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Application of anatomical and histological features of testis to age estimation 睾丸解剖组织学特征在年龄估计中的应用

IF 1.4 4区医学 Q3 MEDICINE, LEGAL

Legal Medicine

Pub Date : 2025-12-24 DOI: 10.1016/j.legalmed.2025.102767

Takato Murai , Masaki Inoue , Kenichi Mukaisho , Mami Nakamura , Kazuki Takaoka , Masahito Hitosugi

In forensic practice, when parts of an unidentified human body are found, age estimation with limited materials is required. This study investigated age-related anatomical and histological changes in testes to evaluate their applicability for forensic age estimation. Testicular samples from 228 male autopsy cases (aged 0–96 years) were analyzed. The Johnsen score, testicular weight, basement membrane thickness, number of seminiferous tubules per field, and percentage of hyalinized tubules were examined. Basement membrane thickness showed a strong positive correlation with age across all subjects (r = 0.733). In individuals under 20 years, testicular weight was positively correlated with age (r = 0.89), while the number of seminiferous tubules negatively correlated (r = − 0.90). In those aged ≥ 20 years, Johnsen score, testicular weight, and hyalinization rate showed significant age-related differences between groups. Receiver operating characteristic curve analysis identified cutoff values for age discrimination: hyalinization rate of ≥ 9.0 % for ≥ 60 years (sensitivity 69.7 %, specificity 89.5 %), and testicular weight of ≤ 10.1 g for ≥ 80 years (sensitivity 85.7 %, specificity 73.3 %). Basement membrane thickness, testicular weight, and seminiferous tubule count are useful indicators for forensic age estimation under 20 years of age; on the other hand, basement membrane thickness, testicular weight, and hyalinization rate are more informative in individuals aged ≥ 20 years. These findings suggest the potential contribution of these indicators to forensic age estimation, while further studies are needed to validate their practical applicability.

在法医实践中，当发现身份不明的人体部分时，需要用有限的材料估计年龄。本研究调查了与年龄相关的睾丸解剖和组织学变化，以评估其在法医年龄估计中的适用性。本文分析了228例男性尸检病例（年龄0 ~ 96岁）的睾丸样本。检查约翰森评分、睾丸重量、基底膜厚度、每野精小管数量和玻璃化小管百分比。基底膜厚度与年龄呈显著正相关（r = 0.733）。在20岁以下的个体中，睾丸重量与年龄呈正相关（r = 0.89），精管数量与年龄呈负相关（r = - 0.90）。在年龄≥20岁的患者中，Johnsen评分、睾丸重量和透明化率在组间存在显著的年龄相关差异。受试者工作特征曲线分析确定了年龄歧视的临界值：≥60岁时透明化率≥9.0%（敏感性69.7%，特异性89.5%），≥80岁时睾丸重量≤10.1 g（敏感性85.7%，特异性73.3%）。基底膜厚度、睾丸重量和精管计数是20岁以下法医年龄估计的有用指标；另一方面，基底膜厚度、睾丸重量和透明化率在年龄≥20岁的个体中更有价值。这些发现表明这些指标对法医年龄估计的潜在贡献，但需要进一步研究来验证其实际适用性。

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引用次数: 0

The stability of novel synthetic cannabinoids in blood samples in different storage conditions 新型合成大麻素在血液样品中不同贮存条件下的稳定性

IF 1.4 4区医学 Q3 MEDICINE, LEGAL

Legal Medicine

Pub Date : 2025-12-18 DOI: 10.1016/j.legalmed.2025.102762

Murat Akbaba , Oğuz Özdemir , Aysun Baransel Isır

The synthetic cannabinoids dominated the market with a detrimental effect on society. Determining the stability of synthetic cannabinoids (SCs) in samples is crucial for accurate detection and quantification in drug testing. Since designer narcotics emerge rather quickly, a new generation of cannabinoid-associated compounds also appears rapidly. Thus, it is crucial to identify, detect, and determine the confidence of drug testing to provide fairer judgments. In this study, we aimed to determine optimal storage conditions to prevent degradation and preserve the samples of four new-generation SCs (MDMB-4en-PINACA, 4-Fluoro MDMB-BICA, 5F-MDMB-PICA, and 5F-MDMB-PINACA) in blood samples due to the lack of available information on the stability. Blood samples were collected from 20 healthy volunteers, treated with cannabinoids at concentrations of 10 and 50 ng/mL, and stored at temperatures of room temperature, +4°C, and −20 °C over 35 days. Our findings revealed a gradual decline in cannabinoid concentrations over time, with 5F-MDMB-PINACA exhibiting the highest degradation rate. Storage temperature significantly influenced degradation rates, with the most rapid reduction observed at room temperature and the slowest degradation at −20 °C. Our findings are a reference study providing valuable insights into the preservation of the samples for the testing of the most prevalent SCs of the present day.

合成大麻素主导了市场，对社会产生了有害影响。确定样品中合成大麻素（SCs）的稳定性对于药物检测中的准确检测和定量至关重要。由于设计麻醉剂出现得相当快，新一代大麻素相关化合物也迅速出现。因此，识别、检测和确定药物检测的可信度，以提供更公平的判断是至关重要的。在本研究中，由于缺乏关于稳定性的可用信息，我们旨在确定最佳储存条件，以防止血液样品中四种新一代SCs （MDMB-4en-PINACA, 4-Fluoro MDMB-BICA， 5F-MDMB-PICA和5F-MDMB-PINACA）的降解和保存。收集20名健康志愿者的血液样本，用浓度为10和50 ng/mL的大麻素处理，并在室温、+4°C和- 20°C的温度下保存35天。我们的研究结果显示，随着时间的推移，大麻素浓度逐渐下降，5F-MDMB-PINACA的降解率最高。储存温度对降解率有显著影响，在室温下降解最快，在- 20℃时降解最慢。我们的研究结果是一项参考研究，为当今最普遍的sc测试的样品保存提供了有价值的见解。

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引用次数: 0

Artificial intelligence in healthcare: Proposal for a new medico-legal methodology in medical liability 医疗保健中的人工智能：医疗责任中新的医学-法律方法论的建议。

IF 1.4 4区医学 Q3 MEDICINE, LEGAL

Legal Medicine

Pub Date : 2025-12-11 DOI: 10.1016/j.legalmed.2025.102764

Rossana Cecchi , Francesco Calabrò , Jessika Camatti , Anna Laura Santunione , Michela Sperti , Eric Adriano Zizzi , Marco Agostino Deriu

The rapid integration of Artificial Intelligence (AI) into healthcare promises significant benefits but also raises unprecedented ethical, clinical, and legal challenges. Current medico-legal frameworks, primarily designed for human decision-making, are often inadequate to address liability issues arising from algorithmic errors or opaque “black box” models. This paper introduces a novel medico-legal methodology that combines proactive and reactive approaches to risk assessment, originally developed within European forensic medicine, and adapts it to the context of AI in healthcare. By systematically analyzing data collection, dataset validation, error identification, and causal reconstruction, the proposed framework provides a structured path for evaluating medical liability when AI systems are involved. This dual approach not only supports clinicians, developers, and policymakers in preventing harm, but also establishes a robust forensic tool for liability assessment. The methodology offers a step toward internationally applicable standards for addressing the medico-legal implications of AI in medicine.

人工智能（AI）与医疗保健的快速融合带来了巨大的好处，但也带来了前所未有的伦理、临床和法律挑战。目前的医疗法律框架主要是为人类决策而设计的，往往不足以解决由算法错误或不透明的“黑箱”模型引起的责任问题。本文介绍了一种新的医学法律方法，该方法结合了欧洲法医学中最初开发的主动和被动风险评估方法，并使其适应医疗保健中的人工智能背景。通过系统地分析数据收集、数据集验证、错误识别和因果重构，该框架为涉及人工智能系统时的医疗责任评估提供了结构化路径。这种双重方法不仅支持临床医生、开发人员和政策制定者预防伤害，而且还为责任评估建立了强大的法医工具。该方法为解决人工智能在医学中的医学法律影响的国际适用标准迈出了一步。

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引用次数: 0

Three deaths, one diagnosis: Forensic perspectives on giant ovarian tumors 三个死亡，一个诊断：巨大卵巢肿瘤的法医视角

IF 1.4 4区医学 Q3 MEDICINE, LEGAL

Legal Medicine

Pub Date : 2025-12-11 DOI: 10.1016/j.legalmed.2025.102765

Veljko Milošević, Bojana Radnić, Tijana Petrović, Milenko Bogdanović, Tatjana Atanasijević, Irina Banjanin

When ovarian tumors (OTs) reach a size of more than 10 cm in diameter, they are classified as a giant ovarian tumor (GOTs). Thanks to modern diagnostics and treatment, GOTs have become rare autopsy findings and are typically associated with cases of severe neglect. Here, we present a series of three autopsy cases involving GOTs. The first case involved a 59-year-old woman with a cystic GOT containing 48 L of fluid. The second case was a 67-year-old woman with multiple cystic and solid GOTs. The third case concerned a 57-year-old woman with a giant, primarily solid OT, accompanied by bilateral pleural effusion, suggestive of Meigs syndrome. All three women were found in a state of advanced putrefaction, which limited the ability to determine the exact cause of death. Although GOTs are rarely fatal, they can lead to death through various complex pathophysiological mechanisms. These include spontaneous haemorrhage, torsion, infection, and tumor rupture resulting in acute peritonitis – conditions that represent surgical emergencies. Additionally, increased intra-abdominal pressure can elevate the diaphragm, impairing the function of the respiratory, cardiovascular, digestive, and urinary systems. Despite the limitations posed by postmortem decomposition, this case series provides an opportunity to summarize and discuss potential mechanisms of death associated with large intra-abdominal masses such as GOTs.

当卵巢肿瘤（OTs）的直径超过10cm时，它们被归类为巨大卵巢肿瘤（GOTs）。由于现代诊断和治疗，got已成为罕见的尸检结果，通常与严重忽视的病例有关。在这里，我们提出了一系列涉及got的三个尸检病例。第一个病例涉及一名59岁的妇女，她患有囊肿性GOT，其中含有48升液体。第二个病例是一名67岁的女性，患有多发性囊性和实性got。第三例患者为一名57岁女性，伴有巨大实性OT，伴双侧胸腔积液，提示Meigs综合征。这三名妇女被发现时都处于严重腐烂状态，这限制了确定确切死因的能力。虽然got很少致死性，但其可通过多种复杂的病理生理机制导致死亡。这些包括自发性出血、扭转、感染和导致急性腹膜炎的肿瘤破裂——这些都是外科紧急情况。此外，腹内压升高可使横膈膜升高，损害呼吸、心血管、消化和泌尿系统的功能。尽管死后分解存在局限性，但本病例系列提供了一个总结和讨论与腹腔内大型肿块（如got）相关的潜在死亡机制的机会。

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引用次数: 0

Mechanism of postmortem drastic increase of blood myoglobin concentration: its permeability through vascular wall 死后血肌红蛋白浓度急剧升高的机制：其通过血管壁的渗透性

IF 1.4 4区医学 Q3 MEDICINE, LEGAL

Legal Medicine

Pub Date : 2025-12-11 DOI: 10.1016/j.legalmed.2025.102763

Sella Takei , Masanobu Miura , Takehiko Murase , Hiroshi Kinoshita , Satoru Miyaishi

We provide the first direct experimental evidence that myoglobin (Mb) diffuses through vascular walls and enters the blood after death. Postmortem Mb concentration in the blood increases rapidly; however, up to this date, no one has reported the responsible mechanism. We hypothesized the direct diffusion of Mb from skeletal muscle into the blood through the vessel wall is causing this concentration change, and proved this morphologically and biochemically, through experiments using animal samples. Firstly, IHC Mb staining of the artery which was directly contacted with skeletal muscle on the adventitia, revealed that the Mb diffuses from adventitia to the intima with time. Then, Mb quantification using ELISA showed Mb exudes through vascular walls into the vessel lumen. For this experiment, a diffusion model was established by sandwiching the artery between gelatin discs with or without Mb. The Mb concentration increased in a time-dependent manner, with approximately 16 % of Mb in its source exuding into the lumen within 5 days. This rate increased significantly when vein was used instead of aorta. These findings clarify a fundamental mechanism of postmortem biochemical redistribution and may enhance the reliability of interpreting postmortem blood protein levels in forensic practice.

我们提供了第一个直接的实验证据，证明肌红蛋白（Mb）在死亡后通过血管壁扩散并进入血液。死后血中Mb浓度迅速升高；然而，到目前为止，还没有人报告负责机制。我们假设Mb从骨骼肌通过血管壁直接扩散到血液中是导致这种浓度变化的原因，并通过动物样本的实验从形态学和生物化学上证明了这一点。首先，对外膜上与骨骼肌直接接触的动脉进行免疫组化Mb染色，发现Mb随时间从外膜向内膜扩散。酶联免疫吸附测定结果显示，Mb可通过血管壁进入血管腔。在本实验中，通过将动脉夹在含有或不含Mb的明胶盘之间建立扩散模型。Mb浓度随时间增加，其来源中约有16%的Mb在5天内渗出到管腔。当使用静脉而不是主动脉时，这一比率显著增加。这些发现阐明了死后生物化学再分配的基本机制，并可能提高法医实践中解释死后血液蛋白水平的可靠性。

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引用次数: 0

MARK4 as a novel biomarker of acute myocardial ischemia-induced sudden cardiac death MARK4作为急性心肌缺血心源性猝死的新生物标志物

IF 1.4 4区医学 Q3 MEDICINE, LEGAL

Legal Medicine

Pub Date : 2025-12-10 DOI: 10.1016/j.legalmed.2025.102766

Xing Ye , Guanghui Hong , Runting Dou , Zhimin Wang , Zijie Lin , Yu Shao , Jiajia Yang , Junyi Lin , Yiwen Shen

Postmortem diagnosis of acute myocardial ischemia (AMI), especially early myocardial ischemia (EMI; ischemic insults occurring within minutes to a few hours, <6h), remains challenging due to nonspecific morphological changes. Microtubules affinity regulated kinase 4 (MARK4) is a serine/threonine kinase involved in the regulation of microtubule dynamics through the phosphorylation of microtubule-associated proteins. Emerging research has highlighted the significant involvement of MARK4 in cardiovascular diseases. The aim of this study is to evaluate whether MARK4 can serve as a postmortem diagnostic marker for sudden cardiac death (SCD) resulting from AMI. Using a mouse AMI model, hypoxia-treated AC16 cardiomyocytes, and human autopsy material (36 SCD hearts: 18 EMI, 18 myocardial infarction (MI) and 20 noncardiac controls), MARK4 expression was assessed by immunohistochemistry and western blotting, and diagnostic performance was examined by receiver operating characteristic (ROC) analysis. MARK4 expression increased with ischemia/hypoxia in vivo and in vitro, peaking at 3 h. Human myocardial MARK4 was significantly elevated in EMI and MI versus controls, independently of age and postmortem interval. ROC analysis discriminated EMI from controls with an AUC of 0.8028 for MARK4, outperforming cardiac troponin I (cTnI; AUC = 0.7556), and combining both markers improved diagnostic accuracy. In hypoxic AC16 cells, MARK4 overexpression increased cytochrome c and phosphorylated Drp1, suggesting a role in ischemia-related mitochondrial dysfunction. These results indicate MARK4 is a promising postmortem biomarker for AMI-induced SCD.

急性心肌缺血（AMI）的死后诊断，特别是早期心肌缺血（EMI；在几分钟到几小时内发生的缺血损伤，<6h），由于非特异性形态学改变，仍然具有挑战性。微管亲和调节激酶4 （MARK4）是一种丝氨酸/苏氨酸激酶，通过微管相关蛋白的磷酸化参与微管动力学的调节。新兴研究强调了MARK4在心血管疾病中的重要作用。本研究的目的是评估MARK4是否可以作为AMI引起的心源性猝死（SCD）的死后诊断标志物。使用小鼠AMI模型、缺氧处理的AC16心肌细胞和人体尸检材料（36个SCD心脏：18个EMI， 18个心肌梗死（MI）和20个非心脏对照），通过免疫组织化学和western blotting评估MARK4表达，并通过受试者工作特征（ROC）分析检查诊断性能。MARK4的表达随体内和体外缺血/缺氧而增加，在3小时达到峰值。与对照组相比，EMI和MI患者心肌MARK4显著升高，与年龄和死后间隔无关。ROC分析将EMI与对照组区分开来，MARK4的AUC为0.8028，优于心肌肌钙蛋白I (cTnI; AUC = 0.7556)，结合这两种标志物可提高诊断准确性。在缺氧的AC16细胞中，MARK4过表达增加细胞色素c和磷酸化Drp1，提示在缺血相关的线粒体功能障碍中起作用。这些结果表明，MARK4是ami诱导的SCD的一个有希望的死后生物标志物。

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引用次数: 0

Microbial toxins in forensic science: detection, classification, and biosecurity implications − a comprehensive review 微生物毒素在法医科学：检测，分类和生物安全的影响-一个全面的审查

IF 1.4 4区医学 Q3 MEDICINE, LEGAL

Legal Medicine

Pub Date : 2025-12-02 DOI: 10.1016/j.legalmed.2025.102761

Gunashree B.S.

Microbial toxins pose a significant threat to forensics due to their potential use in bioterrorism, unintentional exposure to pathogens, and natural outbreaks. This comprehensive review examines existing information and techniques for identifying, characterizing, and studying microbial toxins as forensic evidence. A systematic search was conducted on peer-reviewed literature related to the forensic detection of microbial toxins, classification systems for toxins, and emerging analytical technologies. Major databases were extensively searched using keywords relevant to forensic microbiology, toxin detection, and biosecurity implementation. The three main groups of microbial toxins of particular forensic interest are staphylococcal enterotoxins, clostridial toxins, and mycotoxins. Current advanced detection technologies include surface-enhanced Raman spectroscopy, liquid chromatography-mass spectrometry, and next-generation sequencing, all offering greater sensitivity and specificity than previous methods. The CDC bioterrorism threat classification system is crucial for prioritizing threats and guiding responses. Forensic analysis of microbial toxins requires specialized analytical capabilities, rigorous quality assurance systems, and multidisciplinary expertise in microbiology, analytical chemistry, and threat assessment. Combining existing techniques with new technologies enhances both routine surveillance and emergency response capabilities.

微生物毒素可能用于生物恐怖主义、无意接触病原体以及自然暴发，因此对法医构成重大威胁。这篇全面的综述检查了现有的信息和技术，以识别、表征和研究作为法医证据的微生物毒素。系统检索了与微生物毒素法医检测、毒素分类系统和新兴分析技术相关的同行评审文献。使用与法医微生物学、毒素检测和生物安全实施相关的关键词对主要数据库进行了广泛的搜索。法医特别感兴趣的三大类微生物毒素是葡萄球菌肠毒素、梭状芽孢杆菌毒素和真菌毒素。目前先进的检测技术包括表面增强拉曼光谱、液相色谱-质谱和下一代测序，它们都比以前的方法具有更高的灵敏度和特异性。疾病预防控制中心的生物恐怖主义威胁分类系统对于确定威胁的优先次序和指导应对措施至关重要。微生物毒素的法医分析需要专门的分析能力，严格的质量保证体系，以及微生物学、分析化学和威胁评估方面的多学科专业知识。将现有技术与新技术相结合，可增强日常监测和应急响应能力。

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引用次数: 0

An autopsy case of sudden infant death caused by cardiac fibroma 心脏纤维瘤致婴儿猝死尸检一例。

IF 1.4 4区医学 Q3 MEDICINE, LEGAL

Legal Medicine

Pub Date : 2025-11-23 DOI: 10.1016/j.legalmed.2025.102760

Wataru Irie, Fumiko Satoh, Chizuko Sasaki, Eriko Ochiai, Maho Kondo, Satoshi Kamogawa, Yoshiya Saito

A one-month-old girl in good health being carried by her mother in a baby carrier suddenly went into cardiac arrest. She was rushed to the hospital, but was pronounced dead. A forensic autopsy was performed. On the heart, which weighed 63.6 g, a single large, well-defined, round, white tumor was observed in the left ventricular wall. Tumor cells with spindle-shaped small nuclei proliferated along with collagen fiber proliferation. The diagnosis was cardiac fibroma. The tumor had compressed the left bundle branch, causing fatal arrhythmia and death. This case report describes sudden infant death caused by a primary cardiac fibroma, diagnosed postmortem.

一个健康的一个月大的女婴被妈妈用婴儿背带抱着，突然心脏骤停。她被紧急送往医院，但被宣布死亡。进行了法医尸检。在重63.6 g的心脏上，左心室壁可见一单一的大的、界限分明的圆形白色肿瘤。肿瘤细胞呈梭形小核增生，胶原纤维增生。诊断为心脏纤维瘤。肿瘤压迫左束支，导致致命的心律失常和死亡。本病例报告描述了由死后诊断的原发性心脏纤维瘤引起的婴儿猝死。

引用次数: 0

Design of a 200-SNP panel for individual identification and evaluation of genotyping performance using isolated cells 设计200-SNP面板，用于分离细胞的个体鉴定和基因分型性能评估

IF 1.4 4区医学 Q3 MEDICINE, LEGAL

Legal Medicine

Pub Date : 2025-11-20 DOI: 10.1016/j.legalmed.2025.102759

Ryo Namba , Masaru Asari , Yuta Takahashi , Chisato Hoshina , Kanae Mori , Katsuhiro Okuda , Keiko Shimizu

We developed a novel next-generation sequencing-based genotyping panel for 200 single nucleotide polymorphism (SNP) loci, and evaluated the genotyping performance when using small amounts of DNA. We analyzed 1144 previously characterized autosomal SNPs, and selected 200 informative SNPs, based on the allele coverage ratio (ACR) and amplicon size, to minimize inter-locus depth of coverage imbalances. Analysis of the 200 SNPs was performed using 1 ng of DNA from 66 Japanese individuals. The average ACR of most of the SNP loci ranged from 0.85 to 0.95. We also detected 200-SNP genotypes using diluted DNA samples (500, 250, 125, 60, 30, and 15 pg/reaction), and found high ACRs and concordance from less than 100 pg of DNA: the concordances were as high as 95.7 % and 88.0 %, respectively, when 60 and 30 pg of DNA were used. Our method also showed higher inhibitory tolerance than other methods when humic acid was added to the initial amplification reaction for SNP genotyping. When genotyping in the presence of 10 ng/µL humic acid, no SNP profiles were detected, but profiles with more than 99 % concordance were recovered on addition of bovine serum albumin. The genotyping performance was also evaluated using small groups of cells (10, 5, 4, 3, and 2 cells/reaction) isolated by micromanipulation with micro-tweezers. High concordance was identified on analysis of three cells (96.1 %). The use of isolated cells allowed accurate determination of the sensitivity, indicating that our method is highly sensitive and can provide informative SNP profiles for individual identification.

我们开发了一种新的基于200个单核苷酸多态性（SNP）位点的新一代测序基因分型面板，并评估了使用少量DNA时的基因分型性能。我们分析了1144个以前表征的常染色体snp，并根据等位基因覆盖比（ACR）和扩增子大小选择了200个信息性snp，以最小化基因座间覆盖不平衡的深度。使用来自66名日本人的1ng DNA对200个snp进行了分析。大部分SNP位点的平均ACR在0.85 ~ 0.95之间。我们还使用稀释后的DNA样本（500、250、125、60、30和15 pg/reaction）检测了200-SNP基因型，并在小于100 pg的DNA中发现了高acr和一致性：当使用60和30 pg的DNA时，一致性分别高达95.7%和88.0%。在初始扩增反应中加入腐植酸进行SNP基因分型时，我们的方法也比其他方法表现出更高的抑制耐受性。当在10 ng/µL腐植酸存在下进行基因分型时，没有检测到SNP谱，但在添加牛血清白蛋白后恢复了一致性超过99%的谱。用微镊子对分离的小组细胞（10、5、4、3和2个细胞/反应）进行基因分型评估。3个细胞（96.1%）具有高度的一致性。使用分离细胞可以准确测定灵敏度，表明我们的方法高度敏感，可以为个体鉴定提供信息丰富的SNP图谱。

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引用次数: 0

High-resolution mass spectrometry and enzyme-linked immunosorbent assay for detection of residual botulinum concentrations in a mouse model of botulism 高分辨率质谱法和酶联免疫吸附法检测肉毒杆菌中毒小鼠模型中的残留肉毒杆菌浓度

IF 1.4 4区医学 Q3 MEDICINE, LEGAL

Legal Medicine

Pub Date : 2025-11-19 DOI: 10.1016/j.legalmed.2025.102758

Dongqing Li , Junyan Liang , Ying Chen , Xianglei Wu

Background

Botulinum toxin type A is widely used to block acetylcholine release in the treatment of chronic sialorrhea, muscle spasticity, and dystonia. We aim to develop a user-friendly method for detecting cases of medical botulinum toxin poisoning.

Methods

The mice poisoning model was established by injecting or gavage with Botulax®, and the poisoning dose and symptoms were observed. The residual levels of toxin in poisoned mice were detected by high-resolution mass spectrometry and sandwich ELISA, respectively.

Results

Two hours after poisoning, no residual botulinum toxin was found by mass spectrometry (MS) under our specific untargeted workflow and sample preparation conditions, but ELISA detected residual toxin in various tissues of mice. Among them, the muscle tissue had the highest level. There is no noticeable difference in the levels of toxin residues in the same organs of mice, regardless of the route of poisoning. The sandwich ELISA method is user-friendly for detecting medical botulinum toxin poisoning. The presence of toxin residues can be detected in various tissues two hours after exposure, with muscle being the optimal sampling tissue.

Conclusions

Our research indicates that under specific sample preparation, chromatographic separation, and untargeted detection conditions, mass spectrometry may not be effective for detecting Botulinum toxin at concentrations below the ng/ml level. The study demonstrates that ELISA is a sensitive and practical alternative for early detection. Positive results can be detected within 2 h of poisoning, especially when taken from muscle tissue.

背景A型肉毒杆菌毒素被广泛用于阻断乙酰胆碱的释放，用于治疗慢性唾液分泌、肌肉痉挛和肌张力障碍。我们的目的是开发一种用户友好的方法来检测病例的医用肉毒杆菌毒素中毒。方法采用肉毒毒素®注射或灌胃法建立小鼠中毒模型，观察中毒剂量和中毒症状。分别采用高分辨率质谱法和夹心ELISA法检测中毒小鼠体内毒素残留水平。结果在特定的非靶向工作流程和样品制备条件下，中毒2 h后，质谱法（MS）未检测到肉毒毒素残留，而ELISA法在小鼠各组织中检测到肉毒毒素残留。其中，肌肉组织中含量最高。无论中毒途径如何，在小鼠的同一器官中，毒素残留水平没有明显差异。夹心ELISA法是检测医用肉毒毒素中毒的简便方法。暴露后两小时可在各种组织中检测到毒素残留物的存在，肌肉是最佳取样组织。结论在特定的样品制备、色谱分离和非靶向检测条件下，质谱法可能无法检测ng/ml以下浓度的肉毒杆菌毒素。该研究表明，ELISA是一种灵敏、实用的早期检测方法。中毒后2小时内可检测出阳性结果，特别是从肌肉组织中提取时。

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引用次数: 0