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A modular microfluidic platform to study how fluid shear stress alters estrogen receptor phenotype in ER+breast cancer cells

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Microsystems & Nanoengineering 2024年第1期10卷 287-299页

作者： Braulio Andrés Ortega Quesada Jonathan Cuccia Rachael Coates Blake Nassar Ethan Littlefield Elizabeth C.Martin Adam T.Melvin Cain Department of Chemical Engineering Louisiana State UniversityBaton RougeLA 70803USA Department of Chemical and Biological Engineering Clemson UniversityClemsonSC 29634USA Biological and Agricultural Engineering Louisiana State UniversityBaton RougeLA 70803USA Department Medicine Section Hematology and Medical OncologyTulane UniversityNew OrleansLA 70118USA

Metastatic breast cancer leads to poor prognoses and worse outcomes in patients due to its invasive behavior and poor response to *** is still unclear what biophysical and biochemical factors drive this more aggressive phenotype in metastatic cancer;however recent studies have suggested that exposure to fluid shear stress in the vasculature could cause *** this study a modular microfluidic platform capable of mimicking the magnitude of fluid shear stress(FSS)found in human vasculature was designed and *** device provides a platform to evaluate the effects of FSS on MCF-7 cell line,an estrogen receptor positive(ER+)breast cancer cell line,during circulation in the *** of the effects of FSS on MCF-7 cells was carried out utilizing two approaches:single cell analysis and bulk *** single cell analysis,cells were trapped in a microarray after exiting the serpentine channel and followed by immunostaining on the device(on-chip).Bulk analysis was performed after cells were collected in a microtube at the outlet of the microfluidic serpentine channel for western blotting(off-chip).It was found that cells exposed to an FSS magnitude of 10 dyn/cm^(2) with a residence time of 60 s enhanced expression of the proliferation marker Ki67 in the MCF-7 cell line at a single cell *** understand possible mechanisms for enhanced Ki67 expression,on-chip and off-chip analyses were performed for pro-growth and survival pathways ERK,AKT,and JAK/*** demonstrated that after shearing the cells phosphorylation of p-AKT,p-mTOR,and p-STAT3 were ***,there was no change in p-ERK1/*** is a mediator of ER rapid signaling,analysis of phosphorylated ERαwas carried out and no significant differences between sheared and non-sheared populations were *** together these results demonstrate that FSS can increase phosphorylation of proteins associated with a more aggressive phenotype in circulating cancer *** findin

关键词： fluid breast estrogen

The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

Nutritional Supplement Ocoxin® Combined with Gemcitabine-Based Chemotherapy in Patients with Advanced Pancreatic Adenocarcinoma

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Open Journal of Gastroenterology 2024年第8期14卷 267-287页

作者： Mayté Lima-Pérez Jorge Luis Soriano-García Masiel González-Meisozo Jorge Luis Soriano-Lorenzo Vilma Fleites-Calvo Dunia Morales-Morgado Carlos Domínguez-Álvarez Iván Ramón-Concepción Raidel Rodríguez-Barrios Alicia Tarinas-Reyes Ivis Mendoza-Hernández Rolando Uranga-Piña Clinical oncology Department Ameijeiras Hospital Havana Cuba Clinical Pathology Department Ameijeiras Hospital Havana Cuba Clinical section National Coordinating Centre for Clinical Trials Havana Cuba Biostatistics section National Coordinating Centre for Clinical Trials Havana Cuba

Background: the quality of life (QoL) of patients with pancreatic ductal adenocarcinoma (PDAC), with its limited survival, can be affected by chemotherapy-induced toxicity. The main objective was to evaluate the effect of introducing ocoxin oral solution (OOS) in combination with standard therapy on quality of life. Methods: Thirty patients were enrolled in an exploratory, prospective, single-centre clinical trial in the oncology department of “Hermanos Ameijeiras” University Hospital in Havana, Cuba. Quality of life was measured using the EORTC QLQ-C30 questionnaire and toxicity was assessed using the NCI-CTC-AE classification version 5.0. Results: There was stability in the scores over time for overall QoL and the functional scale criteria, while in terms of symptoms, fatigue, pain and loss of appetite were reduced. No grade 3 - 4 adverse events (AEs) were recorded, and only 14.9% of toxicities were classified as grade 2, and these were considered to be unrelated to OOS. Biochemical and nutritional parameters were normalised at 12 months compared to the baseline values. Conclusions: This clinical study is the first report of the use of OOS in patients with advanced pancreatic cancer, and demonstrates that it is able to maintain optimal quality of life with reduced severity of toxicity during and after combination treatment with gemcitabine-based chemotherapy.

关键词： EORTC QLQ-C30 Ocoxin Chemotherapy Pancreatic Cancer Quality of Life

Antioxidant treatment for oligoasthenoteratozoospermia and varicocele:a DBPC trial to evaluate the impact of age and body mass index

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Asian Journal of Andrology 2024年第3期26卷 239-244页

作者： Gian Maria Busetto Bernarde F Rodrigues Ashraf Virmani Andrea Checchia Antonella Ninivaggi Anna Ricapito Giovanni Barbieri Piero Fischetti Ugo G Falagario Pasquale Annese Nicola d’Altilia Vito Mancini Matteo Ferro Felice Crocetto Angelo Porreca Carlo Bettocchi Luigi Cormio Ashok Agarwal Giuseppe Carrieri University of Foggia Foggia 71122Italy Department of Urology and Renal Transplantation Policlinico of FoggiaFoggia 71122Italy Department of Urology Human Reproduction SectionFederal University of Sao PauloSao Paulo 05403-000Brazil Alfasigma Healthscience Utrecht 3528 BGThe Netherlands Urology Unit “G.Tatarella”HospitalCerignola 71042Italy Urology Unit European Institute of Oncology(IEO)IRCCSMilan 20142Italy University of Naples Federico II Naples80126Italy Department of Oncological Urology Veneto Institute of Oncology(IOV)IRCCSPadua 35039Italy Urology Unit “L.Bonomo”HospitalAndria 70031Italy Global Andrology Forum Moreland HillsOH 44022USA

Oxidative stress is one of the main mechanisms responsible for male *** conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an oxidative imbalance in the *** are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizingthe *** reactive oxygen species can affect sperm metabolism,leading to immobility,impaired acrosome reaction,and celldeath,thereby impairing reproductive *** double-blind randomized study evaluated the effect of supplementation withL-carnitine,acetyl-L-carnitine,vitamins,and other nutrients on semen quality in 104 infertile patients with or without varicocele,while also investigating the impact of factors such as obesity and advanced age on *** concentration significantlyincreased in the supplemented group compared to the placebo group(P=0.0186).Total sperm count also significantly increasedin the supplemented group(P=0.0117),as did sperm motility(P=0.0120).The treatment had a positive effect on patients upto 35 years of age in terms of sperm concentration(P=0.0352),while a body mass index(BMI)above 25 kg m^(−2) had a negativeeffect on sperm concentration(P=0.0110).Results were not showing a net benefit in stratifying patients in accordance withtheir BMI since sperm quality increase was not affected by this *** conclusion,antioxidant supplementation may bebeneficial for infertile patients and has a more positive effect on younger patients with a normal weight.

关键词： aging antioxidants body mass index oligoasthenoteratozoospermia varicocele

Immune mediated support of metastasis:Implication for bone invasion

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Cancer Communications 2024年第9期44卷 967-991页

作者： Zengfeng Xin Luying Qin Yang Tang Siyu Guo Fangfang Li Yuan Fang Gege Li Yihan Yao Binbin Zheng Bicheng Zhang Dang Wu Jie Xiao Chao Ni Qichun Wei Ting Zhang Department of orthopedic Surgery Second Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhouZhejiangP.R.China Cancer Institute(Key Laboratory of Cancer Prevention and Intervention National Ministry of Education)Second Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhouZhejiangP.R.China Department of Radiation oncology Second Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhouZhejiangP.R.China Department of Respiratory Medicine Ningbo Hangzhou Bay HospitalNingboZhejiangP.R.China Department of orthopedic Surgery Second Affiliated Hospital(Jiande Branch)Zhejiang University School of MedicineHangzhouZhejiangP.R.China Department of Breast Surgery Second Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhouZhejiangP.R.China

Bone is a common organ affected by metastasis in various advanced cancers,including lung,breast,prostate,colorectal,and *** a patient is diagnosed with bone metastasis,the patient’s quality of life and overall survival are significantly reduced owing to a wide range ofmorbidities and the increasing difficulty of *** studies have shown that bone metastasis is closely related to bone microenvironment,especially bone immune ***,the effects of various immune cells in the bone microenvironment on bone metastasis remain ***,we described the changes in various immune cells during bone metastasis and discussed their related ***,adipocytes,and other non-immune cells closely related to bone metastasis were also *** review also summarized the existing treatment methods and potential therapeutic targets,and provided insights for future studies of cancer bone metastasis.

关键词： bone metastasis bone microenvironment cancer immune cell therapy

Role of CD36 in central nervous system diseases

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Neural Regeneration Research 2024年第3期19卷 512-518页

作者： Min Feng Qiang Zhou Huimin Xie Chang Liu Mengru Zheng Shuyu Zhang Songlin Zhou Jian Zhao School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina Department of orthopedic oncology Second Affiliated Hospital of Naval Medical UniversityShanghaiChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsJiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury RepairCo-Innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina Department of Stomatology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Medical College of Nantong University NantongJiangsu ProvinceChina

CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic ***36 was recently found to be widely expressed in various cell types in the nervous system,including endothelial cells,pericytes,astrocytes,and ***36 mediates a number of regulatory processes,such as endothelial dysfunction,oxidative stress,mitochondrial dysfunction,and inflammatory responses,which are involved in many central nervous system diseases,such as stroke,Alzheimer’s disease,Parkinson’s disease,and spinal cord ***36 antagonists can suppress CD36 expression or prevent CD36 binding to its ligand,thereby achieving inhibition of CD36-mediated pathways or ***,we reviewed the mechanisms of action of CD36 antagonists,such as Salvianolic acid B,tanshinone IIA,curcumin,sulfosuccinimidyl oleate,antioxidants,and small-molecule ***,we predicted the structures of binding sites between CD36 and *** sites can provide targets for more efficient and safer CD36 antagonists for the treatment of central nervous system diseases.

关键词： animal experiments antagonists CD36 antagonist central nervous system diseases clinical trial curcumin microRNA salvianolic acid B small-molecule drugs sulfosuccinimidyl oleate

Sol-gel derived B_(2)O_(3)-CaO borate bioactive glasses with hemostatic,antibacterial and pro-angiogenic activities

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Regenerative Biomaterials 2024年第1期3卷 108-118页

作者： Kai Zheng Faina Bider Mahshid Monavari Zhiyan Xu Christina Janko Christoph Alexiou Ana M.Beltran Aldo R.Boccaccini Jiangsu Province Engineering Research Center of Stomatological Translational Medicine College of StomatologyNanjing Medical UniversityNanjing 210029China Jiangsu Key Laboratory of Oral Diseases Nanjing Medical UniversityNanjing 210029China Institute of Biomaterials University of Erlangen-Nuremberg91058 ErlangenGermany Department of Oto-Rhino-Laryngology Head and Neck SurgerySection of Experimental Oncology and Nanomedicine(SEON)Else Kroener-Fresenius-Stiftung ProfessorshipUniversitaetsklinikum Erlangen91058 ErlangenGermany Departamento de Ingenier�ıa y Ciencia de los Materiales y del Transporte Escuela Politecnica

Sol-gel borate bioactive glasses(BGs)are promising ion-releasing biomaterials for wound healing ***,we report the synthesis of a series of binary B_(2)O_(3)-CaO borate BGs(CaO ranging from 50 to 90mol%)using a sol-gel-based *** influence of CaO content in B_(2)O_(3)-CaO borate BG on morphology,structure and ion release behavior was investigated in *** dissolution(ion release)and crystallization could be observed in borate BGs when CaO content increased,while the morphology was not significantly altered by increasing CaO *** results evidenced that the ion release behavior of borate BGs could be tailored by tuning the B_(2)O_(3)/CaO molar *** also evaluated the in vitro cytotoxicity,hemostatic,antibacterial and angiogenic activities of borate *** was validated for all borate ***,borate BGs exhibited composition-dependent hemostatic,antibacterial and angiogenic ***,higher contents of Ca in borate BGs facilitated hemostatic activity,while higher contents of B_(2)O_(3) were beneficial for pro-angiogenic *** synthesized sol-gel-derived borate BGs are promising materials for developing advanced wound healing dressings,given their fast ion release behavior and favorable hemostatic,antibacterial and angiogenic activities.

关键词： borate glasses sol-gel processing glass composition wound healing

Biomechanical effects of posterior lumbar interbody fusion with vertical placement of pedicle screws compared to traditional placement

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World Journal of Clinical Cases 2024年第20期12卷 4108-4120页

作者： Ji-Hong Jiang Chang-Ming Zhao Jun Zhang Rong-Ming Xu Lei Chen Department of orthopedic Surgery Zhejiang University Mingzhou HospitalNingbo 315000Zhejiang ProvinceChina

BACKGROUND The pedicle screw technique is widely employed for vertebral body fixation in the treatment of spinal ***,traditional screw placement methods require the dissection of paraspinal muscles and the insertion of pedicle screws at specific transverse section angles(TSA).Larger TSA angles require more force to pull the muscle tissue,which can increase the risk of surgical trauma and ischemic injury to the lumbar *** To study the feasibility of zero-degree TSA vertical pedicle screw technique in the lumbosacral *** Finite element models of vertebral bodies and pedicle screw-rod systems were established for the L4-S1 spinal segments.A standard axial load of 500 N and a rotational torque of 10 N/m were *** screw pull-out experiment was conducted to observe pedicle screw resistance to pull-out,maximum stress,load-displacement ratio,maximum stress in vertebral bodies,load-displacement ratio in vertebral bodies,and the stress distribution in pedicle screws and vertebral *** between the 0-degree and 17-degree TSA were *** At 0-degree TSA,the screw pull-out force decreased by 11.35%compared to that at 17-degree TSA(P<0.05).At 0-degree and 17-degree TSA,the stress range in the screw-rod system was 335.1-657.5 MPa and 242.8-648.5 MPa,separately,which were below the fracture threshold for the screw-rod system(924 MPa).At 0-degree and 17-degree TSA,the stress range in the vertebral bodies was 68.45-78.91 MPa and 39.08-72.73 MPa,separately,which were below the typical bone yield stress range for vertebral bodies(110-125 MPa).At 0-degree TSA,the load-displacement ratio for the vertebral bodies and pedicle screws was slightly lower compared to that at 17-degree TSA,indicating slightly lower stability(P<0.05).CONCLUSION The safety and stability of 0-degree TSA are slightly lower,but the risks of screw-rod system fracture,vertebral body fracture,and rupture are within acceptable limits.

关键词： Vertical pedicle screw Pedicle screw technique Transverse section angle Lumbosacral segment Finite element analysis

Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated,EGFR-mutated,advanced non-small cell lung cancer:data froma randomized phase III trial(AENEAS)

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Cancer Communications 2024年第9期44卷 1005-1017页

作者： Shun Lu Xiaorong Dong Hong Jian Jianhua Chen Gongyan Chen Yuping Sun Yinghua Ji ZipingWang Jianhua Shi Junguo Lu Shaoshui Chen Dongqing Lv Guojun Zhang Chunling Liu Juan Li Xinmin Yu Zhong Lin Zhuang Yu ZhehaiWang Jiuwei Cui Xingxiang Xu Jian Fang Jifeng Feng Zhi Xu RuiMa Jie Hu Nong Yang Xiangdong Zhou XiaohongWu Chengping Hu Zhihong Zhang You Lu Yanping Hu Liyan Jiang Qiming wang Renhua Guo Jianying Zhou Baolan Li Chunhong Hu Wancheng Tong Helong Zhang LinMa Yuan Chen Zhijun Jie Yu Yao Longzhen Zhang JieWeng Weidong Li Jianping Xiong Xianwei Ye Jianchun Duan Haihua Yang Meili Sun HongyingWei JiaweiWei Zheyu Zhang QiongWu Department of Medical oncology Shanghai Chest Hospital Shanghai JiaoTong UniversityShanghaiP.R.China Cancer Center Union Hospital Tongji Medical College Huazhong University of Science and TechnologyWuhanHubeiP.R.China Department of Medical oncology-Chest Hunan Cancer Hospital&The Affiliated Cancer Hospital of Central South University Xiangya School of MedicineChangshaHunanP.R.China Thoracic oncologyMedicine HarbinMedical University Cancer HospitalHarbinHeilongjiangP.R.China Department of oncology Jinan Central HospitalJinanShandongP.R.China Department of oncology First Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenanP.R.China Department of Chest Medicine Beijing Cancer HospitalBeijingP.R.China Department of Internal Medicine Linyi Cancer HospitalLinyiShandongP.R.China Department of Respiratory Medicine Nantong Tumor HospitalNantongJiangsuP.R.China Department of oncology Binzhou Medical University HospitalBinzhouShandongP.R.China Breath Internal Medicine Taizhou Hospital of Zhejiang ProvinceLinhaiZhejiangP.R.China Department of Respiration The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanP.R.China Department of Lung Internal Medicine Affiliated Tumor Hospital of Xinjiang Medical UniversityUrumqiXinjiangP.R.China Department of Thoracic oncology Sichuan Cancer HospitalChengduSichuanP.R.China Thoracic Medical oncology Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)HangzhouZhejiangP.R.China Department of Thoracic oncology The Fifth Subsidiary Sun Yat-sen University HospitalZhuhaiGuangdongP.R.China Department of oncology The Affiliated Hospital of QingdaoUniversityQingdaoShandongP.R.China Department of oncology Shandong Cancer HospitalJinanShandongP.R.China Department of oncology The First BethuneHospital of Jilin UniversityChangchunJilinP.R.China Department of Respiration Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityYangzhouJiangsuP.R.China Department of Internal

Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC).Metastatic disease in the central nervous system(CNS)remains a challenge in the management of *** study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS ***:Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded *** with asymptomatic,stable CNS metastases were ***-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months,then every *** responsewas assessed by a neuroradiological blinded,independent central review(neuroradiological-BICR).The primary endpoint for this subgroup analysis was CNS progression-free survival(PFS).Results:Of the 429 patients enrolled and randomized in the ANEAS study,106 patients were found to have CNS metastases(CNS Full Analysis Set,cFAS)at baseline by neuroradiological-BICR,and 60 of them had CNS target lesions(CNS Evaluable for Response,cEFR).Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS(29.0 vs.8.3 months;hazard ratio[HR]=0.31;95%confidence interval[CI],0.17-0.56;P<0.001)and cEFR(29.0 vs.8.3 months;HR=0.26;95%CI,0.11-0.57;P<0.001).The confirmed CNS overall response rate in cEFRwas 85.7%and 75.0%in patients treated with aumolertinib and gefitinib,*** risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNSmetastases at *** new safety findings were ***:The

关键词： aumolertinib brain metastasis non-small cell lung cancer third-generation EGFR-TKI