Development and Application of Procedures for the Management of Skin Toxicity Related to Immune Checkpoint Inhibitors in Patients with Lung Cancer

Objective: To establish the procedures for the management of skin toxicity related to immune checkpoint inhibitors in patients with lung cancer and explore the effect of application. Methods: A total of 24 evidence-based evidences were collected from 7 aspects, including risk factors, baseline screening, ICIs monitoring, daily skin care, multidisciplinary management, symptom management and health education. A total of 157 lung cancer patients and 94 nurses from 8 wards of the Oncology department of our hospital from November 2022 to May 2023 were selected by convenience sampling. A total of 77 patients and 46 nurses from ward 1 - 4 were divided into the baseline group. There were 80 patients and 48 nurses in Ward 5 - 8 as the evidence-based practice group. In the baseline group, patients were treated with routine methods such as assessing skin symptoms, taking medication according to symptoms, guiding to keep skin clean and moist, eating a light diet, and avoiding scratching. The evidence-based practice group adopts an evidence-based continuous improvement model for nursing. The differences in the severity of symptoms of skin toxicity in the second cycle of medication and the knowledge and practice of self-care of skin toxicity were compared between the two groups before and after the use of the syndrome, as well as the differences in the implementation rate of review indicators, evidence-based ability and knowledge and practice of skin toxicity care before and after the use of the syndrome. Results: The incidence and severity of cutaneous toxicity were significantly lower after treatment than before treatment (P P < 0.05). Conclusion: The implementation of immune checkpoint inhibitor-related skin toxicity management procedures can effectively reduce the incidence and severity of skin toxicity symptoms, optimize the clinical pathway, and improve the quality of care.

Impact of coupling coordination development of port and city environments on urban economic competitiveness:Evidence from the coastal port cities in eastern China

Promoting the coupling coordination development of port and its hinterland city environments is an important way to improve urban economic competitiveness.Based on relevant data of 13 coastal port cities in eastern China from 2000 to 2018,this study explores the coupling coordination development of port and city environments and its impact on urban economic competitiveness by constructing the coupling coordination degree model and the panel threshold model.The research results show that:(1)In terms of the coupling coordination development of port and city environments,most coastal ports and their hinterland cities are in a state of moderate or serious disorder.Overall,the degree of coupling coordination of port and city environments needs to be further improved;(2)The coupling coordination degree of port and city environments has a significant impact on urban economic competitiveness,and this effect gradually increases with the development of the ports and the urban economy.Among the variables that impact the urban economic competitiveness,fixed assets investment and foreign trade are significant factors that can enhance urban economic competitiveness.(3)At present,there is a“U-shaped”relationship between the coupling coordination degree of port-city environments and the urban economic competitiveness.This relationship lies on the right side of the inflection point of the“U-shaped”curve.Therefore,following the concept of assigning priority to ecological development,expanding fixed assets investment and actively developing foreign trade can further enhance the urban economic competitiveness.

Application Strategies of Spatial Refinement Design in Ancient Cities Supported by Digital Te-Zhaoyu Ancient City in Qixian County as an Example

Digital technology provides a method of quantitative investigation and data analysis for contemporary landscape spatial analysis,and related research is moving from image recognition to digital algorithmic analysis,providing a more scientific and macroscopic way of research.The key to refinement design is to refine the spatial design process and the spatial improvement strategy system.Taking the ancient city of Zhaoyu in Qixian County,Shanxi Province as an example,(1)based on obtaining the integrated data of the ancient city through the drone tilt photography,the style and landscape of the ancient city are modeled;(2)the point cloud data with spatial information is imported into the point cloud analysis platform and the data analysis is carried out from the overall macroscopic style of the ancient city to the refinement level,which results in the formation of a more intuitive landscape design scheme,thus improving the precision and practicability of the landscape design;(3)Based on spatial big data,it starts from the spatial aggregation level,spatial distribution characteristics and other evaluation index system to achieve the refinement analysis of the site.Digital technology and methods are used throughout the process to explore the refined design path.

Exploring the Need and Strategy for Intraoperative Freezing to Identify Metastatic Adenocarcinoma of the Lungs

Objective: To explore the necessity and strategy of intraoperative freezing to identify primary and metastatic adenocarcinoma of the lung. Methods: This study retrospectively analyzes the impact of failing to make a definitive diagnosis of metastatic adenocarcinoma of the lung on the clinical surgical approach in four cases of intraoperative freezing. It also examines the reasons for this failure and reviews the relevant literature. Results: All 4 cases of intraoperative freezing were diagnosed as invasive adenocarcinoma, and none of them made a definitive diagnosis of metastatic adenocarcinoma. Conclusion: It is difficult to confirm the diagnosis of metastatic adenocarcinoma of the lung by intraoperative frozen section, and the combination of patient history, rapid immunohistochemistry, and histological morphology of intraoperative frozen section for its identification can guide the surgeon to adjust the surgical approach in time and provide evidence for the establishment of surgical protocols for reference.

文旅融合:“Citywalk”热潮下的冷思考

“Citywalk”(城市漫步)强调慢节奏和沉浸式体验,是深受年轻人追捧的文旅消费新范式。“Citywalk”火爆出圈的背后,也存在着产品辨识度不高、利润低、专业性不强、产品更迭慢等问题。“文旅融合”的有效健康发展,需要在资源供给、产品创新、服务品质等方面开展全方位、多领域的合作联动,成果共享才能形成互利共赢新格局。

LungPoint导航联合吲哚菁绿荧光成像在Ⅰa期非小细胞肺癌淋巴结采样中的应用价值

目的:寻找一种准确定位Ⅰa期非小细胞肺癌患者(NSCLC)前哨淋巴结(SLN)的方法,验证SLN作为淋巴结取样样本的合理性。方法:采用前瞻性研究方法,参照入组标准纳入2021年1月至2023年12月在山东省公共卫生临床中心胸外科临床分期为Ⅰa期NSCLC住院患者50例,术前借助LungPoint导航气管镜下肿瘤周围注射示踪剂吲哚菁绿,通过荧光胸腔镜成像完成SLN定位,并对包括SLN在内的区域淋巴结行病理学检查,使用该方法对SLN的识别率、准确率与假阴性率等验证其作为淋巴结取样样本的合理性。结果:50例患者中,41例检测到SLN,识别率为82.0%(41/50),经病理检测发现3例共计9枚SLN有淋巴结转移(阳性),其中1例亦检出非前哨淋巴结(N-SLN)阳性2枚。9例患者未检测到SLN,清扫淋巴结54枚,未发现转移淋巴结,故SLN准确率为100.0%(41/41),假阴性率为0(0/3)。结论:借助LungPoint气管镜在肿瘤周围注射示踪剂吲哚菁绿,通过荧光胸腔镜成像探寻SLN技术具有较高的区域淋巴结转移预测性,有望成为指导Ⅰa期NSCLC系统性淋巴结采样的依据。

EZH2 is a biomarker associated with lung cancer diagnosis and immune infiltrates without prognostic specificity: a study based on the cancer genome atlas data

Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of polycomb repressive complex 2(PRC2).Dysregulation of EZH2 causes alteration of gene expression and functions,thereby promoting cancer development.Recent studies suggest that EZH2 has a potential prognostic role in patients with nonsmall cell lung cancer(NSCLC).However,the prognostic value of EZH2 expression levels in NSCLC is controversial.In this study,we evaluated the prognostic value in lung cancer(LC-LUAD/LUSC)based on data from The Cancer Genome Atlas(TCGA)database.Kruskal-Wallis test,Wilcoxon signed-rank test,and logistic regression were used to evaluate the relationship between EZH2 expression and clinicopathological features.Cox regression and the Kaplan-Meier method were adopted to evaluate prognosis-related factors.Gene set enrichment analysis(GSEA)was performed to identify the key pathways related to EZH2.The correlations between EZH2 and cancer immune infiltrates were investigated by single-sample Gene Set Enrichment Analysis(ssGSEA).EZH2 was found to be up regulated with amplification in tumor tissues in multiple LC cohorts.High EZH2 expression was associated with poorer overall survival(OS).GSEA suggested that EZH2 regulates innate immune system,ECM affiliated,matrisome,surfactant metabolism.Notably,ssGSEA indicated that EZH2 expression was positively correlated with infiltrating levels of Th2 cells and significantly negatively correlated with mast cell infiltration level.These results suggest that EZH2 is associated with LC immune infiltration and significantly over-expressed in lung cancer,and its diagnostic value is better than prognosis,which lays a foundation for further study of the immunomodulatory role of EZH2 in LC.

Multilevel Attention Unet Segmentation Algorithmfor Lung Cancer Based on CT Images

Lung cancer is a malady of the lungs that gravely jeopardizes human health.Therefore,early detection and treatment are paramount for the preservation of human life.Lung computed tomography(CT)image sequences can explicitly delineate the pathological condition of the lungs.To meet the imperative for accurate diagnosis by physicians,expeditious segmentation of the region harboring lung cancer is of utmost significance.We utilize computer-aided methods to emulate the diagnostic process in which physicians concentrate on lung cancer in a sequential manner,erect an interpretable model,and attain segmentation of lung cancer.The specific advancements can be encapsulated as follows:1)Concentration on the lung parenchyma region:Based on 16-bit CT image capturing and the luminance characteristics of lung cancer,we proffer an intercept histogram algorithm.2)Focus on the specific locus of lung malignancy:Utilizing the spatial interrelation of lung cancer,we propose a memory-based Unet architecture and incorporate skip connections.3)Data Imbalance:In accordance with the prevalent situation of an overabundance of negative samples and a paucity of positive samples,we scrutinize the existing loss function and suggest a mixed loss function.Experimental results with pre-existing publicly available datasets and assembled datasets demonstrate that the segmentation efficacy,measured as Area Overlap Measure(AOM)is superior to 0.81,which markedly ameliorates in comparison with conventional algorithms,thereby facilitating physicians in diagnosis.

Secondary metabolites of mulberry leaves exert anti-lung cancer activity through regulating the PD-L1/PD-1 signaling pathway

Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully elucidated.We synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis.MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells.Chemical proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory function.Cell-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 protein.Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein.MAN downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8^(+)GZMB^(+)T cells and the decrease of CD8^(+)PD-1^(+)T cells.It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling.In vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic effect.Taken together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer.Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.

Understanding the Relationship Between Shrinking Cities and Land Prices:Spatial Pattern,Effectiveness,and Policy Implications

Urban shrinkage has emerged as a widespread phenomenon globally and has a significant impact on land,particularly in terms of land use and price.This study focuses on 2851 county-level cities in China in 2005–2018(excluding Hong Kong,Macao,Taiwan,and‘no data’areas in Qinhai-Tibet Plateau)as the fundamental units of analysis.By employing nighttime light(NTL)data to identify shrinking cities,the propensity score matching(PSM)model was used to quantitatively examine the impact of shrinking cities on land prices,and evaluate the magnitude of this influence.The findings demonstrate the following:1)there were 613 shrinking cities in China,with moderate shrinkage being the most prevalent and severe shrinkage being the least.2)Regional disparities are evident in the spatial distribution of shrinking cities,especially in areas with diverse terrain.3)The spatial pattern of land price exhibits a significant correlated to the economic and administrative levels.4)Shrinking cities significantly negatively impact on the overall land price(ATT=–0.1241,P<0.05).However,the extent of the effect varies significantly among different spatial regions.This study contributes novel insights into the investigation of land prices and shrinking cities,ultimately serving as a foundation for government efforts to promote the sustainable development of urban areas.

Nursing effect of narrative nursing intervention on postoperative patients with severe lung cancer

BACKGROUND Lung cancer is a common disease with high mortality,and psychological support is very important in the diagnosis and treatment of postoperative patients with cancer pain.AIM To explore the application effect of the narrative nursing method in postoperative lung cancer patients in the intensive care unit.METHODS A total of 120 patients diagnosed with lung cancer and experiencing cancer-related pain were randomly allocated into two groups:an observation group and a control group,each consisting of 60 cases.The control group was given routine analgesic and psychological care,while the research group applied the five-step narrative nursing method based on routine care,comparing the visual analogue scale scores,sleep status,anxiety and depression status,and quality of life of the two groups of patients before and after the intervention.RESULTS The pain scores,anxiety scores,and depression scores of the study group were lower than those of the control group after the intervention using the narrative nursing method,and the difference was statistically significant(P<0.05).CONCLUSION Using narrative nursing methods to intervene in patients with lung cancer combined with cancerous pain can help patients to correctly recognize their disease,adjust their mentality,establish confidence,alleviate patients'subjective pain feelings,and improve their adverse emotions.

Gastric metastasis of small cell lung carcinoma:Three case reports and review of literature

BACKGROUND Small cell lung carcinoma(SCLC)is highly susceptible to metastasis in the early stages of the disease.However,the stomach is an uncommon site of metastasis in SCLC,and only a few cases of this type of metastasis have been reported.Therefore,SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed.CASE SUMMARY We report three cases of gastric metastasis from SCLC in this article.The first patient presented primarily with cough,hemoptysis,and epigastric fullness.The other two patients presented primarily with abdominal discomfort,epigastric distension,and pain.All patients underwent gastroscopy and imaging examinations.Meanwhile,the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma.Finally,the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis.The three patients did not receive appropriate treatment and died within a short time.CONCLUSION Here,we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians'understanding of this disease.

Construction land expansion and influencing factors of typical river valley cities in Northeast China: Taking Jilin City as an example

Jilin City is a typical river valley city in Northeast China.In this paper,the authors studied the spatial and temporal expansion characteristics of the built-up areas in Jilin City from 1990 to 2020 using the analysis of expansion speed and strength,fractal dimension,barycenter coordinate transfer index and sector analysis.The ultimate-goal is to analyze the driving and restrictive factors that affect the spatial expansion of river valley cities.The results indicate that(1)the expansion speed of urban land in Jilin City has been re-latively slow in the past 30 years,while only slightly faster in 2010–2020;(2)in the spatial dimension,Jilin City mainly expanded to the south,then to the west,and extensive expansion has resulted in complex mor-phology with little stability and compactness;(3)the expansion is affected by multiple factors,of which the positive factor is industrial development,while the restrictive factors include natural factors,population loss,etc.This study provides a case for the formulation of land use policies and land space planning in river valley cities.

Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

Enhanced recovery after surgery in elderly patients with non-small cell lung cancer who underwent video-assisted thoracic surgery

BACKGROUND This study was designed to investigate the clinical outcomes of enhanced recovery after surgery(ERAS)in the perioperative period in elderly patients with nonsmall cell lung cancer(NSCLC).AIM To investigate the potential enhancement of video-assisted thoracic surgery(VATS)in postoperative recovery in elderly patients with NSCLC.METHODS We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS(the ERAS group)and 327 elderly NSCLC patients who received routine care(the control group)after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017.After propensity score matching of baseline data,we analysed the postoperative stay,total hospital expenses,postoperative 48-h pain score,and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection.RESULTS After propensity score matching,ERAS significantly reduced the postoperative hospital stay(6.96±4.16 vs 8.48±4.18 d,P=0.001)and total hospital expenses(48875.27±18437.5 vs 55497.64±21168.63 CNY,P=0.014)and improved the satisfaction score(79.8±7.55 vs 77.35±7.72,P=0.029)relative to those for routine care.No significant between-group difference was observed in postoperative 48-h pain score(4.68±1.69 vs 5.28±2.1,P=0.090)or postoperative complication rate(21.2%vs 27.1%,P=0.371).Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection.CONCLUSION ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.

Importance of Urban Wetland Parks under the Development of Green Healthy Cities:A Case Study of Nanjing City

Wetlands are widely distributed all over the world,and have many wildlife resources,which are the main pieces of the puzzle for natural resource conservation and sustainable development on earth and have important irreplaceability.In this paper,through questionnaire survey,field research,literature review,etc.,importance weight analysis was conducted by using principal component analysis,and field survey and questionnaire were carried out to collect data on ecological environment function,environmental protection function,landscape beautification function,disaster prevention and mitigation function of urban wetlands.The problems in wetland parks of Nanjing were discussed,such as lack of awareness of landscape planning,deficient late management of wetland parks,weak ability of sustainable development,and unreasonable landscape layout and function.Finally,corresponding solutions were proposed,such as adhering to the planning and design of urban wetland parks with green as the base and health as the basis,persisting in the construction of a wetland system with high biodiversity and near-natural characteristics,adhering to the principle of sustainable development,adopting the construction idea of symbiosis and circulation of urban wetland parks,strengthening education and publicity work,and paying attention to the organic combination of system protection and coordinated construction.The research can build a new development direction for the model of urban wetland parks and green healthy cities,and provide theoretical support for urban sustainable construction.

物质循环视角下的“可持续漂浮城市”解析——以BIG事务所“Oceanix City”方案为例

随着时代发展,现代城市正面临着土地短缺、住房紧张、能源枯竭以及海平面上升等一系列问题。因而探索陆地之外的生存空间,进而缓解多种城市问题是人们长久以来的愿景。近年来,联合国人居署提出可持续发展的漂浮城市概念,并由BIG事务所设计了世界上第一个弹性化和可持续的漂浮城市原型——Oceanix City。该城市通过引入城市农业,配置能量、水分、养分等循环系统实现最大限度自给自足,满足居民日常生活需求,达到可持续发展的目标。文章运用文献研究法梳理了从漂浮建筑、漂浮社区到漂浮城市的发展历程,并以“Oceanix City”方案为案例分析对象,从物质循环视角入手解析方案的规划设计与建造、循环系统的运作等方面,总结得出拓展海上空间、引入城市农业并构建物质循环系统是应对上述城市问题的有效方式,以期为未来城市的可持续发展提供启示。

Influence of Urban Street Greening Design under the Concept of Green Healthy Cities:A Case Study of Hefei City

In order to explore the influence of urban street greening,the street landscape of Changjiang West Road and Xiyou Road in Hefei City was selected as the research sample to study the design of urban street landscape under the concept of green healthy cities.The results show that the urban street landscape of Hefei City is single in design and plant type,and plant maintenance management is not good.It is proposed to strengthen the maintenance and management of street greening,increase the types of native plants,and improve cultural connotation,so as to enhance the artistry,regionalism and functionality of urban street landscape in Hefei City.

Between the City and Images:An Analysis of Mainstream Media’s Paths of Constructing the Cultural Memory of a City:Taking Chengdu Radio and Television’s“Hi Chengdu”as an Example

Mainstream media play a crucial role in constructing the cultural memory of a city.This study used 319 short videos released by“Hi Chengdu,”a new media product of Chengdu Radio and Television,as samples.Based on the grounded theory,a research framework encompassing“content,technology,and discourse”was established to explore the paths through which mainstream media construct the cultural memory.Regarding content,this paper emphasized temporal and spatial contexts and urban spaces,delving deep into the themes of the cultural memory and vehicles for it.In terms of technology,this paper discussed the practice of leveraging audio/visual-mode discourse to stitch together the impressions of a city and evoke emotional resonance to create a“flow”of memory.As for discourse,this paper looked at the performance of a communication ritual to frame concepts and shape urban identity.It is essential to break free from conventional thinking and leverage local culture as the primary driving force to further boost a city’s productivity,in order to excel in cultural communication.

Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment:A Case report

BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung cancer(NSCLC).CASE SUMMARY A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment.Secondary pathological tissue biopsy confirmed squamous cell carcinoma(SCC)transformation.Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time,while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC.Notably,EGFR-TKIs resistance includes primary and acquired.Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs,with SCC transformation being relatively rare.Our results provide more detailed results of the patient’s diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma.CONCLUSION Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.