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Identification and validation of a new prognostic signature based on cancer-associated fibroblast-driven genes in breast cancer

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World Journal of Clinical Cases 2024年第4期12卷 700-720页

作者： Zi-Zheng Wu Yuan-Jun Wei Tong Li Jie Zheng yin-feng Liu Meng Han Diagnosis and Treatment Center The First Hospital of QinhuangdaoQinhuangdao 066000Hebei ProvinceChina Department of General Surgery Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina Breast Disease Diagnosis and Treatment Center The First Hospital of QinhuangdaoHebei Medical UniversityQinhuangdao 066000Hebei ProvinceChina Breast Disease Diagnosis and Treatment Center Chengde Medical CollegeChengde 067000Hebei ProvinceChina

BACKGROUND Breast cancer(BC),a leading malignant disease,affects women all over the world.Cancer associated fibroblasts(CAFs)stimulate epithelial-mesenchymal transition,and induce chemoresistance and immunosuppression.AIM To establish a CAFs-associated prognostic signature to improve BC patient out-come estimation.METHODS We retrieved the transcript profile and clinical data of 1072 BC samples from The Cancer Genome Atlas(TCGA)databases,and 3661 BC samples from the The Gene Expression Omnibus.CAFs and immune cell infiltrations were quantified using CIBERSORT algorithm.CAF-associated gene identification was done by weighted gene co-expression network analysis.A CAF risk signature was established via univariate,least absolute shrinkage and selection operator regression,and mul-tivariate Cox regression analyses.The receiver operating characteristic(ROC)and Kaplan-Meier curves were employed to evaluate the predictability of the model.Subsequently,a nomogram was developed with the risk score and patient clinical signature.Using Spearman's correlations analysis,the relationship between CAF risk score and gene set enrichment scores were examined.Patient samples were collected to validate gene expression by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS Employing an 8-gene(IL18,MYD88,GLIPR1,TNN,BHLHE41,DNAJB5,FKBP14,and XG)signature,we attemp-ted to estimate BC patient prognosis.Based on our analysis,high-risk patients exhibited worse outcomes than low-risk patients.Multivariate analysis revealed the risk score as an independent indicator of BC patient prognosis.ROC analysis exhibited satisfactory nomogram predictability.The area under the curve showed 0.805 at 3 years,and 0.801 at 5 years in the TCGA cohort.We also demonstrated that a reduced CAF risk score was strongly associated with enhanced chemotherapeutic outcomes.CAF risk score was significantly correlated with most hallmark gene sets.Finally,the prognostic signature were further validated by qRT-PCR.CONCLUSION We introduced a newly-discovered

关键词： Breast cancer Prognosis Gene signature The Cancer Genome Atlas The Gene Expression Omnibus

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Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair

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Chinese Journal of Integrative Medicine 2024年第3期30卷 243-250页

作者： XU Han XU Si-cong LI Li-yan WU Yu-huang TAN yin-feng CHEN Long LIU Pei LIANG Chang-fu HE Xiao-ning LI Yong-hui Hainan Provincial Key Lab of Research&Development on Tropic Herbs Hainan Medical UniversityHaikou571199China Department of Stomatology the Second Affiliated Hospital of Hainan Medical UniversityHaikou571199China

Objective:To investigate the effects of Danmu Extract Syrup(DMS) on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice and explore the mechanism.Methods:Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table(n=12),including control(normal saline),LPS(5 mg/kg),LPS+DMS 2.5 mL/kg,LPS+DMS 5 mL/kg,LPS+DMS 10 mL/kg,and LPS+Dexamethasone(DXM,5 mg/kg) groups.After pretreatment with DMS and DXM,the ALI mice model was induced by LPS,and the bronchoalveolar lavage fluid(BALF) were collected to determine protein concentration,cell counts and inflammatory cytokines.The lung tissues of mice were stained with hematoxylin-eosin,and the wet/dry weight ratio(W/D) of lung tissue was calculated.The levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-1βin BALF of mice were detected by enzyme linked immunosorbent assay.The expression levels of Claudin-5,vascular endothelial(VE)-cadherin,vascular endothelial growth factor(VEGF),phospho-protein kinase B(p-Akt) and Akt were detected by Western blot analysis.Results:DMS pre-treatment significantly ameliorated lung histopathological changes.Compared with the LPS group,the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment(P<0.05 or P<0.01).The number of cells in BALF and myeloperoxidase(MPO) activity decreased significantly after DMS pretreatment(P<0.05 or P<0.01).DMS pre-treatment decreased the levels of TNF-α,IL-6 and IL-1β(P<0.01).Meanwhile,DMS activated the phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) pathway and reversed the expressions of Claudin-5,VE-cadherin and VEGF(P<0.01).Conclusions:DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier.It might be a potential therapeutic drug for LPS-induced lung injury.

关键词： Danmu Extract Syrup acute lung injury inflammatory factors vascular endothelial growth factor phosphoinositide 3-kinase/protein kinase B Chinese medicine Nauclea officinalis

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Heliangin acts as a covalent ligand of RPS2 that disrupts pre-rRNA metabolic processes in NPM1-mutated acute myeloid leukemia

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Acta Pharmaceutica Sinica B 2023年第2期13卷 598-617页

作者： yin feng Yefan Han Anni Hu Yi Qu Yili Hu Hao Wu Xinzhi Wang Li He College of Pharmacy Nanjing University of Chinese MedicineNanjing 210046China China Jiangsu Key Laboratory of Research and Development in Marine Bio-resource Pharmaceutics Nanjing 210046China Experiment Center for Science and Technology Nanjing University of Chinese MedicineNanjing 210046China Department of Hematology Zhongnan Hospital of Wuhan UniversityWuhan 430071China

Although NPM1 mutations are frequently found in acute myeloid leukemia patients,therapeutic strategies are scarce and unsuitable for those who cannot tolerate intensive chemotherapy.Here we demonstrated that heliangin,a natural sesquiterpene lactone,exerts favorable therapeutic responses in NPM1 mutant acute myeloid leukemia cells,with no apparent toxicity to normal hematogenous cells,by inhibiting their proliferation,inducing apoptosis,causing cell cycle arrest,and promoting differentiation.In-depth studies on its mode of action using quantitative thiol reactivity platform screening and subsequent molecular biology validation showed that the ribosomal protein S2(RPS2)is the main target of heliangin in treating NPM1 mutant AML.Upon covalent binding to the C222 site of RPS2,the electrophilic moieties of heliangin disrupt pre-rRNA metabolic processes,leading to nucleolar stress,which in turn regulates the ribosomal proteins-MDM2-p53 pathway and stabilizes p53.Clinical data shows that the pre-rRNA metabolic pathway is dysregulated in acute myeloid leukemia patients with the NPM1 mutation,leading to a poor prognosis.We found that RPS2 plays a critical role in regulating this pathway and may be a novel treatment target.Our findings suggest a novel treatment strategy and lead compound for acute myeloid leukemia patients,especially those with NPM1 mutations.

关键词： Acute myeloid leukemia Heliangin NPM1-mutation Differentiation Pre-rRNA Covalent RPS2 p53 stabilization

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数据规制政策差异与服务业价值链关联

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国际贸易问题 2024年第2期 17-33页

作者：党修宇殷凤上海大学经济学院

本文基于ECIPE-DTE提供的数据规制政策信息构建了数据规制政策差异指数,并利用2000—2018年54个经济体19个细分服务行业的增加值数据,检验了数据规制政策差异对服务业价值链关联的影响。基准分析结果表明,数据规制政策差异对服务业价值... 详细信息

本文基于ECIPE-DTE提供的数据规制政策信息构建了数据规制政策差异指数,并利用2000—2018年54个经济体19个细分服务行业的增加值数据,检验了数据规制政策差异对服务业价值链关联的影响。基准分析结果表明,数据规制政策差异对服务业价值链关联存在显著的负向影响,该结论在一系列稳健性检验后依然成立。异质性分析结果表明,与跨境数据规制政策差异不同,国内数据规制政策差异对服务业价值链关联的抑制作用存在时滞性且抑制作用相对较弱。此外,数据规制政策差异对数字密集型服务行业以及南—南经济体的服务业价值链关联的抑制作用也更加显著。扩展性分析结果表明,贸易成本和生产率是数据规制政策差异影响服务业价值链关联的重要渠道;经济体通过缔结数据跨境流动类规则以及合作包容类规则有助于削弱数据规制政策差异对服务业价值链关联的负向影响。

关键词：数据规制政策差异贸易成本生产率服务业价值链关联

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中小学课后服务质量评价体系构建:意蕴、依据与维度

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教育理论与实践 2024年第14期44卷 12-16页

作者：晋银峰洛阳师范学院教育科学学院河南洛阳471934

要实现中小学课后服务长远发展,必须研制切实可行的质量评价体系,以评价提升课后服务质量。中小学课后服务质量评价体系构建应满足多元利益诉求、促进多方协商共识、体现学生身心发展特点,其构建应顺应教育行政机构的政策需求,体现利益... 详细信息

要实现中小学课后服务长远发展,必须研制切实可行的质量评价体系,以评价提升课后服务质量。中小学课后服务质量评价体系构建应满足多元利益诉求、促进多方协商共识、体现学生身心发展特点,其构建应顺应教育行政机构的政策需求,体现利益相关者理论和CIPP评价理论模型的理论阐释,奠基于学校教育高效运行的实践需求。在课后服务质量评价体系构建过程中,可以从四个维度共同发力:科学的服务目标是构建方向,充足的教育资源投入是构建保障,完善的服务过程是构建依托,客观的服务评价是构建要求。

关键词：中小学课后服务质量评价体系服务目标教育资源服务过程服务评价

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Effect of L-theanine combined with geniposide on depression-like behavior induced by the chronic unpredictable mild stress(CUMS) in mice

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Food Science and Human Wellness 2024年

作者： Qi-Ming Yu Yan Zhu Tao Jiang ying Gao Nan Ling Na Wang John Shi Wei-Chun Pan Qi-Zhen Du Jun-feng yin Tea Research Institute Chinese Academy of Agricultural Sciences Key Laboratory of Tea Biology and Resources Utilization Ministry of Agriculture College of Food and Health Sciences Zhejiang A & F University Zhejiang Gongshang University Guelph Food Research Center Agriculture and Agri-Food Canada College of Public Health Guilin Medical University

Depression is a prevalent mental disorder with limited effective treatments， posing a significant global issue. This study explored L-theanine and geniposide， key components in "food-medicine homology" materials， to determine if their combination (TG) could alleviate depression-like behaviors and hippocampal neuronal damage in a chronic unpredictable mild stress (CUMS) mouse model. Male C57BL/6J mice were divided into control， CUMS model， and CUMS+TG groups with varying doses. The CUMS group displayed depression-like behaviors， including reduced activity and sucrose preference. TG treatment partially reversed these changes， significantly increasing antioxidant enzyme activities， decreasing pro-inflammatory cytokine levels， and improving neuromodulator levels. RNA-seq analysis identified the transthyretin (TTR) gene， upregulated in the model group but downregulated after TG treatment. TG treatment modulated intestinal microbiota composition compared to the CUMS group， including increased Firmicutes， reduced Bacteroidetes and Prevotella， and variable changes in Bifidobacterium abundance. In conclusion， our study indicates that CUMS exposure upregulates stress hormones and TTR expression， associated with neuroinflammation， oxidative stress， monoamine depletion， depression-like behaviors， and intestinal microbiota dysbiosis. TG treatment alleviates these effects and modulates intestinal microbiota， suggesting L-theanine and geniposide’s potential as a novel depression therapy.

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数字普惠金融、融资约束与中小企业投资效率

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科学管理研究 2024年第1期42卷 106-114页

作者：李梁殷凤春盐城师范学院商学院江苏盐城224007

通过构建异质性随机前沿模型,利用北京大学数字普惠金融指数市级数据和上市公司财务数据,探究数字普惠金融对中小企业融资约束和融资不确定性的作用,从而估算出投资效率。研究发现:我国中小企业在投资时面临显著的融资约束,融资约束的... 详细信息

通过构建异质性随机前沿模型,利用北京大学数字普惠金融指数市级数据和上市公司财务数据,探究数字普惠金融对中小企业融资约束和融资不确定性的作用,从而估算出投资效率。研究发现:我国中小企业在投资时面临显著的融资约束,融资约束的存在使得实际投资水平比最优投资水平低了30%-40%,平均投资效率仅为64%,且投资效率存在明显的异质性特征。数字普惠金融的发展能缓解中小企业融资约束,提高投资效率,这一作用在东部地区和非国有企业样本中更加显著。但是,数字普惠金融的发展同时也增加了中小企业的融资不确定性,加剧了金融市场风险。研究为数字普惠金融的发展缓解中小企业融资约束,提升投资效率提供了经验证据,为如何更好地发挥金融市场对中小企业的支持作用,促进经济高质量发展提供了理论依据和政策启示。

关键词：数字普惠金融融资约束投资效率异质性随机前沿模型中小企业

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Influence of stress anisotropy on the cylindrical cavity expansion in undrained elastic-perfectly plastic soil

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Science China(Technological Sciences) 2018年第3期61卷 370-380页

作者： ZHOU Hang LIU HanLong ZHA YaHui yin feng Key Laboratory of New Technology for Construction of Cities in Mountain Area School of Civil Engineering Chongqing University State Key Laboratory for Geomechanics and Deep Underground Engineering China University of Mining and Technology

This work presents an analysis of the influence of stress anisotropy on cylindrical cavity expansions in an undrained elastic-perfectly plastic soil. This problem was formulated by assuming a large strain in both the elastic and plastic zones around the cavity and a plain strain condition during the cavity expansion process. The solutions for the limit pressure, stress, and excess pore pressure were obtained by introducing the anisotropic initial stress coefficient K_0 into the conventional cylindrical cavity expansion method.The proposed solutions were then used to interpret the piezocone penetration test, and the suitability of the solutions was verified by comparing the prediction with the piezocone penetration test data. Subsequently, parametric studies were carried out to investigate the influence of stress anisotropy on the stress, excess pores pressure distributions around an expanding cylindrical cavity, and limit pressure. The results show that the proposed cylindrical cavity expansion method under stress anisotropy is suitable and can be used to investigate the piezocone cone test. The present work improves upon the conventional theoretical framework of cavity expansion and can be applied to the determination of the stresses around axially loaded piles and around in-situ testing devices such as penetrometers.

关键词：压力系数圆柱塑料橡皮土壤测试数据各向异性压力分布

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Oxygen Isotopic Compositions in a Plagioclase-Olivine Inclusion from Ningqiang Similar to Those in Al-rich Chondrules

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Acta Geologica Sinica(English Edition) 2021年第5期95卷 1583-1590页

作者： DAI Deqiu BAO Haimei LIU Shuang yin feng Department of Geology Hunan University of Science and TechnologyXiangtanHunan 411201China Institute of Geochemistry Chinese Academy of SciencesGuiyang 550081China Hunan Provincial Key Laboratory of Shale Gas Resource Utilization Hunan University of Science and TechnologyXiangtanHunan 411201China

We report the petrology and oxygen isotopic composition,using a Cameca Nano SIMS 50L ion microprobe,of a plagioclase-olivine inclusion,C#1,found in the Ningqiang carbonaceous chondrite.In addition to major phases(plagioclase,spinel and olivine),C#1 is also surrounded by a pyroxene rim(64 vol%Ca-rich and 36 vol%Ca-poor pyroxenes).On a three-isotope oxygen diagram,δ^(17)O vs.δ^(18)O,the compositions of individual minerals analyzed in C#1 fall along the carbonaceous chondrite anhydrous mineral line(CCAM),and oxygen isotopic compositions in C#1 show significant variability in δ^(18)O and δ^(17)O.The oxygen isotopic compositions of the pyroxene rim minerals are similar to those of the other host minerals,which suggests that the rim likely formed from the same melting process as the host.The rim is considered to have formed as a result of interaction between an ^(16)O-poor gas and a melt.Some spinel grains are typically ^(16)O-rich and likely of relict origin,which is similar to ^(16)O-rich Ca-,Al-rich inclusions,which are probably a precursor of C#1.The inclusion then likely melted in an ^(16)O-poor region where chondrules form,accompanied by oxygen isotope exchange with an ^(16)O-poor gas.Some anorthite,pyroxene and spinel might have undergone fluid-assisted thermal metamorphism on the Ningqiang chondrite parent body.The oxygen isotope data and evolution of the C#1 plagioclase-olivine inclusion are similar with those of Al-chondrules in chondrites.

关键词： meteorite petrology oxygen isotopes CAIs plagioclase–olivine inclusion Al-rich chondrules Ningqiang chondrite Shanxi

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Wave equation tomographyin baseband with phase correction from the first arrival traveltimes

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石油物探 2017年第1期56卷 69-74页

作者： yin feng Jerry HARRIS Department of Geophysics Stanford University

We use the first arrival traveltime to correct the phase distortion in a nonlinear wave equation inversion scheme.This improves the precision of tomographic reconstruction of a velocity structure with large variations and helps solve the ill-posed problem of wave equation inversion.When the variation of the velocity distribution is large,general non-linear wave equation inversions are very ill-posed and for such strong nonlinear we can not obtain a correct inversion.One of main reasons is that the calculated and observed phase of the wavefield differs greatly if the initial model is far from the true model.This leads to highly mismatched phase between the calculated and the observed wave field.This is so-called"Cycle Skipping"problem in the full waveform inversion.The phase mismatch is even more pronounced if a high operating frequency is employed in order to increase resolution.To address this problem,we use the first arrival to"demodulate"the wave field in the frequency domain with a goal of restoring the phase of wave field.Then we minimize an objective function consisting of so called"demodulated"wave field to solve wave equation inversion problem.In this way,we find that the inversion is much improved,and when the velocity perturbation in a complicated model reaches 35%,we can still obtain a good inversion.A computer simulation shows that our method is very robust for acoustical wave inversion with good reconstruction precision.

关键词：全波形反演随机边界异构并行作业池速度反演

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