埃克替尼与吉非替尼治疗既往化疗失败的局部晚期或转移性非小细胞肺癌患者的系统性评价

目的:比较埃克替尼与吉非替尼治疗既往化疗失败的局部晚期或转移性非小细胞肺癌(NSCLC)患者的近期疗效及不良反应情况。方法:通过Medline、Embase、Cochrane图书馆、中国生物医学文献数据库、中国期刊全文数据库、中文生物医学期刊文献数据库和数字化期刊全文数据库等全面检索国内外相关文献,纳入埃克替尼和吉非替尼治疗既往化疗失败的局部晚期或转移性NSCLC的随机对照试验(RCTs),并对文献进行筛选、评价与分析。采用RevMan 4.2软件对入选研究的近期疗效及不良反应进行Meta分析。结果:共纳入符合标准的RCTs 2项,涉及423例病例。系统评价显示,异质性检验结果良好,可用固定效应模型进行分析。埃克替尼组与吉非替尼组比较,4周疾病控制率、半年总生存率、1年总生存率均无明显差异;埃克替尼组的28周疾病控制率优于吉非替尼组(P=0.01);埃克替尼组与吉非替尼组的皮疹、腹泻、咯血发生率均无显著差异,但埃克替尼治疗组的总不良反应发生率显著低于吉非替尼(P<0.000 01)。结论:对于既往化疗失败的局部晚期或转移性NSCLC,埃克替尼的疗效与吉非替尼相当,且总的耐受性优于吉非替尼。     

埃克替尼联合化疗治疗EGFR突变型晚期非小细胞肺癌患者的临床疗效研究

目的 探讨埃克替尼联合化疗治疗EGFR突变型晚期非小细胞肺癌患者的临床疗效.方法 回顾性选取2019年6月至2020年6月期间在我院接受治疗的60例EGFR突变型晚期非小细胞肺癌患者作为研究对象,依据治疗方法的不同将其分为两组,采用埃克替尼治疗的30例患者为常规组,采用埃克替尼联合化疗的30例患者为观察组.比较两组患者治疗后的临床疗效及不良反应总发生率.结果 观察组治疗后的客观缓解率和疾病控制率分别为63.33％、93.33％,均高于常规组的43.33％、80.00％ (P＜0.05);观察组治疗后的不良反应发生率与常规组差异无明显差异(P＞0.05).结论 埃克替尼联合化疗有助于阻止EGFR突变型晚期非小细胞肺癌患者的疾病进展,不良反应发生率与常规组无明显差异.     

埃克替尼联合化疗治疗EGFR突变型晚期非小细胞肺癌患者的临床疗效研究

目的 探讨埃克替尼联合化疗治疗EGFR突变型晚期非小细胞肺癌患者的临床疗效.方法 回顾性选取2019年6月至2020年6月期间在我院接受治疗的60例EGFR突变型晚期非小细胞肺癌患者作为研究对象,依据治疗方法的不同将其分为两组,采用埃克替尼治疗的30例患者为常规组,采用埃克替尼联合化疗的30例患者为观察组.比较两组患者治疗后的临床疗效及不良反应总发生率.结果 观察组治疗后的客观缓解率和疾病控制率分别为63.33％、93.33％,均高于常规组的43.33％、80.00％ (P＜0.05);观察组治疗后的不良反应发生率与常规组差异无明显差异(P＞0.05).结论 埃克替尼联合化疗有助于阻止EGFR突变型晚期非小细胞肺癌患者的疾病进展,不良反应发生率与常规组无明显差异.     

吉非替尼与厄洛替尼治疗非小细胞肺癌临床疗效比较及药物经济学评价

目的比较吉非替尼与厄洛替尼治疗非小细胞肺癌的临床疗效和药物经济学评价。方法比较实验组(服用吉非替尼)38例和对照组(服用厄洛替尼)34例NSCLC患者分别给予吉非替尼和厄洛替尼治疗的临床疗效、不良反应发生情况及药物经济学评价结果。结果两组患者有效率及临床控制率比较,差异无统计学意义(P0.05);两组肿瘤进展时间及1年生存率比较,差异无统计学意义(P0.05);两组患者不良反应发生率及严重程度比较,差异无统计学意义(P0.05);实验组患者治疗费用及费用疗效比均显著低于对照组,差异具有统计学意义(P0.05)。结论吉非替尼与厄洛替尼治疗NSCLC疗效相当,但吉非替尼更加经济适用。     

NP化疗方案联合埃克替尼治疗EGFR敏感突变型ⅢB-Ⅳ期非小细胞肺癌患者的疗效评价

目的 探讨NP化疗(长春瑞滨注射液+顺铂)方案联合埃克替尼治疗表皮细胞生长因子受体(EGFR)敏感突变型ⅢB-Ⅳ期非小细胞肺癌(NSCLC)的疗效.方法 选取2017年1月-2019年1月我院EGFR敏感突变型ⅢB-Ⅳ期NSCLC患者126例,按治疗方案不同分联合组(n=63)、对照组(n=63).对照组予以埃克替尼治疗,联合组予以NP化疗方案联合埃克替尼治疗.比较两组疗效、治疗前、治疗4个周期后血清糖类抗原125(CA125)、癌胚抗原(CEA)和细胞角蛋白19片段(CYFRA21-1)、生存质量(KPS评分)、中位生存期、不良反应发生情况.结果 联合组客观缓解率(ORR)68.25％高于对照组49.21％(P<0.05);治疗4个周期后两组血清CA125、CEA、CYFRA21-1水平较治疗前降低,且联合组低于对照组(P<0.05);治疗4个周期后两组KPS评分升高,且联合组高于对照组(P<0.05);联合组中位生存期19.5个月长于对照组16.0个月(P<0.05);两组不良反应均以1～2级为主,联合组恶心呕吐、谷丙转氨酶升高、白细胞减少、脱发、血小板减少、贫血、中性粒细胞减少1～2级发生率高于对照组(P<0.05),但患者均可耐受,未影响治疗效果.结论 NP化疗方案联合埃克替尼治疗EGFR敏感突变型ⅢB-Ⅳ期NSCLC患者效果显著,能有效降低肿瘤标志物水平,提高患者生存质量,延长生存期,且具有安全性.     

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。     

盐酸埃克替尼与吉非替尼治疗化疗失败的非小细胞肺癌28例

目的:探讨盐酸埃克替尼和吉非替尼治疗化疗失败的非小细胞肺癌(NSCLC)的疗效和不良反应。方法:28例NSCLC患者,随机分为试验组和对照组,分别予以盐酸埃克替尼(125 mg,po,tid)和吉非替尼(250 mg,po,qd),观察两组患者的近期疗效和不良反应。结果:试验组14例患者无完全缓解(CR),部分缓解(PR)率21.4%,病情稳定(SD)率35.7%、疾病进展(PD)率28.6%,1例患者因瘫痪退出,1例患者死亡,近期有效率为21.4%,疾病控制率为57.1%。对照组14例患者无CR,PR 7.1%,SD 50%,PD 14.3%,死亡4例,近期有效率为7.1%,疾病控制率为57.1%。两组的近期有效率和疾病控制率、无疾病进展期(PFS)和总生存期(OS)无明显差异。主要不良反应为皮疹,两组比较无显著差异。结论:盐酸埃克替尼与吉非替尼疗效相似,但安全性高,能有效治疗化疗失败的NSCLC。     

吉非替尼治疗EGFR突变晚期肺腺癌的疗效与安全性研究

目的探究使用吉非替尼治疗表皮生长因子受体(EGFR)突变晚期肺腺癌的临床疗效和安全性。方法以2013年1月～2016年3月本院收治的EGFR突变晚期肺腺癌患者72例为研究对象,按照阳性突变位点的不同将之分为19号外显子缺失突变的19del组和21号外显子L858R突变的L858R组,分析吉非替尼治疗的临床疗效和安全性。结果 L858R组疾病控制率、客观缓解率分别为92.86%、61.90%,19del组分别为100.00%、66.67%,两组疾病控制率、客观缓解率无显著差异且均处于较高水平(P 0.05);经吉非替尼治疗后患者总的无进展生存期和总生存期分别为(11.46±2.15)、(21.67±4.38)个月,并且发现19del组患者的无进展生存期、总生存期均显著长于L858R组(P 0.05);患者总的不良反应发生率为23.61%(17/72),以皮疹为主且症状均较轻,两组的不良反应发生率分别为23.81%和23.33%,差异无统计学意义(P 0.05)。结论使用吉非替尼对EGFR突变晚期肺腺癌进行治疗临床效果较好,可有效延长患者生存时间,并且具有较高的安全性。     

吉非替尼治疗非小细胞肺癌脑转移的临床研究

目的探讨吉非替尼治疗非小细胞肺癌（NSCLC）脑转移的疗效及安全性。方法回顾性分析11例采用吉非替尼治疗的NSCLC脑转移患者的临床资料。所有患者均口服吉非替尼250mg,1次／d,直至疾病进展或出现不可耐受的不良反应。结果11例患者颅内病灶的有效率（RR）和疾病控制率（DCR）分别为27．3％和81．8％。全身病灶的RR和DCR分别为36．4％和81．8％。接受吉非替尼联合脑部放疗的患者RR上优于接受埃克替尼单药治疗者,但差异无统计学意义（P〉0．05）。RR和DCR与年龄、性别、病理类型、ECOG评分、脑转移种目、吉非替尼治疗情况、脑部放疗及表皮生长因子受体（EGFR）突变状况均无关。全组中位无进展生存时间（PFS）为6．1个月,其中EGFR突变型为10．1个月。PFS与EG．FR基因突变状况有关,而与其他临床病理特征无关。主要不良反应为皮肤干燥、皮疹和腹泻,以1～2级为主。结论吉非替尼对NSCLC脑转移有一定疗效,且不良反应可耐受,值得临床进一步研究验证。     

吉非替尼治疗晚期非小细胞肺癌的疗效观察

目的：评价吉非替尼治疗晚期非小细胞肺癌（NSCLC）的疗效和安全性。方法：270例晚期NSCLC患者按用药情况分为吉非替尼组与多西他赛组,两组患者在年龄、性别、病理类型、分期等方面大致平衡。吉非替尼组口服吉非替尼250mg/d;多西他赛组静脉滴注多西他赛75mg/m2,1h,每3周重复给药,直到病变进展或出现不可耐受的不良反应。结果：吉非替尼组与多西他赛组疾病控制率分别为70.9%和57.4%（P〈0.05）;中位无疾病进展生存时间分别为7.6个月和4.1个月（P〈0.05）。因不良反应调整药物剂量,吉非替尼组有4例（2.8%）,多西他赛组有21例（16.3%）（P〈0.05）。3～4级不良反应发生率,吉非替尼组为12.1%,多西他赛组为41.1%（P〈0.05）。结论：吉非替尼治疗晚期NSCLC安全、有效、不良反应轻,患者耐受性较多西他赛更好。     

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.