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Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

Neural Regeneration Research 2025年第3期20卷 613-631页

作者： Yanxin Shen Guimei Zhang Chunxiao Wei Panpan Zhao Yongchun Wang Mingxi Li Li Sun Department of Neurology and Neuroscience center The First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina Cognitive Impairment center Department of NeurologyThe First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinica

关键词： apoptosis ferroptosis inflammation lipid peroxidation natural plant products neurodegenerative disorder neuroprotection oxidative stress small-molecule drugs

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Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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Science China Life Sciences 2025年第1期 263-271页

作者： Siyi He Zhiyi Zhang Guohui Song Zhenhai Wang Chunyun Dai Shipeng Yan Kun Jiang Bingbing Song He Li Maomao Cao Dianqin Sun Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen Office of Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian Cancer Institute Linzhou Cancer Hospital center for disease control and prevention of Sheyang County Department of Cancer prevention and control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University Luoshan center for disease control and prevention Office for Cancer control and Research Affiliated Cancer Hospital of Harbin Medical University

Surveillance recommendations for gastric cancer（GC） in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates（CIRs） of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic（atrophic gastritis/intestinal metaplasia） and neoplastic lesions（low-grade/high-grade dysplasia）, respectively(Ptrend<0.001). Four predictors, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients（≥3 risk factors） with non-neoplastic lesions showed higher GC risks（adjusted HR=7.73, 95%CI: 4.29–13.92）, and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions（aHR=3.07, 95%CI: 1.67–5.64） and high-risk patients with mild lesions（aHR=7.29, 95%CI: 3.58–14.86） showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

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An NIR-Ⅱ-emissive Ru(Ⅱ) metallacycle for efficient and safe immunotherapy

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Science China Chemistry 2025年第01期 5-7页

作者： Chonglu Li Jianbo Zhan Biao Dong Institute of Health Inspection and Testing Hubei Provincial Center for Disease Control and Prevention State Key Laboratory on Integrated Optoelectronics College of Electronic Science and Engineering Jilin University

Immunotherapy, as a groundbreaking cancer treatment, has gained considerable attention for its utilization of the body’s immune system to combat tumors [1]. This therapy induces tumor cell apoptosis, triggering a sustained anti-tumor immune response and effectively preventing tumor recurrence and metastasis [2]. The fundamental principle lies in inducing tumor cell death through specific treatment modalities, leading to the release of a cascade of signaling molecules and antigens, thereby mobilizing the immune system to actively identify and attack tumor cells [3].

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COVID-19 Super Spreading Event Amongst Elderly Individuals—jilin Province,China,January 2021

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China cdc weekly 2021年第10期3卷 211-213页

作者： Laishun Yao Mingyu Luo Tiewu Jia Xingang Zhang Zhulin Hou Feng Gao Xin Wang Xiaogang Wu Weihua Cheng Guoqian Li Jing Lu Bing Zhao Tao Li Enfu Chen Dapeng Yin Biao Huang jilin center for disease control and prevention ChangchunJilinChina Zhejiang center for disease control and prevention HangzhouZhejiangChina Chinese center for disease control and prevention BeijingChina Tonghua center for disease control and prevention TonghuaJilinChina.

Summary What is already known on this topic?Clusters of COVID-19 cases often happened in small settings(e.g.,families,offices,school,or workplaces)that facilitate person-to-person virus transmission,especially from a common *** is added by this report?On January 10 and 11,2021,an individual gave three product promotional lectures in Tonghua City.

关键词： promotion jilin happen

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Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

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Neural Regeneration Research 2025年第5期20卷 1455-1466页

作者： Ju Zheng Yixin Li Ting Zhang Yanlin Fu Peiyan Long Xiao Gao Zhengwei Wang Zhizhong Guan Xiaolan Qi Wei Hong Yan Xiao Key Laboratory of Endemic and Ethnic diseases Ministry of Education&Key Laboratory of Medical Molecular Biology of Guizhou ProvinceGuizhou Medical UniversityGuiyangGuizhou ProvinceChina Guizhou center for disease control and prevention GuiyangGuizhou ProvinceChina Department of Histology and Embryology Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Collaborative Innovation center for prevention and control of Endemic and Ethnic Regional diseases Co-constructed by the Province and Ministry GuiyangGuizhou ProvinceChina

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion *** occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains *** this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion *** found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced ***,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating *** autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion *** from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

关键词： apoptosis ATF4 autophagy C/EBP homologous protein cerebral ischemia/reperfusion injury eIF2α endoplasmic reticulum stress PERK

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Index and First-Generation Cases in a COVID-19 Outbreak—jilin Province,China,2021

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China cdc weekly 2021年第19期3卷 405-408页

作者： Weihua Cheng Bing Zhao Enfu Chen Guoqian Li Jun Ma Yanling Cui Changxi Xu Yong Cui Bo Shen Mingyu Luo Dapeng Yin Laishun Yao Tonghua center for disease control and prevention TonghuaJilinChina Chinese center for disease control and prevention BeijingChina Zhejiang center for disease control and prevention HangzhouZhejiangChina jilin center for disease control and prevention ChangchunJilinChina.

Summary What is already known on this topic?Contact tracing and testing with isolated medical care of identified cases is a key strategy for interrupting chains of transmission of COVID-19 and reducing mortality associated with *** the early phases of the COVID-19 pandemic,due to test capacity limitations,case finding often started from suspected *** is added by this report?

关键词： COV limitations chains

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Effectiveness of Interventions to control Transmission of Reemergent Cases of COVID-19--jilin Province,China,2020

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China cdc weekly 2020年第34期2卷 651-654页

作者： Qinglong Zhao Meng Yang Yao Wang Laishun Yao Jianguo Qiao Zhiyong Cheng Hanyin Liu Xingchun Liu Yuanzhao Zhu Zeyu Zhao Jia Rui Tianmu Chen jilin provincial center for disease control and prevention ChangchunJilinChina State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics School of Public HealthXiamen UniversityXiamenFujianChina jilin Municipal center for disease control and prevention Jilin CityJilin ProvinceChina Shulan center for disease control and prevention ShulanJilin CityJilin ProvinceChina

What is already known about this topic?COVID-19 has a high transmissibility calculated by mathematical *** dynamics of the disease and the effectiveness of intervention to control the transmission remain unclear in jilin Province,*** is added by this report?This is the first study to report the dynamic characteristics and to quantify the effectiveness of interventions implemented in the second outbreak of COVID-19 in jilin Province,*** effective reproduction number of the disease before and after May 10 was 4.00 and pdisease in other areas of China even in many other countries.

关键词： Province,China jilin COV

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Serological Investigation of Laboratory-Confirmed and Suspected Ebola Virus disease Patients During the Late Phase of the Ebola Outbreak in Sierra Leone

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Virologica Sinica 2018年第4期33卷 323-334页

作者： Yang Liu YuLan Sun Wei Wu AQian Li XianDa Yang Shuo Zhang Chuan Li QiuDong Su ShaoJian Cai DaPeng Sun HaiYang Hu Zhe Zhang XiuXu Yang Idrissa Kamara Sheku Koroma Gerald Bangura Alie Tia Abdul Kamara Matt Lebby Brima Kargbo Jiandong Li Shiwen Wang XiaoPing Dong YueLong Shu WenBo Xu George F. Gao GuiZhen Wu DeXin Li William J. Liu MiFang Liang Key Laboratory of Medical Virology and Viral diseases Ministry of Health National Institute for Viral Disease Control and Prevention (IVDC) Chinese Center for Disease Control and Prevention (China CDC) Beijing 102206 China Beijing center for disease control and prevention (Beijing cdc China) Beijing 100013 China jilin provincial center for disease control and prevention (jilin cdc China) Jilin 130021 China Fujian provincial center for disease control and prevention (Fujian cdc China) Fuzhou 350001 China Shandong provincial center for disease control and prevention (Shandong cdc China) Jinan 250014 China Jiangsu provincial center for disease control and prevention (Jiangsu cdc China) Nanjing 210009 China Beijing Institute of Biotechnology Beijing 100071 China Sierra Leone-China Friendship Biological Safety Laboratory (SLE-CHN Bio-safety Lab) Freetown 999127 Sierra Leone The Ministry of Health and Sanitation (MoHS SL) Freetown 999127 Sierra Leone CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China

This study aimed to investigate the serological characteristics of Ebola virus(EBOV) infection during the late phase of the Ebola outbreak in Sierra Leone. In total, 877 blood samples from 694 suspected Ebola virus disease(EVD) cases assessed from March to December 2015, were analyzed via real-time reverse transcription polymerase chain reaction(RT-PCR) for viral RNA and enzyme-linked immunosorbent assay(ELISA) and Luminex to detect antibodies against EBOV. Viral load and EBOV-specific IgM/IgG titers displayed a declining trend during March to December 2015. Viral RNA load decreased rapidly at earlier stages after disease onset, while EBOV-specific IgM and IgG still persisted in 58.1%(18/31) and 93.5%(29/31) of the confirmed EVD patients and in 3.8%(25/663) and 17.8%(118/663) of the RNA-negative suspected patients in the later phase, respectively. Dynamic analysis of longitudinally collected samples from eight EVD patients revealed typically reversed trends of declining viral load and increasing IgM and/or IgG titers in response to the EBOV *** present results indicate that certain populations of Sierra Leone developed immunity to an EBOV infection in the late phase of the outbreak, providing novel insights into the risk assessment of EBOV infections among human populations.

关键词： Ebola virus (EBOV) Late phase Serologic investigation IgM IgG

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China cdc weekly 2022年第47期4卷 1043-1050页

作者： Hui Liu Qiyu Zhu Lei Zhang Yujing Liu Peng Xu Maohe Yu Jixiang Fan Xiaohong Pan Xi Chen Huifang Xu Qinying He Mengjie Han National center for AIDS/STD control and prevention Chinese Center for Disease Control and PreventionBeijing MunicipalityChina Chinese Association of STD and AIDS prevention and control Beijing MunicipalityChina Beijing Chaoyang Kangzhong Health and Education center Beijing MunicipalityChina Tianjin center for disease control and prevention Tianjin MunicipalityChina jilin provincial center for disease control and prevention Changchun CityJilin ProvinceChina Zhejiang provincial center for disease control and prevention Hangzhou CityZhejiang ProvinceChina Hunan provincial center for disease control and prevention Changsha CityHunan ProvinceChina Guangdong provincial Association of STD and AIDS prevention and control Guangzhou CityGuangdong ProvinceChina Chengdu center for disease control and prevention Chengdu CitySichuan ProvinceChina.

Summary What is already known about this topic?The number of newly diagnosed human immunodeficiency virus(HIV)cases among Chinese youth 15–24 years of age shows an upward trend between 2010 and *** is added by this report?This survey is on a larger scale as compared to previous *** shows inadequate HIV knowledge—especially on HIV treatment,self-testing,and postexposure prophylaxis—among college students.A significant gap exists between knowledge and behavior as indicated by the low condom use rate despite a high knowledge level.

关键词： knowledge Attitude testing

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Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China

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Biomedical and Environmental Sciences 2024年第2期37卷 178-186页

作者： SONG Yun HE Ying LU Xue Xin ZHANG Xiao Mei JIANG XIAO Lin SONG Qing HUANG Xue Yong MA Hong Xia YU Peng Cheng ZHU Wu Yang Henan provincial center for disease control and prevention Infectious Disease Prevention and Control InstituteHenan Provincial Key Laboratory of Infectious Disease PathogensZhengzhou 450000HenanChina National Institute for Viral disease control and prevention China CDCKey Laboratory of BiosafetyNational Health CommissionBeijing 102206China Shandong provincial center for disease control and prevention Jinan 250014ShandongChina Qingdao Chengyang District center for disease control and prevention Qingdao 266108ShandongChina

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and *** Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120after the first ***,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death *** a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28and 42 after the first *** A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P0.05)in RVNAs levels at any time *** post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05).Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14–28 d)on the immunization potential.

关键词： Rabies Post-exposure immunization Essen regimen RVNAs

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