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Sorafenib sensitization in tumor therapy by iron overload and AMPK activation

Nano Research 2024年第7期17卷 6386-6399页

作者： Jun Zhu Shoujie Zhao Yejing Zhu Shouzheng Ma Tenghui Han Fenghua Xu Huichen Li Bo Wang Zhixiong guo Da Chen Yongquan Qu Zhimin Tian Junlong Zhao Lei Liu State Key laboratory of Holistic Integrative Management of gastrointestinal Cancers National Clinical Research Center for Digestive DiseasesXijing HospitalFourth Military Medical UniversityXi’an 710032China Department of general Surgery The Southern Theater Air Force HospitalGuangzhou 510602China Department of general Surgery Tangdu HospitalFourth Military Medical UniversityXi’an 710038China Department of Thoracic Surgery Tangdu HospitalFourth Military Medical UniversityXi’an 710038China Department of Neurology Airborne Army HospitalWuhan 430012China Key laboratory of Modern teaching Technology(Ministry of Education) Shaanxi Normal UniversityXi’an 710062China State Key laboratory of Holistic Integrative Management of gastrointestinal Cancers Department of Biochemistry and Molecular BiologySchool of Basic MedicineFourth Military Medical UniversityXi’an 710032China Key laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an 710072China State Key laboratory of Holistic Integrative Management of gastrointestinal Cancers Department of Medical Genetics and Developmental BiologyFourth Military Medical UniversityXi’an 710032China Department of Pediatrics Tangdu HospitalFourth Military Medical UniversityXi’an 710000China

Sorafenib,as a first-line drug for advanced hepatocellular carcinoma(HCC),could trigger ferroptosis by inhibiting cystine/glutamate ***,low-level intracellular iron and insufficient activation of adenosine monophosphate(AMP)-activated protein kinase(AMPK)confer impaired response to *** this study,a unique sorafenib nanocomposite dexterously modified with Fe-Material of Institut Lavoisier(sora@Fe-MIL)was synthesized to escalate intracellular iron level and activate AMPK,further potentiating the ferroptotic effect of ***,this strategic deployment of sora@Fe-MIL triggered an extensive demise of cancer cells,while manifesting negligible deleterious impact on normal *** prominent ferroptosis biomarkers,glutathione peroxidase 4(gPX4)and solute carrier family 7 member 11(SLC7A11),underwent pronounced downregulation,underscoring the efficacy of this strategy in inducing ***,the bioactivity of AMPK was considerably elevated,and its downstream targets were conspicuously inhibited by the treatment with sora@*** orthotopic HCC animal models,we observed a substantial suppression of primary in situ tumor growth,and ribonucleic acid(RNA)sequencing elucidated an elevated degree of ferroptosis and AMPK activation with the treatment of sora@*** conclusion,we proposed that the meticulously designed strategy for secure and efficacious iron release and AMPK activation could significantly potentiate the ferroptotic impact of sorafenib,thus resuscitating its therapeutic response in HCC patients.

关键词： anti-tumor ferroptosis Fe-Material of Institut Lavoisier(Fe-MIL) sorafenib adenosine monophosphate(AMP)-activated protein kinase(AMPK)

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Drug repurposing for cancer therapy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia Ming Sun Hai Huang Wei-Lin Jin Center for clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The First Affiliated hospital of guizhou university of Traditional Chinese Medicine Guiyang 550001PR China School of clinical laboratory Science Guizhou Medical UniversityGuiyang 550004PR China Division of gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

Cancer,a complex and multifactorial disease,presents a significant challenge to global *** significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic ***,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer *** promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved *** repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety *** light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat *** describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor *** addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug *** also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy *** conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

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Optimized new Shengmai powder(优化新生脉散方) inhibits myocardial fibrosis in heart failure by regulating the rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway

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Journal of Traditional Chinese Medicine 2024年第3期44卷 448-457页

作者： ZHANg Zeyu JIA Zhuangzhuang SONg Yuwei ZHANg Xuan WANg Ci WANg Shuai ZHANg Peipei REN Qiuan WANg Xianliang MAO Jingyuan Department of Cardiovascular the First Teaching Hospital of Tianjin University of Traditional Chinese MedicineNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion

OBJECTIVE: Exploring the effect of Optimized New Shengmai powder(优化新生脉散方, ONSMP) on myocardial fibrosis in heart failure(HF) based on rat sarcoma(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase kinase(MEK)/extracellular regulated protein kinases(ERK) signaling pathway. METHODS: Randomized 70 Sprague-Dawley rats into sham(n = 10) and operation(n = 60) groups, then established the HF rat by ligating the left anterior descending branch of the coronary artery. We randomly divided the operation group rats into the model, ONSMP [including low(L), medium(M), and high(H) dose], and enalapril groups. After the 4-week drug intervention, echocardiography examines the cardiac function and calculates the ratios of the whole/left heart to the rat's body weight. Finally, we observed the degree of myocardial fibrosis by pathological sections, determined myocardium collagen(COL) Ⅰ and COL Ⅲ content by enzyme-linked immunosorbent assay, detected the m RNA levels of COL Ⅰ, COL Ⅲ, α-smooth muscle actin(α-SMA), and c-Fos proto-oncogene(c-Fos) by universal real-time, and detected the protein expression of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ETS-like-1 transcription factor(p-ELK1), p-c-Fos, α-SMA, COL Ⅰ, and COL Ⅲ by Western blot. RESULTS: ONSMP can effectively improve HF rat's cardiac function, decrease cardiac organ coefficient, COL volume fraction, and COL Ⅰ/Ⅲ content, down-regulate the m RNA of COL Ⅰ/Ⅲ, α-SMA and c-Fos, and the protein of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ELK1, c-Fos, COL Ⅰ/Ⅲ, and α-SMA. CONCLUSIONS: ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.

关键词： extracellular regulated protein kinases heart failure mitogen-activated protein kinases myocardial fibrosis optimized new Shengmai powder rapidly accelerated fibrosarcoma sarcoma

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Association between body mass index and in vitro fertilization/intra-cytoplasmic sperm injection outcomes:An analysis of 15,124 normal ovarian responders in China

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Chinese Medical Journal 2024年第7期137卷 837-845页

作者： Danlei Zheng Yuanyuan Wang Lixue Chen Lin Zeng Rong Li Department of Obstetrics and gynecology Center for Reproductive MedicinePeking University Third HospitalBeijing 100191China Research Center of clinical Epidemiology Peking University Third HospitalBeijing 100191China

Background:High body mass index(BMI)results in decreased fecundity,and women with high BMI have reduced rates of clinical pregnancy and live birth in in vitro fertilization/intra-cytoplasmic sperm injection(IVF/ICSI).Meanwhile,ovarian responses show great heterogeneity in patients with a high *** study aimed to analyze the effects of a high BMI on IVF/ICSI outcomes in the Chinese female with normal ovarian ***:We performed a retrospective cohort study comprising 15,124 patients from the medical record system of the Reproductive Center of Peking university Third hospital,with 3530(23.3%)in the overweight group and 1380(9.1%)in the obese group,who had a normal ovarian response(5-15 oocytes retrieved)and underwent fresh embryo transfer(ET)cycles from January 2017 to December 2018,followed by linked frozen-thawed embryo transfer(FET)cycles from January 2017 to December *** live birth rate(CLBR)was used as the primary ***,a generalized additive model was applied to visually illustrate the curvilinear relationship between BMI and the *** used a decision tree to identify the specific population where high BMI had the greatest effect on IVF/ICSI ***:High BMI was associated with poor IVF/ICSI outcomes,both in cumulative cycles and in separate fresh ET or FET *** cumulative cycles,compared with the normal weight group,obesity was correlated with a lower positive pregnancy test rate(adjusted odds ratio[aOR]:0.809,95%confidence interval[CI]:0.682-0.960),lower clinical pregnancy rate(aOR:0.766,95%CI:0.646-0.907),lower live birth rate(aOR:0.706,95%CI:0.595-0.838),higher cesarean section rate(aOR:2.066,95%CI:1.533-2.785),and higher rate of large for gestational age(aOR:2.273,95%CI:1.547-3.341).In the generalized additive model,we found that CLBR declined with increasing BMI,with 24 kg/m^(2)as an inflection *** the decision tree,BMI only made a difference in the population aged≤34.5 years,with anti-Muller

关键词： Obesity Body mass index fertilization Live birth Decision trees Normal ovarian response

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Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

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Biomedical and Environmental Sciences 2024年第3期37卷 303-314页

作者： YANg Liu WANg Shi Yu JIANg Ting Ting DENg Wen CHANg Min WU Shu Ling CAO Wei Hua LU Yao SHEN ge LIU Ru Yu gAO Yuan Jiao XU Meng Jiao HU Lei Ping ZHANg Lu XIE Yao LI Ming Hui Department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Center for Infectious Diseases Second Affiliated Hospital of Air Force Medical UniversityXi'an 710038ShaanxiChina Department of Hepatology Division 2 Peking University Ditan Teaching HospitalBeijing 100015China

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and *** This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow *** In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P allg intermittent interferon therapy in patients with chronic hepatitis B.

关键词： CHB Dendritic Cells Intermittent Interferon Therapy Plateau Phase

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DNA framework signal amplification platform-based highthroughput systemic immune monitoring

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1115-1131页

作者： Ye Chen Xingyu Chen Bowen Zhang Yuxin Zhang Songhang Li Zhiqiang Liu Yang gao Yuxuan Zhao Lin Yan Yi Li Taoran Tian Yunfeng Lin State Key laboratory of Oral Diseases National Center for StomatologyNational Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041 SichuanPR China Department of Prosthodontics Tianjin Stomatological HospitalSchool of MedicineNankai UniversityTianjin 300041PR China Department of laboratory Medicine West China HospitalSichuan UniversityChengdu 610041 SichuanPR China Sichuan Provincial Engineering Research Center of Oral Biomaterials Chengdu 610041 SichuanChina

Systemic immune monitoring is a crucial clinical tool for disease early diagnosis,prognosis and treatment planning by quantitative analysis of immune ***,conventional immune monitoring using flow cytometry faces huge challenges in large-scale sample testing,especially in mass health screenings,because of time-consuming,technical-sensitive and high-cost ***,the lack of high-performance detection platforms hinders the development of high-throughput immune monitoring *** address this bottleneck,we constructed a generally applicable DNA framework signal amplification platform(DSAP)based on post-systematic evolution of ligands by exponential enrichment and DNA tetrahedral framework-structured probe design to achieve high-sensitive detection for diverse immune cells,including CD4+,CD8+T-lymphocytes,and monocytes(down to 1/100μl).Based on this advanced detection platform,we present a novel high-throughput immune-cell phenotyping system,DSAP,achieving 30-min one-step immune-cell phenotyping without cell washing and subset analysis and showing comparable accuracy with flow cytometry while significantly reducing detection time and *** a proof-of-concept,DSAP demonstrates excellent diagnostic accuracy in immunodeficiency staging for 107 HIV patients(AUC>0.97)within 30 min,which can be applied in HIV infection monitoring and ***,we initially introduced promising DSAP to achieve high-throughput immune monitoring and open robust routes for point-of-care device development.

关键词： diagnosis monitoring initially

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Inflection point Age in the Middle and Older Women—Jiangxi Province,China,2020-2022

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China CDC weekly 2024年第9期6卷 162-167页

作者： Shanlan Yang Langlang Zhang Helang Huang Jiaofeng Wang Lei Wu Zhijun Bao Shanghai Institute of Infectious Disease and Biosecurity Fudan UniversityShanghaiChina Department of gerontology Huadong Hospital Affiliated to Fudan UniversityShanghai Key Laboratory of Clinical Geriatric MedicineResearch Center on Aging and MedicineFudan UniversityShanghaiChina Jiangxi Provincial Key laboratory of Preventive Medicine School of Public HealthNanchang UniversityNanchang CityJiangxi ProvinceChina

Summary What is already known about this topic?Previous studies have predominantly examined the micro-level aspects of women aging inflection points,while macro-level research using big data on the inflection points o... 详细信息

关键词： Middle Jiangxi currently

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Rapid and sensitive detection of urinary KIM-1 using fully printed photonic crystal microarrays

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Nano Research 2024年第5期17卷 4329-4337页

作者： Yang Liu Xuwei He Zewei Lian Qian guo Jimei Chi Xiaoxue Lin Liyue Zhang Zheng Liu Yingyuan Liu Meng Su Keyu Wang Qiangguo Ao Qingli Cheng Department of Nephrology The Second Medical Center of Chinese PLA General HospitalNational Clinical Research Centre for Geriatric DiseasesBeijing 100853China Chinese PLA Medical School Beijing 100853China Key laboratory of green Printing CAS Research/Education Center for Excellence in Molecular SciencesBeijing Engineering Research Center of Nanomaterials for Green Printing TechnologyBeijing National Laboratory for Molecular Sciences(BNLMS)Institute of ChemistryChinese Academy of Sciences(ICCAS)Beijing 100190China Department of Rheumatology and Immunology Peking University International HospitalBeijing 102206China Department of clinical laboratory The Second Medical Center of Chinese PLA General HospitalNational Clinical Research Centre for Geriatric DiseasesBeijing 100853China

Urinary kidney injury molecule 1(uKIM-1)serves as a reliable marker for the early diagnosis of acute kidney injury(AKI).The rapid and facile detection of changes in uKIM-1 is essential for early AKI diagnosis,ultimately improving the prognosis of *** this study,we developed a fully printed photonic crystal-integrated microarray with photonic crystal-enhanced fluorescence properties,which can detect uKIM-1 levels at the *** confirmed its efficacy in the early diagnosis of AKI using clinical urine *** quantitative detection of uKIM-1 was achieved within 10 *** lowest limit of detection is 8.75 pg·mL^(-1) with an accuracy of 94.2%.The diagnostic efficacy was validated using 86 clinical urine samples,highlighting the high sensitivity and stability of the photonic crystal ***,a facile and reliable immunoassay was designed and prepared for the rapid quantitative detection of uKIM-1,which is crucial for the early identification and convenient detection of AKI in hospital or community ***,convenient,cost-effective,and long-term monitoring of changes in uKIM-1 levels can assist clinicians in making timely adjustments to treatment regimens,preventing the transition from AKI to chronic kidney disease(CKD),improving the quality of life of patients with AKI,and reducing healthcare *** highlights the advantages of utilizing urine samples as a noninvasive and easily accessible medium for early detection and monitoring of kidney-related conditions.

关键词： photonic crystal point-of-care testing urine kidney injury molecule-1(KIM-1) acute kidney injury

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Cancer cachexia:Focus on cachexia factors and inter-organ communication

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Chinese Medical Journal 2024年第1期137卷 44-62页

作者： Yongfei Wang Zikai Dong Ziyi An Weilin Jin The First clinical Medical College of Lanzhou university LanzhouGansu 730000China Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhouGansu 730000China

Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs,which is mediated by cancer cachexia *** cachexia factors,being the general name of inflammatory factors,circulating proteins,metabolites,and microRNA secreted by tumor or host cells,play a role in secretory or other organs and mediate complex signal communication between organs during cancer *** cachexia factors are also a potential target for the diagnosis and *** pathogenesis of cachexia is unclear and no clear effective treatment is ***,the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently *** the point of signal communication between organs mediated by cancer cachexia factors,finding a deeper understanding of the pathogenesis,diagnosis,and treatment of cancer cachexia is of great significance to improve the level of diagnosis and *** review begins with cancer cachexia factors released during the interaction between tumor and host cells,and provides a comprehensive summary of the pathogenesis,diagnosis,and treatment for cancer cachexia,along with a particular sight on multi-organ signal communication mediated by cancer cachexia *** summary aims to deepen medical community’s understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.

关键词： Cancer cachexia Cancer cachexia factors Inter-organ communication Tumor ecosystem Tumor microenvironment

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Attitude and willingness on gamete donation among medical students:An experience from a state university in Sri Lanka

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Asian pacific Journal of Reproduction 2024年第3期13卷 120-125页

作者： S.Raguraman K.Muhunthan R.Niroje Department of Obstetrics and gynaecology Faculty of MedicineUniversity of JaffnaJaffnaSri Lanka teaching hospital Jaffna JaffnaSri Lanka

Objective:To assess the attitude and willingness of medical students of the Faculty of Medicine,university of Jaffna,regarding gamete ***:An institutional-based descriptive cross-sectional study was conducted at the Faculty of Medicine,university of Jaffna,from September 2022 to May 2023 among undergraduate medical students who gave their voluntary participation.A self-administered questionnaire was used as a study instrument to collect data regarding their attitude and willingness toward gamete ***:A total of 345 participants were recruited and their sociodemographic data revealed that 56.8%of the participants were female,62.3%aged between 26 and 30 years,and 92.2%were *** of them received information regarding gamete donations during their clinical *** half(67.8%)of them showed a negative attitude towards gamete *** willingness,only 39.7%of participants had a positive approach for being a gamete donor;among them,84.7%preferred anonymous *** and ethnicity had a significant influence on their attitudes and *** addition,male was also found to be more willing to donate ***:Most medical students have negative views about gamete *** awareness and knowledge of assisted reproductive technology and gamete donation within medical students'sociocultural and ethical backgrounds might facilitate a change in attitude towards gamete donation amongst future medical practitioners.

关键词： Medical students gamete donation Assisted reproductive technology Attitude Viewpoint

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