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.     

Molecular profiling of ctDNA in pancreatic cancer: Opportunities and challenges for clinical application

Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related mortality within the next decade, with limited effective treatment options and a dismal long-term prognosis for patients. Genomic profiling has not yet manifested clinical benefits for diagnosis, treatment or prognosis in PDAC, due to the lack of available tissues for sequencing and the confounding effects of low tumour cellularity in many biopsy specimens. Increasing focus is now turning to the use of minimally invasive liquid biopsies to enhance the characterisation of actionable PDAC tumour genomes. Circulating tumour DNA (ctDNA) is the most comprehensively studied liquid biopsy analyte in blood and can provide insight into the molecular profile and biological characteristics of individual PDAC tumours, in real-time and in advance of traditional imaging modalities. This can pave the way for identification of new therapeutic targets, novel risk variants and markers of tumour response, to supplement diagnostic screening and provide enhanced scrutiny in treatment stratification. In the roadmap towards the application of precision medicine for clinical management in PDAC, ctDNA analyses may serve a leading role in streamlining candidate biomarkers for clinical integration. In this review, we highlight recent developments in the use of ctDNA-based liquid biopsies for PDAC and provide new insights into the technical, analytical and biological challenges that must be overcome for this potential to be realised.     

液体活检在结直肠癌诊断中的应用进展

结直肠癌(Colorectal cancer,CRC)作为全球第三大常见癌症,是导致人类死亡的重要原因之一。目前针对CRC的诊断手段仍在不断完善,液体活检作为一种新兴的无创活检组织检查技术,受到广泛关注。液体活检主要对生物源液体特定成分进行分析,其中主要包括循环肿瘤细胞、循环肿瘤DNA、细胞游离DNA、外泌体、肿瘤相关血小板及循环肿瘤相关微粒等。本文就以上生物源液体特定成分在CRC诊断中的最新应用研究进行综述。     

Method development of immunoglobulin G purification from micro-volumes of human serum for untargeted and targeted proteomics-based antibody repertoire studies

Immunoglobulins (Igs) are major serum proteins which play important roles in immunity. Both untargeted and targeted proteomic workflows can be applied to investigate antigen-binding sites and the glycosylation profiles of Igs. For a more-comprehensive picture of IgG from human serum, we developed an IgG purification process and coupled the standardized method to untargeted and targeted proteomic workflows for IgG investigations. Parameters such as the type of purification beads, volume of the bead slurry, incubation conditions, and binding capacities were evaluated in this study. Only 2 μL of human serum was required for each sample. The performance of coupling the purification process to untargeted proteomics in the IgG analysis was evaluated by comparing normalized abundances of IgG subclass-specific peptides with quantification results from an ELISA. Pearson's correlation values were all >0.82. Targeted proteomic workflow was applied to serum samples from patients with autoimmune pancreatitis and from healthy controls, and the results corresponded to clinical findings that IgG4-related peptides/glycopeptides showed higher abundances in the diseased group. The developed IgG purification process is simple and requires small sample volume, and it can be coupled to targeted and untargeted proteomic workflows for clinical investigations in the future.     

Dynamics of lipid adsorption at the electrified water∣1,2-dichloroethane interface

A recently introduced setup to measure the dynamic interfacial tension of expanding drops was used to compare the adsorption behaviour of a series of lipids at the electrified water∣dichloroethane interface. Phospholipids with saturated carbon chains of different length (DMPC, DPPC, DSPC, DAPC, DBPC), an unsaturated phospholipid (DOPC) and an ethanolamine (DSPE) were compared. It was found that the adsorption decreases with increasing chain length. Also, the increase of the flow rate reduces the degree of adsorption effectively. On the timescale of the experiments, the DSPE, DAPC and DBPC adsorption showed no potential dependence, whereas the adsorption of DOPC was stronger than that of the saturated lipids. Adsorption was modelled using the Langmuir adsorption isotherm; the potential dependence of adsorption is discussed.     

保肾口服液影响IgA肾病小鼠T细胞增殖及分泌IL-2的实验研究

观察保肾口服液对IgA肾病小鼠T细胞^3H-TdR掺入及其分泌IL-2水平的影响，结果表明低、中、高3种浓度的保肾口服液均能显著促进IgA肾病小鼠的自发性和ConA刺激的T细胞^3H-TdR掺入，促进T细胞合成，分泌IL-2，提前给药作用相同。提示保肾口服液有显著增强IgA肾病小鼠细胞免疫功能的作用。     

Radium-228 determination of natural waters via concentration on manganese dioxide and separation using Diphonix ion exchange resin

The objective of this work was to establish a new procedure for ²²⁸Ra determination of natural waters via preconcentration of radium on MnO₂ and separation of its daughter, ²²⁸Ac, using Diphonix ion exchange resin. Following removal of potential interferences via passage through an initial Diphonix Resin column, the first daughter of ²²⁸Ra, ²²⁸Ac, is isolated by chromatographic separation via a second Diphonix column. A holding time of >30 h for ²²⁸Ac ingrowth in between the two column separations ensures secular equilibrium. Barium-133 is used as a yield tracer. Actinium-228 is eluted from the second Diphonix Resin with 5 ml 1 M 1-Hydroxyethane-1,1-diphosphonic acid (HEDPA) and quantified by addition of scintillation cocktail and LSC counting. Radium (and ¹³³Ba) from the load and rinse solutions from the 2nd Diphonix column may be prepared for alpha spectrometry (for determination of ²²³Ra, ²²⁴Ra, and ²²⁶Ra) by BaSO₄ microprecipitation and filtration. Decontamination tests indicate that U, Th, and Ra series nuclides do not interfere with these measurements, although high contents of ⁹⁰Sr (⁹⁰Y) require additional treatment for accurate measurement of ²²⁸Ra. Addition of stable Sr as a “hold back” carrier during the initial MnO₂ preconcentration step was shown to remove most ⁹⁰Sr interference.     

Double layer capacitance and a microscopic structure of electrified liquid–liquid interfaces

We develop a theory of the double layer at electrolyte–electrolyte interfaces taking in to account the microscopic structure of the interfacial region. This includes a “mixed boundary layer” where the overlapping of two space-charge regions occurs, and the effects of ion association and adsorption at the interface. Theoretical results are in good agreement with experimental data obtained for various organic solvents and electrolytes. The theory suggests a framework for the treatment of the capacitance data and establishes a relationship between experimental results and the microscopic structure of interfaces between two immiscible electrolyte solutions (ITIES).     

自制与进口氯化十六烷基吡啶抑菌作用的比较研究

以液体稀释法比较了自制与进口十六烷基吡啶作用于4种口腔常见微生物的最低抑菌浓度和最低杀菌浓度的实验结果,经t检验证明两者间无显著差异,提示自制氯化十六烷基吡啶的药效质量可靠。并就控制接种菌量及杀菌机理等问题作了初步探讨。