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Programmed cell death-1 inhibitor combination treatment for recurrent proficient mismatch repair/miscrosatellite-stable type endometrial cancer:A case report

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World Journal of Clinical Cases 2022年第21期10卷 7474-7482页

作者： Chong-Ya Zhai Lu-Xi Yin wei-dong han Department of Medical Oncology Xiasha CampusSir Run Run Shaw HospitalCollege of MedicineZhejiang UniversityHangzhou 310020Zhejiang ProvinceChina Department of Medical Oncology Sir Run Run Shaw HospitalCollege of MedicineZhejiang UniversityHangzhou 310020Zhejiang ProvinceChina

BACKGROUND Endometrial cancer(EC)is one of the most common cancers of the female reproductive tract,and the incidence is increasing *** using programmed cell death-1(PD-1)inhibitors is an emerging research topic and treatment strategy for refractory gynecological ***,clinical management of EC with checkpoint inhibitors requires ***,we discuss a case of refractory proficient mismatch repair(pMMR)/miscrosatellitestable(MSS)EC treated with a combination of PD-1 and angiogenesis inhibitors and offer a review of the pathophysiology and clinical outcomes based on previous *** SUMMARY A 62-year-old woman diagnosed with invasive or metastatic EC in 2015 was treated with six courses of chemotherapy and refused further *** years later,she developed chest pain,and lung biopsy indicated thyroid transcription factor-1(-),Napsin A(-),estrogen receptor(+),progesterone receptor(+),anaplastic lymphoma kinase(D5F3)(-),and receptor tyrosine kinase(D4D6)(-)metastatic *** testing results showed low tumor mutation burden,pMMR,PD ligand 1(-),MSS,and HLA-class 1 heterogeneous *** patient was started on toripalimab combined with nab-paclitaxel for seven cycles(every 3 wk),but this regimen was terminated because of an intolerable chemotherapy adverse *** disease progressed in 2020,and the patient’s treatment was switched from nab-paclitaxel to anlotinib,while immunotherapy using toripalimab was *** patient achieved a major partial response with well-tolerated toxicities,and treatment is *** Molecular testing is advised for clinical classifications of EC owing to its high *** this case,the patient had pMMR/MSS EC and achieved a positive outcome with combination PD-1 inhibitor *** results warrant further clinical exploration.

关键词： Refractory endometrial cancer Proficient mismatch repair Miscrosatellite-stable Immunotherapy Case report

Biomimetic design of highly flexible metal oxide nanofibrous membranes with exceptional mechanical performance for superior phosphopeptide enrichment

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Nano Research 2024年第5期17卷 4270-4278页

作者： Xue Mao Zhen-Zhen Li dong-Lian Hao wei-dong han Gao-Peng Li Yao-Yu Wang Kun Zhang School of Textile Science and Engineering Key Laboratory of Functional Textile Material and Product(Ministry of Education)Xi’an Polytechnic UniversityXi’an 710048China Key Laboratory of Magnetic Molecules&Magnetic Information Materials of the Ministry of Education School of Chemistry&Material ScienceShanxi Normal UniversityTaiyuan 030031China Department of Clinical Laboratory The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004China Shanghai iProteome Biotechnology Co. LtdShanghai 201210China College of Chemistry&Materials Science Northwest UniversityXi'an 710127China

Developing free-standing and mechanical robust membrane materials capable of superior enrichment of phosphopeptides for analyzing and identifying the specific phosphoproteome of cancer cells is significant in understanding the molecular mechanisms of cancer development and exploring new therapeutic approaches,but still a significant challenge in materials *** this end,we firstly constructed highly flexible ZrTiO_(4) nanofibrous membranes(NFMs)with excellent mechanical stability through a cost-effective and scalable electrospinning and subsequent calcination ***,to further increase the enrichment capacity of the phosphopeptide,the biomimetic TiO_(2)@ZrTiO_(4) NFMs with root hair or leaf like branch microstructure are developed by the hydrothermal post-synthetic modification of ZrTiO_(4) NFMs through growing unfurling TiO_(2) nanosheets onto the ZrTiO_(4) ***,remarkable flexibility and mechanical stability enable the resulting TiO_(2)@ZrTiO_(4) NFMs excellent practicability,while the biomimetic microstructure allows it outstanding enrichment ability of the phosphopeptide and identification ability of the specific phosphoproteins in the digest of cervical cancer ***,6770 phosphopeptides can be enriched by TiO_(2)@ZrTiO_(4) NFMs(2205 corresponding phosphoproteins can be identified),and the value is much higher than that of ZrTiO_(4) NFMs(6399 phosphopeptides and 2132 identified phosphoproteins)and commercial high-performance TiO_(2) particles(4525 phosphopeptides and 1811 identified phosphoproteins).These results demonstrate the super ability of TiO_(2)@ZrTiO_(4) NFMs in phosphopeptide enrichment and great potential for exploring the pathogenesis of cancer.

关键词： inorganic nanofibers flexible ceramic nanofibrous membranes biomimetic materials exceptional mechanical performance flexibility

Genetically engineered T cells for cancer immunotherapy

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Signal Transduction and Targeted Therapy 2019年第1期4卷 330-346页

作者： Dan Li Xue Li wei-Lin Zhou Yong Huang Xiao Liang Lin Jiang Xiao Yang Jie Sun Zonghai Li wei-dong han wei Wang Department of Biotherapy State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan Universityand the Collaborative Innovation Center for Biotherapy610041 ChengduChina Department of Medical Oncology Cancer CenterWest China HospitalWest China Medical SchoolSichuan Universityand the Collaborative Innovation Center for Biotherapy610041 ChengduChina Department of Cell Biology and Bone Marrow Transplantation Center of the First Affiliated HospitalZhejiang University School of Medicine310058 ZhejiangChina Institute of Hematology Zhejiang University&Laboratory of Stem cell and Immunotherapy Engineering310058 ZhejingChina State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteRenji HospitalShanghai Jiaotong University School of Medicine200032 ShanghaiChina CARsgen Therapeutics 200032 ShanghaiChina Molecular&Immunological Department Biotherapeutic DepartmentChinese PLA General HospitalNo.28 Fuxing Road100853 BeijingChina

T cells in the immune system protect the human body from infection by pathogens and clear mutant cells through specific recognition by T cell receptors(TCRs).Cancer immunotherapy,by relying on this basic recognition method,boosts the antitumor efficacy of T cells by unleashing the inhibition of immune checkpoints and expands adaptive immunity by facilitating the adoptive transfer of genetically engineered T cells.T cells genetically equipped with chimeric antigen receptors(CARs)or TCRs have shown remarkable effectiveness in treating some hematological malignancies,although the efficacy of engineered T cells in treating solid tumors is far from *** this review,we summarize the development of genetically engineered T cells,outline the most recent studies investigating genetically engineered T cells for cancer immunotherapy,and discuss strategies for improving the performance of these T cells in fighting cancers.

关键词： immunotherapy immunity fighting

Clinicopathological significance of LRP16 protein in 336 gastric carcinoma patients

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World Journal of Gastroenterology 2009年第38期15卷 4833-4837页

作者： Ya-Zhuo Li Po Zhao wei-dong han Department of Pathology ChinesePeople's Liberation Army General Hospital Beijing 100853China Department of Molecular Biology Instituteof Basic Medicine Chinese People's Liberation Army GeneralHospital Beijing 100853 China

AIM： To investigate the expression of leukemia related protein 16 （LRP16）, and the possible relationship between LRP16 expression and clinicopathological indices in 336 gastric carcinoma patients. METHODS： Immunohistochemistry was used to detect LRP16 expression in 336 cases of paraffin-embedded gastric carcinoma tissues and 60 cases of distal normal mucosa. The relationships between LRP16 expression and patients＇ age, tumor size, histological grade, clinical stage, metastatic status and prognosis were analysed. RESULTS： The expression of LRP16 was 58.6% （197/336） in gastric carcinoma and 31.7% （19/60） in distal normal gastric mucosa. The expression of LRP16 in carcinoma was significantly higher than that in normal mucosa tissues （x^2 = 14.929, P = 0.001）. LRP16 protein expression was found in 44.1% （63/143） carcinomas at stage Ⅰ and Ⅱ, and 69.4% （134/193） carcinomas at stage Ⅲ and Ⅳ （Z2 = 21.804, P = 0.001）, and in 56.9% （182/320） of cancers without metastasis but 93.8% （15/16） of those with metastasis （2 = 8.543, P = 0.003）. The expression of LRP16 was correlated with tumor size, infiltrative depth, clinical stage, lymphatic invasion and distant metastasis （all P 〈 0.05）. Follow-up data showed that there was a significant difference in median survival time between cancer patients with expression of LRP16 （27.0 mo） and those without （48.0 mo, Log rank =31.644, P = 0.001）. CONCLUSION： The expression of LRP16 may be associated with invasion, metastasis and prognosis of gastric cancer.

关键词： Gastric neoplasms Immunohistochemistry Leukemia related protein 16 Prognosis

Long-term safety and efficacy of CART-20 cells in patients with refractory or relapsed B-cell non-Hodgkin lymphoma:5-years follow-up results of the phase I and IIa trials

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Signal Transduction and Targeted Therapy 2017年第1期2卷 85-88页

作者： Wen-ying Zhang Yang Liu Yao Wang Chun-meng Wang Qing-ming Yang Hong-li Zhu wei-dong han Biotherapeutic Department Chinese PLA General HospitalBeijingChina Department of Geriatric Hematology Chinese PLA General HospitalBeijingChina Department of Immunology Institute of Basic MedicineSchool of Life SciencesChinese PLA General HospitalBeijingChina

For refractory or relapsed(r/r)B-cell non-Hodgkin lymphoma(NHL),the response rates to conventional salvage chemotherapy are 27–44%.1 Chimeric antigen receptors(CARs)efficiently redirect T-cell specificity and cytotoxicity to cells expressing the targeted Ag in an HLA-independent manner.2 The early phase clinical trials of CART cells for(r/r)B-cell NHL have demonstrated promising results..

关键词： lymphoma specificity chemotherapy

Congenital cholesteatoma of the middle ear-a report of 10 cases

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Journal of Otology 2007年第2期2卷 119-123页

作者： SHEN wei-dong, han wei-ju, YANG Shi-ming, DAI Pu, LIU Liang-fa, FENG Bo, WANG Jia-ling, ZHOU Qi-you, han dong-yi Department of Otolaryngology, head and Neck Surgery, PLA General Hospital, Beijing, China 100853 Department of Otolaryngology head and Neck Surgery PLA General Hospital Beijing China 100853

Objectives To study clinical, imaging features and treatment outcomes of congenital cholesteatoma of middle ear (CCME). Methods This is a retrospective review of 10 CCME cases selected from 952 cholesteatoma cases treated between January 1995 and December 2005 at the Department of Otolaryngology-Head and Neck Surgery, Chinese PLA General Hospital. The main outcome measures were the site of origin, clinical features, surgical findings, imaging characteristics and hearing results. Results The mean age of the 10 patients was 16 years(ranged from 10 to 24 years), with 6 being older than 18 years. There were 7 males and 3 females. The average delay to diagnosis was longer than 2 years. The mean preoperative PTA was 55 dB HL, with a mean ABG of 45 dB. Typical cholesteatomas were seen behind the tympanic membrane in the superoposterior quadrant on otoscopy only in 2 patients. High resolution CT was completed in all patients. Most of the patients(8/10) were diagnosed with otosclerosis or ossicular abnormality before operation. All patients underwent a one-stage tympanoplasty following transmeatal explorative tympanotomy and complete cholesteatoma removal, except one, who underwent a CWU mastoidectomy due to extensive cholesteatoma involvement. The choleasteatoma lesion was confined to the superoposterior mesotympanum in all patients. The mean postoperative PTA was 20 dB HL. All patients were followed-up for at least 1.5 years postoperatively. Revision procedures were performed in 2 patients for hearing deterioration. No residual or recurrence of cholesteatoma was found. Conclusion CCME is a rare disease that often gets delayed diagnosis. Residual lesions and the prognosis mainly depend on the extent of the lesion.

关键词： congenital cholesteatoma middle ear surgery

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一种分布式人脸识别方法及性能优化

光学精密工程 2017年第3期25卷 779-785页

作者：闵卫东石杰韩清王玮天津工业大学计算机科学与软件学院天津300387 南昌大学信息工程学院江西南昌330031

传统的集中式人脸识别方法在时间效率和可扩展性等方面存在不足,已经不能满足大规模实时人脸识别的需求。针对这个技术瓶颈,本文提出了一种分布式人脸识别方法,该模型由多个代理和一个服务器组成。代理能够同时对多个视频中的行人进行... 详细信息

传统的集中式人脸识别方法在时间效率和可扩展性等方面存在不足,已经不能满足大规模实时人脸识别的需求。针对这个技术瓶颈,本文提出了一种分布式人脸识别方法,该模型由多个代理和一个服务器组成。代理能够同时对多个视频中的行人进行检测、跟踪以及特征提取,服务器则对视频中的行人执行识别操作。针对代理处理的任务分布不均而导致处理视频时间过长、任务量过大引起的CPU利用率激增问题,设计了代理的负载均衡来进行性能优化。利用代理统计处理的视频总数及每个视频中的行人数,并将统计数据发送给服务器。服务器通过负载均衡将视频重新分配给每个代理进行人脸识别。实验结果证明,分布式人脸识别有效地提高了人脸识别方法的效率和可扩展性。对一些较为极端的实验例子,经过性能优化后,代理中最大的CPU利用率降低近40%,有效地缓解了时间延迟问题。

关键词：人脸识别分布式代理负载均衡性能优化

FHL2 Interacts with and Acts as a Functional Repressor of Id2 in Human Neuroblastoma Cells

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Chinese Journal of Cancer Research 2009年第2期21卷 81-89页

作者： wei-dong han Zhi-qiang Wu Ya-li Zhao Yi-ling Si Xiao-bing Fu Department of Molecular Biology Institute of Basic Medicine Chinese PLA General HospitalBeijing 100853 China

Objective： Id2 is a natural inhibitor of the basic helix-loop-helix（bHLH） transcription factors. Although it is well known that active ld2 prevents differentiation and promotes cell cycle progression and tumorigenesis, the molecular events that regulate Id2 activity remain to be investigated. Methods： Yeast two-hybrid, mammalian two-hybrid, GST-pulldown and immunoprecipitation （ColP） assays were used to screen and identify novel Id2 interactors. Luciferase assays were used to detect E47-mediated transcription activity. Colony formation and BrdU incorporation assays were used to determine cellular proliferation abilities. Northorn blot, western blot and quantitative PCR methods were used to measure gene expression levels. Electrophoretic mobility shift assays （EMSAs） were performed to investigate protein/DNA binding. Results： The LIM-only protein FHL2 （four-and-a-half-LIM-only protein 2） was identified to be a novel Id2 interactor. The HLH domain within Id2 is not required for its interaction with FHL2. FHL2 antagonizes the inhibitory effect of Id2 on the basic helix-loop-helix protein E47-mediated transcription. FHL2 prevents the formation of Id2-E47 heterdimer, thus releasing E47 to its target DNA and restoring its transcriptional activity. FHL2 expression was remarkably up-regulated during retinoic acid-induced differentiation of neuroblastoma cells, during which the expression of Id2 is opposite to that. Ectopic FHL2 expression in neuroblastoma cells markedly reduces the transcriptional and cell-cycle promoting functions of Id2. Conclusion： These results indicate that FHL2 is an important repressor of the oncogenic activity of Id2 in neuroblastoma cells.

关键词： FHL2 Id2 Repressor Neuroblastoma Proliferation

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大型市场火灾的扑救战术

消防科学与技术 2015年第6期34卷 789-791页

作者：魏捍东河北省消防总队河北石家庄050000

受经济社会发展及城市区域功能定位等因素影响,大型商业市场日益集中化、规模化、大型化。结合沧州市国富市场服务有限公司火灾扑救,分析了大型市场火灾的特点,研究思考了此类场所火灾扑救的战术措施。

关键词：大型市场火灾灭火救援