EGFR敏感突变晚期NSCLC患者应用盐酸埃克替尼靶向治疗对患者神经钙黏素表达的影响

目的:探究表皮生长因子受体(EGFR)敏感突变晚期非小细胞肺癌(NSCLC)患者应用盐酸埃克替尼靶向治疗对患者神经钙黏素表达的干预.方法:选取2015年4月～2018年7月某院收治的EGFR敏感突变晚期NSCLC患者80例,根据治疗方式不同,将其分为观察组和对照组各40例,对照组给予吉非替尼,观察组采用盐酸埃克替尼.治...     

吉非替尼治疗非小细胞肺癌的疗效与EGFR基因突变的关系

目的探讨吉非替尼治疗晚期非小细胞肺癌(NSCLC)的疗效与表皮生长因子受体(EGFR)基因突变的关系。方法选择36例Ⅲb期或Ⅳ期经铂类治疗方案无效的NSCLC患者,根据有无EGFR基因突变分为有EGFR基因突变组(A组,11例)与无EGFR基因突变组(B组,25例),均予以吉非替尼治疗,分析其疗效与EGFR基因突变的关系。结果 A组吉非替尼治疗有效率优于B组(81.8%vs.16.0%)(P<0.05)。结论 EGFR基因突变的检测可作为吉非替尼治疗NSCLC疗效的一个预测指标。     

非替尼联合多西他赛对EGFR突变阳性晚期非小细胞肺癌患者呼吸功能和不良反应发生率的影响

目的:探讨吉非替尼联合多西他赛用于治疗表皮生长因子受体(EGFR)突变阳性晚期非小细胞肺癌的效果.方法:选择69例EGFR突变阳性晚期非小细胞肺癌患者将其分为对照组(n=35,多西他赛联合顺铂治疗)和观察组(n=34,吉非替尼联合多西他赛),比较两组患者临床疗效、不良反应发生情况.结果:观察组总有效率为70.58％,高于对照组(51.43％),疾病控制率为91.17％高于对照组(80.00％)(P<0.05);观察组不良反应发生率为11.76％低于对照组(31.43％)(P<0.05).结论:EGFR突变阳性晚期非小细胞肺癌患者应用吉非替尼联合多西他赛疗效显著、改善患者呼吸功能、减少不良反应发生率.     

吉非替尼与化疗用于晚期非小细胞肺癌维持治疗疗效的临床观察

目的 表皮生长因子受体酪氨酸激酶抑制剂(Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors,EGFR-TKIs)吉非替尼及细胞毒化疗药物如吉西他滨、培美曲塞均是晚期非小细胞肺癌(Non-Small Cell Lung Cancer,NSCLC)维持治疗的有效手段,为对比两类药物维持治疗的临床疗效,我们进行了本项研究.方法 回顾性分析接受吉非替尼、吉西他滨及培美曲塞维持治疗的65例晚期NSCLC,按照所接受的维持治疗方案种类分为吉非替尼维持治疗组和化疗维持治疗组,分析两组间疾病控制率、无进展生存(Progression-Free Survival,PFS)及总生存(Overall Survival,OS)的差异.结果 65例患者34例为吉非替尼维持治疗(10例已知为EGFR基因突变患者),31例为化疗维持治疗(21例为吉西他滨维持化疗,10例为培美曲塞维持化疗),两种维持治疗方案获得的疾病控制率(70.6％比64.5％,P=0.791)、PFS(6.4月比5.0月,P=0.110)、OS(16.3月比12.0月,P=0.327)比较差异无统计学意义.分层分析发现EGFR突变状态未知时,吉非替尼对比吉西他滨、培美曲塞维持治疗PFS(4.0月比4.0月比5.0月,P=0.462)、OS(14.4月比12.0月比12.2月,P=0.540)比较差异无统计学意义,然而吉非替尼维持治疗组EGFR突变阳性患者较突变状态未知患者PFS(11.2月比4.0月,P=0.001)、OS(31.9月比14.4月,P=0.02)显著延长,差异有统计学意义.结论 晚期NSCLC吉非替尼与化疗维持治疗疗效相似.吉非替尼维持治疗EGFR突变阳性患者较未知患者有明显获益,建议晚期NSCLC予吉非替尼维持治疗时常规行EGFR突变检测.     

吉非替尼联合重组人血管内皮抑制素治疗EGFR突变非小细胞肺癌的临床效果观察

目的 观察吉非替尼联合重组人血管内皮抑制素治疗表皮生长因子受体(EGFR)突变非小细胞肺癌(NSCLC)的临床效果.方法 选取2018年5月—2020年11月本院收治的109例EGFR突变NSCLC,根据治疗方法的不同分为研究组55例(予吉非替尼联合重组人血管内皮抑制素治疗)和对照组54例(仅予吉非替尼治疗),21 d...     

埃克替尼治疗非小细胞肺癌的研究进展

埃克替尼是我国第一个自主创新的小分子靶向抗癌药,用于表皮生长因子受体(EGFR)基因敏感突变的局部晚期或转移性非小细胞肺癌(NSCLC)患者的治疗,是我国继吉非替尼后第二个用于该适应证的一线药物.2021年6月,埃克替尼单药作为Ⅱ～ⅢA期伴有EGFR敏感突变NSCLC术后辅助治疗的新适应证获批上市,成为第一个用于此类型...     

威麦宁胶囊联合奥希替尼治疗EGFR T790M突变晚期肺腺癌的临床疗效

目的 观察威麦宁胶囊联合奥希替尼治疗表皮生长因子受体(EGFR)T790M突变晚期肺腺癌的临床疗效.方法 60例EGFR T790M突变晚期肺腺癌患者随机均分为两组,对照组采用奥希替尼80 mg,1次/天;观察组在奥希替尼治疗的基础上加用威麦宁胶囊6～8粒/次,3次/天.比较两组临床疗效和不良反应发生情况.结果 治疗1...     

安罗替尼靶向治疗对人表皮生长因子受体阳性晚期非小细胞肺癌患者疾病控制率的影响

目的:探讨安罗替尼靶向治疗对人表皮生长因子受体(EGFR)阳性晚期非小细胞肺癌(NSCLC)患者疾病控制率的影响.方法:选取九江学院附属医院2018年12月至2020年12月收治的74例EGFR阳性晚期NSCLC患者,运用随机数字表法将患者分为研究组和对照组,各37例.予对照组患者使用顺铂与培美曲塞进行化疗治疗,而研究...     

达可替尼对比吉非替尼一线治疗EGFR突变晚期或转移性非小细胞肺癌的成本效果分析

目的 比较达可替尼和吉非替尼一线治疗中国表皮生长因子受体(EGFR)突变晚期或转移性非小细胞肺癌(NSCLC)的成本效果.方法 建立无疾病进展、疾病进展和死亡三种健康状态的分区生存模型.基于ARCHER 1050临床试验获取转移概率和安全性数据,根据已发表文献获得健康效用值,从卫生服务体系角度只考虑直接医疗成本,包括药...     

安罗替尼联合厄洛替尼治疗表皮生长因子受体突变阳性晚期非小细胞肺癌患者的临床研究

目的 观察安罗替尼胶囊联合厄洛替尼片治疗表皮生长因子受体(EGFR)突变阳性晚期非小细胞肺癌(NSCLC)患者的临床疗效及安全性。方法 将EGFR突变阳性晚期NSCLC患者随机分为对照组和试验组。对照组给予厄洛替尼片每次150 mg,qd,口服;试验组在对照组治疗的基础上,联合安罗替尼胶囊每次10 mg,qd,口服,连续服药14 d后停药7 d。2组患者1个疗程均为21 d,持续用药至疾病进展或治疗不耐受。比较2组患者的临床疗效、血管生成调节因子水平、生存时间(OS),以及药物不良反应的发生情况。结果 试验组入组50例,脱落2例,最终48例纳入分析;对照组入组50例,脱落1例,最终49例纳入分析。治疗后,试验组和对照组的疾病控制率分别为100.00%(48例/48例)和71.43%(35例/49例),客观缓解率分别为87.50%(42例/48例)和42.86%(21例/49例),差异均有统计学意义(均P<0.01)。治疗后,试验组和对照组的血管内皮生长因子水平分别为(382.53±26.82)和(397.45±26.19)ng·L^-1,基质金属蛋白酶-9水平...     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.