探讨不同肺腺癌标本中EGFR突变和TTF-1表达的关系及临床意义

目的探讨在不同肺腺癌标本中EGFR突变和TTF-1表达的关系及意义。方法收集肺腺癌标本603例(手术标本343例、小活检176例及胸水细胞块86例),用扩增阻滞突变系统(amp1ification refractory mutation system,ARMS)法检测EGFR的突变及用免疫组化方法检测TTF-1表达。结果 EGFR突变在手术组织172例(50.1%)、小活检90例(51.1%)及胸水细胞块48例(57.1%)。TTF-1阳性在手术组织中206例(60.1%)、小活检98例(55.7%)及细胞块50例(59.5%)。所有标本中EGFR突变310例(51.4%),TTF-1阳性356例(58.7%)。所有突变中19外显子157例(50.6%)、21外显子143例(46.1%)、18外显子10例(3.3%)。结论胸水细胞块标本检测EGFR突变与组织标本具有同样的效果。肺腺癌患者TTF-1表达与EGFR的突变在手术标本、小活检及胸水细胞块中都有高度相关性。TTF-1对EGFR突变也有比较好的提示作用。     

非小细胞肺癌患者中EGFR与TTF-1表达及与患者预后关系的研究

目的探索NSCLC患者TTF-1与EGFR突变表达情况及其与患者预后的关系。方法共收集2011.1-2014.12我科NSCLC患者240例组织标本,采用免疫组化法检测TTF-1表达,采用PCR扩增直接测序法检测EGFR突变,采用χ~2检验研究EGFR突变与TTF-1阳性表达的相关性,Kaplan-Meier法分析患者总生存期(OS)与TTF-1及EGFR突变的关系,绘制出生存曲线,P0.05为有显著统计学意义。结果 TTF-1阳性与患者性别,吸烟指数,病理分型,TNM分期,EGFR突变及PS评分有明显相关性,TTF-1阳性、EGFR突变阳性患者与阴性患者生存曲线均无交叉,生存期有差别,尤其EGFR突变中21外显子阳性患者其生存期明显好(P0.001)。结论 TTF-1可作为NSCLC患者预测预后的一个独立指标,联合EGFR突变可以更好的预测预后,指导临床诊疗。     

肺腺癌EGFR基因19、21外显子突变与临床病理特征及预后的关系

目的分析肺腺癌表皮生长因子受体(EGFR)基因19、21外显子突变与临床病理特征及预后的关系。 方法回顾性分析2017年1月至2018年6月100例经病理证实为肺腺癌的患者临床资料与标本,采用PCR-ARMS技术检测标本EGFR基因19、21外显子突变情况,分析EGFR基因突变与临床病理特征及预后的关系。 结果100例肺腺癌标本共检测出47例EGFR突变,突变率为47.00%,其中第19号外显子突变20例(42.55%),包括6种形式的突变,以核苷酸框架缺失为主,最常见的类型为核苷酸从2234-2248位缺失15bp的delE746-A750突变,共11例,占55.00%;第21号外显子突变27例(57.45%),包括5种形式的突变,均是碱基置换突变,最常见的类型为2573位点的T被G取代的L858R,共17例,占62.96%;女性、无吸烟史、临床分期Ⅰ期患者EGFR19与EGFR21突变率高于其他患者(P<0.05);Logisitic回归分析显示性别、吸烟史、肿瘤直径、临床病理分期是影响EGFR19、EGFR21突变的因素。100例肺腺癌患者全部获得有效随访,EGFR19突变患者2年无进展生存率、总生存率分别为80.00%、85.00%,未突变患者分别为65.00%、73.75%;EGFR21突变患者2年无进展生存率、总生存率分别为81.48%、92.59%,未突变患者分别为63.01%、69.86%;女性、临床分期较早、无淋巴结转移、发生EGFR21突变患者2年生存率低于其他患者(P<0.05);Logisitic回归分析显示男性、临床分期较晚、有淋巴结转移、EGFR21未突变是肺腺癌患者不良预后的独立危险因素。 结论肺腺癌EGFR基因19、21外显子突变与性别、吸烟史、肿瘤直径、临床分期有关,同时也是预测预后的有效方法。     

EGFR突变及VEGF表达与吉非替尼治疗晚期肺腺癌疗效关系的研究

目的探讨EGFR突变及VEGF表达与吉非替尼治疗晚期肺腺癌疗效的关系。方法直接测序法检测30例晚期肺腺癌EGFR外显子19及21突变,免疫组化法检测VEGF表达,与吉非替尼疗效进行分析。结果 30例患者EGFR突变率46.7﹪(14/30),其中21外显子8例,19外显子6例;吉非替尼有效率50﹪,疾病控制率60.0﹪;15例有效患者EGFR突变率为80﹪,12例无效者为16.7%,差异显著(P=0.002);EGFR突变者中位无进展生存期为9.5个月,无突变者为1.5个月,差异有显著性(P<0.05)。有效患者VEGF的表达为(-)6例,(+)5例,(■)4例;无效患者为(-)1例,(+)2例,(■)3例,(■)4例,(■)2例,有效者VEGF表达低,差异显著(P<0.05)。VEGF表达与EGFR突变之间无相关性(P=0.104)。结论 EGFR突变者吉非替尼疗效好,VEGF低表达者吉非替尼疗效好。     

肺腺癌组织中IGF1R、Cezanne-1表达与EGFR基因突变的相关性分析

目的探讨肺腺癌组织中胰岛素样生长因子-1受体(IGF1R)、Cezanne-1表达与表皮生长因子受体(EGFR)基因突变情况,分析IGF1R、Cezanne-1表达与EGFR基因突变的相关性。 方法选择2017年3月至2019月4月本医经病理确诊且得到明确肺腺癌肿瘤组织与癌旁组织的肺腺癌患者56例,将其纳入病例组;纳入同期在医院接受手术治疗并在术中获得病灶组织的51例肺部良性病变患者,将其作为对照组。对全部纳入的组织样本进行IGF1R、Cezanne-1表达与EGFR基因突变检查,比较各组IGF1R、Cezanne-1阳性表达与EGFR基因突变检出率;比较不同EGFR基因突变肺腺癌患者临床特征、IGF1R、Cezanne-1阳性检出率;分析IGF1R、Cezanne-1表达与EGFR基因突变的相关性。 结果肺腺癌组织EGFR基因突变、IGF1R、Cezanne-1阳性检出率均高于癌旁组织及肺部良性病变组,差异有统计学意义(P<0.05);EGFR基因突变的肺腺癌患者与其他未检出基因突变的肺腺癌患者的临床特征比较,差异均无统计学意义(P>0.05),但较未检出EGFR基因突变的肺腺癌组织,检出基因突变的组织中IGF1R、Cezanne-1阳性检出率更高,差异有统计学意义(P<0.05);IGF1R、Cezanne-1表达与EGFR基因突变之间均呈正相关(r>0,P<0.05)。 结论肺腺癌组织内IGF1R、Cezanne-1多呈过表达,EGFR基因突变率较其他正常组织高,且这种IGF1R、Cezanne-1的过表达与EGFR基因突变明显相关。     

TTF-1和p63在肺腺癌与鳞癌的鉴别中的意义

目的研究TTF-1和p63在肺腺癌及肺鳞癌中的表达及鉴别诊断中的价值。方法收集肺鳞癌69例,腺癌62例,采用免疫组织化学PV-9000法分别检测TTF-1和p63在肺腺癌及肺鳞癌中的表达情况。结果 TTF-1在肺鳞癌中未见表达(0/69),在肺腺癌中的阳性表达率为87.10%(54/62),TTF-1表达在肺鳞癌与肺腺癌中的表达差异有显著统计学意义(P0.01);P63在肺鳞癌中的阳性表达率为97.10%(67/69),在肺腺癌中的阳性表达为4.84%(3/62),p63表达在肺鳞癌与肺腺癌中的表达差异有显著统计学意义(P0.01)。结论根据TTF-1和p63在肺癌组织的存在特异性表达,联合检测两者有助于在肺活检标本中对肺鳞癌和肺腺癌的鉴别诊断。     

肺腺癌中PD-L1、B7H3的表达与EGFR基因突变的关系

目的探讨程序性凋亡配体1(programmed death-ligand 1,PD-L1)、B7H3在肺腺癌中的表达与表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变状况的关系,为EGFR基因突变的肺腺癌患者提供一种新的临床治疗方法。方法收集78例手术切除的肺腺癌组织,所有标本均有EGFR基因检测结果。应用免疫组织化学PV-6 000法检测PD-L1、B7H3的表达情况。结果肺腺癌组织中有32例(41.0%)发生EGFR突变,其中女性的突变率高于男性(30.8%vs 10.3%,P0.05),不吸烟者比吸烟者有更高的突变率(28.2%vs12.8%,P0.05)。PD-L1、B7H3在EGFR突变型患者中的阳性率分别为71.9%、68.8%,均高于其在野生型患者中的发生率45.7%、43.5%(P0.05),且均与21外显子突变密切相关(P0.05),但未发现与19外显子突变相关(P0.05)。PD-L1在女性、不吸烟者及II~III期中的表达水平高于男性、吸烟者及I期患者(P0.05)。B7H3的表达与TNM分期及淋巴结转移情况相关(P0.05)。PD-L1与B7H3表达呈正相关关系(P0.05)。结论 PD-L1、B7H3高表达在EGFR突变型肺腺癌的发生发展中起重要作用,以PD-L1、B7H3为靶点的免疫治疗,可能成为这部分患者治疗的新方法。     

EGFR基因21外显子L858R突变肺腺癌患者化疗和靶向治疗疗效的回顾性分析

目的探讨EGFR基因21外显子L858R突变肺腺癌患者使用化疗和EGFR-TKI靶向治疗疗效的差异。方法回顾性分析,收集第三军医大学新桥医院2010年1月至2015年12月间EGFR基因检测为21外显子L858R突变的病例资料完整的ⅢB/Ⅳ期一线接受化疗或EGFR酪氨酸激酶抑制剂(EGFR-TKI)靶向治疗的肺腺癌患者作为研究对象,将患者根据一线治疗方式分为化疗组和靶向治疗组,对两组患者近期疗效(客观缓解率ORR、疾病控制率DCR)及生存期(无进展生存期PFS、总生存期OS)进行回顾性研究。结果 1共收集符合纳入标准的EGFR基因21外显子L858R突变的肺腺癌患者68例,其中化疗组患者40例(58.8%),靶向治疗组患者28例(41.2%),两组患者在性别、年龄、吸烟史、PS评分和临床分期等临床资料基线水平一致(P0.05);2化疗和靶向治疗组ORR分别为45.0%和17.9%(P=0.020);DCR分别为95.0%和71.4%(P=0.012),PFS分别为9.901个月和6.746个月(P=0.045);OS分别为21.738个月和23.611个月(P=0.378)。结论与靶向治疗相比,EGFR基因21外显子L858R突变肺腺癌患者化疗治疗在近期疗效及PFS上较有优势,OS未见明显获益。     

EGFR突变状态与肺腺癌新分类中组织学亚型和生存关系

目的本研究选取手术切除的中晚期肺腺癌中常见病理亚型,通过检测EGFR突变状态探讨其对患者生存时间的影响。方法收集我院胸外科经手术切除的Ⅱa-Ⅲa期肺腺癌患者生存资料,通过检测肺腺癌EGFR基因,比较EGFR基因突变阳性与EGFR突变基因阴性(野生型)患者的2年无疾病生存率(DFS)和5年总生存率(OS),分析比较EGFR突变状态对患者生存的影响。结果在120例肺腺癌患者中EGFR基因突变率为46.6%,最常见的突变位点是外显子19(44.6%)和外显子21(42.8%),在所有浸润性肺腺癌组织学类型中,最常见的组织学类型是腺泡为主型(55.8%),其次是伏壁为主型(25.8%),两种组织学类型中的EGFR突变阳性率为(腺泡型61.2%VS伏壁为主型44.7%),EGFR野生型(腺泡型55.3%VS伏壁型33.8%),两者组织学亚型中EGFR突变率差异无统计学意义(P=0.192)。通过比较生存时间分析得出,肺腺癌2年无疾病生存率(EGFR突变阳性55.3%VS EGFR突变野生型55.6%,P=0.367),5年总生存率(EGFR突变阳性55.5%VS EGFR突变野生型40.6%,P=0.143),差异均无统计学意义。结论在手术切除的中晚期肺腺癌患者中,EGFR突变状态本身不是影响肺腺癌术后生存时间的因素。     

非小细胞肺癌患者EGFR突变率及与临床病理关系和TKI靶向治疗效果

目的探讨非小细胞肺癌(NSCLC)患者表皮生长因子受体(EGFR)突变率及与临床病理关系和酪氨酸酶抑制剂(TKI)靶向治疗效果。 方法选取2014年5月至2016年8月我院收治的NSCLC患者100例为研究对象,采用聚合酶链反应-直接测序法检测患者肿瘤组织EGFR基因18-21号外显子突变情况,分析EGFR突变与临床病理的关系及其突变特点,比较EGFR突变型与野生型采用TKI靶向治疗的疗效及1年生存率、2年生存率。 结果本次纳入的100例NSCLC患者中共44例发生EGFR突变,EGFR突变率为44.00%;NSCLC患者EGFR突变率特点：女性高于男性,吸烟患者高于不吸烟患者,腺癌高于非腺癌,差异对比均有统计学意义(P<0.05);Logistic回归分析显示性别为女性、病理类型为腺癌是导致NSCLC患者发生EGFR突变的独立危险因素(P<0.05);EGFR突变类型包括18号外显子点突变4.54%(2/44)、19号外显子缺失突变43.19%(19/44)、20号外显子插入突变及点突变11.36%(5/44)、21号外显子点突变40.91%(18/44);EGFR突变型患者TKI治疗有效率68.18%明显高于EGFR野生型10.71%(P<0.05);EGFR突变型与野生型患者1年、2年生存率对比差异无统计学意义(P>0.05)。 结论性别、病理类型是导致NSCLC患者发生EGFR基因突变的独立危险因素,对于EGFR突变型患者采用TKI靶向治疗可获得较好疗效,但2年生存率与EGFR野生型患者尚无明显差异。     

Cement and Concrete Nanoscience and Nanotechnology

Concrete science is a multidisciplinary area of research where nanotechnology potentially offers the opportunity to enhance the understanding of concrete behavior, to engineer its properties and to lower production and ecological cost of construction materials. Recent work at the National Research Council Canada in the area of concrete materials research has shown the potential of improving concrete properties by modifying the structure of cement hydrates, addition of nanoparticles and nanotubes and controlling the delivery of admixtures. This article will focus on a review of these innovative achievements.     

Medical and Psychology Students' Knowledge and Attitudes Regarding Aging and Sexuality

The current study surveys medical and doctoral psychology students (N = 100) from an urban northeastern university regarding knowledge and attitudes toward elderly sexuality and aging using the Facts on Aging Quiz, the Aging Sexuality Knowledge and Attitudes Scale, and measures of interest in gerontology, academic/clinical exposure to aging and sexuality, and contact with elders. The current study found that psychology students demonstrated greater aging knowledge than medical students; however, both groups showed gaps in knowledge about sexuality. Married students had greater academic/clinical exposure and greater knowledge about aging but less permissive attitudes toward elderly sexuality. Generally, knowledge about aging was the strongest correlate of knowledge about sexuality. Level of knowledge about sexuality was not associated with attitudes. Attitudes toward sexuality and aging may be more strongly tied to demographic variables reflective of religious beliefs or adherence to sociocultural norms.     

Leptin and cellular and innate immunity in abstinent alcoholics and controls

BACKGROUND: Basic studies indicate that in vitro and in vivo doses of leptin modulate cellular immune responses. Given evidence that concentrations of leptin are altered in alcoholics who also show immune abnormalities, this study examined the relationships between circulating levels of leptin and markers of cellular and innate immunity. METHODS: Circulating levels of leptin, natural killer cell (NK) activity, interleukin-2 (IL-2)-stimulated NK activity, and concanavalin A-stimulated production of IL-2, IL-6, IL-10, and IL-12 were compared between abstinent DSM-IV alcohol-dependent men (n = 27) and age- and gender-matched controls (n = 34). RESULTS: As compared with controls, alcoholics showed lower NK activity (p < 0.01) and a trend for lower levels of leptin (p = 0.055). In the total sample, leptin predicted NK activity (beta = 0.33; p < 0.05) after controlling for the confounding influence of body mass index, alcohol intake, and smoking. Leptin was not correlated with any of the cytokine measures. To examine whether the effects of leptin were mediated by its direct action on NK, additional studies examined in vitro effects of leptin on NK activity in healthy volunteers (n = 10); leptin doses (0.1, 1, and 10 nM) yielded levels of NK activity comparable to those with media alone. CONCLUSIONS: These data show that circulating levels of leptin are associated with NK activity in humans and suggest that abnormal in vivo concentrations of leptin may contribute to the declines of NK activity in alcoholics who are at risk for infectious diseases.     

慢性饮酒、吸烟与骨质疏松的相关性研究

目的 探讨长期大量慢性饮酒、吸烟等不良生活方式与骨质疏松的关系.方法 以乏力、腰背痛、双下肢酸困为主诉,且有长期大量慢性饮酒史、吸烟史,无其他慢性疾病史的年轻男性患者45例为观察对象,测定其血钙(Ca)、血磷(P)和血肌酐(Cr)、尿素氮(BUN)、血糖(Glu)、天门冬酸氨基转移酶(AST)、丙氨酸基转移酶(ALT)、血清碱性磷酸酶(ALP)、甲状腺功能、全段甲状旁腺激素(iPTH)、1,25-二羟维生素D3[1,25-(OH) 2D3]、双能X线骨密度仪测定腰椎L1-4及左侧股骨近段(包括颈、股骨颈上部、大粗隆)骨密度(BMD),分析饮酒、吸烟对骨量的影响.以感冒发热就诊、年龄相当、无饮酒、吸烟史及慢性疾病史的45例男性为对照组.结果 观察组1,25(OH)2D3水平均降低,血钙水平偏低,血磷正常,碱性磷酸酶呈不同程度地升高,骨密度T值提示观察组27例骨质疏松,12例骨量减少,6例正常骨量;而对照组仅有6例为骨量减少,1例骨质疏松,38例为正常骨量,两组比较差异有统计学意义(P＜0.05).结论 长期慢性大量饮酒吸烟影响骨量,甚至易导致骨质疏松.     

自身免疫与动脉粥样硬化的发生发展

在动脉粥样硬化的发生发展过程中,自身免疫具有重要作用,本文就近年有关动脉粥样硬化的免疫机制的研究进展作一简要综述.     

Neutropenia and agranulocytosis in England and Wales: incidence and risk factors

The objectives of this study were to estimate the incidence of idiosyncratic neutropenia and agranulocytosis in England and Wales and to evaluate their risk factors and outcomes. The study was conducted using data from the General Practice Research Database. All cases of idiosyncratic neutropenia or agranulocytosis were identified and the incidence was estimated. This was followed by a nested case-control study, estimating odds ratios with drug exposure from conditional logistic regression. From 1987 to 1999, 3,224 patients with idiosyncratic neutropenia (50 with agranulocytosis) were identified. The incidences of neutropenia and agranulocytosis were estimated to be 120 and 7 cases per million people per year, respectively. The adjusted odds ratios for neutropenia were 34.7 (95% confidence interval 12.0-99.7) for current users of thyroid inhibitors, 9.5 (4.4-20.8) for users of disease-modifying antirheumatic drugs, and 7.6 (4.9-11.9) for users of aminosalicylates. Other drugs with statistically significantly increased risks of neutropenia included antibacterial drugs, non-opioid analgesics, NSAIDs, antidepressants, ulcer-healing drugs, and anti-epileptics. The increase in risk of neutropenia predominantly occurred during the first months of treatment. For most drugs investigated in this study, there was no relationship to daily dose. The excess 1-year mortality was low among neutropenia and agranulocytosis cases and mostly explained by the underlying disease state. In conclusion, the highest risks of neutropenia were generally found in patients starting treatment. The excess 1-year mortality was low among neutropenia and agranulocytosis cases and can be mostly explained by the underlying disease state.     

中青年超重和肥胖与高血压及高同型半胱氨酸血症的相关性研究

目的探讨中青年超重和肥胖与高血压及高同型半胱氨酸血症的相关性。方法选取2012年1月—2013年10月在我院进行常规健康体检者750例,测量受试者血压、身高、体质量及血清同型半胱氨酸(Hcy)水平。结果男性超重、肥胖检出率分别为36.87%(198/537)和13.97%(75/537),均高于女性的16.43%(35/213)和7.50%(16/213)(P0.05)。超重者和肥胖者高血压和高同型半胱氨酸血症检出率分别为21.03%(49/233)和11.16%(26/233)、46.12%(42/91)和41.76%(38/91),均高于正常者的9.16%(37/404)和2.23%(9/404),肥胖者高于超重者(P0.01)。收缩压(SBP)、舒张压(DBP)及血清Hcy与BMI呈正相关(r值分别为0.639、0.515、0.497,P0.01)。结论中青年尤其是男性超半数存在超重或肥胖,高血压及高同型半胱氨酸血症与BMI呈正相关,超重和肥胖者高血压及高同型半胱氨酸血症的发生率高,应积极防治。