Background Methcathinone (MCAT), a synthetic cathinone of abuse, causes neurobehavioral toxicity, yet the involvement of gut microbiota and host metabolic reprogramming remains unknown, hindering forensic biomarker discovery. Methods Zebrafish were exposed to MCAT (1.0–10.0 µg/mL, 15 days). Behavioral phenotyping, 16S rRNA sequencing, PICRUSt2-based metabolic prediction, and intestinal histopathology were performed. Results MCAT induced dose-dependent behavioral deficits: hyperlocomotion, aggression, social impairment, anxiety. It reduced gut microbial α-diversity, depleted beneficial genera ( Lactobacillus , Parabacteroides ), enriched Tardiphaga / Sphingomonas , and caused intestinal inflammation. PICRUSt2 predicted reprogramming of relaxin, parathyroid hormone, and GnRH signaling pathways, which correlated with behavioral changes. Conclusion Chronic MCAT exposure reshapes gut microbiota and host metabolism, driving neurobehavioral toxicity via a microbiota-metabolism-behavior axis, offering candidate forensic biomarkers.
BackgroundEpilepsy is a common neurological disorder with high genetic heterogeneity and affects approximately 70 million people worldwide. Although several studies have combined Genome-Wide Association Studies (GWAS) with bulk expression quantitative trait loci (eQTLs) to explore epilepsy risk genes, the cellular context of genetic regulation remains insufficiently defined.MethodsWe integrated epilepsy GWAS data with brain bulk and single-cell eQTLs using summary-data-based Mendelian randomization (SMR) and Bayesian colocalization to identify causal genes. The identified genes were validated in an independent RNA-seq cohort of patients with refractory epilepsy. We then characterized cell-type specificity and intercellular signaling using single-cell RNA sequencing (scRNA-seq) and CellChat. Druggability and drug-repurposing analyses were performed using DSigDB to identify targeted therapeutic compounds for epilepsy.ResultsSeven epilepsy causal genes (FGFR3, PM20D1, ZNF564, HAGH, CAPN15, CCDC117 and DARS1-AS1) were identified, with FGFR3 and HAGH identified as druggable targets. FGFR3 was predominantly expressed in astrocytes and involved in an astrocyte-centered FGF2-FGFR signaling loop, whereas HAGH was enriched in neurons. DSigDB analysis highlighted the FGFR inhibitor, Ro-4396686, as the top candidate compound.ConclusionsMulti-scale integration of eQTL, GWAS and transcriptomic datasets reveals the genetic variants of epilepsy, with FGFR3-driven FGF signaling representing a principal molecular axis. This study reveals the cellular context of this disorder and highlights FGFR3 and HAGH as promising therapeutic targets.
Regional traditional plant khat, which have been recreationally used world-wide recently, has been proven to be a mixture of several biologically active ingredients. Herein, a chosen specimen, vitreous humor (VH) and a novel pretreatment, electromembrane extraction (EME), are applied for forensic investigations of such abused plant. VH, as an alternative matrix, is being used for evaluating possible compounds more and more; EME, a novel and efficient pretreatment method, is applied to detect the ingredients from natural complex matrices with advantages of a more sustainable microextraction technique. This study aims to analyze the ingredients of khat, norephedrine (NE), norpseudoephedrine (NPE) and cathinone (CTN), as well as their concentrations in VH of khat-treated mice applying EME. After optimization, 2-ethylnitrobenzene (ENB)/undecanol was used as the support liquid membrane (SLM), HCl (pH = 2) as the acceptor solution, extraction voltage at 60 V, and extraction time for 30 min. The established EME was combined with liquid chromatography–ultraviolet spectrometry (LC–UV) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) to evaluate spiked VH. The LOD of NE, NPE, and CTN were 0.40–1.90 µg/mL with linearity (R2 > 0.9624) and repeatability (< 13
Nitrous oxide (N2O) abuse is becoming increasingly popular worldwide. Moreover, the use of N2O combined with other substances, such as alcohol, is also common. Accidental deaths associated with N2O abuse are rare in forensic practice, with most fatal cases involving continuous inhalation equipment or exposure in a confined space. In contrast, the inhalation of N2O using balloons is traditionally regarded as a relatively safe method. In this report, we present an unusual fatal case of a 16-year-old girl who died after drinking alcohol and inhaling N2O from balloons. The decedent was found in a prone position with the nose and mouth compressed against the bed. Cyanosis of nails, pulmonary and cerebral edema, and the positive expression of HIF-1α in lung, myocardium and brain, were indicative of asphyxiation. Toxicological analysis revealed a peripheral blood ethanol concentration of 140 mg/dL and cardiac blood N2O concentration of 74.5 μL/mL. N2O was also positively detected in the lungs, stomach contents, gastric air, and the brain. In conclusion, we determined that the decedent died from accidental asphyxia related to N2O inhalation, prone positioning, and alcohol consumption. We also investigated chronic N2O abuse from a forensic perspective. This report aims to help forensic pathologists manage similar cases. It also reminds N2O abusers of potential dangers.
Extended suicide, a specific type of homicide-suicide event, has severe social consequences yet remains lacking systematic research. This retrospective study investigated 51 cases of extended suicide involving mental disorders in central China with aim of better understanding risk factors for such events and guiding prevention strategies. Over an 8-year period from 2015 to 2022, cases were collected from forensic institutions, and demographic characteristics, case details, and psychiatric data were recorded. The 51 incidents involved 51 perpetrators and 79 victims, with more female perpetrators (58.8%) and more female victims (54.4%). The average age of the perpetrators was 36.1, and most were married (88.2%). Almost all of the victims were family members of the perpetrator, like the most numerous children (64.6%), followed by spouses (24.1%). The most common homicide mode of death was mechanical asphyxia (38.0%), followed by sharp devices (36.7%) and drug poisoning (16.5%). Depressive disorders (76.5%) were the most common diagnosis of mental disorder for perpetrators. The study analyzed the unique characteristics of extended suicide to enrich such data. These findings help strengthen the screening and identification of potential perpetrators and victims to prevent such cases from occurring.
ObjectiveMalingering of neuropsychological damage is common among traumatic brain injury patients pursuing disability compensation in forensic contexts. There is an urgent need to explore differences in neuropsychological assessment outcomes with different levels of cooperation.MethodsA total of 420 participants with severe traumatic brain injury were classified into malingering group, partial cooperation group, and complete cooperation group according to the Binomial forced-choice digit memory test. The Wechsler Adult Intelligence Scale, event-related potential component, and Symptom Checklist 90 were applied subsequently to assess the psychological status of participants.ResultsParticipants in the malingering group presented lower scores in the binomial forced-choice digit memory test and the Wechsler Adult Intelligence Scale, lower P3 amplitude, and simultaneously higher scores in the Symptom Checklist 90 than the other two groups. The actual intelligence quotient of participants with malingering tendencies ranged mostly between normal and marginal damage, and they often reported elevated whole scale scores in the Symptom Checklist 90. The Cooperation Index (defined as the ratio of positive symptom distress index to global severity index, CI) was proposed and validated to function as an embedded validity indicator of the Symptom Checklist 90, and the area under the receiver operating characteristic (ROC) curve was 0.938. When valued at 1.28, CI has the highest classification ability in differentiating malingering from non-malingering. Combined with the CI and P3 amplitude, the area under the ROC curve for malingering diagnosis further reached 0.952.ConclusionAny non-optimal effort in a forensic context will lead to unexpected deviation in psychology evaluation results. CI is a potential candidate to act as an embedded validity indicator of the Symptom Checklist 90. The combination of CI and P3 amplitude can help to identify malingering in participants after severe traumatic brain injury.
Determination of antipsychotics from biological samples is meaningful in the field of clinical and forensic medicine. Compared to blood, keratinized matrices such as hair and nails have attracted increasing attention in drug analysis for wider detection window. Nevertheless, the distribution and stability of antipsychotics in ker-atinized matrices are not clarified yet. Therefore, we developed a LC-MS/MS based method for simultaneous determination of 10 antipsychotics from blood, hair and nails, with high recovery (78.1-107.4%, 71.3-93.5% and 75.2-90.5%), low LOD (5-10 pg/mL, 5-10 pg/mg and 5 pg/mg) and high accuracy (96.0%-101.6%, 97.5%-102.5% and 97.6-101.7%). The method was applied to sets of blood, hair, and nail samples of 54 pa-tients who received long-term therapy, and significant correlations between drug concentrations in blood and hair was found, while the correlation between nails and other matrices varied depending on the drug. Except for olanzapine, the concentrations of antipsychotics in segmental hair samples were consistent with drug exposure. Besides, the hair and nail samples of suspects in two forensic cases were analyzed and provided supporting evidence for the suspects' psychiatric state. Our research offered a deeper understanding of keratinized matrix as stable and retrospective bio-samples for antipsychotics detection in forensic practice.
Methcathinone (MCAT) belongs to the designer drugs called synthetic cathinones, which are abused worldwide for recreational purposes. It has strong stimulant effects, including enhanced euphoria, sensation, alertness, and empathy. However, little is known about how MCAT modulates neuronal activity in vivo. Here, we evaluated the effect of MCAT on neuronal activity with a series of functional approaches. C-Fos immunostaining showed that MCAT increased the number of activated neurons by 6-fold, especially in sensory and motor cortices, striatum, and midbrain motor nuclei. In vivo single-unit recording and two-photon Ca2+ imaging revealed that a large proportion of neurons increased spiking activity upon MCAT administration. Notably, MCAT induced a strong de-correlation of population activity and increased trial-to-trial reliability, specifically during a natural movie stimulus. It improved the information-processing efficiency by enhancing the single-neuron coding capacity, suggesting a cortical network mechanism of the enhanced perception produced by psychoactive stimulants.
Abstract Rationale: After severe traumatic brain injury, patients often present with signs of increased intracranial hypertension and partially require decompressive craniectomies. Artificial materials are usually required to repair skull defects and spontaneous skull ossification is rarely observed in adults. Patient concerns: This study reported a 64-year-old man was admitted to the hospital with a coma due to a traffic accident. Diagnosis: Emergency computed tomography (CT) examination upon admission showed a left temporo-occipital epidural hematoma with a cerebral hernia and skull fracture. Interventions: The patient underwent urgent craniotomy for hematoma removal and decompression under general anesthesia. The patient was discharged after 1 month of treatment. Outcomes: The patient returned to the hospital for skull repair 145 days after the craniotomy. Pre-operative CT showed island skull regeneration in the skull defect area; therefore, skull repair was postponed after clinical evaluation. Regular follow-up is required. Twenty-three months after surgery, head CT showed that the new skull had completely covered the defect area. Lesson: We collected other 11 similar cases of spontaneous human skull regeneration in a literature search to analyze the possible factors impacting skull regeneration. The analysis of the cases indicated that maintaining the integrity of the periosteum, dura, and blood vessels during craniotomy may play an important role in skull regeneration. Skull regeneration predominantly occurs in young patients with rapid growth and development; therefore, an appropriate postponement of the cranioplasty time under close monitoring could be considered for young patients with skull defects.
Rationale: After severe traumatic brain injury, patients often present with signs of increased intracranial hypertension and partially require decompressive craniectomies. Artificial materials are usually required to repair skull defects and spontaneous skull ossification is rarely observed in adults. Patient concerns: This study reported a 64-year-old man was admitted to the hospital with a coma due to a traffic accident. Diagnosis: Emergency computed tomography (CT) examination upon admission showed a left temporo-occipital epidural hematoma with a cerebral hernia and skull fracture. Interventions: The patient underwent urgent craniotomy for hematoma removal and decompression under general anesthesia. The patient was discharged after 1 month of treatment. Outcomes: The patient returned to the hospital for skull repair 145 days after the craniotomy. Pre-operative CT showed island skull regeneration in the skull defect area; therefore, skull repair was postponed after clinical evaluation. Regular follow-up is required. Twenty-three months after surgery, head CT showed that the new skull had completely covered the defect area. Lesson: We collected other 11 similar cases of spontaneous human skull regeneration in a literature search to analyze the possible factors impacting skull regeneration. The analysis of the cases indicated that maintaining the integrity of the periosteum, dura, and blood vessels during craniotomy may play an important role in skull regeneration. Skull regeneration predominantly occurs in young patients with rapid growth and development; therefore, an appropriate postponement of the cranioplasty time under close monitoring could be considered for young patients with skull defects.
Background: Cathinones have emerged as a worldwide health concern due to their increasing use. Objectives: The aim of this study was to perform a bibliometric review of global research trends in psychoactive cathinones as illegal addictive substances. Methods: We developed a search strategy and established several databases based on Web of Science (WoS) screening. After screening, 944 scientific papers from 1994 to 2018 (including 99 in the substance-abuse category) were used for scientometric analysis regarding various indicators, including outputs trends, institution/country/territory contributions, and high-frequency terms. Results: Analyses indicated that annual publications increased dramatically after 2011, then showed fluctuating increases. Institutions in developed countries, especially the United States and European countries, demonstrated high contribution to outstanding papers and top-cited publications. High-frequency terms, which are indicative of widely covered research topics, included pharmacological effects, chemical analysis, clinical neurology, as well as toxicity, psychology, and behavior. Conclusions: This bibliometric analysis revealed the emerging trends in research interest on cathinones, especially designer drug synthesis. Therefore, regulations should be updated to set clear boundaries related to potential medical and illegal use. With joint academic and societal effort, research strategies and prevention policies related to these illegal stimulants could be improved.
新冠疾病(COVID-19)传染性强,潜伏期长,已在全球快速蔓延,给司法鉴定带来新的挑战.本文对COVID-19疫情下法医精神病鉴定的日常工作相关环节如何避免感染,COVID-19导致的器质性与功能性精神损伤特点及其损伤/伤残评定,COVID-19与精神卫生医疗机构医疗纠纷的防范及法医学鉴定思路等方面进行了探讨,并提出相应建议,以期增进鉴定机构、鉴定人和精神卫生医疗机构防范感染及化解纠纷的风险意识,根据疫情变化做好应对预案.
Substance abuse has become a global problem due to drug-induced addiction and neurotoxicity, which causes a huge physical, social, and financial burden. Various kinds of drugs can hijack the users'/abusers' behavior and associated neurocircuitry. To summarize recent scientific advances on drug abuse, we reviewed relevant publications to analyze research progress and such trends through bibliometric ways. Based on retrieval strategies, a total of 681 scientific records published from 1997 to 2021 were screened and included in the Web of Science (WoS) database. Further scientometric analysis revealed that annual publication output increased across this period, with the United States of America (USA) contributing a significant number of reasons. Research has focused on neurotransmitter, oxidative stress, mitochondrial system injury, and other neurotoxic mechanisms. Neuroimmune, neurotoxic targets, and new psychoactive substances have been hot topics in recent years, which deserve continued research in the future. Specific research on molecular mechanisms has progressed across this period, with an emphasis on the root cause of toxicity and molecular targets for therapy. Moreover, collaborations of international multi-disciplinary research teams have been efficient and need to be encouraged for addiction research and the development of appropriate therapeutic processes.
Background: Globally lung cancer is one of the most common cancers, and is responsible for almost 20% of all cancer care costs. As a potential treatment for lung cancer, anti-PD-1/ PD-L1 therapy has become a novel scientific hotspot in recent decades. The present study aims at exploring the status and trends of the top frequently cited publications about the anti-PD-1/PD-L1 therapy for lung cancer via bibliometric analysis. Methods: The publications concerning anti-PD-1/PD-L1 therapy for lung cancer were searched on the core collection database of Web of Science, setting the time period for retrieval from 1950 to 2019. The top 100 most frequently cited publications were retrieved, and the bibliometric data were mainly accessed through an open online analysis platform and VOSviewer software. Results: The cited frequencies about the top 100 cited publications ranged from 218 to 6248. These articles were published in 39 publications, which were mainly ranked in Q1. The top journal in terms of the number of the articles was the New England Journal of Medicine (16 articles). The most frequently nominated author was Brahmer, JR from Sidney Kimmel Comprehensive Cancer Center, while the most contributing institution was Memorial Sloan Kettering Cancer. The United States acted as the pioneer in this new field of research and led plentiful of national and international co-operations. Immunotherapy, nivolumab, cell lung-cancer, safety, and docetaxel appeared more frequently as keywords. Discussions: To sum up, high quality journals, influential authors and institutions and research with high quality evidence were apt to attract more attention and possess more public credibility. Moreover, the bibliometric analysis is yielding up its advantage of identifying and analyzing the characteristics and changes in the intellectual structures of a special topic.
目的 通过探索创伤性脑损伤(TBI)伤者智商值(IQ)与听觉P300的相关性,寻找能够反映伤者真实智能状态的评价指标.方法 征集需进行智能损害司法鉴定的TBI伤者,进行二项必选数字记忆测验,选取测验合作者427名,分别进行流行病学统计、中国修订韦氏成人智力量表(WAIS-RC)和P300检测,分析IQ与被试者基本情况及P300各成分之间的相关性.结果 年龄、受教育程度及TBI的严重程度对被试者的智能状态均有一定程度的影响;智能损害程度越严重,TBI伤者的P3波潜伏期和N2波潜伏期越长(P<0.01),IQ和P3波潜伏期之间呈显著负相关(r=-0.71,P<0.01),IQ和N2波潜伏期之间表现出弱负相关(r=-0.32,P<0.01).结论 P3波潜伏期比N2波潜伏期更能代表TBI伤者的真实智能水平,可作为评估脑外伤后智能损害的重要参考指标.
目的 运用Citespace软件对法医临床学相关文献绘制知识图谱、进行可视化分析,探究该学科领域研究热点和动态发展,梳理鉴定难点脉络.方法 汇总CNKI收录《中国法医学杂志》《刑事技术》《法医学杂志》《中国司法鉴定》刊登的法医临床学相关论文,利用Citespace分析其关键词、研究热点、基金资助、作者、发文机构及所在地等.结果 法医临床学作为法医学分支学科之一,近年来呈现的科研成果部分获基金资助,多由开设法医学专业的院校完成;随着科研理论、技术方法 推陈出新,法医临床学鉴定标准、版本也得以构建、更迭、完善,鉴定体量位居法医"四大类"之首.结论 作为最具中国特色的法医学分支学科,法医临床学研究着重服务司法实践、以期用成果技术反哺鉴定,实现学术、实践的交流、转化.通过Citespace知识图谱可视化分析学科发展历程,有助于回溯此间规律,提示未来研究方向,提升鉴定业务水平,为持续增强法医临床学学科影响力提供借鉴.
1Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, People’s Republic of China; 2Grade 2018 Clinical Medicine, Army Medical University, Chongqing, People’s Republic of China; 3Grade 2017 Nursing, Shenzhen University Health Science Center, Shenzhen, People’s Republic of China; 4Department of Radiology, Affiliated Hospital of Beihua University, Jilin, People’s Republic of China; 5Department of Forensic Science, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People’s Republic of China; 6Department of Pathology, Shenzhen University Health Science Center, Shenzhen, People’s Republic of China
Synthetic cathinones, produced by a subtle chemical modification or a designed screening based on the structural basis of controlled drugs, are structurally and functionally similar to amphetamine-type stimulants, which could induce similar or even stronger excitatory or hallucinatory effects, cognitive dysfunction, etc. Nowadays, with an increasing diversity, popularity and illegal potential, the abuse seriously endangers public health. However, the mechanisms of their toxicity damaging brain function are still unclear. As an overview of chemical structure, classification and pharmacological effects of synthetic cathinones, this review summarizes research advances of mechanisms, behavior disorder and neurocognitive dysfunction, and presents a series of recent behavioral and neurobiological results of methcathinone-treated mice to shed light on the novel mechanism of synthetic cathinone abuse.
Substance-related disorders are a group of medical conditions that affect a person's brain and behavior and lead to an inability to control the use of legal or illegal drug(s) or medication. Substance-related disorder is a serious public health and society problem worldwide. Genetic factors have been proven to have an important role. Researchers have carried out a lot of work in this field, and a large number of research results have been published in academic journals around the world. However, there are few overviews of research progress, presentation, and development trends in this field. In this study, a total of 636 articles related to genetic factors of substance-related disorders were retrieved from the Web of Science (WoS) database from 1997 to 2018, and the scientific literatures were analyzed by bibliometrics. The study found that the United States (US) has maintained a leading position in the field of research, with many core institutions and plenty of high-quality research results. Alcohol use disorder is still the most concerning issue in this field. Over the past 20 years, new techniques such as genome-wide association study (GWAS) based on high-throughput sequencing technology have replaced family studies, twin studies, and retrospective studies in this field. We believe that it is urgent to study the genetic factors of substance-related disorders, which can greatly deepen the understanding of the pathogenesis of substance-related disorders and may provide potential targets for precise treatment of such diseases.
生态环境损害问题困扰着大部分发达国家及发展中国家,各国日益重视生态环境损害的评估、赔偿及修复工作,环境损害司法鉴定开始登上历史舞台.通过文献计量学方法应用CiteSpace和VOSviewer软件,针对生态环境损害和司法对策文献的学科、国家、机构及作者分布特征,以及文献的共被引等信息可视化进行研究.研究发现:20世纪70年代起,美国的一些机构持续引领研究热潮,无论是空气颗粒污染、土壤或水体的重金属污染等均受到重视;作为发展中国家的代表,我国相关研究自21世纪初开始迅速崛起,近年发布的一系列针对环境损害司法鉴定相关的法律、法规,不仅承袭了前期成果和客观需求,更为将来的研究成果及司法实践奠定基础.