Objective To set up a method to detect the mutation of CYP2C9 1075A ＞ C and VKORC1-1639 G ＞ A in clinical practice,investigate the distribution of CYP2C9 1075A ＞ C and VKORC1-1639 G ＞ A in Beijing Han native,and evaluate the correlations between CYP2C9 1075A ＞ C,VKORC1-1639 G ＞ A and Warfarin maintenance dose,so that the results will contribute to Warfarin therapy.Methods A total of 145 Han Beijing patients received long-term Warfarin anticoagulant therapy orally in the people's hospital between May to September in 2011 were enrolled in this study.The patients suffer from atrial fibrilation,thromboembolism and heart operation respectively.The ARMS-TaqMan real time PCR technique was used to detect the mutation of CYP2C9 1075A ＞ C and VKORC1-1639 G ＞ A.The data were collected on gender,age and BSA.The correlations between stable warfarin dosage and each factor were analysised.Results The detection limit of ARMS-TaqMan real time PCR technique was 105 copies/ml in this assay.The intra-and inter-coefficients of variations (CV) were less than 5.5％ and less than 9.0％ respectively.The coincidence rate of ARMS-TaqMan real time PCR and direct sequencing was 100％ for testing 50 paralled samples.Among the 145 patients,the frequencies of CYP2C9 1075 AA,AC and CC was 93.8％ (136/145),6.2％ (9/145),0(0/145) respectively.The frequencies of VKORC1-1639 GG,GA and AA was 0.7 ％ (1/145),21.4％ (31/145),77.9％ (113/145) respectively.Allele frequencies of genotypes were in Hardy-Weinberg equilibrium.Every patients' INR was within range 2.0-3.0.Among the 145 patients,dosage requirements were higher in CYP2C9 1075 AA phenotype than that in AC type (F =0.199,P ＜0.05) and were higher in VKORC1-1639 GA phenotype than that in AA type (F=1.745,P ＜0.001).Irrespective of other factors,age,BSA,CYP2C9 1075 and VKORC1-1639 was accounted for 11.9％,12.9％,4.4％ and 16.7％ of interindividual variation of Warfarin dosage respectively.Linear stepwise regression analysis was used to identify factors contributing to Warfarin stable does.The final equation accounted for 40.4％ of interindividual variation of Warfarin dose.Conclusions The ARMS-TaqMan real time PCR technique was established to analyse CYP2C9 1075 and VKORCl-1639 genotype.The technique can achieve the needs of clinical practice.Warfarin dosing by multivariable regression equation in patients could increase efficiency for Warfarin dose adjustment,and could give suggestion for the individualization and rationalization for Warfarin dose.

Objective To know water quality of different sectors of Yangtse River after the Three Gorges reservoir kept 135 m water level. Methods Eight locations in six cities sectors(Fengdu,Wushan) of Yangtse River were selected as the monitor point and water samples were collected according to the related national standard (GB12997,1991). 96 samples were collected in May and August, 16 parameters (pH, DO, BOD5, CODCr, Ar,OH, TCN,As, Hg, Cr6+, oil, Pb, Cd, NH3,N, TP, TN, CODMn) of every sample were detected based on the methods documented in the related national standards and compared the results with the results of past years. Results 135 m water level had no significant influence on the water quality of different sectors of Yangtse River(II, III grade). Water quality had no significant change before and after 135 m water level emerged the primary contaminations which effect water quality were total nitrogen and total phosphors. Conclusion No significant change of water quality of Yangtse River has been seen after the Three Gorges reservoir kept 135 m water level.

BACKGROUND:Neurotrophic factors have been conformed to have the effects of promoting the survival, differentiation and axonal regeneration of the injured neurons, so that the structural integrity of the injured spinal cord can be reserved as much as possible.OBJECTIVE: To observe the effects of nerve growth factor (NGF) on the neural regeneration and motor function following spinal cord injury in rats.DESIGN: A randomized controlled observation.SETTING: Department of Neurology, Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: Thirty healthy adult male Wistar rats of common degree, were provided by the Experimental Animal Center, Tongji Medical College of Huazhong University of Science and Technology.METHODS:The experiment was carried out in the Department of Neurology, Union Hospital of Tongji Medical College,Huazhong University of Science and Technology. The 30 rats were randomly divided into NGF-treated group (n=15) and control group (n=15). ① T8 spinal injury was induced by the improved Allen method. ③ The improved Rivlin method (namely, slope test) was used to assess the motor function following spinal cord injury in rats before model establishment and at 3 days, 1, 2 and 3 weeks after treatment respectively. ④ At 2 days and 3 weeks postoperatively, 7 rats in the NGF-treated group and 8 rats in the control group were selated and the cross-sectional tissue(0.5 cm) of the injured spinal cord was removed, fixed in neutral formalin, dehydrated, and embedded with paraffin, and then cut into 5 μm sections.MAIN OUTCOME MEASURES:① The results of the slope test before model establishment and at 3 days,1, 2 and 3weeks after treatment respectively; ② Axonal count in white matter at 2 days and 3 weeks after model establishment.RESULTS:① The scores of slope test after spinal cord injury at 1, 2 and 3 weeks postoperatively in the NGF-treated group were obviously higher than those in the control group [(45.2±3.2), (51.2±3.8), (53.4±4.6)°; (45.2±3.2), (51.2±3.8),(53.4±4.6)°, P ＜ 0.05].② At 3 weeks after treatment, a few dispersal and heterogeneous NGF200 spots were observed in the white matter of rats in the control group, but there were plentiful and symmetrical NGF200 spots in the NGF-treated group. The axonal count in white matter at 3 weeks following spinal cord injury in the NGF-treated group was obviously higher than that in the control group (363.6±34.2, 187.5±32.1, P＜ 0.05).CONCLUSION:NGF can promote the neural regeneration following spinal cord injury to a certain extent, and help to im prove the functional recovery.

Adolescent ; Adult ; Aged ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B, Chronic ; complications ; drug therapy ; Hepatitis C, Chronic ; complications ; drug therapy ; Humans ; Liver Cirrhosis ; drug therapy ; etiology ; Male ; Middle Aged ; Phytotherapy

@@

Objective To evaluate the hypoxia selectivity of 99 Tcm O?labeld MAG3?nitroimidazole complexes with different spacers. Methods Four kinds of 99 Tcm O?labeled MAG3?2?nitroimidazole hypoxia imaging agents with different spacers were synthesized and radiolabeled. The stability and lipid solubility of BzMAG3?2NIEA(1), BzMAG3?2NIPA(2), BzMAG3?2NIHA(3) and BzMAG3?2NIUA(4) were measured. The uptake was investigated by biodistribution experiment using S180?bearing mice. Two?sample t test was used for statistical analysis. Results All 4 99 Tcm O?MAG3 complexes were stable and negatively charged, showing an increasing trend in fat solubility with the increase of spacer length. In biodistribution study, tumor uptake of 99TcmO?1 and 99TcmO?2 with medium? and short?carbon chain were (0.67±0.18) and (0?65±0.18) %ID/g 2 h post injection, which were (0.19±0.03) and (0.39±0.05) %ID/g for 99TcmO?3 and 99TcmO?4 with long?carbon chain (t=2.78-5.88, all P<0.05). Conclusion Molecular structure of spacers has a significant effect on the physicochemical properties and tumor targeting of 99 Tcm O?labeled MAG3?2?nitroimidazole hypoxia imaging agents, such that the medium?and short?carbon chain spacers show the best hypoxia?selective property.

Objective To establish a non-traumatic mouse model of acid aspiration-induced lung injury which al-lows longitudinal studies.Method C57BL/6 mice were anesthetized and orotracheally intubated with a 20 gauge angio-catheter guided by optical fiber.The mice were subsequently placed in the right lateral decubitus position and external com-pression to the left lung was manually applied.A polyethylene catheter was advanced into the right lung and used to instill either hydrochloric acid (2.5μL/g, 0.1 mol/L, pH 1.5) or saline as control.Then the mice were recovered with supple-mental oxygen for 4 hours.The pulmonary physiological function and survival of mice within 2 weeks after surgery were as-sessed.Results Methylene blue instillation showed that the staining fluid went into the right lung of the non-traumatically intubated mice.The survival rate of the mice with non-traumatic instillation was 80%, statistically significantly higher than those with tracheostomy instillation.Histological examination and lung function ( wet/dry ratio, elastance and arterial oxy-gen saturation) assay demonstrated that acid instillation caused a profound pathological changes and functional impairment of the lung.Besides, acid aspiration into the mouse lung caused a significant increase in neutrophil infiltration in mouse pulmonary alveoli and high concentrations of inflammatory factors (TNF-α, IL-6, CXCL1 and CXCL2) in the bronchoalve-olar lavage fluid.Conclusions We successfully established a mouse model of acid aspiration-induced lung injury, which may serve as a reliable model for longitudinally studying pulmonary immune-inflammatory mechanism in humans.

Objective To obtain the incidence of “clopidogrel low response”( CLR ) of acute coronary syndrome ( ACS ) patients after percutaneous coronary intervention ( PCI ) by Thrombelastography ( TEG) and Light transmission aggregometry( LTA) ,and explore the correlation of CLR with clinical related factors and major adverse cardiac events.Methods This study is a cohort study.214 ACS patients in the Department of Cardiology of Peking University People′s Hospital,who were ready to treat with PCI between May 2014 and November 2014 were enrolled.Among them, 168 cases(78.5%) were male with an average age of (61.32 ±10.79) years;46 cases(21.5%) were female with an average age of (68.72 ±8.38) years.The clinical data were recorded, such as history of present illness, the past medical history, clinical medication, and the results of coronary angiography.After taken clopidogrel 75 mg per day at least for 4 days,all patients were detected the contribution from ADP-stimulated platelets to maximal clot strength by TEG( TEG-ADP-Inhib), and detected ADP induced maximal platelet aggregation ratio by LTA ( LTA-ADPMAX ) .The occurrence rate of CLR was calculated, and the correlation between results of the two assays were anylysed.Patients were divided into two groups according to CLR.Univariate analysis was used to compare the difference of clinical data between CLR group and non-CLR group, then Logistic regression analysis was conducted to find out the related risk factors that may influence the occurrence rate of CLR.Compare the correlation between CLR and MACE according to 6-month followed-up.Results There was negative correlations between LAT and TEG in the adenosine diphosphate induced platelet reactivity ( r=-0.282,P=0.000).CLR was found in 115 (53.7%) patients by LTA and in 74(34.6%) patients by TEG and the difference between the two CLR ratio was significant (χ2 =10.486, P =0.001 ) .There were significant differences in age,smoking history and prior PCI/CABG history between CLR group and non-CLR group according to LTA grouping(t=2.829,P=0.005;χ2 =11.058,P=0.001;χ2 =4.252,P=0.039), and there was significant differences in history of cerebrovascular accident between CLR group and non-CLR group according to TEG grouping (χ2 =4.584, P=0.032 ).Logistic regression analysis showed smoking history was the protective factor for CLR ( OR=0.390,P=0.001) , while history of cerebrovascular accident was the independent risk factor (OR=2.499,P=0.037) for CLR.According to 6-month followed-up, the incidence of clinical ischemic events and bleeding events in CLRLTA group was 5.2%and 0 respectively, in N-CLRLTA group was 10.1% and 3% respectively;the occurrence rate of clinical ischemic events and bleeding events was no significant difference between two groups(χ2 =1.834,P=0.176;χ2 =1.682,P=0.195).The incidence of clinical ischemic events and bleeding events in CLRTEG group was 8.1% and 0 respectively, in N-CLRTEG group was 7.1%and 2.1%respectively;the occurrence rate of clinical ischemic events and bleeding events was no significant difference between two groups(χ2 =0.065,P=0.798;χ2 =0.432,P=0.511 ).Conclusions The correlation between the testing results of TEG and LTA in ACS patients treated with clopidogrel was poor, CLR ratios detected by two assays were significantly different.Smoking history was the protective factor for CLR , while history of cerebrovascular accident was the independent risk factor for CLR.CLR was not the risk factor for MACE in ACS patients.

Objective To study the pathogenesis mechanism of hepatitis C vires (HCV) core protein (CORE), the subcellular localization of different truncated genotype 1b HCV CORE was observed. Methods HepG2 cells were transiently transfected with the enhanced green fluorescence protein (EGFP-CORE) recombinant plasmids, which expresses EGFP and COREs from three different genotype lb HCV strains and different truncated COREs from one HCV strain. The localizations of different truncated COREs was analyzed by the laser scanning confocal microscope and fluorescence microscope. Results N terminal 1-172 an of different HCV strains of genotype 1b expressed mainly in cytoplasm. Among the different truncated COREs, the longer of the CORE containing N terminal, the more expressed in cytoplasm. The N terminal 1-58 aa mainly expressed in nucleus. CORE of 59-126 aa and 127-172 aa expressed both in cytoplasm and nucleus. Conclusion The different localizations of different truncated COREs might have some relationships with their functions in pathogenesis.

Objective: To evaluate fracture resistance of teeth restored with inlay restorations of direct and indirect composite resin. Methods:Three dimensional finite element analysis (3D FEA) was used in present research. Two types of load were applied to investigate the change of tooth fracture resistance after restored with MOD inlay. Group 1,2,3,and 4 were restored with four kinds of materials:group 1,indirect composite resin inlay( Tescera, Bisco USA);group 2, direct composite inlay(Renew Bisco USA);group 3,ceramic; and group 4, Co-Cr alloy. Defect tooth or intact one was served as the control group. Results:Tooth fracture resistance in group 1,2,3 and 4 were improved, Fracture resistance in group 1 and 2 were similar to intact tooth group, while the fracture resistance in group 3 and 4 was different effect when compared to intact tooth. Conclusion: Both direct and indirect composite resin inlay could strengthen fracture resistance of restored teeth. No obvious difference between direct and indirect composite resin on tooth resistance was found.