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Biocompatible reduced graphene oxide stimulated BMSCs induce acceleration of bone remodeling and orthodontic tooth movement through promotion on osteoclastogenesis and angiogenesis

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Bioactive Materials 2022年第9期7卷 409-425页

作者： delong jiao Jing Wang Wenting Yu Ke Zhang Ning Zhang Lingyan Cao Xinquan Jiang Yuxing Bai Institute of Dental Research Beijing Stomatological Hospital&School of StomatologyCapital Medical UniversityBeijing100050China Department of Orthodontics Beijing Stomatological Hospital&School of StomatologyCapital Medical UniversityBeijing100050China Department of Prosthodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai200011China

We has synthesized the biocompatible gelatin reduced graphene oxide(GOG)in previous research,and in this study we would further evaluate its effects on bone remodeling in the aspects of osteoclastogenesis and angiogenesis so as to verify its impact on accelerating orthodontic tooth movement.The mouse orthodontic tooth movement(OTM)model tests in vivo showed that the tooth movement was accelerated in the GOG local injection group with more osteoclastic bone resorption and neovascularization compared with the PBS injection group.The analysis on the degradation of GOG in bone marrow stromal stem cells(BMSCs)illustrated its good biocompatibility in vitro and the accumulation of GOG in spleen after local injection of GOG around the teeth in OTM model in vivo also didn’t influence the survival and life of animals.The co-culture of BMSCs with hematopoietic stem cells(HSCs)or human umbilical vein endothelial cells(HUVECs)in transwell chamber systems were constructed to test the effects of GOG stimulated BMSCs on osteoclastogenesis and angiogenesis in vitro.With the GOG stimulated BMSCs co-culture in upper chamber of transwell,the HSCs in lower chamber manifested the enhanced osteoclastogenesis.Meanwhile,the co-culture of GOG stimulated BMSCs with HUVECs showed a promotive effect on the angiogenic ability of HUVECs.The mechanism analysis on the biofunctions of the GOG stimulated BMSCs illustrated the important regulatory effects of PERK pathway on osteoclastogenesis and angiogenesis.All the results showed the biosecurity of GOG and the biological functions of GOG stimulated BMSCs in accelerating bone remodeling and tooth movement.

关键词： Bone remodeling Reduced graphene oxide Angiogenesis Osteoclastogenesis Orthodontic tooth movement

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Overcoming Resistance to Drugs Targeting KRAS^(G12C) Mutation

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The Innovation 2020年第2期1卷 71-81页

作者： delong jiao Shengyu Yang Department of Cellular and Molecular Physiology Penn State College of MedicineHersheyPA 17033USA

Activating KRAS mutations are present in 25%of human cancer.Although oncogenic Ras was deemed“undruggable”in the past,recent efforts led to the development of pharmacological inhibitors targeting the KRAS^(G12C) mutant,which have shown promise in early clinical trials.The development of allele-specific K-Ras^(G12C) inhibitors marked a new chapter in targeting oncogenic KRAS mutant in cancer.However,drug resistance against these new drugs will likely limit their efficacy in the clinic.Genome-wide approaches have been used to interrogate the mechanisms of resistance to K-Ras^(G12C ) inhibitors,which would facilitate the development of therapeutics overcoming drug resistance.This article reviews the latest progress in resistance to K-Ras^(G12C)-targeted therapies and aims to provide insight in future research targeting drug resistance in cancer.

关键词： ONCOGENE KRAS INHIBITOR TARGETED THERAPY DRUG RESISTANCE

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Bidirectional differentiation of BMSCs induced by a biomimetic procallus based on a gelatin-reduced graphene oxide reinforced hydrogel for rapid bone regeneration

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Bioactive Materials 2021年第7期6卷 2011-2028页

作者： delong jiao Ao Zheng Yang Liu Xiangkai Zhang Xiao Wang Jiannan Wu Wenjun She Kaige Lv Lingyan Cao Xinquan Jiang Department of Prosthodontics Shanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyNational Clinical Research Center for Oral DiseasesShanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineChina The State Key Laboratory of Bioreactor Engineering East China University of Science and Technology130 Meilong RoadShanghai 200237China

Developmental engineering strategy needs the biomimetic composites that can integrate the progenitor cells,biomaterial matrices and bioactive signals to mimic the natural bone healing process for faster healing and reconstruction of segmental bone defects.We prepared the gelatin-reduced graphene oxide(GOG)and constructed the composites that mimicked the procallus by combining the GOG with the photo-crosslinked gelatin hydrogel.The biological effects of the GOG-reinforced composites could induce the bi-differentiation of bone marrow stromal cells(BMSCs)for rapid bone repair.The proper ratio of GOG in the composites regulated the composites’mechanical properties to a suitable range for the adhesion and proliferation of BMSCs.Besides,the GOG-mediated bidirectional differentiation of BMSCs,including osteogenesis and angiogenesis,could be activated through Erk1/2 and AKT pathway.The methyl vanillate(MV)delivered by GOG also contributed to the bioactive signals of the biomimetic procallus through priming the osteogenesis of BMSCs.During the repair of the calvarial defect in vivo,the initial hypoxic condition due to GOG in the composites gradually transformed into a well-vasculature robust situation with the bi-differentiation of BMSCs,which mimicked the process of bone healing resulting in the rapid bone regeneration.As an inorganic constituent,GOG reinforced the organic photo-crosslinked gelatin hydrogel to form a double-phase biomimetic procallus,which provided the porous extracellular matrix microenvironment and bioactive signals for the bi-directional differentiation of BMSCs.These show a promised application of the bio-reduced graphene oxide in biomedicine with a developmental engineering strategy.

关键词： Biomimetic procallus Bio-reduced graphene oxide Photo-crosslinked gelatin hydrogel Methyl vanillate Developmental engineering

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Computed tomography radiogenomics:A potential tool for prediction of molecular subtypes in gastric stromal tumor

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1296-1308页

作者： Xiao-Nan Yin Zi-Hao Wang Li Zou Cai-Wei Yang Chao-Yong Shen Bai-Ke Liu Yuan Yin Xi-jiao Liu Bo Zhang Gastric Cancer Research Center West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Paediatric Surgery West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Radiology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Gastrointestinal Surgery Sichuan University West China HospitalChengdu 610041Sichuan ProvinceChina

BACKGROUND Preoperative knowledge of mutational status of gastrointestinal stromal tumors(GISTs)is essential to guide the individualized precision therapy.AIM To develop a combined model that integrates clinical and contrast-enhanced computed tomography(CE-CT)features to predict gastric GISTs with specific genetic mutations,namely KIT exon 11 mutations or KIT exon 11 codons 557-558 deletions.METHODS A total of 231 GIST patients with definitive genetic phenotypes were divided into a training dataset and a validation dataset in a 7:3 ratio.The models were constructed using selected clinical features,conventional CT features,and radiomics features extracted from abdominal CE-CT images.Three models were developed:ModelCT sign,modelCT sign+rad,and model CTsign+rad+clinic.The diagnostic performance of these models was evaluated using receiver operating characteristic(ROC)curve analysis and the delong test.RESULTS The ROC analyses revealed that in the training cohort,the area under the curve(AUC)values for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic)for predicting KIT exon 11 mutation were 0.743,0.818,and 0.915,respectively.In the validation cohort,the AUC values for the same models were 0.670,0.781,and 0.811,respectively.For predicting KIT exon 11 codons 557-558 deletions,the AUC values in the training cohort were 0.667,0.842,and 0.720 for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic),respectively.In the validation cohort,the AUC values for the same models were 0.610,0.782,and 0.795,respectively.Based on the decision curve analysis,it was determined that the model_(CT sign+rad+clinic)had clinical significance and utility.CONCLUSION Our findings demonstrate that the combined modelCT_(sign+rad+clinic)effectively distinguishes GISTs with KIT exon 11 mutation and KIT exon 11 codons 557-558 deletions.This combined model has the potential to be valuable in assessing the genotype of GISTs.

关键词： Gastrointestinal stromal tumor Radiomics Gene mutation Computed tomography Model

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NOD2 和 TLR2 ligands 由在遗传性过敏症的像皮炎的皮肤发炎与真皮的成纤维细胞交往触发 basophils 和嗜曙红血球的激活

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Cellular & Molecular Immunology 2016年第4期13卷 535-550页

作者： delong jiao Chun-Kwok Wong Huai-Na Qiu Jie Dong Zhe Cai Man Chu Kam-Lun Hon Miranda Sin-Man Tsang Christopher Wai-Kei Lam Department of Chemical Pathology The Chinese University of Hong Kong Prince of Wales Hospital Shatin NT Hong Kong China Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China The Chinese University of Hong Kong Hong Kong China Department of Paediatrics The Chinese University of Hong Kong Prince of Wales Hospital Shatin NT Hong Kong China State Key Laboratory of Quality Research in Chinese Medicine Macao institute for Applied Research in Medicine and Health Macao University of Science and Technology Taipa Macao People's Republic of China

The skin of patients with atopic dermatitis （AD） has a unique predisposition for colonization by Staphylococcus aureus （S. aureus）, which contributes to the inflammation and grim prognosis of AD. Although the mechanism underlying the S. aureus-induced exacerbation of AD remains unclear, recent studies have found a pivotal role for pattern recognition receptors in regulating the inflammatory responses in S. aureus infection. In the present study, we used a typical mouse model of AD-like skin inflammation and found that S. aureus-associated nucleotide-binding oligomerization domain-containing protein 2 （NOD2） and toll-like receptor 2 （TLR2） ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. Subsequent histological analyses revealed that dermal fibroblasts were pervasive in the AD-like skin lesions, Co-culture of human dermal fibroblasts with basophils and eosinophils resulted in a vigorous cytokine/chemokine response to the NOD2/TLR2 ligands and the enhanced expression of intercellular adhesion molecule-1 on the dermal fibroblasts. Basophils and eosinophils were primarily responsible for the AD-related cytokine/chemokine expression in the co-cultures. Direct intercellular contact was necessary for the crosstalk between basophils and dermal fibroblasts, while soluble mediators were sufficient to mediate the eosinophil-fibroblast interactions. Moreover, the intracellular p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and nuclear factor-kappa B signaling pathways were essential for NOD2/TLR2 ligand-mediated activation of basophils, eosinophils, and dermal fibroblasts in AD-related inflammation. This study provides the evidence of NOD2/TLR2-mediated exacerbation of AD through activation of innate immune cells and therefore sheds light on a novel mechanistic pathway bv which S. aureus contributes to the DathoDhvsiology of AD.

关键词： atopic dermatitis basophils, eosinophils NOD2 TLR2

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高校本科生创新训练项目培育路径研究——以内蒙古牧区乳业发展创新项目为例

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创新创业理论研究与实践 2024年第3期7卷 188-192页

作者：李德龙王晓婷张可管歆怡刘娇内蒙古财经大学工商管理学院内蒙古呼和浩特010070 内蒙古财经大学财政税务学院内蒙古呼和浩特010070 内蒙古财经大学会计学院内蒙古呼和浩特010070 内蒙古财经大学外国语学院内蒙古呼和浩特010070

高校本科生创新训练项目的培育是一项系统性育人工程,不仅要做到“以本为本”和“以学生为中心”,还需回归高校创新教育的本质要求。该文以内蒙古牧区乳业发展创新训练项目为例,在“竞赛导向+理论融合+家国情怀”的基本育人思路下,借助... 详细信息

高校本科生创新训练项目的培育是一项系统性育人工程,不仅要做到“以本为本”和“以学生为中心”,还需回归高校创新教育的本质要求。该文以内蒙古牧区乳业发展创新训练项目为例,在“竞赛导向+理论融合+家国情怀”的基本育人思路下,借助第九届中国国际“互联网+”大学生创新创业大赛的评分标准,从教育维度、创新维度、团队维度、商业维度和社会价值维度5个方面,探讨了“以赛促学”视角下本科生创新训练项目的基本培育思路,即本科生创新项目培育要注重高校教育成果的延展性、注重项目与高校和地区需求的统一、注重项目的阶段性和成员的互补性、注重创新初心的回归、注重扩大就业和回馈家乡。

关键词：创新训练项目 “以赛促学” 以本为本以学生为中心 “互联网+” 乳业

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基于单细胞组学预测肝内胆管癌根治性切除患者预后的研究

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中华外科杂志 2024年第4期62卷 316-323页

作者：陈家璐唐玥覃德龙李宗龙汤朝晖全志伟上海交通大学医学院附属新华医院普外科上海200092

目的:基于单细胞组学分析肝内胆管癌(ICC)根治性切除术后患者的生存获益。方法:本研究为回顾性病例系列研究。整合基因表达综合数据库中4个数据集的ICC单细胞测序结果,共获得46例患者根治性切除样本,探索ICC微环境的特征。同时分析附有... 详细信息

目的:基于单细胞组学分析肝内胆管癌(ICC)根治性切除术后患者的生存获益。方法:本研究为回顾性病例系列研究。整合基因表达综合数据库中4个数据集的ICC单细胞测序结果,共获得46例患者根治性切除样本,探索ICC微环境的特征。同时分析附有生存数据的EMBI数据库共100例ICC组织芯片数据,通过ssGSEA算法计算芯片数据每个样本中各个上皮细胞亚群的浸润丰度,探索与患者较差预后相关的关键上皮细胞亚群,并研究该亚群关键标志(marker)基因的临床价值。通过单因素与多因素 Cox 比例风险模型筛选预后相关marker基因,使用目标基因构建 Cox比例风险模型并绘制列线图,使用Kaplan-Meier 生存分析验证评分与患者预后的关系,通过受试者工作特征(ROC)曲线、校准曲线及决策曲线(DCA)对模型预测效能进行评估。结果:上皮细胞亚群几乎仅在肿瘤组织中浸润。表达 MT2A的上皮细胞亚群与患者更差的预后相关且浸润丰度很高,以该亚群浸润为特征的患者被定义为抗氧化型。经单因素与多因素Cox比例风险模型筛选该亚群的marker基因,其中 FILPIL、 NAKBIA、 PEG10、 SERPINB5是患者的独立预后因素。用这4个基因表达量构建Cox比例风险模型,根据该模型所区分的高风险组患者的术后1、3、5年总体生存率均低于低风险组患者( P值均<0.05);所构建的列线图具有较好的区分度及有效性。ROC曲线显示,模型1、3、5年预测的曲线下面积分别为0.779、0.844、0.845;经校准曲线与DCA检验,对比临床指标,该模型具有较好的预测效能。结论:MT2A阳性上皮细胞亚群与ICC患者根治性切除术后的生存获益相关,可将ICC组织分为抗氧化型与非抗氧化型,抗氧化型预示患者预后较差,可考虑通过术后辅助治疗等手段改善生存。

关键词：肝肿瘤外科手术单细胞组学预后模型抗氧化型

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重视代谢功能障碍相关性脂肪性肝病相关肝内胆管癌的研究

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中国普通外科杂志 2024年第2期33卷 176-183页

作者：李宗龙陈家璐唐玥覃德龙汤朝晖全志伟上海交通大学医学院附属新华医院普通外科上海200092

过去20年中,代谢障碍相关性脂肪性肝病(MAFLD)的全球发病率急剧上升,影响着全球30%以上的人口。同时,过去40年全球肝内胆管癌(ICC)的发病率也增长了140%。此外,既往研究表明,多种形式的肝脏炎症都与ICC发生发展密切相关。这提示MAFLD在... 详细信息

过去20年中,代谢障碍相关性脂肪性肝病(MAFLD)的全球发病率急剧上升,影响着全球30%以上的人口。同时,过去40年全球肝内胆管癌(ICC)的发病率也增长了140%。此外,既往研究表明,多种形式的肝脏炎症都与ICC发生发展密切相关。这提示MAFLD在ICC的发生、发展及预后等方面可能起着重要作用。本文旨在梳理MAFLD相关ICC的研究现状,回顾现有研究的不足之处,并展望未来的研究方向,为相关研究的进一步开展和深入提供基础。

关键词：胆管肿瘤胆管,肝内代谢障碍相关性脂肪性肝病

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基于三种机器学习方法的慢性阻塞性肺疾病人群早筛模型的建立与验证

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现代预防医学 2024年第9期51卷 1677-1683页

作者：母应姣王子云苏旭李凌周婕王艺颖刘涛贵州医科大学公共卫生与健康学院环境污染与疾病监控教育部重点实验室贵州省疾病预防控制中心

目的构建慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）患者筛检模型。方法采用多阶段分层随机抽样的方法，抽取贵州省≥40岁的常住居民4 587名，对其进行问卷调查、体格检查及肺功能检查。经过单因素分析初步筛... 详细信息

目的构建慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）患者筛检模型。方法采用多阶段分层随机抽样的方法，抽取贵州省≥40岁的常住居民4 587名，对其进行问卷调查、体格检查及肺功能检查。经过单因素分析初步筛选模型纳入变量，经多因素logistic回归确定最终纳入变量。分别应用logistic回归（logistic regression,LR）、随机森林（random forest,RF）、支持向量机（support vector machine,SVM）构建COPD患者筛检模型，使用受试者工作曲线下面积（area under the curve,AUC）评价模型效果。使用delong法检验模型之间AUC的差异。结果根据多因素logistic回归分析结果，本研究将年龄、14岁前经常咳嗽、哮喘、每日吸烟量（支）、烹饪燃料与排风、有害气体暴露6种因素纳入LR、RF、SVM模型。三种模型训练集AUC分别为73.64%、87.14%、73.30%，测试集AUC分别为76.10%、70.96%、76.08%，均具有较好的筛检效果。delong法结果显示，三种模型的筛检效果在训练集与测试集均存在一定差异。结论本研究通过年龄、哮喘等6个简单变量建立经济、快捷且有效的COPD患者筛检模型。

关键词： Logistic回归随机森林支持向量机慢性阻塞性肺疾病筛检

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Protein & Cell 2016年第7期7卷 538-543页

作者： Yuan-Qin Yang Wen-Jie Dong Xiao-Fei Yin Yan-Ni XU Yu Yang jiao-jiao Wang Su-Jing Yuan Jing Xiao Jonathan Howard delong Liang Chu Hai-Neng Xu Xiu- Mei Zhou Ru-Wei Wang Ling Fang Xin-Yuan Liu Kang-Jian Zhang Xinyuan Institute of Medicine and Biotechnology Zhejiang Sci-Tech University Hangzhou 310018 China State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China Sichuan Huiyang Life Science and Technology Corp. Chengdu 610021 China College of Life Sciences Northwest Agriculture and Forestry University Yangling 712100 China Central China Normal University Wuhan 430079 China Department of Pathobiology School of Veterinary Medicine University of Pennsylvania Philadelphia PA 19104 USA Department of Radiation Oncology University of Pennsylvania Perelman School of Medicine 3400 Civic Center Blvd. Philadelphia PA 19104 USA Zhejiang Conba Pharmaceutical Co. Ltd Hangzhou 310018 China

Dear Editor, PD-L1, also known as CD274, plays a vital role in tumor cell related immune escape. It can be expressed on the cell surface of many solid tumors （Brahmer et al., 2012） and inhibits T cell proliferation and cytokine production by bind- ing to the Tcell surface receptor programmed death 1 （PD-1） or B7-1 （McClanahan et al., 2015）. In 2013, targeting PD-1/ PD-L1 signaling for cancer immunotherapy was selected as the No.1 scientific breakthrough of the year by the editors of Science. Interferons （IFNs） are a group of pleiotropic cytokines, demonstrated anti-viral, anti-tumor, and immune regulatory functions （York et al., 2015）. Type I interferon binds a heterodimeric receptor composed of IFNAR1 and IFNAR2. This activates a canonical JAK/STAT signaling pathway that ultimately induces a set of interferon-stimulated genes to exert its biological activity （Ejlerskov et al., 2015）. Recently, PD-L1 was reported to be downstream of IFN signaling in human oral squamous carcinoma, melanoma, and human acute myeloid leukemia blast cells （Chen et al., 2012; Furuta et al., 2014; Kronig et al., 2014）.

关键词： B16F10 Cell Acute Myeloid Leukemia Blast Murine B16F10 Melanoma Cell B16F10 Tumor Cell Syngeneic Splenocytes

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