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Epidemiology of insertional and midportion Achilles tendinopathy in runners:A prospective cohort study

Journal of Sport and Health Science 2024年第2期13卷 256-263页

作者： Wenbo Chen Kyra L.A.Cloosterman Sita M.A.Bierma-Zeinstra Marienke van Middelkoop Robert-Jan de Vos Department of Orthopaedic Surgery and Sports Medicine Erasmus MC University Medical CenterRotterdam 3015GDthe Netherlands Department of General Practice Erasmus MC University Medical CenterRotterdam 3015GDthe Netherlands Department of Sports Medicine Huashan HospitalFudan UniversityShanghai 200040China

Background:Achilles tendinopathy(AT)is a common problem among *** is only limited evidence for risk factors for AT,and most studies have not defined the AT *** study has compared the incidence and risk factors between insertional AT and midportion AT,though they are considered *** study aimed to assess incidence and risk factors of AT based on data from a large prospective *** secondary aim was to explore differences in risk factors between insertional and midportion ***:Participants were recruited from among registered runners at registration for running *** were completed at baseline,1 month before the event,1 week before the event,and 1 month after the *** concerning demographics,training load,registered events,and running-related injuries were collected at *** follow-up questionnaires collected information about new injuries.A pain map was used to diagnose midportion and insertional *** primary outcome was the incidence of *** logistic regression analysis was applied to identify risk factors for the ***:We included 3379 participants with a mean follow-up of 20.4 *** incidence of AT was 4.2%.The proportion of insertional AT was 27.7%and of midportion AT was 63.8%;the remaining proportion was a combined type of insertional and midportion *** had a significantly higher incidence(5%,95%confidence interval(95%CI):4.1%-6.0%)than women(2.8%,95%CI:2.0%-3.8%).AT in the past12 months was the most predominant risk factor for new-onset AT(odds ratio(OR)=6.47,95%CI:4.27-9.81).This was similar for both subcategories of AT(insertional:OR=5.45,95%CI:2.51-11.81;midportion:OR=6.96,95%CI:4.24-11.40).Participants registering for an event with a distance of 10/10.55 km were less likely to develop a new-onset AT(OR=0.59,95%CI:0.36-0.97)or midportion AT(OR=0.47,95%CI:0.23-0.93).Higher age had a significant negative association with insertional AT(OR=0.97,95%CI:0.9

关键词： Achilles tendon injury Incidence Risk factor Running-related injury

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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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Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions

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Virologica Sinica 2024年第1期39卷 123-133页

作者： Hongbo Guo Dan Liu Kuan Liu Yao Hou Chunyang Li Qiudi Li Xiaohui Ding Monique M.A.Verstegen Jikai Zhang Lingli Wang Yibo Ding Renxian Tang Xiucheng Pan Kuiyang Zheng Luc J.Wvan der Laan Qiuwei Pan Wenshi Wang Department of Pathogen Biology and Immunology Jiangsu Key Laboratory of Immunity and MetabolismJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhou221004China Department of Gastroenterology and Hepatology Erasmus MC-University Medical CenterRotterdamNL-3015 CNthe Netherlands Department of Surgery Erasmus MC Transplant InstituteUniversity Medical CenterRotterdam3015CENL-3015 CNthe Netherlands Department of Infectious Diseases The Affiliated Hospital of Xuzhou Medical UniversityXuzhou221002China

Hepatitis E virus(HEV)infection can cause severe complications and high mortality,particularly in pregnant women,organ transplant recipients,individuals with pre-existing liver disease and immunosuppressed ***,there are still unmet needs for treating chronic HEV ***,we screened a best-in-class drug repurposing library consisting of 262 drugs/*** screening,we identified vidofludimus calcium and pyrazofurin as novel anti-HEV *** calcium is the next-generation dihydroorotate dehydrogenase(DHODH)inhibitor in the phase 3 pipeline to treat autoimmune diseases or SARS-CoV-2 *** selectively targets uridine monophosphate synthetase(UMPS).Their anti-HEV effects were further investigated in a range of cell culture models and human liver organoids models with wild type HEV strains and ribavirin treatment failure-associated HEV ***,both drugs exhibited a sizeable therapeutic window against *** instance,the IC50 value of vidofludimus calcium is 4.6–7.6-fold lower than the current therapeutic doses in ***,their anti-HEV mode of action depends on the blockage of pyrimidine ***,two drugs robustly inhibited ribavirin treatment failure-associated HEV mutants(Y1320H,G1634R).Their combination with IFN-αresulted in synergistic antiviral *** conclusion,we identified vidofludimus calcium and pyrazofurin as potent candidates for the treatment of HEV *** on their antiviral potency,and also the favorable safety profile identified in clinical studies,our study supports the initiation of clinical studies to repurpose these drugs for treating chronic hepatitis E.

关键词： Hepatitis Evirus(HEV) Drug repurposing Vidofludimus calcium Pyrazofurin Pyrimidine biosynthesis

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C19mc miRNA-520G induces SP100 antiviral gene transcription and inhibits melanin production in skin cutaneous melanoma

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Genes & Diseases 2024年第1期11卷 60-63页

作者： Goodwin G.Jinesh Marian T.Smallin Nino Mtchedlidze Isha Godwin Marco Napoli Nicole Hackel Manali S.Phadke Avani A.Deshpande Xiaobo Li John H.Lockhart Jaden R.Baldwin Suehelay Acevedo-Acevedo Yifeng Gao Michelle A.Reiser Keiran S.M.Smalley Elsa R.Flores Andrew S.Brohl Department of Molecular Oncology H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Molecular Medicine Program H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Saveetha Medical College ChennaiTamil Nadu 602105India Tumor Biology Department H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Sarcoma Department H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA

SP100 is an antiviral protein that restricts the productive stage of human papillomavirus(HPV)and multiple other viruses,and viruses in turn block sUMO-1-mediated stabilization of SP100 and promotes its degradation(Table S1).Interferon(IFN)signaling could still produce more SP100 through transcription to counteract viruses.1 Viruses also disable the transcriptional up-regulation of SP100 to achieve persistent infection in hosts.

关键词： SP100 melanoma stabilization

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DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

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Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li Department of Medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA Division of Cellular&Molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or mc38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant mc38 mouse cell line(mc38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against mc38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

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Genetic investigation of the ubiquitin-protein ligase E3A gene as putative target in Angelman syndrome

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World Journal of Clinical Cases 2024年第3期12卷 503-516页

作者： Wiem Manoubi Marwa Mahdouani Dorra Hmida Ameni Kdissa Aida Rouissi Ilhem Turki Neji Gueddiche Najla Soyah Ali Saad Christian Bouwkamp Ype Elgersma Soumaya Mougou-Zerelli Moez Gribaa Laboratory of Human Cytogenetics Molecular Genetics and Reproductive BiologyFarhat Hached University HospitalSousse 4000Tunisia Higher institute of Biotechnology of Monastir University of MonastirMonastir 3000Tunisia Department of Neuropediatry La Rabta HospitalTunis 2000Tunisia Department of Pediatric Farhat Hached University HospitalSousse 4000Tunisia Department of Neuroscience Erasmus MCthe NetherlandsRotterdam 3112 tdNetherlands

BACKGROUND Angelman syndrome(AS)is caused by maternal chromosomal deletions,imprinting defects,paternal uniparental disomy involving chromosome 15 and the ubiquitin-protein ligase UBE3A gene *** the genetic basis remains unclear for several *** To investigate the involvement of UBE3A gene in AS and identifying new potential genes using exome *** We established a cohort study in 50 patients referred to Farhat Hached University Hospital between 2006 and 2021,with a strong suspicion of AS and absence of chromosomal *** UBE3A gene was screened for mutation *** unrelated patients issued from consanguineous families were subjected to exome *** We describe seven UBE3A variants among them 3 none previously described including intronic variants c.2220+14T>C(intron14),c.2507+43T>A(Exon15)and insertion in Exon7:c.30-47_*** exome sequencing revealed 22 potential genes that could be involved in AS-like syndromes that should be investigated *** Screening for UBE3A mutations in AS patients has been proven to be useful to confirm the *** exome findings could rise to new potential alternative target genes for genetic counseling.

关键词： Angelman syndrome Ubiquitin-protein ligase E3A Exome Consanguinity Polymorphism

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In vitro bench testing using patient-specific 3D models for percutaneous pulmonary valve implantation with Venus P-valve

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Chinese Medical Journal 2024年第8期137卷 990-996页

作者： Yu Han Zehua Shao Zirui Sun Yan Han Hongdang Xu Shubo Song Xiangbin Pan Peter P.T.de Jaegere Taibing Fan Gejun Zhang Department of Structure Heart Disease Central China Fuwai Hospital of Zhengzhou UniversityZhengzhouHenan 451460China Children’s Heart Center Central China Fuwai Hospital of Zhengzhou UniversityZhengzhouHenan 451460China Department of Anesthesiology Central China Fuwai Hospital of Zhengzhou UniversityZhengzhouHenan 451460China Department of Structure Heart Disease Fuwai Hospital Chinese Academy of Medical SciencesBeijing 100037China Department of Cardiology Erasmus MCRotterdam 3015 GDNetherlands

Background:Due to the wide variety of morphology,size,and dynamics,selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation(PPVI).This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional(3D)-printed models for planning PPVI with the Venus ***:Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou ***:3D model bench testing altered treatment strategy in all patients(100%).One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor *** the remaining 14 patients,valve size and/or implantation location was altered to avoid valve migration and/or compression coronary *** four patients,it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract(RVOT)(n=2)or risk of compression coronary artery(n=2).Concerning sizing,we found that an oversize of 2-5 mm *** of the valve was dictated by the flaring of the in-and outflow portion in the pulmonary *** was successful in all 14 patients(absence of valve migration,no coronary compression,and none-to-mild residual pulmonary regurgitation[PR]).The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group(36[2]vs.32[4],Z=-3.77,P<0.001).Conclusions:In vitro testing indicated no need to oversize the Venus P-valve to the degree recommended by the balloon-sizing technique,as 2-5 mm sufficed.

关键词： Heart valve prosthesis implantation Percutaneous pulmonary valve intervention Pulmonary regurgitation bench testing 3D printing Venus P-valve

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A Review of Lightweight Security and Privacy for Resource-Constrained IoT Devices

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Computers, Materials & Continua 2024年第1期78卷 31-63页

作者： Sunil Kumar Dilip Kumar Ramraj Dangi Gaurav Choudhary Nicola Dragoni Ilsun You Department of Computer Science and Engineering National Institute of Technology JamshedpurJamshedpurIndia School of Computing Science and Engineering VIT University BhopalBhopal466114India Center for Industrial Software The Maersk Mc-Kinney Moller InstituteUniversity of Southern DenmarkSonderborgOdenseDenmark Department of Applied Mathematics and Computer Science Technical University of DenmarkLyngby2800Denmark Department of Information Security Cryptologyand MathematicsKookmin UniversitySeoulSouth Korea

The widespread and growing interest in the Internet of Things(IoT)may be attributed to its usefulness in many different *** settings are probed for data,which is then transferred via linked *** are several hurdles to overcome when putting IoT into practice,from managing server infrastructure to coordinating the use of tiny *** it comes to deploying IoT,everyone agrees that security is the biggest *** is due to the fact that a large number of IoT devices exist in the physicalworld and thatmany of themhave constrained resources such as electricity,memory,processing power,and square *** research intends to analyse resource-constrained IoT devices,including RFID tags,sensors,and smart cards,and the issues involved with protecting them in such restricted *** lightweight cryptography,the information sent between these gadgets may be *** order to provide a holistic picture,this research evaluates and contrasts well-known algorithms based on their implementation cost,hardware/software efficiency,and attack resistance *** also emphasised how essential lightweight encryption is for striking a good cost-to-performance-to-security ratio.

关键词： IoT a sensor device lightweight cryptography block cipher smart card security and privacy

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Does community-based health insurance affect lifestyle and timing of treatment seeking behavior?Evidence from Ethiopia

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Global Health Journal 2024年第2期8卷 83-90页

作者： Zecharias Fetene Anteneh Anagaw D.Mebratie Zemzem Shigute Getnet Alemu Arjun S.Bedi Center for Health Economics University of YorkYorkUnited Kingdom School of Public Health College of Health SciencesAddis Ababa UniversityAddis AbabaEthiopia International institute of Social Studies Erasmus University Rotterdamthe Haguethe Netherlands institute of Development and Policy Research Addis Ababa UniversityAddis AbabaEthiopia

Objectives This paper aims to investigate the effects of enrollment in the Ethiopian community-based health insurance(CBHI)scheme on household preventive care activities and the timing of treatment-seeking behavior for illness *** is growing concern about the financial sustainability of CBHI schemes in developing ***,few empirical studies have identified potential contributors,including ex-ante and ex-post moral *** We implement a household fixed-effect panel data regression model,drawing on three rounds of household survey data collected face to face in districts where CBHI scheme is operational and in districts where it is not operational in *** The findings show that enrolment in CBHI does not significantly influence household behaviour regarding preventive care activities such as water treatment before drinking and handwashing before ***,CBHI significantly increases delay in treatment-seeking behaviour for diseases ***,on average,we estimate about 4-6 h delay for malaria symptoms,a little above 4 h for tetanus,and 10-11 h for tuberculosis among the insured *** While there is evidence that CBHI improve the utilization of outpatient or primary care services,our study suggests that insured members may wait longer before visiting health *** delay could be partly due to moral hazard problems,as insured households,particularly those from rural areas,may consider the opportunity costs associated with visiting health facilities for minor ***,it is essential to identify the primary causes of delays in seeking medical services and implement appropriate interventions to encourage insured individuals to seek early medical attention.

关键词： Community-based health insurance Financial sustainability Preventive care Treatment-seeking behavior Household fixed effect Ethiopia

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Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small cell lung cancer cell lines

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Journal of Integrative Medicine 2024年第4期22卷 503-514页

作者： Li-hua Zhu Yu-pei Liang Lian Yang Feng Zhu Li-jun Jia He-gen Li Department of Oncology Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China cancer institute of Traditional Chinese Medicine Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Department of Laboratory Medicine Huadong HospitalFudan UniversityShanghai 200237China

Objective:Studies have demonstrated that cycloastragenol induces antitumor effects in prostate,colorectal and gastric cancers;however,its efficacy for inhibiting the proliferation of lung cancer cells is largely *** study explores the efficacy of cycloastragenol for inhibiting non-small cell lung cancer(NSCLC)and elucidates the underlying molecular ***:The effects of cycloastragenol on lung cancer cell proliferation were assessed using an adenosine triphosphate monitoring system based on firefly luciferase and clonogenic formation ***-induced apoptosis in lung cancer cells was evaluated using dual staining flow cytometry with an annexin V-fluorescein isothiocyanate/propidium iodide *** elucidate the role of cycloastragenol in the induction of apoptosis,apoptosis-related proteins were examined using Western *** and Western blotting were used to determine whether cycloastragenol could induce autophagy in lung cancer *** techniques,including small interfering RNA technology,were used to investigate the underlying *** effects against lung cancer and biosafety of cycloastragenol were evaluated using a mouse subcutaneous tumor ***:Cycloastragenol triggered both autophagy and ***,cycloastragenol promoted apoptosis by facilitating the accumulation of phorbol-12-myristate-13-acetate-induced protein 1(NOXA),a critical apoptosis-related ***,cycloastragenol induced a protective autophagy response through modulation of the adenosine 5'-monophosphate-activated protein kinase(AMPK)/unc-51-like autophagy-activating kinase(ULK1)/mammalian target of rapamycin(mTOR)***:Our study sheds new light on the antitumor efficacy and mechanism of action of cycloastragenol in *** insight provides a scientific basis for exploring combination therapies that use cycloastragenol and inhibiting the AMPK/ULK1/mTOR pathway as a promising approach to

关键词： Non-small cell lung cancer Cycloastragenol Autophagy Apoptosis

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