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TIR-domain-containing adapter-inducing interferon-βdeficiency promote retinal ganglion cell survival and axon regeneration by microglial inactivation

TIR-domain-containing adapter-inducing interferon-βdeficien...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： sen LIN~(1,2.,Ya-Jie LIANG~2.Qiang GUO~2.Hong-Li ZHOU~1,Ji-Qiang ZHANG~2.Chen BIAN~2.Can WEN~2.Yan-Ling ZHANG~2.Ying XIONG~2.Shu-Rong LI~(1,3,*),Bing-Yin SU~(1,*) 1 Development and Regeneration Key Laboratory of Sichuan Province,department of Histo-embryology and Neurobiology,Chengdu Medical College,Chengdu 610083,{2. 2.department of Neurobiology,Third Military Medical university,Chongqing 400038,{2. 3 department of pathology,Chengdu Medical College,Chengdu 610083,{2.

TIR-domain-containing adapter-inducing interferon-β(TRIF) is a downstream adaptor of Toll-like receptor(TLR) 4 which is one of the major signal pathways in immune cells leading to neuroinflammtion in central nervous *** present study was to elucidate the effect of TRIF deficiency on optic nerve(ON) regeneration and retinal ganglion cell(RGC) survival in ON crush model,by means of immunoflurosence,fluro-gold retrograde label,co-culture and real-time PCR(polymerase chain reaction).Using TRIF knock-out(KO) mice,however,no significant regeneration was found in RGC *** survival ratio of RGCs was remarkably higher in TRIF KO group when compared with wild type(WT) group in the crush *** immunostained microglia and found that optic nerve lesion induced more microglial activation in WT group(409±34,per retina) than TRIF"’" group(2.4±2.,per retina).Also in a transwell co-cultured system,WT microglia migrated through the transwell *** contrast,few TRIF microglia did so when performed in in vitro crush model on *** immediate consequence of inactivation of microglia is reduced production of cytokines like interferon-β(IFN-β).This is supported by our finding that the relative mRNA expression of IFN-βin TRIF group was decreased about 50%than that in WT group and the degenerated function of IFN-βwas reduced by IFN-βantibody in a transwell co-culture ***,our results indicated that TRIF deficiency promotes axon regeneration in ON via attenuation of microglia activation and consequent reduction in release of harmful cytokines,especially IFN-β.

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狼疮性肾炎患者肾组织白介素-10的表达与巨噬细胞浸润的关系及其意义

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肾脏病与透析肾移植杂志 2004年第2期13卷 107-112页

作者：陈晓岚杨念生南通医学院附属医院肾内科南通226001 广州中山大学附属第一医院肾内科

目的 :研究白介素 10 (IL 10 )在狼疮性肾炎 (LN)患者肾组织中表达及巨噬细胞的浸润与肾脏病理和功能损害的关系。　方法 :采用微波免疫组织化学双重染色法测定正常肾组织和 2.0例LN肾组织巨噬细胞浸润和IL 10的表达及与狼疮肾组织活... 详细信息

目的 :研究白介素 10 (IL 10 )在狼疮性肾炎 (LN)患者肾组织中表达及巨噬细胞的浸润与肾脏病理和功能损害的关系。　方法 :采用微波免疫组织化学双重染色法测定正常肾组织和 2.0例LN肾组织巨噬细胞浸润和IL 10的表达及与狼疮肾组织活动指数、肾脏组织学指标和功能损害的相关关系。　结果 :①正常肾小球及肾小管间质仅个别巨噬细胞存在 ,几乎无IL 10表达 ,而在各型LN ,肾小球和肾小管间质见浸润的巨噬细胞及IL 10阳性细胞明显增多 ,且病变严重的Ⅳ型LN尤为明显。②肾小球KP1+ 巨噬细胞与肾小球细胞数增多 ,LN活动指数、慢性指数均呈显著相关 ,IL 10 + 细胞数也与这些指标相关。肾小管间质中KP1+ 巨噬细胞数及IL 10 + 细胞与小管损害、狼疮肾组织活动指数和慢性指数 (特别是慢性指数 )显著正相关。③肾小球肾小管间质中KP1+ 细胞数与2.4h尿蛋白排泄量、尿NAG排泄量有关 ,IL 10 + 细胞也与上述指标有关 ,而与血清学免疫指标无关。④肾小球KP1+ 与IL 10 + 细胞呈高度相关性 ,r=0 .79(P <0 .0 0 1) ,小管间质中KP1+ 与IL 10 + 细胞也呈高度相关性 :r =0 .76(P <0 .0 0 1)。 70 %KP1+ 细胞聚集在肾组织损害严重部位 ,同时IL 10阳性染色物主要存在于KP1+ 细胞中。　结论 :肾脏IL 10表达增加与巨噬细胞浸润?

关键词：狼疮性肾炎肾组织白介素-10 基因表达巨噬细胞细胞浸润 LN IL-10 肾小球

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透明细胞乳头状肾细胞肿瘤临床病理研究

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临床与病理杂志 2024年第2期44卷 261-267页

作者：彭森孙辉王雪王朝夫吴迪徐州市中心医院病理科江苏徐州221000 上海交通大学医学院附属瑞金医院病理科上海200025

目的:透明细胞乳头状肾细胞肿瘤(clear cell papillary renal cell tumor,CCPRCT)是一种少见但重要的肾肿瘤类型,与其他肾细胞肿瘤具有类似的形态学特征,易导致误诊。本研究旨在探讨CCPRCT的临床病理特征、诊断及鉴别诊断要点,以提高其... 详细信息

目的:透明细胞乳头状肾细胞肿瘤(clear cell papillary renal cell tumor,CCPRCT)是一种少见但重要的肾肿瘤类型,与其他肾细胞肿瘤具有类似的形态学特征,易导致误诊。本研究旨在探讨CCPRCT的临床病理特征、诊断及鉴别诊断要点,以提高其病理诊断的准确性。方法:收集15例CCPRCT患者,观察其临床及影像学特点,分析其镜下形态、免疫表型,并复习相关文献。结果:15例患者中,男10例,女5例,年龄为(54±17)岁,10例患者肿瘤位于左肾,5例患者肿瘤位于右肾。组织学上肿瘤均由增厚的纤维囊包裹,并局限于肾实质内;肿瘤细胞排列成乳头状、管状、囊状、腺泡及实性等结构;乳头由小到中等大小、透明细胞质的单层细胞组成,肿瘤均为世界卫生组织/国际泌尿病理学会(World Health Organization/International Society of Urological pathology,WHO/ISUP)1级或2.;细胞核反极性分布,即核上移,靠近腔面,远离基底,类似鲨鱼牙齿排列。免疫组织化学染色显示:细胞角蛋白7、碳酸酐酶9(carbonic anhydrase 9,CA9)和高分子量细胞角蛋白(34βE12.均为阳性表达;α甲基酰基辅酶A消旋酶、CD117、转录因子E3均为阴性表达;CCPRCT中典型的CA9表现方式是“U型”着色,即腔缘不表达,基底和侧面表达。患者术后随访均未见复发或转移。结论:CCPRCT是一种惰性肾细胞肿瘤,预后好,临床可能存在过诊断,其形态学为特征性的核朝向腔缘的线性排列,特殊的免疫表型CA9呈“U型”阳性,可以与其他肾细胞肿瘤区分开来,但仍然需要积累更多患者来阐释其预后。

关键词：透明细胞乳头状肾细胞肿瘤病理学特征诊断鉴别诊断

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A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

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Acta Pharmaceutica Sinica B 2024年第1期14卷 223-240页

作者： Lei sun Arabella H.Wan Shijia Yan Ruonian Liu Jiarui Li Zhuolong Zhou Ruirui Wu Dongshi Chen Xianzhang Bu Jingxing Ou Kai Li Xiongbin Lu Guohui Wan Zunfu Ke department of pathology the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(Cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202USA department of Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA department of Hepatic Surgery and Liver Transplantation Center Third Affiliated HospitalOrgan Transplantation InstituteSun Yat-sen UniversityOrgan Transplantation Research Center of Guangdong ProvinceGuangdong Province Engineering Laboratory for Transplantation MedicineGuangzhou 510630China Guangdong Provincial Key Laboratory of Liver Disease Research Guangzhou 510630China department of Ultrasound Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Melvin and Bren Simon Comprehensive Cancer Center Indiana UniversityIndianapolisIN 46202USA

Lenvatinib,a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer,facing limitations due to drug ***,we applied a multidimensional,high-throughput screening platform comprising patient-derived resistant liver tumor cells(PDCs),organoids(PDOs),and xenografts(PDXs)to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant *** and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment,expediting drug repurposing *** screening identified romidepsin,YM155,apitolisib,NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO ***,romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway.A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX ***,our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer,providing a feasible multidimensional platform for personalized medicine.

关键词： Lenvatinib Drug resistance High-throughput screening Drug discovery Patient-derived model Romidepsin EGFR Liver cancer

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巨噬细胞移动抑制因子和肝细胞生长因子在鼻咽癌组织中的表达及其对预后的影响

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实用肿瘤杂志 2005年第4期20卷 297-302页

作者：李智林素暇梁惠珍何洁华梁英杰中山大学中山医学院病理学教研室广东广州510089 中山大学肿瘤医院病理科广东广州510089

目的研究巨噬细胞移动抑制因子(macrophagemigrationinhibitoryfactor,MIF)和肝细胞生长因子(hepatocytegrowthfactor,HGF)在鼻咽癌组织中的表达水平及其对预后的影响作用。方法对45例确诊未治的鼻咽原发癌活检组织标本,采用LSAB免疫组... 详细信息

目的研究巨噬细胞移动抑制因子(macrophagemigrationinhibitoryfactor,MIF)和肝细胞生长因子(hepatocytegrowthfactor,HGF)在鼻咽癌组织中的表达水平及其对预后的影响作用。方法对45例确诊未治的鼻咽原发癌活检组织标本,采用LSAB免疫组化法检测鼻咽癌组织中MIF和HGF-α亚单位的表达,同时计数癌组织中新生血管热区的CD34阳性微血管密度(intratumoralmicrovesseldensity,IMD),并将各检测指标与患者的病理临床特点及随访资料相联系,采用Kaplan-Meier法比较各因素与患者生存率之间的关系。结果在45例鼻咽原发癌组织中,癌细胞MIF的阳性表达率为77.8%(35/45),但仅有1例鼻咽癌细胞表达HGF。Kaplan-Meier生存率分析显示,MIF和HGF均高表达病例的生存率明显降低(P=0.033),高IMD病例的生存率与低IMD病例相比差异也有显著性(P=0.048)。结论细胞因子MIF和HGF与肿瘤微血管生成有较密切的关系,并可能在癌细胞的早期淋巴结转移过程中起重要促进作用,两者同步高表达则提示鼻咽癌患者的预后较差。

关键词：鼻咽肿瘤/病理学肝细胞生长因子巨噬细胞游走抑制因子新生血管化病理性预后淋巴转移

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Cytoplasmic Mislocalization of p2. kipl Protein Resulted from Akt Correlates with Poor Prognosis in Lung Adenocarcinoma

Cytoplasmic Mislocalization of p27 kipl Protein Resulted fro...

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2.08年中国病理生理学会第十一届肿瘤和第十二届免疫专业委员会学术会议

作者： Yah Xie~(1a▲) Xin Wang~(1b▲) Huiling Yang~(1a※) Ruiying Zhao~2.Xiang Tao~(1a) Huizhong Zhang~(1b) Chunhong Yan~(1a) Yubiao Guo~(1c) Chun-Hui Su~2.Changju Qu~(1a) Mong-Hong Lee~2.1.1a.department of Pathophysiology,the School of Preclincal Medicine,1b.department of Thoracic Oncology and {2.,Cancer Center,1c.Respiratory Division,The first Affiliated hospital,sun Yat-sen university,Guangzhou 510080,P.R.china 2.department of Molecular and Cellular Oncology,university of Texas,MD Anderson Cancer Center,Houston,TX,USA

To cell cycle,Akt is a positive regulator,while nuclear p2.Kipl is a negative *** was shown that Akt or P-Akt was related with p2.Kipl in cancer cell *** non-small cell lung cancer (NSCLC),Akt was overexpressed,which was associated with the poor *** primary breast cancer,we found the P-S473Akt was upregulated,tumor suppressor 14-3-3σwas downregulated,and the down- regulated 14-3-3σand upregulated P-S473Akt were strongly inverse *** acute myelogenous leukemia,Akt regulated phosphorylation at Thr157 of ***, we detected the localization and expression of p2.Kip1 and Akt protein,and evaluated the relationship of Akt and p2.Kip1 and their impact on prognosis,stage or tumor grade in human lung adenocarcinoma *** observed that Akt (88%,52.of 59) and P-S473Akt (32.,2.of 59) in tumor tissue were overexpressed compared with that in nornal tissue (2.%,6 of 2. and 3.85%,1 of 2. respectively) (P2.Kip1(Np2. Kip1) (37%,18 of 59) in tumor tissue was predominantly lower than that in normal tissues (2. of 2.,81%) (P2.Kipl(Cp2. Kipl) (81%,48 of 59) in tumor tissue was predominantly higher than that(42.31%,11 of 2.) in normal tissues (P473Akt (R=0.365, P2.Kip 1 correlated inversely with that of Cp2.Kipl (R=-0.312.P473Akt was negatively related to Cp2.Kipl (R=-0.347,P473Akt and Akt was positively associated with Cp2.Kipl level (R=0.308 and 0.319,P473Akt and Np2.Kip1 had significant correlations with many clinicopathologic variables (P473Akt or N p2.Kipl protein as a significant independent prognostic factor (P=0.04 and 0.014,respectively).Live-cell imaging and western blot analyses of the cell nu

关键词： Akt p2.Kip 1 lung adenocarcinoma immunohistochemistry Live-cell imaging

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MicroRNA-195 Suppresses Tumorigenicity and Regulates G1/S Transition of Human Hepatocellular Carcinoma Cells

MicroRNA-195 Suppresses Tumorigenicity and Regulates G1/S Tr...

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中国病理生理学会受体、肿瘤和免疫专业委员会联合学术会议

作者： Tengeng Xu~(1*),Ying Zhu~(1*),Yujuan Xiong,~1 Yi-Yuan Ge,~1 Jing-Ping Yun,~(2.3) Shi-Mei Zhuang~(1,2. From the 1 Key Laboratory of Gene Engineering of the Ministry of Education,State Key Laboratory of Biocontrol,School of Life Sciences,State Key Laboratory of Oncology in Southern china,department of {2.,Cancer Center,sun Yat-sen university,Guangzhou,P.R.china

Growing evidences indicate that deregulation of microRNAs(miRNAs) contributes to *** of miR-195 has been observed in various types of ***,the biological function of miR-195 is still largely *** this study,we aimed to elucidate the pathophysiologic role of *** results showed that miR-195 expression was significantly reduced in as high as 85.7%of hepatocellular carcinoma(HCC) tissues and in all of the five HCC cell lines ***,introduction of miR-195 dramatically suppressed the ability of HCC and colorectal carcinoma cells to form colony in vitro and to develop tumor in nude ***,ectopic expression of miR-195 blocked G1/S transition,while inhibition of miR-195 promoted cell cycle progression. Subsequent investigation characterized multiple G1/S transition-related molecules,including cyclin D1, CDK6 and E2.3,as direct targets of *** of cyclin D1,CDK6 or E2.3 phenocopied the effect of miR-195,while overexpression of these proteins attenuated miR-195-induced G1 *** addition,miR-195 significantly repressed the phosphorylation of Rb as well as the transactivation of downstream target genes of *** results imply that miR-195 may block G1/S transition by repressing the Rb-E2. signaling through targeting multiple molecules,including cyclin D1,CDK.6 and E2.3. Conclusions:Our data highlight an important role of miR-195 in cell cycle control and in the molecular etiology of HCC,and implicate the potential application of miR-195 in cancer therapy.

关键词： HCC,hepatocellular carcinoma FACS,fluorescence-activated cell sorting miRNA,microRNA ppRb,phosphorylated pRb 3'UTR,3'-untranslated region

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狼疮样肾炎小鼠脾、肾组织中钙调磷酸酶活性的检测及其意义

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现代免疫学 2004年第1期24卷 36-40页

作者：梁鸣阳晓顾海峪李幼姬孔庆喻叶任高许韩师余学清广州市第一人民医院广州510180 中山大学附属第一医院肾脏科广州510080

为检测狼疮样肾炎小鼠脾、肾组织中钙调磷酸酶 (CaN )活性 ,以探讨其与肾炎小鼠肾组织RANTES表达及肾组织病理改变的关系。采用慢性移植物抗宿主小鼠 (GVHD )狼疮样肾炎模型 ,CaN活性检测采用发色底物法。结果 :(1) 12.模型组肾小球硬... 详细信息

为检测狼疮样肾炎小鼠脾、肾组织中钙调磷酸酶 (CaN )活性 ,以探讨其与肾炎小鼠肾组织RANTES表达及肾组织病理改变的关系。采用慢性移植物抗宿主小鼠 (GVHD )狼疮样肾炎模型 ,CaN活性检测采用发色底物法。结果 :(1) 12.模型组肾小球硬化指数及小管间质损伤总积分显著高于 8周模型组 (P 2.) 12.模型组RANTES蛋白及mRNA表达显著高于 8周模型组 (P 4 )狼疮样肾炎小鼠脾组织中CaN活性与血清抗dsDNA抗体水平呈正相关关系 (r1=0 92.5 ,P 2.=0 6 2.6 ,P 2.,P 4=0 6 2.5 ,P 4 ,P <0 0 5 )。表明狼疮样肾炎小鼠脾细胞存在CaN异常活化。

关键词：狼疮样肾炎脾组织钙调磷酸酶活性检测肾组织肾脏病理

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颅骨骨折断面细微结构的观察研究

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中国法医学杂志 1989年第2期4卷 70-74页

作者：左芷津祝家镇中山医科大学法医病理学教研室

作者利用扫描电子显微镜,对颅骨骨折断面上微细结构的形态学特征进行了观察与研究,发现在颅骨骨折断面上有微细的骨折裂线,向断面深部的骨质中延伸,其宽度为5至100um不等,主要分布在颅骨外板内,或外板与板障的交界处.分布于板障内的微... 详细信息

作者利用扫描电子显微镜,对颅骨骨折断面上微细结构的形态学特征进行了观察与研究,发现在颅骨骨折断面上有微细的骨折裂线,向断面深部的骨质中延伸,其宽度为5至100um不等,主要分布在颅骨外板内,或外板与板障的交界处.分布于板障内的微细裂线可造成骨小梁横行、纵行和螺旋形骨折.骨折时,骨基质中的胶原纤维束可被分离或断裂,各胶原纤维层可分开.骨内血管可被骨折裂线横断或纵形撕裂,损伤的血管可被从哈佛氏管中拉出.生前骨折时,在微细裂线的深方可清楚见到纤维蛋白网和红细胞相互粘集,死后骨折则未见到此现象.本文还探讨了颅骨骨折发生的机理和推断生前骨折的可能性.

关键词：颅骨骨折断面结构法医

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CT guided radioactive 12.I seed implantation compared with first-line chemotherapy in treating localized advanced pulmonary carcinoma:a control study

CT guided radioactive 125I seed implantation compared with f...

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中国(第七届)肿瘤微创治疗学术大会暨世界影像导引下肿瘤微创治疗学会成立筹备大会

作者： Zhang Fu-Jun1,Wu Pei-Hong 1,Li Chuan-Xing1,Wu Yue-Xia1,Huang Jin-Hua1, Fan Wei-Jun1,Jiao De-Chao1,liu Jian2.Li Yu-Liang3 1.department of Medical Imaging and Interventional Radiology,Cancer Center,sun Yat-{2. university,Guangzhou, Guangdong,5 10060,P.R.china 2.Intervention department,Henan Provincial People’s hospital,Zhengzhou,Henan,450003,P.R.china 3.Intervention department,The Second Affiliated hospital of Shandong university,Jinan,Shangdong,2.0033,P.R.china

Objective To investigate the clinical value of CT guided radioactive seed 12.I implantation(CTRISI) in the treatment of localized advanced pulmonary *** Thirty-two patients(Group A) with localized advanced pulmonary carcinoma,received radioactive seed 12.I implantation after failure in first line chemotherapy. There were 15 males,and 17 females,ageing from 31 to 73 years old,52.0 on the *** were 48 lesions in the 32.patients altogether and all the lesions had a clear border with the adjacent normal *** diameter of tumors was 4.5-7.5cm,the average was *** the cases had been confirmed as malignant by pathology(percutaneous aspiration biopsy).12.I seeds of 2.2.3.3×107 megabecquerel(MBq)were implanted into these *** total number of the seeds implanted in each lesion was 10～*** dosage of the region around the tumor was *** to Treatment Planning System(TPS),we implant the 12.I seeds into the tumors under CT *** picked 30 patients (Group B) to be treated by first line chemotherapy in our hospital randomly as the control *** The results of CT follow-up after two months proved that the local control rate of the group treated with 12.I seeds implantation was 78.1%,one year survival rate was 65.0%,median survival time was 15 *** amount of effusion was observed in these patients during *** happened in 4 cases with one of the lungs compressed less than 30 percent and got improved healthy after conservative *** week after the procedure,bloody sputum occured in 15 *** medullary suppression and other serious complications occurred in these *** local control rate of the control group was 43.3%,one year survival rate was 48.0%,median survival time was 11 months,the incidence rate of medullary suppression is 46.3%.There was a significant difference between the two *** CTGRISI procedure is safe and well-tolerated in treating localized advanc

关键词： Iodine radioisotopes interventional brachytherapy localized advanced stage pulmonary carcinoma evaluation studies

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