Background:Lung invasive mucinous adenocarcinoma(LIMA)is a rare,unique,and heterogeneous subtype of lung cancer whose patterns of lymph node(LN)metastasis are unknown,and a consensus on LN dissection(LND)has not been reached.This study aimed to evaluate LN metastasis patterns in LIMAs and establish optimal LND strategies. Methods:Data about 19,596 LNs from 1474 LIMA patients collected between January 2010 and December 2021 at 8 lung cancer research centers and tertiary hospitals across China,and data from 5304 LIMA patients between 2004 and 2021 in the SEER database were analysed.Metastasis probabilities were calculated for each LN station to construct a metastasis atlas.Statistical methods,including LOWESS fitting,restricted cubic spline,Kaplan-Meier,and logistic regression analyses,were employed to identify optimal LND strategies. Results:Compared with non-mucinous adenocarcinoma patients,LIMA patients exhibited distinct clinicopathological features and a significantly lower probability of LN metastasis(4.20%vs.7.19%,P<0.05).Metastasis was most common in the peripheral and hilar/interlobar zones(especially stations 14 and 10),with minimal involvement in the lower zone(stations 8 and 9).A U-shaped relationship between the LN count and prognosis(including overall survival,relapse-free survival,and cancer-specific survival)was found,with 6-20 and 18 LNs as the optimal range and cut-off point,respectively.Excessive or insufficient dissection was linked to poorer outcomes.A predictive model(area under the receiver operating characteristic cure=0.8367)revealed that patients with a probability≥0.5 had a significantly greater proportion of patients with stage N1+disease(including N1 and N2 patients)(68.09%vs.11.63%,P<0.001)and worse overall survival[hazard ratio(HR)=4.00,95%CI 2.72-5.87,P<0.001]and relapse-free survival(HR=5.53,95%CI 3.97-7.71,P<0.001).The minimum numbers of LNs for the low-(probability<0.1),medium-(probability 0.1-0.5),and high-(probability>0.5)risk patients were 7,14,and 17,respectively.For those with uncertain metastatic risk,dissecting 18 LNs may be the most appropriate and robust strategy. Conclusions:This study systematically revealed the pattern of LIMA-specific LN metastasis and proposed a risk-stratified LND strategy.These recommendations balance the imperatives of accurate staging with the preservation of long-term patient prognosis,offering a practical guideline for surgical decision-making.

Since the emergence of the Corona Virus Disease in 2019 (COVID-19), it has become a serious health problem affecting the human respiratory system. At present, automatic segmentation of lung infection areas from Computed Tomography has been playing a crucial role in the diagnosis of this disease because of its ability to perform pathological studies based on the lung infection areas. However, due to the lung infection areas scattered distribution, the existing segmentation methods generally have the problems of missing and incomplete segmentation. The Convolutional Neural Network (CNN)-based approaches generally lack the ability to model explicit long-range relation, and the transformer-based methods are not conducive to capturing the detailed boundaries of infected areas. Whereas the infected regions of the coronavirus images are scattered and boundary information plays an important role, both the boundaries and the global infected areas need to be taken into account. Therefore, we propose a novel coronavirus image segmentation network alternately using Swin transformer and CNN (STCNet). Firstly, to enable network to capture richer features, the ReSwin transformer block is proposed and added after each level of convolution block in the encoder-decoder. Secondly, to effectively retain the infected areas boundary information, the skip connection cross attention module is used to provide spatial information to each decoder. And through the fine-tuned scale-aware pyramid fusion module to fuse multi-scale context information. Experimental results show that STCNet at can achieve state-of-the-art performance on two coronavirus segmentation datasets, with Dice achieves 79.92 % and 82.78 %, respectively. Our code is available at https://github.com/sineagles/STCNet.

Background Pathological cardiac hypertrophy is associated with cardiac dysfunction and is a key risk factor for heart failure and even sudden death. This study investigates the function of Mycn in cardiac hypertrophy and explores the interacting molecules. Methods A mouse model of cardiac hypertrophy was induced by isoproterenol (ISO). The cardiac dysfunction was assessed by the heart weight-to-body weight ratio (HW/BW), echocardiography assessment, pathological staining, biomarker detection, and cell apoptosis. Transcriptome alteration in cardiac hypertrophy was analyzed by bioinformatics analysis. Gain- or loss-of-function studies of MYCN proto-oncogene (Mycn), ubiquitin specific peptidase 2 (USP2), and junction plakoglobin (JUP) were performed. The biological functions of Mycn were further examined in ISO-treated cardiomyocytes. The molecular interactions were verified by luciferase assay or immunoprecipitation assays. Results Mycn was poorly expressed in ISO-treated mice, and its upregulation reduced HW/BW, cell surface area, oxidative stress, and inflammation while improving cardiac function of mice. It also reduced apoptosis of cardiomyocytes in mice and those in vitro induced by ISO. Mycn bound to the USP2 promoter to activate its transcription. USP2 overexpression exerted similar myocardial protective functions. It stabilized JUP protein by deubiquitination modification, which blocked the Akt/β-catenin pathway. Knockdown of JUP restored phosphorylation of Akt and β-catenin protein level, which negated the protective effects of USP2. Conclusion This study demonstrates that Mycn activates USP2 transcription, which mediates ubiquitination and protein stabilization of JUP, thus inactivating the Akt/β-catenin axis and alleviating cardiac hypertrophy-induced heart failure.

Background:Long non-coding RNAs (lncRNAs) were demonstrated to be key to cancer progression and highly associated with the tumor immune microenvironment. Oxidative stress and immune may modulate the biological behaviors of tumors. Therefore, biomarkers that combined oxidative stress, immune, and lncRNA can be a promising candidate bioindicator in clinical therapy of cancers.Methods:Immune-related genes (IRGs) and oxidative stress-related genes (ORGs) were identified based on a detailed review of published literatures. The transcriptome data and clinical information of lung adenocarcinoma (LUAD) patients were obtained from TCGA database. Lasso and Cox regression analyses were conducted to develop a prognostic model. Additionally, the link between immune checkpoints, immune cells, and the prognostic model was investigated, and predict the sensitivity of immunotherapy.Results:2498 IRGs and 809 ORGs were extracted from previous studies, and 190 immune- and oxidative stress-related genes (IOGs) were acquired by overlapping the above genes. 658 immune- and oxidative stress-related lncRNAs (IOLs) were screened by Pearson correlation analysis. A total of 25 prognosis-related IOLs were screened by univariate regression analysis. Finally, LASSO Cox regression analysis was adopted for determining a 12-IOLs prognostic risk signature. The signature performance was confirmed in the training cohort and the testing cohort, and cases were classified into low- and high-risk groups by the risk score calculated from the signature. Patients in the high-risk group had poor prognoses and immunosuppression, while the risk score was significantly associated with tumor-infiltrating immune cells, immune checkpoint expression, and immunotherapy responses. In vitro experiments further confirmed the expression of key signature gene.Conclusion:Our new IOLs-related prognostic signature can be reliable prognostic tools and therapeutic targets for LUAD patients.

It has been reported before that acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B) plays roles in many cancers, yet no report of its role in lung cancer exists. In this study, we documented an elevation of ANP32B within lung cancer tissues and cells. Knockdown of ANP32B hindered the proliferation as well as migration of lung cancer cells, whereas overexpression of ANP32B helps to promote the malignant progression of lung cancer. ANP32B also regulates lung cancer cells' apoptosis and cell cycling. In addition, voltage-dependent anion channel 1 (VDAC1) has been found to be a downstream targeted gene of ANP32B and is positively regulated by ANP32B in lung cancer cells. According to our research, the expression of VDAC1 was positively associated with ANP32B expression in lung adenocarcinoma (r = 0.61, P < 0.001) samples by Pearson's correlation coefficient analysis. Furthermore, rescue experiments demonstrated that VDAC1 could rescue the effect of ANP32B expression on lung cancer cell proliferation and migration. Our results suggest that ANP32B overexpression facilitates lung cancer progression by increasing the expression of VDAC1. As such, we have revealed a novel mechanism regulating the connection between ANP32B and VDAC1 and a potential role of ANP32B as an oncogene and a clinical therapeutic target in lung cancer.

目的 探讨小整合膜蛋白22(SMIM22)在肺癌恶性进展中的作用及分子机制.方法 使用TCGA数据库获取SMIM22在肺癌组织中的表达水平;在H1299和H1975细胞中干扰SMIM22基因表达,定量聚合酶链反应(qPCR)观察其干扰效果并用CCK8检测干扰对肺癌细胞增殖的影响、流式细胞术检测干扰肺癌细胞凋亡和周期的影响;蛋白免疫印迹(Western Blot)检测干扰SMIM22对H1299细胞中p-MEK、MEK和c-myc蛋白水平的影响;qPCR检测干扰SMIM22对c-myc下游基因Cyclin D2、Cyclin E1、CDK2和CDK4的mRNA表达的影响.结果 与癌旁组织相比,SMIM22在肺癌组织中表达升高(P＜0.05);SMIM22高表达与肺癌患者不良预后相关.SMIM22表达降低,能抑制肺腺癌细胞增殖、促进细胞凋亡并将细胞周期阻滞在G0/G1期.敲低SMIM22后,与MEK-MYC通路相关的蛋白(如p-MEK、c-MYC)表达水平降低,相关基因(如Cyclin D2、Cyclin E1、CDK2、CDK4)表达水平也降低(P<0.05).结论 SMIM22在肺癌组织中高表达,通过调控MEK-MYC通路参与肺癌的恶性发展,可能成为肺癌新的潜在诊断指标及治疗靶点.

Lung cancer is one of the most common causes of cancer-related death. In the past decade, the treatment and diagnosis of lung cancer have progressed significantly in early efforts to promote the survival of lung cancer patients. Kruppel like factor 16 (KLF16) is a zinc finger transcription factor that regulates a diverse array of developmental events and cellular processes. KLF16 is involved in the progression of various cancer types. However, the role of KLF16 in the development of lung cancer remains unknown. In this study, KLF16 was overexpressed in lung cancer samples. KLF16 downregulation inhibited lung cancer cell proliferation and migration. Conversely, KLF16 overexpression promoted lung cancer cell growth and invasion. Mechanistically, the expression level LMNB2 was suppressed by KLF16 knockdown and was promoted by KLF16 overexpression. The overall survival of patients with high LMNB2 levels was poor. Luciferase assays showed that KLF16 promoted the transcription activity of LMNB2 gene. Concomitantly, the expression level of LMNB2 was also higher in lung adenocarcinoma (LUAD) than in normal tissues, and its knockdown or overexpression can reverse the effect of KLF16 overexpression or knockdown on lung cancer cell proliferation, migration, and even tumorigenesis, indicating that LMNB2 also functions as an oncogene. In conclusion, KLF16 can be used as a potential therapeutic and preventive biomarker in lung cancer treatment and prognosis by actively regulating the expression of LMNB2.

Background The aim of this study was to draw a comprehensive mutational landscape of nasopharyngeal carcinoma (NPC) tumors and identify the prognostic factors for distant metastasis-free survival (DMFS). Methods A total of forty primary nonkeratinizing NPC patients underwent targeted next-generation sequencing of 450 cancer-relevant genes. Analysis of these sequencing and clinical data was performed comprehensively. Univariate Cox regression analysis and multivariate Lasso-Cox regression analyses were performed to identify factors that predict distant metastasis and construct a risk score model, and seventy percent of patients were randomly selected from among the samples as a validation cohort. A receiver operating characteristic (ROC) curve and Harrell's concordance index (C-index) were used to investigate whether the risk score was superior to the TNM stage in predicting the survival of patients. The survival of patients was determined by Kaplan-Meier curves and log-rank tests. Results The twenty most frequently mutated genes were identified, such as KMT2D, CYLD, and TP53 et al. Their mutation frequencies of them were compared with those of the COSMIC database and cBioPortal database. N stage, tumor mutational burden (TMB), PIK3CA, and SF3B1 were identified as predictors to build the risk score model. The risk score model showed a higher AUC and C-index than the TNM stage model, regardless of the training cohort or validation cohort. Moreover, this study found that patients with tumors harboring PI3K/AKT or RAS pathway mutations have worse DMFS than their wild-type counterparts. Conclusions In this study, we drew a mutational landscape of NPC tumors and established a novel four predictor-based prognostic model, which had much better predictive capacity than TNM stage.

IntroductionThe present work demonstrates the synthesis of Ag nanoparticles (Ag NPs) by aqueous extract of Thymus ‎capitatus as green reductant and capping agent without any toxic reagent. ‎Material and methodsPhysicochemical characteristics of the said nanocomposite were elucidated by field emission scanning electron ‎microscopy (FE-SEM), fourier-transform infrared spectroscopy (FTIR), and UV-Vis Spectroscopy. ‎ResultsThe biogenic Ag NPs are uniformly globular. The Ag NPs has been explored biologically in the anticancer and ‎antioxidant assays. In the cellular and molecular part of the recent study, the treated cells with Ag NPs were ‎assessed by MTT assay for 48h about the cytotoxicity and anti-human lung adenocarcinoma properties on ‎normal (HUVEC) and lung adenocarcinoma cell lines i.e. lung well-differentiated bronchogenic adenocarcinoma ‎‎(HLC-1), lung moderately differentiated adenocarcinoma (LC-2/ad), and lung poorly differentiated ‎adenocarcinoma (PC-14). The viability of malignant lung cell line reduced dose-dependently in the presence of ‎Ag NPs. The IC50 of Ag NPs were 209, 185, and 106 µg/mL against HLC-1, LC-2/ad, and PC-14 cell lines, ‎respectively. In the antioxidant test, the IC50 of Ag NPs and BHT against DPPH free radicals were 86 and 76 ‎‎µg/mL, respectively. ‎ConclusionsAfter clinical study, Ag NPs containing Thymus capitatus leaf aqueous extract may be used to formulate a new ‎chemotherapeutic drug or supplement to treat the several types of human lung adenocarcinoma. ‎

目的 比较肺结核(tuberculosis,TB)及肺炎支原体肺炎(Mycoplasma pneumoniae pneumonia,MPP)患儿外周血炎性反应指标水平及淋巴细胞亚群比例.方法 156例TB患儿(TB组)、149例MPP患儿(MPP组)及156例健康查体儿童(对照组)采集外周静脉血,TB及MPP组检测血白细胞(white blood cell,WBC)、C-反应蛋白(C reactive protein,CRP)及降钙素原(procalcitonin,PCT),采用流式细胞仪测算三组外周血淋巴细胞亚群比例.结果 TB组外周血WBC计数、CRP及PCT水平分别为8.90(6.98,11.23)×109/L、12.83(1.00,33.15)mg/L及0.06(0.040,0.152)μg/L;MPP组分别为8.80(6.70,11.50)×109/L、12.79(4.72,32.46)mg/L及0.075(0.042,0.187)μg/L,组间各炎症指标比较,P均>0.05.TB组外周血WBC、CRP及PCT阳性率分别为38.50％、57.80％及48.30％;MPP组分别为32.90％、57.00％及59.10％,组间各指标比较,P均>0.05.与对照组比较,TB组外周血CD3+T、CD4+T、CD8+T及CD56+NK比例低(P均<0.01),CD19+B比例高(P<0.001);MPP组外周血CD3+T、CD4+T、CD4+CD8+T比例及CD4+/CD8+低(P均<0.05),CD4-CD8-T及CD19+B占比高(P均<0.001);与MPP组比较,TB组外周血CD8+T、CD4-CD8-T及CD56+NK低,CD4+T、CD4+/CD8+及CD19+B高(P均<0.05).结论 TB与MPP患儿患病初期外周血WBC、CRP及PCT水平相近.与MPP患儿比较,TB患儿外周血CD8+T、CD4-CD8-T及CD56+NK低,CD4+T、CD4+/CD8+及CD19+B高.

Platinum-based combination therapy is more effective and less toxic, but lack of targeting, and is not capable to enrich in the tumor zone. To obstacle these drawbacks, prodrug and nanotechnology strategies have been investigated in this study. GSH-responsive and pH-responsive cisplatin prodrug was synthesized. Cisplatin prodrug and paclitaxel co-loaded nanoparticles: DDP-P/PTX NPs were constructed. The drug release behavior and cytotoxicity of nanoparticles was assessed in vitro. In vivo anticancer efficiency and toxicity were evaluated on lung cancer bearing mice animal model. DDP-P/PTX NPs had a nanoscale size of 112.9 ± 3.5 nm. A reduction and pH triggered drug release with a synergistic tumor cell inhibition ability was observed by DDP-P/PTX NPs. DDP-P/PTX NPs also exhibited high tumor distribution, low systemic toxicity and remarkable antitumor effects in vivo. DDP-P/PTX NPs could be applied as promising anticancer system for the treatment of NSCLC.

目的 探讨钾双孔域通道亚家族K成员1(potassium two pore domain channel subfamily K member 1,KCNK1)在肺癌中的功能及其作用机制.方法 利用TCGA数据分析KCNK1在肺癌组织中的表达水平,在H1299和H1975中用克隆形成实验检测KCNK1基因敲减后对肺腺癌细胞增殖的影响,探讨KCNK1在肺腺癌细胞增殖中的作用,并用CCK8等细胞增殖、转移实验进一步验证其功能;将KCNK1干扰后,用Western blot和qPCR实验检测下游通路基因以分析KCNK1基因可能的作用机制.结果 KCNK1基因在肺癌组织与癌旁组织相比表达显著升高(P<0.05),且KCNK1敲减后抑制细胞增殖和转移;干扰KCNK1可以抑制CREB3及靶基因的表达水平.结论 KCNK1基因在肺癌的恶性进展中起重要的作用,该作用通过调控环磷酸腺苷反应元件结合蛋白3(CREB3)机制进行,KCNK1基因是肺癌新的潜在分子诊断指标及靶点.

目的 探讨MAL2(myelin and lymphocyte protein 2)在肺癌中的功能及作用机制.方法 分析TCGA数据中MAL2在肺癌组织中的表达情况,在H1299和A549细胞中用克隆形成实验检测MAL2基因敲减后对肺癌细胞增殖的影响,探讨MAL2在肺腺癌细胞增殖中的作用,并用CCK8等细胞增殖、转移、凋亡实验进一步验证其功能;将MAL2干扰后,采用Western blot实验检测下游通路基因表达情况以分析MAL2基因可能的作用机制.结果 MAL2基因在肺癌组织与癌旁组织相比表达显著升高(P<0.05),且MAL2敲减后抑制细胞增殖和转移、促进细胞凋亡(P<0.05);MAL2可能通过调控SGK1通路发挥作用.结论 MAL2基因在肺癌的恶性进展中起重要的作用,该作用通过调控SGK1机制进行,MAL2基因是肺癌的一个新的潜在的分子诊断指标及治疗靶点.

目的 了解河北省儿童医院住院患儿EB病毒(EBV)感染的流行病学特征,为儿童EBV感染的诊断和预防提供科学依据.方法 收集2017年1—12月河北省儿童医院0～14岁EBV感染住院患儿的全血样本,采用酶联免疫吸附试验(ELISA)检测其EBV衣壳抗原(VCA)IgG及IgM抗体,抗早期抗原(EA)IgG抗体和抗核抗原1(NA1)IgG抗体,以检测结果 为研究样本的抗体谱.根据4种EBV抗体的检测结果分为现症感染(抗VCA-IgM抗体阳性,抗NA1-IgG抗体阴性、抗VCA-IgG抗体、抗EA-IgG抗体阳性或阴性)、亚急性感染(抗VCA-IgG抗体阳性,抗VCA-IgM抗体、抗NA1-IgG抗体、抗EA-IgG抗体阳性或阴性)、既往感染(抗NA1-IgG抗体阳性,抗VCA-IgG抗体阳性或阴性,其他抗体均为阴性)和未感染(4种抗体均阴性).按照患儿年龄、检出月份和性别分析各组的阳性率.结果共纳入符合要求的样本4451例,其中3257例(73.17％)抗体谱提示EBV感染,包括现症感染380例(8.54％)、亚急性感染616例(13.84％)、既往感染2261例(50.80％).不同年龄组原发阳性检出率差异有统计学意义(P<0.05),其中学龄前(>3岁)组的阳性检出率最高(P<0.05);不同检出月份组阳性检出率差异有统计学意义(P<0.05),7月份阳性检出率高于其他月份(P<0.05);男性患儿与女性患儿EBV感染率差异无统计学意义(P>0.05).380例现症感染患儿的疾病谱以血液系统疾病[传染性单核细胞增多症、急性粒细胞缺乏症、血小板减少性紫癜、EBV相关嗜血细胞综合征]为主,其中传染性单核细胞增多症为临床常见疾病;其次是呼吸系统疾病(急性支气管炎、疱疹性咽峡炎、急性扁桃体炎);其他疾病谱包括神经系统疾病及血流感染、肾病综合征、川崎病.结论 河北省儿童医院住院患儿EBV阳性检出率有年龄和检出月份差异,现症感染以血液系统疾病患儿为主,医院应根据流学病学特征制定相应预防措施.

In this study, we set out to characterize the expression status of long non-coding RNA (lncRNA) Myocardial Infarction Associated Transcript (MIAT) in non-small cell lung cancer (NSCLC) and elucidate its mechanistic contribution to this disease. Relative expression levels of MIAT, Pellino E3 Ubiquitin Protein Ligase Family Member 3 (PELI3), and microRNA (miR)-128-3p were analyzed by real-time polymerase chain reaction. PELI3 protein level was determined by immunoblotting. Cell viability and proliferation were evaluated by the MTT assay and colony formation assay, respectively. Cell invasion and migration were assessed by wound-healing closure and transwell assays, respectively. The regulatory actions of miR-128-3p on both MIAT and PELI3 were interrogated by luciferase reporter assay. We demonstrated the aberrant upregulation of MIAT in NSCLC and its association with tumor progression. We further uncovered the negative correlation among MIAT, PELI3, and miR-128-3p. MIAT deficiency significantly compromised cell viability, proliferation, invasion, and migration, while increased miR-128-3p and decreased PELI3 expressions. Application of miR-128-3p inhibitor significantly stimulated luciferase activities driven by both MIAT and PELI3 promoter and phenotypically promoted cell viability, proliferation, migration, and invasion. Our study highlighted the mechanistic contribution of the MIAT/miR-128-3p/PELI3 signaling cascade in NSCLC.

目的 探讨肺力咳胶囊联合阿莫西林治疗急性气管–支气管炎的临床效果.方法 选取2016年6月—2019年6月北京市东城区第一人民医院收治的96例急性气管–支气管炎,随机分为对照组和治疗组,每组各48例.对照组口服阿莫西林胶囊,0.5 g/次,3次/d.治疗组在对照组治疗基础上口服肺力咳胶囊,3粒/次,3次/d.两组均连续治疗2周.比较两组的临床疗效,比较两组典型症状的消失时间、白细胞计数(WBC)、中性粒细胞百分率(NEUT％)异常情况、血清肿瘤坏死因子(TNF)-α、白介素(IL)-8、超敏C反应蛋白(hs-CRP).结果 治疗后,对照组和治疗组的总有效率分别是83.3％、95.8％,两组比较差异有统计学意义(P<0.05).治疗组在典型症状咳嗽、咳痰的消失时间上均显著短于对照组(P<0.05).两组治疗后WBC、NETU％异常率均显著低于治疗前(P<0.05);但治疗后,治疗组血象情况优于对照组同期(P<0.05).两组治疗后血清各项炎症标志物(TNF-α、IL-8、hs-CRP)水平均显著低于治疗前(P<0.05),且治疗组下降更显著(P<0.05).结论 肺力咳胶囊联合阿莫西林治疗急性气管–支气管炎整体疗效良好,可迅速减轻患者症状,恢复血象,拮抗机体炎症反应,具有一定的临床推广应用价值.

目的 探讨微创Ivor-Lewis食管切除术(minimally invasive Ivor-Lewis esophagectomy,MI-ILE)治疗食管胃结合部腺癌的可行性.方法 回顾性分析2018年1月～2019年6月MI-ILE治疗食管胃结合部腺癌48例资料.SiewertⅠ型11例,Ⅱ型31例,Ⅲ型6例.病灶距门齿距离(38.8±2.5)cm.结果 手术时间(250.8±42.0)min,术中出血(120.3±67.0)ml.均行R0切除.27例术前新辅助治疗,26例(96％)术后病理显示部分缓解.清扫淋巴结(28.6±10.6)枚,36例淋巴结转移(8.0±5.0)枚.术后吻合口漏2例(4％),1例手术治疗,1例保守治疗,均痊愈.术后住院日(9.7±3.2)d.平均随访14个月(5～22个月),肿瘤均无复发,无死亡.结论 MI-ILE治疗食管胃结合部腺癌可以保证满意的上下切缘和足够的淋巴结清扫范围,手术安全可靠.

Aim: Demonstrate the function of dysregulated miR-365a-5p-PELI3 signaling axis in the generation of gefitinib resistance during treatment for non-small-cell lung cancer (NSCLC). Patients & methods: All the NSCLC patients who participated in this research were recruited from the Second Hospital of Hebei Medical University. PC9 cells and PC9GR cells were cultured for in vitro experiments. Results: Patients who were primary resistant to EGFR-tyrosine kinase inhibitor had lower miR-365a-5p levels. MiR-365a-5p directly targeted PELI3 mRNA. MiR-365a-5p overexpression enhanced the function of gefitinib in inhibiting cell viability. Tumor growth was suppressed through miR-365a-5p in nude mice. Conclusion: Dysregulated miR-365a-5p-PELI3 signaling axis triggered the generation of gefitinib resistance in NSCLC.

e18547 Background: Even though local and regional controls have been substantially improved in nasopharyngeal carcinoma (NPC) in the contemporary era of intensity-modulated radiotherapy with extensive use of combined chemotherapy, the distant metastasis becomes the major cause of treatment failure and cancer-related death. To date, the genes contributed to metastasis of NPC is still unclear. The aim of this study was to identify the genes which lead to distant metastasis. Methods: A total of forty primary nonkeratinizing NPC patients were diagnosed at Shandong Cancer Hospital in this study. The formaldehyde-fixed paraffin embedded (FFPE) taken from primary sites or metastatic lymph nodes were performed next-generation sequencing (NGS) panel (Shanghai OrigiMed Co., Ltd.) to determine variated genes, such as single nucleotide variants (SNV), copy number variants (CNV) and rearrangement. These patients were followed up until Febr. 8, 2020. The genes related to distant metastasis were identified by logistic regression. Moreover, this study compared the frequency of mutated gene between our data and Catalog of Somatic Mutations in Cancer (COSMIC) database by the Chi-square test or Fisher’s exact test. Results: The study included 31 men and 9 women. The median age of the patients at diagnosis was 47 years (range 15–71 years). With the median follow-up of 10.6 months (range 16.8–72.3 months), 7 patients had distant metastasis and 1 undergone recurrent. Notably, EMSY and MCL1 variants were contributed to NPC distant metastasis (OR = 31, P = 0.049). The top eight SNV of genes in our study were CYLD, KMT2D, BAP1, EP300, TP53, ATM, NFKBIA and SPEN. When compared to COSMIC database, the mutant frequencies of CYLD, EP300 and BAP1 in our study were significantly higher than that of COSMIC database. However, the mutant frequencies of IDH2 and KMT2C were significantly lower than COSMIC database. Conclusions: This is the first study which suggests that EMSY and MCL1 variants were involved in the metastasis of NPC. The study identified 5 genes, which mutation frequency is significantly different from the COSMIC database. The study provided a molecular basis for a comprehensive understanding of, and exploring targeted therapies for nasopharyngeal carcinoma.

目的 探讨微创Ivor-Lewis食管切除术(minimally invasive Ivor-Lewis esophagectomy,MI-ILE)与Sweet手术治疗Siewert Ⅱ型食管胃结合部腺癌(adenocarcinoma of esophagogastric junction,AEG)的疗效.方法 选择2017年12月～2019年3月Siewert Ⅱ型AEG 82例,按照前瞻性非随机方法分为2组,行MI-ILE手术41例,Sweet手术41例,2组术前一般资料差异无显著性(P>0.05).比较2组手术指标、术后并发症及短期生存和复发率.结果 MI-ILE组手术时间长于Sweet组[(244.0±39.5)min vs.(186.9±24.8)min,t=7.840,P=0.000],但术中出血量少[(88.9±34.1)ml vs.(107.7±42.4)ml,t=-2.211,P=0.030],术后第1天胸腔引流量少[(205.9±73.3)ml vs.(287.7±126.3)ml,t=-3.587,P=0.001],胸腔引流时间短[(6.2±2.2)d vs.(8.8±2.8)d,t=-4.666,P=0.000],术后排气早[(3.0±1.0)d vs.(3.7±1.3)d,t=-2.739,P=0.008],术后住院时间短[(9.2±3.2)d vs.(11.2±2.6)d,t=-2.982,P=0.004].MI-ILE组清扫淋巴结(28.6±10.0)枚,其中胸腔清扫(7.2±4.4)枚,腹腔清扫(21.4±8.9)枚,均高于Sweet组的(22.2±7.3)、(4.8±4.0)、(17.4±7.3)枚(P均<0.05).2组胸腔、腹腔淋巴结转移数目差异无显著性(P>0.05).随访1年,2组均无死亡;MI-ILE复发1例(2.5％),Sweet组复发3例(7.3％)(χ2=1.051,P=0.305).结论 MI-ILE治疗Siewert Ⅱ型AEG安全、可行,与Sweet手术比较,不增加风险,近期疗效满意.