硫酸镁对全麻下止血带相关高血压和术后疼痛的影响

目的探讨硫酸镁对全麻下止血带相关高血压和术后疼痛的影响。方法选择全麻下行单侧下肢手术且需要使用止血带的患者60例,男25例,女35例,年龄30～65岁,ASAⅠ或Ⅱ级,随机分为硫酸镁组(M组)和对照组(C组),每组30例。M组于诱导后5 min使用止血带前静脉泵注硫酸镁30 mg/kg,泵注时间为10 min,随后以15 mg·kg~(-1)·h~(-1)速度维持至松开止血带,C组同样方法泵注等容量生理盐水。记录入室后(T_0)、诱导后5 min(T_1)、止血带充气30 min(T_2)、充气1 h(T_3)、放气前(T_4)、放气后5 min(T_5)时HR、SBP、DBP、每搏量(SV)、心输出量(CO)、心脏指数(CI)。记录术中止血带相关高血压发生情况和降压药使用情况。记录术后3、6、24和48 h静息时VAS评分和Ramsay镇静评分。记录术后补救镇痛情况和寒战、恶心、呕吐、心动过缓、低血压、腱反射消失、呼吸抑制等不良反应发生情况。结果 T_2—T_5时M组HR明显慢于C组(P0.05);T_2—T_4时M组SBP和DBP明显低于C组(P0.05);T_2—T_5时M组SV明显高于C组(P0.05);M组术中止血带相关高血压发生率和降压药物使用率明显低于C组(P0.05)。术后3、6和24 h M组静息时VAS评分明显低于C组(P0.05)。结论全麻下静脉应用硫酸镁可以降低止血带相关高血压发生率和缓解术后疼痛。     

医药类高职院校生物化学实验教学改革实践与思考

生物化学是医学类课程中一门重要的基础学科。生物化学实验是医药类高职院校各专业的必修课。当今生物化学实验不断翻新，教学改革迫在眉睫。针对当前高职院校生化实验基本情况，结合江苏医药职业学院的生物化学实验教学的改革情况，从所需物资设备、完善规章制度、实训内容安排等方面总结和提出相应的改革措施，以及具体问题和意见，可为同类院校生化实验教学改革提供借鉴。     

Increasing radiofrequency ablation volumes with the use of internally cooled electrodes and injected hydrochloric acid in ex vivo bovine livers

Purpose: We used an impedance-controlled generator with an internally cooled electrode to perform radiofrequency ablation (RFA) in ex vivo bovine livers, with a single injection of either 38.5% sodium chloride (NaCl) or 10% hydrochloric acid (HCl), to determine the relative effects of these two solutions on tissue impedance, temperature and ablation volume.

Materials and methods: We performed 10 ablations each with injections of NaCl (NaCl-RFA), HCl (HCl-RFA) or nothing (RFA-alone), with a power setting of 200 W for 15?minutes. We recorded tissue impedance before and after injection. We logged temperatures obtained from thermocouple probes positioned 5, 10, 15 and 20?mm from the internally cooled RF electrode. After ablation, we measured ablation zone longitudinal and transverse diameters, and we calculated a spherical ratio (SR) for each ablation.

Results: Mean post-injection impedance of 30.3 (standard deviation [SD] 2.5) ohms for HCl was significantly lower than that of 55.4 (SD 3.5) ohms for NaCl (p?<?.001). Mean maximum temperatures recorded at each respective distance from the RFA electrode were all highest for HCl-RFA and lowest for RFA-alone (p?<?.001). Mean longitudinal and transverse diameters after HCl-RFA (5.50 [SD 0.25] cm and 5.28 [SD 0.22] cm, respectively) were significantly larger than those after NaCl-RFA (4.24 [SD 0.35] cm and 3.55 [SD 0.43] cm, respectively) and after RFA-alone (3.60 [SD 0.10] cm and 2.70 [SD 0.13] cm, respectively) (p?<?.001). Mean SR after HCl-RFA (0.93, SD 0.02) was significantly higher than mean SR after NaCl-RFA (0.76, SD 0.06) and RFA-alone (0.72, SD 0.04) (p?<?.001).

Conclusion: Monopolar, impedance-controlled RFA, with an internally cooled electrode and a single 10% HCl injection may allow larger tumors to be treated, potentially resulting in improved patient outcomes.     

RPV‐modified epirubicin and dioscin co‐delivery liposomes suppress non‐small cell lung cancer growth by limiting nutrition supply

Chemotherapy for non‐small cell lung cancer (NSCLC) is far from satisfactory, mainly due to poor targeting of antitumor drugs and self‐adaptations of the tumors. Angiogenesis, vasculogenic mimicry (VM) channels, migration, and invasion are the main ways for tumors to obtain nutrition. Herein, RPV‐modified epirubicin and dioscin co‐delivery liposomes were successfully prepared. These liposomes showed ideal physicochemical properties, enhanced tumor targeting and accumulation in tumor sites, and inhibited VM channel formation, tumor angiogenesis, migration and invasion. The liposomes also downregulated VM‐related and angiogenesis‐related proteins in vitro. Furthermore, when tested in vivo, the targeted co‐delivery liposomes increased selective accumulation of drugs in tumor sites and showed extended stability in blood circulation. In conclusion, RPV‐modified epirubicin and dioscin co‐delivery liposomes showed strong antitumor efficacy in vivo and could thus be considered a promising strategy for NSCLC treatment.     

TP53 alterations in relapsed childhood acute lymphoblastic leukemia

TP53 alterations are frequent relapse‐acquired mutations in childhood acute lymphoblastic leukemia (ALL). The present study evaluated the clinical significance of relapsed childhood ALL in Taiwan. Diagnostic and/or relapsed bone marrow or peripheral blood was obtained from 111 children with relapsed ALL who were initially treated by using Taiwan Pediatric Oncology Group (TPOG) ALL protocols from January 1997 to May 2018. Mutations were detected by PCR and sequencing, as well as by multiplex ligation‐dependent probe amplification to detect copy number alterations. Copy number and/or sequence alterations of TP53 were detected in 29% (28 of 98) and in 46% (6 of 13) of patients with relapsed B‐cell and T‐cell ALL, respectively. This incidence was much higher than that in several similar studies conducted in Caucasian populations. Seventy percent of all TP53 alterations were gained at relapse in 67 matched samples by back‐tracking matched diagnostic samples. TP53 alterations were associated with lower 5‐year event‐free survival (EFS) and overall survival (OS) rates (P = .013 and P = .0002, respectively). Multivariate analysis confirmed the prognostic significance of TP53 alterations. Forty‐five patients received hematopoietic stem‐cell transplantations post‐relapse. Patients with TP53 alterations (14/45) had inferior 5‐year EFS and OS than patients without TP53 alterations after transplantation (P = .002 and P = .001, respectively). The significance of these TP53 alterations for patients who received transplantations was confirmed by multivariate analysis. In conclusion, TP53 alterations were enriched and useful as prognostic markers in relapsed childhood ALL.     

伊贝母异甾体生物碱通过Wnt/β-catenin信号通路调节哮喘大鼠气道炎症和气道重塑机制的研究

目的 探讨伊贝母异甾体生物碱对哮喘大鼠气道炎症、气道重塑及Wnt/β-catenin信号通路的影响。方法 本研究采用吸入卵清蛋白（OVA）致敏和激发的方法建立大鼠哮喘模型，连续给予药物7天；抽取支气管肺泡灌洗液（BALF）进行白细胞分类计数，酶联免疫吸附法（ELISA）检测BALF中白介素4（IL-4）、白介素5（IL-5）和白介素13（IL-13）的水平；取肺组织进行苏木精-伊红（HE）染色，观察药物对哮喘大鼠气道重塑的影响；采用Western blot技术考察异甾体生物碱对Wnt/β-catenin信号通路上Wnt5a、Wnt7b和β-catenin蛋白的调节作用。结果 与模型组比较，异甾体生物碱组大鼠肺泡间质炎性细胞浸润和支气管管腔狭窄均显著改善，支气管壁厚度和平滑肌厚度均明显降低；Western blot结果显示异甾体生物碱对于哮喘大鼠Wnt/β-catenin通路上的Wnt5a、Wnt7b和β-catenin蛋白表达均有显著的调节作用。结论 异甾体生物碱对于哮喘相关的病理变化-炎症和气道重塑均有一定的治疗作用，且该治疗作用与Wnt/β-catenin信号通路有关。     

双氢青蒿素诱导肿瘤细胞铁死亡及其机制研究

目的阐明双氢青蒿素(DHA)诱导肿瘤细胞铁死亡的作用及其机制。方法利用3,3′,5,5′-四甲基联苯胺(TMB)检测DHA与FeSO_4体外芬顿样(Fenton)反应生成氧自由基(·OH)的能力;MTT法检测DHA对人肝癌HepG2细胞的毒性(包括FeSO_4与去铁胺预处理组)。MTT法考察谷胱甘肽(GSH)与铁死亡抑制剂(Fer-1)对DHA细胞毒性的影响;采用DCFH-DA染料考察DHA(包括FeSO_4预处理组)诱导的细胞内活性氧的生成能力;采用C11-BODIPY581/591与DiO分别考察DHA(包括FeSO_4预处理组)对细胞内脂质过氧化物生成能力以及细胞膜结构的影响;利用谷胱甘肽过氧化物酶4(GPX-4)试剂盒测定DHA(包括FeSO_4预处理组)对HepG2细胞内GPX-4活性的影响。结果 Fe~(2+)能够催化DHA发生芬顿样反应并生成·OH;DHA的半数抑制浓度(IC_(50))为(39.96±8.78)μmol/L,FeSO_4与去铁胺分别能够增加或者降低DHA的细胞毒性;DHA处理后细胞内活性氧含量与脂质过氧化物含量升高,细胞形态变大,细胞膜呈散点状分布并呈现解离状态。FeSO_4预处理组与DHA组相比较进一步增加细胞内活性氧含量与脂质过氧化物含量,并且细胞膜形态完全破坏。FeSO_4能够增强DHA对GPX-4活性的抑制作用。结论 DHA通过芬顿样反应升高细胞内活性氧而最终诱导肿瘤细胞铁死亡。另外,外源性铁可以加速DHA发生芬顿样反应进而加速肿瘤细胞铁死亡的发生与发展。     

桃红四物汤化学成分、药理作用、临床应用的研究进展及质量标志物的预测分析

桃红四物汤,活血祛瘀之经典名方。该文对近年来桃红四物汤的化学成分、药理作用以及临床应用研究进展进行总结与分析。目前,桃红四物汤不同提取部位化学成分的研究较为系统,其药理作用研究主要集中在活血化瘀、调经镇痛、促进骨折愈合等方面,临床可应用于多系统、多脏腑疾病的治疗,例如妇科疾病、内科疾病、骨伤科疾病、皮肤科疾病等。在此基础上,依照质量标志物(Q-marker)有效、特有、传递与溯源、可测和处方配伍的"五原则"对桃红四物汤Q-marker进行预测分析,提示阿魏酸、芍药苷、苦杏仁苷、芍药内酯苷、梓醇、没食子酸、羟基红花黄色素A可作为该复方的Q-marker,后续可选择这些Q-marker为指标,根据药材、饮片、中间体、对应实物的量值传递进行桃红四物汤全程质量控制并创建其质量可溯源体系。     

黄酮类化合物及其纳米制剂在肿瘤防治中的研究进展

传统的肿瘤治疗方法依然存在肿瘤组织可及性差和药物不良反应普遍的问题。黄酮类化合物已被证实对多种类型肿瘤有效，但其安全性和作用部位特异性尚未被评估。然而，膳食黄酮类化合物因溶解度小、代谢快、口服吸收差等特点限制了其在体内抗肿瘤活性的发挥。此外，黄酮类化合物在某些情况下还能通过生物转化等作用与药物相互作用而影响生物利用度。纳米载体因可改变药物的药动学和药效学特征而被设计用于靶向药物传递，提高难溶性药物的生物利用度，将大分子传递到细胞内的作用位点，同时还能减少药物不良反应。体内、外研究均表明，纳米类黄酮制剂，特别是槲皮素、柚皮素、芹菜素、儿茶素和非瑟酮等在多种肿瘤的预防和治疗方面具有潜在作用，但其临床应用价值仍有待阐明。本文就纳米类黄酮制剂在提高生物利用度、肿瘤治疗效果和安全性方面的作用展开综述，为肿瘤治疗药物的开发利用提供新思路。