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Expression and Regulatory Network Analysis of Function of Small Nucleolar RNA Host Gene 4 in Hepatocellular Carcinoma

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Journal of Clinical and Translational Hepatology 2022年第2期10卷 297-307页

作者： Jing Cao Cuicui Xiao Christ-Jonathan Tsia Hin Fong Jiao Gong Danyang Li Xiangyong Li Yusheng Jie yutian chong Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Anesthesiology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Gastroenterology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Laboratory Medicine The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina

Background and Aims:Long non-coding RNA small nucleolar RNA host genes(SNHGs)play a critical role in the occurrence and development of tumors.In this study,we aimed to investigate the role of SNHG4 in hepatocellular carcinoma(HCC)and its underlining mechanism.Methods:Datasets were acquired from The Cancer Genome Atlas(TCGA)database.lncLocator 2.0 was used to identify the distribution of SNHG4 in HCC cells.Gene expression,Kaplan-Meier survival,microRNA and transcription factor target analyses were performed with the University of Alabama Cancer(UALCAN)Database,Kaplan-Meier Plotter,LinkedOmics,WebGestalt and gene set enrichment analysis,respectively.Gene Ontology and pathway enrichment analyses and assessment of RNA binding proteins were performed by R software,circlncRNAnet and Encyclopedia of RNA Interactomes(EN-CORI).In addition,CirclncRNAnet and ENCORI were used to find the correlation between SNHG4 and important proteins,while the prognostic value was assessed with the Human Protein Atlas database and Kaplan-Meier Plotter.Results:Expression of SNHG4 in HCC is higher in HCC tissue than in normal healthy liver tissues and is mainly distributed in the nucleus.SNHG4 positively correlated with poor prognosis(p<0.01 for overall survival and recurrence-free survival).Functional enrichment analysis revealed SNHG4 involve-ment with regulation of ribosomal RNA synthesis and the RNA processing and surveillance pathway.SNHG4 is closely associated with miR-154 and miR-206,transcription factor target E2F family and the signaling pathway for MAPK/ERK and mTOR.U2 auxiliary factor 2(U2AF2)showed strong correlation with SNHG4,while low-expression of U2AF2 showed good prognosis.Conclusions:Based on our find-ings,we infer SNHG4 may play a role in the formation of HCC via regulation of tumor-related pathways.

关键词： Small nucleolar RNA host gene 4 Hepatocellular carcinoma Prog-nosis Bioinformatic analysis

A Prognostic Nomogram with High Accuracy Based on 2D-SWE in Patients with Acute-on-chronic Liver Failure

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Journal of Clinical and Translational Hepatology 2022年第5期10卷 803-813页

作者： Lili Wu Jieyang Jin Taicheng Zhou Yuankai Wu Xinhua Li Xiangyong Li Jie Zeng Jinfen Wang Jie Ren yutian chong Rongqin Zheng Department of Medical Ultrasonics Third Affiliated Hospital of Sun Yat-Sen UniversityGuangdong Key Laboratory of Liver Disease ResearchGuangzhouGuangdongChina Department of Gastroenterological Surgery and Hernia Center Sixth Affiliated Hospital of Sun Yat-Sen UniversityGuangdong Institute of GastroenterologyGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesSupported by National Key Clinical DisciplineGuangzhouGuangdongChina Department of Infectious Diseases Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdongChina

Background and Aims:Acute-on-chronic liver failure(ACLF)is associated with very high mortality.Accurate prediction of prognosis is critical in navigating optimal treatment decisions to improve patient survival.This study was aimed to develop a new nomogram integrating two-dimensional shear wave elastography(2D-SWE)values with other independent prognostic factors to improve the precision of predicting ACLF patient outcomes.Methods:A total of 449 consecutive patients with ACLF were recruited and randomly allocated to a training cohort(n=315)or a test cohort(n=134).2D-SWE values,conventional ultrasound features,laboratory tests,and other clinical characteristics were included in univariate and multivariate analysis.Factors with prognostic value were then used to construct a novel prognostic nomogram.Receiver operating curves(ROCs)were generated to evaluate and compare the performance of the novel and published models including the Model for EndStage Liver Disease(MELD),MELD combined with sodium(MELD-Na),and Jin’s model.The model was validated in a prospective cohort(n=102).Results:A ACLF prognostic nomogram was developed with independent prognostic factors,including 2D-SWE,age,total bilirubin(TB),neutrophils(Neu),and the international normalized ratio(INR).The area under the ROC curve(AUC)was 0.849 for the new model in the training cohort and 0.861 in the prospective validation cohort,which were significantly greater than those for MELD(0.758),MELD-Na(0.750),and Jin’s model(0.777,all p<0.05).Calibration curve analysis revealed good agreement between the predicted and observed probabilities.The new nomogram had superior overall net benefit and clinical utility.Conclusions:We established and validated a 2D-SWE-based noninvasive nomogram to predict the prognosis of ACLF patients that was more accurate than other prognostic models.

关键词： Acute-on-chronic liver failure Two-dimensional shear wave elastography Hepatitis B virus Prognosis

A novel nomogram based on routine clinical indicators for screening for Wilson's disease

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Liver Research 2023年第1期7卷 82-89页

作者： Jiahui Pang Shuru Chen Weiqiang Gan Guofang Tang Yusheng Jie Zhanyi Li yutian chong Youming Chen Jiao Gong Xinhua Li Yongyu Mei Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Guangzhou Eighth People's Hospital Guangzhou Medical UniversityGuangzhouGuangdongChina Department of Laboratory Medicine The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Infectious Diseases National Regional Medical Center for Infectious DiseasesKashgar Hospital Affiliated to Sun Yat-sen UniversityKashgarXinjiangChina

Background and aims:There is currently no single model for predicting Wilson's disease(WD).We aimed to create a nomogram using daily clinical parameters to improve the accuracy of WD diagnosis in patients with abnormal liver function.Methods:Between July 2016 and December 2020,we identified 90 WD patients with abnormal liver function who had homozygous or compound heterozygous mutations in the ATP7B gene.The control group included 128 patients with similar liver function but no WD during the same time period.To create a nomogram,we screened potential predictive variables using the least absolute shrinkage and selection operator model and multivariate logistic regression.Results:We developed a nomogram for screening for WD based on six predictive factors:serum copper,direct bilirubin,uric acid,cholinesterase,prealbumin,and reticulocyte percentage.In the training cohort,the area under curve(AUC)of the nomogram reached 0.967(95%confidence interval(CI)0.946e0.988),while the area under the precision-recall curve was 0.961.Based on the optimal cutpoint of 213.55,our nomogram performed well,with a sensitivity of 96%and a specificity of 87%.In the validation cohort,the AUC of the nomogram was as high as 0.991(95%CI 0.970e1.000).Conclusions:We developed a nomogram that can predict the risk of WD prior to the detection of serum ceruloplasmin or urinary copper,greatly increasing screening efficiency for patients with abnormal liver function.

关键词： Wilson's disease(WD) Diagnosis Nomogram Probabilistic model Predictor

泛癌中SPARC表达水平与预后及其与免疫微环境的关系

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热带医学杂志 2024年第3期24卷 305-312,344,F0002页

作者：李斌龚娇林宇曦邓婧崇雨田中山大学附属第三医院感染科广东广州510630 中山大学附属第三医院检验科广东广州510630

目的研究富含半胱氨酸的酸性分泌蛋白(SPARC)基因在人不同类型肿瘤组织中的表达水平,并探讨其与患者预后及免疫微环境的关系。方法使用癌症基因组图谱(TCGA)、基因型和基因表达量关联(GTEx)和癌症细胞系百科全书(CCLE)等多个数据库获... 详细信息

目的研究富含半胱氨酸的酸性分泌蛋白(SPARC)基因在人不同类型肿瘤组织中的表达水平,并探讨其与患者预后及免疫微环境的关系。方法使用癌症基因组图谱(TCGA)、基因型和基因表达量关联(GTEx)和癌症细胞系百科全书(CCLE)等多个数据库获取泛癌的基因表达谱、体细胞突变数据和临床预后信息。采用ESTIMATE和TIMER算法评估泛癌的免疫微环境,分析SPARC在泛癌中的表达及其与肿瘤预后、免疫浸润、免疫检查点基因、肿瘤突变负荷和微卫星不稳定性的关系。对SPARC相关基因进行功能富集分析,通过实时荧光定量PCR验证SPARC在多种不同肿瘤细胞系的表达,并用细胞计数试剂盒-8(CCK-8)法分析SPARC对多种肿瘤细胞系增殖的影响。结果与正常组织比较,SPARC在食管癌、肝癌、胃癌、结肠癌、急性髓系白血病、胰腺癌、肾透明细胞癌、肾上腺皮质癌、卵巢癌、皮肤黑色素瘤、脑低级别胶质瘤、直肠癌、乳腺癌、胆管癌、多形性胶质细胞瘤、头颈鳞癌、甲状腺癌和子宫肉瘤等18种肿瘤组织中高表达(P均<0.05),而在宫颈癌、肾嫌色细胞癌、前列腺癌、肺腺癌和子宫内膜癌等5种肿瘤组织中低表达(P均<0.05)。总生存期分析显示,在肾上腺皮质癌(HR=1.40,P=0.030 0)、膀胱尿路上皮癌(HR=1.19,P=0.000 5)、肾乳头状细胞癌(HR=1.37,P=0.007 9)、胃癌(HR=1.21,P=0.002 9)、葡萄膜黑色素瘤(HR=2.07,P=0.000 7)和间皮瘤(HR=1.33,P=0.000 6)等6种肿瘤中,高表达SPARC的患者预后更差;而在肾透明细胞癌(HR=0.83,P=0.006 5)中,低表达SPARC患者预后更差。SPARC表达与泛癌中多种免疫细胞浸润成正相关(P<0.05),尤其是巨噬细胞。SPARC与PDCD1和CTLA4等多个免疫检查点基因以及免疫治疗反应标志物显著相关(P<0.05)。体外实验表明,在肝癌细胞系(HepG2和SNU-449)和胃癌细胞系(HGC-27)中降低SPARC的表达导致其增殖能力减弱。结论 SPARC在多种肿瘤中表达异常,其表达不但影响患者的临床预后,还与肿瘤的多种免疫特征密切相关,可作为肿瘤预后、免疫治疗反应评估的生物标志物,有望成为肿瘤治疗的新靶点。

关键词：富含半胱氨酸的酸性分泌蛋白泛癌预后免疫微环境生物信息学

Association between the nasopharyngeal microbiome and metabolome in patients with COVID-19

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Synthetic and Systems Biotechnology 2021年第3期6卷 135-143页

作者： Jing Liu Sheng Liu Zhao Zhang Xuejun Lee Wenxuan Wu Zhanlian Huang Ziying Lei Wenxiong Xu Dabiao Chen Xing Wu Yang Guo Liang Peng Bingliang Lin yutian chong Xiangyu Mou Mang Shi Ping Lan Tao Chen Wenjing Zhao Zhiliang Gao Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong510630China The Center for Infection and Immunity Study(CIIS) School of MedicineSun Yat-sen UniversityShenzhenChina Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases The Sixth Affiliated HospitalSchool of MedicineSun Yat-sen UniversityGuangzhouChina South China Institute of Biomedicine GuangzhouGuangdong510535China

SARS-CoV-2,the causative agent for COVID-19,infect human mainly via respiratory tract,which is heavily inhabited by local microbiota.However,the interaction between SARS-CoV-2 and nasopharyngeal microbiota,and the association with metabolome has not been well characterized.Here,metabolomic analysis of blood,urine,and nasopharyngeal swabs from a group of COVID-19 and non-COVID-19 patients,and metagenomic analysis of pharyngeal samples were used to identify the key features of COVID-19.Results showed lactic acid,L-proline,and chlorogenic acid methyl ester(CME)were significantly reduced in the sera of COVID-19 patients compared with non-COVID-19 ones.Nasopharyngeal commensal bacteria including Gemella morbillorum,Gemella haemolysans and Leptotrichia hofstadii were notably depleted in the pharynges of COVID-19 patients,while Prevotella histicola,Streptococcus sanguinis,and Veillonella dispar were relatively increased.The abundance of G.haemolysans and L.hofstadii were significantly positively associated with serum CME,which might be an anti-SARS-CoV-2 bacterial metabolite.This study provides important information to explore the linkage between nasopharyngeal microbiota and disease susceptibility.The findings were based on a very limited number of patients enrolled in this study;a larger size of cohort will be appreciated for further investigation.

关键词： Metabolome Nasopharyngeal microbiome COVID-19 SARS-CoV-2 Susceptibility

Real-world effectiveness and safety of OBT/PTV/r and dasabuvir for patients with chronic HCV genotype 1b infection in China:A multicenter prospective observational study

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Liver Research 2020年第3期4卷 153-158页

作者： Yusheng Jie Chaoshuang Lin Jing Yuan Zhixin Zhao Yujuan Guan Yuanping Zhou Xiaohui Zhou Bihui Zhong Yinong Ye Lihua Zhang Ling Tao Jianping Li Xiaohong Zhang yutian chong Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Department of Infectious Diseases The Third People’s Hospital of ShenzhenShenzhenGuangdongChina Department of Infectious Diseases The Eighth People’s Hospital of GuangzhouGuangzhouChina Department of Infectious Diseases and Hepatology Unit The Nanfang Hospital of Southern Medical UniversityGuangzhouChina Department of Infectious Diseases The First Affiliated Hospital of Shantou University Medical CollegeShantouGuangdongChina Department of Infectious Diseases The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Department of Infectious Diseases The First People’s Hospital of FoshanFoshanGuangdongChina Department of Infectious Diseases The Third People’s Hospital of DongguanDongguanGuangdongChina Department of Pharmacy The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina

Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients.Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(ITT)and modified ITT(mITT)populations were used in the analysis.Results:One hundred forty patients were included,among whom 90.0%(126/140)were newly diagnosed,9.3%(13/140)had compensated cirrhosis,92.9%(130/140)received 12 weeks of treatment,and 7.1%(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4%(108/112),and at the end of treatment was 100%(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4%)patients,and none were considered to be drug-related.Sixty-six(47.1%)patients did not return to receive the HCV RNA test at 12 weeks post-treatment.Conclusions:The rate of SVR12 was consistent with Phase III clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.

关键词： Hepatitis Cvirus(HCV) Direct-acting antiviralagent(DAA) Real-worldresearch Ombitasvir(OBT) Paritaprevir(PTV) Ritonavir

人工智能数据采集在慢性乙型肝炎患者真实世界研究中的应用

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暨南大学学报（自然科学与医学版） 2024年第1期45卷 77-83页

作者：周晓梅曾涛廖莹颖张一博李青海 Jaime Smith 张麟王超崇雨田李新华中山大学附属第三医院信息中心广东广州510630 中山大学附属第三医院感染性疾病科∥广东省肝病重点实验室广东广州510630 广东精点数据科技股份有限公司广东广州510635 精鼎医药研究开发(上海)有限公司上海200120

目的:开发一套慢性乙型肝炎(乙肝)的人工智能(AI)数据采集工具,以解决传统的多中心数据采集效率低下的问题。方法:基于国际通用的数据标准,将AI的文字识别和自然语言处理应用于慢性乙肝真实世界队列研究数据采集,实现多种格式数据(包括... 详细信息

目的:开发一套慢性乙型肝炎(乙肝)的人工智能(AI)数据采集工具,以解决传统的多中心数据采集效率低下的问题。方法:基于国际通用的数据标准,将AI的文字识别和自然语言处理应用于慢性乙肝真实世界队列研究数据采集,实现多种格式数据(包括图片格式的原始数据)的电子化采集、结构化处理,随后自动将数据填入研究电子数据采集(REDCap)系统中的电子病历报告表(eCRF)。结果:AI工具辅助数据采集与纯人工数据采集具有相同的平均准确率,均达到98.66%(P=0.23),但前者所需时间减少75.49%(P<0.05)。结论:本研究开发的AI数据采集工具可显著提高研究数据采集效率,为真实世界研究数据采集提供了新的模式。

关键词：数据采集慢性乙型肝炎人工智能(AI) 自然语言处理文字识别

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重型肝炎内科治疗的思路及策略

广东医学 2005年第8期26卷 1024-1025页

作者：崇雨田中山大学附属第三医院感染病科广州510630

经过多年的探索及努力,目前重型肝炎内科治疗缺乏特效药物,仍然依靠综合治疗的手段,并未取得实质性的突破,病死率仍然较高,治疗费用对社会、家庭造成巨大的负担.由于重型肝炎实质上是一种全身性疾病,尤其在重型肝炎晚期可导致多脏器的... 详细信息

经过多年的探索及努力,目前重型肝炎内科治疗缺乏特效药物,仍然依靠综合治疗的手段,并未取得实质性的突破,病死率仍然较高,治疗费用对社会、家庭造成巨大的负担.由于重型肝炎实质上是一种全身性疾病,尤其在重型肝炎晚期可导致多脏器的功能不全或衰竭,所以重型肝炎的治疗所涉及多个方面.在重型肝炎治疗中,正确的思路非常重要.

关键词：重型肝炎内科疾病肝功能黄疸肝衰竭

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遗传代谢性肝病的临床基因诊断

中华肝脏病杂志 2018年第12期26卷 894-897页

作者：陈淑如崇雨田李新华中山大学附属第三医院感染性疾病科广州510630

遗传代谢性肝病临床表型差异显著,尽管每种疾病的发病率不高,由于疾病谱广,总体受累人群并不少见,临床应予重视。这类疾病临床罕见,相对认识不足,临床误诊问题较为突出,现以临床实践过程中所遇到的问题为出发点,探讨一下遗传代谢性肝病... 详细信息

遗传代谢性肝病临床表型差异显著,尽管每种疾病的发病率不高,由于疾病谱广,总体受累人群并不少见,临床应予重视。这类疾病临床罕见,相对认识不足,临床误诊问题较为突出,现以临床实践过程中所遇到的问题为出发点,探讨一下遗传代谢性肝病的临床基因诊断。

关键词：遗传基因诊断遗传代谢陛肝病