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Injectable thermo-sensitive hydrogel enhances anti-tumor potency of engineered Lactococcus lactis by activating dendritic cells and effective memory T cells

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Bioactive Materials 2024年第7期37卷 331-347页

作者： Aoxing Chen Junmeng Zhu Rui liu Yi Mei Lin Li Yue Fan Yaohua Ke baorui liu Qin liu Department of Oncology Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese MedicineThe Clinical Cancer Institute of Nanjing University321 Zhongshan RoadNanjing210008China The Comprehensive Cancer Centre Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing University321 Zhongshan RoadNanjing210008China The Comprehensive Cancer Centre China Pharmaceutical University Nanjing Drum Tower Hospital321 Zhongshan RoadNanjing210008China

Engineered bacteria have shown great potential in cancer immunotherapy by dynamically releasing therapeutic payloads and inducing sustained antitumor immune response with the crosstalk of immune *** previous studies,FOLactis was designed,which could secret an encoded fusion protein of Fms-related tyrosine kinase 3 ligand and co-stimulator OX40 ligand,leading to remarkable tumor suppression and exerting an abscopal effect by intratumoral ***,it is difficult for intratumoral administration of FOLactis in solid tumors with firm texture or high internal *** patients without lesions such as abdominal metastatic tumors and orthotopic gastric tumors,intratumoral injection is not feasible and peritumoral maybe a better ***,an engineered bacteria delivery system is constructed based on in situ temperature-sensitive poloxamer 407 *** injection of FOLactis/P407 results in a 5-fold increase in the proportion of activated DC cells and a more than 2-fold increase in the proportion of effective memory T cells(TEM),playing the role of artificial lymph ***,administration of FOLactis/P407 significantly inhibits the growth of abdominal metastatic tumors and orthotopic gastric tumors,resulting in an extended survival ***,these findings demonstrate the delivery approach of engineered bacteria based on in situ hydrogel will promote the efficacy and universality of therapeutics.

关键词： Cancer immunotherapy Engineered bacteria Thermos-sensitive hydrogel Localized drug delivery Artificial lymph node

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A novel nomogram for predicting the prognosis of hepatocellular carcinoma patients following immune checkpoint inhibitors treatment beyond progression:a single center study based on Chinese population

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Hepatobiliary Surgery and Nutrition 2024年第5期13卷 771-787页

作者： Chao Chen Xiaoyuan Chu Hong liu Mingzhen Zhou Zhan Shi Anfeng Si Ying Zhao Xiufeng liu Jie Shen baorui liu Comprehensive Cancer Center Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjingChina Department of Oncology Jinling HospitalNanjing Medical UniversityNanjingChina Department of Cardiothoracic Surgery Nanjing Hospital Affiliated to Nanjing University of Chinese MedicineNanjingChina Department of Surgical Oncology of PLA Cancer Center Jinling HospitalNanjing Medical UniversityNanjingChina Department of Radiology Jinling HospitalNanjing Medical UniversityNanjingChina

Background:Hepatocellular carcinoma(HCC)persists as a dominant cause of cancer-related mortality globally,with a notably rapid escalation in mortality *** advent of immunotherapy,particularly immune checkpoint inhibitors(ICIs),has ushered in a new era in the management of liver cancer,albeit with unresolved challenges in the context of treatment beyond progression(TBP)and stratified prognosis in diverse *** study aimed to develop and validate a novel nomogram model to identify factors that predict the benefit of continued immunotherapy for hepatocellular carcinoma patients following disease progression in clinical ***:This study retrospectively analyzed the efficacy of ICIs in TBP,focusing on the Chinese population with advanced liver cancer.A nomogram was constructed based on four independent risk factors identified through Cox multivariate analysis,aiming to predict patient prognosis post-ICI *** model was validated through receiver operating characteristic(ROC)curve analysis and categorized patients into high-,intermediate-,and low-risk groups,with further validation using calibration plots and decision curve analysis(DCA).Results:The low-risk group demonstrated significantly enhanced overall survival(OS)compared to the high-risk group,with the nomogram predictions aligning closely with actual outcomes for 6-and 9-month *** model exhibited commendable predictive accuracy,achieving a C-index exceeding 0.7 in both training and validation *** DCA underscored the clinical utility of the nomogram-based prognostic model,further substantiated by the area under the ROC curve(AUC).Conclusions:The developed nomogram presents a potentially valuable tool for predicting the prognosis of HCC patients undergoing ICI therapy beyond progression,particularly within the Chinese ***,the study is constrained by its retrospective,single-center nature and necessitates further validation through large-scale,multicente

关键词： Hepatocellular carcinoma(HCC) immune checkpoint inhibitors(ICIs) novel nomogram

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Mycobacterium smegmatis enhances shikonin-induced immunogenic cell death—an efficient in situ tumor vaccine strategy

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Journal of Biomedical Research 2024年第4期38卷 369-381页

作者： Zhaoye Qian Zhe Zhang Lanqi Cen Yaohua Ke Jie Shao Manman Tian baorui liu Department of Oncology Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjingJiangsu 210008China Department of Oncology the Affiliated Huai'an No.1 People's HospitalNanjing Medical UniversityHuai'anJiangsu 223000China Center of Clinical Oncology the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu 221000China Department of Oncology China Pharmaceutical University Nanjing Drum Tower HospitalNanjingJiangsu 210008China The Comprehensive Cancer Center Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu 210008China Department of Oncology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu 210008China

Tumor vaccines are a promising avenue in cancer *** the progress in targeting specific immune epitopes,tumor cells lacking these epitopes can evade the ***,we aimed to construct an efficient in situ tumor vaccine called Vac-SM,utilizing shikonin(SKN)to induce immunogenic cell death(ICD)and Mycobacterium smegmatis as an immune adjuvant to enhance in situ tumor vaccine *** showed a dose-dependent and time-dependent cytotoxic effect on the tumor cell line and induced ICD in tumor cells as evidenced by the CCK-8 assay and the detection of the expression of relevant indicators,*** with the control group,the in situ Vac-SM injection in mouse subcutaneous metastatic tumors significantly inhibited tumor growth and distant tumor metastasis,while also improving survival *** smegmatis effectively induced maturation and activation of bone marrow-derived dendritic cells(DCs),and in vivo tumor-draining lymph nodes showed an increased maturation of DCs and a higher proportion of effector memory T-cell subsets with the Vac-SM treatment,based on flow cytometry analysis ***,the Vac-SM vaccine effectively induces ICD,improves antigen presentation by DCs,activates a specific systemic antitumor T-cell immune response,exhibits a favorable safety profile,and holds the promise for clinical translation for local tumor immunotherapy.

关键词： Mycobacterium smegmatis shikonin immunogenic cell death tumor vaccines immunogenicity cytotoxicity

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Strategic design of self-generated Ni-N-C hybrid sites in 3D network structures as counter electrodes in photovoltaics

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Resources Chemicals and Materials 2023年第1期2卷 1-10页

作者： Genhui Teng baorui liu Zhe Kang Yanhui Xie Dongying Hu Dawei Zhao School of Resources Environment and MaterialsGuangxi UniversityNanning530004China Key Laboratory on Resources Chemicals and Materials of Ministry of Education Shenyang University of Chemical TechnologyShenyang 110142P.R.China MOE Key Laboratory of New Processing Technology for Non-ferrous Metals and Materials&Guangxi Key Laboratory of Processing for Non-ferrous Metals and Featured Materials Guangxi UniversityNanning 530004China

The technical bottleneck of carbon materials as counter electrodes(CEs)lies in their limited electrical conduc-tivity,extended ion diffusion paths,poor dispersion,and high contact ***-oriented in-situ self-grown N-doped CNTs-coated Ni nanoparticles based on N-doped carbonaceous structures derived from pitaya peel(PC)are adopted to construct Ni-N-C hybrid 3D ionized network sites(Ni@NCNTs/PC-4)as *** characterization,micromorphological and chemical composition analyses revealed the 3D network structure of Ni@NCNTs/PC-4 with abundant active *** effectively shorten the diffusion distance of I 3−ions with a smaller charge transfer resistance(5.21Ω)than that of PC(12.53Ω).DSSCs based on Ni@NCNTs/PC-4 display good optoelectronic properties,in which the short-circuit current density(Jsc)is 13.27 mA/cm^(2),higher than those of Pt(11.66 mA/cm^(2))and PC(6.99 mA/cm^(2)).The PCE value(5.13%)of DSSCs based on Ni@NCNTs/PC-4 is also higher than that of DSSCs based on PC(2.47%).Overall,this work provides a preliminary research and new ideas for further in-depth study of biomass-derived 3D structured-carbons that contribute to key electrodes in DSSCs.

关键词： Ni-doping Biomass-derived carbon Dye-sensitized solar cell N-doped carbon nanotubes

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Culture of cryopreserved rat hepatocyte

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Journal of Nanjing Medical University 2006年第4期20卷 248-252页

作者： Haitao Yin GaojunTen Lifeng Wang baorui liu Xiaoping Qian Department of Oncology Gulou Hospital Nanjing University Nanjing 210008 Department of Radiology Zhongda Hospital Southeast University Nanjing 210009 China

Objective： To study the method of cryopreserving rat hepatocytes and double collagen gel culture measurement after its cryopreservation. Methods： Rat hepatocytes, isolated by two-step perfusion with collagenase using an extra corporeal perfusion apparatus, were cryopreserved in double collagen gel with culture medium added by epidermal growth factor（EGF）. The expression of cell function and cellular morphology were examined during culture. Results： The hepatocytes cryopreserved in double collagen gel concluding EGF showed good morphology and biological characteristics. After thawing, the MTT metabolism and protein synthesis of hepatocytes in sandwich ± EGF groups were better than those in control group. And the morphology and function of hepatocytes in sandwich group was better than that in EGF group（P 〈 0.05）. Conclusion： Double collagen gel culture can keep hepatocyte＇s activities. Thawed hepatocytes can be cultivated with collagenous matrix, which provides an environment that more closely resembles that in vivo and maintain the expression of certain liver-specific function of hepatocytes.

关键词： hepatocyte cryopreserve thaw

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First-line penpulimab(an anti-PD1 antibody)and anlotinib(an angiogenesis inhibitor)with nab-paclitaxel/gemcitabine(PAAG)in metastatic pancreatic cancer:a prospective,multicentre,biomolecular exploratory,phase II trial

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2960-2969页

作者： Huizi Sha Fan Tong Jiayao Ni Yi Sun Yahui Zhu Liang Qi Xiaoqin Li Wei Li Yan Yang Qing Gu Xing Zhang Xiaoxuan Wang Chan Zhu Dongsheng Chen baorui liu Juan Du The Comprehensive Cancer Center Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing University&Clinical Cancer Institute of Nanjing UniversityNanjingChina The Comprehensive Cancer Center Nanjing Drum Tower HospitalClinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjingChina Department of Oncology The Affiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Oncology The First Affiliated Hospital of Soochow UniversitySuzhouChina Department of Oncology The Affiliated Jiangning Hospital of Nanjing Medical UniversityNanjingChina National Institute of Healthcare Data Science at Nanjing University NanjingChina State Key Laboratory of Neurology and Oncology Drug Development Jiangsu Simcere Diagnostics Co.Ltd.Nanjing Simcere Medical Laboratory Science Co.Ltd.NanjingChina

Metastatic pancreatic cancer(mPC)has a dismal ***,we conducted a prospective,multicentre,single-arm,phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine(PAAG)in patients with first-line mPC(NCT05493995).The primary endpoints included the objective response rate(ORR)and disease control rate(DCR),while secondary endpoints encompassed progression-free survival(PFS),overall survival(OS),and *** 66 patients analysed for efficacy,the best response,indicated by the ORR,was recorded at 50.0%(33/66)(95%CI,37.4–62.6%),with 33 patients achieving partial response(PR).Notably,the DCR was 95.5%(63/66,95%CI,87.3–99.1%).The median PFS(mPFS)and OS(mOS)were 8.8(95%CI,8.1–11.6),and 13.7(95%CI,12.4 to not reached)months,*** 3/4 treatment-related adverse events(TRAEs)were reported in 39.4%of patients(26/66).In prespecified exploratory analysis,patients with altered SWI/SNF complex had a poorer ***,low serum CA724 level,high T-cell recruitment,low Th17 cell recruitment,and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable *** conclusion,PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for *** biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.

关键词： CA724 prospective centre

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基于Voxel有限元网格对球形夹杂复合材料的应力分析

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复合材料学报 2015年第6期32卷 1769-1776页

作者：刘宝瑞方国东梁军北京强度环境研究所可靠性与环境工程技术重点实验室北京100076 哈尔滨工业大学复合材料与结构研究所哈尔滨150001

通过Voxel有限元网格对球形夹杂复合材料进行应力分析时,由于Voxel网格在两相界面呈现阶梯状,所以在两相界面附近的单元会表现出明显的应力集中现象。提出采用局部应力平均方法来处理由于Voxel有限元网格而引起的应力集中,并且考虑应力... 详细信息

通过Voxel有限元网格对球形夹杂复合材料进行应力分析时,由于Voxel网格在两相界面呈现阶梯状,所以在两相界面附近的单元会表现出明显的应力集中现象。提出采用局部应力平均方法来处理由于Voxel有限元网格而引起的应力集中,并且考虑应力平均区域、应力平均加权函数以及网格密度的影响。结果表明:该局部应力平均方法能够有效地去除两相界面附近单元的应力集中,但应力平均区域不能过大也不能过小。通过计算发现采用2个Voxel网格深度的平均区域为最优,并且具有网格不依赖性。该方法也可以进一步用于球形夹杂复合材料的积累损伤演化分析。

关键词： Voxel网格有限元局部应力平均应力集中应力分析

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成像型可见光定位系统优化研究

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电子与信息学报 2022年第12期44卷 4246-4255页

作者：刘翔宇刘保睿宋嵩郭磊重庆邮电大学通信与信息工程学院智能通信与网络安全研究院重庆400065 东北大学计算机科学与工程学院沈阳110819 杭州中科先进技术研究院杭州310005

现有室内成像型可见光定位系统多注重定位精度的提高,而忽略了系统的解码识别成功率和定位算法的适用性。表现在:(1)接收端捕获带有模糊效应的图像会导致解码识别率变低;(2)定位系统移动状态下采用单一算法定位,且双灯(dual-LED)算法的... 详细信息

现有室内成像型可见光定位系统多注重定位精度的提高,而忽略了系统的解码识别成功率和定位算法的适用性。表现在:(1)接收端捕获带有模糊效应的图像会导致解码识别率变低;(2)定位系统移动状态下采用单一算法定位,且双灯(dual-LED)算法的旋转角存在非确定性,导致定位精度大幅度变化,甚至定位系统失效。该文首先提出基于条纹宽度比的解码算法,消除人为设定硬阈值的缺陷;然后,提出基于旋转角优化的联合定位算法,利用方向传感器辅助确认旋转角并联合定位;此外,还设计了简易导航功能。实验结果表明,该算法使得解码识别率在1.5 m内可达99%,系统平均定位误差为3.998 cm。

关键词：可见光定位条纹宽度比定位算法优化系统

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对图书馆学学科教育的思考

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图书情报知识 2005年第6期22卷 11-13页

作者：刘宝瑞长春师范学院政法学院长春130032

本文从图书馆学学科能力的教习和图书馆学学科思维品质,即专业文化精神的养成两个方面重新审视了图书馆学学科教育。并试图用图书馆学的精神内核、学科知识技能的培养、学科思维能力的培养三个要素,对新时期图书馆学学科教育的内容体系... 详细信息

本文从图书馆学学科能力的教习和图书馆学学科思维品质,即专业文化精神的养成两个方面重新审视了图书馆学学科教育。并试图用图书馆学的精神内核、学科知识技能的培养、学科思维能力的培养三个要素,对新时期图书馆学学科教育的内容体系进行建构。

关键词：图书馆学学科教育图书馆学理论研究学科思维

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间皮素靶向药物用于肿瘤免疫治疗的机遇与挑战

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中国肿瘤生物治疗杂志 2024年第9期31卷 841-848页

作者：王颖刘宝瑞南京大学医学院附属鼓楼医院肿瘤中心暨南京大学临床肿瘤研究所江苏南京210008

肿瘤免疫治疗是一种新兴且发展前景广阔的治疗模式。间皮素是一种细胞表面膜蛋白,通过糖基化磷脂酰肌醇锚定在细胞膜上。间皮素在多种恶性实体肿瘤及血液恶性肿瘤中呈高表达,在少数正常组织的间皮细胞中呈低表达,是一个有潜力的肿瘤免... 详细信息

肿瘤免疫治疗是一种新兴且发展前景广阔的治疗模式。间皮素是一种细胞表面膜蛋白,通过糖基化磷脂酰肌醇锚定在细胞膜上。间皮素在多种恶性实体肿瘤及血液恶性肿瘤中呈高表达,在少数正常组织的间皮细胞中呈低表达,是一个有潜力的肿瘤免疫治疗靶点。间皮素的高表达与患者不良预后密切相关,可溶性间皮素已成为多种肿瘤的诊断性生物标志物。应用抗体药物偶联物和CAR-T细胞治疗等免疫治疗策略,针对间皮素阳性实体瘤进行转化研究并取得了初步进展。本文对间皮素的结构、体内分布、生物学功能、肿瘤细胞内信号传导机制及其作用、基于核素的靶向成像与治疗策略、抗体偶联药物和CAR-T细胞的治疗策略,以及面临的挑战进行系统阐述,为进一步探索以间皮素为靶点的免疫治疗提供新思路。

关键词：间皮素肿瘤免疫治疗靶向治疗

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