Pressurized IntraPeritoneal Aerosol Chemotherapy with one minute of electrostatic precipitation (ePIPAC) is feasible,but the histological tumor response in peritoneal metastasis is insufficient

IntroductionElectrostatic precipitation Pressurized IntraPeritoneal Aerosol Chemotherapy (ePIPAC) has shown superior penetration depth and tissue uptake compared to standard PIPAC. We investigated the feasibility and objective tumor response to ePIPAC with 1 min of precipitation in patients with peritoneal metastasis (PM).Materials and methodsPatients with PM from various abdominal cancers were included in an amendment to the ongoing prospective PIPAC-OPC2 trial. Colorectal and appendiceal PM were treated with oxaliplatin, patients with PM from other primaries were treated with a combination of cisplatin and doxorubicin. Three ePIPAC procedures were planned in each patient including repeated peritoneal biopsies for response evaluation. After emission to the peritoneal cavity, the aerosolized chemotherapeutics were precipitated for 1 min followed by immediate exsufflation and abdominal closure. Histological regression from the first to the third ePIPAC was evaluated according to the Peritoneal Regression Grading Score (PRGS) and compared to data from the PIPAC-OPC1 trial. Complications and toxicities were recorded according to Dindo-Clavien and CTCAE.ResultsSixty-five ePIPAC procedures were performed in 33 patients (median 2, range 1–6). Ten patients were eligible for response evaluation based on biopsies from the first and third ePIPAC procedure. Four patients had disease progression, four patients had regressive disease, and two patients had stable disease according to PRGS. No life threatening adverse reactions and no mortality was observed following ePIPAC.ConclusionOne minute ePIPAC was feasible and safe, but the histological tumor response was insufficient compared to standard PIPAC directed therapy with 30 min passive diffusion time.     

载As2O3 pH敏感钙砷复合物脂质体的制备及体外评价

目的 制备pH敏感释药的As₂O₃脂质体，并进行体外评价。方法 采用薄膜分散法制备含钙离子脂质体，然后用离子沉淀法孵育制备钙砷复合物脂质体（CaAs-LP）。测定CaAs-LP的粒径、Zeta电位及多分散系数（PDI）；透射电子显微镜观察脂质体的形态；电感耦合等离子体发射光谱仪测定纳米药物的载药量与包封率；透析袋法考察其体外释药特性。噻唑蓝（MTT）法考察未载药脂质体及CaAs-LP对人源性乳腺癌MCF-7细胞、人源性脑胶质瘤U87细胞和人源性肝癌HepG2细胞的毒性；共聚焦显微镜考察U87细胞对CaAs-LP的摄取效率。结果 制备的CaAs-LP呈规整类球型，粒径约为（117.16±1.94）nm，包封率和载药量分别为（74.31±2.11）%、（8.31±0.13）%。体外释放研究表明，CaAs-LP具有明显的缓释以及pH响应释药特征。未载药的脂质体在MCF-7、U87、HepG2和L02细胞中的生物相容性良好；CaAs-LP抑制肿瘤细胞生长的作用较原药有所上升，半数抑制浓度（IC₅₀）值分别为11.91、4.90、19.41、27.59 μmol/L。细胞摄取研究表明肝癌细胞对脂质体具有良好的摄取。结论 CaAs-LP具备显著的缓释以及pH响应释药的特性，在肿瘤治疗方面具有较好的应用前景。     

分步醇沉对玛咖多糖单糖组成及抗氧化活性的影响

目的:分析分步醇沉所得玛咖多糖的单糖组成,并对各部分玛咖多糖的抗氧化能力进行研究。方法:采用水提醇沉法得到玛咖粗多糖,通过分步醇沉对玛咖粗多糖进行分离、纯化;采用气相色谱分析法对各玛咖多糖的单糖组成进行分析;最后采用三氯乙酸法和清除DPPH自由基的方法考察各部分玛咖多糖的抗氧化能力。结果:分步醇沉随乙醇浓度增加依次得到0~40%乙醇多糖部分,40%~50%乙醇多糖部分,50%~60%乙醇多糖部分,60%~70%乙醇多糖部分及70%~80%乙醇多糖部分,依次命名为MP1,MP2,MP3,MP4和MP5;其中收率最大的为MP1,纯度最高的为MP4,分别为0.856%和68.5%;经气相色谱技术分析发现不同体积分数乙醇所得玛咖多糖的单糖组成种类及比例不同;抗氧化能力试验结果表明各部分玛咖多糖的抗氧化能力存在显著性差异,其中抗氧化能力最强的为MP5,MP4抗氧化能力次之,抗氧化能力最弱的为MP1。结论:分步醇沉所得各部分玛咖多糖的抗氧化能力有较大差异,玛咖多糖的抗氧化活性与其单糖组成的种类、比例及其空间构象密切相关,分步醇沉对分离纯化玛咖多糖具有重要意义,为玛咖多糖进一步分离纯化、结构组成和药理研究提供可靠的参考依据。     

超声波-化学沉淀法制备牙科纳米氧化铝陶瓷粉体

目的:制备分散性好,粒度均匀的纳米α-A l2O3粉体。方法:应用超声波-化学沉淀法,制备氢氧化铝前驱体,经900℃、1 000℃、1 100℃、1 200℃煅烧后测试粉体性能。结果:1 200℃煅烧得到的A l2O3粉体为α-A l2O3,其晶粒平均粒径为D202=31.44 nm。结论:以乙醇为反应溶剂,在低频超声波作用下可制备出分散性好、粒度均匀的纳米级α-A l2O3粉体。     

热毒宁注射液青蒿金银花浓缩过程近红外快速定量检测方法的建立

目的建立热毒宁注射液青蒿金银花醇沉浓缩过程主要药效成分的定量校正模型,实现生产过程在线监控。方法采用近红外光谱技术(NIRS)结合偏最小二乘法(PLSR)分别建立新绿原酸、绿原酸、隐绿原酸的定量校正模型。结果新绿原酸、绿原酸、隐绿原酸定量校正模型的决定系数(R~2)分别为0.954 5、0.975 2、0.9691;校正集误差均方根(RMSEC)为0.213、0.676、0.225,交叉验证集误差均方根(RMSECV)分别为0.233、0.692、0.258。采用所建模型进行在线分析,新绿原酸、绿原酸、隐绿原酸的预测值与实测值的决定系数分别为0.984 2、0.983 7、0.9870,预测相对误差(RPD)分别为4.77、5.29、4.37,预测相对偏差(RSEP)分别为3.519%、3.778%、3.895%。结论所建的模型可以用于热毒宁注射液青蒿金银花醇沉浓缩过程中新绿原酸、绿原酸、隐绿原酸的在线定量测定。     

Can the Reaction Mechanism of Radical Solution Polymerization Explain the Microgel Final Particle Volume in Precipitation Polymerization of N‐Isopropylacrylamide?

Precise particle size customization is a key requirement for the applications of stimuli‐sensitive poly(N‐isopropylacrylamide) microgels. No empirically supported mechanism has been presented to explain the microgel particle size dependence on polymerization conditions. In this work, nonstirred precipitation polymerization is employed to address this question. It is argued that the reaction proceeds by radical solution polymerization mechanism rather than as emulsion polymerization. The number of particles in the batch, and the microgel particle volume, is shown to correlate with the charge density of the particles determined by the kinetic chain length. Cross‐linking efficiency is recognized to be an important factor in the particle nucleation. Properties of radical solution polymerization, such as differences in the rate of decomposition of thermally decomposing initiator and redox initiator, are used to tune the particle number density in the batch. Contemporary synthesis approaches, including temperature‐programmed synthesis, are discussed in the context of these results.

     

六味地黄汤水提醇溶部位对2型糖尿病大鼠胰岛及肾脏组织形态结构的影响

目的 研究六味地黄汤水提醇溶部位对2型糖尿病大鼠胰岛及肾脏的影响.方法 采用高糖、高脂饲料喂养4周后,再行腹腔注射小剂量链脲佐菌素(STZ)且空腹血糖(FBG)≥16.7 mmol/L的大鼠建立2型糖尿病动物模型,将其随机分为空白组、模型组、罗格列酮组和六味地黄汤水提醇溶部位组,观察给药1个月后大鼠空腹血糖(FBG)和大鼠胰岛、肾脏组织的形态结构.结果 六味地黄汤水提醇溶部位能降低2型糖尿病大鼠FBG值(P＜0.01),对其受损的胰岛及肾脏有修复作用.结论 六味地黄汤水提醇溶部位能够修复2型糖尿病大鼠的胰岛及肾脏,胰岛及肾脏是具干预2型糖尿病作用的靶位之一.     

直接蛋白沉淀-超高效液相色谱法测定氟尿嘧啶血药浓度

建立直接蛋白沉淀-超高效液相色谱法测定血浆中微量氟尿嘧啶的方法。以6%高氯酸为沉淀剂,5-氯尿嘧啶为内标物,样品经涡旋振荡等处理后,高速离心获取上清液作为供试液。供试液测定采用Acquity HSS T₃色谱柱,水-乙腈为流动相,流速为0.2 mL/min,进样量为5 μL,柱温为20 ℃。方法的专属性、准确度、精密度、线性等指标经验证后完全符合定量测定要求,与传统的测定方法相比,可显著缩短进样分析时间、降低试剂成本。本方法已经被成功用于临床病人的血药浓度检测,具有良好的临床应用前景。     

Box-Behnken响应面法优化热毒宁注射液金银花和青蒿(金青)的醇沉工艺研究

目的优化热毒宁注射液金银花和青蒿(金青)的醇沉工艺,并获得关键工艺参数与质量属性的关系方程,为醇沉过程自动化控制提供理论依据。方法以新绿原酸、绿原酸、隐绿原酸、咖啡酸、断氧化马钱子苷转移率及醇沉液中固含量为指标,通过单因素试验设计,考察醇沉前液相对密度、醇沉前液温度、醇沉终点乙醇体积分数、醇沉搅拌速度、加醇速度、静置温度、静置时间7个因素对醇沉工艺的影响趋势,同时通过方差分析确定影响醇沉工艺的关键因素。再采用Box-Behnken响应面法对关键因素的参数范围进行进一步的研究与探讨。结果单因素试验结合Box-Behnken响应面法研究得到金青醇沉的最佳工艺参数:搅拌速度为550 r/min、加醇体积流量为4.0 m L/s、醇沉终点乙醇体积分数75%、静置温度30℃、静置时间24 h、醇沉前液相对密度1.10 g/m L(25℃)、醇沉前液温度25℃,在此条件下新绿原酸、绿原酸、隐绿原酸、咖啡酸、断氧化马钱子苷转移率分别为94.8%、97.6%、97.4%、97.2%、96.1%,醇沉液中固含量为4.2%。结论采用响应面法优化了热毒宁注射液金青的醇沉工艺,有助于进一步提升金青醇沉工艺的稳定性。