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| 1 | Interleukin-33 drives hepatic fibrosis through activation of hepatic stellate cells显示文摘Liver fibrosis is a consequence of chronic liver disease,causing morbidity and mortality.Interleukin-33(IL-33)is a critical mediator of inflammation,which may be involved in the development of liver fibrosis.Here,we investigated the role of IL-33 in human patients and experimental bile-duct ligation(BDL)-induced fibrosis in mice.We report increased hepatic IL-33 expression in the murine BDL model of fibrosis and in surgical samples obtained from patients with liver fibrosis.Liver injury,inflammatory cell infiltration and fibrosis were reduced in the absence of the IL-33/ST2 receptor,and the activation of hepatic stellate cells(HSCs)was decreased in ST2-deficient mice.Recombinant IL-33 activated HSCs isolated from C57BL/6 mice,leading to the expression of IL-6,TGF-β,α-SMA and collagen,which was abrogated in the absence of ST2 or by pharmacological inhibition of MAPK signaling.Finally,administration of recombinant IL-33 significantly increased hepatic inflammation in sham-operated BL6 mice but did not enhance BDL-induced hepatic inflammation and fibrosis.In conclusion,BDL-induced liver inflammation and fibrosis are dependent on ST2 signaling in HSCs,and therefore,the IL-33/ST2 pathway may be a potential therapeutic target in human patients with chronic hepatitis and liver fibrosis. | Zhongming Tan Qianghui Liu Runqiu Jiang Long Lv Siamak S Shoto Isabelle Maillet Valerie Quesniaux Junwei Tang Wenjie Zhang Beicheng Sun Bernhard Ryffel | 2018 | Cellular & Molecular Immunology2018，15，4： | 24 |
| 2 | Attenuated Listeria monocytogenes as a cancer vaccine vector for the delivery of CD24, a biomarker for hepatic cancer stem cells显示文摘稀释 Listeria monocytogenes (LM ) 是为癌症疫苗的交货的有希望的候选人向量。在由介绍抗原的房间的吞噬作用以后,这个细菌刺激主要 histocompatibility 建筑群(MHC ) 我和 MHC-II 小径并且导致抗原特定的 T 淋巴细胞的增长。包含复制缺乏的 LM 种类 Δ 的基因修正的新策略; dalΔ dat (Lmdd ) 被开发了表示并且藏匿人的 CD24 蛋白质。CD24 是仔细与 hepatocellular 癌(HCC ) 的 apoptosis,转移和复发被联系的肝的癌症干细胞 biomarker。在在老鼠的静脉内的管理以后, Lmdd-CD24 首先在怒气和肝被散布并且没引起严重机关损害。Lmdd-CD24 有效地增加了干扰素(IFN ) 的数字 -γ-producing CD8 + T 房间和 IFN-γ分泌物。Lmdd-CD24 也提高了 IL-4- 和 IL-10-producing T 助手 2 房间的数字。Lmdd-CD24 疫苗的功效进一步对 Hepa1-6-CD24 肿瘤被调查,它腹股沟地被接种进老鼠。Lmdd-CD24 显著地在老鼠减少了肿瘤尺寸并且增加了他们的幸存。尤其是, T 规章的房间(Treg ) 的减小数并且特定的 CD8 +T 房间活动的改进在渗入肿瘤的淋巴细胞(TIL ) 被观察。这些结果对 HCC 建议 Lmdd-CD24 疫苗的一个潜在的应用程序。 | Yu Yang Jiajie Hou Zhe Lin Han Zhuo DianyuChen Xudong Zhang Yun Chen Beicheng Sun | 2014 | Cellular & Molecular Immunology2014，11，2： | 9 |
| 3 | EBV LMP2A-specific T Cell Immune Responses Elicited by Dendritic Cells Loaded with LMP2A Protein显示文摘类型 II Epstein-Barr 病毒(EBV ) 联系了象鼻咽的癌和 non-Hodgkin 的淋巴瘤那样的恶意一致地快速的潜伏的膜 2A (LMP2A ) 蛋白质,它被建议了是为免疫疗法的一个理想的目标。在我们表明了的以前的研究,那使用的 LMP2A 蛋白质装载了树枝状的房间,在身体处理房间的最强大的抗原能得到特定、柔韧的反肿瘤在 vitro 的细胞的有免疫力的反应。在这份报纸,我们进一步调查了反肿瘤免疫者反应的 T 房间侧面。我们发现 LMP2A 特定的 CD4+ 和 CD8+ T 房间能被 LMP2A 蛋白质刺激装载树枝状的房间(DC ) 。Th1 类型免疫者反应在有免疫力的反应是主导的由 LMP2A 特定的 CD4+ T 房间调停了。有效地并且明确地忍受房间的 CD8+ 细胞毒素的 T 房间罐头细胞溶解 LMP2A。CD8+ 细胞毒素的 T 房间能也分泌细胞内部的 IFN- 的高水平,它显示这些房间是 EBV-LMP2A 特定的细胞毒素的 T 房间。总的来说,我们的研究证明了装载 DC 能得到的那 LMP2A 蛋白质是反肿瘤细胞的有免疫力的回答高效地。这研究对表示恶意的 EBV-LMP2A 为基于 DC 的免疫疗法提供一个基本原理。 | Yun Chen Hua Sun Genyan Liu Bing Wang Fang Wang Beicheng Sun Kun Yao | 2009 | Cellular & Molecular Immunology2009，6，4： | 6 |
| 4 | The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection显示文摘Epigenetic modifications to histones dictate the differentiation of naïve CD4^(+) T cells into different subsets of effector T helper(TH)cells.The histone methyltransferase enhancer of zeste homolog 2(EZH2)has been implicated in the mechanism regulating the differentiation of TH1,TH2 and regulatory T(Treg)cells.However,whether and how EZH2 regulates follicular helper T(TFH)cell differentiation remain unknown.Using a mouse model of acute lymphocytic choriomeningitis virus(LCMV)infection,we observed abundant EZH2 expression and associated H3K27me3 modifications preferentially in the early committed virus-specific TFH cells compared to those in TH1 cells.Ablation of EZH2 in LCMV-specific CD4^(+) T cells leads to a selective impairment of early TFH cell fate commitment,but not late TFH differentiation or memory TFH maintenance.Mechanistically,EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for TFH fate commitment,particularly B cell lymphoma 6(Bcl6),and thus directs TFH cell commitment.Therefore,we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early TFH differentiation during acute viral infection. | Xiangyu Chen Guoshuai Cao Jialin Wu Xinxin Wang Zhiwei Pan Jianbao Gao Qin Tian Lifan Xu Zhirong Li Yaxing Hao Qizhao Huang Pengcheng Wang Minglu Xiao Luoyingzi Xie Shupei Tang Zhenyu Liu Li Hu Jianfang Tang Ran He Li Wang Xinyuan Zhou Yuzhang Wu Mengjie Chen Beicheng Sun Bo Zhu Jun Huang Lilin Ye | 2020 | Cellular & Molecular Immunology2020，17，3： | 4 |
| 5 | IL-17A Plays a Critical Role in the Pathogenesis of Liver Fibrosis through Hepatic Stellate Cell Activation显示文摘 | Zhongming Tan Xiaofeng Qian Runqiu Jiang Qianghui Liu Youjing Wang Chen Chen Xuehao Wang Bernhard Ryffel Beicheng Sun | 2013 | The Journal of Immunology2013，，4： | 2 |
| 6 | The BH3-only protein BAD mediates TNFα cytotoxicity despite concurrent activation of IKK and NF-κB in septic shock显示文摘煽动性的 cytokine TNF 在许多煽动性、传染的疾病的病理起一个关键作用。然而,在这些疾病位于 TNF cytotoxicity 下面的机制不完全地被理解。这里,我们报导 pro-apoptotic BCL-2 家庭成员坏调停尽管有在由由得到多重机关的织物损坏并且贡献死亡在在有教养的房间并且在 vivo 导致 apoptosis 的 vitro 的 IKK 和 NF-B 的并发的激活的 TNF cytotoxicity 腐败吃惊。在高剂量, TNF 显著地通过 Src-p190GAP 小径的激活使 RhoA 失去活性,导致巨大的肌动朊压力纤维 destabilization,从细胞骨架由实质的坏版本列在后面到 cytosol。在这个条件下面,激活 IKK 没有通过所有 cytosolic 到 phosphorylate 坏,允许对线粒体不适宜的 non-phosphorylated 的 translocation 触发 apoptosis。Polymicrobial 感染利用象高剂量的 TNF 的一样的机制得到多重机关的联系 apoptosis 的织物损坏。因而,损失坏或坏 pro-apoptotic 活动的消除保护老鼠免受多重机关和还原剂死亡率的织物损坏的伤害。我们的结果支持在的一个模型坏调停尽管有在有教养的哺乳动物的房间并且在的 IKK-NF-B 小径的并发的激活的 TNF cytotoxicity 腐败吃惊。 | Jie Yan Hao Zhang Jialing Xiang Yu Zhao Xiang Yuan Beicheng Sun Anning Lin | 2018 | Cell Research2018，28，7： | 2 |
| 7 | Inflammation and liver tumorigenesis显示文摘Inflammation has been considered as one of the hallmarks of cancer,and chronic hepatitis is a major cause of liver cancer.This review will focus on the pathogenic role of inflammation in hepatocarcinogenesis and will discuss recent advances in understanding the chronic hepatitis-liver cancer link based on hot spots in liver cancer research,including cellular interaction,cytokines,microRNA and stem cells.All of these mechanisms should be taken into consideration because they are crucial for the development of more efficacious therapeutic strategies for preventing and treating human chronic hepatitis and hepatocellular carcinoma. | Beicheng Sun Michael Karin | 2013 | Frontiers of Medicine2013，7，2： | 2 |
| 8 | TOX deficiency facilitates the differentiation of IL-17A-producingγδT cells to drive autoimmune hepatitis显示文摘The specification of theαβ/γδlineage and the maturation of medullary thymic epithelial cells(mTECs)coordinate central tolerance to self-antigens.However,the mechanisms underlying this biological process remain poorly clarified.Here,we report that dual-stage loss of TOX in thymocytes hierarchically impaired mTEC maturation,promoted thymic IL-17A-producingγδT-cell(Tγδ17)lineage commitment,and led to the development of fatal autoimmune hepatitis(AIH)via different mechanisms.Transfer ofγδT cells from TOX-deficient mice reproduced AIH.TOX interacted with and stabilized the TCF1 protein to maintain the balance ofγδT-cell development in thymic progenitors,and overexpression of TCF1 normalizedαβ/γδlineage specification and activation.In addition,TOX expression was downregulated inγδT cells from AIH patients and was inversely correlated with the AIH diagnostic score.Our findings suggest multifaceted roles of TOX in autoimmune control involving mTEC and Tγδ17 development and provide a potential diagnostic marker for AIH. | Qifeng He Yijun Lu Wenfang Tian Runqiu Jiang Weiwei Yu Yong Liu Meiling Sun Fei Wang Haitian Zhang Ning Wu Zhongjun Dong Beicheng Sun | 2022 | Cellular & Molecular Immunology2022，19，10： | 1 |
| 9 | Combination of Radiofrequency Ablation with Transarterial Chemoembolization for Hepatocellular Carcinoma: A Meta-Analysis显示文摘 | Shushan Yan Donghua Xu Beicheng Sun | 2012 | Digestive Diseases and Sciences2012，，11： | 1 |
| 10 | MTHFR C677T polymorphism contributes to the risk for gastric cancer显示文摘 | Shushan Yan Donghua Xu Pingping Wang Ping Wang Chengcheng Liu Changjiang Hua Tao Jiang Bin Zhang Zengcai Li Lei Lu Xianzhong Liu Bingji Wang Donghua Zhang Rongsheng Zhang Shaoheng He Beicheng Sun Xuan Wang | 2014 | Tumor Biology2014，，3： | 1 |
| 11 | The polymorphism of methylenetetrahydrofolate reductase C677T but not A1298C contributes to gastric cancer显示文摘 | Long Lv Ping Wang Beicheng Sun Gong Chen | 2014 | Tumor Biology2014，，1： | 1 |
| 12 | IL-17A Plays a Critical Role in the Pathogenesis of Liver Fibrosis through Hepatic Stellate Cell Activation显示文摘 | Zhongming Tan Xiaofeng Qian Runqiu Jiang Qianghui Liu Youjing Wang Chen Chen Xuehao Wang Bernhard Ryffel Beicheng Sun | 2013 | The Journal of Immunology2013，，4： | 1 |
| 13 | IL-33/ST2 signaling in liver transplantation显示文摘In a study published in Cellular&Molecular Immunology,we described a novel mechanism by which IL-33 drives hepatic fibrosis through the MAPK pathway.The study demonstrated that hepatocyte-derived IL-33 is elevated upon bile duct ligation(BDL)-induced liver injury and fibrogenesis and activates hepatic stellate cells in a JNK/ERK/p38-dependent manner. | Zhongming Tan Beicheng Sun | 2021 | Cellular & Molecular Immunology2021，18，3： | 0 |
| 14 | Characteristics of SARS-CoV-2-specific cytotoxic T cells revealed by single-cell immune profiling of longitudinal COVID-19 blood samples显示文摘Dear Editor,The SARS-CoV-2 virus outbreak that started in December 2019 is now a global pandemic with over 42.7 million confirmed cases and 1.15 million deaths as of October 25,2020.It has been predicted that resurgence in contagion may be possible as late as 2024.1 A persistent anti-SARS-CoV-2 adaptive immune surveillance post infection is critical to lower the risk of resurgence and transmission.T cells are the primary effectors of cellular adaptive immunity that not only clear virus-infected cells during infection but also provide long-term protection post infection as memory cells in some pathogen infections.However,little is known regarding the longitudinal T cell response during and after SARSCoV-2 infection.Single-cell T cell receptor(TCR)sequencing allows rapid identification of expanded T cell clones that are potentially the antigen-specific clonotypes.2 To further characterize the anti-SARS-CoV-2 T cells,we sequenced the circulating T cells of five moderate or severe COVID-19 patients at different stages of infection(two patients at 1,7 and 16 weeks and three patients at 1 and 17 weeks post symptom onset)and of two healthy donors(Supplementary Tables S1,S2 and S7). | Qing Xiong Cheng Peng Xiaomin Yan Xueqi Yan Lin Chen Beicheng Sun Shiping Jiao | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 0 |
| 15 | A bystander cell-based GM-CSF secreting vaccine synergized with a low dose of cyclophosphamide presents therapeutic immune responses against murine hepatocellular carcinoma显示文摘Granulocyte 巨噬细胞刺激殖民地的因素(GM-CSF ) secreting 细胞的肿瘤疫苗在鼠科的模型和病人受不了癌症贡献有势力 antitumor 免疫者回答的正式就职。Hepatocellular 癌(HCC ) 是在中国的最经常、恶意的癌症之一。第一次,我们描述释放向与这类癌症作斗争代表步的疫苗的策略的 GM-CSF。在这研究,一个旁观者对鼠科的 HCC 的基于房间的 GM-CSF secreting 疫苗, Hepa1-6/B78H1-GM-CSF,与 cyclophosphamide (CY ) 的低剂量被共同管理。在与肿瘤和种痘质问以后,免疫学的试金证明细胞的 antitumor 免疫者回答高效地被激活并且肿瘤开发显著地被延迟,它依赖于有 CY 的协同作用。在鼠科的模型的 anti-HCC 疫苗的有希望的结果表明未来的可行性为在 HCC 病人的这治疗的临床的申请。 | Chen Chen Jiajie Hou Zhe Lin Ming Yao Runqiu Jiang Youjing Wang Yun Gao Qing Shao Lei Deng Yun Chen Beicheng Sun | 2013 | Cellular & Molecular Immunology2013，10，4： | 0 |
| 16 | PTPROt maintains T cell immunity in the microenvironment of hepatocellular carcinoma显示文摘Intratumoral T cells play a central role in anti-tumor immunity,and the balance between T effector cells(Teff)and regulatory T cells(Treg)affects the prognosis of cancer patients.However,educated by tumor microenvironment,T cells frequently fail in their responsibility.In this study,we aimed to investigate the role of truncated isoform of protein tyrosine phosphatase receptor-typeO(PTPROt)in T cell-mediated anti-tumor immunity.We recruited 70 hepatocellular carcinoma(HCC)patients and 30 healthy volunteers for clinical investigation,and analyzed cellular tumor immunity by using ptpro^(-/-) C57BL/6 mice and NOD/SCID mice.PTPROt expression was significantly downregulated in human HCC-infiltrating T cells due to the hypoxia microenvironment;PTPROt expression highly correlated with the intratumoral Teff/Treg ratio and clinicopathologic characteristics.Moreover,PTPROt deficiency attenuated T cell-mediated anti-tumor immunity and remarkably promoted mouse HCC growth.Mechanistically,deletion of PTPROt decreased Teff quantity and quality through phosphorylation of lymphocyte-specific tyrosine kinase,but increased Treg differentiation through phosphorylation of signal transducer and activator of transcription 5.In support of the Teff/Treg homeostasis,PTPROt serves as an important tumor suppressor in HCC microenvironment. | Jiajie Hou Lei Deng Han Zhuo Zhe Lin Yun Chen Runqiu Jiang Dianyu Chen Xudong Zhang Xingxu Huang Beicheng Sun | 2015 | Journal of Molecular Cell Biology2015，7，4： | 0 |
| 17 | TNFR2 is a potent prognostic biomarker for post-transplant lung metastasis in patients with hepatocellular carcinoma显示文摘Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great value.Methods:The mRNA profiles of primary and paired lung metastatic lesions were analyzed to determine key signaling pathways.We enrolled 241 HCC patients who underwent liver transplantation from three centers.Tissue microarrays were used to evaluate the prognostic capacity of tumor necrosis factor(TNF),tumor necrosis factor receptor 1(TNFR1),and TNFR2,particularly for post-transplant lung metastasis.Results:Comparison of primary and lung metastatic lesions revealed that the TNF-dependent signaling pathway was related to lung metastasis of HCC.The expression of TNF was degraded in comparison to that in para-tumor tissues(P<0.001).The expression of key receptors in the TNF-dependent signaling pathway,TNFR1 and TNFR2,was higher in HCC tissues than in para-tumor tissues(P<0.001).TNF and TNFR1 showed no relationship with patients’outcomes,whereas elevated TNFR2 in tumor tissue was significantly associated with worse overall survival(OS)and increased recurrence risk(5-year OS rate:31.9%vs.62.5%,P<0.001).Notably,elevated TNFR2 levels were also associated with an increased risk of post-transplant lung metastasis(hazard ratio:1.146;P<0.001).Cox regression analysis revealed that TNFR2,Hangzhou criteria,age,and hepatitis B surface antigen were independent risk factors for post-transplant lung metastasis,and a novel nomogram was established accordingly.The nomogram achieved excellent prognostic efficiency(area under time-dependent receiver operating characteristic=0.755,concordance-index=0.779)and was superior to conventional models,such as the Milan criteria.Conclusions:TNFR2 is a potent prognostic biomarker for predicting post-transplant lung metastasis in patients with HCC.A nomogram incorporating TNFR2 deserves to be a helpful prognostic tool in liver transplantation for HCC. | Huigang Li Zuyuan Lin Jianyong Zhuo Modan Yang Wei Shen Zhihang Hu Yichen Ding Hao Chen Chiyu He Xinyu Yang Siyi Dong Xuyong Wei Beicheng Sun Shusen Zheng Ren Lang Di Lu Xiao Xu | 2023 | Chinese Journal of Cancer Research2023，35，1： | 0 |
| 18 | Living Donor Liver Transplantation for End-stage Liver Disease显示文摘 | Xuehao Wang Feng Zhang Xiangcheng Li Lianbao Kong Beicheng Sun Guoqiang Li Feng Cheng Ling Lv | 2008 | 器官移植内科学杂志2008，3，3： | 0 |
| 19 | Characteristics of SARS-CoV-2-specific cytotoxic T cells revealed by single-cell immune profiling of longitudinal COVID-19 blood samples显示文摘Dear Editor,The SARS-CoV-2 virus outbreak that started in December 2019 is now a global pandemic with over 42.7 million confirmed cases and 1.15 million deaths as of October 25,2020.It has been predicted that resurgence in contagion may be possible as late as 2024.1 A persistent anti-SARS-CoV-2 adaptive immune surveillance post infection is critical to lower the risk of resurgence and transmission.T cells are the primary effectors of cellular adaptive immunity that not only clear virus-infected cells during infection but also provide long-term protection post infection as memory cells in some pathogen infections.However,little is known regarding the longitudinal T cell response during and after SARSCoV-2 infection.Single-cell T cell receptor(TCR)sequencing allows rapid identification of expanded T cell clones that are potentially the antigen-specific clonotypes. | Qing Xiong Cheng Peng Xiaomin Yan Xueqi Yan Lin Chen Beicheng Sun Shiping Jiao | 2021 | Signal Transduction and Targeted Therapy2021，6，1： | 0 |
| 20 | Emergency adult living donor right lobe liver transplantation for fulminant hepatic failure显示文摘Fulminant hepatitis is fatal in most cases and timely liver transplantation is the only effective treatment.This study evaluates the survival outcomes of patients who underwent living-donor liver transplantation(LDLT)using right lobe liver grafts for fulminant liver failure due to hepatitis B infection.Nine cases of adult right lobe LDLT were performed in our department from September 2002 to August 2005 and the clinical and following-up data were reviewed.According to the pre-transplant Child-Pugh-Turcotte classification,the nine patients were classified as grade C.The model for end-stage liver disease(MELD)score of these patients ranged from 16 to 42.The principal complications before transplantation included abnormal renal function,hepatic coma of different degrees and alimentary tract hemorrhage.The main complications after transplantation included pulmonary infection in two cases,acute renal failure in three cases and transplantation-related encephalopathy in one case.No primary failure of vascular or biliary complications occurred.The one-year survival rate was 55.6%.There were no serious complications or deaths in donors.In general,it is extremely difficult to treat fulminant hepatitis by conservative regimen,particularly,in cases with rapid progression.Emergency adult living-donor liver transplantation is an effective treatment for fulminant hepatitis patients and is relatively safe for donors. | ZHANG Feng WANG Xuehao LI Xiangcheng KONG Lianbao SUN Beicheng LI Guoqiang QIAN Xiaofen CHEN Feng WANG Ke LU Sheng PU Liyong LU Ling | 2007 | Frontiers of Medicine2007，1，3： | 0 |
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