地鳖纤溶蛋白口服时间/pH依赖结肠靶向微囊的开发及评价＊

地鳖中的纤溶活性蛋白是从地鳖中提取的具有抗栓及抗肿瘤作用的有效成分，其口服易被上消化道酶分解从而限制了应用。采用恒流泵滴制法开发地鳖纤溶活性蛋白时间/pH依赖口服结肠靶向微囊（EnpolypHaga fibrinolytic protein oral colon targeting microcapsules， CTM-EFP）。采用单因素实验和正交实验相结合的方法寻找到包封率为60.17 % ± 2.72 %、载药量为15.50 % ± 0.44 % 的最佳配方。扫描电子显微镜（SEM）显示微囊呈球形、表面光滑，在人工肠液中24 h的累积释放度为99.53 % ± 0.69 %，在人工胃液中24 h累积释放度为7.43 ± 1.04 %，通过时间/pH依赖达到结肠靶向作用。CTM-EFP在人工肠液中的体外释放曲线符合Korsmeyer方程，提示地鳖纤溶活性蛋白（EnpolypHaga fibrinolytic protein， EFP）是通过扩散和侵蚀机制结合释放的。CTM-EFP为EFP的口服给药提供了一种新的剂型，为EFP应用于临床提供参考。     

Multivariate optimization of mebeverine analysis using molecularly imprinted polymer electrochemical sensor based on silver nanoparticles

Thin film of a moleculary imprinted polymer (MIP) based on electropolymerization method with sensitive and selective binding sites for mebeverine (MEB) was developed. This film was cast on pencil graphite electrode (PGE) by electrochemical polymerization in solution of pyrrole (PY) and template MEB via cyclic voltammetry scans and further electrodeposition of silver nanoparticles (AgNPs). Several parameters controlling the performance of the silver nano particles MIP pencil graphite electrode (AgNPs-MIP-PGE) including concentration of PY(mM) concentration of mebeverine (mM), number of cycles in electropolymerization, scan rate of CV process (mV. s^?1), deposition time of AgNPs on to the MIP surface (s), stirring rate of loading solution (rpm), electrode loading time (min), pH of Britton–Robinson Buffer (BRB) solution were examined and optimized using multivariate optimization methods such as Plackett–Burman design (PBD) and central composite design (CCD). Two dynamic linear ranges of concentration for the MIP sensor were obtained as. 1 × 10 ^?8 to 1 × 10 ^?6 and 1 × 10 ^?5 to1 × 10^?3 M with the limit of detection (LOD) of 8.6 × 10 ^?9M (S/N = 3). The proposed method was successfully intended for the determination of MEB in real samples (serum, capsule). The sensor was showed highly reproducible response (RSD 1.1%) to MEB concentration.     

The compromise of virtual screening and its impact on drug discovery

Introduction: Docking and structure-based virtual screening (VS) have been standard approaches in structure-based design for over two decades. However, our understanding of the limitations, potential, and strength of these techniques has enhanced, raising expectations.

Areas covered: Based on a survey of reports in the past five years, we assess whether VS: (1) predicts binding poses in agreement with crystallographic data (when available); (2) is a superior screening tool, as often claimed; (3) is successful in identifying chemical scaffolds that can be starting points for subsequent lead optimization cycles. Data shows that knowledge of the target and its chemotypes in postprocessing lead to viable hits in early drug discovery endeavors.

Expert opinion: VS is capable of accurate placements in the pocket for the most part, but does not consistently score screening collections accurately. What matters is capitalization on available resources to get closer to a viable lead or optimizable series. Integration of approaches, subjective hit selection guided by knowledge of the receptor or endogenous ligand, libraries driven by experimental guides, validation studies to identify the best docking/scoring that reproduces experimental findings, constraints regarding receptor–ligand interactions, thoroughly designed methodologies, and predefined cutoff scoring criteria strengthen VS’s position in pharmaceutical research.     

中药渗漉提取工艺研究进展

渗漉法是将经过处理的药材粉末置于渗漉器中,不断加入溶剂,并收集渗漉液的一种中药常用提取方法,具有设备简单,操作容易,适用药材范围广,能有效提取热不稳定成分或组分等优点,但也存在溶剂消耗量大,提取耗时长,后续浓缩工艺能耗大等不足。该文主要综述了中药渗漉常见设备类型、工艺影响因素、参数优化方法以及过程监测方面的研究进展。分析文献后认为粉末粒度、溶剂组成、浸渍时间、渗漉流速、溶剂用量是渗漉工艺的重要影响因素。目前在渗漉工艺在线监测时采用近红外光谱技术较多,偏最小二乘法是常用的定量建模方法。笔者认为借鉴"质量源于设计"理念进行工艺控制,深入探究渗漉工艺机制并研发工艺控制方法是今后的发展趋势,所以应该深入探索过程建模技术,完善过程优化技术,研发过程监测技术。构建渗漉过程模型时可考虑借鉴柱色谱工艺的机制模型和经验模型。优化渗漉工艺参数时应考虑药材品质变化的影响,也需要研发更加简便易用的方法以监测渗漉过程状态和渗漉液关键性质。     

基于动态优化算法的复杂生物网络的状态调控

近年研究表明,某些药物能改变基因调控网络(GRNs)中的调控反应参数,促使细胞从病变状态转移到正常状态。在此基础上,有学者构建了基于吸引子和分岔理论的状态调控框架。现有的控制策略中,控制信号规律都是自行拟定的,并且所使用的参数扰动法仅能求出单控制变量情况下状态转移所需的时间。因此,针对以非线性常微分方程组(ODEs)形式描述的复杂生物网络,本文提出了一种基于动态优化算法改变网络状态的最优调控方法,在掌握生物网络基本特性的基础上建立了动态优化问题,并以简单低维的三节点GRN和复杂高维的癌症GRN为例,利用MATLAB计算得到单控制变量及多控制变量条件下的最优控制策略。本文所提方法旨在实现精确且快速的状态调控,为试验研究和实际治疗提供参考依据。     

青霉素杂质谱分析方法的优化与转换

目的建立青霉素杂质谱HPLC分析方法,并将其转换成UPLC/UHPLC方法。方法以青霉素混合降解溶液为样品;首先分析《中国药典》(2010年版,ChP2010)方法甲醇-缓冲盐二元流动相色谱系统的缺陷;再利用实验设计理念,以响应曲面法(response surface methodology,RSM)的中心组合设计(central composition design,CCD)对色谱系统进行优化,满意度函数法确定最优色谱条件,并优化梯度洗脱条件;最后,利用软件对HPLC方法的流速、进样体积和梯度时间进行几何缩放,并通过色谱柱的选择,将其分别转换为UPLC方法和UHPLC方法。结果新HPLC方法:色谱柱为Capcell Pak C18 MGII(4.6mm×250mm,5μm),流速:1.0m L/min,进样体积:20μL;UPLC方法:色谱柱为Cortecs C18(2.1mm×100mm,1.6μm),流速:0.35m L/min,进样体积:2.0μL;UHPLC方法:Cortecs C18(4.6mm×150mm,2.76μm),流速:0.8mL/min,进样体积:10μL。3种方法的检测波长均为225nm,柱温均为34℃;流动相A均为磷酸盐缓冲液(取磷酸二氢钾10.6g,加水至1000mL,用磷酸调pH至3.4)-甲醇(72:14,V/V),流动相B均为乙腈;均为梯度洗脱,但梯度洗脱表不同。结论 3个色谱系统的分离效果(出峰顺序和个数)相似。新HPLC方法可以分离出更多的降解杂质,并明显改善了青霉素峰的拖尾,缩短了分析时间。     

The Association between Reasons for a Rapid Response Team Alert and Immediate Patient Management in Total Hip Arthroplasty Patients

BackgroundThe purpose of this study is to evaluate the value and efficacy of rapid response teams (RRTs) for different triggering events in total hip arthroplasty (THA) patients.MethodsA retrospective review of all RRT events at a single, tertiary referral center from 2014 to 2016 was performed. Inclusion criteria were defined as patients >18 years old that underwent primary or revision THA. Information queried included demographics, primary reason for RRT, Charlson Comorbidity Index (CCI), underlying etiology, whether any changes in management occurred, and whether the patient was uptriaged.ResultsIn total, 168 RRTs were called on 153 hip arthroplasty patients (mean age 65.2 ± 14.1 years; mean body mass index 32.3 ± 4.8, 66% female). Length of stay in RRT for primary and revision THA was 3.4 and 6.2 days, respectively. This was significantly longer than the length of stay for primary THA patients (2.4 days, P < .001) and revision THA patients (4.6 days, P = .005) that did not require an RRT. There were no mortalities. RRTs for hypotension/presyncope (11%) and for syncope (11%) resulted in significantly fewer changes in management (P < .01) than tachycardia (77%), hypoxia (57%), AMS (79%), and other (47%). RRTs for hypotension/presyncope (28%), syncope (15%), and hypoxia (30%) resulted in significantly fewer patients being uptriaged (P < .001) than tachycardia (81%). Hypotension/presyncope was found to be significantly more commonly due to volume depletion (67%) (P < .001) than other etiologies. Hypoxia was significantly more commonly due to atelectasis (57%) and opioids/oversedation (30.4%) (P = .037). AMS/delirium was also significantly more commonly caused by opioids/over-sedation (71%) (P < .001).ConclusionIn patients undergoing THA, RRTs for hypotension/presyncopal symptoms and syncope were significantly less likely to result in changes in management or uptriaging compared to tachycardia. The most common etiologies were potentially preventable, including volume depletion and opioid use.     

基于二维码的电子诊疗卡系统的设计

目的构建一个以二维码作为电子诊疗卡替代医院传统诊疗卡的系统。方法依托医院微医疗平台,对患者唯一标识和时间戳进行MD5计算生成字符串,并以此内容生成二维码作为电子诊疗卡,同时对HIS进行相应改造,实现电子诊疗卡在全院的应用。结果利用时间戳和MD5签名生成二维码保证了电子诊疗卡加密的唯一性、时效性,医院每年节约成本5万元,患者每次就诊时间减少5 min,提升了患者满意度。结论本文构建的二维码电子诊疗卡系统,解决了使用实体诊疗卡过程中经常出现的忘带卡和重复办卡等问题,提高了医院服务质量,改善了患者就医体验。     

Assessing sialic acid content in food by hydrophilic chromatography-high performance liquid chromatography

We have established a novel hydrophilic chromatography (HILIC)-high performance liquid chromatography (HPLC) method to assess sialic acid content in food products. Single-factor and response surface methodologies (RSM) were used to systematically optimize the hydrolysis conditions of the food samples to extract the maximum amount of sialic acid. Chromatographic conditions were also adjusted. In foods containing sialic acid, we observed a strong linear relationship between sialic acid and peak area, ranging from 5 to 100 μg/mL (R² = 0.9998). The lowest detectable sialic acid concentration (RSN = 3) was 0.2 μg mL⁻¹, and the method detection limit was 0.02mg kg⁻¹. Sample recovery ranged from 95.85% to 99.78%, with an RSD of 1.46% (n = 6). Thus, the described method can be applied to the study of sialic acid content in foods.