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.     

Magnetron Sputtered CsPbCl3 Perovskite Detectors as Real-Time Dosimeters for Clinical Radiotherapy

The aim of this study is to investigate the feasibility of manufacturing thin real-time relative dosimeters for clinical radiotherapy (RT) with potential applications for transmission monitoring in vivo dosimetry and pre-treatment dose verifications. Thin (≈1 μm) layers of a high sensitivity, wide bandgap semiconductor, the inorganic perovskite CsPbCl₃, have been grown for the first time by magnetron sputtering on plastic substrates equipped with electrode arrays. Prototype devices have been tested in real-time configuration to evaluate the dose delivered by a 6 MV photon beam from a linear accelerator. Linearity of the charge with the dose has been verified over three order of magnitudes, linearity of the current signal with the dose rate has been also successfully tested in the range 0.5-4.3 Gy/min. The combination of high sensitivity per unit volume and wide bandgap provides high signal-to-noise ratios, up to 70, even at moderate applied voltages. The Schottky diode configuration allows the detector to operate without bias voltage (null bias).The blocking-barrier structure allows to confine the active volume within sub-millimetric sizes, a quite attractive feature in view to increase granularity and achieve the high spatial resolutions required in modern RT techniques. All the above-mentioned features indeed pave the way to a novel generation of flexible, transmission, real time dosimeters for clinical radiotherapy.     

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。     

Visumax飞秒激光辅助制瓣LASIK术中不透明气泡层及相关因素

目的：研究Visumax飞秒激光辅助的准分子激光原位角膜磨镶术（LASIK）术中不透明气泡层（OBL）产生的类型、相关影响因素及其临床意义。方法：回顾性分析。收集2016 年7 月1 日至8 月20 日在南京医科大学附属眼科医院行飞秒LASIK的患者154 例（300 眼）的临床资料，等效球镜度为（-5.88±1.51）D。飞秒激光采用Zeiss公司 Visumax飞秒激光仪，将术中产生的OBL分为瓣外OBL、瓣内快速OBL和瓣内慢速OBL。300 眼按角膜曲率平均K值分为A组（<42 D）、B组（42～46 D）和C组（>46 D）；按角膜瓣的厚度分为D组（100 μm）、E组（110 μm）和F组（120 μm）；按角膜厚度分为G组（<500 μm）、H组（500～540 μm）和I组（>540 μm）。统计不同角膜曲率、角膜瓣厚度、角膜厚度情况下3 种OBL产生的比例，并采用多元Logistic回归模型进行统计分析。结果：300 眼均发生OBL。以瓣外OBL作为参照，角膜瓣越薄，越容易出现瓣内快速OBL（r=-0.719，P=0.034）和瓣内慢速OBL（r=-0.875，P=0.044）。以瓣内慢速OBL作为参照，角膜曲率越高，越容易出现瓣内快速OBL（r=0.923，P=0.046）；角膜瓣越厚，越容易出现瓣外OBL（r=0.897，P=0.044）。结论：OBL的产生与角膜曲率、角膜瓣厚度、角膜厚度均存在一定的相关性，但瓣外OBL、瓣内快速OBL和瓣内慢速OBL对Visumax飞秒激光辅助的LASIK术后视觉质量的影响及远期疗效仍有待进一步观察研究。     

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.