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Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase

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Chinese Journal of Integrative Medicine 2024年第6期30卷 499-506页

作者： LI Qi KONG Zhao-di WANG Huan GU Hong-hui CHEN Zhong Li Shi-guang CHEN Yi-qi CAI Yu YANG Zhen-jiang Department of Oncology and hematology Shenzhen Traditional Chinese Medicine HospitalShenzhenGuangdong Province518033China College of Pharmacy/International Cooperative laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of China Jinan UniversityGuangzhou510632China Guangdong Key lab of Traditional Chinese Medicine Information Technology Jinan UniversityGuangzhou510632China

ObjectiveTo provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction(JP)and to explore its mechanism of anti-cancer *** mouse model of colon cancer(CT26)-induced cancer cachexia(CC)was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate(MPA).Thirty-six mice were equally divided into 6 groups:normal control,CC,MPA(100 mg·kg^(−1)·d^(−1)),MPA+low-dose(20 mg·kg^(−1)·d^(−1))JP(L-JP),MPA+medium-dose(30 mg·kg^(−1)·d^(−1))JP(M-JP),and MPA+high-dose(40 mg·kg^(−1)·d^(−1))JP(H-JP)*** successful modeling,the mice were administered by gavage for 11 *** body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after *** liver,heart,spleen,lung,kidney,tumor and gastrocnemius muscle of mice were collected and *** pathological changes of the tumor was observed,and the cross-sectional area of the gastrocnemius muscle was *** protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western *** addition,an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle *** vitro experiments were divided into control,model,and JP serum *** 2-d administration,microscopic photographs were taken and myotube diameters were *** blot was performed to measure the protein expressions of STAT3 and E3 *** combined with MPA restored tumor-induced weight loss(P<0.05,***)and muscle fiber size(P<0.01,***).Mechanistically,JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo(P<0.05,***).In addition,JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation(P<0.05 or P<0.01 *** group)in C2C12 myotubes treated with dexamethasone in *** of JP combined with MPA restores t

关键词： cancer cachexia muscle atrophy Jianpi Decoction Chinese medicine E3 ubiquitin ligases

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Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis

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Journal of Biomedical Research 2024年第4期38卷 397-412页

作者： Jiaqi Tang Lin Luo Bakwatanisa Bosco Ning Li Bin Huang Rongrong Wu Zihan Lin Ming Hong Wenjie Liu Lingxiang Wu Wei Wu Mengyan Zhu Quanzhong Liu Peng Xia Miao Yu Diru Yao Sali Lv Ruohan Zhang Wentao Liu Qianghu Wang Kening Li Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjingJiangsu 211166China Department of hematology of the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University Northern Jiangsu Institute of Clinical MedicineHuai'anJiangsu 223300China Collaborative Innovation Center for Personalized Cancer Medicine Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentNanjing Medical UniversityNanjingJiangsu 211166China Department of hematology the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key laboratory of hematology of Nanjing Medical University NanjingJiangsu 210029China Department of Pharmacology School of Basic Medical SciencesNanjing Medical UniversityNanjingJiangsu 211166China The Affiliated Cancer Hospital of Nanjing Medical University Jiangsu Cancer HospitalJiangsu Institute of Cancer ResearchNanjingJiangsu 210002China

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is *** surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and *** the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression *** using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML *** predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome *** Cox regression analysis showed that the risk score was an independent prognostic factor for the AML *** AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low ***,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy ***,PI3K inhibitors were identified as potential treatments for these high-risk *** conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.

关键词： acute myeloid leukemia cell surface markers prognosis drug sensitivity multi-model analysis

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PD-L1表达指导的信迪利单抗与帕博利珠单抗联合或不联合含铂双药化疗治疗未经治晚期非小细胞肺癌患者:一项2期随机对照试验(CTONG1901)

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Science Bulletin 2024年第4期69卷 535-543页

作者：刘思阳黄婕邓嘉怡徐崇锐严红虹杨明意黎扬斯柯娥娥郑明英王震林嘉欣甘彬张绪超陈华军汪斌超涂海燕杨衿记钟文昭李扬秋周清吴一龙 Department of hematology The First Affiliated HospitalJinan UniversityGuangzhou 510632China Guangdong Lung Cancer Institute Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China Chinese Thoracic Oncology Group(CTONG) Guangzhou 510055China Institute of hematology School of MedicineKey Laboratory for Regenerative Medicine of Ministry of EducationJinan UniversityGuangzhou 510632China

No direct comparison has been performed between different programmed cell death-1(PD-1)inhibitors for first-line treatment in patients with advanced non-small cell lung cancer(NSCLC).The feasibility of using PD-L1-expression-guided immunotherapy remains *** this open-label,phase 2 study(NCT04252365),patients with advanced NSCLC without EGFR or ALK alterations were randomized(1:1)to receive sintilimab or pembrolizumab monotherapy(PD-L1 expression≥50%),or sintilimab or pembrolizumab plus platinum-based chemotherapy(PD-L1 expression<50%).The sample size was calculated by optimal two-stage *** primary endpoint was the objective response rate(ORR).The study included 71 patients(sintilimab arms,n=35;pembrolizumab arms,n=36)and met its primary endpoint,with a confirmed ORR of 51.4%(18/35)in the sintilimab *** confirmed ORR(95%confidence interval)was 46.2%(19.2%,74.9%)and 42.9%(17.7%,71.1%)for patients treated with sintilimab and pembrolizumab monotherapy;and 54.5%(32.2%,75.6%)and 45.4%(24.4%,67.8%)for those treated with sintilimab-and pembrolizumab-based combination *** median progression-free survival was6.9 versus 8.1 months for all sintilimab-treated versus all pembrolizumab-treated patients,respectively,in which it was 7.6 versus 11.0 months in monotherapy and 7.4 versus 7.1 months in combination *** median overall survival was 14.9 versus 21.3 months for all sintilimab-treated versus all pembrolizumab-treated patients,respectively,in which it was 14.9 versus 22.6 months in monotherapy and 14.7 versus 17.3 months in combination ***-related adverse events were consistent with safety outcomes of monotherapy and combination therapy in previous phase III ***,the incidence of rash was higher with sintilimab than pembrolizumab *** is the first prospective phase 2 study to directly compare two anti-PD-1 antibodies as first-line treatment in advanced *** was efficacious and well-tolera

关键词： PD-1 inhibitor Non-small cell lung cancer Pembrolizumab Sintilimab PD-L1 expression

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mtDNA-triggered pH response signal-amplified fluorescent probe for multiple cell discrimination

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Chinese Chemical Letters 2024年第3期35卷 363-368页

作者： Tianping Xia Yanxian Hou Zhuoran Xia Gengwen Chen Peichen Tang Jiangli Fan Xiaojun Peng State Key laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical EngineeringDalian University of TechnologyDalian 116024China hematology Reagent R&D Department Mindray Bio-medical Electronics Co.Ltd.Shenzhen 518132China Research Institute of Dalian University of Technology in Shenzhen Shenzhen 518057China

Developing fluorescence probes with multiple responses has vital significance but remains ***,for the first time,we present a mitochondrial DNA(mtDNA)-triggered pH response signalamplified fluorescent probe(QCY-DBT)for multiple cell *** probe exhibited a large stokes shift(229 nm),excellent DNA selectivity over RNA,and ultrasensitivity of detection limit(DL;74.0 ng/mL).Thus,QCY-DBT was successfully applied to analyze multiple human peripheral blood cells and visualize mtDNA in healthy and apoptotic *** the tumor acidic environment(pH 6.0–7.0),the absorbance of QCY-DBT at 436 nm increased,and the fluorescence signal(665 nm)was amplified by mtDNA,which enabled the direct observation of tumor *** study provides help in designing smart probes with multiple responses for efficient abnormal cell detection.

关键词： Fluorescence probe Mitochondrial DNA pH response Peripheral blood cells Multiple cell detection

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FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2010年第10期11卷 762-770页

作者： Lei WANG Wei-lai XU Hai-tao MENG Wen-bin QIAN Wen-yuan MAI Hong-yan TONG Li-ping MAO Yin TONG Jie-jing QIAN Yin-jun LOU Zhi-mei CHEN Yun-gui WANG Jie JIN Department of hematology the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China Institute of hematology Zhejiang University Hangzhou 310003 China Key lab of Hematopoietic Malignancy Zhejiang University Hangzhou 310003 China

Mutations of fins-like tyrosine kinase 3 （FLT3） and nucleophosmin （NPM1） exon 12 genes are the most common abnormalities in adult acute myeloid leukemia （AML） with normal cytogenetics. To assess the prognostic impact of the two gene mutations in Chinese AML patients, we used multiplex polymerase chain reaction （PCR） and capillary electrophoresis to screen 76 AML patients with normal cytogenetics for mutations in FLT3 internal tandem duplication （FLT3/ITD） and exon 12 of the NPM1 gene. FLT3/ITD mutation was detected in 15 （19.7%） of 76 subjects, and NPM1 mutation in 20 （26.3%） subjects. Seven （9.2%） cases were positive for both FLT3/ITD and NPM1 mutations Significantly more FLT3/ITD aberration was detected in subjects with French-American-British （FAB） M1 （42.8%）. NPM1 mutation was frequently detected in subjects with M5 （47.1%） and infrequently in subjects with M2 （11.1%）. FLT3 and NPM1 mutations were significantly associated with a higher white blood cell count in peripheral blood and a lower CD34 antigen expression, but not age, sex, or platelet count. Statistical analysis revealed that the FLT3/ITD- positive group had a lower complete remission （CR） rate （53.3% vs. 83.6%）. Survival analysis showed that the FLT3/ITD-positive/NPM1 mutation-negative group had worse overall survival （OS） and relapse-free survival （RFS）. The FLT3/ITD-positive/NPM1 mutation-positive group showed a trend towards favorable survival compared with the FLT3/ITD-positive/NPM1 mutation-negative group （P=0.069）. Our results indicate that the FLT3/ITD mutation might be a prognostic factor for an unfavorable outcome in Chinese AML subjects with normal cytogenetics, while NPM1 mutation may be a favorable prognostic factor for OS and RFS in the presence of FLT3/ITD.

关键词： Acute myeloid leukemia (AML) Normal cytogenetics Prognosis fms-like tyrosine kinase 3 interna tandem duplication (FLT3/ITD) Nucleophosmin (NPM1) Mutation

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Case Report:CD19-positive acute myeloblastic leukemia with trisomy 21 as a sole acquired karyotypic abnormality

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2009年第11期10卷 833-838页

作者： Hua-feng WANG Yi-zhi CHENG Huan-ping WANG Zhi-mei CHEN Ji-yu LOU Jie JIN Department of hematology the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China Institute of hematology Zhejiang University Hangzhou 310003 China Key lab of Combined Multi-Organ Transplantation Ministry of Public Health Hangzhou 310003 China

We report that a 63-year-old Chinese female had acute myeloblastic leukemia （AML） in which trisomy 21 （＋21） was found as the sole acquired karyotypic abnormality. The blasts were positive for rnyeloperoxidase, and the immunophenotype was positive for cluster of differentiation 19 （CD19）, CD33, CD34, and human leukocyte antigens （HLA）-DR. The chromosomal analysis of bone marrow showed 47,XX,＋21 [2]/46,XX[ 18]. Fluorescent in situ hybridization （FISH） showed that three copies of AML1 were situated in separate chromosomes, and that t（8;21） was negative. The patient did not have any features of Down syndrome. A diagnosis of CD 19-positive AML-M5 was established with trisomy 21 as a sole acquired karyotypic abnormality. The patient did not respond well to chemotherapy and died three months after the diagnosis. This is the first reported case of CD19-positive AML with trisomy 21 as the sole cytogenetie abnormality. The possible prognostic significance of the finding in AML with ＋21 as the sole acquired karyotypic abnormality was discussed.

关键词： Trisomy 21 Acute myeloid leukemia Cluster of differentiation 19 (CD 19)

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Two tyrosines in CD3ε-ITAM are required to induce T lymphocyte apoptosis

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Chinese Science Bulletin 1998年第17期43卷 1480-1485页

作者： ZHENG Dexian 1,2, HE Yiping+1, LIU Yanxin+1, ZHENG Yong,XIAO Sheng+1, LIU Yin+1 and LIU Shilian+1 1. State Key laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China State Key lab. of Med. Molec. Biol. Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Beijing 100005 China State Key lab. of Exp. hematology Institute of Hematology Chinese Academy of Medical Sciences Tianjin 300020 China

CD3ε of T cell antigen receptor complex (TCR/CD3) plays an important role in the resembling of the complex and activation signaling through its conservative immunoreceptor tyrosine-based activation motif (ITAM) in the cytoplasmic tail. Previous study showed that a chimera molecule, consisting of the extracellular-transmembrane domain of human CD8α fused to the cytoplasmic domain of CD3ε, induced apoptosis of T lymphocytes, indicating that apoptotic signals were transduced through the CD3ε- ITAM. To elineate involvement of the two tyrosines in apoptotic signaling pathway, cDNAs with mutations at Y170F, Y181F and Y170F/Y181F in CD8-ε-ITAM were made by point mutation and PCR, and then cloned into pcDNA3 eukaryotic expression vectors. Stable expression cell lines were established after transfection of the expression vectors into CD8+- Jurkat T lymphocytes. Stimulation of these cell lines with anti-CD8 monoclonal antibody showed that only the cells with expression of wild type chimera CD8-ε died by apoptosis, but not those cells with expressions of mutated CD8-ε chimera, indicating that the two tyrosines in CD3ε-ITAM were required for the apoptotic signal transduction in T lymphocytes.

关键词： apoptosis CD3ε-ITAM tyrosine.

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Lack of Association of Common Polymorphism of LRP1 Gene with Myocardial Infarction in a Chinese Han Population

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2011年第3期31卷 295-300页

作者：任红刚郭涛王华芳孙春艳张小平梅恒胡豫 Institute of hematology and the Ministry of Education Key lab of Targeted Biotherapy Union HospitalTongji Medical CollegeHuazhong University of Science and Technology

This study examined the association of a common polymorphic allele（25G） of the low-density lipoprotein receptor-related protein1（LRP1） gene with myocardial infarction（MI）.The genotypes of LRP1 25CG（rs35282763） were determined in 347 MI patients and 347 age-and sex-frequency-matched controls from an unrelated Chinese Han *** Ⅷ（FⅧ） levels were measured in the MI patients and controls by chromogenic assay and enzyme-linked immunosor-bent assay（ELISA）.The results showed that LRP1 25CG（rs35282763） genotype distribution did not differ significantly between patients（n=206 for 25CC,n=122 for 25CG） and controls（n=191 for 25CC,n=126 for 25CG;P0.05）.The 25G allele was not associated with a reduced risk of MI（P0.05）.Further stratifications for age,sex,and other cardiovascular risk factors did not affect the negative *** was concluded that the presence of the G allele at the 25CG（rs35282763） polymorphism of the LRP1 is not associated with a reduced risk of MI,and genotyping for LRP1 25CG（rs35282763） polymor-phism is not useful in assessing the individual risk of MI.

关键词： low-density lipoprotein receptor-related protein1 myocardial infarction polymorphism

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RFLPS ANALYSIS OF VON WILLEBRAND FACTOR GENE IN CHINESE POPULATION

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Chinese Science Bulletin 1992年第2期37卷 160-164页

作者：吴庆宇潘峻亮顾建明程大卫李佩霞阮长耿 Jiangsu Institute of hematology Thrombosis and Hemostasis Research lab Suzhou Medical College Suzhou 215007 PRC

Ⅰ. INTRODUCTION von Willebrand factor (vWF), a large adhesive plasma glycoprotein, plays a central role in the adhesion of platelets to injured vessel wall and also serves as a carrier protein for coagulant factor Ⅷ (FⅧ), stabilizing the activity of FⅧ in plasma. The vWF gene of 178 kb in length is localized at chromosome 12p12-pter. The gene contains 52

关键词： von Willebraud factor(vWF) von Willebrand disease(vWD) ristriction fragment length polymorphisms (RFLPs).

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Association of Human Whole-blood NAD+Levels with Nabothian Cyst

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Biomedical and Environmental Sciences 2024年第5期37卷 471-478页

作者： XU Ling WANG Yue Xuan WANG Wei FAN Xue CHEN Xue Yu ZHOU Tian Yun LIU Yu He YU Ye YANG Fan JU Zhen Yu ZHOU Yong WANG Deng Liang Clinical Research Institute Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China NHC Key lab of Reproduction Regulation Shanghai Engineering Research Center of Reproductive Health Drugs and DevicesShanghai Institute for Biomedical and Pharmaceutical TechnologiesShanghai 200237China Department of Applied Statistics Johannes Kepler University LinzLinz 4040Austria hematology Center Beijing Key Laboratory of Pediatric Hematology OncologyNational Key Discipline of Pediatrics(Capital Medical University)Key Laboratory of Major Diseases in ChildrenMinistry of EducationBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Department of Biostatistics School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012ShandongChina Clinical Medicine School of Basic MedicineShanghai Medical College Fudan UniversityShanghai 200032China Department of Biochemistry and Molecular Biology Hengyang Medical SchoolUniversity of South ChinaHengyang 421001HunanChina Administrative Office Total Quality Management OfficeTotal Quality Management InstituteShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China The First Affiliated Hospital of Jinan University Institute of Aging and Regenerative MedicineJinan UniversityJinan 510632GuangzhouChina Department of Scientific Research The First Affiliated Hospital of Huzhou UniversityHuzhou 313000ZhejiangChina Department of Neurosurgery Neurosurgery Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhou 350005FujianChina Department of Neurosurgery Binhai Branch of National Regional Medical CenterThe First Affiliated HospitalFujian Medical UniversityFuzhou 350209FujianChina Fujian Provincial Institutes of Brain Disorders and Brain Sciences The First Affiliated HospitalFujian Medical UniversityFuzhou 350005FujianChina Fujian Provincial Clinical Research Center for Neurological

Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD^(+))levels and nabothian *** study aimed to assess the association between NAD^(+)levels and nabothian cysts in healthy Chinese *** Multivariate logistic regression analysis was performed to analyze the association between NAD^(+)levels and nabothian *** The mean age was 43.0±11.5 years,and the mean level of NAD^(+)was 31.3±5.3μmol/*** cysts occurred in 184(27.7%)participants,with single and multiple cysts in 100(15.0%)and84(12.6%)participants,*** total nabothian cyst prevalence gradually decreased from37.4%to 21.6%from Q1 to Q4 of NAD^(+)and the prevalence of single and multiple nabothian cysts also decreased across the NAD^(+)*** compared with the highest NAD^(+)quartile(≥34.4μmol/L),the adjusted odds ratios with 95%confidence interval of the NAD^(+)Q1 was 1.89(1.14–3.14)for total nabothian *** risk of total and single nabothian cysts linearly decreased with increasing NAD^(+)levels,while the risk of multiple nabothian cysts decreased more rapidly at NAD^(+)levels of 28.0 to35.0μmol/***:Low NAD^(+)levels were associated with an increased risk of total and multiple nabothian cysts.

关键词： Nicotinamide adenine dinucleotide Nabothian cyst Female Risk factor

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