1.KINETICS OF AP-1 IN LPS-STIMULATED RAT ALVEOLAR MACROPHAGES AND ITS REGULATION ON TNF-? EXPRESSION
Chunxue LI ; Jianxin JIANG ; Youan SHAN
Medical Journal of Chinese People's Liberation Army 1982;0(03):-
To investigate the kinetics of activation of the activator protein-1(AP-1) and elucidate its role in TNF-? expression induced by lipopolysaccharide(LPS) in rat alveolar macrophages(AM), dynamic changes of the activity of AP-1 were detected with electrophoretic mobility shift assay(EMSA). The phosphorothioate oligodeoxynucleotide (S-ODN) decoy was transfected into AM prior to LPS stimulation. The level of TNF-? in culture supernatants was measured with an ELISA kit. The results showed that after LPS stimulation for 0.5 hour, remarkable activation of AP-1 could be detected and reached the highest level. The activation of AP-1 rapidly decreased at 1 hour, then increased at 3 hours again and reduced at 5 and 8 hours after LPS stimulation. The activation of AP-1 could persist at least 8 hours and showed a dose-dependent manner to LPS within 1000ng/ml. AP-1 S-ODN decoys could markedly inhibit the LPS-induced TNF-? production by rat AM, but it could not completely inhibit the production of TNF-? induced by LPS in rat AM. It is suggested that LPS could induce activation of AP-1 in rat AM; AP-1 played an important role in LPS-induced inflammatory response. It is also suggested that AP-1 involved in the regulation on LPS-induced TNF-? production by rat AM, however, entirely inhibition of the activity of AP-1 could not completely prevent TNF-? production by rat AM. It is also implied that other nuclear factors might also play an important role in the regulation on LPS-induced TNF-? expression by rat AM.
2.Kinetics of nuclear factor ?B in LPS stimulated rat alveolar macrophages and its regulative effect on tumor necrosis factor ? expression
Chunxue LI ; Jianxin JIANG ; Youan SHAN
Chinese Journal of Trauma 1993;0(05):-
Objective To investigate the activation of nuclear factor ?B (NF-?B) induced by lipopolysaccharides (LPS) in rat alveolar macrophages (AM) and its regulative role in tumor necrosis factor (TNF-?) expression. Methods The dynamic activity changes of NF-?B DNA induced by LPS (E.coli 026:B6) were determined with electrophoretic mobility shift assay (EMSA). The phosphorothioate oligodeoxynucleotides (S-ODN) decoy was transfected into AM 12 hours prior to LPS stimulation. The effect of NF-?B S-ODN decoy on expression of TNF-? in AM stimulated by LPS were measured with enzyme-linked immunosorbent assay (ELISA) kit. Results NF-?B could be activated remarkably after 0.5 hour of LPS stimulation at concentration of 100 ng/ml, reached the highest level 1 hour after LPS stimulation and gradually decreased. But the activation of NF-?B could last at least 8 hours. The dose for LPS stimulation was related to activation of NF-?B in a dose-dependent fashion, ie, the activation of NF-?B gradually strengthened with dose increase of LPS. Supershift assays proved that p50 and p65 were involved in the activation of NF-?B. NF-?B S-ODN decoy could markedly (not completely) inhibit LPS-induced TNF-? production. Conclusions NF-?B plays an important role in LPS induced inflammatory response. However, entire inhibition of the activity of NF-?B can not completely prevent TNF-? expression induced by LPS in rat AM, which implies that other nuclear factors may participate in TNF-? expression.
3.The influence of the aqueous extract of ephedra sinica treating in brain damage after subarachnoid hemorrhage in rats
Zhengheng TANG ; Shihao GAO ; Tunan CHEN ; Fei LI ; Dongyi CHEN ; Youan SHAN ; Hua FENG ; Yuan CHENG
Chongqing Medicine 2015;(25):3481-3484
Objective To observe the therapeutic effect and mechanism of the aqueous extract of ephedra sinica on brain damage after subarachnoid hemorrhage(SAH)in rats.Methods Totally 50 rats of Sprague-Dawley were randomly divided into control group,model group and three groups treated with different concentrations(4,12,36 mg/kg).The changes of the cerebral water content,malondialdehyde(MDA),glutathione peroxidase(GSH-Px)and hydroxy radical of brain tissue were recorded,and he-matoxylin-eosin(HE)staining was used to test the subarachnoid haemorrhagia and oedema,and immunohistochemistry and western blot were carried out to assay the expression of complement C3 in brains of different animal in different group 3d after operation. Results On the postoperative 3 days,compared with the model group,the content of MDA、GSH-Px activity and hydroxyl radical of 12、36 mg/kg treatment groups significantly reduced(P <0.01 ),the content of MDA of 4 mg/kg treatment group not change (P >0.05),but GSH-Px activity and inhibition of hydroxyl radical significantly reduced(P <0.01),and the cerebral water content of 12,36 mg/kg groups were obviously lower compared with model group.The expression of complement C3 was significantly lower on 36 mg/kg treatment group and edema reduced.Conclusion The aqueous extract of ephedra could significantly inhibit the activity of complement C3,prevent the production of MDA、GSH-Px and hydroxyl radical,reduce the severity of cerebral edema and the in-flammatory response,which has a better therapeutic effect SAH animals.
4.Current research on hepatitis C virus resistance to direct-acting antiviral agents
Journal of Clinical Hepatology 2015;31(11):1807-1812
In recent years, direct-acting antiviral agent(DAA) that target specific enzymes in the life cycle of hepatitis C virus (HCV) have been developed rapidly. However, there are specific resistance-related mutation sites for DAA, which is associated with the gene types/subtypes of HCV. This article describes the resistance-related mutation sites for DAA and their impacts on the treatment regimen according to the mechanism of action of DAA. It is pointed out that some natural mutation sites lead to drug resistance in the treatment for patients with some HCV subtypes, so careful evaluation is needed before treatment to determine the appropriate regimen. For patients experiencing failure in the previous interferon therapy, the pre-existing drug resistance should be studied if DAA in combination with the therapy or interferon-free DAA therapies are to be used.
5.Effect of splenectomy on mortality and brain water content of rats with brain injury
Mei LI ; Fei LI ; Lijun ZHANG ; Zhi CHEN ; Xiang ZHANG ; Youan SHAN ; Jiangkai LIN ; Gang ZHU ; Zhiyong YIN ; Hua FENG
Chinese Journal of Trauma 2010;26(1):9-12
Objective To observe the effect of splenectomy on mortality and brain water content of rats with brain injury so as to explore novel way for better clinical management of patients with severe traumatic brain injury. Methods Adult male SD rats were randomly divided into three groups, ie, sham operation on brain and spleen (Group A, n = 23), experimental brain trauma & sham operation on spleen (Group B, n =48) and experimental brain injury & splenectomy (Group C, n = 47). Modified Feeney' s method was used to create the animal model of experimental brain trauma, Longa' s scale was applied to evaluate the neurologic defect. Mortality within seven days following brain injury was calculat-ed. In the meantime, the brain water content was detected at days 1 (n = 8), 2 (n = 8), 3 (n = 8) and 7 (n = 7) after brain injury in each group, Results No statistical difference of Longs' s scale was found between Group B and Group C (P > 0.05). The mortalities within seven days after brain injury were 0%, 35.42 and 14.89% in Groups A, B and C respectively, with statistical difference between groups (P<0.05). The brain water content of Groups B and C at days 1, 2, 3 and 7 were (81.98±0.35)% & (81.78±0.41)%, (82.58±0.63)% & (81.81±0.48)% (P<0.05),(82.54±0.54)% & (81.52±0.84)% (P<0.05) and (81.50±0.41)% & (81.21±0.36)% (P>0.05) respectively. Conclusion Splenectomy can effectively reduce brain water content and significantly decrease mortality in rata with brain injury.
6.Role of autoimmune ecological factors in the pathogenesis of autoimmune hepatitis
Jie CHEN ; Chunyang HUANG ; Jing SHAN
Journal of Clinical Hepatology 2019;35(10):2339-2341
Autoimmune hepatitis (AIH) is a chronic liver inflammatory disease with unknown etiology, and at present, both genetic and environmental factors are thought to be involved in the pathogenesis of AIH. Environmental exposure has an important impact on the development of AIH. Autoimmune ecology is the study of the interactions between individuals and their environment, the development of imbalance between individuals and environment, and the mechanism of such imbalance in promoting the development of autoimmune disease. This article reviews the research advances in the role of autoimmune ecology in the pathogenesis of AIH.
7.Value of fumarate hydratase antibody in differential diagnosis of autoimmune hepatitis and drug-induced liver injury
Ying HAN ; Jie CHEN ; Jing SHAN
Journal of Clinical Hepatology 2019;35(6):1326-1329
ObjectiveTo investigate the value of fumarate hydratase antibody (anti-FH) in the differential diagnosis of autoimmune hepatitis (AIH) and drug-induced liver injury (DILI). MethodsFrom March 2014 to December 2016, 105 patients with AIH who were hospitalized in Beijing You’an Hospital were enrolled as AIH group, and 92 patients with DILI were enrolled as DILI group. A total of 128 healthy individuals were enrolled as control group. ELISA was used to measure the serum level of anti-FH. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. A consistency analysis of diagnostic compliance of anti-FH based on the Kappa test. The sensitivity, specificity, positive predictive value, and negative predictive value of anti-FH in the diagnosis of AIH were analyzed. ResultsCompared with the DILI group, the AIH group had significantly higher positive rate of anti-nuclear antibody (72.4% vs 55.4%, χ2 = 6147, P=0.013) and level of IgG ((18.3±6.1) g/L vs (15.2±5.4) g/L, t=-2566, P=0.011)). The AIH group had a significantly higher positive rate of anti-FH than the DILI group and the control group (36.2% (38/67) vs 6.5% (6/92) and 2.3% (3/128), χ2=59.959, P<0.001). In the diagnosis of AIH, anti-FH had a sensitivity of 36.2%, a specificity of 93.5%, a positive predictive value of 86.4%, and a negative predictive value of 93.5%. ConclusionSerum anti-FH has a certain reference value in the differential diagnosis of AIH and DILI.
9.Hepatitis B vaccine: From prevention to treatment
Yisi LIU ; Shan REN ; Sujun ZHENG ; Xinyue CHEN
Journal of Clinical Hepatology 2024;40(5):1021-1025
Hepatitis B vaccination is the most economical and effective way to prevent HBV infection. The advances in molecular biology and genetic engineering have continuously improved the manufacturing process of vaccines, and hepatitis B vaccine has gradually developed from the initial plasma-derived vaccine to the currently used recombinant vaccine. Preventive hepatitis B vaccine has been clinically tested in patients with HBsAg seroclearance to increase the level of anti-HBs, with certain safety and efficacy. As one of the multiple targets for new drugs in the treatment of chronic hepatitis B, a therapeutic hepatitis B vaccine based on HBsAg is already in the stages of research and development and clinical trial.
10.The cut off value of liver stiffness measurement needs to be lowered to predict liver fibrosis after sustained virologic response in chronic hepatitis C patients
Lixia QIU ; Jingjing SONG ; Shan LIANG ; Yali LIU ; Jing ZHANG
Journal of Clinical Hepatology 2021;37(12):2808-2812
Objective To further verify the ability of noninvasive diagnostic method for liver fibrosis in predicting liver fibrosis in chronic hepatitis C patients followed up after sustained virologic response (SVR) based on liver biopsy. Methods A prospective cohort study was performed for the chronic hepatitis C patients who attended Beijing YouAn Hospital, Capital Medical University, from October 2015 to December 2017, and all patients were followed up regularly after SVR and underwent liver biopsy. The diagnostic efficiency of the noninvasive diagnostic method for liver fibrosis was verified based on pathological results. The receiver operating characteristic (ROC) curve was used to evaluate the ability of LSM, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) in the diagnosis of liver fibrosis, and STATA and R language were used to compare the area under the ROC curve (AUC). Results A total of 96 patients were successfully enrolled. The LSM after SVR was significantly lower than that at baseline, and LSM had a significantly larger AUC than APRI (0.89 vs 0.67, P < 0.05) and FIB (0.89 vs 0.69, P < 0.05) in the diagnosis of liver cirrhosis after SVR. LSM at a cut-off value of 7.95 kPa, and based on the best specificity, the diagnosis of liver cirrhosis could be considered when LSM was greater than 9.15 kPa, with a positive likelihood ratio of 5.91%; progressive liver fibrosis could be excluded based on LSM < 6.85 kPa, with a negative predictive value of 0.98. Follow-up time and antiviral regimen had no influence on the diagnostic ability of LSM. Conclusion The cut off value of LSM needs to be lowered to predict liver fibrosis after SVR in chronic hepatitis C patients.