Angiotensin Ⅱ receptor blockers(ARBs) and statins are commonly used cardiovascular drugs.Their combination use has become a new topic in the research field of cardiovascular drugs.At present,many studies suggest great potential of the combination use of ARB and statins.

Objective To analyze the viral dynamics and clinical significance during the antiviral treatment by a mathematical model.Methods Six chronic hepatitis B patients were evaluated with a kinetic model(Neumann model)during dose of 0.5 mg/d oral entecavir.Blood samples were drawn for HBV DNA measurement at week 0,2,4,12,24.Non-linear modeling was used to fit individual patient data.Results The median effectiveness in blocking viral production was 99.970%(n=6).The median half-life of viral turn-over was 1.6 d(n=6).The median half-life of infected hepatocytes was 21.3 d(n=5).Compared with the other patients,the c(virions are cleared at a rate)、ε(effectiveness)、δ(infected cell are lost at a rate)value of one patient(eg.6)were all lower and the half-life of virus and infected cells were higher,and eg.6 developed viral break-through after 38 weeks of follow-up.Conclusions Viral load decay showed a biphasic pattern during entecavir therapy which can be described with a mathematical model.The model relates processes of viral infection and replication as well as drug efficacy to model parameters.It indicates the prediction of bio-mathematical model during antiviral treatment.

Objective To construct human apolipoprotein O (apolipoprotein O, ApoO) expression vector and obtain recombinant fusion protein thioredoxin (Trx)-ApoO by pET prokaryotic expression system. Methods The ApoO gene fragment from the human liver cDNA library was amplified by PCR. The resulting product was cloned into pET-32a(+) vector and sequenced. The confirmed cDNA was cloned into plasmid E.coli DH10B and then transformed into E.coli BL 21 (DE3) where it was induced to express protein by isopropyl β-D-1-thiogalactopyranoside (IPTG).The fusion protein was purified by Ni-NTA resin. Results The ApoO gene was cloned by PCR and a 519 bp DNA fragment was shown on the agarose electrophoresis. The cloned gene was sequenced and demonstrated to have the same sequence as that of human ApoO gene in GenBank which justified a successful construction of recombinant plasmid. ApoO cDNA gene fragment was induced by IPTG, and a 34 kD recombinant fusion protein Trx-ApoO was tested on sodium dodecyl sulfate polyacrylamide (SDS-PAGE). Conclusion Human ApoO gene is successfully cloned and its recombinant fusion protein Trx-ApoO is expressed.

Aim To explore the effect of high density lipoprotein and apolipoprotein A-I mimetic peptide on the secretion and the expression of adiponectin in fully differentiated 3T3-L1 adipocytes in inflammatory status and the possible mechanism.Methods Fully differentiated 3T3-L1 adipocytes were incubated in the medium containing various concentrations of high density lipoprotein(10~100 mg?L-1) and apolipoprotein A-I mimetic peptide(1~50 mg?L-1)with 100 ?g?L-1 lipopolysaccharide(n=3).Evaluate the levels of adiponectin in supernatant,the mRNA expression of adiponectin and PPAR?,and the activity of NF-?B.Results During LPS stimulation adiponectin concentrations in supernatant decreased from 0.25?0.03 ?g?L-1 to 0.14?0.02 ?g?L-1(P

3T3-L1 adipocytes were cultured with various concentrations of high-density lipoprotein ( HDL, 0, 10, 50, and 100 μg/ml ) for 16 h and with lipopolysaccharide ( LPS, 100 ng/ml ) for another 6 h. Interleukin-8 in the medium was determined by ELISA, and PPAR-γ mRNA expression by reverse transacription polymerase chain reaction (RT-PCR). Interleukin-8 levels were increased in LPS-treated cells ( P＜0.05 ), but decreased in HDL-treated cells in the dose-dependent manner. PPARγ mRNA expressions were increased in HDL-treated groups than those treated only with LPS. These results suggested HDL may decrease interleukin-8 secretion via up-regulating PPARγ expression in adipocytes.

Objective To characterize the profile and clinical significance of hepatitis B virus (HBV) quasispecies in patients infected with hepatitis B virus based on the sequence of reverse transcriptase (RT) region.Methods Fifty HBV infected treatment-naive patients were enrolled and divided into three groups,asymptomatic carriers (ASC) group (10 cases),chronic hepatitis B (CHB) group (30 cases) and liver cirrhosis (LC) group (10 cases).HBV genomes were extracted from serum samples.The sequence of RT region was amplified by polymerase chain reaction (PCR) and cloned into vectors.Fifteen to thirty clones per sample were selected,sequenced and analyzed by bioinformatics software.The mean values among groups were compared by analysis of variance.The median values among groups were compared by nonparametric statistics.The enumeration data were analyzed by x2 test.Results Totally 1221 HBV RT region nucleotide sequences were obtained (152from ASC patients,780 from CHB patients and 289 from LC patients).Genotype distribution showed no difference among three groups.However,the quasispecies complexity showed significant differences among the three groups,LC group ＞CHB group＞ ASC group (F=33.400,P＜0.05).The quasispecies diversity was LC group ＞CHB group＞ ASC group,and that of LC group was significantly different from the other two groups (F=18.070,P＜0.05),while there was no significant difference between CHB and ASC patients.Conclusions The HBV isolated from patients in immune clearance phase have higher variability than those isolated from patients in immune tolerance phase.The longer the infection persists and the more severe the disease is,the more variable HBV quasispecies are.

Atherosclerosis ; prevention & control ; Cholesterol, LDL ; blood ; Humans ; Hypercholesterolemia ; drug therapy ; United States

Objective:To explore the postprandial plasma low-density lipoprotein cholesterol (LDL-C) changes by various detection methods.Methods:A total of 85 subjects admitted to the Second Xiangya Hospital of Central South University from November 2017 to May 2019 were included. Serum samples were collected from fasting and the 2 nd hour and the 4 th hour after breakfast. Serum lipid levels were measured with enzymatic assays and nuclear magnetic resonance spectroscopy (NMRS), and proprotein invertase subtilisin/kexin type 9 (PCSK9) levels were measured with enzyme-linked immunosorbent assays. The differences of blood lipid components at different time points were compared by Friedman two-way rank analysis of variance and Wilcoxon signed rank test, and the correlation between PCSK9 level and lipoprotein particles was analyzed by Spearman correlation. Results:Measured by enzymatic assays, compared with the fasting state, LDL-C decreased at the 2 nd hour and the 4 th hour after the meal (2.58[2.09, 3.12], 2.47[1.92, 3.02], 2.37[1.82, 2.80] mmol/L, P<0.001). Measured by NMRS, the concentration of LDL particles (1 086[830, 1 239], 1 083[848, 1 213], 1 061[814, 1 213] nmol/L, P=0.417) did not change significantly, and cholesterol in LDL particles were 2.13 (1.56, 2.54), 2.16 (1.68, 2.50), 2.06 (1.58, 2.50) mmol/L, respectively ( P=0.047)，and postprandial cholesterol in LDL particles in the 2 nd hour and in the 4 th hour did not change significantly compared with fasting ( P>0.05). while the concentration of large LDL particles (185.2[150.6,221.6], 173.0[144.8,220.3], 178.1[144.0,233.6] nmol/L, P=0.001), and the cholesterol level in large LDL particles (0.49[0.39, 0.57], 0.47[0.38, 0.57], 0.46[0.37, 0.58]mmol/L, P<0.001) decreased after the meal. The PCSK9 level also decreased significantly after the meal (299[233, 397], 257[208, 342], 251[215, 340] ng/ml, P<0.001). There was an independent positive correlation between the decrease of PCSK9 levels and the increase of remnant cholesterol detected by MNRS after the meal ( r=0.232, P=0.035). Conclusions:The postprandial LDL-C level measured by NMRS and enzymatic assays is not consistent. The decrease of LDL-C measured by enzymatic assays is not caused by the clearance of LDL particles, but by the redistribution of cholesterol in each LDL subfraction.