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Effectiveness of mindfulness-based interventions on the well-being of healthcare workers:a systematic review and meta-analysis

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General Psychiatry 2024年第3期37卷 335-344页

作者： Natasha Yixuan Ong Finn Jing Jie Teo Jane Zi Ying Ee Chun En Yau Julian Thumboo Hiang Khoon Tan Qin Xiang Ng NUS Yong Loo Lin School of Medicine National University of SingaporeSingapore Health Services Research Unit Singapore General HospitalSingapore SingHealth Duke-NUS Medicine Academic Clinical Programme Duke-NUS Medical SchoolSingapore Singhealth Duke-NUS Global Health Institute Singapore Duke Global Health Institute Duke UniversityDurhamNorth CarolinaUSA division of Surgery and Surgical oncology Singapore General HospitalSingapore Saw Swee Hock School of Public Health National University of Singapore and National University Health SystemSingapore

Background Growing evidence attests to the efficacy of mindfulness-based interventions(MBIs),but their effectiveness for healthcare workers remains *** To evaluate the evidence for MBIs in improving healthcare workers’psychological *** A systematic literature search was conducted on Medline,Embase,Cumulative Index for Nursing and Allied Health Literature,PsycINFO and Cochrane Central Register of Controlled Trials up to 31 August 2022 using the keywords‘healthcare worker’,‘doctor’,‘nurse’,‘allied health’,‘mindfulness’,‘wellness’,‘workshop’and‘program’.Randomised controlled trials with a defined MBI focusing on healthcare workers and quantitative outcome measures related to subjective or psychological well-being were eligible for inclusion.R V.4.0.3 was used for data analysis,with the standardised mean difference as the primary outcome,employing DerSimonian and Laird’s random effects *** of Recommendations,Assessment,Development and Evaluation framework was used to evaluate the quality of ***’s Risk of Bias 2 tool was used to assess the risk of bias in the included *** A total of 27 studies with 2506 participants were included,mostly from the USA,involving various healthcare *** such as stress reduction programmes,apps,meditation and training showed small to large effects on anxiety,burnout,stress,depression,psychological distress and job strain outcomes of the *** effects were also seen in self-compassion,empathy,mindfulness and ***,long-term outcomes(1 month or longer postintervention)varied,and the effects were not consistently *** MBIs offer short-term benefits in reducing stress-related symptoms in healthcare *** review also highlights limitations such as intervention heterogeneity,reduced power in specific subgroup analyses and variable study quality.

关键词： nurse sustained workers

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Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia

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Genes & Diseases 2024年第1期11卷 413-429页

作者： Dongsheng Zhang Wenjuan Tang Haitao Niu William Tse Hai-Bin Ruan Helmut Dolznig Thomas Knosel Friedrich Karl-Heinz Madeleine Themanns Jiang Wang Mingquan Song Lee Denson Lukas Kenner Richard Moriggl Yi Zheng Xiaonan Han division of Hematology and oncology Division of Cancer BiologyDepartment of MedicineMetroHealth Medical Center(MHMC)Case Western Reserve University(CWRU)School of MedicineClevelandOH 44109USA Cancer Genomics and Epigenomics Program Case Comprehensive Cancer CenterCase Western Reserve University(CWRU)ClevelandOH 44106USA division of Gastroenterology Hepatology and NutritionCincinnati Children’s Hospital Medical Center(CCHMC)CincinnatiOH 45229USA Children’s Hospital of Fudan University Shanghai 201102China School of Medicine Jinan UniversityGuangzhouGuangdong 510632China Laboratory Animal Science(ILAS) Chinese Academy of Medical Science(CAMS)and Peking Union Medical College(PUMC)Beijing 100006China Department of Integrative Biology and Physiology University of Minnesota Medical SchoolMinneapolisMI 55455USA Institute of Medical Genetics Medical University of ViennaVienna 1040Austria Institute of Pathology Ludwig-Maximilians-University MunichMunich 80539Germany Institute of Biochemistry II University Hospital JenaJena 07743Germany Laboratory Animal Pathology University of Veterinary Medicine ViennaVienna 1210Austria Department of Pathology University of CincinnatiCincinnatiOH 45221USA Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266005China Department of Pathology Medical University of ViennaVienna 1040Austria Ludwig Boltzmann Institute for Cancer Research Vienna 1090Austria Medical University of Vienna Vienna 1040Austria Institute of Animal Breeding and Genetics University of Veterinary Medicine ViennaVienna 1210Austria division of Experimental Hematology CCHMCCincinnatiOH 45229USA

CDC42 controls intestinal epithelial(IEC)stem cell(IESC)*** aberrant CDC42 initiates intestinal inflammation or neoplasia is *** utilized models of inflam-matory bowel diseases(IBD),colorectal cancer,aging,and IESC injury to determine the loss of intestinal Cdc42 upon inflammation and *** specimens were collected to determine the levels of CDC42 in IBD or colorectal ***42 floxed mice were crossed with Villin-Cre,Villin-CreERT2 and/or Lgr5-eGFP-IRES-CreERT2,or Bmi1-CreERT2 mice to generate Cdc42 deficient ***,colitis,aging,and intestinal organoid were used to evaluate CDC42 upon mucosal inflammation,IESC/progenitor regenerative capacity,and IEC *** studies revealed that increased CDC42 in colorectal cancer correlated with lower survival;in contrast,lower levels of CDC42 were found in the inflamed IBD *** Cdc42 depletion significantly reduced Lgr5+IEsCs,increased progenitors'hyperplasia,and induced mucosal inflammation,which led to crypt *** Cdc42 depletion markedly enhanced irra-diation-or chemical-induced *** or inhibition of Cdc42 reduced colonic Lgr5+IESC *** conclusion,depletion of Cdc42 reduces the IESC regeneration and IEC repair,leading to prolonged mucosal *** monogenic loss of Cdc42 in-duces mucosal inflammation,which could result in intestinal neoplasia in the context of aging.

关键词： Cell divisioncycle 42(CDC42) Colitis Colorectal cancer(CRC) Inflammatory bowel diseases(IBD) Intestinal epithelial cell(IEC) Intestinal epithelial stem cell(IESC) Irradiation

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Microbiota enterotoxigenic Bacteroides fragilis-secreted BFT-1 promotes breast cancer cell stemness and chemoresistance through its functional receptor NOD1

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Protein & Cell 2024年第6期15卷 419-440页

作者： Wei Ma Lu Zhang Weilong Chen Zhaoxia Chang Juchuanli Tu Yuanyuan Qin Yuwen Yao Mengxue Dong Jiajun Ding Siqin Li Fengkai Li Qiaodan Deng Yifei Yang Tingting Feng Fanrong Zhang Xiying Shao Xueyan He Lixing Zhang Guohong Hu Quentin Liu Yi-Zhou Jiang Shu Zhu Zhi Xiao Dan Su Tong Liu Suling Liu Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences State Key Laboratory of Genetic EngineeringCancer InstitutesDepartment of OncologyKey Laboratory of Breast Cancer in ShanghaiThe Shanghai Key Laboratory of Medical EpigeneticsShanghai Key Laboratory of Radiation OncologyThe International Co-laboratory of Medical Epigenetics and MetabolismMinistry of Science and TechnologyShanghai Medical CollegeFudan UniversityShanghai 200032China Intelligent Pathology Institute and Department of Pathology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230071China Department of Thyroid Breast and Vascular SurgeryXijing HospitalFourth Military Medical UniversityXi’an 710032China Institute of Immunology CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Department of Pathology The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Department of Breast Surgery The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Department of Breast 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 SciencesHangzhou 310022China Shanghai Institute of Nutrition and Health University of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China Department of Breast Surgery Xiangya HospitalChangsha 410008China Department of Breast Surgery Tumor Hospital of Harbin Medic

Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant ***,targeting microbiota to improve the effects of breast cancer therapy has not been investigated in ***,we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis(ETBF)was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant ***,albeit at low biomass,secreted the toxic protein BFT-1 to promote breast cancer cell stemness and *** studies showed that BFT-1 directly bound to NOD1 and stabilized NOD1 ***1 was highly expressed on ALDH+breast cancer stem cells(BCSCs)and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation,thereby activating the NOTCH1-HEY1 signaling pathway to increase ***1 inhibition and ETBF clearance increase the chemosensitivity of breast cancer by impairing BCSCs.

关键词： NOD1 breast chemotherapy

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Re-evaluating the role of pelvic radiation in the age of modern precision medicine and systemic therapy

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World Journal of Clinical oncology 2024年第1期15卷 1-4页

作者： Tao-Wei Ke Yu-Min Liao Sheng-Chi Chang Che-Hung Lin William Tzu-Liang Chen Ji-An Liang Chun-Ru Chien Department of Colorectal Surgery China Medical University HospitalTaichung 40402Taiwan School of Chinese Medicine College of Chinese MedicineChina Medical UniversityTaichung 40402Taiwan division of Hematology and oncology Department of Internal MedicineChina Medical University HospitalTaichung 40402Taiwan Department of Colorectal Surgery China Medical University Hsinchu HospitalHsinchu 30272Taiwan School of Medicine College of MedicineChina Medical UniversityTaichung 40402Taiwan Department of Radiation oncology China Medical University HospitalTaichung 40402Taiwan

The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC(J Clin Oncol 2019;37:3223-3233),NCT04165772(N Engl J Med 2022;386:2363-2376),and PROSPECT(N Engl J Med 2023;389:322-334).In this review,we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.

关键词： Radiotherapy Locally advanced stage rectal cancer Precision medicine Systemic therapy Clinical trial

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Impact of frailty on endoscopic retrograde cholangiopancreatography outcomes in nonagenarians:A United States national experience

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World Journal of Gastrointestinal Endoscopy 2024年第3期16卷 148-156页

作者： Sanket Dhirubhai Basida Dushyant Singh Dahiya Muhammad Nadeem Yousaf Brinda Basida Bhanu Siva Mohan Pinnam Manesh Kumar Gangwani Hassam Ali Sahib Singh Yash R Shah Daksh Ahluwalia Mihir Prakash Shah Saurabh Chandan Neil R Sharma Shyam Thakkar Department of Internal Medicine University of Missouri-ColumbiaColumbiaMO 65212United States division of Gastroenterology Hepatology&MotilityThe University of Kansas School of MedicineKansas CityKS 66160United States division of Gastroenterology and Hepatology University of MissouriColumbiaMO 65212United States Department of Rheumatology Medical College of GeorgiaAugusta UniversityNorth AugustaGA 30912United States Department of Internal Medicine John H.Stroger Hospital of Cook CountyChicagoIL 60612United States Department of Internal Medicine The University of ToledoToledoOH 43606United States division of Gastroenterology and Hepatology East Carolina University/Brody School of MedicineGreenvilleNC 27858United States Department of Internal Medicine Sinai HospitalBaltimoreMD 21215United States Department of Internal Medicine Trinity Health Oakland/Wayne State UniversityPontiacMI 48341United States division of Gastroenterology and Hepatology Creighton University School of MedicineOmahaNE 68131United States division of Interventional oncology&Surgical Endoscopy GI Oncology Tumor Site TeamParkview Cancer InstituteParkview HealthFort WayneIN 46845United States Section of Gastroenterology&Hepatology West Virginia University School of MedicineMorgantownWV 26505United States

BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)is an essential therapeutic tool for biliary and pancreatic *** and elderly patients,especially those aged≥90 years are generally considered a higher-risk population for ERCP-related *** To investigate outcomes of ERCP in the Non-agenarian population(≥90 years)concerning *** This is a cohort study using the 2018-2020 National Readmission *** aged≥90 were identified who underwent ERCP,using the international classification of diseases-10 code with clinical *** Hopkins’s adjusted clinical groups frailty indicator was used to classify patients as frail and *** primary outcome was mortality,and the secondary outcomes were morbidity and the 30 d readmission rate related to *** used univariate and multivariate regression models for *** A total of 9448 patients were admitted for any indications of *** and non-frail patients were 3445(36.46%)and 6003(63.53%)*** for ERCP were Choledocholithiasis(74.84%),Biliary pancreatitis(9.19%),Pancreatico-biliary cancer(7.6%),Biliary stricture(4.84%),and Cholangitis(1.51%).Mortality rates were higher in frail group[adjusted odds ratio(aOR)=1.68,P=0.02].The Intra-procedural complications were insigni-ficant between the two groups which included bleeding(aOR=0.72,P=0.67),accidental punctures/lacerations(aOR=0.77,P=0.5),and mechanical ventilation rates(aOR=1.19,P=0.6).Post-ERCP complication rate was similar for bleeding(aOR=0.72,P=0.41)and post-ERCP pancreatitis(aOR=1.4,P=0.44).Frail patients had a longer length of stay(6.7 d vs 5.5 d)and higher mean total charges of hospitalization($78807 vs$71392)compared to controls(P<0.001).The 30 d all-cause readmission rates between frail and non-frail patients were similar(P=0.96).CONCLUSION There was a significantly higher mortality risk and healthcare burden amongst nonagenarian frail patients undergoing ERCP compared

关键词： Endoscopic retrograde cholangiopancreatography Nonagenarians Frailty Mortality Healthcare burden

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Interleukin-1β:Friend or foe for gastrointestinal cancers

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World Journal of Gastrointestinal oncology 2024年第5期16卷 1676-1682页

作者： Kullanat Khawkhiaw Jutatip Panaampon Thanit Imemkamon Charupong Saengboonmee Department of Biochemistry Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Center for Translational Medicine Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Cholangiocarcinoma Research Institute Khon Kaen UniversityKhon Kaen 40002Thailand Department of Medical oncology Dana-Farber Cancer InstituteHarvard Medical SchoolBostonMA 02215United States Department of Medicine Harvard Medical SchoolBostonMA 02215United States division of Hematopoiesis Joint Research Center for Human Retrovirus InfectionKumamoto UniversityKumamoto 860-0811Japan Department of Medicine Faculty of MedicineKhon Kaen UnivsersityKhon Kaen 40002Thailand

Gastrointestinal(GI)cancer is a malignancy arising in the digestive system and accounts for approximately a third of increasing global cancer-related mortality,especially in the colorectum,esophagus,stomach,and ***-1β(IL-1β)is a leukocytic pyrogen recognized as a tumor progression-related ***-1βsecretion and maturation in inflammatory responses could be regulated by nuclear factor-kappaB-dependent expression of NLR family pyrin domain containing 3,inflammasome formation,and activation of IL-1 converting *** studies have documented the pro-tumorigenic effects of IL-1β in tumor microenvironments,promoting proliferation and metastatic potential of cancer cells in vitro and tumorigenesis in *** application of IL-1β inhibitors is also promising for targeted therapy development in some cancer ***,as a leukocytic pro-inflammatory cytokine,IL-1β may also possess anti-tumorigenic effects and be type-specific in different *** editorial discusses the up-to-date roles of IL-1β in GI cancers,including underlying mechanisms and down-stream signaling *** and clarifying the roles of IL-1β would significantly benefit future therapeutic targeting and help improve therapeutic outcomes in patients suffering from GI cancer.

关键词： Cancer Gastrointestinal tract Inflammation Interleukin-1β Tumor microenvironment

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The exploration of cell population data in clinical use: Beyond infectious diseases

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iLABMED 2024年第2期2卷 125-140页

作者： Shayuanzi Huang Yin Liu Liu Qian Juan Zhou Dong Wang Department of Laboratory Medicine the First Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdongChina Department of Laboratory Medicine Guangxi Hospital Division of the First Affiliated HospitalSun Yat-Sen UniversityNanningGuangxiChina Department of Medical Affair Danaher Diagnostic PlatformShanghaiChina Department of oncology General Hospital of the Southern Theatre CommandPLAGuangzhouGuangdongChina

Cell population data(CPD)is regarded as the fingerprint of a blood cell at a given *** parameters harbor information associated with cell morphology and can be automatically generated using modern hematological *** studies have revealed many unique clinical applications for CPD,especially for infectious diseases,such as *** example,one monocyte-related CPD parameter is the monocyte distribution width(MDW),which can be generated using a Beckman Coulter hematological *** has received FDA and CE approval for aiding in sepsis diagnosis in adult patients in the emergency ***,MDW can serve as a diagnostic biomarker in patients infected with *** has also been widely explored for possible clinical applications beyond infectious dis-eases,such as for predicting myelodysplastic syndromes,screening for he-matological malignancies,and detecting sterile *** parameter measurements are easily obtained and quite cost-effective,making them practical for clinical ***,there are some potential drawbacks of CPD *** pre-analytical conditions can affect CPD ***-more,CPD are specific to certain hematological analyzers and the result cannot be transferred between different *** practical usefulness of CPD reference intervals is also still *** this review,wesummarize the current studies related to CPD and its clinical *** well-designed clinical studies related to CPD are still expected.

关键词： cell population data Coulter principle hematology analyzer infectious diseases white blood cell

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Overcoming geographical and socioeconomic limitations in colorectal cancer screening

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World Journal of Gastrointestinal oncology 2024年第5期16卷 1683-1689页

作者： Sofia Rozani Panagis M Lykoudis School of Medicine National and Kapodistrian University of AthensAthens 11527Greece division of Surgery and Interventional Science University College LondonLondon WC1E 6BTUnited Kingdom

Despite colorectal cancer’s(CRC)high global incidence,residents of low-and middle-income countries,as well as low-income minorities in advanced economies have low screening *** studies demonstrate that in these groups higher incidence of CRC is observed,yet screening rates remain low for consistent *** income,low educational background,and lack of awareness in combination with inadequate social security of certain population groups impede access and compliance rates to CRC *** the other hand,despite the global availability of multiple screening approaches(colonoscopy,sigmoidoscopy,faecal occult blood test,faecal immunochemical test,computed tomography-colonography,etc.)with proven diagnostic validity,many low-income countries still lack established screening *** absence of screening guidelines in these countries along with the heterogeneity of guidelines in the rest of the world,demonstrate the need for global measures to tackle this issue *** essential step forward is to develop a global approach that will link specific elements of screening with the incidence and available resources in each country,to ensure the achievement of at least a minimum screening program in low-income *** cheaper,cost-effective techniques,which can be carried out by less specialized healthcare providers,might not be equivalent to endoscopy for CRC screening but seems more realistic for areas with fewer *** has been highlighted as the most pivotal element for the effective implementation of any screening program concerning ***,multiple studies have demonstrated that outreach strategies and community-based educational programs are associated with encouraging outcomes,yet a centrally coordinated expansion of these programs could provide more consistent ***,patient navigator programs,wherever implemented,have increased CRC screening and improved ***,global coordin

关键词： Colorectal cancer Screening Low-and middle-income countries Socioeconomic disparities Cancer

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Pyrotinib and chrysin synergistically potentiate autophagy in HER2-positive breast cancer

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Signal Transduction and Targeted Therapy 2024年第1期9卷 295-307页

作者： Xiaoxiao Liu Xing Zhang Zhiying Shao Xiaorong Zhong Xin Ding Liang Wu Jie Chen Ping He Yan Cheng Kunrui Zhu Dan Zheng Jing Jing Ting Luo Institute for Breast Health Medicine Cancer CenterBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Department of Radiation oncology Cancer CenterAffiliated Hospital of Xuzhou Medical UniversityJiangsu Center for the Collaboration and Innovation of Cancer BiotherapyCancer InstituteXuzhou Medical University221000 XuzhouChina Department of Orthopedics Trauma and Reconstructive SurgeryUniversity Hospital RWTH AachenAachen 52074Germany Cancer Institute Xuzhou Medical University221000 XuzhouJiangsuChina division of Nephrology and Transplantation Department of Internal MedicineUniversity Medical Center Rotterdam Erasmus MCRotterdam 3015 GDThe Netherlands Institute for Breast Health Medicine Department of General SurgeryBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Institute for Breast Health Medicine West China HospitalSichuan University610041 ChengduSichuanChina

Human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC)has been the most challenging subtype of BC,consisting of 20%of BC with an apparent correlation with poor *** that pyrotinib,a new HER2 inhibitor,has led to dramatic improvements in prognosis,the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired ***,identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing ***,we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in HER2-positive *** determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest,inhibit the proliferation of BT-474 and SK-BR-3 BC cells,and repress in vivo tumor growth in xenograft mice *** may be attributed to enhanced autophagy induced by endoplasmic reticulum ***,the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase(G6PD)degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16(ZBTB16)in tumorigenesis of ***,we identified that miR-16-5p was a potential upstream regulator of ZBTB16,and it showed a significant inverse correlation with *** of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against HER2-positive ***,these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.

关键词： HER2 synergistic Together

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High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

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Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of Genetics and Medicine TIGEMPozzuoliNaples 80131Italy Medical Genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Department of Internal Medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2

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