Carcinoma, Hepatocellular ; surgery ; Hepatectomy ; Humans ; Liver Neoplasms ; surgery ; Neoplasm Recurrence, Local ; surgery ; Reoperation

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.

Myocardial infarction (MI) is a major cause of death and disability worldwide.The definition of myocardial infarction has been updated.Released in 2012,Third Universal Definition of Myocardial Infarction of ESC/ACCF/AHA/WHF Expert Consensus,made the clinical application value of troponin clear and suggested to monitor the dynamic changes of cTn in patients with suspected,emphasized the importance of clinical differential diagnosis.In consensus,it also noted that the application of high sensitive troponin can lead to false positives results,and pointeds out that in the assessment of cardiac injury associated with percutaneous or surgical coronary procedures,the rational cut-off value of cTn remains controversival.In addition to acute coronary syndrome,cTn elevations are common in many disease states,and with the improvement of detection sensitivity,low level increase of cTn,will be more.In acute and chronic heart failure,the cTn is elevated,and ACS may be the cause of worsening heart failure,So we should identify whether the cTn elevation is pure from the myocardial injury of heart failure or myocardial necrosis caused by ACS.Nowadays,the increased incidence of myocardial infarction has much to do with the wide application of cTn.Clinical applications of cardiac biomarkers and imaging techniques are flexible as the differences in the diagnostic techniques of myocardial infarction among countries and regions result.

To evaluate the items of critical values and alert limits of the test results , to optimize the critical values report procedure , to modify the laboratory information system ( LIS ) and the hospital information system ( HIS ) , the critical values monitoring platform was designed .Through the monitoring platform,the critical value report rate and critical value report timely rate could be calculated , so reduce medical risks and improve the level of hospital management .

Lp-PLA2 is widely concerned in recent years as a vascular inflammation factor that plays an important role in the development of atherosclerosis .The level of plasma Lp-PLA2 is related to the stability of carotid artery atherosclerotic plaque .it is an independent predictor of coronary heart disease risk . Its specific inhibitor Darapladib also becomes a hotspot of clinical cardiovascular pharmaceutical research . However,two randomized, placebo-controlled, double-blind, international, multicenter, event-driven trials, STABILITY and SOLID-TIMI 52, have shown that Darapladib could not significantly reduce the risk of cardiovascular events.

Infants cholestasis is a common disorder of hepatobiliary system which is caused by abnormal cholestasis of hepatocytes or substances accumulation in the liver, blood and extrahepatic tissue due to the disorder of the intrahepatic or extrahepatic bile ducts.Serum Gamma-glutamyl transpeptidase(GGT) was widely distributed in one side of the capillary bile duct and the whole bile duct system of hepatocytes.When hypersynthesis in the liver or disorder of cholorrhagia, serum GGT increased.This review summarized the changes of GGT cholestasis of different causes in infants and its significance in differential diagnosis, for better understand the disease and provide references for clinical practice.

This study is to evaluate the HAART pharmacodynamics with dolutegravir as the "anchor" in vitro. A nucleoside reverse transcriptase inhibitors (NRTIs) resistant recombinant virus model (VSVG/HIV-1(RT-D67N,K70R,T215F)) and an integrase inhibitors (INIs) resistant recombinant virus model (VSVG/HIV-1(IN-G140S,QI48H)) were constructed and established. The anti-viral pharmacodynamics was evaluated with drug combinations including two NRTIs along with one INI or one NNRTI. The results showed that the combination with an INI gave a stronger synergism on wild type HIV-1 replication comparing to that with an NNRTI. Comparing the two INIs as the "anchor" for HAART, DTG exhibited an equivalent CI to that of RAL on wild type HIV-1 replication; but a greater synergy than RAL on INI-resistant HIV-1 replication. Besides of the pharmacodynamics results of DTG-based drug combination, the results may contribute to clinical antiviral therapy.
Antiretroviral Therapy, Highly Active ; Cells, Cultured ; Drug Resistance, Viral ; HIV Integrase Inhibitors ; pharmacology ; HIV-1 ; drug effects ; physiology ; Heterocyclic Compounds, 3-Ring ; pharmacology ; Humans ; Virus Replication ; drug effects

Objective: To observe the biological difference of multi-drug resistant nasopharyngeal carcinoma (NPC) cell line CNE2/DDP and its parental cell line CNE2, as well as analyze the characteristics of multi-drug resistant cells. Methods: The difference in morphological features, growth characteristics and colony formation rate in vitro were examined and compared under light microscope. Flow cytometry was used to evaluate the cell cycle distribution and the expression of P-170 and ABCG2 proteins. Drug sensitivity was measured by MTT assay. Tumorigenicity was evaluated after subcutaneous injection of 1 × 106 CNE2/DDP or CNE2 cells into BALB/c nude mice. Results: Under light microscope CNE2/DDP cells were smaller and showed a round shape and the CNE2 cells appeared polygonal cell bodies. CNE2/DDP cells had relatively longer colony doubling time than CNE2 cells (29.46 h vs 21.03 h) indicating that the growth of CNE2/DDP cells was slower. There was significant difference in the cell cycle distribution between CNE2/DDP and CNE2 cells [ (65.12 ± 1.67) % vs (44.9 ± 2.2) % in G0/G1 phase, (23.63 ± 0.42)% vs (39.67 ± 1.27) % in S phase, and (10.93 ± 0.25) % vs (13.23 ± 0.31)% in G2/M phase, P < 0.01]. Expression of P-170 and ABCG2 proteins in CNE2/DDP cells were significantly higher than that in CNE2 cells [(75.93 ± 0.86)% vs (2.83 ± 0.40)%, (43.37 ± 0.42) % vs (4.07 ± 0.59)% P < 0.01]. There was no significant difference in the resistance indexes of CNE2/DDP cells to DDP,5-FU and VCR before and after transplantation. The tumorigenicity time was (17.17 ± 1.17) d and (10.00 ± 2.68) d respectively for CNE2/DDP and CNE2 cells after being transplanted into BALB/c nude mice. Conclusion: CNE2/DDP has typical multi-drug resistance features and could be used for the research of drug-resistant NPC.

Carcinoma, Hepatocellular ; surgery ; Hepatectomy ; methods ; Humans ; Liver Neoplasms ; surgery

Objective To detect the mutation of A379,we develop a TaqMan fluorogenic probe based amplification refractory mutation system (TaqMan-ARMS) and investigate whether the A379V variant and activity of Lp-PLA2 are the risk factors for CAD.Methods According to the amplification refractory mutation system(ARMS-PCR)combined with a TaqMan fluorogenic probe,we established and evaluated the assay teehnique of TaqMan-ARMS for measuring the genotype of variant.At the same time,we tested the aetivity of Lp-PLA2 in 395 patients with coronary heartdisease and 396 controls,whose clinical information [ages,CHO,GLU,TG,HDL,LDL,Hs-CRP,Lp (a)] were collected.Date was analyzed by using Independent-samples t test,Chi-square test,One-Way ANOVA,Binary Logistic Regression.Results CAD group had significantly higher Lp-PLA2 activity than the controls(31.51 nmol · ml-1 · min-1 ＞21.31 nmol ·ml-1 · min-1,F =16.40,P ＜ 0.001).Comparing the highest quartile of Lp-PLA2 activitv to the bottom quartile,OR was 7.50 (95％ CI:2.34-24.05) after adjustment for various traditional cardiovascular risk factors,including ages,sex,CHO,TG,Hs-CRP,Lp (a) and GLU; the genotype VV of A379V was associated with higher risk of CAD (OR =2.95; 95％ CI:1.22-7.15,P ＜ 0.05).Conclusions The TaqMan-ARMS real time PCR technique is established to analyze A379V genotype.Lp-PLA2 activity is significantly higher in CAD group and is a risk factor for CAD; the genotype VV of A379V is also a risk factor for CAD.