舒芬太尼复合TCI异丙酚抑制前列腺电切术老年患者尿道镜置入反应的半数有效效应室靶浓度

目的 确定舒芬太尼复合TCI异丙酚抑制经尿道前列腺电切术(TURP)老年患者尿道镜置入反应的半数有效效应室靶浓度(EC50).方法 拟行TURP的患者22例,年龄65～79岁,体重47～81 kg,ASA分级Ⅰ～Ⅲ级.TCI异丙酚,血浆靶浓度4 μg/ml,异丙酚达到靶浓度后开始TCI舒芬太尼;采用序贯法,按照患者是否发生尿道镜置入反应确定舒芬太尼的效应室靶浓度,初始效应室靶浓度为0.3 ng/ml,相邻浓度比值为1.1.计算舒芬太尼的EC50及其95%可信区间.结果 舒芬太尼抑制尿道镜置入反应的EC50为0.23 ng/ml,95%可信区间为0.12～0.44 ng/ml.结论 复合TCI异丙酚(血浆靶浓度4 μg/ml)时,舒芬太尼抑制TURP老年患者尿道镜置入反应的EC50为0.23 ng/ml.

Abstract：

Objective To determine the half-effective target effect-site concentration (EC50 ) of sufentanil inhibiting the urethroscope insertion response when combined with propofol by target-controlled infusion (TCI) in the elderly patients undergoing transurethral resection of prostate (TURP) . Methods Twenty-two ASA Ⅰ- Ⅲ patients, aged 65 -79 yr, weighing 47-81 kg, undergoing TURP, were enrolled in the study. Anesthesia was performed with TCI of propofol and sufentanil. The target plasma concentration of propofol was 4 μg/ml. The target effect-site concentration of sufentanil was determined by up-and-down sequential trial. The initial target effect-site concentration of sufentanil was 0.3 ng/ml and the ratio of the target concentrations between the two consecutive patients was 1.1. The ECW and 95% confidence interval of sufentanil required to inhibit the response to urethroscope insertion were calculated. Results The EC50 of sufentanil required to inhibit the urethroscope insertion response was 0.23 ng/ml (95% confidence interval 0.12-0.44 ng/ml). Conclusion When combined with propofol by TCI (target plasma concentration 4 μg/ml), the EC50 of sufentanil inhibiting the response to urethroscope insertion is 0,23 ng/ml in the elderly patients undergoing TURP.     

粉防己碱逆转大肠癌耐药细胞株LOVO/5-Fu多药耐药性的实验研究

目的 探讨粉防己碱(tetrandrine,Tet)逆转人大肠癌多药耐药细胞LOVO/5-Fu的多药耐药性(multidrug resistance,MDR)及其机制.方法 Tet作用于LOVO/5-Fu细胞48 h后,用噻唑蓝法检测LOVO/5-Fu细胞耐药性,流式细胞术检测细胞凋亡、周期变化及其p-糖蛋白(P-glycoprotein,P-gp)的表达水平,实时荧光定量PCR检测各组细胞MDR1 mRNA表达水平,Western blot检测各组细胞P-gp蛋白的表达水平.结果 经过Tet作用48 h后,大肠癌LOVO/5-Fu细胞株的IC50降低为(4.15±0.31)μg/ml(P＜0.05),细胞凋亡率增加为(3.44%±0.28%)(P＜0.05),MDR1 mRNA转录水平降低为(570 ±85)(P＜0.05),P-gp的表达水平下降.结论 Tet能逆转大肠癌多药耐药细胞LOVO/5-Fu的MDR,其机制可能是抑制MDR1基因的表达,使P-gp的表达降低,从而增强了LOVO/5-Fu细胞对5-Fu的敏感性.

Abstract：

Objective To explore the reversal effect on MDR1 gene-mediated multidrug resistance in human colon carcinoma LOVO/5-Fu cells by tetrandrine ( Tet) and to clarify its molecular mechanism.Methods LOVO/5-Fu cells were treated for 48 h with Tet.Drug sensitivity was measured by MTT.The cell cycle, apoptosis of cells and expression of P-glycoprotein (P-gp) were determined by flow cytometry assay.Expression of MDR1 mRNA was detected by real-time quantitative PCR (real-time PCR).P-gp expression was detected by Western blot.Results After LOVO/5-Fu cells were treated for 48 h with Tet, the IC50 of 5-Fu decreased to ( 4.15 ± 0.31 ) μg/ml ( P ＜ 0.05 ) ; and the apoptotic rate increased to (3.44% ± 0.28% ) ( P ＜ 0.05) ; the expression of MDR1 mRNA reduced to (570 ± 85) (P ＜ 0.05 ).Conclusions Tetrandrine reverses MDR1 gene-mediated multidrug resistance in human colon carcinoma LOVO/5-Fu cells possibly by inhibiting the expression of MDR1, decreasing the expression of P-gp, thus enhancing the sensitivity of LOVO/5-Fu cells to 5-fluorouracil.     

吴茱萸碱对人结肠癌细胞自吞噬的影响

目的 观察吴茱萸碱对结肠癌Lovo细胞自噬的影响,探讨吴茱萸碱对Lovo细胞的生长抑制作用及其机制.方法 联合应用MTT法和形态学变化观察吴茱萸碱对Lovo细胞的生长抑制作用,借助激光共聚焦显微镜观察自噬现象,并用丹(磺)酰戊二胺染色测定对自噬进行定量分析,Western blot方法检测微管相关蛋白轻链3的表达,确认自噬的发生.同时检测吴茱萸碱和3-甲基腺嘌呤对Lovo细胞活力及凋亡的影响.结果 吴茱萸碱呈浓度依赖性抑制结肠癌Lovo细胞的生长活力(P＜0.05),尤其在浓度为60 μmol/L时最为明显(60%),且在光镜下形态表现为细胞裂解和细胞间隙增宽.吴茱萸碱可诱导结肠癌Lovo细胞发生自噬(P＜0.05),阻断自噬后,吴茱萸碱抑制结肠癌Lovo细胞生长活力的能力进一步增强(P＜0.01).结论 吴茱萸碱可诱导结肠癌Lovo细胞发生自噬,但自噬却拮抗吴茱萸碱的抗肿瘤活性.联合应用吴茱萸碱和自噬凋节剂可增强其抗肿瘤作用,逆转其对化疗药物的耐药性.

Abstract：

Objective To investigate the effects of evodiamine on autophagy of human colon a cleno carcinoma lovo cells, and to explore the role and mechanism of autophagy which was induced by evodiamine (EVO). Methods MTT assay combined with the morphologic changes were used to observe the cell viability. Monodansylcadaverine was used to detect autophagy by fluorospectrophotometer and the confocal laser fluorescence microscopy respectively. Immunoblotting assay was used to observe the microtubule-associated protein 1 light chain 3. Finally, evodiamine combined with 3-methyladenine to detect the cell viability with MTT assay and the apoptosis with the flow cytometry, respectively.Results Evodiamine inhibited the viability of Lovo cells in dose-dependent manner ( P ＜ 0. 05 ), especially in 60 μmol/L that was obviously(60% ). Further more, the cell lysis and cell gap widened was observed by the light microscope. Evo triggered the autophagy, and after inhibition the autophagy by 3-MA, the killing capacities of the Evo was enhanced ( P ＜ 0. 01 ). However, autophagy prohibited the apoptosis pathways.Conclusions Evodiamine can trigger the autophagy, which might play a self-defense role in evodiamineinduced cell death. The cytototoxicity of evodiamine can be augmented by the autophagy inhibitors. The joint application of autophagy regulators with the chemotherapeutic agents might enhance the cell killing effects of chemotherapeutic drugs and show a potent role in cancer drug resistance.     

长期饮酒对异丙酚使患者意识消失的半数有效效应室靶浓度的影响

目的 拟通过探讨长期饮酒对异丙酚使患者意识消失的半数有效效应室靶浓度(EC50)的影响,评价长期饮酒对异丙酚镇静效力的影响.方法 择期拟行外科手术的男性患者50例,年龄25～60岁,体重50～80kg,ASA分级Ⅰ或Ⅱ级,根据是否有长期饮酒史分为2组(n=25),对照组:日饮酒量＜25 g;长期饮酒组:日饮酒量超过45 g持续2年或2年以上.采用序贯法确定异丙酚使患者意识消失的EC50其95%可信区间,长期饮酒组和对照组异丙酚初始效应室靶浓度分别为2.0和1.5μg/ml,各相邻靶浓度之比为1.05.以睫毛反射消失及对言语指令无反应作为判断意识消失的标准.结果 长期饮酒组和对照组异丙酚使患者意识消失时的EC50及其95%可信区间分别为3.92(3.56～4.63)g/ml和2.73(2.26～3.31)μg/ml,长期饮酒组EC50高于对照组(P＜0.05).结论 长期饮酒可增加异丙酚使患者意识消失时的EC50,降低其镇静效力.

Abstract：

Objective To evaluate the effect of chronic alcohol intake on the sedative potency of propofol through investigating the effect of chronic alcohol intake on the half-effective target effect-site concentration ( EC50 )of propofol required for loss of consciousness in patients. Methods Fifty male ASA Ⅰ or Ⅱ patients, aged 25-60 yr, weighing 50-80 kg, scheduled for elective surgery, were divided into 2 groups according to the history of chronic alcoholic intake ( n = 25 each): control group (alcoholic intake per day ＜ 25 g) and chronic alcoholic group (alcoholic intake per day＞45 g, lasting for 2 yr or more). The EC50 and 95% confidence interval (CI)were determined by up-and-down sequential method. The initial target effect-site concentration was 2 μg/nl in chronic alcoholic group and 1.5μg/ml in control group, and the ratio between the two successive concentrations was 1.05. Loss of consciousness was defined as loss of response to verbal command and eyelash stimulation. Results The EC50 of propofol that produced loss of consciousness was 3.92 (95 % CI 3.56-4.63 ) μg/ml in chronic alcoholic group and 2.73 (95%CI 2.26-3.31)μg/ml in control group. The EC50 of propofol was significantly higher in chronic alcoholic group than in control group ( P ＜ 0.05). Conclusion Chronic alcohol intake can increase the EC50 of propofol required to induce loss of consciousness and reduce sedative potency in patients.     

抗雄激素药物联合应用治疗女性中重度迟发型痤疮的临床疗效评价

目的：探讨抗雄激素药物联合应用治疗女性中重度迟发型痤疮的最佳方案和疗效。方法：将112例患者按完全随机设计法分成三组：治疗Ⅰ组采用达英-35联合小剂量甲泼尼龙口服,治疗Ⅱ组采用螺内酯联合小剂量甲泼尼龙口服,对照组采用维胺酯口服,4周为1个疗程,连续治疗12周后观察疗效及不良反应,治疗前后检测三组患者血清睾酮（T）、雌二醇（E2）。结果：12周后,治疗Ⅰ组有效率为73.7%,与对照组比较差异无统计学意义（P〉0.05）;治疗Ⅱ组有效率为41.2%,与对照组比较差异有统计学意义（P〈0.05）;治疗Ⅰ、Ⅱ组治疗前后血清T差异有统计学意义（P〈0.05）,E2差异无统计学意义（P〉0.05）;对照组治疗前后T、E2差异均无统计学意义（P〉0.05）。结论：达英-35联合小剂量甲泼尼龙可有效治疗女性迟发型中重度痤疮。     

分子影像技术在多药耐药监测中的研究进展

肿瘤的多药耐药（MDR）是导致癌症复发和转移的重要因素。ATP结合盒转运蛋白（ABC转运蛋白）在人体广泛存在,并且ABC转运蛋白的过度表达是导致肿瘤细胞产生MDR的主要原因之一。利用分子影像技术对MDR肿瘤进行早期监测,有利于临床医师制定有效的治疗方案,并在一定程度上能改善肿瘤患者的预后。笔者就分子影像技术在监测MDR方面的研究进展进行简要综述。     

脂质体递药系统与奥沙利铂脂质体对结直肠癌治疗的研究

奥沙利铂对晚期结直肠癌的临床治疗有较好效果,但有剂量限制性毒性.脂质体作为药物载体,具有缓释性、靶向性和降低药物毒副作用的特点.脂质体的主动靶向修饰对改变抗肿瘤药物的生物分布,减少或逆转肿瘤细胞的多药耐药性,提高抗肿瘤药物的作用也具有意义.利用脂质体的特性,将奥沙利铂制成脂质体治疗结直肠癌有一定意义.     

胃肠间质瘤靶向治疗耐药的分子机制及治疗策略

胃肠间质瘤（GIST）是胃肠道最常见的间叶源性肿瘤。功能获得性突变所致的c-kit或PDGFRA受体酪氨酸激酶异常活化是大多数GIST发病的关键因素。伊马替尼及舒尼替尼等分子靶向药物可特异性抑制酪氨酸激酶受体活化．其作为治疗晚期GIST及高危GIST术后辅助治疗的一线治疗地位已经得到广泛认可,并成为了实体肿瘤分子靶向治疗的经典模型。但同时以上药物的耐药问题一直是临床治疗中的棘手难题和研究热点。许多因素与发生伊马替尼或舒尼替尼耐药有关,其中．KIT／PDGFRA的基因突变是决定耐药与否的主要原因。此外,可能还涉及基因扩增、杂合性丢失和近膜热点区域之外的旁路激活及药物血浆浓度等原因。对于出现肿瘤耐药的患者,应根据不同的耐药原因,采取相应的个体化治疗策略,以期提高治疗效果,改善患者生活质量。     

Development of Research Agenda in Prostate Artery Embolization: Summary of Society of Interventional Radiology Consensus Panel

PurposeTo summarize the Society of Interventional Radiology Foundation’s Research Consensus Panel development of a research agenda on prostate artery embolization (PAE).Materials and MethodsPAE for the treatment of lower urinary tract symptoms has been shown to be safe and effective in decreasing symptoms and prostate size. Lack of randomized controlled trials (RCTs) on PAE in the United States has prevented inclusion in American Urologic Association guideline recommendations for treatment of lower urinary tract symptoms resulting from benign prostatic hyperplasia. Recognizing the need for well-designed trials, the SIR Foundation funded a Research Consensus Panel to prioritize a research agenda. The panel included interventional radiologists, urologists, SIR Foundation leadership, and industry representatives. The goal of the meeting was to discuss weaknesses with current data and study design for development of US trials to report long-term outcomes data.ResultsFinal consensus on a research design could not be made because the group was split on 3 research designs: (i) RCT of PAE versus sham with crossover of the sham group. (ii) RCT of PAE versus simple prostatectomy. (iii) RCT of PAE versus holmium laser enucleation of the prostate/thulium laser enucleation of the prostate. The panel recommended a nonindustry-funded registry to obtain real-world data.ConclusionsLevel 1 data are required to be included in the American Urologic Association guidelines for treatment of benign prostatic hyperplasia. Because of concerns with all 3 study designs, the panel did not reach a consensus. Further meetings are planned with the panel to select among these research designs.