Medición automática de la zona avascular foveal de ojos sanos en angiografía por tomografía de coherencia óptica de dominio espectral Heidelberg

PurposeTo develop and evaluate an automated method to measure the foveal avascular zone (FAZ) area in healthy eyes on Heidelberg Spectralis Optical Coherence Tomography Angiography (HS-OCTA). This method is referred to as the modified Kanno-Saitama macro (mKSM) which is an evolution of the Kanno-Saitama macro (KSM) approach.MethodsThis cross-sectional study included 29 eyes of 25 healthy volunteers who underwent HS-OCTA at the macular area twice at the same time. Regardless of the quality of the images, all of them were included. Macular data on the superficial vascular plexus, intermediate capillary plexus (ICP) and deep capillary plexus were processed by mKSM. The FAZ area was measured twice automatically using the mKSM and KSM and twice manually by two independent examiners.ResultsFrom 174 images, KSM could not measure correctly 31% while mKSM could successfully measure all of them. Intrascan intraclass coefficient ranged from 0.948 to 0.993 for manual measurements and was 1 for mKSM method. Despite that the difference between human examiners is smaller than between human examiners and mKSM according to Bland-Altman plots, the scatterplots show a strong correlation between human and automatic measurements. The best results are obtained in ICP.ConclusionsWith mKSM, the automated determination of the FAZ area in HS-OCTA is feasible and less human-dependent. It solves the inability of KSM to measure the FAZ area in suboptimal quality images which are frequent in daily clinical practice. Therefore, the mKSM processing could contribute to our understanding of the three vascular plexuses.     

The usefulness of measuring n-butyric acid concentration as a new indicator of blood decomposition in forensic autopsy

In forensic medicine, although various alcohols have been reported as indicators of decomposition in collected blood, no studies have examined short-chain fatty acids as indicators. In this study, the blood n-butyric acid concentration was quantified, and the association between n-butyric acid and decomposition was investigated to determine whether the detection of n-butyric acid could be a new indicator of decomposition. Among the forensic autopsies performed from 2016 to 2018 in our laboratory, the cases were divided into decomposed (n = 20) and non-decomposed (n = 20) groups based on macroscopic findings. Blood samples collected at the time of autopsy were derivatized with 3-nitrophenylhydrazine hydrochloride after solid-phase extraction. The n-butyric acid concentration was measured using liquid chromatography–tandem mass spectrometry. In addition, ethanol and n-propanol were measured using a gas chromatography-flame ionization detector. There was a significant difference (p < 0.01) in the concentrations of n-butyric acid between the decomposed and non-decomposed groups (0.343 ± 0.259 [0.030–0.973] and 0.003 ± 0.002 [0.001–0.007] mg/mL, respectively). In the decomposed group, n-butyric acid was detected at high concentrations, even in cases where n-propanol was low. These results suggest that n-butyric acid is more likely to be an indicator of blood decomposition than n-propanol.     

黄连解毒汤对重度颅脑损伤合并肺部感染患者血气指标和炎症因子影响分析

目的:观察黄连解毒汤对重度颅脑损伤合并肺部感染患者血气指标和炎症因子的影响,探讨其治疗效果。方法:随机抽签方式将77例重度颅脑损伤合并肺部感染患者分为两组。对照组35例接受常规治疗,研究组42例在常规治疗基础上,联合黄连解毒汤直肠灌注及全身擦浴治疗。评估两组临床效果,记录两组呼吸机使用时间、ICU入住时间及治疗费用,测定两组治疗前后血气指标和炎症因子。结果:两组临床治疗效果间差异无统计学意义(P>0.05)。与对照组比,研究组呼吸机使用时间和ICU入住时间明显缩短,ICU治疗费用显著减少(P<0.01)。治疗后两组SaO、PaO₂水平明显上升,PaCO₂及血清PCT、IL-1β、HMGB-1、CRP水平明显下降(P<0.05)。组间比较,研究组SaO、PaO₂水平高于对照组,PaCO₂及血清PCT、IL-1β、HMGB-1、CRP水平低于对照组(P<0.05)。结论:黄连解毒汤直肠灌注联合全身擦浴可明显控制重度颅脑损伤合并肺部感染患者感染病症,改善血气指标,调节炎症反应,缩短呼吸机使用时间和ICU入住时间,减少患者的治疗费用。     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

薄层色谱法在当前中药质量标准中的应用探讨

薄层色谱鉴别在历版《中国药典》中的应用经历了从无到有、从少到多的过程；而薄层扫描含量测定在最近几版《中国药典》中的应用比例逐渐降低。随着对中药质量标准体系要求的进一步提高，薄层色谱法的不足之处陆续显现，如仪器普及率低、设备并不简单、结果重复性和稳定性较差、鉴别速度及准确性不及高效液相色谱法、展开剂毒性大等，逐渐不合时宜。在制定中药质量标准时，研究者不应该墨守成规，薄层色谱鉴别也不应该是雷打不动的定性鉴别必备选项。高效液相色谱法具备完全取代薄层色谱法的可行性，薄层色谱法可作为高效液相色谱法的补充。为充分降低检测成本、缩短检测周期、提高鉴别效率，笔者建议中药质量标准体系应该大幅减少薄层色谱鉴别方法的应用，增加高效液相特征图谱鉴定，尽量做到“一个条件，一张图谱”；除非确有必要，《中国药典》等国家质量标准体系应将薄层色谱鉴别作为推荐方法，而非强制标准。     

基于化学模式识别技术提升参威骨痹片的质量标准并监测其生产中质控指标的转移率变化

目的:提升参威骨痹片的质量标准,初步探索其质量控制指标成分在批间含量差异较大的原因。方法:采用HPLC建立参威骨痹片的指纹图谱,以Diamonsil C18(4. 6 mm×250 mm,5μm)为色谱柱,流动相乙腈(A)-0. 1%磷酸水溶液(B)梯度洗脱(0～5 min,10%A;5～15 min,10%～12%A;15～30 min,12%～26%A;30～43 min,26%～31%A,43～50 min,31%～40%A,50～70 min,40%～55%A;70～84 min,55%～72. 5%A),检测波长230 nm。以共有峰为自变量绘制正交偏最小二乘法-判别分析-变量重要性投影(OPLS-DA-VIP)图,将共有峰对该制剂各批次间指纹图谱差异的贡献度量化,寻找差异较大的色谱峰,结合相关文献,筛选出与参威骨痹片临床适应症相关的成分并进行其含量测定的专属性试验,最终选定质控指标。通过HPLC-二极管阵列检测器(DAD)同时对本品及其生产过程中间体中质控指标进行测定,检测波长236,276,230,322 nm,其他条件同HPLC指纹图谱检测方法。结果:HPLC指纹图谱共标定了26个共有峰,各批次样品指纹图谱与对照指纹图谱的相似度均≥0. 950。优选出马钱苷酸、龙胆苦苷、芍药苷、蛇床子素为参威骨痹片的质控指标,四者的平均质量分数分别为161. 02,401. 80,255. 54,80. 68μg·g-1。结论:所建立的指纹图谱及多指标定量分析方法稳定、可靠,可用于参威骨痹片的质量控制。原料药批间质控指标成分含量差异和生产过程中间体的质控方法不够完善是引起该制剂批间质控指标成分含量差异较大的主要原因。     

鼻塞式同步间歇正压通气(NIPPV)联合布地奈德雾化治疗新生儿急性呼吸窘迫综合征疾病的临床应用研究

目的:分析鼻塞式同步间歇正压通气(NIPPV)联合布地奈德雾化治疗ARDS(新生儿急性呼吸窘迫综合征)疾病的临床应用效果。方法:纳入病例是2017年5月—2019年11月收治的104例ARDS新生儿,随机平均分为两组。参照组52例采纳CPAP(持续气道正压通气通气)治疗,实验组52例采纳NIPPV+布地奈德雾化治疗,对比两组呼吸机通气时间、用氧时间、住院时间、血气指标以及并发症发生情况。结果:实验组呼吸机通气时间、用氧时间、住院时间均明显短于参照组,差异有统计学意义P<0.05;实验组治疗3 d后PaCO2明显低于参照组,实验组治疗3 d后PH以及PaO2明显高于参照组,差异有统计学意义P<0.05;实验组并发症发生率(3.85%,2/52)明显低于参照组(21.15%,11/52),差异有统计学意义P<0.05。结论:NIPPV+布地奈德雾化可有效缩短ARDS患者机械通气时间,改善血气指标,降低并发症发生率,值得借鉴。