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Radiation-induced tumor immune microenvironments and potential targets for combination therapy

Signal Transduction and Targeted Therapy 2023年第6期8卷 2773-2794页

作者： Siyu Guo Yihan Yao Yang Tang zengfeng xin Dang Wu Chao Ni Jian Huang Qichun Wei Ting Zhang Department of Radiation Oncology Second Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhouChina Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province Second Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhouChina Cancer Institute(Key Laboratory of Cancer Prevention and Intervention National Ministry of Education)Second Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhouChina Cancer Center Zhejiang UniversityHangzhouChina Department of Orthopedic Surgery Second Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhouChina Department of Breast Surgery Second Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhouChina

As one of the four major means of cancer treatment including surgery,radiotherapy(RT),chemotherapy,immunotherapy,RT can be applied to various cancers as both a radical cancer treatment and an adjuvant treatment before or after *** RT is an important modality for cancer treatment,the consequential changes caused by RT in the tumor microenvironment(TME)have not yet been fully ***-induced damage to cancer cells leads to different outcomes,such as survival,senescence,or *** RT,alterations in signaling pathways result in changes in the local immune ***,some immune cells are immunosuppressive or transform into immunosuppressive phenotypes under specific conditions,leading to the development of *** who are radioresistant respond poorly to RT and may experience cancer *** that the emergence of radioresistance is inevitable,new radiosensitization treatments are urgently *** this review,we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of ***,this review highlights the possibilities of synergistic therapy by building on existing research.

关键词： microenvironment alterations surgery

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胫骨平台骨折术后不同期感染的治疗

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中华创伤杂志 2019年第2期35卷 136-142页

作者：辛曾峰李抗浙江大学医学院附属第二医院骨科杭州310009

目的探讨胫骨平台骨折术后早期和迟发性感染的治疗方法选择。方法采用回顾性病例系列研究分析2013年2月—2017年2月浙江大学医学院附属第二医院收治的21例胫骨平台骨折术后感染患者临床资料,其中男16例,女5例;年龄28~68岁,平均51.9岁。... 详细信息

目的探讨胫骨平台骨折术后早期和迟发性感染的治疗方法选择。方法采用回顾性病例系列研究分析2013年2月—2017年2月浙江大学医学院附属第二医院收治的21例胫骨平台骨折术后感染患者临床资料,其中男16例,女5例;年龄28~68岁,平均51.9岁。所有患者根据情况积极清创,感染区予局部抗生素硫酸钙或骨水泥控制感染,闭合创面时若存在软组织缺损则行腓肠肌肌瓣转移术予以覆盖。早期感染12例均保留内置物,予以彻底清创、抗生素使用控制感染。迟发性感染患者9例,其中1例予以局部换药至骨折愈合,后拆除内置物并予以清创闭合伤口;2例关节面已破坏严重,无法重建,其中1例Ⅰ期直接行股骨下段截肢术,另外1例Ⅰ期拆除钢板改用外固定支架固定,反复清创后Ⅱ期行关节融合术;其余6例均采取拆除内置物改外固定支架固定,予以彻底清创及抗生素使用,其中3例骨缺损患者Ⅱ期行植骨术。定期复查所有患者感染情况、膝关节功能美国特种外科医院(HSS)评分及骨折愈合情况。结果患者均获随访18~60个月,平均37.4个月。患者均局部予抗生素硫酸钙或骨水泥控制感染,其中10例感染患者行腓肠肌肌瓣转移术,伤口均愈合良好,无再发骨折或感染复发。12例早期感染患者均成功保留内置物,骨折均愈合。根据HSS评分标准:优7例,良3例,中2例,优良率为83%(10/12)。9例迟发性感染患者除外截肢及关节融合2例,其余7例迟发性感染患者骨折或骨缺损均愈合。根据HSS评分标准:优1例,良3例,中2例,差1例,优良率为57%(4/7)。结论对于胫骨平台术后早期感染患者,可首先尝试保留内置物,早期清创并联合抗生素使用积极控制感染;对于迟发性感染患者,除骨折稳定且尚在愈合的患者可尝试保留内置物外,采用拆除内置物并彻底清创、局部联合全身抗生素使用可有效控制感染。同时,腓肠肌肌瓣转移、抗生素硫酸钙及骨水泥局部使用等均有利于感染控制,可以取得良好的临床治疗效果。

关键词：胫骨骨折感染治疗

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Immune mediated support of metastasis:Implication for bone invasion

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Cancer Communications 2024年第9期44卷 967-991页

作者： zengfeng xin Luying Qin Yang Tang Siyu Guo Fangfang Li Yuan Fang Gege Li Yihan Yao Binbin Zheng Bicheng Zhang Dang Wu Jie Xiao Chao Ni Qichun Wei Ting Zhang Department of Orthopedic Surgery Second Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhouZhejiangP.R.China Cancer Institute(Key Laboratory of Cancer Prevention and Intervention National Ministry of Education)Second Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhouZhejiangP.R.China Department of Radiation Oncology Second Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhouZhejiangP.R.China Department of Respiratory Medicine Ningbo Hangzhou Bay HospitalNingboZhejiangP.R.China Department of Orthopedic Surgery Second Affiliated Hospital(Jiande Branch)Zhejiang University School of MedicineHangzhouZhejiangP.R.China Department of Breast Surgery Second Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhouZhejiangP.R.China

Bone is a common organ affected by metastasis in various advanced cancers,including lung,breast,prostate,colorectal,and *** a patient is diagnosed with bone metastasis,the patient’s quality of life and overall survival are significantly reduced owing to a wide range ofmorbidities and the increasing difficulty of *** studies have shown that bone metastasis is closely related to bone microenvironment,especially bone immune ***,the effects of various immune cells in the bone microenvironment on bone metastasis remain ***,we described the changes in various immune cells during bone metastasis and discussed their related ***,adipocytes,and other non-immune cells closely related to bone metastasis were also *** review also summarized the existing treatment methods and potential therapeutic targets,and provided insights for future studies of cancer bone metastasis.

关键词： bone metastasis bone microenvironment cancer immune cell therapy

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E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2

E3 ubiquitin ligase NEDD4L negatively regulates inflammation...

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浙江省免疫学会第十三次学术大会

作者： Hui Li Ning Wang Yu Jiang Haofei Wang zengfeng xin Huazhang An Hao Pan Wangqian Ma Ting Zhang Xiaojian Wang Wenlong Lin Institute of Immunology and The Second Affiliated Hospital Zhejiang University School of Medicine Department of Medical Oncology the Cancer Hospital of the University of Chinese Academy of Sciences (ZhejiangCancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of Sciences Cancer Institute Institute of Translational MedicineSecond Military Medical University & Shanghai Key Laboratory of Cell Engineering Department of Urology The First Affiliated HospitalCollege of MedicineZhejiang University Department of Gastroenterology The Second Affiliated HospitalZhejiang University School of Medicine Department of Radiation Oncology The Second Affiliated HospitalZhejiang University School of Medicine

Background:Inflammation represents an adaptive and dynamic host response against pathogens,physical/chemical injuries,toxins,or *** stimulant triggers leukocyte infiltration,cytokines,and chemokines expression,and eventual subsiding of proinflammatory *** or prolonged inflammation has been closely related to a variety of human diseases such as autoimmune diseases,cancer,cardiovascular disease,and metabolic ***,immune-regulatory and negative feedback mechanisms are critically required to harness inflammation and prevent excessive immunopathology ***:Neural precursor cell expressed developmentally down-regulated gene 4-like（NEDD4 L） is a highly conserved HECT type E3 *** recent data demonstrate that NEDD4 L promotes Lys-29-linked ubiquitination of TRAF3,and thus positively regulates antivirus innate *** also showed in a previous study that NEDD4 L negatively regulates keratinocyte hyperplasia by promoting Lys-27-linked ubiquitination of GP130 and proteasomal degradation in ***,the physiologic role of NEDD4 L in autoimmune diseases remains largely *** and methods:Male age-matched Nedd4 l and Nedd41 littermates were treated with IL-17 or MOG to induce IL-17-associated inflammation or *** vitro,pull-down assay,ubiquitination assay,and co-immunoprecipitation assay were employed for mechanism ***:Here we identify neural precursor cell expressed developmentally down-regulated gene 4-like（NEDD4 L）,a HECT type E3 ligase,as a common negative regulator of signaling induced by TNF-α,IL-1,and ***4 L modulates the degradation of mitogen-activated protein kinase kinase kinase 2（MEKK2） via constitutively and directly binding to MEKK2 and promotes its *** interleukin-17 receptor（IL-17 R） signaling,Nedd41 knockdown or deficiency enhances IL-17-induced p38 and NF-κB activation and the production of proinflammatory cytokines and chemok

关键词： NEDD4L MEKK2 IL-17R signaling ubiquitination inflammation

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富血小板血浆治疗单纯髌股关节炎1例

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中华关节外科杂志（电子版） 2022年第1期16卷 127-130页

作者：刘安吴浩波辛曾峰浙江大学医学院附属第二医院骨科浙江大学骨科研究所杭州310009

近年来,富血小板血浆(platelet-rich plasma,PRP)因其所富含的生长因子如转化生长因子(trans forming growth factor-β,TGF-β)、血小板源性生长因子(platelet-derived growth factor,PDGF)、胰岛素生长因子(insulin growth factor,IGF)及血管内皮生长因子(vascular endothelial growth factor,VEGF)等在组织再生修复领域备受关注。目前通过PRP关节腔注射治疗膝骨关节炎(knee osteo arthritis,KOA)的治疗方式逐渐普及,然而其临床疗效仍存在争议[1-2]。

关键词：富血小板血浆血小板源性生长因子膝骨关节炎髌股关节炎胰岛素生长因子转化生长因子临床疗效

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NEDD4L mediates intestinal epithelial cell ferroptosis to restrict IBDs and tumorigenesis in humans and mice

NEDD4L mediates intestinal epithelial cell ferroptosis to re...

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浙江省免疫学会第十三次学术大会

作者： Jingjing Liang Ning Wang Xiang An Haofei Wang Hui Liu Yu Jiang Huan Li Wang Yingmei zengfeng xin Ting Zhang Xiaojian Wang Wenlong Lin Hangzhou City University and Institute of Immunology Zhejiang University School of Medicine Institute of Basic and Translational Medicine Xi'an Medical University Department of Medical Oncology the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of Sciences Department of Clinical Laboratory Medicine Second Affiliated HospitalSchool of MedicineZhejiang University State Key Laboratory of Cancer Biology Department of PathologyXijing Hospital and School of Basic Medicinethe Fourth Military Medical University Department of Orthopedic Surgery The Second Affiliated HospitalZhejiang University School of Medicine Department of Radiation Oncology The Second Affiliated HospitalZhejiang University School of Medicine

Background:Various factors such as genetic variation,environment, diet,and intestinal flora play a key role in maintaining the homeostasis of the *** intestinal homeostasis could cause intestinal inflammatory diseases,including Crohn's disease(CD),ulcerative colitis(UC),and even colorectal cancer(CRC).It has been reported that many key genes' loss or gain function results in severe dysregulated intestinal ***,the regulatory role of NEDD4 L in IBD and colitis-associated colorectal cancer(CAC) remains ***:Neural precursor cells expressed developmentally down-regulated 4-like protein,NEDD4 L(NEDD4-2) appear to control the ubiquitination of various membrane proteins,essential for maintaining cell *** NEDD4 L gene is highly expressed in intestinal systems,however,its role in the homeostasis of the GI tract remains *** sought to identify the roles of NEDD4 L in maintaining homeostasis of the GI *** and methods:The expression of NEDD4 L was determined by immnohistochemistry and western blot ***4 L knockout and wild-type mice were administered dextran sulfate sodium(DSS),2,4,6-trinitrobenzene sulfonic acid(TNBS),or azoxymethane(AOM)/DSS to induce experimental colitis or colorectal cancer,and the mice were assessed based on colitis symptoms and biochemical *** mechanism was analyzed using immunoprecipitation and ubiquitination ***:Our research demonstrated that NEDD4 L,a kind of HECT family E3 ubiquitin ligase,plays an important role in maintaining intestinal ***4 L gene and protein expression are significantly inhibited in intestinal epithelial cells(IECs) of patients with UC,CD,and ***4 L global knockout or NEDD4 L deficiency in IECs significantly exacerbated DSS-/TNBS-induced colitis and AOM/DSS-induced colorectal ***,NEDD4 L deficiency in IECs reduces the protein expression of soluble amino acid transport protein SLC3 A2 wit

关键词： intestinal inflammatory diseases colitis-associated colorectal cancer NEDD4L ferroptosis

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问题式教学法联合仿真实验室在肿瘤放射治疗学靶区勾画教学中的应用

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中国高等医学教育 2023年第8期 110-111页

作者：辛曾峰张婷浙江大学医学院附属第二医院

目的：分析问题式教学法联合仿真实验室(联合教学)在靶区勾画教学中的应用效果。方法：选取2019年1月至2022年1月60名培训学员随机分为对照组(n=28)和试验组(n=32),分别实施传统教学和联合教学。比较两组学员培训结束成绩。结果：试验... 详细信息

目的：分析问题式教学法联合仿真实验室(联合教学)在靶区勾画教学中的应用效果。方法：选取2019年1月至2022年1月60名培训学员随机分为对照组(n=28)和试验组(n=32),分别实施传统教学和联合教学。比较两组学员培训结束成绩。结果：试验组学员成绩更优秀(P<0.05)。结论：联合教学更有效。

关键词：肿瘤放射治疗靶区勾画问题式教学法仿真实验室

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骨折内固定术后感染保留内固定的疗效分析

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中华创伤骨科杂志 2022年第7期24卷 598-603页

作者：朱晗晓李杭薛德挺辛曾峰章相锋李伟栩冯刚谭延斌浙江大学医学院附属第二医院骨科杭州310009

目的分析骨折内固定术后6周内出现骨折相关感染(FRI)后保留内固定的疗效。方法回顾性分析2013年2月至2021年2月浙江大学医学院附属第二医院收治的81例骨折术后6周内发生FRI并接受保留内固定治疗的患者资料。其中男61例,女20例;年龄11~73... 详细信息

目的分析骨折内固定术后6周内出现骨折相关感染(FRI)后保留内固定的疗效。方法回顾性分析2013年2月至2021年2月浙江大学医学院附属第二医院收治的81例骨折术后6周内发生FRI并接受保留内固定治疗的患者资料。其中男61例,女20例;年龄11~73岁,平均51岁。患者入院后接受细菌培养、彻底清创、负压吸引、软组织修复重建、局部及静脉使用抗生素等方法治疗。如感染累及关节,行关节腔清理并引流。定期复查所有患者感染控制情况及骨折愈合情况。如将内固定保留至骨折愈合认定为治疗成功,骨折愈合前内固定拆除认定为治疗失败。从性别、年龄、吸烟、糖尿病、骨折类型(开放性、闭合性)、是否为耐甲氧西林金黄色葡萄球菌(MRSA)感染、是否为甲氧西林敏感葡萄球菌(MSSA)感染、是否为铜绿假单胞菌感染、是否为大肠杆菌感染、是否两种细菌感染、是否细菌培养阴性、感染是否为早期(2周内)、是否局部使用抗菌药物中分析治疗失败相关的危险因素。结果所有患者术后获平均30个月(6~84个月)随访。62例(76.5%)患者在控制感染并保留内固定的情况下获得骨折愈合。其中2例患者使用了Masquelet技术处理骨缺损,11例使用了肌瓣或皮瓣技术重建软组织覆盖,2例存在窦道的患者通过抗菌药物和换药达到骨折愈合。19例失败中,有1例因感染无法控制而截肢;剩余18例患者均拆除内固定改外固定,其中有3例患者使用了Masquelet技术获得最终骨愈合,7例患者使用骨搬运技术获得最终骨愈合,3例患者使用皮瓣技术重建软组织覆盖。铜绿假单胞菌感染、开放性骨折以及2周以上的FRI是保留内固定失败的高危因素(P<0.05)。结论对于骨折内固定术后6周内发生FRI的患者,如内固定仍稳定有效,可首先尝试保留内固定。对于软组织缺损的患者,在彻底有效清除的条件下尽早行肌瓣或皮瓣手术,可有效控制感染并有助于骨折愈合。开放性骨折病史、铜绿假单胞菌感染和2周以上的FRI是保留内固定失败的危险因素。

关键词：骨折感染骨折固定术,内骨折愈合

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经关节截骨治疗Schatzker Ⅱ型胫骨平台骨折畸形愈合1例报道

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中华骨与关节外科杂志 2019年第11期12卷 903-905页

作者：胡东才辛曾峰黄路李伟栩浙江大学医学院附属第二医院骨科浙江大学骨科研究所

解剖复位和稳定固定是治疗伴有移位的胫骨平台骨折的金标准[1]。尽管如此,由于各种各样的原因,包括漏诊、误诊以及其他一些客观限制导致骨折未能及时接受手术治疗,或者术中关键骨块未予重视、复位不良或固定不牢固,胫骨平台骨折后畸形... 详细信息

解剖复位和稳定固定是治疗伴有移位的胫骨平台骨折的金标准[1]。尽管如此,由于各种各样的原因,包括漏诊、误诊以及其他一些客观限制导致骨折未能及时接受手术治疗,或者术中关键骨块未予重视、复位不良或固定不牢固,胫骨平台骨折后畸形愈合仍然时有发生[2]。畸形愈合影响膝关节功能,引起长期慢性疼痛、关节不稳或关节僵硬,容易早期发生创伤性骨关节炎;此外膝关节功能异常还会引起髋、踝关节的代偿作用,从而影响正常的髋、踝关节功能[3]。因此,胫骨平台骨折畸形愈合往往需要行手术治疗,手术的目的是恢复下肢力线、提高膝关节稳定性、尽可能恢复膝关节活动度。本文介绍1例经关节截骨治疗Schatzker II型胫骨平台骨折畸形愈合病例。

关键词：胫骨平台骨折畸形愈合经关节截骨

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Application of confocal laser Raman spectroscopy on marine sediment microplastics

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Journal of Oceanology and Limnology 2020年第5期38卷 1502-1516页

作者： LIU Jing ZHANG xin DU zengfeng LUAN Zhendong LI Lianfu XI Shichuan WANG Bing CAO Lei YAN Jun Key Laboratory of Marine Geology and Environment&Center of Deep Sea Research Institute of OceanologyChinese Academy of SciencesQingdao 266071China Laboratory for Marine Geology Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266237China University of Chinese Academy of Sciences Beijing 100049China Center for Ocean Mega-Science Chinese Academy of SciencesQingdao 266071China

Marine sediment is the primary sink of microplastics and is an indicator of pollution ***,although there are well-developed detection methods,detection is rarely focused on lowmicrometer-sized particles,mainly due to technique *** this study,a simplifi ed process omitting digestion procedures was developed to pretreat microplastics obtained from marine sediment and was coupled with micro-Raman spectroscopy to identify *** on the overall analysis of the characteristic peak assignments,a Raman spectral reference library was constructed for 18 types of *** addition,the eff ects of the measurement parameters were systematically *** research was then conducted to validate the developed process and investigate microplastic contamination in Huiquan Bay,Qingdao,*** simplifi ed process could retain the original appearance of microparticles and accomplish the detection of<500μm-sized microplastics in environmental *** in the size range of 10-150μm accounted for 76%of all microplastics,and 56%of the total particles was particles smaller than 50μ***(42%)and polyethylene(20%)were predominant components of the *** particular,polypropylene particles smaller than 10μm were identifi ed in marine *** work demonstrates that Raman spectroscopy is not only an eff ective tool for detecting environmental particles but also highly applicable for identifying particles extracted from marine sediment.

关键词： microplastics confocal Raman spectroscopy marine sediment

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