Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 80–85

Background: The anti-phagocytic molecule CD47 is upregulated in the atherosclerotic plaques of patients with cerebrovascular disease; however, the molecular mechanisms responsible for the development and progression of atherosclerotic lesions have not been fully established. In this study, we postulate how endothelial-specific CD47 promotes endothelial-to-mesenchymal transition (EndoMT) in potentiating atherosclerosis and assess the efficacy of the development of novel therapeutic interventions for cardiovascular disease. Methods: Using single-cell RNA sequencing (scRNA-seq), combined with molecular, cellular, and biochemical analyses, we investigated the role of endothelial CD47 in stimulating EndoMT using knock-out in ApoE-/- atherosclerotic mouse models. Results: ScRNA-seq revealed that CD47 promotes EndoMT, and the loss of endothelial CD47 inhibits EndoMT marker expression as well as transforming growth factor-beta signaling in vitro and atherosclerotic mice, which is associated with smaller lesions in Apoe-/- mouse model. In endothelial cells, CD47 hinders efferocytosis of senescent ECs and represses macrophage’s efferocytotic capacity to propel arterial inflammation and atherogenesis. Mechanistically, the interaction between CD47 and efferocytic receptor MerTK exacerbates inflammation by inhibiting the process of efferocytosis in endothelial cells and macrophages under atherogenic conditions. In response to atherogenic stimuli, endothelial CD47 upregulates the endocytic adaptor protein epsin, causing fibroblast growth factor receptor-1 (FGFR1) signal attenuation that upregulates TGF-β signaling and promoting EndoMT and potentiating atherosclerosis. Conclusion: We conclude that endothelial CD47 potentiates EndoMT during atherogenesis by increasing TGF-β signaling through FGFR1 internalization and degradation and targeted manipulating CD47 expression with precision nanomedicine offering a novel approach for mitigating cardiovascular disease.

目的 探讨分层递进式教学法在胸外科住院医师规范化培训 日常教学活动中的实施效果.方法 选取2021年11月至2022年6月在该院胸外科轮转的30名住院医师规范化培训(以下简称"住培")学员作为分层递进式教学组,另选取2020年11月至2021年6月接受传统培训的住培学员34名作为传统教学组.分层递进式教学组学员入科后明确不同阶段的培训 目标和要求,带教老师明确对不同阶段学员的教学方法,进行分层递进式教学.出科后对分层递进式教学组学员和老师进行满意度调查,并比较分层递进式教学组与传统教学组学员的理论和技能成绩.结果 分层递进式教学模式下,学员与带教老师满意度均达到100％;分层递进式教学组学员技能成绩和理论成绩均高于传统教学组,差异有统计学意义(P＜0.05).结论 分层递进在胸外科的临床实践教学中体现出明显的优越性,值得在临床教学中推广.

Restenosis is a severe complication after percutaneous transluminal coronary angioplasty which limits the long-term efficacy of the intervention. In this study, we investigated the efficiency of exosomes derived from AT2R-overexpressing bone mesenchymal stem cells on the prevention of restenosis after carotid artery injury. Our data showed that AT2R-EXO promoted the proliferation and migration of vascular endothelial cells and maintained the ratio of eNOS/iNOS. On the contrary, AT2R-EXO inhibited the proliferation and migration of vascular smooth muscle cells. In vivo study proved that AT2R-Exo were more effectively accumulated in the injured carotid artery than EXO and Vehicle-EXO controls. AT2R-EXO treatment could improve blood flow of the injured carotid artery site more effectively. Further analysis revealed that AT2REXO prevents restenosis after carotid artery injury by attenuating the injury-induced neointimal hyperplasia. Our study provides a novel and more efficient exosome for the treatment of restenosis diseases after intervention.

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.

临床手术能力教学是贯穿整个住院医师规范化培训阶段的重点和难点内容,有效解决办法较少,临床手术能力教学的高效实施和保证培训效果关系到住院医师规范化培训质量.该院将多模态的数据、影像、3D重建、手术规划、手术导航等混合现实技术应用于住院医师规范化培训,在临床手术能力教学中提高了学员学习积极性、效率和质量,这种基于医疗大数据与人工智能技术平台的培训方法值得推广.

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.

Traumatic rib fractures are the most common injury in thoracic trauma. Previously，the patients with traumatic rib fractures were mostly treated non-surgically，of which 50%，especially those combined with flail chest presented chronic pain or chest wall deformities and over 30% had long-term disabilities，being unable to retain a full-time job. In the past two decades，thanks to the development of internal fixation material technology，the surgical treatment of rib fractures has achieved good outcomes. However，there are still some problems in clinical treatment，including inconsistency in surgical treatment and quality control in medical services. The current consensuses on the management of regional traumatic rib fractures published at home and abroad mainly focus on the guidance of the overall treatment decisions and plans，and relevant clinical guidelines abroad lacks progress in surgical treatment of rib fractures in recent years. Therefore，the Chinese Society of Traumatology affiliated to Chinese Medical Association and Chinese College of Trauma Surgeons affiliated to Chinese Medical Doctor Association，in conjunction with national multidisciplinary experts，formulate the Chinese Consensus for Surgical Treatment of Traumatic Rib Fractures（2021）following the principle of evidence-based medicine，scientific nature and practicality. This expert consensus puts forward some clear，applicable，and graded recommendations from aspects of preoperative imaging evaluation，surgical indications，timing of surgery，surgical methods，rib fracture sites for surgical fixation，internal fixation methods and material selections，treatment of combined injuries in rib fractures，in order to provide references for surgical treatment of traumatic rib fractures.

Restenosis is a serious problem in patients who have undergone percutaneous transluminal angioplasty. Endothelial injury resulting from surgery can lead to endothelial dysfunction and neointimal formation by inducing aberrant proliferation and migration of vascular smooth muscle cells. Exosomes secreted by mesenchymal stem cells have been a hot topic in cardioprotective research. However, to date, exosomes derived from mesenchymal stem cells (MSC-Exo) have rarely been reported in association with restenosis after artery injury. The aim of this study was to investigate whether MSC-Exo inhibit neointimal hyperplasia in a rat model of carotid artery balloon-induced injury and, if so, to explore the underlying mechanisms. Characterization of MSC-Exo immunophenotypes was performed by electron microscopy, nanoparticle tracking analysis and western blot assays. To investigate whether MSC-Exo inhibited neointimal hyperplasia, rats were intravenously injected with normal saline or MSC-Exo after carotid artery balloon-induced injury. Haematoxylin-eosin staining was performed to examine the intimal and media areas. Evans blue dye staining was performed to examine re-endothelialization. Moreover, immunohistochemistry and immunofluorescence were performed to examine the expression of CD31, vWF and α-SMA. To further investigate the involvement of MSC-Exo-induced re-endothelialization, the underlying mechanisms were studied by cell counting kit-8, cell scratch, immunofluorescence and western blot assays. Our data showed that MSC-Exo were ingested by endothelial cells and that systemic injection of MSC-Exo suppressed neointimal hyperplasia after artery injury. The Evans blue staining results showed that MSC-Exo could accelerate re-endothelialization compared to the saline group. The immunofluorescence and immunohistochemistry results showed that MSC-Exo upregulated the expression of CD31 and vWF but downregulated the expression of α-SMA. Furthermore, MSC-Exo mechanistically facilitated proliferation and migration by activating the Erk1/2 signalling pathway. The western blot results showed that MSC-Exo upregulated the expression of PCNA, Cyclin D1, Vimentin, MMP2 and MMP9 compared to that in the control group. Interestingly, an Erk1/2 inhibitor reversed the expression of the above proteins. Our data suggest that MSC-Exo can inhibit neointimal hyperplasia after carotid artery injury by accelerating re-endothelialization, which is accompanied by activation of the Erk1/2 signalling pathway. Importantly, our study provides a novel cell-free approach for the treatment of restenosis diseases after intervention.

目的：探讨重症风湿性瓣膜病的术后管理方法。方法回顾分析126例重症瓣膜性心脏病行瓣膜置换术患者的临床资料。结果126例患者中，围术期死亡10例（死亡率7．94％），包括术中左心室破裂死亡1例，术后低心排综合征死亡5例，术后恶性心律失常死亡2例，术后5 d 突发左心房破裂死亡1例，术后9 d 突发左心衰死亡1例；术后远期死亡1例。其余患者发生严重并发症32例，其中，27例并发低心排综合征，2例发生恶性心律失常，1例出现急性肾功能衰竭，2例出现术后心包填塞，经相应处理后恢复。结论术后细致恰当的管理对重症瓣膜病患者手术恢复有非常重要的意义。

呼吸机治疗是胸心外科危重症患者的重要救治方法，也是临床带教的重点内容。开胸术后使用呼吸机的患者，多为呼吸衰竭、行抢救性治疗的危重患者，病情变化大，还可能发生呼吸机的机械故障等各种异常情况，如果医生基础功不扎实，不能根据报警做出及时正确的处理，甚至可能危及患者生命[1]。一个优秀的胸外科医生，不仅外科手术熟练，而且能够处理危重症患者。那么，呼吸机的熟练掌握也就是必不可少的技术。对于来我科进修学习的胸心外科医生，为了更好地进行呼吸机治疗的学习，我们总结了历年带教的经验，现将其介绍如下。

Objective To analyze and summarize the skills and complications of extracorporeal membrane oxygenation( ECMO) cannu-lation and vein intubation. Methods The clinical data of 21 patients of V-A or V-V ECMO in our hospital from January 2009 to July 2014 were analyzed retrospectively. And the techniques of different catheter sites were summarized. Results Three cases were successfully insert-ed catheter by jugular vein puncture with one time. Four patients with ascending aorta intubation died from uncontrolled severe hemorrhage. Eight peripheral catheter site had a small amount of bleeding,with no more bleeding after pressurized bandage. There were no complications like bleeding, hematoma, hemothorax and pneumothorax in the period of ECMO. Conclusion In the process of the ECMO catheter, the standardized operation could reduce the incidence of serious complicaions including bleeding.

Abstract We sought to elucidate the role of Rho guanine nucleotide exchange factor 5 (ARHGEF5) in tumorigenesis of lung adenocarcinoma cells. ARHGEF5 protein levels were assessed in 91 human lung adenocarcinoma specimens, and A549 and NCI-H1650 cells, by IHC and Western blotting. In addition, ARHGEF5 mRNA expression was evaluated by quantitative reverse transcriptase-PCR. Furthermore, ARHGEF5 long and short isoform coexpression was detected by immunofluorescence. Finally, flow cytometry; CCK8 and wound-healing assays; cell invasion, migration and adhesion; and xenografts were used to evaluate the biologic significance of ARHGEF5. ARHGEF5 was significantly increased in lung adenocarcinoma tissues and cell lines. Interestingly, ARHGEF5 levels were significantly associated with tumor grade and pathologic stage, but not age, gender, T stage, or lymph node metastasis status. ARHGEF5 knockdown by RNAi resulted in dramatically reduced proliferation, adhesion, invasion, and migratory capability of A549 and NCI-H1650 cells. Likewise, protein levels of p-Src, p-Akt, and NF-κB were significantly decreased after ARHGEF5 knockdown. In parallel, increased S-phase population and MMP-2/cyclin D1 expression were observed in the cancer cells, which were not apoptotic. In addition, ARHGEF5 knockdown A549 and NCI-H1650 cells injected s.c. and i.v. into nude mice exhibited decreased xenograft volume and overtly reduced metastasis. Conversely, ARHGEF5 overexpression in A549 and NCI-H1650 cells increased their tumorigenicity in vitro. ARHGEF5 acts as a proto-oncogene in human lung adenocarcinoma cell tumorigenesis. Mol Cancer Ther; 14(7); 1671–9. ©2015 AACR.

Objective Explore the ‘dual‐tutorial teaching’ model in the application of cardiac surgical teaching .Methods 93 eighth grade clinical medicine students of 2011‐2013 school year in our depart‐ment trainee ,were divided into two groups according to the exam scores for sorting before entering the unit :the dual‐tutorial teaching group(odd number sorting ,46 students) and the control groups(e‐ven number sorting ,46 students) .The dual‐tutorial teaching group was including cardiac surgeons and intensive care physicians ,the control group was only include cardiac surgeons .The exam scores and the satisfaction of students of two groups were appraised by the same total teaching teachers .Re‐sults The theory and practical skills record of clinical skill of dual‐tutorial teaching group were signifi‐cantly higher than that of control group (P<0 .05) ,and the students of dual‐tutorial teaching group were more satisfied (P< 0 .05) .Conclusion ‘Dual‐tutorial teaching’ model enhanced the teaching effect in the eighth grade students of medicine ,more in line with the specialized characteristic of cardi‐ac surgery clinical teaching .

Percutaneous coronary interventions (PCIs) are an effective treatment for obstructive coronary artery diseases. However, the procedure's success is limited by remodeling and formation of neointima. In the present study, we engineered rat mesenchymal stem cells (MSCs) to express type 2 angiotensin II receptor (AT2R) using a tetracycline-regulated system that can strictly regulate AT2R expression. We tested the ability of the modified MSCs to reduce neointima formation following arterial injury. We subjected rats to balloon injury, and reverse transcriptase polymerase chain reaction (RT-PCR) indicated no significant AT2R expression in normal rat arteries. Low expression of AT2R was observed at 28 days after balloon-induced injury. Interestingly, MSCs alone were unable to reduce neointimal hyperplasia after balloon-induced injury; after transplantation of modified MSCs, doxycycline treatment significantly upregulated neointimal AT2R expression and inhibited osteopontin mRNA expression, as well as neointimal formation. Taken together, these results suggest that transplantation of MSCs conditionally expressing AT2R could effectively suppress neointimal hyperplasia following balloon-induced injury. Therefore, MSCs with a doxycycline-controlled gene induction system may be useful for the management of arterial injury after PCI.

Many important protein–protein interactions in eukaryotic signaling networks are mediated by peptide recognition domains (PRDs), which bind short linear sequence motifs in other proteins. However, high ligand cross-reactivity is observed within most PRD families, rendering a broad specificity for the family members. In the present study, we attempt to explore the molecular mechanism and physicochemical origin of PRD cross-reactivity. In the procedure, a structure-based method called atomic cross-nonbonded interaction analysis (ACNIA) is described to extract atomic-level nonbonded interaction information at domain–peptide interface and to correlate the information with peptide affinity based on a set of structure-solved, affinity-known protein–peptide complex samples compiled from numerous literatures and databases. The ACNIA-derived affinity predictor is tested rigorously with statistical validation approach, which is also demonstrated to be capable of perceiving slight structural change in the interface using three distinct panels of SH3-binding peptide data. Subsequently, with help of the affinity predictor we adopt the human c-Src SH3 domain, one of the most sophisticated PRDs, as a paradigm to investigate the ligand cross-reactivity within SH3 family. It is found that most of the family members have only few non-essential residue differences in their peptide-binding pockets, and thus exhibit a similar peptide recognition profile and high cross-reactivity. The cross-reactivity is even shared by different subclasses of SH3 domains. The findings suggest that inherent binding specificity is not the only factor to select appropriate binders for specific SH3 domains, and other aspects such as cellular context and the rest of the SH3-containing proteins may play important roles in reducing their ligand cross-reactivity.

At present eight years of clinical medicine teaching in all Medical Universities are in the stage of exploration .Some problems appeared in the clinical teaching of our eight years medical program of&nbsp;cardiothoracic surgery .We also summarized some preliminary experience .This paper has carried on the preliminary discussion in practicing teaching in eight‐year medical students of cardiothoracic sur‐gery .