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Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer

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Journal of Innovative Optical Health Sciences 2024年第1期17卷 87-103页

作者： Shan Long Yibing zhao Yuanyuan Xu Bo Wang Haixia Qiu hongyou zhao Jing Zeng Defu Chen Hui Li Jiakang Shao Xiaosong Li Ying Gu School of Medicine Nankai University Tianjin300072P.R.China Department of Laser Medicine The First Medical Center of Chinese PLA General Hospital Beijing 100853 P.R.China Department of Oncology The Seventh Medical Center of Chinese PLA General Hospital Beijing 100039 P.R.China School of Basic Medicine Guizhou Medical University Guiyang 550025GuizhouP.R.China College of Medical Technology Beijing Institute of Technology Beijing 100081P.R.China Medical School of Chinese PLA Beijing 100853 P.R.China

Photodynamic therapy(PDT)has limited effects in treating metastatic breast *** checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is *** study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and *** checkpoints on T cells were analyzed byflow cytometry after *** combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were *** HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be *** checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT *** PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with ***-PDT could not combat metastatic breast ***1 and LAG-3 were upregulated after ***-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.

关键词： Photodynamic therapy anti-PD1 antibody anti-LAG-3 antibody anti-tumor im-mune effects metastatic breast cancer

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Immune response induced by hematoporphyrin derivatives mediated photodynamic therapy:Immunogenic cell death and elevated costimulatory molecules

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Journal of Innovative Optical Health Sciences 2022年第4期15卷 49-60页

作者： Shan Long Yibing zhao Yuanyuan Xu Hui Li hongyou zhao Defu Chen Jing Zeng Haixia Qiu Xiaosong Li Ying Gu School of Medicine Nankai University Tianjin 300072P.R.China Department of Laser Medicine The First Medical Center of Chinese PLA General Hospital Beijing 100853 P.R.China Department of Oncology The Seventh Medical Center of Chinese PLA General Hospital Beijing 100039 P.R.China College of Medical Technology Beijing Institute of Technology Beijing 100081P.R.China

Photodynamic therapy(PDT)not only destroys tumor cells directly but also induced anti-tumor immune response through damage-associated molecular patterns(DAMPs).It is reported that anti-tumor response was associated with light dose and photosensitizer used in *** this study,4T1 tumor cells were implanted on both the right and left flanks of *** the right tumor was treated by HpD-PDT,while the left tumor was not *** anti-tumor immune response induced by HpD-PDT was *** expression of DAMPs and costimulatory molecules induced by HpD-PDT were tested by immuno fluorescence and flow cytometry in *** light doses of PDT were designed to treat 4T1 *** killing effect was assessed by CCK-8 kit and apoptosis *** expression of DAMPs on 4T1 cells after HpDPDT were evaluated by flow cytometry,western blot and ATP *** study showed that CD4^(+)T,CD8^(+)T and the production of IFN-γwere increased significantly on day 10 in righttumor after PDT treatment compared with control ***-PDT enhanced the expression of calreticulin(CRT)on tumor ***,co-stimulatory molecular OX-40 and 4-1BB were elevated on CD8^(+)T *** vitro,immunogenic death of 4T1 cells was induced after ***,the expression of DAMPs increased with the increasing of energy *** study indicates that anti-tumor immune effect was induced by *** knowledge of the involvement of CRT,ATP and co-stimulatory molecules uncovers important mechanistic insight into the anti-tumor *** was the first time that co-stimulatory molecules were investigated and found to elevate after PDT.

关键词： Photodynamic therapy hematoporphyrin derivatives anti-tumor immune effect immunogenic cell death costimulatory molecule

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国产龙血竭基原植物类黄酮3'-羟化酶基因(F3'H)克隆及表达分析

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分子植物育种 2024年第19期22卷 6310-6317页

作者：李爽赵宏友杨春勇王艳芳李戈彭建明严珍王延谦中国医学科学院北京协和医学院药用植物研究所云南分所云南省南药可持续利用研究重点实验室景洪666100

类黄酮3'-羟化酶(flavonoid 3'-hydroxylase,F3'H)作为植物类黄酮代谢的关键酶之一,参与龙血树中龙血竭树脂的生物合成。为了揭示国产龙血竭基原龙血树中F3'H基因序列和表达模式等信息,本研究以剑叶龙血树、海南龙血树和岩棕为研究对象... 详细信息

类黄酮3'-羟化酶(flavonoid 3'-hydroxylase,F3'H)作为植物类黄酮代谢的关键酶之一,参与龙血树中龙血竭树脂的生物合成。为了揭示国产龙血竭基原龙血树中F3'H基因序列和表达模式等信息,本研究以剑叶龙血树、海南龙血树和岩棕为研究对象,采用同源克隆法克隆3种龙血竭基原植物的F3'H基因序列并进行生物信息学分析,利用实时荧光定量PCR(RT-qPCR)法分析其在不同组织的表达量。结果表明,在3种龙血树中均获得一条编码区长1533 bp的F3'H基因序列,编码510个氨基酸残基。生物信息学分析表明,它们的序列同源性达到99.57%,氨基酸序列的理化性质、二级结构和三级结构几乎完全一致。系统进化分析表明龙血树属植物F3'H基因聚为一支且进化上非常接近,在F3'H进化树上龙血树属并未与同科植物聚为一类,单子叶植物和双子叶植物亦并未分别聚为一类。RT-qPCR分析发现,剑叶龙血树中F3'H在茎中的表达量远高于根和叶,海南龙血树和岩棕中F3'H在茎中的表达量低于根和叶。本研究有利于揭示F3'H在龙血竭生物合成中的潜在作用,为龙血竭人工结脂技术开发提供一定分子基础。

关键词：龙血树龙血竭类黄酮3'-羟化酶

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Comparative study on Photobiomodulation between 630 nm and 810 nm LED in diabetic wound healing both in vitro and in vivo

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Journal of Innovative Optical Health Sciences 2022年第2期15卷 58-67页

作者： hongyou zhao Tengda Ji Tianzhen Sun Haolin Liu Yidi Liu Defu Chen Ying Wang Yizhou Tan Jing Zeng Haixia Qiu Ying Gu Department of Laser Medicine The First Medical Centre Chinese PLA General Hospital Beijing 100853P.R.China Institute of Engineering Medicine Beijing Institute of Technology Beijing 100081P.R.China Precision Laser Medical Diagnosis and Treatment Innovation Unit Chinese Academy of Medical Sciences Beijing 100000P.R.China Medical School of Chinese PLA Beijing 100853P.R.China

Photobiomodulation(PBM)promoting wound healing has been demonstrated by many ***,630 nm and 810 nm light-emitting diodes(LEDs),as light sources,are frequently used in the treatment of diabetic foot ulcers(DFUs)in ***,the dose-effect relationship of LED-mediated PBM is not fully ***,among the 630 nm and 810 nm LEDs,which one gets a better effect on accelerating the wound healing of diabetic ulcers is not *** aim of this study is to evaluate and compare the effects of 630 nm and 810 nm LED-mediated PBM in wound healing both in vitro and in *** results showed that both 630 nm and 810 nm LED irradiation significantly promoted the proliferation of mouse fibroblast cells(L929)at different light irradiances(1,5,and 10 mW/cm^(2)).The cell proliferation rate increased with the extension of irradiation time(100,200,and 500 s),but it decreased when the irradiation time was over 500 *** 630 nm and 810nm LED irradiation(5 mW/cm^(2))significantly improved the migration capability of L929 *** difference between 630 nm and 810 nm LED-mediated PBM in promoting cell proliferation and migration was *** vivo results presented that both 630 nm and 810 nm LED irradiation promoted the wound healing and the expression of the vascular endothelial growth factor(VEGF)and transforming growth factor(TGF)in the wounded skin of type 2 diabetic ***,these results suggested that LED-mediated PBM promotes wound healing of diabetic mice through promoting fibroblast cell proliferation,migration,and the expression of growth factors in the wounded ***(630 nm and 810 nm)have a similar outcome in promoting wound healing of type 2 diabetic mice.

关键词： Photobiomodulation(PBM) light-emitting diode(LED) wound healing diabetic ulcers

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Cyclin G2,a novel target of sulindac to inhibit cell cycle progression in colorectal cancer

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Genes & Diseases 2021年第3期8卷 320-330页

作者： hongyou zhao Bin Yi Zhipin Liang Ches’Nique Phillips Hui-Yi Lin Adam I.Riker Yaguang Xi Department of Genetics and Stanley S.Scott Cancer Center Louisiana State University Health Sciences CenterNewOrleans70112USA School of Public Health Louisiana State University Health Sciences CenterNew Orleans70112USA Geaton and JoAnn DeCesaris Cancer Institute Anne Arundel Medical CenterLuminis HealthAnnapolisMD21401USA

Sulindac has shown significant clinical benefit in preventing colorectal cancer pro-gression,but its mechanism of action has not been fully *** have found that sulin-dac sulfide(SS)is able to inhibit cell cycle progression in human colorectal cancer cells,particularly through G1 *** understand the underlying mechanisms of sulindac inhibitory activity,we have demonstrated that Cyclin G2 up-regulation upon SS treatment can substan-tially delay cell cycle progression by enhancing the transcriptional activity of FOXO3a in human colorectal tumor ***-182,an oncogenic microRNA known to inhibit FOXO3a gene expres-sion,is also involved in the suppressive effect of SS on cell cycle *** process be-gins with the down-regulation of miR-182,followed by the enhancement of FOXO3a transcriptional activity and the up-regulation of Cyclin *** further determine the clinical utility of this axis,we analyzed the expression of miR-182/FOXO3a/Cyclin G2 in human colo-rectal tumor *** results show not only that there are significant dfferences in miR-182/FOXO3a/Cyclin G2 between tumors and normal tissues,but also that the synergetic effect of miR-182 and FOXO3a is associated with predicting tumor *** study dem-onstrates a novel mechanistic axis consisting of miR-182/FOXO3a/Cyclin G2 that mediates su-lindac inhibition of cell cycle progression.

关键词： Cell cycle Colorectal cancer Gene regulation miRNA Sulindac

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无创光疗调控真皮成纤维细胞在糖尿病足溃疡愈合的研究进展

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中国激光医学杂志 2024年第3期33卷 164-170页

作者：王子萱冀全博赵洪友王颖曾晶顾瑛邱海霞解放军医学院北京市100853 中国人民解放军总医院第一医学中心激光医学科中国人民解放军总医院第四医学中心骨科学部北京理工大学医学技术学院

糖尿病足(diabetic foot,DF)是糖尿病最严重的慢性并发症之一,糖尿病足溃疡(diabetic foot ulcers,DFUs)对糖尿病患者的截肢率和存活率有着直接影响。作为真皮最丰富的细胞,真皮成纤维细胞在糖尿病足溃疡的愈合过程中发挥着关键作用。... 详细信息

糖尿病足(diabetic foot,DF)是糖尿病最严重的慢性并发症之一,糖尿病足溃疡(diabetic foot ulcers,DFUs)对糖尿病患者的截肢率和存活率有着直接影响。作为真皮最丰富的细胞,真皮成纤维细胞在糖尿病足溃疡的愈合过程中发挥着关键作用。目前对于糖尿病足溃疡缺乏特异有效的治疗方法,增加真皮成纤维细胞的功能促进溃疡愈合是一种有效的治疗策略。无创光疗(non-damage phototherapy,NDPT)作为一种无创、无毒副作用、非接触式的新辅助治疗方法,在糖尿病足溃疡的治疗中极具应用潜力。本文就糖尿病足溃疡中真皮成纤维细胞的异常改变及无创光疗通过调控真皮成纤维细胞治疗糖尿病足的基础和临床研究进展进行综述。

关键词：糖尿病足溃疡成纤维细胞无创光疗光生物调节

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316L不锈钢波纹管腐蚀失效分析

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金属热处理 2015年第7期40卷 183-186页

作者：赵洪友中冶京城(秦皇岛)工程技术有限公司河北秦皇岛066004

采用光学显微镜、场发射扫描电镜(FESEM)及EDS能谱仪、X射线衍射仪、硬度计等对腐蚀失效316L不锈钢波纹管显微组织、表面形貌、腐蚀前后的物相及显微硬度进行了分析。结果表明,腐蚀失效316L不锈钢波纹管显微组织中的相组成为奥氏体和少... 详细信息

采用光学显微镜、场发射扫描电镜(FESEM)及EDS能谱仪、X射线衍射仪、硬度计等对腐蚀失效316L不锈钢波纹管显微组织、表面形貌、腐蚀前后的物相及显微硬度进行了分析。结果表明,腐蚀失效316L不锈钢波纹管显微组织中的相组成为奥氏体和少量的铁素体,铁素体相在使用过程中最先被腐蚀是造成316L不锈钢波纹管的耐蚀性能下降的主要原因。316L不锈钢波纹管腐蚀表面含有较多铁的氧化物和硫化物以及铝的氧化物,蚀坑深度达30.6μm。

关键词： 316L不锈钢波纹管腐蚀失效显微组织

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窄带LED无创光疗对糖尿病足真皮成纤维细胞增殖及分泌功能的影响

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中国激光医学杂志 2024年第2期33卷 61-66,116,117页

作者：王子萱祝闽辉王颖王贺冉冀全博赵洪友褚万立顾瑛邱海霞解放军医学院北京市100853 中国人民解放军总医院第一医学中心激光医学科中国人民解放军总医院第四医学中心烧伤整形医学部中国人民解放军总医院第二医学中心老年医学研究所中国人民解放军总医院第四医学中心骨科医学部北京理工大学医学技术学院

目的研究窄带发光二极管(light emitting diode,LED)无创光疗对糖尿病足真皮成纤维细胞(diabetic foot dermal fibroblasts,DFFs)增殖和分泌功能的影响。方法将糖尿病足溃疡患者的足部皮肤标本使用酶消化法原代分离培养获得DFFs,采用细... 详细信息

目的研究窄带发光二极管(light emitting diode,LED)无创光疗对糖尿病足真皮成纤维细胞(diabetic foot dermal fibroblasts,DFFs)增殖和分泌功能的影响。方法将糖尿病足溃疡患者的足部皮肤标本使用酶消化法原代分离培养获得DFFs,采用细胞免疫荧光实验进行成纤维细胞鉴定。以DFFs为研究对象,实验分为两部分:(1)窄带LED对DFFs细胞增殖情况的影响。细胞增殖实验分为3组,分别为非光疗组(A组)即仅接种细胞但不进行LED光照;光疗组(B组),采用波长630 nm,带宽16 nm,功率密度10 mW/cm^(2)的LED光分别照射60 s、100 s、500 s、1000 s、2000 s和2500 s。空白对照组(C组)即不接种细胞也不进行LED光照。各组处理后24 h检测细胞吸光度计算各组细胞活力以评估增殖情况。(2)窄带LED对DFFs细胞因子分泌的影响。实验分为光疗组和非光疗组两组,优选促进DFFs增殖作用最强的光剂量作为光疗组的光剂量;非光疗组不进行光照,两组干预后12 h,比较两组DFFs分泌转化生子因子-β1(transforming growth factor-beta 1,TGF-β1)、基质金属蛋白酶抑制剂1(matrix metalloproteinase inhibitor 1,TIMP1)和血管生成素(angiopoietin 1,Ang1)的差异。结果(1)细胞免疫荧光鉴定发现酶消化法分离培养的原代DFFs中成纤维细胞纯度接近100%。(2)窄带LED照射DFFs细胞后细胞增殖情况。光疗组(B组)的细胞增殖随照射时间的增加先升高达到最大值后开始降低。光疗组(B组)中以波长630nm,功率密度10 mW/cm^(2)的LED照射500 s和1000 s时能够促进原代培养的DFFs的增殖,与非光疗组(A组)比较差异具有统计学意义(P0.05)。结论窄带LED无创光疗可以促进DFFs增殖,并增加与成纤维细胞增殖相关的因子TGF-β1、血管生成相关的因子Ang1的分泌。

关键词：窄带LED 无创光疗糖尿病足真皮成纤维细胞细胞因子

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浅谈汽车发动机捣缸事故

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山西焦煤科技 2007年第Z1期31卷 95-96页

作者：赵宏有山西焦煤集团公司西山公用事业总公司

分析了汽车发动机捣缸事故发生的5种常见原因,并提出了相应的预防措施,可为汽车驾驶人员和维修人员提供借鉴与参考,从而避免捣缸事故的发生。

关键词：汽车发动机捣缸事故发生原因预防措施

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Recycling arsenic-containing bio-leaching residue after thermal treatment in cemented paste backfill:Structure modification,binder properties and environmental assessment

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International Journal of Minerals,Metallurgy and Materials 2024年第10期31卷 2136-2147页

作者： Dengfeng zhao Shiyu Zhang Yingliang zhao Department of Mining Engineering Lyuliang UniversityLvliang 033000China School of Civil and Environmental Engineering University of Science and Technology BeijingBeijing 100083China School of Mining Engineering Taiyuan University of TechnologyTaiyuan 030024China Department of Civil and Environmental Engineering The Hong Kong Polytechnic UniversityHong Kong 00852China

The substantial arsenic(As)content present in arsenic-containing bio-leaching residue(ABR)presents noteworthy environ-mental challenges attributable to its inherent instability and susceptibility to *** its elevated calcium sulfate content,ABR exhibits considerable promise for industrial *** study delved into the feasibility of utilizing ABR as a source of sulfates for producing super sulfated cement(SSC),offering an innovative binder for cemented paste backfill(CPB).Thermal treatment at varying temperatures of 150,350,600,and 800℃ was employed to modify ABR’s *** investigation encompassed the examination of phase transformations and alterations in the chemical composition of As within ***,the hydration characteristics of SSC utilizing ABR,with or without thermal treatment,were studied,encompassing reaction kinetics,setting time,strength development,and *** findings revealed that thermal treatment changed the calcium sulfate structure in ABR,consequently impacting the resultant sample ***,calcination at 600℃ demonstrated optimal modification effects on both early and long-term strength *** enhanced performance can be attributed to the augmented formation of reaction products and a densified ***,the thermal treatment elicited modifications in the chemical As fractions within ABR,with limited impact on the As immobilization capacity of the prepared binders.

关键词： cemented paste backfill bio-leaching residue arsenic immobilization binder hydration calcination

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