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Flurbiprofen microneedle patches for the management of acute postoperative pain

Nano Research 2024年第8期17卷 7493-7503页

作者： Huaqing Chu Yanyan Zhang Yuan Yang Jiangtao Xue Cong Li Wei Zhang Zhou Li Hui Zheng national cancer Center/national Clinical Research Center for cancer/cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Beijing institute of Nanoenergy and Nanosystems Chinese Academy of SciencesBeijing 101400China Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases School of Integrated Chinese and Western MedicineHunan University of Chinese MedicineChangsha 410208China School of Life Science Institute of Engineering MedicineBeijing Institute of TechnologyBeijing 100081China institute of Process Engineering Chinese Academy of SciencesBeijing 100190China

Acute postoperative pain is commonly treated with flurbiprofen(FBP),but conventional delivery methods are *** study prepared a new non-burst release microneedles(MNs)using genipin cross-linked gelatin(cGel).By adding varying amounts of genipin to modulate the crosslinking degree of cGel,the drug release behavior of the drug-loaded MNs in the skin can be *** crosslinking parameters that meet therapeutic requirements are selected,thus providing rapid and longlasting analgesic *** solutions were successfully cross-linked,altering matrix material microstructure,confirmed by scanning electron microscope imaging and fourier transform infrared *** demonstrated increasing mechanical strength with higher *** release rates were rapid initially,then slowed,exhibiting a characteristic of decreased release rates with increasing degrees of *** vivo,FBP/cGel MNs significantly reduced allodynia and hyperalgesia post-surgery,with the greatest effect observed at 2–3 h post-surgery,and can maintain analgesia for up to 6 *** tests confirmed good ***/cGel MNs effectively penetrate the stratum corneum,safely delivering drugs with significant analgesic effects,excellent mechanical properties,and good biocompatibility,representing a promising strategy for managing acute postoperative pain.

关键词： microneedle postoperative pain flurbiprofen non-steroid anti-inflammatory drug cross-linked gelatin

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The E3 ubiquitin ligase TRAF6 controls CTLA-4 turnover and promotes T-cell-mediated antitumor immunity

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Cellular & Molecular Immunology 2024年第1期21卷 97-99页

作者： Xiao-Liang Jie Hua Guo Guang-Biao Zhou State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College100021 BejingChina

Yu et al.[1]reported that the tumor necrosis factor(TNF)receptor OX40(CD134)-TNF receptor-associated factor 6(TRAF6)axis mediates Lys63-linked ubiquitination and subsequent lysosomal degradation of cytotoxic T-lymphocyte antigen 4(CTLA-4),leading to the enhancement of CD8^(+)T-cell-mediated antitumor *** findings unveil a previously unknown mechanism in controlling the stability of the immune checkpoint CTLA-4 and provide a potential therapeutic target for the improvement of Tcell-based immunotherapy.

关键词： immunity OX40 ubiquitin

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World Journal of Gastroenterology 2024年第9期30卷 1224-1236页

作者： Hai-Yang Li Lin-Lin Zheng Nan Hu Zhi-Hao Wang Chang-Cheng Tao Ya-Ru Wang Yue Liu Zulihumaer Aizimuaji Hong-Wei Wang Rui-Qi Zheng Ting Xiao Wei-Qi Rong Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Hepatobiliary Hernia Surgery Liaocheng Dongcangfu People’s HospitalLiaocheng 252000Shandong ProvinceChina State Key Laboratory of Molecular Oncology Department of Etiology and CarcinogenesisNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and treatment of HCC has gained much attention over the past two *** To perform a bibliometric analysis to systematically assess the current state of research on HCC-related *** The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to“articles”and“reviews”published in English.A total of 873 relevant publications related to HCC and telomerase were *** employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications,such as the trends in the publications,citation counts,most prolific or influential writers,and most popular journals;to screen for keywords occurring at high frequency;and to draw collaboration and cluster analysis charts on the basis of coauthorship and *** was utilized to compile and visualize the bibliometric *** A surge of 51 publications on HCC/telomerase research occurred in 2016,the most productive year from 1996 to 2023,accompanied by the peak citation count recorded in *** to December 2023,35226 citations were made to all publications,an average of 46.6 citations to each *** United States received the most citations(n=13531),followed by China(n=7427)and Japan(n=5754).In terms of national cooperation,China presented the highest centrality,its strongest bonds being to the United States and *** the 20 academic institutions with the most publications,ten came from China and the rest of Asia,though the University of Paris Cité,Public Assistance-Hospitals of Paris,and the national institute of Health and Medical Research(INSERM)were the most *** for individual contributions,Hisatomi H,Kaneko S,and Ide T were the three most prolific a

关键词： Telomerase Bibliometric analysis Telomerase reverse transcriptase Prognosis Treatment Hepatocellular carcinoma

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Neddylation Regulation of Immune Responses

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Research 2024年第3期2023卷 545-559页

作者： Hongmei Mao Xin Lin Yi Sun cancer institute(Key Laboratory of cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China institute for Immunology School of MedicineTsinghua UniversityBeijing 100084China Changping Laboratory Beijing 102206China cancer Center of Zhejiang University Hangzhou 310029China Zhejiang Provincial Clinical Research Center for cancer HangzhouZhejiang ProvinceChina Key Laboratory of Molecular Biology in Medical Sciences HangzhouZhejiang ProvinceChina Research Center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China.

Neddylation plays a vital role in post-translational modification, intricately shaping the regulation of diverse biological processes, including those related to cellular immune responses. In fact, neddylation exerts control over both innate and adaptive immune systems via various mechanisms. Specifically, neddylation influences the function and survival of innate immune cells, activation of pattern recognition receptors and GMP-AMP synthase–stimulator of interferon genes pathways, as well as the release of various cytokines in innate immune reactions. Moreover, neddylation also governs the function and survival of antigen-presenting cells, which are crucial for initiating adaptive immune reactions. In addition, neddylation regulates T cell activation, proliferation, differentiation, survival, and their effector functions, thereby ensuring an appropriate adaptive immune response. In this review, we summarize the most recent findings in these aspects and delve into the connection between dysregulated neddylation events and immunological disorders, especially inflammatory diseases. Lastly, we propose future directions and potential treatments for these diseases by targeting neddylation.

关键词： activation thereby initiating

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Effectiveness of colorectal cancer screening integrating non-genetic and genetic risk: a prospective study based on UK Biobank data

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cancer Biology & Medicine 2024年第8期21卷 712-723页

作者： Yu Zhang Chao Sheng Zhangyan Lyu Hongji Dai Fangfang Song Fengju Song Yubei Huang Kexin Chen Department of Epidemiology and Biostatistics Key Laboratory of Molecular Cancer EpidemiologyKey Laboratory of Prevention and Control of Human Major DiseasesMinistry of EducationNational Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin Medical UniversityTianjin 300060China

Objective: Few studies have evaluated the benefits of colorectal cancer(CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model(Qcancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and ***: We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the UK Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios(HRs) and absolute risk reductions(ARRs) for CRC incidence and mortality according to risk ***: During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediateand high-risk groups [incidence: HR: 0.87, 95% confidence interval(CI): 0.81±0.94;0.81, 0.73±0.90;mortality: 0.75, 0.64±0.87;0.70, 0.58±0.85], which composed approximately 60% of the study population. The ARRs(95% CI) were 0.17(0.11±0.24) and 0.43(0.24±0.61), respectively, for CRC incidence, and 0.08(0.05±0.11) and 0.24(0.15±0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk ***: After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources.

关键词： Colorectal cancer screening polygenic risk score incidence mortality

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Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis

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Signal Transduction and Targeted Therapy 2024年第2期9卷 738-750页

作者： Yun Zhang Lijun Du Chenxi Wang Zhangsheng Jiang Qingchi Duan Yiping Li Zhijun Xie Zhixing He Yi Sun Lin Huang Liwei Lu Chengping Wen Key Laboratory of Chinese medicine rheumatology of Zhejiang Province Research Institute of Chinese Medical Clinical Foundation and ImmunologyCollege of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China Department of General Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China cancer institute(Key Laboratory of cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China cancer Center of Zhejiang University Hangzhou 310029China Department of Pathology and Shenzhen institute of Research and Innovation The University of Hong KongHong KongChina Chongqing International institute for Immunology Chongqing 400038China

Systemic lupus erythematosus(SLE),a severe autoimmune disorder,is characterized by systemic inflammatory response,autoantibody accumulation and damage to *** dysregulation of double-negative(DN)T cells is considered as a crucial commander during ***,a significant type of protein post-translational modification(PTM),has been well-proved to regulate T cell-mediated immune ***,the function of neddylation in SLE is still ***,we reported that neddylation inactivation with MLN4924,a specific inhibitor of NEDD8-activating enzyme E1(NAE1),or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus *** investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells,contributing to the apoptosis of the accumulated DN T cells in lupus *** double knockout(KO)lupus-prone mice(Ube2m-/-Bim-/-lpr)were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus *** findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus ***,we also found that in SLE patients,the proportion of DN T cells was raised and their apoptosis was ***,compared to healthy groups,SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation ***,the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE ***,our findings provide the direct evidence about the function of neddylation during lupus,suggesting a promising therapeutic approach for this disease.

关键词： inactivation double finding

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Epigenetics and environmental health

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Frontiers of Medicine 2024年第4期18卷 571-596页

作者： Min Zhang Ting Hu Tianyu Ma Wei Huang Yan Wang Key Laboratory of cancer and Microbiome State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100021China Beijing Key Laboratory of cancer Invasion and Metastasis Research Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCapital Medical UniversityBeijing100069China

Epigenetic modifications including DNA methylation,histone modifications,chromatin remodeling,and RNA modifications complicate gene regulation and heredity and profoundly impact various physiological and pathological *** recent years,accumulating evidence indicates that epigenetics is vulnerable to environmental changes and regulates the growth,development,and diseases of individuals by affecting chromatin activity and regulating gene *** exposure or induced epigenetic changes can regulate the state of development and lead to developmental disorders,aging,cardiovascular disease,Alzheimer's disease,cancers,and so ***,epigenetic modifications are *** use of specific epigenetic inhibitors targeting epigenetic changes in response to environmental exposure is useful in disease ***,we provide an overview of the role of epigenetics in various ***,we summarize the mechanism of epigenetic alterations induced by different environmental exposures,the influence of different environmental exposures,and the crosstalk between environmental variation epigenetics,and genes that are implicated in the body's ***,the interaction of multiple factors and epigenetics in regulating the initiation and progression of various diseases complicates clinical *** discuss some commonly used epigenetic drugs targeting epigenetic modifications and methods to prevent or relieve various diseases regulated by environmental exposure and epigenetics through diet.

关键词： epigenetics environmental exposure health prevention and therapy

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AKT2^(S128)/CCTα^(S315/319/323)-positive cancer-associated fibroblasts (CAFs) mediate focal adhesion kinase (FAK) inhibitors resistance via secreting phosphatidylcholines (PCs)

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Signal Transduction and Targeted Therapy 2024年第2期9卷 782-796页

作者： Jie Chen Lingyuan Zhang Yuheng Zhu Di Zhao Jing Zhang Yanmeng Zhu Jingyuan Pang Yuanfan Xiao Qingnan Wu Yan Wang Qimin Zhan Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&Institute100142 BeijingChina Peking University International cancer institute Peking University100191 BeijingChina Research Unit of Molecular cancer Research Chinese Academy of Medical SciencesBeijingChina Soochow University cancer institute Suzhou 215000China institute of cancer Research Shenzhen Bay LaboratoryShenzhen 518107China

Abnormal metabolism is regarded as an oncogenic hallmark related to tumor progression and therapeutic *** study employed multi-omics,including phosphoproteomics,untargeted metabolomics and lipidomics,to demonstrate that the pAKT2 Ser128 and pCCTαSer315/319/323-positive cancer-associated fibroblasts(CAFs)substantially release phosphatidylcholines(PCs),contributing to the resistance of focal adhesion kinase(FAK)inhibitors in esophageal squamous cell carcinoma(ESCC)***,we observed extremely low levels of FAK Tyr397 expression in CAFs,potentially offering no available target for FAK inhibitors playing their anti-growth role in ***,FAK inhibitor increased the intracellular concentration of Ca2+in CAFs,promoting the formation of AKT2/CCTαcomplex,leading to phosphorylation of CCTαSer315/319/323 sites and eventually enhancing stromal PC *** activation could stimulate the intratumoral Janus kinase 2(JAK2)/Signal transducer and activator of transcription 3(STAT3)pathway,triggering resistance to FAK *** of clinical samples demonstrated that stromal pAKT2 Ser128 and pCCTαSer315/319/323 are related to the tumor malignancy and reduced patient ***-targeted lipidomics and further validation cohort quantitatively showed that plasma PCs enable to distinguish the malignant extent of ESCC *** conclusion,inhibition of stroma-derived PCs and related pathway could be possible therapeutic strategies for tumor therapy.

关键词： CAFs metabolism resistance

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Magnetic resonance imaging-based lymph node radiomics for predicting the metastasis of evaluable lymph nodes in rectal cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1849-1860页

作者： Yong-Xia Ye Liu Yang Zheng Kang Mei-Qin Wang Xiao-Dong Xie Ke-Xin Lou Jun Bao Mei Du Zhe-Xuan Li Department of Radiology The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina Department of Colorectal Surgery Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210000Jiangsu ProvinceChina1 Department of Pathology The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina Colorectal Center The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina

BACKGROUND Lymph node(LN)staging in rectal cancer(RC)affects treatment decisions and patient *** radiologists,the traditional preoperative assessment of LN metastasis(LNM)using magnetic resonance imaging(MRI)poses a *** To explore the value of a nomogram model that combines Conventional MRI and radiomics features from the LNs of RC in assessing the preoperative metastasis of evaluable *** In this retrospective study,270 LNs(158 nonmetastatic,112 metastatic)were randomly split into training(n=189)and validation sets(n=81).LNs were classified based on pathology-MRI *** MRI features[size,shape,margin,T2-weighted imaging(T2WI)appearance,and CE-T1-weighted imaging(T1WI)enhancement]were *** radiomics models used 3D features from T1WI and T2WI ***,a nomogram model combining conventional MRI and radiomics features was *** model used univariate analysis and multivariable logistic *** employed the receiver operating characteristic curve,with DeLong test for comparing diagnostic *** performance was assessed using calibration and decision curve *** The nomogram model outperformed conventional MRI and single radiomics models in evaluating *** the training set,the nomogram model achieved an area under the curve(AUC)of 0.92,which was significantly higher than the AUCs of 0.82(P<0.001)and 0.89(P<0.001)of the conventional MRI and radiomics models,*** the validation set,the nomogram model achieved an AUC of 0.91,significantly surpassing 0.80(P<0.001)and 0.86(P<0.001),*** The nomogram model showed the best performance in predicting metastasis of evaluable LNs.

关键词： Radiomics Lymph node metastasis Rectal cancer Magnetic resonance imaging

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Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression

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Signal Transduction and Targeted Therapy 2024年第1期9卷 279-294页

作者： Liping Chen Shihao Zhu Tianyuan Liu Xuan Zhao Tao Xiang Xiao Hu Chen Wu Dongxin Lin Department of Etiology and Carcinogenesis National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key Laboratory of cancer Genomic Biology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Collaborative Innovation Center for cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China CAMS Oxford institute Chinese Academy of Medical SciencesBeijing 100006China Sun Yat-sen University cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China

Epithelial-mesenchymal transition(EMT)and proliferation play important roles in epithelial cancer formation and progression,but what molecules and how they trigger EMT is largely *** we performed spatial transcriptomic and functional analyses on samples of multistage esophageal squamous-cell carcinoma(ESCC)from mice and humans to decipher these critical *** investigating spatiotemporal gene expression patterns and cell–cell interactions,we demonstrated that the aberrant epithelial cell interaction via EFNB1-EPHB4 triggers EMT and cell cycle mediated by downstream SRC/ERK/AKT *** aberrant epithelial cell interaction occurs within the basal layer at early precancerous lesions,which expands to the whole epithelial layer and strengthens along the cancer development and *** analysis revealed that the aberrant EFNB1-EPHB4 interaction is caused by overexpressedΔNP63 due to TP53 mutation,the culprit in human ESCC *** results shed new light on the role of TP53-TP63/ΔNP63-EFNB1-EPHB4 axis in EMT and cell proliferation in epithelial cancer formation.

关键词： esophageal TP53 squamous

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