法医学杂志最新文献

Ketamine is a dissociative anesthetic. It is clinically used as a surgical anesthetic or anesthetic inducer and has a certain degree of mental dependence. Its abuse can lead to nerve damage, adverse emotional reactions and other toxic side effects. The primary mechanism by which ketamine exerts its pharmacological effects is to block N-methyl-D-aspartate receptors (NMDAR). It also functions through pathways such as α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid receptors (AMPAR), opioid receptors, γ-aminobutyric acid (GABA) receptors, monoaminergic receptors, cholinergic receptors, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, voltage-gated sodium channels, and L-type voltage-dependent calcium channels (VDCC). This article summarizes the molecular mechanism and toxic effects of ketamine's pharmacological functions, in order to provide a basis for forensic applications such as the identification of symptomatic phenotypes of ketamine toxic effects and the identification of ketamine abuse.

Doxorubicin is a commonly used antitumor drug for the treatment of various cancers. However, its clinical application is greatly restricted by its severe cardiotoxicity. At present, doxorubicin-induced cardiotoxicity is categorized into acute and chronic forms, depending on the dosage and duration of exposure, which may eventually lead to the occurrence of heart failure. The pathogenesis of doxorubicin cardiotoxicity is associated with oxidative stress, mitochondrial damage, calcium overload, dysregulation of autophagy, and apoptosis. In forensic medical practice, cases of poisoning or even cardiac death caused by doxorubicin showed no obvious changes in cardiac morphology through routine forensic pathological examinations. The paper aims to summarize the research on the mechanisms of action of doxorubicin-induced cardiotoxicity in recent years, analyze and discuss the possible pathways of cardiomyocyte injury caused by doxorubicin, and provide references for research on the mechanisms of doxorubicin-induced cardiotoxicity and forensic application.

Objectives: To explore the mechanism of myocardial toxicity caused by N-methyl-3,4-methyle-nedioxyamphetamine (MDMA), the changes of intracellular calcium oscillation mode and calcium handling proteins during acute exposure to different concentrations of MDMA were detected, and the involvement of nuclear factor κB (NF-κB) and its effect on calcium handling proteins were investigated.

Methods: Primary rat cardiomyocytes were cultured to establish MDMA acute exposure model, and a control group was set up. The MDMA poisoning model was divided into three concentration groups of 10, 100 and 1 000 μmol/L. After 1 h of exposure, the morphological changes of cardiomyocytes were observed, the cytotoxicity and changes in calcium signals were measured, and the changes in calcium handling proteins RyR2, SERCA2a, PLN, NCX1 and Cav1.2 were detected. The changes of NF-κB activity and the expression of nucleoprotein p-p65 (Ser311) and PKCζ after MDMA exposure, and the intervention of NF-κB inhibitors pyrrolidine dithiocarbamate ammonium (PDTC) and protein kinase C (PKC) inhibitor chelerythrine (CHE) were detected by electrophoretic mobility shift assay (EMSA) and Western blotting. The effects of PDTC intervention on calcium signals, and the expressions of RyR2, SERCA2a, PLN, NCX1 and Cav1.2 after acute MDMA exposure were also observed.

Results: No obvious changes were observed in the morphology of cardiomyocytes after acute exposure to MDMA, whereas the oscillation waveform of intracytoplasmic calcium ion showed irregular changes with increased oscillation amplitude, intense fluctuations, irregular frequency, and increased fluctuation range of relative optical density values. The expression of RyR2, SERCA2a and NCX1 increased, while the expression of Cav1.2 and PLN decreased. Acute MDMA exposure could increase NF-κB activity, while PDTC and CHE intervention could inhibit NF-κB activity. In MDMA exposed group, the expression of PKCζ and nucleoprotein p-p65 (Ser311) both increased and could be inhibited by CHE. After the intervention of PDTC to block NF-κB, the amplitude of calcium oscillation was lower than that of the MDMA exposed group, and the expression of RyR2, SERCA2a and NCX1 decreased. There was no significant change in PLN, while the expression of Cav1.2 increased.

Conclusions: MDMA can lead to an increase of calcium ion concentration in cardiomyocytes. Calcium ions are involved in myocardial toxicity of MDMA. The mechanism is related to changes in calcium handling proteins, mainly associated with the increased expression of RyR2. MDMA can up-regulate the intracellular activity of NF-κB through the PKCζ-NF-κB pathway and affect calcium handling proteins, which aggravate intracellular calcium overload during acute MDMA exposure.

Objectives: To explore whether ferroptosis is involved in α-amanitin-induced hepatocyte injury by detecting iron deposition in mice liver tissues, oxidative stress indicators in hepatocytes and L-02 cells, and expressions of ferroptosis-related proteins after α-amanitin exposure.

Methods: The poisoning models of α-amanitin C57BL/6J mice and L-02 cell were established. The Lillie ferrous iron staining and Prussian blue staining were used to detect iron deposition; the kits were applied to detect the levels of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione (GSH). Western blotting was performed to analyze expressions of p53, solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4).

Results: Compared with the control group, after α-amanitin exposure, positive cell rates of Fe²⁺ and Fe³⁺ in mice liver tissues increased significantly. In the liver tissues of medium (0.35 mg/kg) and high (0.45 mg/kg) dose groups and L-02 cells treated with 1 μmol/L α-amanitin, the level of GSH decreased, the level of MDA increased, and the activities of SOD and CAT decreased significantly. In addition, α-amanitin upregulated the expression of p53 in a concentration- and time-dependent manner and inhibited the expressions of SLC7A11 and GPX4.

Conclusions: Ferroptosis plays an important role in α-amanitin-induced hepatocyte injury. Abnormalities of ferroptosis-related indicators can provide references for the forensic identification of α-amanitin poisoning.

Bongkrekic acid (BA) is a toxin with stable properties and no distinctive smell. It exists in common foods such as fermented edible grain products, potato products, spoiled tremella fuciformis and auricularia polytricha, as well as auricularia polytricha that has been soaked too long. It can easily cause food poisoning. At present, there is still a lack of complete method to detect BA, and no specific antidote of BA has been found. Therefore, BA poisoning is easy to be misdiagnosed or missed diagnosed, and its mortality rate remains high. In recent years, studies have revealed the toxic mechanism of BA and found that BA can inactivate some enzymes containing thiol groups (-SH) and inhibit the synthesis and transport of adenosine triphosphate (ATP), causing damage to liver, kidney, brain and other parenchymal organs. This article reviews the autopsy cases and literature of deaths caused by BA poisoning at home and abroad, systematically summarizes the epidemiology, clinical manifestations, pathological changes, toxicological mechanisms, detection methods, forensic diagnostic key points and challenges of BA in forensic medicine, with the aim of providing a reference for forensic identification of related cases.

Insulin is an important protein hormone that participates in multiple metabolic pathways. Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes. Currently, the number of reported cases of insulin overdose both at home and abroad is gradually increasing, and insulin homicide is no longer a means of "committing murder without leaving a trace". At present, there are no systematic protocols for the identification of insulin overdose in the field of forensic medicine in China. This article introduces the causes, toxicological characteristics, forensic examination, laboratory testing methods and indicator reference of insulin overdose. Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad, this paper aims to provide recommendations and references for the formulation of forensic identification guidelines for insulin overdose cases.

Objectives: To analyze the characteristics of methadone-related poisoning cases and provide a reference for forensic identification.

Methods: A total of 71 cases of methadone-related poisoning reported from 1998 to 2023 in China and 26 cases of methadone-related deaths reported from 2013 to 2018 in Italy were retrieved from databases including PubMed, Wanfang and CNKI. The general information, forensic pathological and toxicological characteristics were analyzed.

Results: Among the 71 methadone-related poisoning cases in China, there were 54 cases (76.06%) of poisoning without death and 17 cases (23.94%) of death from poisoning. There were 54 male cases (76.06%), and 51 cases (71.83%) aged 19 to 39 years old. There were 35 cases (49.30%) of poisoning caused by methadone alone, and 32 cases (45.07%) were poisoning caused by methadone combined with other substances or drugs including heroin and benzodiazepines. Most of the poisoned showed coma, respiratory depression and miosis. Signs of asphyxia were often found by autopsy. The mass concentration of methadone detected in the blood of 6 deceased ranged from 0.112 to 3.000 mg/L. Among the 26 methadone-related deaths in Italy, 22 cases were male (84.62%). There were 6 cases (23.08%) caused by methadone alone, and 20 cases (76.92%) died from methadone combined with other substances or drugs. The mass concentration of methadone in blood ranged from 0.181 to 4.059 mg/L.

Conclusions: The proportions of poisoning cases caused by methadone alone and methadone combined with other substances or drugs are comparable in China. The majority of deceased caused by methadone poisoning shows typical triad of coma, respiratory depression and miosis, which helps forensic experts determine the cause of death related to methadone. Additionally, it is necessary to increase the routine testing of the concentration of methadone and its combined substances or drugs in deceased, and collect data for the interpretation of the results of related cases.