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Heat-shocked tumor cell lysate-pulsed dendritic cells induce effective anti-tumor immune response in vivo

World Journal of Gastroenterology 2006年第3期12卷 473-478页

作者： Jian Qiu Guo-Wei Li yan-fang sui Hong-Ping Song Shao-yan Si Wei Ge Department of General Surgery TheSecond Hospital of Xi'an Jiaotong University Xi'an 710004Shaanxi Province China State Key Laboratory of Cancer Biology Department of PathologyThe Fourth Military Medical University Xi'an 710032 ShaanxiProvince China

AIM. To study whether heat-shocked tumor cells could enhance the effect of tumor cell lysate-pulsed dendritic cells （DCs） in evoking anti-tumor immune response in vivo. METHODS： Mouse undifferentiated colon cancer cells （CT-26） were heated at 42℃ for 1 h and then frozenthawed. The bone marrow-derived DCs pulsed with heatshocked CT-26 cell lysate （HSCT-26 DCs） were recruited to immunize syngeneic naive BALB/c mice. The cytotoxic activity of tumor specific cytotoxic T lymphocytes （CTLs） in mouse spleen was evaluated by IFN-enzyme-linked immunospot （ELISpot） and LDH release assay. The immunoprophylactic effects induced by HSCT-26 DCs in mouse colon cancer model were compared to those induced by single CT-26 cell lysate-pulsed DCs （CT-26 DCs） on tumor volume, peritoneal metastasis and survival time of the mice. RESULTS： Heat-treated CT-26 cells showed a higher hsp70 protein expression. Heat-shocked CT-26 cell lysate pulsing elevated the co-stimulatory and MHC-Ⅱ molecule expression of bone marrow-derived DCs as well as interleukin-12 p70 secretion. The IFN-y secreting CTLs induced by HSCT-26 DCs were significantly more than those induced by CT-26 DCs （P=0.002）. The former CTLs＇ specific cytotoxic activity was higher than the latter CTLs＇ at a serial E/T ratio of 10：1, 20：1, and 40：1. Mouse colon cancer model showed that the tumor volume of HSCT-26 DC vaccination group was smaller than that of CT-26 DC vaccination group on tumor volume though there was no statistical difference between them （24 mm^3 vs 8 mm^3, P=0.480）. The median survival time of mice immunized with HSCT-26 DCs was longer than that of those immunized with CT-26 DCs （57 d vs 43 d, P = 0.0384）. CONCLUSION： Heat-shocked tumor cell lysate-pulsed DCs can evoke anti-tumor immune response in vivo effectively and serve as a novel DC-based tumor vaccine.

关键词： Heat shock Tumor Dendritic cell Immune

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Preparation and activity of conjugate of monoclonal antibody HAb18 against hepatoma F( ab′ )_2 fragment and staphylococcal enterotoxin A

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World Journal of Gastroenterology 2001年第2期7卷 216-221页

作者： Lian Jun yang yan fang sui Zhi Nan Chen Department of Pathology, Fourth Military Medical University. Xi’an 710032, Shaanxi Province, China Department of Pathology Fourth Military Medical University Xi'an 710032 Shaanxi ProvinceChina. yangsi@***

AIM To prepare the conjugate of staphylococcal enterotoxin A (SEA) protein which is a bacterial SAg and the F(ab')2 fragment of mAb HAbl8 against human hepatocellular carcinoma (HCC), and identify its activity in order to use SAg in the targeting therapy of *** MAb HAbl8 was extracted from the abdominal dropsy of Balb/ c mice, and was purified through chromatography column SP-40HR with Fast protein liquid chromatography (FPLC) system. The F(ab')2 fragment of mAb HAb18 was prepared by papainic digestion method. The conjugate of mAb HAb18 F(ab')2fragment and SEA was prepared with chemical conjugating reagent N-succinimidyl-3-( 2-pyridyldithio) propionate (SPDP) and purified through chromatography column Superose 12with FPLC system. The molecular mass and purity of each collected peak were identified with SDS-PAGE assay. The protein content was assayed by Lowry's method. The antibody activity of HAb18 F (ab')2 against HCC in the conjugate was identified by indirect immunocytochemical ABC method, and the activity of SEA in the conjugate to activate peripheral blood mononuclear cells (PBMC) was identified with MTT *** The lgG mAb HAb18 was extracted,and purified successfully. Immunocytochemical staining demonstrated that it reacted with most of HHCC cells of human HCC cell line. There were two peaks in the process of purification of the prepared HAb18 F(ab)2-SEA conjugate. SDS-PAGE assay demonstrated that the molecular mass of the first peak was about 130 ku, and the second peak was the mixture of about 45 ku and a little 100 ku proteins. The immunocytochemical staining was similar in HAb18 F (ab ')2-SEAconjugate and HAb18 F (ab ')2, i.e., thecytoplasm and/or cell membranes of most HHCC cells were positively stained. The MTT assay showed that the optical absorbance (A) value at 490 nm of HAb18 F (ab')2-SEA conjugate was 0.182 ± 0.012, that of negative control was 0.033± 0.009, and there was significant difference between them ( P < 0.05).CONCLUSION SPDP

关键词： carcinoma, hepatocellular/immunology liver neoplasms/immunology superantigens enterotoxins antibodies, monoclonal

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Effects of Repetitive Transcranial Magnetic Stimulation on Astrocytes Proliferation and nNOS Expression in Neuropathic Pain Rats

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Current Medical Science 2018年第3期38卷 482-490页

作者： Lu yanG Sai-hua WANG yan HU yan-fang sui Tao PENG Tie-cheng GUO Department of Rehabilitation Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Department of Rehabilitation Medicine Hankou Hospital Wuhan 430014 China Department of Rehabilitation Medicine Wuhan FirstHospital Wuhan 430022 China Department of Rehabilitation Medicine Zhongnan Hospital of Wuhan University Wuhan 430071 China Department of Rehabilitation Medicine Haikou Hospital Haikou 570208 China

This study investigated the effects of different frequencies of repetitive transcranial magnetic stimulation （rTMS） on chronic neuropathic pain in rats. The behavior of rats with experimental chronic neuropathic pain was observed, and the expression of neuronal nitric oxide synthase （nNOS） in the ipsilateral dorsal root ganglions （DRGs） and the activation and proliferation of astrocytes in the ipsilateral spinal dorsal horn were detected. Thirty-two male Sprague-Dawley rats were randomly divided into four groups： sham-operated group, sham-rTMS group, 1 Hz group and 20 Hz group （8 rats in each group）. Chronic constriction nerve injury induced by sciatic nerve ligation was made to establish the models of the chronic neuropathic pain in rats except those in the sham-operated group. Then we applied different frequencies of rTMS to the primary motor cortex （M1） contralateral to the pain side once daily for 10 consecutive days. Pain behavior scores were observed before and after treatment. Western blot analysis was used to detect the expression of nNOS in ipsilateral L4-6 DRGs. Double immunofluorescent labeling for glial fibrillary acidic protein （GFAP） and 5-bromo-2- deoxyuridine （BrdU） was employed to observe the activation and proliferation of astrocytes in the ipsilateral L4-6 spinal dorsal horn. After rTMS treatment, the spontaneous pain behavior scores were significantly lower in the 20 Hz group than those in the sham-rTMS group （P〈0.05）. Moreover, the brush-evoked pain behavior scores were significantly lower in the 20 Hz group than those in the sham-rTMS and 1 Hz group （P〈0.05）, suggesting that the spontaneous pain and brush-evoked pain in the 20 Hz group were significantly alleviated. Western blot analysis revealed that the expression of nNOS in ipsilateral L4-6 DRGs was significantly decreased in the 20 Hz group as compared with the sham-rTMS group and the 1 Hz group （P〈0.01） after rTMS treatment. Double immunofluorescence suggested that the expression of GFAP a

关键词： neuropathic pain repetitive transcranial magnetic stimulation neuronal nitric oxide synthase astrocyte glial fibrillary acidic protein 5-bromo-2-deoxyuridine

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Effect of Paired Associative Stimulation on Motor Cortex Excitability in Rats

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Current Medical Science 2018年第5期38卷 903-909页

作者： Xiang-yu ZHANG yan-fang sui Tie-cheng GUO Sai-hua WANG yan HU Yin-shan LU Department of Rehabilitation Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Rehabilitation Medicine the 5th Hospital of Zhengzhou UniversityZhengzhou 470000China Department of Rehabilitation Medicine the 1st People's Hospital of HaikouHaikou 570208China Department of Rehabilitation Medicine the 1st Hospital of WuhanWuhan 430022China Department of Rehabilitation Medicine Zhongnan HospitalWuhan UniversityWuhan 430071China

Paired associative stimulation (PAS),combining transcranial magnetic stimulation (TMS) with electrical peripheral nerve stimulation (PNS) in pairs with an optimal interstimulus interval (ISI)in between,has been shown to influence the excitability of the motor cortex (MC)in ***,the underlying mechanisms remain *** study was designed to explore an optimal protocol of PAS,which can modulate the excitability of MC in rats,and to investigate the underlying mechanisms. The resting motor thresholds (RMTs) of TMS-elicited motor evoked potentials (MEPs) recorded from the gastrocnemius muscle and the latency of P1 component of somatosensory evoked potentials (SEPs) induced by electrical tibial nerve stimulation were determined in male Sprague-Dawley rats (n=10).Sixty rats were then randomly divided into 3 groups:a PAS group (further divided into 10 subgroups at various ISIs calculated by using the latency of P1,n=5,respectively),a TMS (only)group (n=5)and a PNS (only)group (n=5).Ninety repetitions of PAS,TMS and PNS were administered to the rats in the 3 groups,respectively,at the frequency of 0.05 Hz and the intensity of TMS at 120% RMT and that of PNS at 6 *** and motor evoked potentials'amplitude (MEPamp)were recorded before and immediately after the *** was found that the MEPamp significantly decreased after PAS at ISI of 5 ms (P0.05).PAS at other ISis as well as the sole use of TMS and PNS induced no remarkable changes in MEPamp and *** conclusion,PAS can influence motor cortex excitability in *** TMS alone nor PNS alone shows significant effect.

关键词： paired associative stimulation transcranial magnetic stimulation peripheral nerves electrical stimulation resting motor thresholds motor evoked potentials somatosensory evoked potentials

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Role of18F-FDG SPECT/CT imaging in the diagnosis and initial staging of lymphoma

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Journal of Hainan Medical University 2020年第17期26卷 52-56页

作者： Liang-Qian Tong yan-fang sui yan-Hai Yin Li-Qing Fu Jia-Ling Zhong Sheng-NanJiang Department of Nuclear Medicine Central South University Xiangya School Affiliated Haikou HospitalHaikou 570208HainanChina Department of Rehabilitation Medicine Central South University Xiangya School Affiliated Haikou HospitalHaikou 570208HainanChina Department of Nuclear Medicine Hainan Medicine College Affiliated Hainan HospitalHaikou 570311HainanChina

Objective:To investigate the role of18F-FDG SPECT/PET in the diagnosis and initial staging of ***:A retrospective analysis was carried out on 48 patients in Haikou Hospital from January 2015 to June 2018,who were eventually pathologically diagnosed with lymphoma and had undergone18F-FDG SPECT/PET before definite diagnosis.(1)Patients were divided into Hodgkin's lymphoma group,diffuse large B cell lymphoma group and other non-Hodgkin's lymphoma group according to Pathological classification;and were divided into nodal lymphoma group and extranodal lymphoma group according to the presence of invasion to the tissues beyond lymph node;and were divided into stage I+Ⅱgroup and stageⅢ+IV group according to clinical Ann Arbor *** diagnostic consistencies of18F-FDG SPECT/PET and conventional imaging(CI)in each group were calculated,the T/N ratios of the lymphoma lesion were analyzed as well.(2)Clinical Ann Arbor staging,SPECT/PET staging and CI staging were performed in 48 patients,*** the efficacy of SPECT/PET staging and CI staging was compared,and the consistency of SPECT/PET staging and clinical Ann Arbor staging was compared as ***:(1)In this study,the diagnostic consistent rates of18F-FDG SPECT/PET and CI were 45.8%(22/48)and 16.6%(8/48),respectively(χ2=9.503,P=0.0020.05).(3)The diagnostic consistent rates of18F-FDG SPECT/PET in nodal group and extranodal group were 100.0%(19/19)and 21.1%(4/19)(χ2=24.783,P=0.000<0.01),respectively.(4)The diagnostic consistent rates of18F-FDG SPECT/PET and CI were 25%(2/8)and 0(0/8)in lymphoma with early

关键词： Lymphoma Staging Tomography emission-computed single-photon Fluorodeoxyglucose

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热休克肿瘤细胞抗原负载的树突状细胞瘤苗对原位接种结肠肿瘤的免疫预防作用

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世界华人消化杂志 2005年第5期13卷 635-639页

作者：邱健李国威隋延仿宋宏萍司少艳葛伟西安交通大学第二医院普外科陕西省西安市710004 中国人民解放军第四军医大学病理学教研室陕西省西安市710032

目的:研究热休克肿瘤细胞抗原负载的树突状细胞的体内抗肿瘤作用以及对原位接种结肠肿瘤小鼠的免疫保护作用. 方法:肿瘤细胞CT-26经热休克处理后制备冻融抗原,体外负载树突状细胞,免疫同源小鼠(热休克组).以IFN-γELISPOT实验、LDH释放... 详细信息

目的:研究热休克肿瘤细胞抗原负载的树突状细胞的体内抗肿瘤作用以及对原位接种结肠肿瘤小鼠的免疫保护作用. 方法:肿瘤细胞CT-26经热休克处理后制备冻融抗原,体外负载树突状细胞,免疫同源小鼠(热休克组).以IFN-γELISPOT实验、LDH释放实验检测小鼠体内肿瘤特异性T细胞免疫反应,以原位接种结肠肿瘤的体积以及荷瘤小鼠的生存时间来评价该树突状细胞瘤苗对结肠原位接种CT-26小鼠的免疫保护作用,并与非热休克肿瘤细胞抗原负载的树突状细胞的免疫效果(非热休克组)作一比较. 结果:热休克处理肿瘤细胞可提高肿瘤细胞抗原负载的树突状细胞表面MHC-Ⅱ类分子(66.3% vs 59.1%)、共刺激分子CD86的表达(39.4% vs 36.7%);热休克组小鼠脾淋巴细胞中肿瘤特异性CTL数量高于非热休克组(P=0.001),相同效靶比下前者肿瘤特异性细胞毒活性强于后者:热体克组与非热休克组小鼠原位接种结肠肿瘤14 d后的肿瘤体积均明显小于单纯DC免疫组(P=0,000),但HSCT-26DC免疫组与CT-26 DC免疫组间差异无显著性(P=0.480).单纯DC免疫组50% (3/6)可见腹膜转移,CT-26 DC免疫组以及HSCT- 26DC免疫组均未见腹腔转移;热休克组小鼠荷瘤生存时间显著长于非热休克组(P=0.0384). 结论:热休克处理肿瘤细胞可以提高肿瘤细胞抗原负载的树突状细胞的体内抗肿瘤作用,热休克肿瘤细胞抗原负载的树突状细胞瘤苗对原位接种结肠肿瘤小鼠具有良好的免疫保护作用.

关键词：树突状细胞瘤苗肿瘤细胞原位接种抗原负载结肠肿瘤免疫预防作用体内抗肿瘤作用免疫保护作用 MHC-Ⅱ类分子肿瘤特异性CTL 热休克处理 ELISPOT 细胞免疫反应肿瘤小鼠生存时间 IFN-γ 共刺激分子脾淋巴细胞细胞毒活性

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Engineered Cancer Nanovaccines:A New Frontier in Cancer Therapy

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Nano-Micro Letters 2025年第2期17卷 134-168页

作者： Yijie Wang Congrui Liu Chao fang Qiuxia Peng Wen Qin Xuebing yan Kun Zhang Central Laboratory and Department of Medical Ultrasound Sichuan Academy of Medical SciencesSichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaNo.32West Second SectionFirst Ring RoadChengdu 610072People’s Republic of China Department of Stomatology and Central Laboratory School of MedicineShanghai Tenth People’s HospitalTongji UniversityNO.301 Yan‑Chang‑Zhong RoadShanghai 200072People’s Republic of China Jiangsu Provincial Innovation and Practice Base for Postdoctors Suining People’s HospitalAffiliated Hospital of Xuzhou Medical UniversityNo.2Bayi West RoadSuiningXu Zhou 221000Jiangsu ProvincePeople’s Republic of China

Vaccinations are essential for preventing and treating disease,especially cancer nanovaccines,which have gained considerable interest recently for their strong anti-tumor immune *** can prompt the immune system to generate antibodies and activate various immune cells,leading to a response against tumor tissues and reducing the negative effects and recurrence risks of traditional chemotherapy and *** enhance the flexibility and targeting of vaccines,nanovaccines utilize nanotechnology to encapsulate or carry antigens at the nanoscale level,enabling more controlled and precise drug delivery to enhance immune *** nanovaccines function by encapsulating tumor-specific antigens or tumor-associated antigens within *** small size of these nanomaterials allows for precise targeting of T cells,dendritic cells,or cancer cells,thereby eliciting a more potent anti-tumor *** this paper,we focus on the classification of carriers for cancer nanovaccines,the roles of different target cells,and clinically tested cancer nanovaccines,discussing strategies for effectively inducing cytotoxic T lymphocytes responses and optimizing antigen presentation,while also looking ahead to the translational challenges of moving from animal experiments to clinical trials.

关键词： Cancer nanovaccines Immunotherapy Nanobiotechnology Immune targets Signaling pathway

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High Fe‑Loading Single‑Atom Catalyst Boosts ROS Production by Density Effect for Efficient Antibacterial Therapy

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Nano-Micro Letters 2025年第2期17卷 187-203页

作者： Si Chen fang Huang Lijie Mao Zhimin Zhang Han Lin Qixin yan Xiangyu Lu Jianlin Shi Department of Cardiology Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200092People’s Republic of China Shanghai Institute of Ceramics Chinese Academy of SciencesShanghai 200050People’s Republic of China Shanghai Frontiers Science Center of Nanocatalytic Medicine School of MedicineTongji UniversityShanghai 200092People’s Republic of China

The current single-atom catalysts(SACs)for medicine still suffer from the limited active site ***,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with *** constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial ***,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading ***,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/*** addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)*** in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound *** work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.

关键词： Nanocatalytic medicine Single-atom catalysts Reactive oxygen species(ROS) High metal loading Oxidase catalysis

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The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons

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Neural Regeneration Research 2025年第1期20卷 209-223页

作者： Shi-yan Sun Lingyun Nie Jing Zhang Xue fang Hongmei Luo Chuanhai Fu Zhiyi Wei Ai-Hui Tang Hefei National Research Center for Physical Sciences at the Microscale CAS Key Laboratory of Brain Function and DiseaseMinistry of Education Key Laboratory for Membrane-less Organelles and Cellular DynamicsDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina CAS Center for Excellence in Molecular Cell Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Neurobiology School of Life SciencesSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Brain Research Center Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina

Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and ***-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains *** this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative ***,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic *** of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and *** down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive *** together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

关键词： actin cytoskeleton dendrite KANK1 KIF21A microtubule spine morphology spine synaptic plasticity talin1

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指向高质量课堂的听评课量表设计及其关键问题

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教学与管理 2025年第1期 24-28页

作者：户艳茹方妍清华大学教育研究院北京100084 清华大学附属中学北京100084

在建设高质量课堂的时代背景下,重新设计课堂听评课框架与维度,有助于倒逼教师专业成长,反促课堂提质增效。在深刻反思现有听评课量表存在不足、尤其是缺乏科学量化标准的前提下,重新设计的旨在提升课堂质量的听评课量表主要包括2个观... 详细信息

在建设高质量课堂的时代背景下,重新设计课堂听评课框架与维度,有助于倒逼教师专业成长,反促课堂提质增效。在深刻反思现有听评课量表存在不足、尤其是缺乏科学量化标准的前提下,重新设计的旨在提升课堂质量的听评课量表主要包括2个观察维度、6个观察要素、13个观察指标和26个观察点。在教学实践中应用这一听评课量表,需要注意凸显学生的主体性、全面性与个性化,构建民主平等的课堂生命共同体,展现时代风格与学校特色,形成良性教研文化和沟通合作机制。

关键词：高质量课堂听评课量表教研制度

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