BackgroundWhen thyroid cancer invades the trachea, tumor resection and trachea reconstruction are required. Although the traditional way of anesthesia and tracheal intubation can maintain the necessary ventilation function during the operation, tracheal intubation affects the surgical field of vision and is not conducive to the protection of the recurrent laryngeal nerve beside the trachea during the operation.Case presentationExtracorporeal membrane oxygenation (ECMO) is used to replace traditional tracheal intubation in the process of resection and end-to-end anastomosis of tracheal tumors, and complete tracheal tumor resection and trachea reconstruction are achieved.ConclusionUsing ECMO for thyroid carcinoma resection, invaded trachea resection, and trachea reconstruction is safe and effective, which reduces the obstruction of endotracheal intubation on the operative field, guarantees the rapid and efficient end-to-end anastomosis in the upper trachea, and clearly avoids laryngeal recurrent nerve injury in the process of anastomosis.

Background Postoperative lung cancer patients belong to the high-risk group for venous thromboembolism (VTE). The standardized preventive measures for perioperative VTE in lung cancer are not perfect, especially for the prevention and treatment of catheter-related thrombosis (CRT) caused by carried central venous catheters (CVCs) in lung cancer surgery. Patients and methods This study included 460 patients with lung cancer undergoing video-assisted thoracic surgery (VATS) in our center from July 2020 to June 2021. Patients were randomized into two groups, and intraoperatively-placed CVCs would be carried to discharge. During hospitalization, the control group was treated with low-molecular-weight heparin (LMWH), and the experimental group with LMWH + intermittent pneumatic compression (IPC). Vascular ultrasound was performed at three time points which included before surgery, before discharge, and one month after discharge. The incidence of VTE between the two groups was studied by the Log-binomial regression model. Results CRT occurred in 71.7% of the experimental group and 79.7% of the control group. The multivariate regression showed that the risk of developing CRT in the experimental group was lower than in the control group (Adjusted RR = 0.889 [95%CI0.799–0.989], p = 0.031), with no heterogeneity in subgroups (P for Interaction > 0.05). Moreover, the fibrinogen of patients in the experimental group was lower than control group at follow-up ( P = 0.019). Conclusion IPC reduced the incidence of CRT during hospitalization in lung cancer patients after surgery. Trial registration No. ChiCTR2000034511.

Video 1 everse-direction video-assisted thoracoscopic surgery left upper lobectomy via interlobar fissure.

Background: Our Study have been focusing on investigating the immune components to increase immunotherapy efficacy and to assist patient stratification for immunotherapy NSCLC patients, we explored predict property of the mutations characteristics with immunotherapy survival benefit and Tumor Immune Microenvironment(TME)characteristics. Methods: A training cohort of 344 immunotherapy NSCLC were obtained from MSK database with Clinical and biological data. intersecting Candidate genes related to survival(p_value < 0.05)with immunity-related genes (IRGs), following an independent cohort of 75 patients with immunotherapy NSCLC was assessed. Applying the same patients RNA-Seq data calculated TME by CIBERSORT from TCGA database. Results: The result divided the patients into two groups: 54 samples in the MT group ( two or more of the 18 candidate genes mutated) and 290 samples in the WT group (less two mutations in the 18 genes).The TMB status frequency in WT_H/L and MT_H/L cohort were 11.9% vs 3.8% and 21.5% vs 62.8%(MT_H vs WT_H, P < 0.01 ; MT_L vs WT_L, P = 0.046 ). Discovery training cohort showed a high Overall Survial for patients with MT group which was 15.7% and 84.3% for WT group( P_value < 0.0001). The genes mutation signature degree of most immune cells (such as CD4\8+ T cells and M1 macrophages \natural killer ) were higher in the MT group. Conclusions: Our study offers genes mutation biomarker for OS prediction and potential addition development of tumor exemption, to be served as a convenient tool for identifying high relapse individuals with immunotherapy NSCLC patients. Citation Format: Shixin Zhang, Xintong Wang. A predictive biomarker classififier in NSCLC treated with immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5093.

目的 探讨miR-451a通过调控PI3K/Akt通路对食管鳞状细胞癌顺铂(cisplatin,DDP)耐药的作用及其可能机制.方法 人正常食管鳞状上皮细胞系Het-1A、人食管鳞状细胞癌细胞系Eca109、人食管鳞状细胞癌顺铂耐药细胞系Eca109/DDP,采用实时荧光定量PCR法检测3种细胞miR-451a相对表达量,采用Western blot法检测3种细胞KIF2A蛋白相对表达量.对数生长期Eca109/DDP细胞分为空白对照组(不进行转染操作)、miR-NC组(转染miR-NC)、miR-451a模拟物组(转染miR-451a模拟物),采用实时荧光定量PCR法检测3组细胞miR-451a相对表达量,采用Western blot法检测3组细胞KIF2A蛋白相对表达量.采用荧光素酶报告实验检测miR-451a和KIF2A的靶向关系.对数生长期Eca109/DDP细胞再分为对照组(不进行转染操作)、miR-NC+ oe-NC组(转染miR-NC+ oe-NC)、miR-451a模拟物+oe-NC组(转染miR-451a模拟物+oe-NC)、miR-451a模拟物+oe-KIF2A组(转染miR-451a模拟物+ oe-KIF2A),4组细胞分别加入不同浓度DDP,采用CCK-8实验检测细胞活力及DDP对细胞的半数抑制浓度,确定DDP在后续实验中的浓度.采用实时荧光定量PCR法检测4组细胞miR-451a相对表达量,采用Western blot法检测4组细胞KIF2A、p-PI3K、PI3K、p-Akt、Akt蛋白相对表达量,比较p-PI3K/PI3K、p-Akt/Akt,采用EdU实验检测4组细胞增殖情况,采用流式细胞术检测4组细胞凋亡率.结果 Eca109/DDP细胞miR-451a相对表达量(0.32±0.06)低于Het-1A细胞(1.00±0.09)、Eca109细胞(0.62±0.07)(P＜0.05),KIF2A蛋白相对表达量(0.65±0.10)高于Het-1A细胞(0.21±0.05)、Eca109细胞(0.41±0.08) (P＜0.05);Eca109细胞miR-451a相对表达量低于Het-1A细胞(P＜0.05),KIF2A蛋白相对表达量高于Het-1A细胞(P＜0.05).miR-451a模拟物组细胞miR-451a相对表达量(2.47±0.13)高于miR-NC组(0.96±0.04)、空白对照组(1.00±0.03) (P＜0.05),KIF2A蛋白相对表达量(0.21±0.03)低于miR-NC组(0.74土0.06)、空白对照组(0.76土0.05)(P＜0.05);miR-NC组细胞miR-451a和KIF2A蛋白相对表达量与空白对照组比较差异均无统计学意义(P＞0.05).荧光素酶报告实验结果显示,miR-451a靶向调控KIF2A.DDP在后续实验中的浓度为90μmol/L.miR-451a模拟物+oe-NC组、miR-451a模拟物+oe-KIF2A组细胞miR-451a相对表达量高于miR-NC+ oe-NC组、对照组(P＜0.05),miR-451a模拟物+oe-NC组与miR-451a模拟物+oe-KIF2A组比较差异无统计学意义(P＞0.05);miR-451a模拟物+oe-NC组细胞KIF2A蛋白相对表达量低于对照组、miR-NC+ oe-NC组、miR-451a模拟物+oe-KIF2A组(P＜0.05),对照组、miR-NC+ oe-NC组低于miR-451a模拟物+oe-KIF2A组(P＜0.05).miR-451a模拟物+oe-NC组不同浓度DDP作用下的细胞活力、DDP对细胞的半数抑制浓度、EdU阳性细胞数、p-PI3K/PI3K、p-Akt/Akt均低于对照组、miR-NC+oe-NC组、miR-451a模拟物+oe-KIF2A组(P＜0.05),miR-451a模拟物+oe-KIF2A组均低于对照组、miR-NC+ oe-NC组(P＜0.05);miR-451a模拟物+oe-NC组细胞凋亡率高于对照组、miR-NC+ oe-NC组、miR-451a模拟物+oe-KIF2A组(P＜0.05),miR-451a模拟物+oe-KIF2A组高于对照组、miR-NC+oe-NC组(P＜0.05);以上指标对照组与miR-NC+oe-NC组比较差异均无统计学意义(P＞0.05).结论 miR-451a通过抑制KIF2A表达,从而抑制PI3K/Akt通路,增加食管鳞状细胞癌耐药细胞对DDP的敏感性,发挥抗肿瘤作用.

目的:探讨肺挫伤患者血清可溶性髓系细胞触发受体-1(sTREM-1)、白细胞介素-8(IL-8)的动态变化及其对患者预后的预测价值.方法:分别将肺挫伤、单纯肋骨骨折及健康体检者设为肺挫伤组(n=98)、肋骨骨折组(n=70)和对照组(n=68);比较三组对象第1天、第3天、第7天血清sTREM-1、IL-8水平及其在肺挫伤患者血清中的动态变化情况.肺挫伤组再依据病情分为轻度组(n=30)、中度组(n=45)和重度组(n=23);根据1个月后愈合情况分为预后良好组(n=80)和预后不良组(n=18),比较不同病情及不同预后肺挫伤患者第1天、第3天、第7天血清sTREM-1、IL-8水平,分析其对患者预后评估的价值.结果:肺挫伤组及肋骨骨折组患者不同时间点血清sTREM-1、IL-8水平均高于对照组(P＜0.05),且肺挫伤组高于肋骨骨折组(P＜0.05),第3天及第7天低于第1天,第7天低于第3天(P＜0.05);肺挫伤中度组及重度组不同时间点血清sTREM-1、IL-8水平高于轻度组(P＜0.05),且重度组高于中度组(P＜0.05),第3天及第7天低于第1天,第7天低于第3天(P＜0.05);预后不良组不同时间点血清sTREM-1、IL-8水平高于预后良好组(P＜0.05),且第3天及第7天低于第1天,第7天低于第3天(P＜0.05);血清sTREM-1、IL-8单独及联合评估肺挫伤预后的AUC分别为0.761、0.751、0.860(P＜0.05).结论:肺挫伤患者血清sTREM-1、IL-8明显上调,且水平越高,肺挫伤越重,预后越差,二者均可作为评估患者预后的重要指标之一.

Background Esophageal cancer (EC) is a common malignancy of the digestive tract, with high incidence. The objective of this study was to investigate the effect of miR-630 expression on esophageal cancer (EC) cell invasion and migration. Methods The study group comprised 58 EC patients admitted to our hospital from April 2014 to 2016, and the control group comprised 60 healthy people visiting the hospital during the same period. miR-630 levels in the peripheral blood of the two groups were compared, and the diagnostic value of miR-630 for EC was analyzed. EC cell lines were used to evaluate the influence of miR-630 expression on EC cell invasion and migration. Results miR-630 expression was low in EC (p < 0.050). A receiver operating characteristic curve analysis showed that miR-630 expression had a good diagnostic value for EC (p < 0.050) and was associated with disease course, pathological stage, differentiation degree, tumor metastasis, and patient prognosis and survival (p < 0.05). The ROC curve analysis showed that when cutoff value was 5.38, the diagnostic sensitivity and specificity of miR-630 for EC were 73.33% and 76.67%, respectively; area under the ROC curve was 0.778 (95%CI 0.695-0.861). Transfection of miR-630 into EC cells indicated that miR-630 overexpression can reduce EC cell invasion and migration (p < 0.05). miR-630 expression is low in EC and has good diagnostic value for EC. Conclusion miR-630 overexpression can reduce EC cell invasion and migration, showing a possible key role of miR-630 in EC diagnosis and treatment in the future.

目的 观察中晚期食管鳞癌患者血清肿瘤坏死因子受体相关蛋白1 (tumor necrosis factor receptor associated protein 1,TRAP1)水平、癌组织癌胚抗原(carcinoembryonic antigen,CEA)表达变化,探讨其与中晚期食管鳞癌患者化疗效果的相关性.方法 中晚期食管鳞癌患者147例,均行紫杉醇+顺铂方案化疗2个周期,化疗结束时行CT检查评估化疗疗效,完全缓解及部分缓解者为缓解组,稳定及进展者为未缓解组.比较2组年龄、性别、病程、发病部位、分化程度、临床分期;取2组化疗前内镜活检食管癌组织,采用免疫组织化学染色法评估癌组织CEA阳性表达情况;化疗前1d采用ELISA法检测2组血清TRAP1水平;多因素logistic回归分析中晚期食管鳞癌患者化疗后未缓解的影响因素;绘制ROC曲线,评估血清TRAP1、癌组织CEA阳性表达预测中晚期食管鳞癌患者化疗后未缓解的价值.结果 147例患者化疗未缓解率为56.46％(83/147).未缓解组血清TRAP1水平[(55.51土5.17)ng/L]及癌组织CEA阳性表达率(65.06％)均高于缓解组[(48.62±4.39)ng/L、46.88％](P＜0.05),年龄、性别、病程、发病部位、分化程度、临床分期与缓解组比较差异均无统计学意义(P＞0.05).多因素logistic回归分析结果显示,血清TRAP1(OR=1.357,95％CI:1.228～1.501,P＜0.001)、癌组织CEA阳性表达(OR=9.540,95 ％CI:4.245～21.441,P＜0.001)是中晚期食管鳞癌患者化疗后未缓解的影响因素.ROC曲线分析结果显示,血清TRAP1以52.60 ng/L为最佳截断值,预测中晚期食管鳞癌患者化疗后未缓解的AUC为0.712(95％CI:0.774～0.907,P＜0.001),灵敏度为75.0％,特异度为83.1％;CEA阳性表达预测中晚期食管鳞癌患者化疗后未缓解的AUC为0.591(95％CI:0.498～0.684,P=0.049),灵敏度为53.1％,特异度为65.1％.结论 中晚期食管鳞癌化疗未缓解患者血清TRAP1水平及癌组织CEA阳性表达率升高,血清TRAP1预测中晚期食管鳞癌患者化疗效果有一定价值.

住院医师规范化培训制度对培养合格临床医师至关重要.通过总结既往思政建设方面存在的问题,探索将"医学人文-思政教育"纳入医科大学附属教学医院胸外科专业基地住院医师规范化培训工作中,对于年轻规培医师的思想觉悟、道德水准和知识技能提升有很大的帮助.以"医学人文-思政教育"为特色的住院医师规范化培训教学改革是响应新时期住院医师规范化培训乃至医学人文教育改革的必经之路,将为培养符合人民需求的德才兼备的医师起到积极作用.

BACKGROUND:Lung squamous cell carcinoma (LUSC) accounts for about 30% of all non-small cell lung cancers (NSCLC). However, only a small percentage of LUSC patients gain benefit from immune checkpoint inhibitors (ICIs).METHODS:This study analyzed LUSC patients from The Cancer Genome Atlas (TCGA), which were divided into 2 groups: PD-L1 high-expression/TMB-high (TPH) and PD-L1 low-expression/TMB-low (TPL) group based on programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) status. The differences in tumor-infiltrating immune cells were estimated between the 2 groups. The overlap of differentially expressed genes and proteins (DEGs and DEPs) between 2 groups were used as candidate biomarkers. Kaplan-Meier curves were used to evaluate the association between risk score and overall survival (OS).RESULTS:More abundant immune infiltration fractions were found in TPH group. Janus kinase 2 (JAK2) and forkhead box protein M1 (FOXM1) were identified as DEGs between the TPH and TPL groups. Subsequently, we developed a risk score that combined the expression of JAK2 and FOXM1 in an effort to accurately determine the survival risk of LUSC patients. Patients with high-risk [hazard ratio (HR), median OS, 43.1 months 1.924; 95% confidence interval (CI): 1.256 to 2.945; P=0.002) had shorter survival than those with low-risk (median OS, 70.0 months). External data verification found that JAK2 and FOXM1 were significantly expressed at a higher level in the responders receiving immunotherapy (P=0.038 and P=0.009, respectively).CONCLUSIONS:The expressions of JAK2 and FOXM1 can be used as novel candidate biomarkers for predicting the benefit of immunotherapy in LUSC.

Objective . To investigate the clinical significance of the mRNA expression of RRM 1, TUBB 3, and ERCC 1 in non-small-cell lung cancer (NSCLC) tissues for the selection of adjuvant/postoperative chemotherapy regimens. Methods . Patients diagnosed with stage Ib-IIIa NSCLC were enrolled and randomly divided into a control group (undetected group) and an experimental group (detected group) after radical operation. The control group randomly received chemotherapy with gemcitabine plus cisplatin or paclitaxel plus cisplatin. The mRNA expression of RRM 1, TUBB 3, and ERCC 1 was detected in the experimental group before chemotherapy, and based on the detected expression, the chemotherapy regimen of cisplatin plus gemcitabine or cisplatin plus paclitaxel was chosen. The disease-free survival (DFS) of the control group and experimental group was compared. Results . Pathological type, stage, gene expression detection, and treatment method were not significantly correlated with DFS ( P > 0.05). In the subgroups treated with gemcitabine, the median DFS was 17 months in the detected group and 10.5 months in the undetected group (hazard ratio = 0.2147, 95% confidence interval: 0.07909–0.5827, P = 0.0025). Multivariate regression analysis was performed to analyse whether gene expression detection was independently correlated with DFS in the subgroups treated with gemcitabine ( P = 0.025). In the detected group, the prognosis of patients with low expression of RRM 1 was better than that of patients with high expression of RRM 1 after paclitaxel treatment ( P = 0.0039). Conclusions . The selection of chemotherapy regimen based on mRNA expression of the RRM 1, TUBB 3, and ERCC 1 genes may improve selection of candidate patients to receive clinical chemotherapy. However, large-scale prospective clinical studies are needed for in-depth investigation.

Background : The early diagnosis of non-small cell lung cancer is of great significance to the prognosis of patients. However, traditional histopathology and imaging screening have certain limitations. Therefore, new diagnostical methods are urgently needed for the current clinical diagnosis. In this study we evaluated the sensitivity and specificity of CanPatrol TM technology for the detection of circulating tumor cells in patients with non-small cell lung cancer (NSCLC). Methods: CTCs in the peripheral blood of 98 patients with NSCLC and 38 patients with benign pulmonary diseases were collected by the latest typing of CanPatrol TM detection technology. A 3-year follow-up was performed to observe their recurrence and metastasis. Kruskal-Wallis test was used to compare multiple groups of data, Mann-Whitney U test was used to compare data between the two groups, and ROC curve analysis was used to obtain the critical value. The COX risk regression and Kaplan-Meier survival analysis were performed in the 63 NSCLC patients who were effectively followed up. Results: The epithelial, epithelial-mesenchymal, and total CTCs were significantly higher in NSCLC patients than that in patients with benign lung disease (P < 0.001). The mesenchymal CTCs of NSCLC patients was slightly higher than that of benign lung diseases (P = 0.013). The AUC of the ROC curve of the total CTCs was 0.837 (95% CI: 0.76-0.914), and the cut-off value corresponding to the most approximate index was 0.5 CTCs/5 ml, at which point the sensitivity was 81.6% and the specificity was 86.8%. COX regression analysis revealed that the clinical stage was correlated with patient survival (P = 0.006), while gender, age, and smoking were not (P > 0.05). After excluding the confounders of staging, surgery, and chemotherapy, Kaplan-Meier survival analysis showed that patients in stage IIIA with CTCs ≥ 0.5 had significantly lower DFS than those with CTCs < 0.5 (P = 0.022). Conclusions : CTC positive can well predict the recurrence of NSCLC patients. CanPatrol TM technology has good sensitivity and specificity in detecting CTCs in peripheral blood of NSCLC patients and has a certain value for clinical prognosis evaluation.

Multidrug resistance is a major obstacle to the effective treatment of esophageal carcinoma. It occurs more readily in hypoxia and acidosis microenvironment. TTLL6 is one of Tubulin tyrosine ligase-like family members. In this study, the effect of TTLL6 on the regulation of cisplatin (CDDP) sensitivity was evaluated in CDDP-resistant esophageal carcinoma (EC) cells both in vitro and in vivo. In hypoxia/acidosis condition, overexpression of TTLL6 in EC109/CDDP cells significantly lowered the IC50 of CDDP and increased the CDDP-induced apoptosis; while knockdown of TTLL6 expression in EC109/CDDP cells exhibited the opposite effects. Further study showed that, mechanistically, TTLL6 was inversely correlated with ERBB2 and TOPOIIA, and positively correlated with apoptosis-associated factor Caspase 9. Furthermore, animal model confirmed that TTLL6 negatively regulated the growth of xenograft tumor after chemotherapy. Alternated expression of TTLL6 also regulated the expression of ERBB2, TOPOIIA and Caspase 9 in EC109/CDDP cells in vivo. In conclusion, our results suggest that TTLL6 could reverse the drug resistant of EC109/CDDP cells, it might provide a potential treatment strategy for the clinical reversing the chemotherapy resistance.

An increasing number of long noncoding RNAs (lncRNAs) have been discovered, and dysregulation of lncRNAs plays critical roles in tumorigenesis and tumor progression. In this study, we identified a novel lncRNA LINC01980, located in both the cytoplasm and nucleus, which was significantly upregulated in esophageal squamous cell carcinoma (ESCC) tissues through microarray profiling. Further analysis revealed that LINC01980 overexpression was positively correlated with deeper invasion of cancer, positive lymph node metastasis, and advanced TNM stage. Additionally, high LINC01980 expression in ESCC tissues was associated with poor prognosis. In vitro and in vivo experiments demonstrated that LINC01980 promoted ESCC growth. EdU incorporation assay implied that LINC01980 accelerated ESCC proliferation. Flow cytometry analysis showed that knockdown of LINC01980 induced cell cycle arrest and increased apoptosis. Microarray analysis indicated that LINC01980 upregulated the expression of growth arrest and DNA damage inducible 45 alpha (GADD45A). Further experiments demonstrated that GADD45A promoted ESCC cell growth, indicating that GADD45A may be a downstream target of LINC01980. In conclusion, this study identified LINC01980 as a novel potential oncogene in ESCC, which can be a promising biomarker for prognosis and therapeutic targeting in ESCC.

Objective To summerize the clinical outcomes and experience of extracorporeal membrane oxygenation (ECMO)-supported inter-hospital transport for critically ill patients. Methods Clinical data of 10 critically ill patients undergoing ECMO-supported inter-hospital transport by our ECMO team during June 2016 and January 2018 were collected in this study. The transport distance, transport complications and treatment outcomes were summarized. Results The transport distance of 10 cases was 3.4 to 248.0 km, at an average of 72.6 km. During the transportation, 1 case of V-V ECMO patients (drainage from the right femoral vein and reflux to the right internal jugular vein) had twist of venous tubes, which affected ECMO flow, and 2 cases of V-A ECMO patients (drainage from the right femoral vein and reflux to the right femoral artery) had incision bleeding. All of the 10 cases safely reached our hospital. One patient was cured and discharged, 1 was successfully removed from ECMO but died of pulmonary infection and multiple organ failure, 1 patient died, 2 patients discharged from hospital by themselves because their family finally gave up the treatment, and the left 5 patients became brain death donors for the liver and/or kidneys. Conclusion Inter-hospital transport on ECMO can be safely performed in critically ill patients, and the complications associated with ECMO transport can be controlled. The staffs involved should pay attention to the construction of ECMO multidisciplinary team and standardize the operating procedures.

Background How to maximally improve the drainage of intracranial and upper body venous and to reduce neurological complications during thoracic tumor‐causedsuperior vena cava replacement are still clinical problems to be solved. Methods We have innovatively used the bilateral jugular vein‐left femoral vein ECMO shunting to perform mediastinal tumor resection and superior vena cava replacement in a 50‐year‐old woman. Results During the operation, this technique maintained the patient's hemodynamic stability, improved the cerebral oxygen saturation and reduced the cerebral ischemia, hypoxia as well as the neurological complications. Conclusion It is indicated for patients with superior vena cava replacement who are unable to perform venous bypass (such as innominate vein to right atrial bypass) or venous shunting (such as differential pressure drainage from internal jugular vein to femoral vein).

Carina resection and reconstruction is required when a tracheal tumor invades the tracheal carina. It is a relatively complicated surgical procedure that requires complex reconstruction to maintain airway continuity. The technical difficulty lies in minimizing the influence of anesthetic endotracheal intubation and maintaining good ventilation function during surgery by establishing appropriate ventilation channels, which are contradictory in many cases. Therefore, in order to achieve the optimal surgical outcome, we performed intratracheal tumor resection and carina reconstruction with the help of extracorporeal membrane oxygenation.

Multidrug resistance (MDR) often leads to chemotherapy failure of lung cancer and has been linking to the cellular expression of several DNA transcription- and repair-related genes such as Trps1 and MGMT. However, their roles in the formation of MDR are largely unknown. In this study, overexpression/knockdown, luciferase assay and ChIP assay were performed to study the relationship between Trps1 and MGMT, as well as their roles in MDR formation. Our results demonstrated that Trps1 and MGMT expression both increased in drug-resistant lung cancer cell line (H446/CDDP). Silencing of Trps1 resulted in downregulation of MGMT expression and decrease in the multidrug sensitivity of H446/CDDP cells, while Trps1 overexpression exhibited the opposite effects in H446 cells. Ectopic expression of MGMT had no effect on Trps1 expression, but enhanced the IC50 values of H446 cells or rescued the IC50 values of Trps1-silenced H446/CDDP cells in treatment of multidrug. Our data further showed that, mechanistically, Trps1 acted as a transcription activator that directly induced MGMT transcription by binding to the MGMT promoter. Taken together, we consider that upregulation of Trps1 induces MGMT transcription contributing to the formation of MDR in lung cancer cells. Our findings proved potential targets for reversing MDR in clinical chemotherapy of lung cancer.

The underlying molecular mechanism of lung cancer drug resistance is poorly understood. The mediator of endoplasmic reticulum stress CHOP (DNA damage inducible transcript 3) promotes stress-induced apoptosis and appears to function as a transcription factor in multiple diseases. However, its potential contributions to multidrug resistance in solid tumors is unknown. Here, we investigated CHOP expression in tumor tissues form 69 lung cancer patients, finding that deficient CHOP expression is associated with poor prognosis. Cisplatin-resistant lung cancer cells exhibited lower expression of CHOP compared to that in sensitive lung cancer cells, and silencing or augmenting CHOP expression enhanced or impaired cisplatin resistance, respectively. Mechanistic investigations revealed that CHOP is directly associated with the regulation of autophagy or apoptosis-regulatory genes including LC3-II, death receptor 5 (DR5), and telomere repeat-binding factor 3. Notably, CHOP was identified as a target of miR-146a, and increased miR-146a expression in lung cancer cells was suggested to be responsible for CHOP mRNA down-regulation. Further, animal models confirmed that abnormally expressed miR-146a in lung cancer cells does not affect growth, but rather alters chemotherapy sensitivity. Together, CHOP is a useful prognostic marker and miR-146a is a potential therapeutic target for multidrug-resistant lung cancer.

目的 探索体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)技术在心死亡供体肝脏维护中的应用.方法 对2014年9月至2018年1月本院36例心死亡的供体肝脏器官采用不同的方式进行保护,分为使用ECMO保护心脏死亡器官捐献(donation after cardiac death,DCD)供体肝脏组(ECMO组)与未使用ECMO保护DCD供体肝脏组(无ECMO组).供体肝脏器官在进行分类保护之前,均评估及维护供体内环境稳定,积极纠酸治疗,肝功能异常时予以护肝治疗.在供体维持治疗过程中,ECMO组采用ECMO技术维护供体.无ECMO组及时撤除生命支持,待心停跳5 min后获取供体.观察移植前供体肝脏病理、原发性移植肝无功能发生率、缺血性胆道病发生率、急性排斥反应发生率、移植后肝功能等.结果 移植前供体肝,ECMO组与无ECMO组在肝细胞坏死方面差异有统计学意义(P =0.026),在肝细胞脂肪变性及肝细胞变性上差异均无统计学意义(P＞0.05).ECMO组与无ECMO组在原发性移植肝无功能发生率、缺血性胆道病变发生率上差异均有统计学意义(P=0.045,0.026).移植肝后,ECMO组与无ECMO组的肝功能各指标(ALT、AST、TBIL、Alb与PT等)均随着时间的推移慢慢降低,且ECMO组各指标值均低于无ECMO组,差异均有统计学意义(P＜0.05).结论 体外肺氧合技术在心死亡供体肝脏维护中有良好效果.