基于在线数据库和真实世界样本探讨肺腺癌患者POLE/POLD1突变的临床意义

摘要 目的：POLE和POLD1突变导致DNA聚合酶校对功能丧失可能会影响基因组稳定性并导致突变增加和肿瘤形成。本文结合在线数据库和真实世界样本进一步分析肺腺癌（LUAD）患者POLE和/或 POLD1 突变的临床意义。方法：纳入2021年1月～2021年8月徐州医科大学附属医院肺癌术后组织标本115例,利用二代测序技术（NGS）检测基因突变;从癌症基因组图谱（TCGA）数据库收集肺腺癌数据集,通过Cbioportal在线数据库获得肿瘤突变分布图,通过Cibersort法计算获得样本的免疫相关细胞浸润情况。结果：真实世界样本中POLE/ POLD1突变的比例为7.83%（9/115）。TCGA数据显示POLE/POLD1突变的LUAD患者总生存期（OS）减少（P=0.0359）。然而,携带该突变的患者并发其他基因改变的频率明显增加,尤其是与TP53突变存在正相关;同时,POLE/POLD1突变与LUAD组织浸润性免疫杀伤细胞呈正相关,与免疫抑制细胞呈负相关,提示这部分患者对免疫检查点抑制剂（ICI）敏感。结论：LUAD患者POLE/POLD1突变预示较高的肿瘤突变负荷和免疫微环境改变,可作为ICI疗效预测的潜在生物标志物,值得临床关注。     

肺鳞癌和肺腺癌FGFR融合基因的临床意义

目的:探讨肺鳞癌和肺腺癌FGFR融合基因状态及其临床病理意义。方法:采用逆转录-聚合酶链反应(RT-PCR)和直接测序的方法检测2011年1月到2013年12月在我科行手术切除治疗的肺鳞癌和肺腺癌样本的FGFR融合基因,分析患者的临床病理学资料如性别、年龄、吸烟状况、肿瘤大小、病理类型、分化程度,并与对应样本的EGFR、KRAS、HER2、BRAF等常见驱动基因突变进行比较研究。结果:入组患者共512例,包括119例鳞癌和393例腺癌。FGFR融合基因的发生频率为1.2%(6/512),该分子亚型好发于病理证实为肺鳞癌(66.7%,p=0.029)、直径大于3厘米(83.3%,p=0.029)的男性(83.3%,p=0.028)吸烟患者(83.3%,p=0.038)。腺癌融合基因样本均含有实体病理亚型。结论:FGFR融合基因是肺鳞癌和肺腺癌的重要分子亚型,可能起驱动基因作用,具有该特征的肺癌亚群患者很可能将受益于FGFR靶基因研究与靶向治疗。     

探讨免疫球蛋白超级家族成员9促进肺腺癌细胞增殖的作用及机制

肺癌是全球发病率与死亡率均位于第一位的恶性肿瘤。肺腺癌(lung adenocarcinoma,LUAD)大约占整个肺癌的40%。但是,目前对肺腺癌发生发展的机制尚未阐明。TCGA在线数据库GEPIA证实,免疫球蛋白超级家族成员9(immunoglobulin superfamily member 9,IGSF9)在肺腺癌中的平均表达量是6.56,其在正常癌旁组织中的平均表达量是0.55,提示IGSF9在肺腺癌中的表达量是正常癌旁组织的11.93倍。人类蛋白组学数据库也提示,IGSF9在肺腺癌中高表达。通过qRT-PCR检测IGSF9在肺腺癌细胞中的表达量,发现其在A549和H1299细胞中的表达量分别是其在BEAS-2B细胞中的4.17倍和6.6倍。细胞功能实验发现,过表达IGSF9,其LUAD细胞的增殖能力显著增加。平板克隆形成实验发现,在A549细胞中,对照组平板克隆大约有240个,过表达IGSF9后,该组细胞的平板克隆数大约是385个,实验组的克隆数目是对照组的1.60倍(P<0.01)。敲低IGSF9,则LUAD细胞增殖能力明显降低。平板克隆形成实验发现,在H1299细胞中,对照组平板克隆大约有320个,敲低IGSF9后,该组细胞的平板克隆数大约是164个,实验组的克隆数目仅为对照组的51.25%(P<0.01)。生物信息学预测结合后期研究证实,IGSF9可显著抑制叉头蛋白K2(forkhead box protein K2,FOXK2)的表达。MTS实验发现,过表达FOXK2可显著逆转IGSF9对LUAD细胞增殖的促进作用,而敲低FOXK2则可明显补偿敲低IGSF9对LUAD细胞的增殖抑制作用。这些结果提示,IGSF9通过下调FOXK2从而促进LUAD细胞的增殖。     

靶向KRAS治疗肺腺癌研究进展

KRAS是一种致癌驱动因子,它的突变能促进肿瘤细胞增殖,诱发肿瘤产生。KRAS突变是肺腺癌中最常见的突变,存在KRAS基因突变的肺腺癌患者数量占肺腺癌患者数的30%左右,这表明它可能是肺癌潜在的治疗靶点。近年来,针对存在KRAS突变的肺腺癌治疗进行了广泛的研究。该文首先对KRAS的分子结构、生物学功能及其在肺腺癌中的主要突变进行了阐述,然后综述了直接靶向和间接靶向KRAS突变体的肺癌治疗方案,这对于肺癌治疗候选药物的确定,评估新的靶向药物和组合,为肺癌患者提供量身定制的治疗方案具有重要意义。     

EGFR在晚期肺腺癌患者中的表达及临床意义

目的探讨表皮生长因子受体(EGFR)在晚期肺腺癌患者中的表达及其意义。方法收集60例晚期肺腺癌患者的胸腔积液及活检肺癌组织,采用免疫组化检测EGFR的表达,并探讨其表达与临床病理特征的关系。结果 EGFR在胸腔积液及肺癌组织中的阳性表达率分别为75.0%(45/60)、63.3%(38/60),两者差异无统计学意义(P0.05)。结论 EGFR均高表达于肺腺癌胸腔积液及腺癌组织,且与年龄、性别、吸烟史、分化程度及肿瘤的大小无明显相关,可指导肺腺癌患者的靶向治疗。     

MMP11在肺鳞癌和腺癌组织中的表达及与预后的关系

MMP11属于MMPs家族,它与肿瘤的浸润转移密切相关.探讨MMP11在肺鳞癌和腺癌组织中的表达,及其与浸润转移和预后的关系.应用免疫组化检测50例肺鳞癌和38例肺腺癌组织中MMP11蛋白的表达.结果显示,MMP11在肺鳞癌和腺癌组织中的阳性率分别为68.0%(34/50)和73.7%(28/38)(P=0.563).MMP11的阳性率随着肺癌T分期的增加、淋巴结转移和TNM分期的增加而增加(P<0.05).Kaplan-meier单因素生存分析显示,MMP11表达(P=0.001)、T分期(P=0.009)、淋巴结转移(P<0.001)和TNM分期(P<0.001)对生存期的影响有统计学意义.Cox多因素分析显示,只有TNM分期(P=0.028)是肺癌的独立预后危险因素,MMP11(P=0.105)不是肺癌的独立预后危险因素.MMP11的表达与肺癌的浸润、转移及生存期密切相关.     

肺腺癌转移相关的免疫特征开发及潜在中药预测

本研究旨在确定具有免疫相关基因的可靠预后特征,该特征可以预测预后并对肺腺癌(lung adenocarcinoma, LUAD)患者的个体化管理提供帮助。从癌症基因组图谱(The Cancer Genome Atlas, TCGA)数据库下载LUAD患者的mRNA表达谱和相应的临床数据;使用单因素COX和LASSO模型来构建预后模型;使用基于风险评分的方法开发预后特征;通过Kaplan-Meier分析比较高风险患者和低风险患者之间的总生存期(overall survival, OS), OS的独立预测因子通过单变量和多变量COX分析确定;单样本基因集富集分析(single sample gene set enrichment analysis, ssGSEA)用于评估免疫细胞浸润程度;通过LASSO和COX回归分析构建生存预后特征。根据预后特征,在OS方面将患者显著分层为高风险组和低风险组,与低风险组相比,高风险组的LUAD患者OS显著降低。通过ROC曲线分析证实了预后基因标记的预测能力。多因素COX分析显示,风险评分是OS的独立预测因子。通过免疫分析,发现了肺腺癌转移组与未转移组的不...     

ILK在肺鳞状细胞癌和肺腺癌的表达及其与临床病理特征和预后的关系

目的 探讨ILK在肺鳞状细胞癌和肺腺癌组织中的表达情况,及其与病理分型、肿瘤分化、分期、淋巴结转移及预后的关系。方法采用S-P免疫组织化学方法和Western Blot法,检测肺鳞状细胞癌和肺腺癌组织及相应癌旁肺组织中整合连接激酶（integrin-linkedkinase,ILK）的表达情况,并结合临床和病理资料进行分析。结果免疫组化结果显示：ILK在53／76（70％）的肺癌组织中阳性表达。其中鳞状细胞癌阳性率75％（33／44）,腺癌阳性率62．5％（20／32）,其表达与肺鳞状细胞癌的分化呈负相关（P〈0．01）,与临床分期（P〈0．01）、淋巴结转移（P〈0．01）呈正相关;与肺腺癌的临床分期（P〈0．01）和淋巴结转移（P〈0．01）正相关,与分化程度无相关性（P〉0．05）。同时,其表达与患者的生存时间呈负相关（P〈0．01）,与年龄、性别、肿瘤大小和组织类型等因素无关。Western Blot法进一步证实ILK在肺癌组织中的表达显著高于癌旁正常肺组织（P〈0．01）,其表达与肺癌的分化（P〈0．01）显著负相关。结论肺鳞状细胞癌和肺腺癌中,ILK与肺癌的侵袭和转移有关。ILK可作为判断肺鳞状细胞癌和肺腺癌预后的参考指标。     

PTEN与P-糖蛋白在肺鳞癌与肺腺癌组织中的表达及其意义

目的通过检测突变型PTEN、P-糖蛋白在肺鳞癌和肺腺癌组织中的表达差异,探讨肺鳞癌和肺腺癌在肿瘤发生及预后方面出现差异的有关机制,并探讨这两种蛋白表达在肺癌病理临床方面的意义。方法利用免疫组织化学方法对65例肺癌患者手术切除的肺癌组织进行染色,镜下观察PTEN、P-糖蛋白的表达并分析其阳性表达率在肺鳞癌和肺腺癌组织中的差异及与这两种类型肺癌有关生物学行为之间的相关性。结果PTEN在肺腺癌组织中的表达明显高于肺鳞癌组织,差异具有统计学意义（P〈0.05）。PTEN的表达随肿瘤分化程度降低而逐渐降低,差异有统计学意义（P〈0.05）。P-糖蛋白在肺腺癌组织的表达率明显高于肺鳞癌,差异具有统计学意义（P〈0.05）。P-糖蛋白的表达在高分化肺癌组织中的表达明显高于低分化肺癌,差异有统计学意义（P〈0.05）。结论PTEN在肺鳞癌和腺癌的演进过程中,可能起到一定作用,与肿瘤细胞,尤其与肺腺癌的的分化调节有关;P-糖蛋白表达可能与肺鳞癌、肺腺癌的耐药性有关,并可能是肺腺癌及高分化肺癌对化疗药物不敏感的原因之一。     

过表达BTG2增强人肺腺癌细胞的辐射敏感性

在肺癌类型中,肺腺癌占大多数,其总体生存率差,BTG2是抗增殖基因家族的一员,属于BTG/TOB家族。许多研究表明,B细胞易位基因2(BTG2)多种类型的肿瘤中存在异常表达,但其在肺腺癌放疗敏感性中发挥的调控作用尚不明确。本研究通过肺腺癌组织样本及在线数据库,探究BTG2在肺腺癌患者中的表达水平及其表达与临床预后之间的相关性,结果提示在具有放疗抗性的肺腺癌患者中,BTG2的表达水平显著降低,且在肺腺癌细胞系中,BTG2能对放疗产生响应,其在肺腺癌患者中的低表达状态与不良的预后相关(P＜0.05);在人肺腺癌A549和H1299细胞系中转染过表达BTG2(OE-BTG2)慢病毒,通过克隆形成检测过表达BTG2对肺腺癌细胞系的辐射敏感性的影响,实验证实过表达BTG2可显著增强A549和H1299细胞系的辐射敏感性(P＜0.05);并进一步通过WB、免疫组化检测BTG2及凋亡相关蛋白BAX的表达水平,结果证实:过表达BTG2可显著增加A549和H1299细胞辐射后的凋亡水平。最后通过裸鼠成瘤试验检测BTG2在活体中对肺腺癌辐射敏感性的影响,结果提示:在动物实验中,过表达BTG2可显著增强肺腺癌的辐射敏感性(P＜0.05)及增加辐射后BAX的表达水平。综上所述,BTG2在肺腺癌组织中处于低表达状态,并且与不良的临床预后紧密相关,过表达BTG2可促进凋亡过程,增加人肺腺癌细胞系的辐射敏感性,能为克服肺腺癌的辐射抗性提供新的靶点。     

Relative and combined effects of ethanol and protein deficiency on strontium and barium bone content and fecal and urinary excretion

To elucidate accumulation of minerals in human iliac arteries with aging, the content of minerals was analyzed by inductively coupled plasma atomic emission spectrometry. Bilateral common, internal, and external iliac arteries of 16 men and 8 women, ranging ages from 65 to 93 yr, were examined. It was found that an extremely high accumulation of calcium and phosphorus occurred in the common iliac artery at old age, being higher than that of the internal and external iliac arteries. It should be noted that the accumulation of calcium and phosphorus is the highest in the common iliac artery among the human arteries examined to date. Regarding sexual differences, the content of calcium and phosphorus in the common and internal iliac arteries was higher in women than in men, whereas their content in the external iliac artery was lower in women than in men.     

New amino-dithiaphospholanes and phosphoramidodithioites and their rhodium and iridium complexes

New sulfur derivatives of phosphoramidite ligands were synthesized and the impact of the sulfur unit on the spectroscopic properties of their rhodium and iridium complexes was investigated. The new ligands Bn₂NPSCH₂CH₂S^a(P-S^a) (Bn = benzyl, 4), Bn₂NPSCHCHS^a(CH₂)₃C^aH₂(P-S^a)(C^a-S^a) (6) and Bn₂NP(4-XC₆H₄OMe)₂ (X = S, 7a; X = O, 7b) were converted to the rhodium and iridium complexes trans-[Rh(CO)Cl(L)₂] (L = 4, 6, 7), [RhCl(COD)(L)] (L = 4, 6, 7), [IrCl(COD)(7a)] and [IrCl₂Cp∗(6)]. For comparison, some phosphoramidite complexes of these formulations also were synthesized. The new metal complexes were spectroscopically analyzed. For the carbonyl complexes, the ν_CO IR stretching frequencies were lower than for the corresponding phosphite and phosphoramidite ligands. The ¹J_PRh coupling constants for the rhodium complexes with the new ligands were also smaller than for the respective phosphoramidite and phosphite complexes. Finally, the ¹J_PSe coupling constants of the selenides of the new ligands were lower than those of the phosphoramidite ligands but higher than for PPh₃. The spectroscopic data reveal that the new thio ligands 4, 6 and 7a are more electron donating than phosphites and phosphoramidites but less electron donating than PPh₃.     

Astrocytes and Synaptosomes Transport and Metabolize Lactate and Acetate Differently

Astrocytes transport the monocarboxylate acetate, but synaptosomes do not. The reason for this is unknown, because both preparations express monocarboxylate transporters (MCT). The transport and metabolism of lactate, another monocarboxylate, was examined in these two preparations, and the results were compared to those for acetate. Lactate transport is more rapid in astrocytes than in synaptosomes, but of lower affinity (Kms of 17 and 4 mM, respectively). Lactate (0.2 mM) is metabolized to CO2 more rapidly in synaptosomes than in astrocytes (rates of 0.37 and 0.07 nmol x mg protein(-1) x min(-1), respectively). The reason for this is unclear, but cellular differences in lactate dehydrogenase isotype expression may be involved. Acetate is metabolized to CO2 more rapidly in astrocytes than in synaptosomes (rates of 0.43 and 0.02 nmol x mg protein(-1) x min(-1), respectively). This is likely due to cellular differences in the expression of monocarboxylate transporter subtypes.     

Rapporteur report: Basics and technology and metrology and standards

The first and second sessions of the Workshop focussed on the basics of ultrasound and infrasound, their applications in both industry and medicine, and metrology and protection standards for ultrasound applications.     

Prostaglandin and thromboxane production by human and guinea-pig macrophages and leucocytes

The ability of partially purified human and guinea-pig haematogenous cell populations, when cultured in vitro, to metabolise arachidonic acid (AA) has been studied. Supernatants from 24 hour cell culture have been subjected to analysis for products of AA metabolism by gas chromatography with electron-capture detection.The cell types studied were human peripheral blood monocytes (both glass adherent and non-adherent), neutrophils, eosinophils and leukemic leucocytes; thoracic duct lymphocytes and lung alveolar macrophages. From the guinea-pig, induced and non-induced macrophage or neutrophil enriched peritoneal exudate populations, lymph node cells, peritoneal eosinophils and peripheral blood platelets were examined. Supernatants were assayed for the presence of PGE₂, PGD₂, PGF_2α, TXB₂ and 6-keto-PGF_1α. In all types studied PGE₂ and TXB₂ were the major products formed. The identification of PGE₂ and TXB₂ was confirmed by GC/MS with multiple ion monitoring.The results have been compared with other reports and their possible significance discussed in relation to the proposed role of prostaglandins as mediators and modulators in immunopathology.     

白蚁与动物及微生物的共生类型及其机制

综述了白蚁螱客的主要种类、共生关系及相关机制的研究进展。白蚁螱客中,已报道的动物种类达170种。在与动物的共生关系中存在偏利共生（宾主共栖和异种共栖）、互利共生和无关共生三种;在与微生物的共生关系中,存在与内生菌（原生动物、细菌、真菌和放线菌）和外生菌（蚁巢伞菌等）间的互利关系。指出了白蚁与螱客研究中存在的问题,给出了解决方案,并提出了今后可能的研究热点或方向,为白蚁的综合利用（如纤维素酶）及今后研究物种间的协同进化提供了基础资料。     

Acidophilic and acid-tolerant fungi and yeasts

Fungi have not been systematically studied from mines and mine drainage waters, even though they are often encountered there. This paper provides a key from literature sources and lists morphological characteristics and habitat information for the 81 fungal species that have been collected or identified in pH <4 environments.