1.Changes of hepatitis B core antigen-specific cytotoxic T lymphocytes in chronic hepatitis B patients during antiviral treatment and relapse after withdrawal of treatment
Bixia LIU ; Lunli ZHANG ; Wenfeng ZHANG
Chinese Journal of Infectious Diseases 2016;34(8):480-484
Objective To explore the potential mechanism of severe liver injury shortly after withdrawal of antiviral therapy in chronic hepatitis B (CHB) patients.Methods Forty-nine patients with chronic hepatitis B virus (HBV) infection from the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University and 8 healthy volunteers from August 2014 to March 2015 were included in this study.All of them were human leukocyte antigen (HLA)-A2-positive.CHB patients were classified into three groups,including 15 cases in immune-tolerance group,20 cases in sustained antiviral treatment group,and 14 cases in recurrence of drug withdrawal group.The frequency of peripheral HLA-A0201-restricted hepatitis B core antigen (HBcAg)18-27 pentamer complex specific CD8+ T cells in CHB patients was analyzed by flow cytometry.Enzyme linked immunospot assay(ELISPOT) was used to detect interferon-gamma (IFN-γ) and tumor necrosis factor-α (TNF-α) secretions of HBcAg18-27-specific CD8+ T cells.The experimental data were analyzed using non-parametric U tests.Results In healthy control group,immune-tolerance group,sustained antiviral treatment group and recurrence of drug withdrawal group,the frequencies of HBcAg-specific CD8+T cells were (0.17 ± 0.16) %,(1.46±0.72)%,(3.24± 1.60)% and (4.67±2.43)%,respectively.Compared with healthy control group,the difference were all statistically significant in the three groups (Z=-3.583,-4.018 and-3.823,respectively;all P<0.01).The frequencies of HBcAg-specific CD8+T cells in immune tolerance group or recurrence of drug withdrawal group were both significantly different from that in sustained antiviral therapy group (Z=-3.400 and-2.030,respectively;both P<0.05).The difference between immune-tolerance group and recurrence of drug withdrawal group was also significant (Z =-3.230,P<0.01).The secretion levels of IFN-γ of HBcAg-specific CD8+T cells in healthy control group,immune-tolerance group,sustained antiviral treatment group and recurrence of drug withdrawal group were2 (0-6),16 (2-53),106 (14-254) and 156 (28-395) spot forming cell (SFC)/106 peripheral blood mononuclear cell (PBMC),respectively.The differences between healthy control group and immune-tolerance group,sustained antiviral treatment group or recurrence of drug withdrawal group were all statistically significant (Z=-3.585,-4.069 and-3.824,respectively;all P<0.01).The IFN-γ level of HBcAg-specific CD8+ T cells in recurrence of drug withdrawal group was significantly higher than that in sustained antiviral therapy group (Z=-2.205,P=0.027),and that in sustained antiviral therapy group was significantly higher than that in immune-tolerance group (Z=-4.700,P< 0.01).The TNF-α levels secreted by HBcAg-specific CD8+ T cells in each group were 2 (0-5),16 (2-32),112 (15-283),and 195 (55-537) SFC/106PBMC,respectively.The differences between healthy control group and immune-tolerance group,sustained antiviral treament group or recurrence of drug withdrawal group were all statistically significant (Z=-3.619,-4.069 and-3.824,respectively;all P<0.01).The TNF-α level secreted by HBcAg-specific CD8+T cells in recurrence of drug withdrawal group was significantly higher than that in sustained antiviral therapy group (Z=-2.449,P=0.014),and that in sustained antiviral therapy group was significantly higher than that in immune-tolerance group (Z=-4.350,P<0.01).Conclusions The changes of frequency and immune function of HBcAg-specific CD8+T cells in CHB patients may be one of the reasons causing severe liver damage after irregular withdrawal of nucleoside analogues.
2.Relationship between IL-17 and autoimmune diseases
Bixia TANG ; Xuan ZHANG ; Fulin TANG
Basic & Clinical Medicine 2006;0(01):-
IL-17 is the cytokine secreted by the subgroup of CD4+T cells named Th17.The differentiation,proliferation and cytokine secretion of Th17 are regulated by TGF-?,IL-6,IL-15 and IL-23.IL-17 modulates the production and secretion of proinflammative factors,CXCs,affecting the transfer of neutrophil,the activation and the absorption of bone.It suggests that IL-17 also plays an important role in the pathogenesis of autoimmune diseases.
3.Comparison study between transcatheter closure and surgical repair in over 50-year old patients with secundum atrial septal defect
Bixia FENG ; Xinsheng HUANG ; Jingfang ZHANG ; Al ET ;
Chinese Journal of Thoracic and Cardiovascular Surgery 2003;0(03):-
Objective: The aim of this study is to compare the clinical data and result between transcatheter closure and surgical repair for the treatments of secundum ASD in patients above 50 years old, and explore the indications for these two methods. Methods: From January 1998 to December 2003, 53 patients with surgical repair and 42 patients with transcatheter closure were enlisted according to the diagnosis of ASD. The ages of all of cases were above 50 years old. The interventional approach was administrated with Amplatzer device. The surgical approach mended the defect directly or with autologous pericardium. These patients were followed up by echocardiography (Echo). The clinical data including the diameter of the right ventricle (RVD), the pulmonic flow velocity, the pulmonary pressure and the tricuspid valve regurgitation. Results: In surgery group, surgical mortality was 1 9% (1/53). Cerebral embolism occurred in 4 (7 5%) patients. Pericardial effusion and other complications occurred in 24.5%. All 42 patients with ASD were effectively closed with Amplatzer occlude. One occluder displaced and moved into pulmonary artery on the fourth day after the treatment. The short term effective rate was 97 6% in transcatheter closure group. The diameter of ASD showed by Echo was significantly less in patients treated with transcatheter closure than that in surgical repair group. The hospitalization time was significantly less in patients treated with transcatheter closure. The follow up data recorded decreased load of right ventricle, the decreased diameter of right ventricle as well as the relief of pulmonary artery hypertension. Conclusion: The data suggested that of surgical approach of ASD has a wider indication for patients in different stages of the disease, whereas surgical morbidity may increase in elderly patients due to their pre existed diseases. However, the transcatheter closure for ASD is feasible for patients with smaller defects.
5.The effect of p53 expression in fibrablast-like synaviocytes on CD4+ T lymphocytes in patients with rheumatoid arthritis
Bixia TANG ; Xin YOU ; Lidan ZHAO ; Ting ZHANG ; Lei ZHANG ; Xuan ZHANG ; Fulin TANG
Chinese Journal of Rheumatology 2009;13(9):587-591
Objective To investigate that p53 expression in fibroblast-like synoviocytes (FLS) and its effects on CD4+ T lymphocytes from active rheumatoid arthritis (RA) patients. Methods Human FLS was transfected with p53siRNA and cocultured with CD4+ T lymphocytes from active RA patients. The expression of osteoprotegerin and IL-6 secretion was detected in the transfected FLS. In addition, the expressions of IFN-γ, IL-17, IL-4 and CD25 as well as mRNA levels of IFN-γ RORγt, IL-17 and Foxp3 in cocuhured CD4+ T lymphocytes were also measured. Results IL-6 secretion decreased in p53-inhibited FLS while osteopro-tegerin expression was not altered, p53-inhibited FLS could significantly increase IL-17 and IFN-γ expres-sions. It also upregulated Foxp3 expression though had no effect on CD4+CD25high T lymphocytes. Conclusion p53 expression in FLS regulates Th1 and Th17 cells of RA patients, and therefore participate in the pathogenesis of RA.
6.Epigallocatechin gallate suppresses 1-methy1-4-phenyl-pyridinium-induced the damage of oxidative stress in PC12 cells by activating nuclear factor-related factor 2
Qinyong YE ; Xianjie XU ; Linfeng YE ; Xiaodong ZHANG ; Bixia HUANG ; Yuangui ZHU ; Xiaochun CHEN
Chinese Journal of Neurology 2012;45(6):387-391
Objective To investigate the relationship between the neuroprotective effect of epigallocatechin gallate ( EGCG ) for PC12 cells induced by 1-methyl-4-phenyl-pyridinium ( MPP+ ) and activating nuclear factor-related factor 2 ( NRF2 ).Methods Well differentiated PC12 cells treated with MPP+ were used as the in vitro cell models,and PC12 cells were pretreated with different concentrations of EGCG.MTT assay was used to investigate the cell viability.Western blot was used to observe the expression of NRF2 in cells and distribution in the nucleus and the cytoplasm.Real-time PCR was used to observe the antioxidant enzymes,HO-1 and NQO1 mRNA expression.Results Pretreatment of PC12 cells with different concentrations of EG CG for an hour could restore cell viability.Western blot showed that expression of NRF2 in cells treated with MPP+ for 24 hours was increased 148% +5% compared with the control group (t =6.102,P <0.01 ).The level of NRF2 in EGCG pretreated group was 188% + 6% compared with the control group(t =11.172,P <0.01 ).Moreover the NRF2 protein level in the nuclear was also increased.Western blot showed that the NRF2 protein level in the nuclear was 258% +2% compared with the control group (t =21.995,P < 0.01 ).Further research found U 120,an inhibitor of ERK,could inhibit the effect of EGCG.The levels of NRF2 in both samples were 148% ± 15% and 158% ± 1% compared with their respective control groups(t =6.118,8.058,both P <0.01 ).In accordance with the NRF2 data,real-time PCR indicated that the levels of HO-1 and NQO1 mRNA expression increased obviously in the group pretreated with EGCG.Likewise,U120 could also inhibit HO-1 and NQO1 mRNA expression induced by EGCG.Conclusions EGCG can repair oxidative damage to PC12 cells induced by MPP+.The protective effect may be related through the ways to activate ERK-NRF2 and induce downstream of antioxidant enzyme expression,such as HO-1 and NQO1.
7.Distribution and Drug Resistance Status of Extended-Spectrum ?-Lactamases Producing Klebsiella pneumoniae
Dejun ZHAO ; Weichan FU ; Bixia ZHANG ; Yujiang REN ; Yan CAO ; Yue MAO ; Wei YANG
Chinese Journal of Nosocomiology 2006;0(05):-
OBJECTIVE To investigate the distribution and drug resistance status of extended-spectrum ?-lactamases producing(ESBLs) Klebsiella pneumoniae and to provide the basis for clinic anti-infective treatment.METHODS To use ATB-expression analyzer to identify the microbe.The drug susceptibility was tested with the K-B method and the ESBLs producing strains detected by diffusion confirmed test.RESULTS Among 137 strains of identified K.pneumoniae,34.3% of them(47 strains)produced ESBLs,and most had been shown in geriatrics ward.The drug resistance rate of ESBLs producing K.pneumoniae was higher than that in non-producing ESBLs one.So imipenem should be considered to be a preferred antibiotic when used on K.pneumoniae seriously infected cases.CONCLUSIONS The drug resistance of K.pneumoniae is a serious problem,we should pay attention on the status of ESBLs distribution,based on the susceptibility to choose the reasonable antibacterial to avoid the producing ESBLs bacteria spread out.
8.Detection of and Surveillance on Drug Resistance of Extended-spectrum ?-Lactamases Producing Escherichia coli in Community-acquired Urinary Tract Infection
Dejun ZHAO ; Weichan FU ; Bixia ZHANG ; Zhaoyu HU ; Yujiang REN ; Yan CAO ; Yue MAO ; Wei YANG
Chinese Journal of Nosocomiology 2005;0(11):-
OBJECTIVE To investigate the drug resistance of ESBLs-producing Escherichia coli in community-acquired urinary tract infection for guiding the clinical drug-using.METHODS ATB-Expression analysis system was used for identification of bacteria,extra-susceptibility tests were detected by K-B method.RESULTS Totally 104 E.coli strains were detected,the isolation rate of ESBLs-producing E.coli was 13.5%,the resistant rates of E.coli were up to 70% to ampicillin,piperacillin and Co-trimoxazole,the resistant rate was up to 55% to ciprofloxacin and levofloxacin,and the susceptible rate was 100% to imipenem.CONCLUSIONS The E.coli is a main pathogen in community-acquired urinary tract infection,Its drug resistance is extremely severe.To enhance detecting drug resistance of pathogenic bacteria is of important significance for guiding the clinical rational drug-using and reducing drug-resistant strains.
9.Detection and Surveillance on Drug Resistance of ESBLs-producing Escherichia coli and Klebsiella pneumoniae in Nosocomial Infection
Dejun ZHAO ; Weichan FU ; Weitao TIAN ; Bixia ZHANG ; Yujiang REN ; Yan CAO ; Yue MAO ; Wei YANG
Chinese Journal of Nosocomiology 2009;0(13):-
OBJECTIVE To investigate the drug resistance of ESBLs-producing Escherichia coli and Klebsiella pneumoniae in local nosocomial infection,for guiding the clinical drug resistance. METHODS ATB analysis system was used for identification of bacteria,extra-susceptibility tests were detected by K-B method. RESULTS The isolation rate of ESBLs-producing E. coli and the K. pneumoniae was 29.9% and 30.8%,respectively. The drug susceptibility was indicated the resistance rate of ESBLs producing strains to antibacterial agents except imipenem was higher than that of non-ESBLs producing strains. CONCLUSIONS Detecting drug resistance of ESBLs producing strains is of important significance for guiding the clinical rational use of antibacterials and controling the epidemics.
10.Hospital-acquired Infection in General ICU: Analysis of Pathogen Distribution and Related Factors
Chuan ZHANG ; Hui XIE ; Lidong JIANG ; Jinchuan CHENG ; Bixia ZHENG ; Qi WEI ; Xiaojin LI
Chinese Journal of Nosocomiology 2006;0(02):-
OBJECTIVE To investigate the distribution of bacteria in general ICU then discuss the susceptible factors and the treatment.METHODS A retrospective analysis of clinical information was performed on 123 patients diagnosed infection who stayed in ICU from May 2002 to May 2004.RESULTS Most of bacteria resulted in infection of general ICU were Gram-negative(62.88%) and then Gram-positive(19.65%). Fungal infection accounted for 17.47%.Pseudomonas aeruginosa occupied the highest percentage among Gram-negative bacteria.Most of Gram-positive bacteria were Staphylococcus aureus and all of them were MRS.The infection site in ICU focused on lower respiratory tract(89.09%).The second was urinary tract(11.79%).CONCLUSIONS Most of the bacteria causing infection in general ICU locate in respiratory tract.They are mainly Gram-negative.All of the Gram-positive bacteria are MRS.The risk factors of hospital-acquired infection are related with patient′s age,underlying disease,intensive care time,ventilation time and invasive operation.