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High baseline tumor burden-associated macrophages promote an immunosuppressive microenvironment and reduce the efficacy of immune checkpoint inhibitors through the IGFBP2-STAT3-PD-L1 pathway

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Cancer Communications 2023年第5期43卷 562-581页

作者： Zhaowei Wen Huiying Sun Zhihua Zhang Yannan Zheng Siting Zheng jianping bin Yulin Liao Min Shi Rui Zhou Wangjun Liao Department of Oncology Nanfang HospitalSouthern Medical UniversityGuangzhou510515GuangdongP.R.China Department of Cardiology Nanfang HospitalSouthern Medical UniversityGuangzhou510515GuangdongP.R.China

Background:Several clinical studies have uncovered a negative correlation between baseline tumor burden and the efficacy of immune checkpoint inhibitor(ICI)*** study aimed to uncover the specific mechanisms underlying the difference in sensitivity to ICI treatment between tumors with high(HTB)and low(LTB)tumor ***:For in vivo studies,several mouse models of subcutaneous tumors were established,and transcriptome sequencing,immunohistochemistry,and flow cytometry assays were used to detect the immune status in these subcutaneous *** in vitro experiments,co-culture models,cytokine antibody arrays,western blotting,flow cytometry,and enzyme-linked immunosorbent assays were used to explore the underlying molecular mechanisms Results:We found that MC38 or B16 subcutaneous tumors from the HTB group did not show any response to anti-programmed cell death protein-1(PD-1)*** flow cytometry assays,we found that the infiltration with CD8^(+)T cellswas significantly decreasedwhereasM2-like macrophageswere enriched in subcutaneous tumors of HTB groups compared with those of LTB *** changes were not affected by the initial number of injected tumor cells or tumor age,nor could they be reversed by surgical tumor *** colony-stimulating factor 1 receptor(CSF-1R)inhibitor PLX3397 injection at different time points of tumor growth only had an effect when administered in the early tumor stage to maintain the“heat”of the tumor microenvironment during the process of tumor growth,thereby achieving a response to ICI treatment when the tumor grew to a large ***,we found that insulin-like growth factor binding protein 2(IGFBP2)expression levelswere significantly elevated in HTB tumor ***2 promoted the programmed death-ligand 1(PD-L1)expression in M2-like macrophages by activating signal transducer and activator of transcription 3(STAT3),and PD-L1^(+)M2-likemacrophages exerted an immunosuppressive e

关键词： CD8^(+)T cell IGFBP2 immune checkpoint inhibitor macrophage PD-L1 STAT3 tumor burden tumor immune microenvironment

Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/β_(2)-AR/MACC1 axis

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Cancer Communications 2021年第10期41卷 1049-1070页

作者： Changqie Pan Jianhua Wu Siting Zheng Huiying Sun Yisheng Fang Zhenhua Huang Min Shi Li Liang jianping bin Yulin Liao Jinzhang Chen Wangjun Liao Department of Oncology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515P.R.China Department of Pathology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515P.R.China Department of Cardiology Nanfang HospitalSout4hern Medical UniversityGuangzhouGuangdong 510515P.R.China

Background:Depression is a common,easily ignored,accompanied disease of gastric cancer(GC)patients and is often observed with elevated plasma catecholamine *** frequently promotes GC progression and leads to poor clinical outcomes;however,the molecular mechanisms underlying depression-induced GC progression remain poorly *** aimed to study the effects of depression on GC progression and explore possible mechanisms mediating the action of depression-associated catecholamines on ***:Depression states of GC patients were graded using the Patient Health Questionnaire-9,and plasma catecholamine levels were examined by high performance liquid chromatography coupled with tandem mass *** and invasive GC cells were examined using transwell assays,and metastatic GC niches were imaged using bioluminescence technology in a depression mouse model established with chronic unpredictable mild *** depression-like behaviors were assessed through sucrose preference,forced swimming,and tail suspension *** of the neuroendocrine phenotype were observed via RT-PCR,Western blotting,flow cytometry,and transmission electron ***:Fifty-one GC patients(age:53.61±1.79 years;cancer duration:3.71±0.33 months;depression duration:2.37±0.38 months;male-to-female ratio:1.55:1)were enrolled in the *** grade was significantly higher in GC patients showing higher plasma levels of catecholamines(epinephrine:P=0.018;noradrenaline:P=0.009),higher oncogene metastasis-associated in colon cancer-1(MACC1)level(P=0.018),and metastasis(Pbinding betweenMACC1 and ***,the neuroendocrine phenotypic transformation accelerated GC invasion in vitro and metastasis in ***

关键词： catecholamines depression gastric cancer MACC1 neuroendocrine phenotype psychological stress tumor metastasis

Evolution of tumor microenvironment in colorectal liver metastases under treatment stress

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Cancer Communications 2022年第5期42卷 471-475页

作者： Na Huang Dongqiang Zeng Xiaoxiang Rong Chunlin Wang Zhenzhen Wu Jian Guo Yuqi Wang Jin Li Jing Li Jiao Wang Siting Zheng Genjie Huang jianping bin Yulin Liao Qian Li Xin Yi Wangjun Liao Min Shi Department of Oncology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515P.R.China Department of Research and Development GenePlus-BeijingBeijing 102206P.R.China Department of Cardiology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515P.R.China

Dear editor,The tumor microenvironment(TME)heavily impacts disease biology and may influence responses to systemic treatments,and thereby,affects patients’*** our previous study,we found that immune features could predict prognosis and guide the therapy choices for stage I-III colon cancer[1,2].Increasing evidence shows that therapyinduced TME changes can promote tumor progression,metastasis,and the development of resistance[3,4].However,the TME dynamics in colorectal liver metastases(CRLM)under treatment are still incompletely clear.

关键词： colorectal metastases treatment

Fundamental geological elements for the occurrence of Chinese marine oil and gas accumulations

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Science Bulletin 2007年第S1期 28-43页

作者： ZHANG ShuiChang, LIANG DiGang, ZHU GuangYou, ZHANG XingYang, ZHANG BaoMin, CHEN jianping & ZHANG bin Research Institute of Petroleum Exploration and Development, PetroChina, Beijing 100083, China

关键词： marine facies carbonate rocks Paleozoic Tarim Basin Sichuan Basin Ordos Basin

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鄱阳湖苔草枯水期的水分利用策略

陕西师范大学学报（自然科学版） 2018年第1期46卷 97-103页

作者：潘国艳曹夏禹张翔邴建平武汉大学水资源与水电工程科学国家重点实验室湖北武汉430072 江西师范大学鄱阳湖湿地与流域研究教育部重点实验室江西南昌330022 长江水利委员会水文局水资源处湖北武汉430010

选取鄱阳湖湿地典型植物苔草为对象,通过野外采样,对苔草的土壤水、植物水稳定氢氧同位素组成进行分析,研究鄱阳湖湿地苔草在枯水期的水分利用策略。结果发现:土壤水的氢氧稳定同位素比之间有明显的线性相关关系,在水位更低的2016年土... 详细信息

选取鄱阳湖湿地典型植物苔草为对象,通过野外采样,对苔草的土壤水、植物水稳定氢氧同位素组成进行分析,研究鄱阳湖湿地苔草在枯水期的水分利用策略。结果发现:土壤水的氢氧稳定同位素比之间有明显的线性相关关系,在水位更低的2016年土壤水经历了更严峻的蒸发,根据氧同位素比和土壤含水率随深度变化可以将土壤水分为表层土壤水、深层土壤水和地下水三层;在枯水期,苔草对三种水源的利用比例为28.2%~41.4%,对各水源利用比例总体上大致相当,但断面之间的表现差异明显,各采样点之间有所差别,且在2016年枯水期差别更加明显。

关键词：鄱阳湖枯水期苔草水分来源

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血管内超声检测易损斑块的研究进展

临床超声医学杂志 2009年第10期11卷 684-686页

作者：宾建国宾建平南方医科大学南方医院心内科广州市510515

早期检测易损斑块对于急性冠脉综合征的防治有重要意义。血管内超声是检测易损斑块的重要方法,有着独特优势。本文就血管内超声及其衍生技术检测易损斑块的基本原理和研究进展作一综述。

关键词：斑块血管内超声

在静息血流无限制的慢性冠状动脉狭窄中静息心肌收缩功能与血流储备的关系

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中国循环杂志 2000年第5期15卷 302-303页

作者：宾建平刘伊丽查道刚 Sanjiv Kaul 中国人民解放军第一军医大学南方医院心内科广东省广州市510515 美国弗吉尼亚大学医学中心心内科

目的 :评价静息心肌收缩功能与血流储备的关系。　　方法 :以安放“水膨胀”式缩窄器的方法建立 11只慢性多支冠状动脉 (冠脉 )狭窄闭胸犬。术后 7～ 10天在静息状态下以二维超声心动图测定室壁增厚百分率 (% WT) ,同时以放射性微球测... 详细信息

目的 :评价静息心肌收缩功能与血流储备的关系。　　方法 :以安放“水膨胀”式缩窄器的方法建立 11只慢性多支冠状动脉 (冠脉 )狭窄闭胸犬。术后 7～ 10天在静息状态下以二维超声心动图测定室壁增厚百分率 (% WT) ,同时以放射性微球测定心肌血流量 (MBF)和 MBF储备。　　结果 :在 40个心室壁运动异常的心肌节段与 42个心室壁收缩功能正常的心肌节段之间 ,静息心室壁和心内膜下血流均无明显差异 ,但后者的心室壁和心内膜下血流储备均明显低于前者。静息状态 % WT与 MBF储备密切相关 (P<0 .0 0 1)。　　结论 :在静息状态血流无限制的慢性冠脉狭窄犬 ,% WT异常心肌节段的 MBF储备明显降低 ,静息状态 % WT与MBF储备密切相关 ,表明局部收缩功能异常可能是由于反复“需氧增多”性心肌缺血所致。

关键词：心肌血流储备冠状动脉狭窄静息心肌收缩功能

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载硫化氢气体超声微泡的制备及其性能评价

南方医科大学学报 2015年第12期35卷 1672-1677页

作者：陈钢彬杨莉李新忠钟林涛吴爵非宾建平南方医科大学南方医院心内科广东广州510515 南方医科大学南方医院药学部广东广州510515

目的制备一种新型的载硫化氢气体的脂质微泡(HSMB)并评价其理化特性和超声显影能力。方法硫化氢和全氟丙烷按4∶0、3∶1、2∶2、1∶3和0∶4混合后,机械震荡法制备5种载相应混合气体的HSMB,即HSMB4∶0、HSMB3∶1、HSMB2∶2、HSMB1∶3和HS... 详细信息

目的制备一种新型的载硫化氢气体的脂质微泡(HSMB)并评价其理化特性和超声显影能力。方法硫化氢和全氟丙烷按4∶0、3∶1、2∶2、1∶3和0∶4混合后,机械震荡法制备5种载相应混合气体的HSMB,即HSMB4∶0、HSMB3∶1、HSMB2∶2、HSMB1∶3和HSMB0∶4。检测微泡的粒径及浓度并评价其稳定性,优化气体混合比例。选取优化的混合气体制备的HSMB,观察超声辐照对微泡浓度及下清液中硫化氢浓度的影响;观察大鼠心肌及肾脏的超声显影效果。结果 HSMB外观呈乳白色,镜下呈球形结构,无聚集现象。HSMB4∶0和HSMB3∶1微泡初始浓度较HSMB2∶2明显减少(P0.05),72 h内浓度无变化(P>0.05)。超声辐照后,HSMB2∶2微泡浓度显著减少(P<0.05),而下清液中的硫化氢浓度明显增加(P<0.05)。HSMB2∶2静脉注射后获得良好的心脏及肾脏超声显影效果。结论硫化氢和全氟丙烷以2∶2混合制备的HSMB浓度高、稳定性良好,可在超声辐照下释放硫化氢,具有良好的超声显像效果,有望实现硫化氢气体可视化靶向传输。

关键词：微泡超声硫化氢

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原发性干燥综合征辨证因子的分级量化研究

中国民族民间医药 2017年第20期26卷 4-6页

作者：金亮甘建平吴斌重庆市中医院风湿科重庆400021 雅安职业技术学院四川雅安625000

目前,原发性干燥综合征的中医证候量化体系亟待完善,为此从量化分级的必要性、辨证因子的选取、分级量化的制定原则,从定性、定位、主症、次症等角度确定了该病的24个辨证因子,拟定出轻、中、重3个等级的评分细则,以期为干燥综合征的病... 详细信息

目前,原发性干燥综合征的中医证候量化体系亟待完善,为此从量化分级的必要性、辨证因子的选取、分级量化的制定原则,从定性、定位、主症、次症等角度确定了该病的24个辨证因子,拟定出轻、中、重3个等级的评分细则,以期为干燥综合征的病情与疗效评估提供参考。

关键词：原发性干燥综合征辨证因子分级量化评分细则