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Preliminary study of the urinary proteome in Li and Han ethnic individuals from Hainan

Science China(Life Sciences) 2020年第1期63卷 125-137页

作者： fanshuang zhang Xundou Li Yanying Ni Guangliang Shan Youhe Gao Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Pathophysiology Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China Department of Epidemiology and Statistics Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China Department of Biochemistry and Molecular Biology Beijing Normal UniversityGene Engineering Drug and Biotechnology Beijing Key LaboratoryBeijing 100875China

Biomarkers indicate changes associated with disease. Blood is relatively stable due to the homeostatic mechanisms of the body;however, urine accumulates metabolites from changes in the body, making it a better source for early biomarker discovery. The Li ethnic group is a unique minority ethnic group that has only lived on Hainan Island for approximately 5,000 years. Studies have shown that various specific genetic variations are different between the Li and Han ethnic groups. However, whether the urinary proteome between these two ethnic groups is significantly different remains unknown. In this study, differential urinary proteins were identified in the Li and Han ethnic groups using liquid chromatography tandem mass spectrometry(LC-MS/MS).In total, 1,555 urinary proteins were identified. Twenty-five of the urinary proteins were statistically significantly different, 16 of which have been previously reported to be biomarkers of many diseases, and that these significantly different proteins were caused by ethnic differences rather than random differences. Ethnic group differences may be an influencing factor in urine proteome studies and should be considered when human urine samples are used for biomarker discovery.

关键词： proteomics urine biomarker Li ethnic group Han ethnic group

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Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model

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Science China(Life Sciences) 2018年第11期61卷 1369-1381页

作者： fanshuang zhang Yanying Ni Yuan Yuan Wei Yin Youhe Gao Department of Pathology National Cancer Center/Cancer HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100021China Department of Pathophysiology Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China Department of Pathology Beijing Tiantan HospitalCapital Medical University Beijing 100050China Department of Biochemistry and Molecular Biology Beijing Normal UniversityGene Engineering Drug and Biotechnology Beijing Key LaboratoryBeijing 100875China

Biomarker is the change associated with the disease. Blood is relatively stable because of the homeostatic mechanisms of the body. However, urine accumulates changes of the body, which makes it a better early biomarker source. Liver fibrosis is a reversible pathological condition, whereas cirrhosis, the end-stage of liver fibrosis, is irreversible. Consequently, noninvasive early biomarkers for fibrosis are desperately needed. In this study, differential urinary proteins were identified in the thioacetamide liver fibrosis rat model using tandem mass tagging and two-dimensional liquid chromatography tandem mass spectrometry. A total of 766 urinary proteins were identified, 143 and 118 of which were significantly changed in the TAA 1-week and3-week groups, respectively. Multiple reaction monitoring(MRM)-targeted proteomics was used to further validate the abundant differentially expressed proteins. A total of 40 urinary proteins were statistically significant, 15 of which had been previously reported as biomarkers of liver fibrosis, cirrhosis or other related diseases and 10 of which had been reported to be associated with the pathology and mechanism of liver fibrosis. These differential proteins were detected in urine before the alanine aminotransferase and aspartate transaminase changes in the serum and before fibrosis was observed upon hematoxylin and eosin(HE) and Masson's staining.

关键词： urine proteomics biomarker animal model liver fibrosis

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Early candidate biomarkers found from urine of glioblastoma multiforme rat before changes in MRI

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Science China(Life Sciences) 2018年第8期61卷 982-987页

作者： Yanying Ni fanshuang zhang Manxia An Wei Yin Youhe Gao Department of Pathophysiology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Department of Pathology Aviation General Hospital of China Medical University Department of Biochemistry and Molecular Biology Beijing Normal University Gene Engineering Drug and Biotechnology Beijing Key Laboratory

Dear Editor, Gliomas are the most frequent primary tumors of the central nervous system, accounting for more than 60% of all brain tumors （Wang and Bettegowda, 2015）. Among them, glio-blastoma multiforme （GBM） is the most common aggressive glioma, and the average survival rate remains low （Chen et al., 2015）. The standard combination of surgery and radio-therapy or chemotherapy can only extend the progression-free survival time for 12-18 months, with a high risk of re-currence （Li et al., 2008）. In addition, the incidence of GBM has increased annually by 1%-2% in the past years （Louis et al., 2007）. Therefore, a precise early diagnosis of GBM is crucial for the early determination of appropriate therapeutic strategies.

关键词：候选人 MRI 老鼠神经系统放射疗法脑肿瘤尿治疗学

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Early candidate biomarkers found from urine of astrocytoma rat before changes in MRI

Early candidate biomarkers found from urine of astrocytoma r...

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2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青年科学家论坛

作者： Yanying Ni fanshuang zhang Manxia An Wei Yin Youhe Gao Department of Pathophysiology Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical College Department of Biochemistry and Molecular Biology Beijing Normal UniversityGene Engineering and Biotechnology Beijing Key Laboratory

Aim:Looking for early candidate biomarkers from urine of astrocytoma rats Method:C6 cells were injected into Wistar rats brain as astrocytoma model. Urine samples were collected at day 2, day 6, day 10 and day 13 after injection, and the urinary proteomes were analyzed by LC-MS/MS. Results:On the 10 th day, lesions appeared in magnetic resonance imaging. On the 13 th day, clinical symptoms started. But differential urinary proteins were changed with the development of the astrocytoma, and can provide clues even on the 2 nd and 6 th day. Twenty seven differential proteins with human orthologs had been reported to associate with astrocytoma. Conclusions:A panel of differential urinary proteins may provide sensitive early biomarkers for the early diagnose of astrocytoma.

关键词： Urine proteome Animal model Biomarker Astrocytoma

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基于二代测序技术的循环肿瘤DNA检测在表皮生长因子受体酪氨酸激酶抑制剂耐药肺癌患者耐药基因检测中的应用

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中华病理学杂志 2018年第12期47卷 904-909页

作者：李研张繁霜郭蕾应建明国家癌症中心/国家肿瘤临床研究中心/中国医学科学院北京协和医学院肿瘤医院病理科 100021

目的通过对晚期肺癌初治及耐药患者的血浆循环肿瘤DNA(ctDNA)标本应用高通量二代测序(NGS)技术进行基因检测分析来评估基于ctDNA的NGS技术的临床应用价值。方法共纳入381例2017年3月至2018年5月期间在中国医学科学院肿瘤医院就诊的肺部... 详细信息

目的通过对晚期肺癌初治及耐药患者的血浆循环肿瘤DNA(ctDNA)标本应用高通量二代测序(NGS)技术进行基因检测分析来评估基于ctDNA的NGS技术的临床应用价值。方法共纳入381例2017年3月至2018年5月期间在中国医学科学院肿瘤医院就诊的肺部恶性肿瘤患者的血液标本,采用基于杂交捕获法的NGS技术,检测患者血浆ctDNA中与肺癌相关的10个驱动基因的变异状态。通过对比分析39例血浆-组织/细胞学配对标本,分析基于NGS方法检测ctDNA中驱动基因变异的灵敏度及特异度。另外分析了一代及三代表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKI)靶向耐药患者的ctDNA检测基因变异的耐药机制。结果该研究中39例血液标本有抽血2周内的组织/细胞学配对标本,均来自非小细胞肺癌患者,其中21例为女性,18例男性;年龄最小者29岁,最大者82岁,平均年龄59岁。血浆与组织NGS检测一致率为84.62%(33/39);39例配对标本中有34例为Ⅲ~Ⅳ期的晚期肺癌患者,晚期病例血浆与组织NGS检测一致率为88.24%(30/34)。未接受过靶向治疗的基线检测患者231例,其中10例为肺鳞癌,未检出驱动基因突变;221例肺腺癌中EGFR基因突变最为常见(32.58%,72/221),其次为ALK基因变异(7.69%,17/221)及KRAS基因突变(5.81%,13/221)。接受过一代TKI治疗并已耐药的病例133例,其中39.10%(52/133)的患者检出T790M突变;另外有3.01%(4/133)的患者检出耐药原因为旁路激活。在能够检测出原敏感突变的耐药患者中,约53.06%(52/98)的患者能检测出T790M突变。接受过三代TKI治疗并已耐药的病例17例,其中4例患者检出耐药原因为出现与原T790M突变位点顺式的C797S错义突变。结论虽然基于血浆ctDNA的二代测序检测存在一定的假阴性率,但其与组织基因突变检测的一致性较高。EGFR-TKI耐药肺癌患者中约有近一半可通过血浆ctDNA二代测序检测找到耐药原因,为基于二代测序的液体活检技术在临床的应用提供了直接证据。

关键词：癌,非小细胞肺分子靶向治疗抗药性,肿瘤序列分析,DNA DNA,肿瘤:液体活检

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细菌性脑膜炎大鼠模型的尿液蛋白质组学变化

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生物工程学报 2017年第7期33卷 1145-1157页

作者：倪艳颖张繁霜安满霞高友鹤中国医学科学院基础医学研究所北京协和医学院基础学院病理生理学系北京100005 北京师范大学生物化学与分子生物学系北京基因工程与生物技术重点实验室北京100875

与脑脊液和血液不同,尿液不受到稳态机制的调节,更倾向于积累和反应机体生理和病理状态下的变化。生物标志物的本质特征是变化,因此尿液是寻找疾病早期标志物的更好来源。在世界范围内,细菌性脑膜炎依然是引起新生儿和儿童疾病的主要原... 详细信息

与脑脊液和血液不同,尿液不受到稳态机制的调节,更倾向于积累和反应机体生理和病理状态下的变化。生物标志物的本质特征是变化,因此尿液是寻找疾病早期标志物的更好来源。在世界范围内,细菌性脑膜炎依然是引起新生儿和儿童疾病的主要原因。为了降低死亡率和致残率,需要用无创的方法寻找细菌性脑膜炎的相关线索。本研究中,使用大鼠脑室内注射大肠杆菌模型模拟细菌性脑膜炎,在第1天和第3天的大鼠尿液中寻找尿液蛋白谱的差异变化,为进一步寻找大肠杆菌性脑膜炎的早期生物标记物研究进行初步的探索。通过膜上酶切和胶内酶切将尿蛋白切成肽段并通过液相色谱串联质谱技术(LC-MS/MS)分析肽段信息。第1天的尿液通过胶内酶切方法鉴定到17个差异蛋白,通过膜上酶切鉴定到20个差异蛋白;第3天的尿液通过膜上酶切方法鉴定到5个差异蛋白。这些差异蛋白为寻找细菌性脑膜炎早期生物标志物的初步探索奠定了基础。

关键词：细菌性脑膜炎早期诊断液相色谱与串联质谱偶联技术尿液蛋白质组学动物模型

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肿瘤分子病理诊断中大数据的应用研究

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中华病理学杂志 2018年第7期47卷 562-564页

作者：张繁霜应建明鲁海珍马建辉国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院病理科 100021 国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院泌尿外科 100021

大数据（big data）是信息技术领域内继云计算和物联网之后又一重要的技术革新。技术的发展推动着大数据在生物、医学、金融等领域的应用。大数据主要是指用传统的数据处理方法分析结果不够理想的大规模复杂数据集合。国内外许多科学家... 详细信息

大数据（big data）是信息技术领域内继云计算和物联网之后又一重要的技术革新。技术的发展推动着大数据在生物、医学、金融等领域的应用。大数据主要是指用传统的数据处理方法分析结果不够理想的大规模复杂数据集合。国内外许多科学家都对大数据的概念进行过解读，汇总起来可以用＂5V＂来表示，即数据量（Volume）大、产生和更新速率（Velocity）快、数据类型（Variety）多、数据准确性（Verification/Veracity）高和深入研究与挖掘价值（Value）大。

关键词：数据处理分子病理诊断应用肿瘤数据准确性技术革新信息技术数据类型

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高效液相色谱法同时测定人参制剂中20种人参皂苷方法的建立

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食品科学 2016年第22期37卷 131-135页

作者：杨艳文孟凡双郜玉钢张连学吉林农业大学中药材学院吉林长春130118

为了更加有效评价人参制剂生产质量,建立了一种同时测定人参制剂中20种人参皂苷的高效液相色谱方法。结果表明,20种人参皂苷Rg1、Re、Rg2、Rg3、Rg5、Rf、F1、F2、Rc、Rd、Rb1、Rb2、Rb3、Rh2、compound K、20(R)-Rh1、Rk3、Rh4、原人... 详细信息

为了更加有效评价人参制剂生产质量,建立了一种同时测定人参制剂中20种人参皂苷的高效液相色谱方法。结果表明,20种人参皂苷Rg1、Re、Rg2、Rg3、Rg5、Rf、F1、F2、Rc、Rd、Rb1、Rb2、Rb3、Rh2、compound K、20(R)-Rh1、Rk3、Rh4、原人参二醇及原人参三醇均得到良好分离,线性关系良好(R≥0.999 2)。该方法快捷简便、稳定可靠,能够精确全面检测分析人参皂苷含量,对于人参加工品及其制剂的质量控制更为全面准确可行。

关键词：人参人参皂苷高效液相色谱含量测定

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Glucocorticoid receptor signaling in the brain and its involvement in cognitive function

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Neural Regeneration Research 2025年第9期20卷 2520-2537页

作者： Chonglin Su Taiqi Huang Meiyu zhang Yanyu zhang Yan Zeng Xingxing Chen Brain Science and Advanced Technology Institute Hubei Province Key Laboratory of Occupational Hazard Identification and ControlSchool of MedicineWuhan University of Science and TechnologyWuhanHubei ProvinceChina

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental *** the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and *** glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic *** interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive *** appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive *** with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor *** review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive *** emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive *** provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

关键词： brain-derived neurotrophic factor calcium signaling glucocorticoid receptor glucocorticoid glutamate transmission hypothalamic-pituitary-adrenal axis long-term potentiation neurocognitive disorders neuroplasticity stress

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Lipid levels and insulin resistance markers in patients with colorectal cancer:Propensity score matching analysis

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 130-142页

作者： Ren-Hao Hu Dong-Yi Yan Ke-Hui zhang Di zhang Xi-Mao Cui Xiao-Hua Jiang Shun zhang Department of Gastrointestinal Surgery Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China School of Medicine Tongji UniversityShanghai 200092China Department of Emergency Medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China

BACKGROUND Colorectal cancer(CRC)is a prevalent malignant neoplasm characterized by subtle early *** To investigate the correlation among serum lipid profiles,the triglyceride-glucose(TyG)index,and the atherosclerotic index(AI)in patients with ***,it explored the clinical diagnostic utility of combining serum lipids with cancer antigens in the context of *** A retrospective analysis encompassed 277 patients with CRC and 1034 healthy *** Following propensity score matching,patients with CRC exhibited significantly reduced levels of serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol,and low-density lipoprotein cholesterol(LDL-C),as well as a diminished TyG ***,they displayed elevated AI levels compared to their healthy *** in advanced stages exhibited lower serum levels of TG,TC,and LDL-C compared to those in early *** with positive lymph node metastasis demonstrated reduced levels of TG,LDL-C,and the TyG *** operating characteristic analysis revealed that the combination of the TyG index,carcinoembryonic antigen,and carbohydrate antigen 19-9 yielded the highest positive prediction rate for CRC at 75.3%.CONCLUSION Preoperative serum lipid profiles exhibit a robust association with patients with *** concurrent assessment of multiple serum lipids and cancer antigens effectively enhances the diagnostic accuracy for CRC.

关键词： Colorectal cancer Serum lipids Triglyceride-glucose index Atherosclerotic index Diagnostic marker

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