 10.0 mg·L-1 ,or NH4Cl 5 mmol · L- 1+extracellular regulated kinase1/2(ERK1/2) inhibitor UO126 10 mmol · L- 1 and NH4Cl 5 mmol · L-1+p38 mitogen-activated protein kinase(p38 MAPK)inhibitor SB239063 10 mmol · L-1 for 48 h. The levels of glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),malondaldehyde(MDA), nitric oxide(NO)and nitric oxide synthase(NOS)were detected by UV spectrophotometry. The phos?phorylation levels of ERK1/2 and p38 MAPK were detected by Western blotting. The expression of c-fos and c-jun mRNA was detected by RT-PCR. RESULTS Compared with NH4Cl 5 mmol · L- 1 group, ammonia-induced astrocytes oxidative stress was improved by chrysophanol (1.0 and 10.0 mg · L-1). The content of MDA and NO and the activity of NOS were reduced(P<0.05). The activity GSH-Px and SOD was increased(P<0.05). The phosphorylation level of ERK1/2 and p38 MAPK induced by ammonia was reduced in chrysophanol groups (P<0.05). Ammonia-induced c-fos and c-jun mRNA expression downregulation was reversed by chrysophanol (0.1,1.0 and 10.0 mg · L-1)and UO126 and SB239063(P<0.05). CONCLUSION Chrysophanol may improve the downregulated expresion of c-fos and c-jun mRNA in mouse astrocytes exposed to NH4Cl by anti-oxidative stress by inhibiting the ERK1/2 and p38 MAPK phosphorylation.

AIM: To investigate the pharmacokinetic properties and bioequivalence of nifedipine sustained-release tablets after multiple doses administration in healthy volunteers. METHODS: Twenty two male healthy volunteers were enrolled in a randomized two-way crossover design with multiple doses (20 mg·d-1×7 d) study. Nitrendipine was used as the internal standard and the concentrations of nifedipine in plasma were determined by HPLC-APCI-MS. The pharmacokinetic parameters were calculated and the bioequivalence were compared by DAS (ver 1.0) program. RESULTS: The pharmacokinetic parameters of test and reference preparations were as follows: Cmax (52.5±27.4) and (54.0±31.2) ng·ml-1;Cmin (5.4±4.1) and (6.2±5.9) ng·ml-1;Cav (16.8±9.2) and (19.3±12.4) ng·ml-1;Tmax (3.7±0.9) and (4.1±1.1) h;t1/2 (8.9±4.9) and (8.5±3.1) h;AUC0-τ (403.4±221.0) and (461.9±296.6) μg·h·L-1, AUC0-36h (444.4±256.1) and (503.1±330.9) ng·h·ml-1;AUC0-∞ (482.1±268.9) and (542.3±348.4) ng·h·ml-1;DF (299.8±117.7)% and (279.2±97.5)%, respectively. There were no significant differences (P>0.05) in Tmax, Cmax, Cmin, Cav, DF, AUC0-τ, AUC0-36h, AUC0-∞ and t1/2 between the two preparations. The relative bioavailability of test tablets was (100.6±38.6)%. CONCLUSION:The test and reference preparations were bioequivalence.

Objective To investigate the correlation between histone deacetylase 9 gene ( HDAC9 ) single nucleotide polymorphisms and ischemic stroke ( IS) subtypes. Methods A total of 202 patients with IS were enrolled prospectively. According to the Trial of Org 10172 in Acute Stroke Treatment ( TOAST) classification,the patients with IS were divided into large artery atherosclerotic stroke group (LAA,n=149) and the small-artery occlusive stroke group (SAO,n=53). A total of 201 age- and sex-matched healthy subjects over the same period were enrolled as the control group. Polymerase chain reaction-ligase detection reaction ( PCR-LDR ) was used to perform genotyping for HDAC9 gene rs11984041 and rs2107595 loci in all subjects. The correlation between genotype and IS was analyzed with multivariate logistic regression analysis. Results ( 1 ) In all the subjects detected, the genotype detected from rs11984041 loci was type CC,and 3 genotypes including CC,CT,and TT were detected from rs2107595 loci. (2) There were significant differences in dominance model (CT+TT,CC) genotypes and allele frequencies among the LAA, SAO, and control group dominance model ( CT +TT, CC ) and (χ2 =8. 635,P=0. 013, χ2 =10. 309,P=0. 006);and there were no significant differences in dominance model (CT+TT,CC) and allele frequencies among the 3 groups (after adjustment all P>0. 017). Compared with the control group,there were significant differences in the CC,CT,and TT genotypes and allele frequencies in the LAA group (χ2 =7. 446;P=0. 006). In the dominance models (CT+TT),there was significant difference in genotype frequencies between the LAA group ( 65. 1%,97/149 ) and the control group (52. 2%,105/201) (χ2 =5. 800;P=0. 016). (3) Multivariate logistic regression analysis showed that in addition to gender,hypertension,smoking,and high level of low-density lipoprotein,the dominance model CT+TT genotype was associated with the LAA type IS ( CT+TT genotype:OR,1. 909,95% CI 1. 055-3. 454,P =0. 033). Conclusion In addition to the risk factors for cerebrovascular disease such as gender,hypertension,smoking,and high level of low-density lipoprotein,HDAC9 gene polymorphisms may be associated with the LAA type IS. rs2107595 locus CT + TT genotype may be an independent risk factor for LAA type IS.

Objective To observe the influence of bezafibrate on the apoptosis and expression of lectin-like oxidized low density lipoprotein receptor-1(LOX-1) mediated by oxidized low density lipoprotein(ox-LDL) in cultured human umbilical vein endothelial cells(HUVECs).Methodes The apoptosis of HUVECs mediated by ox-LDL were evaluated by flow cytometry and the expression of LOX-1 mRNA were detected by RT-PCR.Results Compared with the control group,ox-LDL could increase apoptosis and the expression of LOX-1(P<0.05),and Bezafibrate could decrease the apoptosis and the expression of LOX-1 in a concentration -dependent manner(P<0.05).Preincubation of HUVECs with polyinosinic acid for 2 hours,the apoptosis and the expression of LOX-1 decreased(P<0.05).Conclusions Bezafibrate inhibits the apoptosis of HUVECs mediated by ox-LDL by reducing the expression of LOX-1,which may be part of the reasons for bezafibrate to prevent and treat atherosclerosis.

Objective The different distribution and clinical significance of mean platelet volume (MPV) in the healthy normoglycemic and impaired fasting glucose (IFG) individuals were discussed.Methods The 499 individuals including 184 male and 315 female,who had undergone health checks in Tianjin Huanhu Hospital during May and July 2012 were studied retrospectively.Average age is forty-five ( thirty-five to eighty).Subjects were categorized into four groups according to fasting plasma glucose ( FPG) levels:G1 (3.89 mmol/L≤FPG<5 mmol/L, n=125),G2(5 mmol/L≤FPG <5.5 mmol/L, n=121), G3(5.5 mmol/L≤FPG<6.1 mmol/L, n=142), and G4(6.1 mmol/L≤FPG<7 mmol/L, n=111).G1, G2, and G3 are defined as normal FPG groups and G 4 is defined as IFG group.Eighty-nine cases in the same age patients with type II diabetes mellitus group ( G5 ) were observed at the same time.Results The MPV increased with the increasing FPG levels in the following order:G1(8.62 ±0.77) fl, G2 (8.85 ±0.80) fl, G3(8.90 ±0.69) fl,G4(9.14 ±0.78) fl and G5(12.03 ±1.42) fl.MPV[(12.03 ±1.42) fl] of type Ⅱdiabetes mellitus group(G5) was higher than that in the IFG group (G4)[(9.14 ±0.78) fl] and normal FPG groups[G1(8.62 ±0.77) fl,G2(8.85 ±0.80) fl,G3(8.90 ±0.69) fl] (F=12.773,P<0.01);MPV of the IFG group [ ( 9.14 ±0.78 ) fl ] was significantly higher than that in normal FPG groups [ G1 (8.62 ±0.77) fl,G2(8.85 ±0.80) fl,G3(8.90 ±0.69) fl] (F=12.773,P<0.01 for G4 vs.G1 and G2, P<0.05 for G4 vs.G3) ;MPV in the high-normal glucose group (G3) [(8.90 ±0.69) fl] was obviously higher than that in the low-normal glucose group (G1) [(8.62 ±0.77) fl] (F=12.773,P<0.05);MPV was positively associated with FPG in normal FPG groups ,IFG group and type Ⅱ diabetes mellitus group (G1-3:r=0.22, P<0.05;G4:r=0.26, P<0.01;G5:r=0.29, P<0.01).Conclusions Significant difference of MPV was observed in population of different FPG levels.Especially, MPV in IFG group was evidently higher than that in normal FPG group and was positively associated with FPG levels.

Aim To express hepatitis C virus glycoprotein E (gE) deleting carboxy-terminal 31 amino acids, and detect anti-E antibody in HCV patients using expressed gE. Methods E gene derived from HCV H strain was inserted into baculovirus transfer vector containing a polyhedrin promotor. The recombinant plasmid was cotransfected into insect cell sf9 with a viral expression vector. The expression of gE was analyzed with Western blot, and the cells were used for dectecting antibodies against E1 and E2 in 35 hepatitis C patients by indirect immunofluorescence. Results A series of proteins with different relative molecular masses(Mr) could be detected by Western blot. Results from indirect immunofluorescence staining showed and only 4 patients were anti-E antibody positive gE was located in cytoplasm. Conclusion HCV gE is expressed successfully in insect cells, the study lay the foundation for further developing HCV vaccine.

Objective To assess the clinical characteristics of postoperative myocardial infarction (PMI) in patients undergoing off-pump coronary artery bypass grafting(OPCAB).Methods Two hundred and sixty-six patients undertook OPCAB in the Shandong Provincial Chest Hospital from January 2008 to June 2015 were selected,there were 22 cases clinical diagnosis of PMI as PMI group,44 cases patients whose general information matched MI group were selected as no PMI group.The data of two groups including preoperative records and postoperative symptoms,electrocardiogram (ECG),cTnI and echocardiography change were compared.Results There were no significant differences about preoperative indexes between the two groups(P ＞0.05).Incidences of severe chest pain and new pathological Q-waves and elevated ST segments were significantly higher in PMI group than those in no PMI group (90.9％ (20/22) vs.18.2％ (8/44),27.3％ (6/22) vs.4.5％(2/44),95.4％(21/22) vs.27.3％(12/44)),the differences were significant(P＜0.005).Peak serum levels of cTnI during the first 24 h after operation were significantly higher in patients of PMI group than those in no PMI group,the difference was significant((4.52±2.81) μg/L vs.(0.26±0.22) μg/L,P=0.04).There was no significant difference in the incidence of myocardial segmental motion.Conclusion It is difficult to predict coronary artery bypass grafting after myocardial infarction.It has great value of postoperative ECG,the patient complained in diagnosis of postoperative myocardial infarction.CTn is a very sensitive indicator,but its diagnosis clinical myocardial infarction boundary value still need to be open to question.

ObjectiveTo study the expressions of Ki-67 and p53 in the surface cells and polygonal cells in pulmonary sclerosing hemangioma(PSH)and investigate the relation of cell proliferation index and biological behaviour of the tumor.MethodsDouble-staining immunohistochemistry was used to detect the expressions of Ki-67 and CK8/18 protein. Double immunofluorescence staining was used to detect the expressions of p53 and AE1/AE3 protein. ResultsThe positive signal of AE1/AE3 and CK8/18 were localized in cytomembrane of surface cells. The positive signal of Ki-67 and p53 were localized in cell nucleus of the two kinds of cells.The positive rate of Ki-67 was under 1％ in surface cells and 1％-10 ％ in polygonal cells. p53 protein was mainly expressed in polygonal cells (6/9, 33.3 ％) and only exsited in seldom surface cells.ConclusionThere are differences on cellular morphous and immunophenotype between the surface cells and polygonal cells.The proliferation index and gene mutation are all predominant in polygonal cells than in surface cells. The biological behaviour of PSH maybe mainly be decided by the polygonal cells.

Objective To explore characteristics of sleep structure and the correlation with cognitive function in cerebral infarction combined with obstructive sleep apnea hypopnea syndrome (CI-OSAHS).Methods The patients with CI-OSAHS and OSAHS in Department of Neurology and Breathing Sleep Monitoring Room of Tianjin Medical University General Hospital from December 2009 till March 2011 were collected All the patients completed polysomography(PSG).Sixty patients were selected and divided into 3 groups based on PSG.These 3 groups were combined group 20 persons (CI-OSAHS),OSAHS group 20persons (OSAHS) and control group 20 persons (without cerebral infarction obstructive sleep apnea hypopnea syndrome).All the patients completed image examinations ( CT and MRI ) evaluation of the cognitive function by Mini-Mental State Examination(MMSE) and Montreal Cognitive Assessment(MoCA).Results Sleep structure:the awake time,non-rapid eye movement sleep (NREM) 1,NREM 2 and NREM periods in combined group and OSAHS group were significantly longer,the NREM3 + 4 and rapid eye movement(REM) periods were shorter than the control group.The NREM and NREM 1 periods in combined group were longer,the NREM 3 +4 and REM periods were shorter than the OSAHS group.The correlation analysis of cognitive function and breathing disorders and low oxygen related index:there was negative correlation between the total scores of cognitive function (MMSE and MoCA)and apnea hyponea index,oxygen desaturation index (ODI) ( MMSE r =-0.450,-0.671,MoCA r =-0.486,- 0.494,all P ＜0.05) while,was positive correlation between them and noctumal average hypoxemia and minimum hypoxemia ( MMSE r =0.477,0.485,MoCA r =0.507,0.482,all P ＜0.05) in the OSAHS group.There was negative correlation between ODI,arousal index and the total scores of MoCA in the combined group (MoCA r=-0.463,0.480,both P＜0.05),there was correlation between the total scores of MMSE and the other sleep parameters,but,there was no difference in statistics.The correlation analysis of cognitive function and sleep stages:There was positive correlation between the total scores of cognitive function ( MMSE and MoCA) and the NREM 3 + 4 periods ( r =0.521,0.474,both P ＜ 0.05 ) while,there was negative correlation between the total scores of MMSE and the N REM 1 + 2 periods (r =-0.458,P ＜ 0.05 )in the OSAHS group.There was positive correlation between the REM period and the total scores of MoCA (r =0.472,P ＜ 0.05 ).There was correlation between the total scores of MMSE and the sleep structure,but,there was no difference in statistics in combined group.Conclusions Patients with OSAHS have obvious sleep structure disorder.The awake time and light sleep periods are significantly longer than the control group,while,the deep sleep and REM periods are significantly shorter than the control group.The NREM 1 of the patients with CI-OSAHS is longer than the patients with OSAHS.The higher the AHI,the lower the night blood oxygen,the more obvious cognitive dysfunction The longer the awake time,the longer the light sleep,the shorter the deep sleep and REM periods,the more serious cognitive dysfunction.The correlation between the cognitive impairment and low oxygen is more apparent than sleep structure.There is apparent correlation among the total scores of MoCA,the degree of hypoxia and sleep structure in the patients with CI-OSAHS.The total scores of MoCA are more sensitivity than MMSE in mild vascular cognitive impairment.