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IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

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Chinese Journal of Cancer Research 2024年第2期36卷 103-113页

作者： Yi-Long wu shun Lu Gongyan Chen Jianxing He Jifeng Feng Yiping Zhang Liyan Jiang Hongming Pan Jianhua Chang Jian Fang Amy Cai Lilian Bu Jane Shi Jinjing Xia Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People's Hospital&Guangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhou 510080China Shanghai Lung Cancer Center Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China Department of Respiration Harbin Cancer HospitalHarbin Medical UniversityHarbin 150081China Department of Thoracic Oncology and Surgery the First Affliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Medical Oncology Jiangsu Cancer HospitalNanjing 210009China Department of Medical Oncology Zhejiang Cancer HospitalHangzhou 330022China Department of Pulmonary Medicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China Department of Medical Oncology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Department of Medical Oncology Shenzhen HospitalCancer Hospital of Chinese Academy of Medical SciencesShenzhen 518116China Department of Thoracic Oncology Beijing Cancer HospitalBeijing 100142China Product Development Shanghai Roche Pharmaceutical LtdShanghai 201203China

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab *** as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian ***: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT ***: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel ***: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

关键词： Atezolizumab East Asia non-small cell lung cancer programmed death-ligand 1 inhibitors monoclonal antibody

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Chinese Guidelines for the Diagnosis and Management of Atrial Fibrillation

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Journal of Geriatric Cardiology 2024年第3期21卷 251-314页

作者： Chang-sheng MA Shu-Lin wu Shao-Wen LIU Ya-Ling HAN Chinese Society of Cardiology Chinese Medical Association Heart Rhythm Committee of Chinese Society of Biomedical Engineering Beijing Anzhen Hospital Capital Medical University Guandong Provincial People’s Hospital Shanghai First People’s Hospital General Hospital of Northern Theater Command 不详

Atrial fibrillation(AF)is the most common sustained cardiac arrhythmia,significantly impacting patients’quality of life and increasing the risk of death,stroke,heart failure,and *** the past two decades,there have been significant breakthroughs in AF risk prediction and screening,stroke prevention,rhythm control,catheter ablation,and integrated *** this period,the scale,quality,and experience of AF management in China have greatly improved,providing a solid foundation for the development of guidelines for the diagnosis and management of *** further promote standardized AF management,and apply new technologies and concepts to clinical practice in a timely and comprehensive manner,the Chinese Society of Cardiology of the Chinese Medical Association and the Heart Rhythm Committee of the Chinese Society of Biomedical Engineering have jointly developed the Chinese Guidelines for the Diagnosis and Management of Atrial *** guidelines have comprehensively elaborated on various aspects of AF management and proposed the CHA2DS2-VASc-60 stroke risk score based on the characteristics of AF in the Asian *** guidelines have also reevaluated the clinical application of AF screening,emphasized the significance of early rhythm control,and highlighted the central role of catheter ablation in rhythm control.

关键词： prevention sustained diagnosis

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Ruxolitinib improves the inflammatory microenvironment,restores glutamate homeostasis,and promotes functional recovery after spinal cord injury

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Neural Regeneration Research 2024年第11期19卷 2499-2512页

作者： Jiang Cao Xiao Yu Jingcheng Liu Jiaju Fu Binyu Wang Chaoqin wu sheng Zhang Hongtao Chen Zi Wang Yinyang Xu Tao Sui Jie Chang Xiaojian Cao Department of Orthopedics The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Trauma Surgery Subei People’s Hospital of JiangsuClinical Medical College of Yangzhou UniversityYangzhouJiangsu ProvinceChina Department of Orthopedics Zhongda HospitalSoutheast UniversityNanjingJiangsu ProvinceChina Department of Orthopedic Surgery Nanjing Drum Tower HospitalThe Affiliated Hospital of Medical School of Nanjing UniversityNanjingJiangsu ProvinceChina

The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord ***,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine *** studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains *** address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord *** sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory ***,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic ***,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.

关键词： astrocytes EAAT2 excitotoxicity glutamate homeostasis JAK-STAT pathway locomotor function neurotoxicity ruxolitinib spinal cord injury transcriptome analysis

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Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis

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Current Medical Science 2024年第3期44卷 611-622页

作者： Ying CHEN Bi-xia LI Ting-ting NIU Shu-jun YANG Li-chao wu Le-huai SHI Duo-bing ZOU Ning-ning wu Li-xia sheng Xiao YAN Gui-fang OUYANG Qi-tian MU Laboratory of Stem Cell Transplantation The First Affiliated Hospital of Ningbo UniversityNingbo315300China Ningbo Clinical Research Center For Hematologic Malignancies Ningbo315300China Department of Hematology The First Affiliated Hospital of Ningbo UniversityNingbo315300China School of Medicine Hangzhou City UniversityZhejiang UniversityHangzhou310000China Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province Ningbo315300China

Objective Acute myeloid leukemia(AML)is an aggressive hematological malignancy characterized by abnormal myeloid blast *** studies have demonstrated that circular RNAs play a role in AML *** this study,we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this *** Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls.A systematic analysis of clinical characteristics and prognostic factors was also *** growth was assessed using the Cell Counting Kit-8(CCK-8)assay,and apoptosis and cell cycle progression were evaluated by flow ***,RNA pull-down was performed to identify target microRNAs,and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA *** Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival(OS)(hazard ratio:2.357;95%confidence interval 1.258–4.415).The circ_0012152 knockdown reduced cell growth,increased apoptosis,and inhibited cell cycle progression in AML cell *** pull-down and sequencing identified miR-652-3p as a target microRNA of circ_*** growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p *** suggested that miR-652-3p targeted SOX4,as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML *** Circ_0012152 is an independent poor prognostic factor for OS in AML,and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

关键词： acute myeloid leukemia circ_0012152 miR-652-3p SOX4 cell growth

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Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor

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National Science Review 2024年第4期11卷 206-215页

作者： Ziyan Liao Jie Jiang Wei wu Jiaqi Shi Yanfang Wang Yuejun Yao Tao sheng Feng Liu Wei Liu Peng Zhao Feifei Lv Jie Sun Hongjun Li Zhen Gu National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang University Liangzhu Laboratory Zhejiang University Bone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology Zhejiang University School of Medicine Department of Medical Oncology The First Affiliated Hospital School of Medicine Zhejiang University Department of Laboratory Medicine The First Affiliated Hospital Zhejiang University School of Medicine Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalSchool of MedicineZhejiang University Jinhua Institute of Zhejiang University MOE Key Laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang University Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University

The limited infiltration and persistence of chimeric antigen receptor(CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading,delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors. This porous device is made from poly(lactic-co-glycolic acid) by a microfluidic technique with the modification of T-cell stimulatory signals, including anti-CD3, anti-CD28 antibodies, as well as cytokines. This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo. Particularly, it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth. This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.

关键词： drug delivery cell therapy bioinspired biomaterials cancer immunotherapy

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岩体暴露面图像中裂隙全自动提取方法研究

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岩土力学 2024年第9期45卷 2621-2632页

作者：吴金吴顺川孙贝贝北京科技大学土木与资源工程学院北京100083 昆明理工大学国土资源工程学院云南昆明650093 自然资源部高原山地地质灾害预报预警与生态保护修复重点实验室云南昆明650093

裂隙显著影响岩体物理与力学性质,针对从岩体暴露面图像中自动提取裂隙存在的提取结果不完整、信噪比低,以及提取方法经验参数多、鲁棒性差等问题,提出一种全自动裂隙提取优化程序。首先,通过引入广义伽马校正初步提升裂隙与岩壁面对比... 详细信息

裂隙显著影响岩体物理与力学性质,针对从岩体暴露面图像中自动提取裂隙存在的提取结果不完整、信噪比低,以及提取方法经验参数多、鲁棒性差等问题,提出一种全自动裂隙提取优化程序。首先,通过引入广义伽马校正初步提升裂隙与岩壁面对比度;其次,考虑裂隙路径像素间相互影响,设计灰度传递算法提升裂隙连续性;最后,通过改进Frangi滤波器提取裂隙并充分抑制噪音像素响应。结果表明:该程序充分融合了裂隙低灰度和高线型两大特征,图像增强与裂隙提取两阶段协同运作,显著改善了裂隙对比度不均问题,在较完整提取裂隙的同时还能够有效防止噪音与伪裂隙的产生,对多种岩体暴露面图像均具有很高的鲁棒性。将该方法与常用的裂隙识别算法进行比较,展现了该算法流程在处理低对比度、高噪声岩体裂隙图像方面的显著优势。

关键词：岩体暴露面裂隙自动提取数字图像处理灰度传递算法 Frangi滤波

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Ultratough Yet Dynamic Crystalline Poly(thiourethane)Network Directly from Low Viscosity Precursors

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CCS Chemistry 2024年第3期6卷 682-692页

作者： Haijun Feng Yi sheng Guancong Chen Binjie Jin Zizheng Fang Bo Yang Xiaorui Zhou Wenxuan wu Tao Xie Ning Zheng State Key Laboratory of Chemical Engineering College of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310058 Department of Colorectal Surgery and Oncology Key Laboratory of Cancer Prevention and InterventionMinistry of EducationThe Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310027

Thermosets based on direct curing of multifunctional monomers offer processing flexibility that thermoplastics cannot ***,this type of thermoset is typically amorphous since it is difficult to meet the stringent requirement of long-range molecular regularity for ***,we report here a crystallizable poly(thiourethane)thermoset synthesized directly from the curing of low-viscosity liquid precursors that does not employ any *** crystalline nature results in superior toughness,comparable to commercial high-density polyethylene,in sharp contrast to the brittleness of the typical,rigid,glassy thermoset *** that,the network polymer exhibits shape-memory behavior in which the crystalline transition is utilized for temporary shape fixing/recovery whereas the dynamic thiourethane bonds can be activated for bond exchange as a mechanism for complex shape *** with these combined features represent attractive options for demanding engineering applications due to their high performance and multifunctinality.

关键词： thermosets crystalline polymer thiourethane thermadapt

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Endovascular treatment of ruptured lobulated anterior communicating artery aneurysms:A retrospective study of 24 patients

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World Journal of Clinical Cases 2024年第15期12卷 2529-2541页

作者： sheng-Xuan Huang Xun-Ping Ai Ze-Hui Kang Zhi-Yong Chen Ren-Man Li Zu-Chao wu Feng Zhu Department of Neurosurgery Sanming First Hospital Affiliated to Fujian Medical UniversitySanming 365000Fujian ProvinceChina

BACKGROUND Lobulated intracranial aneurysm is a special type of aneurysm with at least one additional cyst in the neck or body of the *** intracranial aneurysm is a complex aneurysm with complex morphology and structure and weak tumor wall,which is an independent risk factor for rupture and *** aneurysms located in the anterior communicating artery complex account for 36.9%of all intracranial lobular *** to its special anatomical structure,both craniotomy and endovascular treatment are more *** with single-capsule aneurysms,craniotomy for lobular intracranial aneurysms has a higher risk and complication *** To investigate the efficacy and safety of endovascular treatment for ruptured lobulated anterior communicating artery aneurysm(ACoAA).METHODS Patients with ruptured lobulated ACoAA received endovascular treatment in Sanming First Hospital Affiliated to Fujian Medical University from June 2020 to June 2022 were retrospectively *** demographic,clinical and imaging characteristics,endovascular treatment methods and follow-up results were *** A total of 24 patients with ruptured lobulated ACoAA were included,including 9 males(37.5%)and 15 females(62.5%).Their age was 56.2±8.9 years old(range 39-74).The time from rupture to endovascular treatment was 10.9±12.5 *** maximum diameter of the aneurysms was 5.1±1.0 mm and neck width were 3.0±0.7 *** patients(79.2%)were double-lobed and 5(20.8%)were ***'s grade:Grade 2 in 16 cases(66.7%),grade 3 in 6 cases(25%),and grade 4 in 2 cases(8.3%).Hunt-Hess grade:Grade 0-2 in 5 cases(20.8%),grade 3-5 in 19 cases(79.2%).Glasgow Coma Scale score:9-12 in 14 cases(58.3%),13-15 in 10 cases(41.7%).Immediately postprocedural Raymond-Roy grade:grade 1 in 23 cases(95.8%),grade 2 in 1 case(4.2%).Raymond-Roy grade in imaging follow-up for 2 wk to 3 months:grade 1 in 23 cases(95.8%),grade 2 in 1 case(4.2%).Followup for 2 to 12 months sho

关键词： Intracranial aneurysm Anterior cerebral artery Endovascular surgery Embolism Treatment outcome

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A combined nanotherapeutic approach targeting farnesoid X receptor,ferroptosis,and fibrosis for nonalcoholic steatohepatitis treatment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2228-2246页

作者： Jiangtao Fu Pingping Zhang Zhiguo Sun Guodong Lu Qi Cao Yiting Chen Wenbin wu Jiabao Zhang Chunlin Zhuang Chunquan sheng Jiajun Xu Ying Lu Pei Wang The Center for Basic Research and Innovation of Medicine and Pharmacy(MOE) School of PharmacyNaval Medical UniversityShanghai 200433China National Demonstration Center for Experimental Pharmaceutical Education Naval Medical University/Second Military Medical UniversityShanghai 200433China Department of Diving and Hyperbaric Medicine Naval Special Medical CenterNaval Medical UniversityShanghai 200433China

Obeticholic acid(OCA),a farnesoid X receptor(FXR)agonist with favorable effects on fatty and glucose metabolism,has been considered the leading candidate drug for nonalcoholic steatohepatitis(NASH)***,its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major ***,a newly recognized form of cell death characterized by uncontrolled lipid peroxidation,is involved in the progression of *** oxide(NO)is a versatile biological molecule that can degrade extracellular *** this study,we developed a PEGylated thiolated hollow mesoporous silica nanoparticles(MSN)loaded with OCA,as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol(ONL@MSN).Biochemical analyses,histology,multiplexed flow cytometry,bulk-tissue RNA sequencing,and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle(ONL@MSN)in a mouse NASH *** with the OCA-loaded nanoparticles(O@MSN),ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ***@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis,inhibition of immune response/lipid peroxidation,and correction of microbiota *** findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR,ferroptosis,and fibrosis.

关键词： Nonalcoholic steatohepatitis Nanotherapy Farnesoid X receptor Ferroptosis Fibrosis Obeticholic acid S-Nitrosothiol Liproxstatin-1

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Multimodal imaging diagnosis and analysis of prognostic factors in patients with adult-onset Coats disease

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International Journal of Ophthalmology(English edition) 2024年第8期17卷 1469-1476页

作者： Wei Zhou Hui Zhou Yuan-Yuan Liu Meng-Xuan Li Xiao-Han wu Jiao Liang Jing Hao sheng-Nan Liu Chun-Jie Jin Department of Ophthalmology Tianjin Medical University General HospitalTianjin 300052China Department of Ophthalmology Shanxi Yuncheng Tongde HospitalYuncheng 044000Shanxi ProvinceChina Department of Information Tianjin Medical University General HospitalTianjin 300052China

AIM:To describe the multimodal imaging features,treatment,and outcomes of patients diagnosed with adultonset Coats ***:This retrospective study included patients first diagnosed with Coats disease at≥18 years of age between September 2017 and September *** patients received anti-vascular endothelial growth factor(VEGF)therapy(conbercept,0.5 mg)as the initial treatment,which was combined with laser photocoagulation as *** the patients underwent best corrected visual acuity(BCVA)and intraocular pressure examinations,fundus color photography,spontaneous fluorescence tests,fundus fluorescein angiography,optical coherence tomography(OCT),OCT angiography,and other *** alterations and multimodal image findings in the affected eyes following treatment were compared and the prognostic factors were ***:The study included 15 patients who were aged 24-72(57.33±12.61)y at *** hypertension was the most common associated systemic condition,occurring in 13(86.7%)*** BCVA ranged from 2.0 to 5.0(4.0±1.1),which showed improvement following treatment(4.2±1.0).Multimodal imaging revealed retinal telangiectasis in 13 patients(86.7%),patchy hemorrhage in 5 patients(33.3%),and stage 2B disease(Shield’s staging criteria)in 11 patients(73.3%).OCT revealed that the baseline central macular thickness(CMT)ranged from 129 to 964μm(473.0±230.1μm),with 13 patients(86.7%)exhibiting a baseline CMT exceeding 250μ***,8 patients(53.3%)presented with an epiretinal membrane at baseline or during ***-reflective scars were observed on OCT in five patients(33.3%)with poor visual *** deteriorated in one patient who did not receive *** vision was stable in three patients who received laser treatment,whereas improvement was observed in one of two patients who received anti-VEGF therapy *** addition,8 of 9 patients(88.9%)who received laser treatment and conbercept exhibited sta

关键词： adult-onset Coats disease multimodal imaging anti-vascular endothelial growth factor conbercept

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