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IFIT1 polymorphisms predict interferon-α treatment efficiency for hepatitis B virus infection

World Journal of Gastroenterology 2016年第44期22卷 9813-9821页

作者： dong-ying xie Shi-Ming Wang Jing-Min Yang Liang-Hui Wang Hong-Yan Chen Cong Huai Jia Shang Qing Mao Chun-Liang Lei Guang-Han Luo Ji Qian Da-Ru Lu The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510000Guangdong ProvinceChina State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology Institute of GeneticsSchool of Life SciencesFudan UniversityShanghai 200438China Henan Provincial People’s Hospital Zhengzhou 450000Henan ProvinceChina The First Affiliated Hospital of Third Military Medical University Chongqing 404100China The Eighth People’s Hospital of Guangzhou Guangzhou 510000Guangdong ProvinceChina The First Affiliated Hospital of Guangxi Medical University Nanning 530000Guangxi Zhuang Autonomous RegionChina

AIM To investigate the association between interferoninduced protein with tetratricopeptide repeats 1(IFIT1) polymorphisms and interferon-α(IFNα) treatment efficiency among Chinese hepatitis B virus(HBV) infection *** Two hundred and twenty five newly diagnosed chronichepatitis B(CHB) patients were enrolled in the study. All of these patients received IFNα treatment for a course of 48 wk, and were followed up for 24 wk after the treatment was end. Clinical information about virological response, hepatitis B e antigen(HBe Ag) seroconversion rate and combined response at the end of the treatment, as well as the sustained response by the time of following up 24 wk after the treatment, was collected. Four tag-single nucleotide polymorphisms(SNPs) of IFIT1 were selected and assessed for their association with these clinical *** At the end of the treatment, HBe Ag seroconversion was observed in 27.1% patients. Thirty-six point nine percent patients achieved virological response, and 15.6% patients exhibited combined response. Sustained response was obtained in 26.2% patients. The main HBV genotype of the study was genotype B. Patients who infected with HBV genotype B or C showed better treatment efficiency, no matter which clinical outcome was considered. Among the four SNPs assessed, rs303218(A > G) was found to be significantly associated with the end point virological response when assuming additive model [OR = 0.64(95%CI: 0.42-0.96), P = 0.032]. Patients who carried rs303218 GG genotype had a rather higher rate of achieving virological response(response rate: 52%, OR = 0.40, 95%CI: 0.18-0.91; P = 0.028) when compared to those had AA genotype(response rate: 27%). The most significant interaction was observed in patients who had relative lower baseline aspartate transaminase. No association between SNPs and HBe Ag seroconversion, combined response or sustained response was *** IFIT1 involves in the regulation of IFNα treatment f

关键词： Virological response Hepatitis B virus infection IFIT1 Interferon-α therapy Polymorphism

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Predictive value of Th17 and Treg cells at baseline for HBsAg loss in chronic hepatitis B patients with low HBsAg quantification treated with pegylated interferon and nucleos(t)ide analogue

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Liver Research 2023年第2期7卷 136-144页

作者： Li-Li Wu Xiao-Yan Li Kai Deng Bing-Liang Lin Hong Deng dong-ying xie Geng-Lin Zhang Qi-Yi Zhao Zhi-Shuo Mo Yue-Hua Huang Zhi-Liang Gao Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Guangdong Provincial Key Laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Institute of Human Virology Key Laboratory of Tropical Disease Control of Ministry of EducationZhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdongChina Key Laboratory of Tropical Disease Control(Sun Yat-sen University) Ministry of EducationGuangzhouGuangdongChina

Background and aims:The primary goal of chronic hepatitis B(CHB)treatment is to reduce hepatitis B surface antigen(HBsAg).T helper 17(Th17)and regulatory T(Treg)cells are essential for the development of ***,how Th17 and Treg cells contribute to HBsAg loss is still ***,this study aimed to search for the predictive value of Th17 and Treg cells for HBsAg loss in CHB patients with low HBsAg ***:The study included 99 hepatitis B e antigen(HBeAg)-negative CHB patients who had completed a year of nucleos(t)ide analogue(NA)monotherapy and had received both NA and pegylated interferon(PEG-IFN)treatment for less than 96 weeks(96 wk).In the cured group,48 patients lost HBsAg within 48 wk,while 51 patients did not(uncured group).Blood samples and clinical data were collected for ***:During PEG-IFN and NA combination therapy,the proportion of Th17 cells in the cured group increased significantly,while the proportion of Treg cells in the uncured group *** 0 to 24 wk,the proportion of Th17 cells in the cured group was significantly higher than in the uncured group,while the opposite was true for Treg *** with alanine aminotransferase(ALT)2.5 upper limit of normal(ULN)at 12 wk had a higher proportion of Th17 cells and a lower proportion of Treg cells than those with ALT<2.5 ULN at 12 ***,the proportion of Th17 cells is inversely associated with the level of HBsAg,whereas the level of Treg cells is positively related to HBsAg *** clinical cure index,including age,HBsAg quantification,and the proportions of Th17 and Treg cells,had a higher area under the curve(0.957)for predicting HBsAg loss when compared to the proportions of Th17 and Treg cells and HBsAg quantification ***:Combined with quantification of HBsAg,the proportions of Th17 cells and Treg cells at baseline can be used as good predictors of HBsAg loss in patients with low HBsAg quantification treated with

关键词： Chronic hepatitis B(CHB) T helper 17(Th17)cell Regulatory T(Treg)cell Hepatitis B surface antigen(HBsAg)loss Clinical cure Pegylated interferon(PEG-IFN) Nucleos(t)ide analogue(NA)

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The 96-week clinical outcomes after cessation of nucleos(t)ide analog treatment in chronic hepatitis B patients

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Gastroenterology Report 2021年第4期9卷 313-322,I0002页

作者： Wen-Xiong Xu Yang-Mei Li Jian-Guo Li Yong-Yu Mei You-Ming Chen Xue-Jun Li Chao-Shuang Lin Hong Deng Zhi-Xin Zhao dong-ying xie Zhi-Liang Gao Liang Peng Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Guangdong Key Laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Prevention and Health Care The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China

Background:Chronic hepatitis B(CHB)patients have a high virological relapse rate after cessation of nucleos(t)ide analog(NA)treatment,but the clinical outcome remains *** study aimed to investigate the 96-week clinical outcomes and the risk factors for relapse in CHB after cessation of ***:This study was a prospective trial;74 eligible patients were *** patients underwent NA cessation and follow-up according to the 2012 Asian Pacific Association for the Study of the Liver ***,biochemical(aspartate aminotransferase[AST],alanine aminotransferase[ALT],total bilirubin,urea nitrogen,creatinine),virological data(hepatitis B surface antigen[HBsAg],hepatitis B e antigen[HBeAg],hepatitis B e antibody[HBeAb],hepatitis B virus[HBV]DNA levels),and color Doppler ultrasound examination results were recorded and ***:After NA cessation,19 cases were HBsAg-negative without relapse during the 96-week *** the 55 cases of HBsAg-positive after cessation,four types of clinical outcomes were *** patients had no relapse during the 96-week follow-up(type A,21.8%),7 patients underwent virological relapses but spontaneously had a non-virological relapse(type B,12.7%),10 patients maintained virological relapse(type C,18.2%),and 26 patients turned to clinical relapse,received NA retreatment,and achieved ALT normalization and negative conversion of HBV DNA within 12 months(type D,47.3%).The 2-year overall cumulative rates of virological and clinical relapses were 58.1%and 24.3%,*** factors associated with virological relapse were duration of negative HBV DNA,EOT(end of treatment)HBsAg,and original status of *** EOT HBsAg was also an independent factor for clinical ***:There are four types of clinical outcomes in patients with CHB after cessation of NA *** research is needed to explore the mechanism of different clinical *** EOT HBsAg level is an independent

关键词： chronic hepatitis B nucleos(t)ide analogs cessation relapse hepatitis B virus

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Interferon-b Gene Modified Human Bone Marrow Mesenchymal Stem Cells Attenuate Hepatocellular Carcinoma through Inhibiting AKT/FOXO3a Pathway

Interferon-b Gene Modified Human Bone Marrow Mesenchymal Ste...

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中华医学会第十六次全国病毒性肝炎及肝病学术会议

作者： Chan xie dong-ying xie Geng-lin Zhang Pei-pei Wang Liang Peng Zhi-liang Gao Department of Infectious Diseases the Third Affiliated Hospital of Sun Yat-Sen University

Objective This study aim is to investigate using of bone marrow mesenchymal stem cells(BMSC) genetically engineered to produce interferon-b(IFN-b) as a gene delivery system to treat hepatocellular carcinoma (HCC) in v...

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FOXG1 promote HCC stem cell self-renewal through promoting b-catenin nuclear accumulating by forming TCF4/b-cateinin/FOXG1 complex

FOXG1 promote HCC stem cell self-renewal through promoting b...

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中华医学会第十六次全国病毒性肝炎及肝病学术会议

作者： Chan xie dong-ying xie Geng-lin Zhang Pei-pei Wang Liang Peng Zhi-liang Gao Department of Infectious Diseases the Third Affiliated Hospital of Sun Yat-Sen University

Background Forkhead box G1(FOXG1) is a member of Fox transcription factors family involved in the regulation of stem ***,the role of FOXGl in hepatocellular carcinogenesis(HCC) is largely unclear. The present study ai...

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Application of Percutaneous Endoscopic Gastrojejunostomy in Duodenal Crohn’s Disease-Associated Strictures

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Journal of Nutritional Oncology 2022年第4期7卷 199-203页

作者： Juan Juan Zhang ying dong xie Tian Tian Liu Bin Lin Da Yan Qing Diao Yi Li Zhi Ming Wang Department of General Surgery Affiliated Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu 210002China Ultrasonography Department Affiliated Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu 210002China

Background Duodenal Crohn’s disease(CD)-associated strictures are related to a high risk of malnutrition,and effective methods of enteral nutrition(EN)are needed to support these *** purpose of this study was to evaluate the efficacy and safety of percutaneous endoscopic gastrojejunostomy(PEG-J)for the treatment of duodenal CD-associated *** Patients with strictures associated with duodenal CD were *** clinical data,stricture characteristics,nutritional status,duration of PEG-J tube placement,complications,and follow up periods were *** A total of 24 patients with duodenal CD-associated strictures underwent PEG-J tube *** PEG-J tubes were successfully placed in 100%of the patients within an average of 19.04±2.94 *** were no procedure-related *** were no major complications after PEG-J tube placement,and only two minor complications(8.33%)***-J was well tolerated in all *** mean Karnofsky score was 67.50±7.94 points and 83.33±7.02 points(P=0.000),the mean body mass index was 17.02±1.85 kg/m^(2)and 18.10±1.78 kg/m^(2)(P=0.045),and the mean Alb level was 35.28±5.35 g/dl and 38.68±5.10 g/dl(P=0.029)before PEG-J and 3 months after PEG-J,*** median CD Activity Index(CDAI score)was 144(range 87-280)and the median C-reactive protein(CRP)was 1.90 mg/L(0.5-67.9 mg/L)after PEG-J,which were significantly lower than the respective 196 mg/L(range 114-331 mg/L)(P=0.044)and 3.75 mg/L(range 0.5-67 mg/L)(P=0.033)before *** PEG-J was a safe,well-tolerated and effective method for the treatment of duodenal CD-associated ***-J improved the patient’s nutritional status and reduced disease CD *** findings suggest that PEG-J is an option for EN in patients with duodenal CD-associated strictures.

关键词： Percutaneous endoscopic gastrojejunostomy Crohn’s disease Duodenal strictures Enteral nutrition

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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China Life Sciences 2025年第1期 204-218页

作者： Chen Xiong Hong Ling yingdan Huang Hanzhi dong Bangxiang xie Qian Hao Xiang Zhou Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan University Department of Oncology Shanghai Medical CollegeFudan University Department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University Department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

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Observation of topological charge transformations in acoustic vortex using passive periodic systems

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 140-147页

作者： Di-Chao Chen xie Liu Changqing Xu Da-Jian Wu ying Cheng Xiao-Jun Liu School of Physics and Technology Nanjing Normal University Key Laboratory of Modern Acoustics School of Physics Nanjing University

Vortex transmutation utilizes a periodic system, which not only enables the alteration of the topological charge(TC) of unstable input vortices but also facilitates their transformation into stable structures. This approach is crucial for investigating the characteristics of vortices in various wave systems. Here, we achieve acoustic vortex TC transmutation by employing a welldesigned dual-structured plate external system(DPES). The interactions between the acoustic vortex and the finite-order discrete rotational symmetry lead to the transformation of its topological charge when complete rotational symmetry is broken to Nthorder discrete symmetry. Our results experimentally demonstrate the acoustic vortex TC transmutation based on passive artificial structures, enabling numerous applications in particle manipulation and information multiplexing as well as advancing our understanding and control over free-space acoustic vortices.

关键词： acoustic vortex topological charge transformation artificial structure

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Local-contrastive-learning machine with both generalization and adversarial robustness: A statistical physics analysis

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 109-123页

作者： Mingshan xie Yuchen Wang Haiping Huang PMI Lab School of Physics Sun Yat-sen University Guangdong Provincial Key Laboratory of Magnetoelectric Physics and Devices Sun Yat-sen University

Distinct from human cognitive processing, deep neural networks trained by backpropagation can be easily fooled by adversarial examples. To design a semantically meaningful representation learning, we discard backpropagation, and instead, propose a local contrastive learning, where the representations for the inputs bearing the same label shrink(akin to boson) in hidden layers,while those of different labels repel(akin to fermion). This layer-wise learning is local in nature, being biologically plausible.A statistical mechanics analysis shows that the target fermion-pair-distance is a key parameter. Moreover, the application of this local contrastive learning to MNIST benchmark dataset demonstrates that the adversarial vulnerability of standard perceptron can be greatly mitigated by tuning the target distance, i.e., controlling the geometric separation of prototype manifolds.

关键词： machine learning statistical mechanics adversarial robustness neural networks

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Derivative Formula and Coupling Property for Linear SDEs Driven by Lévy Processes

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Acta Mathematicae Applicatae Sinica 2019年第4期35卷 708-721页

作者： Zhao dong Yu-lin SONG ying-chao xie Institute of Applied Mathematics Academy of Mathematics and Systems Sciences Chinese Academy of Sci- ences Beijing 100190 China School of Mathematical Sciences Beijing Normal University Beijing 100875 China School of Mathematics and Statistics Jiangsu Normal University Jiangsu Province Xuzhou 221116 China

In this paper we investigate an integration by parts formula for Lévy processes by using lower bound conditions of the corresponding Lévy measure. As applications, derivative formula and coupling property are derive... 详细信息

关键词： Lévy processes integration by parts formula derivative formula coupling property

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