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Objective To investigate the influence of nonalcoholic fatty liver disease (NAFLD) on the antiviral response of patients with chronic hepatitis B (CHB), and to provide a reference for clinical treatment of such patients. Methods A total of 187 patients who attended Shenzhen Third People's Hospital from January 2011 to December 2017 were enrolled and divided into CHB group with 43 patients, NAFLD group with 41 patients, and CHB+NAFLD group with 103 patients. Related indices were measured at enrollment different time points of follow-up, including body height, body weight, alanine aminotransferase (ALT), aspartate aminotransferase, four blood lipid parameters, four indicators of liver fibrosis, aspartate aminotransferase-to-platelet ratio index, HBsAg, HBeAg, anti-HBe, and HBV DNA quantification, and the CHB patients and the CHB+NAFLD patients receiving antiviral therapy were compared in terms of treatment outcome at weeks 12, 24, 48, 72, and 96 of antiviral therapy. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Wilcoxon rank-sum test was used for comparison between two groups; the chi-square test was used for comparison of categorical data between groups. Results Compared with the NAFLD group at baseline, the CHB group and the CHB+NAFLD group had significantly lower platelet count, ALT, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase, and right lobe of liver oblique diameter (all P 0.05). At week 12 of antiviral therapy, there were no significant differences in liver fibrosis markers and inflammatory indices between the CHB group and the CHB+NAFLD group (all P > 0.05); compared with the CHB+NAFLD group at weeks 24 and 48, the CHB group had significantly greater reductions in ALT ( Z =-2.128 and -3.055, both P < 0.05) and GGT ( Z =-2.025 and -1.631, both P < 0.05); at week 48, the CHB group and the CHB+NAFLD group had a significant reduction in HBV DNA ( Z =-6.445 and -4.415, both P < 0.001), and the CHB group had a significantly greater reduction. The CHB+NAFLD group had a significantly lower HBV DNA clearance rate than the CHB group at different time points of antiviral therapy ( χ 2 =14.237, 13.961, 15.226, 10.462, and 13.030, all P < 0.05). At week 48 of antiviral therapy, the CHB+NAFLD group had a significantly lower HBeAg clearance rate than the CHB group ( χ 2 =5.309, P =0.021), while there was no significant difference between the two groups at week 96 ( χ 2 =0.117, P =0.732). At weeks 24, 48, 72, and 96 of antiviral therapy, the CHB+NAFLD group had a significantly lower ALT normalization rate than the CHB group ( χ 2 =12.049, 5.287, 11.407, and 11.375, all P < 0.05). Conclusion NAFLD reduces the antiviral response of CHB patients and prolongs the duration of antiviral therapy.
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Objective To explore the association of single nucleotide polymorphism ( SNP ) in TP53 Arg72Pro (rs1042522) locus with thyroid cancer risk in human. Methods Articles involved in the association between SNP in TP53 Arg72Pro ( rs1042522) locus and thyroid cancer risk were retrieved from PubMed, Embase, and Web of Science databases, and studies which met the inclusion criteria were included. The meta-analysis, sensitivity analysis, subgroup analysis, and the assessment of publication-bias were performed by Stata 14. 0 software. The odds ratio ( OR) and their corresponding 95％ Confidence Intervals ( CI) were used to determine the strength of association between SNP in TP53 Arg72Pro locus and thyroid cancer risk. Results Thirteen case-control studies were eligible for this meta-analysis, including 2112 thyroid cancer cases and 4000 control subjects. Overall, mutated homozygous genotype ( Pro/Pro) in TP53 Arg72Pro ( rs1042522) locus was associated with significantly increased thyroid cancer risk(Recessive model, OR=1.78, 95％CI 1.24-2.56, P=0.002), showing a significantly higher Pro mutation frequency among thyroid cancer patients ( Allelic model, OR=1. 35, 95％ CI 1. 12-1. 63, P=0.002). In the stratified analysis, mutated homozygous genotype (Pro/Pro) in TP53 Arg72Pro (rs1042522) locus was only asscociated with significantly increased thyroid cancer risk among Asians, but not among Europeans and South Americans;mutated homozygous genotype ( Pro/Pro) in TP53 Arg72Pro ( rs1042522) locus was asscociated with significantly increased risk of papillary thyroid carcinomas ( PTC) among total population, but not medullary thyroid carcinomas. Conclusion There is a significant association between TP53 Arg72Pro polymorphism in TP53 and thyroid cancer risk, and the mutated homozygous genotype ( Pro/Pro) in this locus of TP53 maybe a risk factor for thyroid carcinoma among Asians.
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Objective: To explore the expression of myocardial levels of connexin 43(Cx43), Cx40 in experimental dog model of sympathomimetic atrial fibrillation (AF). Methods: 15 mongrels dogs were randomly divided into 3 groups: Control group, Rapid atrium pacing (RAP) group and RAP+isoprenaline (ISO) perfusion group. n=5 in each group. The hearts were taken to establish in vitro langendorff cardiac perfusion model. Atrial effective refractory period (AERP) and AF inducing rate were tested;intracellular expression and distribution of nerve growth factor (NGF) and tyrosine hydroxylase (TH) were examined by immunohistochemistry, total protein contents of Cx43 and Cx40 were measured by Western blot analysis, mitochondria morphology was observed by transmission electron microscope and mitochondria reactive oxygen species (ROS) generation was detected by fluorescent colorimetric method. Results: AERP was similar between Control group and RAP group (166±5.1) ms vs (160±3.2) ms which cannot induce AF; while it was shortened in RAP+ISO group (148±3.7) ms, P<0.05 which may successfully induce AF.Compared with Control group, mitochondria was slightly swollen in RAP group and the matrix was intact, while mitochondria was obviously swollen in RAP+ISO group and part of matrix was transparent; total protein contents of Cx43 and Cx40 were lower in both RAP group and RAP+ISO group, P<0.05; in addition, they were even lower in RAP+ISO group than RAP group, P<0.05. Compared with Control group and RAP group, RAP+ISO group had increased expression and distribution of NGF, TH and mitochondria ROS generation, P<0.05; NGF, TH and ROS in RAP group were higher than Control group, P<0.05. Conclusion: Sympathetic AF has been related to the contents and changes of myocardial levels of CX43 and Cx40; sympathetic nerve might trigger AF by oxidative stress induced down-regulation of myocardial CX43 and Cx40 in experimental dog model.
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AIM:To investigate the changes of connexin 43 (Cx43) via establishing a model of sympathomi-metic atrial fibrillation ( AF) .METHODS:The mongrels ( n=15) were randomly divided into control group , rapid atrial pacing (RAP) group and isoprenaline (ISO) perfusion+RAP group (ISO+RAP group).All mongrels’ hearts were taken out rapidly by median sternotomy to establish the cardiac model with Langendorff perfusion in vitro.The atrial effective re-fractory period ( AERP) and AF inducability were tested .The expression and distribution of tyrosine hydroxylase ( TH) were analyzed by immunohistochemistry .Total protein level of Cx 43 and phosphorylation of Cx 43 were determined by West-ern blot.The distribution of Cx43 were also observed by immunofluorescence staining .The cell apoptosis was analyzed by TUNEL staining.The generation of reactive oxygen species ( ROS) in the mitochondria was measured by fluorescence spec-trophotometry .RESULTS:No significant change of AERP was found between control group and RAP group , while that in ISO+RAP group was significantly decreased (P<0.05) and induced AF.Compared with control group, the expression of TH, apoptotic index and the generation of ROS increased gradually (P<0.05), while the content of Cx43 decreased grad-ually both in the total protein and the phosphorylation levels in RAP group and ISO +RAP group (P<0.05).The fluores-cence intensity of Cx43 was also attenuated and Cx43 were lateralized apparently in RAP group , while Cx43 were character-ized as punctate distribution in ISO +RAP group.CONCLUSION:Sympathetic nerves may activate autophagosome at in-tercalated discs and trigger cell apoptosis , resulting in remodeling and downregulation of Cx 43 via oxidative stress , thus having effects on mediating and maintaining AF .
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Objective To make comparisons of the three models of acute and chronic rheumatic carditis to find out an optimal animal model.Methods AntigenⅠwas a emulsifier mixed by complete freund’ s adjuvant( CFA) and Group A streptococcus(GAS).AntigenⅡwas mixed by incomplete freund’s adjuvant(IFA) and GAS.Female Lewis rats were randomly divided into four groups: A, B, C treatmeat groups were immuned with antigenⅠat the foot pad firstly. Subsequently, rats in group A、B、C were injected antigenⅠ, antigenⅡand activated GAS respectively to make the models of RHD.Rats in control group D were immunized with the same protocol outlined as treatment groups but without GAS. Respectively 7, 12, 24 weeks the rats were sacrificed 24 ( each group was 6).The blood biochemical item and Hematoxylin-eosin( HE) staining of hearts were detected.Results In group C the mortality was 25%.In group A, the incidence of carditis was the highest.Histopathological manifestations of group A, C was not only revealed acute damage such as inflammatory cell infiltrate as well as group B, but also the Aschofflike cells in the myocardial cells interstitial.But in group A and C there had a great degree of the inflammatory cells infiltration than group B.At 24th week rats in group A detected the rate and degree of valve fibrosis in chronic damage were higher than group B and C.None of rats in group D presented carditis or valvulitis.Conclusion In group A, giving the GAS with continuous stimulation after using the mixed emulsification of CFA and GAS to immune Lewis rats for five times was a appropriate method which could provide an optimal animal model for experimental study of acute and chronic rheumatic heart disease.
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Objective To investigate the effects of aggressive dosing of atorvastatin on the expression of SOCS1 in CD4 + Tlymphocytes from patients with unstable angina pectoris during peri-operative period of PCI.Methods A cohort of 50 patients with unstable angina pectoris were randomized (random number) to give pretreatment with either an aggressive dose (80 mg/d,n =25) or a routine dose (20 mg/d,n =25)of atorvastatin.Circulating CD4 +T cells were subsequently obtained prior to PCI,and also 18 h to 24 hours after PCI,using a magnetic cell sorting system (MACS).Fluorescence-based quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure expressions of SOCSI mRNA in the isolated CD4 + Tlymphocytes,and western blot analysis was used to detect levels of SOCS1 protein.Serum levels of IFN-γwere quantified using enzyme-linked immunosorbent assays (ELISAs).Results Compared with routine dose group,the expressions of SOCS1 mRNA and protein levels were dramatically increased and those were higher in aggressive dose group following PCI (P ＜ 0.05).In contrast,serum levels of IFN-γsignificantly increased following PCI in both groups,but it was higher in routine dose group than in aggressive dose group (P ＜ 0.05).Conclusions Treatment with aggressive dosing of atorvastatin reduced the post-PCI myocardial inflammatory response in patients with unstable angina pectoris,possibly modulating by up-regulating SOCS1 expression in CD4 + Tlymphocytes.
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Objective To investigate the effects of probucol and losartan on cell proliferation after balloon angioplasty in hypercholesterolaemic rabbits.Methods Forty male New Zealand rabbits were randomly divided into high cholesterol diet group,probucol group,losartan group and combined drugs group.The iliac arteries of the rabbits were balloon-injured and the insulin-like growth factor-I receptor(IGF-IR),vascular endothelial growth factor(VEGF),and proliferating cell nuclear antigen(PCNA) were detected by using immunohistochemical method.Results Compared with high cholesterol diet group,the lumen areas were enlarged and the intimal areas were decreased in the probucol group,losartan group and combined drugs group(all P