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Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

Cellular & Molecular Immunology 2024年第1期21卷 33-46页

作者： Anja Meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel Brian Zanotti Michael V.Volin M.Asif Amin Myles J.Lewis Costantino Pitzalis Shiva Arami Joseph A.Karam Nadera J.Sweiss Shiva Shahrara Jesse Brown VA Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of microbiology and Immunology Midwestern UniversityDowners GroveILUSA Division of Rheumatology and clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA centre for Experimental Medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom centre for Experimental Medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

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Present situation of minimally invasive surgical treatment for early gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1154-1165页

作者： Chun-Yan Li Yi-Feng Wang Li-Kang Luo Xiao-Jun Yang The First clinical Medical School Lanzhou UniversityLanzhou 730000Gansu ProvinceChina The First clinical Medicine College Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina General Surgery clinical centre Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina The Second Department of General Surgery Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Lanzhou University People's clinical Hospital Lanzhou 730000Gansu ProvinceChina Gansu Research Center of Prevention and Control Project for Digestive Oncology Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Gansu Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

Minimally invasive surgery is a kind of surgical operation,which is performed by using professional surgical instruments and equipment to inactivate,resect,repair or reconstruct the pathological changes,deformities and wounds in human body through micro-trauma or micro-approach,in order to achieve the goal of treatment,its surgical effect is equivalent to the traditional open surgery,while avoiding the morbidity of conventional surgical *** addition,it also has the advantages of less trauma,less blood loss during operation,less psychological burden and quick recovery on patients,and these minimally invasive techniques provide unique value for the examination and treatment of gastric cancer *** minimally invasive surgical techniques have developed rapidly and offer numerous options for the treatment of early gastric cancer(EGC):endoscopic mucosal resection(EMR),underwater EMR(UEMR),endoscopic submucosal dissection(ESD),endoscopic full-thickness resection(EFTR),endoscopic submu-cosal excavation(ESE),submucosal tunnel endoscopic resection,laparoscopic and endoscopic cooperative surgery(LECS);Among them,EMR,EFTR and LECS technologies have a wide range of applications and different modific-ations have been derived from their respective surgical operations,such as band-assisted EMR(BA-EMR),conven-tional EMR(CEMR),over-the-scope clip-assisted EFTR,no-touch EFTR,the inverted LECS,closed LECS,and so *** new and improved minimally invasive surgeries are more precise,specific and effective in treating different types of EGC.

关键词： Minimally invasive surgery Early gastric cancer Endoscopic mucosal resection Endoscopic full-thickness resection Laparoscopic and endoscopic cooperative surgery

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clinical associations of corneal neuromas with ocular surface diseases

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Neural Regeneration Research 2024年第1期19卷 140-147页

作者： Charmaine Jan Li Toh Chang Liu Isabelle Xin Yu Lee Molly Tzu Yu Lin Louis Tong Yu-Chi Liu Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore Singapore Eye Research Institute Singapore Department of Cornea and External Eye Disease Singapore National Eye CentreSingapore Ophthalmology and Visual Sciences Academic clinical Program Duke-NUS Medical SchoolSingapore

Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or *** formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ***,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas *** recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface *** neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and *** this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment *** current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more *** imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.

关键词： cornea corneal diseases corneal nerve corneal neuropathy in vivo confocal microscopy microneuroma neuroma ocular surface diseases

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SARS-CoV-2 immunity in animal models

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Cellular & Molecular Immunology 2024年第2期21卷 119-133页

作者： Zhao Chen Yaochang Yuan Qingtao Hu Airu Zhu Fenghua Chen Shu Li Xin Guan Chao Lv Tian Tang Yiyun He Jinling Cheng Jie Zheng Xiaoyu Hu Jingxian Zhao Jincun Zhao Jing Sun State Key Laboratory of Respiratory Disease National Clinical Research Centre for Respiratory DiseaseNational Centre for Respiratory MedicineGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510182China GMU-GIBH Joint School of Life Sciences Guangzhou Medical UniversityGuangzhou 510000China Guangzhou National Laboratory GuangzhouGuangdong 510005China Shanghai Institute for Advanced Immunochemical Studies School of Life Science and TechnologyShanghaiTech UniversityShanghai 201210China Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People’s Hospitalthe Second Affiliated HospitalSchool of MedicineSouthern University of Science and TechnologyShenzhen 518005China

The COVID-19 pandemic,which was caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has become a worldwide health crisis due to its ***-CoV-2 infection results in severe respiratory illness and can lead to significant complications in affected *** complications encompass symptoms such as coughing,respiratory distress,fever,infectious shock,acute respiratory distress syndrome(ARDS),and even multiple-organ *** models serve as crucial tools for investigating pathogenic mechanisms,immune responses,immune escape mechanisms,antiviral drug development,and vaccines against ***,various animal models for SARS-CoV-2 infection,such as nonhuman primates(NHPs),ferrets,hamsters,and many different mouse models,have been *** model possesses distinctive features and *** this review,we elucidate the immune response elicited by SARS-CoV-2 infection in patients and provide an overview of the characteristics of various animal models mainly used for SARS-CoV-2 infection,as well as the corresponding immune responses and applications of these models.A comparative analysis of transcriptomic alterations in the lungs from different animal models revealed that the K18-hACE2 and mouse-adapted virus mouse models exhibited the highest similarity with the deceased COVID-19 ***,we highlighted the current gaps in related research between animal model studies and clinical investigations,underscoring lingering scientific questions that demand further clarification.

关键词： COVID-19 SARS-CoV-2 animal models immune response

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Predictors of the placebo response in a nutraceutical randomized controlled trial for depression

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Journal of Integrative Medicine 2024年第1期22卷 46-53页

作者： Rosemary Arnold Jenifer Murphy-Smith Chee H.Ng David Mischoulon Gerard J.Byrne Chad A.Bousman Con Stough Michael Berk Jerome Sarris Professorial Unit the Melbourne ClinicDepartment of PsychiatryUniversity of MelbourneRichmond 3121Australia Depression clinical and Research Program Department of PsychiatryMassachusetts General HospitalHarvard Medical SchoolBostonMA 02115USA Faculty of Medicine Discipline of PsychiatryCentre for Clinical ResearchRoyal Brisbane&Women’s HospitalHerstonthe University of QueenslandBrisbane 4006Australia Departments of Medical Genetics PsychiatryPhysiology&Pharmacology and Community Health SciencesUniversity of CalgaryCalgaryAB T2N 1N4Canada Department of Psychiatry the University of MelbourneMelbourne 3052Australia centre for Human Psychopharmacology Swinburne UniversityMelbourne 3122Australia The Institute for Mental and Physical Health and clinical Translation School of MedicineBarwon HealthDeakin UniversityGeelong 3220Australia The centre of Excellence in Youth Mental Health the University of MelbourneParkville 3052Australia Florey Institute of Neuroscience and Mental Health the University of MelbourneParkville 3052Australia NICM Health Research Institute Western Sydney UniversityWestmeadNSW 2145Australia

Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive *** well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to *** present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo *** This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo(n=69 in placebo group).We investigated participant characteristics such as socio-demographics,clinical features,and recruitment methods,and their association with the placebo *** genetic polymorphisms were also *** response was measured based on change in Montgomery-Asberg Depression Rating Scale *** association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects *** Greater levels of education,particularly pursuing post-high school education,better self-reported general health,marriage/de facto,greater improvement in the first trial week,and more failed antidepressant therapies in the current depressive episode were associated with greater placebo *** increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant *** nucleotide polymorphisms from the tryptophan hydroxylase 1(TPH1)gene(A779C and A218C)were weakly associated with greater placebo response,although the evidence was attenuated after accounting for multiple *** This is,to our knowledge,the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo *** variables appeared to predict the placebo *** findings may encourage future trial design

关键词： Randomized controlled trial Placebo Depression Nutraceutical Psychiatry

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Dietary cooking oils and cardiometabolic measurements in an elderly Chinese population

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Journal of Geriatric Cardiology 2024年第6期21卷 642-650页

作者： Xin-Yu WANG Chao-Ying MIAO Xiao-Fei YE Wen-Yuan-Yue WANG Jia-Bo ZHU Yi ZHOU Yan LI Ji-Guang WANG School of Public Health Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Cardiovascular Medicine Centre for Epidemiological Studies and Clinical TrialsThe Shanghai Institute of HypertensionRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

OBJECTIVE To investigate three features of dietary cooking oil intake,namely,the consumption,cooking style,and composition of fatty acids in relation to several cardiometabolic measurements in an elderly Chinese *** The elderly(≥65 years)participants for this study were recruited from two community health centers in the urban area of Shanghai.A questionnaire was administered to collect information on dietary oil consumption(low,medium and high)and cooking styles(fry or stir-fry ***)and the composition of fatty acids(poly-unsaturated ***-unsaturated).The cardiometabolic measurements included anthropometry,blood pressure,fasting plasma glucose and serum *** The 1186 study participants had a mean age of 70.9±5.4 *** mean dietary oil consumption was 35.0 g/d,being low(<25 g/d),medium(25-49 g/d)and high(≥50 g/d)in 485,467 and 234 participants,*** proportion of the fry or stir-fry cooking style and oils rich in mono-unsaturated fatty acids was 30.4%and 27.4%,*** before and after adjustment for sex,age,current smoking and alcohol intake,dietary oil consumption was significantly(P≤0.02)and positively associated with the prevalence of treated hypertension and fasting plasma glucose *** similar adjustments as above and additional adjustment for dietary oil consumption,the fry or stir-fry cooking style was significantly(P≤0.048)and positively associated with body mass index,but inversely with systolic and diastolic blood pressure and serum low-density lipoprotein cholesterol,and the dietary intake of oils rich in mono-unsaturated fat acids was significantly(P≤0.02)and positively associated with diastolic blood pressure,serum triglycerides,total cholesterol and low-density lipoprotein cholesterol,and the prevalence of hypertriglyceridemia and *** This study showed that both the consumption and composition of fatty acids of the dietary oils mattered with regard to sev

关键词： cooking elderly unsaturated

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Leisure-time physical activity and all-cause mortality and cardiovascular disease in adults with type 2 diabetes:Cross-country comparison of cohort studies

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Journal of Sport and Health Science 2024年第2期13卷 212-221页

作者： Jakob Tarp Mengyun Luo Miguel Adriano Sanchez-Lastra Knut Eirik Dalene Borja del Pozo Cruz Mathias Ried-Larsen Reimar Wernich Thomsen Ulf Ekelund Ding Ding Department of clinical Epidemiology Aarhus University&Aarhus University HospitalAarhus 8200Denmark Prevention Research Collaboration Sydney School of Public HealthThe University of SydneyCamperdownNSW 2006Australia Charles Perkins centre the University of SydneyCamperdownNSW 2050Australia Department of Sports Medicine Norwegian School of Sports SciencesOslo 0806Norway Department of Special Didactics Faculty of Education and Sports SciencesUniversity of VigoPontevedra 36005Spain Well-Move Research Group Galicia Sur Health Research Institute(IIS Galicia Sur)SERGAS-UVIGOVigo 36213Spain Department of Chronic Diseases Norwegian Institute of Public HealthOslo 0473Norway centre for Active and Healthy Ageing Department of Sports Science and Clinical BiomechanicsUniversity of Southern DenmarkOdense 5230Denmark Faculty of Education University of CadizCadiz 11519Spain Biomedical Research and Innovation Institute of Cadiz(INiBICA)Research Unit Puerta del Mar University HospitalUniversity of CadizCadiz 11009Spain The centre of Inflammation and Metabolism&the centre for Physical Activity Research RigshospitaletUniversity of CopenhagenCopenhagen 2100Denmark Department of Sports Science and clinical Biomechanics University of Southern DenmarkOdense 5230Denmark

Purpose:This study aimed to quantify the dose-response association and the minimal effective dose of leisure-time physical activity(PA)to prevent mortality and cardiovascular disease in adults with type 2 ***:Cross-country comparison of 2 prospective cohort studies including 14,913 and 17,457 population-based adults with type 2 diabetes from the UK and *** leisure-time PA was self-reported and categorized by metabolic equivalent hours per week(MET-h/week)according to World Health Organization recommendations:none,below recommendation(>0-7.49 MET-h/week);at recommended level(7.5-14.9 MET-h/week);above recommendation(>15 MET-h/week).Mortality and cardiovascular disease data were obtained from national ***:During a median follow-up of 12.4 and 9.7 years,in the UK and China cohorts,repectively,higher levels of leisure-time PA were inversely associated with all-cause(1571 and 2351 events)and cardiovascular mortality(392 and 1060 events),mostly consistent with a linear dose-response *** below,at,and above recommendations,compared with no activity,yielded all-cause mortality hazard ratios of0.94(95%confidence interval(95%CI):0.79-1.12),0.90(95%CI:0.74-1.10),and 0.85(95%CI:0.70-1.02)in British adults and 0.87(95%CI:0.68-1.10),0.88(95%CI:0.74-1.03),and 0.77(95%CI:0.70-0.85)in Chinese *** with cardiovascular mortality were more pronounced in British adults(0.80(95%CI:0.58-1.11),0.75(95%CI:0.52-1.09),and 0.69(95%CI:0.48-0.97))but less pronounced in Chinese adults(1.06(95%CI:0.76-1.47),1.01(95%CI:0.80-1.28),and 0.79(95%CI:0.69-0.92)).PA at recommended levels was not associated with lower rates of major adverse cardiovascular events(2345 and 4458 events).Conclusion:Leisure-time PA at the recommended levels was not convincingly associated with lower mortality and had no association with risk of major adverse cardiovascular events in British or Chinese adults with type 2 ***-time PA above current recom

关键词： Complications Epidemiology Exercise Prevention

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Panhypopituitarism caused by a suprasellar germinoma: A case report

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World Journal of clinical Cases 2024年第10期12卷 1844-1850页

作者： Jelena Roganovic Lea Saric Silvije Segulja Ana Dordevic Mia Radosevic Department of Pediatrics Clinical Hospital Centre RijekaRijeka 51000Croatia Faculty of Medicine University of RijekaRijeka 51000Croatia Faculty of Health Sciences University of RijekaRijeka 51000Croatia Department of Business Development Jadran Galenski LaboratorijRijeka 51000Croatia

BACKGROUND Suprasellar germinomas are rare intracranial tumors frequently associated with permanent endocrine *** present the clinical picture,treatment,and complications of suprasellar germinoma at pediatric age which,besides being lifethreatening,has lifelong endocrinological *** SUMMARY A 12-year-old female patient was presented having had intensive headaches for three weeks and visual disturbances for six *** ophthalmological examination revealed bilateral papilledema and a marked loss of *** brain magnetic resonance imaging(MRI)showed a suprasellar tumor,involving the infundibulum and the optic chiasm,extending to the third *** tests confirmed decreased levels of thyroxine,cortisol,gonadotropins,and insulin-like growth factor *** tumor reduction was performed,and immunohistopathology established the diagnosis of suprasellar *** of the spine and cerebrospinal fluid cytology confirmed the localized *** chemotherapy and radiotherapy were performed according to the SIOP CNS GCT II protocol.A post-treatment MRI showed no residual tumor,but pituitary function had not *** and a half years after the end of the treatment,the patient is in a complete remission,requiring hormonal replacement therapy,continuous education,and psychological *** This complex case highlights the importance of timely diagnosis,a multidisciplinary approach,and close follow-up in children with suprasellar germinomas.

关键词： Germinoma Germ cell tumor Suprasellar tumor Hypopituitarism Management Pediatrics Case report

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Survey of hepatitis B virus infection for liver cancer screening in China:A population-based,cross-sectional study

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Chinese Medical Journal 2024年第12期137卷 1414-1420页

作者： Yongjie Xu Changfa Xia He Li Maomao Cao Fan Yang Qianru Li Mengdi Cao Wanqing Chen Office of Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Office of National Cancer Regional Medical centre in Liaoning Province The First Affiliated Hospital of China Medical UniversityShenyangLiaoning 110001China

Background:Hepatitis B virus(HBV)infection is the primary cause of hepatocellular carcinoma(HCC)in *** target population for HCC screening comprises individuals who test positive for hepatitis B surface antigen(HBsAg).However,current data on the prevalence of HBV infection among individuals who are eligible for HCC screening in China are *** aimed to assess the seroepidemiology of HBV infection among Chinese individuals eligible for HCC screening to provide the latest evidence for appropriate HCC screening strategies in ***:Questionnaires including information of sex,age,ethnicity,marital status,educational level,source of drinking water,as well as smoking and alcohol consumption history and serum samples were collected from females aged 45-64 years and males aged 35-64 years in 21 counties from 4 provinces in eastern and central China between 2015 and ***-linked immunosorbent assay methods were used to detect the serum HBV marker ***:A total of 603,082 individuals were enrolled,and serum samples were collected for analysis from January 1,2015 to December 31,*** prevalence of HBsAg positive in the study population was 5.23%(31,528/603,082).The prevalence of HBsAg positive was greater in males than in females(5.60%[17,660/315,183]vs 4.82%[13,868/287,899],χ^(2)=187.52,P<0.0001).The elderly participants exhibited a greater prevalence of HBV infection than younger participants(χ^(2)=41.73,P<0.0001).Birth cohort analysis revealed an overall downward trend in HBV prevalence for both males and *** born in more recent cohorts exhibited a lower prevalence of HBV infection as compared to those born ***:The current prevalence of HBV infection remains above 5%in populations eligible for HCC screening in *** efforts should be made to increase the accessibility of HCC screening among individuals with HBV infection.

关键词： Hepatitis B virus Liver cancer screening China Hepatitis B surface antigens Early detection of cancer

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A review of therapeutic agents for breast cancer with potentially radiosensitizing properties

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Radiation Medicine and Protection 2024年第2期5卷 75-82页

作者： Zhongwei Zhang David Lim Zhihui Feng Department of Occupational Health and Occupational Medicine School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012China centre for Improving Palliative Aged and Chronic Care Through Clinical Research and TranslationFaculty of HealthUniversity of Technology SydneyNSW2007Australia

Breast cancer is the most frequently diagnosed malignant tumor in women worldwide and the leading cause of cancer *** for breast cancer is readily accepted and widely used in clinical *** limitations with radiotherapy include treatment resistance,side effects,and complications caused by high doses of *** search has been on to locate an efficacious *** review summarizes six currently approved pharmaceuticals that have also been investigated for off-label use as radiosensitizers in breast cancer.

关键词： Breast cancer Radiotherapy Radiosensitizer Therapeutic agents

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