胸腔积液中肺腺癌细胞EGFR突变状态与DNA含量的相关性

摘要 目的：探究胸腔积液中肺腺癌细胞表皮生长因子受体（epidermalgrowthfactorreceptor,EGFR）突变状态与DNA含量的相关性,以期探究EGFR突变状态是否同肿瘤的恶性程度存在一定关联。方法：选择2015年1月至2020年1月于我院接受EGFR基因检测以及基因定量分析的591例肺腺癌患者为研究对象,按照其是否出现EGFR基因突变将其分为突变组（335例）与非突变组（256例）,两组患者的胸腔积液均使用激光图像细胞仪开展DNA含量以及非整倍体峰检测,并开展组间差异性比较。结果：（1）将591例患者按照年龄、性别及是否吸烟等临床特征进行分组对比显示,性别（P=0.034）与吸烟（P=0.007）同肺腺癌患者胸腔积液细胞出现EGFR突变具有一定关联,而年龄因素与是否出现突变无明显相关性（P>0.05）;（2）突变组患者的最大DNA指数（DI）、大于5C细胞的平均DI以及大于9C细胞的平均DI均明显高于非突变组,组间差异明显（P<0.05）;（3）开展DNA非整倍体细胞峰比较显示突变组在单峰、双峰占比中明显高于非突变组,而无峰占比明显低于非突变组（P<0.05）,多峰占比方面两组差异不大（P>0.05）。结论：经研究显示,同未出现EGFR突变的肺腺癌患者相比较,发生EGFR突变的肺腺癌患者明显DI值更高,非整倍体细胞以及非整倍体峰值也呈现异常升高态,这提示EGFR发生突变的肺腺癌患者恶变洗吧的侵袭性更强。     

Identification and characterization of proteins isolated from microvesicles derived from human lung cancer pleural effusions

Microvesicles (MVs, also known as exosomes, ectosomes, microparticles) are released by various cancer cells, including lung, colorectal, and prostate carcinoma cells. MVs released from tumor cells and other sources accumulate in the circulation and in pleural effusion. Although recent studies have shown that MVs play multiple roles in tumor progression, the potential pathological roles of MV in pleural effusion, and their protein composition, are still unknown. In this study, we report the first global proteomic analysis of highly purified MVs derived from human nonsmall cell lung cancer (NSCLC) pleural effusion. Using nano‐LC–MS/MS following 1D SDS‐PAGE separation, we identified a total of 912 MV proteins with high confidence. Three independent experiments on three patients showed that MV proteins from PE were distinct from MV obtained from other malignancies. Bioinformatics analyses of the MS data identified pathologically relevant proteins and potential diagnostic makers for NSCLC, including lung‐enriched surface antigens and proteins related to epidermal growth factor receptor signaling. These findings provide new insight into the diverse functions of MVs in cancer progression and will aid in the development of novel diagnostic tools for NSCLC.     

静脉导管留置及胸腔注射尿激酶治疗结核性胸腔积液影响

探讨中心静脉导管胸腔穿刺留置抽液联合胸腔内注入尿激酶(urokinase,UK)治疗结核性渗出性胸膜炎对胸膜肥厚、粘连的预防作用。方法:将52例收治的结核性渗出性胸膜炎所致大量胸腔积液患者随机分为治疗组(27例)和对照组(25例),对照组给于常规抗结核以及传统单纯胸腔穿刺抽液(每周3次)等治疗;全身结核中毒症状严重者,予口服泼尼松30mg．d-1,每周减量5～10mg,疗程约4～6周。在以上药物治疗同时,治疗组第一次穿刺时使用一次性中心静脉导管代替传统胸穿针穿刺置入并保留于胸腔,抽液后从导管注入尿激酶10～20万U,保留24小时后再次抽液;可以再次或多次使用尿激酶10万u注入胸腔;此后不定时抽液,经B超证实抽尽胸水后拔除导管。结果:治疗组住院时间(12．3±6．6)天,住院费用(2219．5±1171．9)元,治疗后第三个月的胸膜厚度(1．00±0．23)mm,无病例发生胸膜增厚、粘连及包裹性胸腔积液。对照组住院时间(20．4±7．9)天,住院费用(2721．9±1711．7)元,治疗后第三个月胸膜厚度(2．1±0．31)mm,另有3例发生胸膜增厚、粘连,2例形成包裹性胸腔积液。各项指标对比差异有显著性。结论:中心静脉导管胸腔穿刺留置抽液及尿激酶胸腔内保留注射治疗结核性胸腔积液具有简便、安全、创伤少、疗效确切;缩短住院时间,降低住院费用;且能有效预防胸膜肥厚和粘连发生。值得临床推广应用。     

Multilevel inhibition of feeding by a peptidergic pleural interneuron in the mollusc<Emphasis Type="Italic"> Lymnaea stagnalis</Emphasis>

The pleural interneuron PlB is a white neuron in the pleural ganglion of the snail Lymnaea. We test the hypothesis that it inhibits neurons at all levels of the feeding system, using a combination of anatomy, physiology and pharmacology. There is just one PlB in each pleural ganglion. Its axon traverses the pedal and cerebral ganglia, running into the buccal ganglia. It has neuropilar branches in the regions of the cerebral and buccal ganglia where neurons that are active during feeding also branch. Activation of the PlB blocks fictive feeding, whether the feeding rhythm occurs spontaneously or is driven by a modulatory interneuron. The PlB inhibits all the neurons in the feeding network, including protraction and retraction motoneurons, central pattern generator interneurons, buccal modulatory interneurons (SO, OC), and cerebral modulatory interneurons (CV1, CGC). Only the CV1 interneuron shows discrete 1:1 IPSPs; all other effects are slow, smooth hyperpolarizations. All connections persist in Ca²⁺/Mg²⁺-rich saline, which reduces polysynaptic effects. The inhibitory effects are mimicked by 0.5 to 100 mol l^–1 FMRFamide, which the PlB soma contains. We conclude that the PlB inhibits neurons in the feeding system at all levels, probably acting though the peptide transmitter FMRFamide.Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00359-004-0503-x     

泡沫敷料对结肠造瘘患者造瘘口周渗出液炎性物质的影响

目的:探讨泡沫敷料对结肠造瘘患者造瘘口周渗出液炎性物质的影响。方法:选取我院普外科收治的结肠造瘘术患者104例,采用随机数字表方法将所有患者平均分为两组,各52例,对照组常规清洁造瘘口,造瘘口及周围皮肤涂抹氧化锌软膏后安装肛门袋;治疗组在对照组治疗的基础上,平铺一层多爱肤有边辅料,安装肛门袋,两组患者均每日更换肛门袋一次,连续治疗2周。采用酶联免疫吸附法(ELISA)检测两组患者治疗前后造瘘口周渗出液炎性物质水平;记录两组患者治疗过程中和治疗后皮肤损伤及造瘘口并发症发生情况。结果:1治疗后,两组患者造瘘口渗出液炎性物质水平较治疗前明显降低,且治疗组下降程度高于对照组(P0.05);2治疗后,治疗组造瘘口皮肤完好率明显高于对照组,差异有统计学意义(P0.05);3对照组造瘘口并发症的发生率明显高于治疗组,差异有统计学意义(P0.05)。结论:泡沫敷料能够降低结肠造瘘患者造瘘口周炎性物质的分泌,减少造瘘口周围皮肤的损伤,降低造瘘口并发症的发生,对结肠造瘘口的护理具有重要临床意义。     

支原体肺炎合并胸腔积液、肺不张27 例临床分析

目的:探讨肺炎支原体肺炎合并胸腔积液、肺不张的诊断和治疗问题。方法:回顾性分析27例MPP合并胸腔积液、肺不张患儿的临床特征、诊治过程的临床资料,并结合文献进行讨论。结果:在27例MPP患儿中,肺CT表现为胸腔积液17例,肺不张10例;24例治愈,1例胸膜肥厚粘连,2例遗留闭塞性细支气管炎。结论:对MPP合并胸腔积液、肺不张患儿应早诊断,早治疗,除应用大环内酯类药物外,应联合应用头孢菌素,激素及丙种球蛋白,疗效肯定。     

Autoantibodies against p53 are not increased in human ascites and pleural effusions

 Mutated human p53 may give rise to the formation of autoantibodies and may be a marker for a worse prognosis. We speculated that ascites or pleural effusions may enhance the formation of such autoantibodies in cancer patients and, therefore, we measured the presence of autoantibodies in the ascites or pleural effusion of 40 patients with advanced malignancies. As controls, p53 autoantibodies were measured in 15 patients with effusions who did not have a malignancy. Using a specific enzyme-linked immunosorbent assay, p53 autoantibodies could only be detected in the effusions of 5/40 patients (12.5%) with known malignancies. The formation of autoantibodies did not correlate with the presence or absence of tumor cells in the effusion. The effusions of the patients without tumor were all negative for p53 autoantibodies. Our study shows that malignant or reactive effusions do not stimulate the local or systemic production of autoantibodies against p53. Received: 14 November 1995 / Accepted: 8 February 1996     

改良手术方法治疗耳廓假性囊肿的疗效分析

目的:评价改进耳廓假性囊肿手术方法后治疗耳廓假性囊肿的疗效。方法:选择2011年2月至2012年7月在我科住院治疗耳廓假性囊肿患者56例,并将其随机分为常规手术组和改进手术组,观察和比较两组患者手术治疗后的痊愈率、显效率及总有效率。结果:所有病人经门诊随访半年以上。常规组1例痊愈(4.6%),4例显效(18.2%),16例有效(72.3%),1例无效(4.6%),总有效率95.5%(21/22);改进组24例痊愈(70.6%),9例显效(26.5%),1例有效(2.9%),总有效率100%(34/34),两组的痊愈率比较差异有显著性意义(P0.05),改进手术组的痊愈率显著高于常规手术组;两组的显效率比较差异有显著性意义(P0.05),改进手术组的显效率显著高于常规手术组;两组的总有效率比较差异没有有显著性意义(P0.05)。结论:改进耳廓假性囊肿手术方法后,术后术腔的渗液明显减少,缩短了换药时间,加快了伤口愈合的速度,避免了手术后因反复换药刺激引起耳廓机化、皮肤增厚而导致的耳廓变形。     

A simple dilute-and-shoot procedure for the determination of platinum in human pleural effusions using HR-CS GF-AAS

BackgroundHigh-resolution continuum source AAS is an emerging technique for the determination of trace elements in clinical analysis. We aimed to develop a method for the direct determination of platinum (Pt) in pleural effusions that could deepen the understanding of the dynamics of intrapleural Pt concentration during cytostatic therapy.Materials and methodsSamples were collected by thoracic drainage from five patients with lung cancer undergoing platinum based chemotherapy. A simple dilute-and-shoot method for Pt determination in the pleural effusions was developed. Ashing of the sample in an oxygen flow in a graphite tube allowed for direct analysis without prior mineralization. The trueness of the method was verified using an independent technique (ICP-MS). As platinum derivatives are only active in its free form (not bound to proteins), Pt in samples was further divided into free and protein-bound forms by means of ultrafiltration.ResultsUsing the proposed method, Pt contents (free and total) were determined in samples collected at different times after the intravenous application of the Pt derivative. The concentration of total Pt reached values of up to 5,000 μg/L and different patterns of its dynamics in intrapleural fluid were observed.ConclusionsThe developed method enables the fast and simple determination of Pt in biological fluids. It may be applied on a large scale to improve the understanding of Pt dynamics during cytostatic therapy, and also to determine the optimal timing of both thoracic drainage and administration of systemic chemotherapy.     

Lethal (2) giant larvae regulates pleural mesothelial cell polarity in pleural fibrosis

Pleural fibrosis is barely reversible and the underlying mechanisms are poorly understood. Pleural mesothelial cells (PMCs) which have apical-basal polarity play a key role in pleural fibrosis. Loss of cell polarity is involved in the development of fibrotic diseases. Partition defective protein (PAR) complex is a key regulator of cell polarity. However, changes of PMC polarity and PAR complex in pleural fibrosis are still unknown. In this study, we observed that PMC polarity was lost in fibrotic pleura. Next we found increased Lethal (2) giant larvae (Lgl) bound with aPKC and PAR-6B competing against PAR-3A in PAR complex, which led to cell polarity loss. Then we demonstrated that Lgl1 siRNA prevented cell polarity loss in PMCs, and Lgl1 conditional knockout (ER-Cre^+/?Lgl1^flox/flox) attenuated pleural fibrosis in a mouse model. Our data indicated that Lgl1 regulates cell polarity of PMCs, inhibition of Lgl1 and maintenance of cell polarity in PMCs could be a potential therapeutic treatment approach for pleural fibrosis.