Rationale: Synaptic deficits occur prior to the emergence of Aβ plaques and tau pathology in Alzheimer's disease (AD). Dysregulated microglia excessively prune synapses, leading to synaptic loss. While microglia phagocytic receptor Mertk participates in synaptic pruning, the role of Mertk in driving early synaptic loss in AD remains elusive. Methods: Single-cell RNA sequencing (scRNA-seq) was used to analyze transcriptional changes of microglia in early stage of AD mice. Mertk-mediated synaptic engulfment was investigated both in vivo and in vitro. Results: Phagocytic-associated microglia with upregulated Mertk were identified in the early stage of AD mice. Dysregulated synaptic pruning by microglia caused hippocampal synaptic loss and memory deficits in two AD mouse models. Notably, Mertk knockout or antagonist treatment reversed excessive synapse elimination by microglia. Mechanistically, Aβo-induced PPARγ promoted Mertk transcription, mediating microglial phagocytosis of synapses. Conclusions: Collectively, our findings suggest that PPARγ-regulated, Mertk-mediated microglial synaptic engulfment contributes to early synaptic loss in AD, highlighting microglial Mertk as a potential therapeutic target for AD.

While genome-wide association studies (GWAS) have implicated immune and metabolic pathways in Alzheimer’s disease (AD), their specific cellular impacts remain unclear. To address this, we employed bidirectional two-sample Mendelian randomization to identify single nucleotide polymorphism (SNP)-mediated, AD-associated immunometabolic signatures, which revealed both positively and negatively correlated immune cell types and metabolic pathways. Integrated single-cell omics analysis further delineated distinct astrocyte subpopulations in patient brains: one enriched for Glutamate-glutamine uptake and metabolism was positively associated with AD, while another characterized by Amino acid metabolism and transport was negatively associated. In peripheral blood, mononuclear cells (PBMCs) primarily displayed AD-negative metabolic signatures accompanied by downregulated immune responses. Leveraging these findings, we developed and optimized a blood transcriptome-based AD prediction model on a gene set derived from blood immune cells that is negatively associated with AD, using multiple machine learning approaches. This model is applicable to both European and Asian populations, enables pre-symptomatic detection for familial AD, effectively discriminates AD from other neurodegenerative disorders, and is readily accessible for clinical implementation. Our study provides novel evidence underscoring the critical role of immunometabolism in AD and delivers a practical predictive tool suitable for large-scale, routine population screening.

Objective: To study the characteristics of postmortem ethanol production and its relation with alcohol congeners in postmortem rat liver and muscle tissues. Method: Postmortem liver and muscle tissues in Sprague-Dawley rats, from postmortem time interval (PMI) day 0-20, were analyzed via headspace gas chromatograph flame ionization detection to observe production of postmortem ethanol and 5 selected alcohol congeners. Result: 1. Putrid ethanol production increased gradually to a peak and then decreased with the prolongation of PMI; 2. Acetaldehyde, 1-propanol, and 3-methyl-butyraldehyde were produced along with postmortem ethanol; 1-butanol was only detected from day 11-20; 3. The concentrations of acetaldehyde, 1-propanol and 3-methylbutyraldehyde was related with ethanol production. Fifteen mathematical models were constructed for putrid ethanol production based on acetaldehyde, 1-propanol, and 3-methyl-butyraldehyde. Conclusion: A peak in postmortem ethanol production was identified. The production trends of acetaldehyde, 1propanol, and 3-methyl-butyraldehyde in the liver, and of 1-propanol in muscle, were consistent with those of ethanol, and could potentially to be used as biomarkers of postmortem ethanol production. Further human samples and data analysis are needed to verify this.

目的 通过案例分析不同原因导致的主动脉夹层(aortic dissection,AD)特征,为AD的法医学鉴定案例提供鉴定思路.方法 收集35例AD的法医学鉴定案例(包括32例死亡鉴定,3例法医临床鉴定),对被鉴定人的外伤史、年龄、性别、发病经过、医疗过程、尸体解剖、病理检验等进行分类分析.结果 35例AD案件中患者平均年龄为47岁,男性居多(32例);涉及外伤的案件13例,其中交通事故最多(8例);被鉴定人首发症状主要为胸痛或呼吸困难(18例),余依次为腹痛或呕吐(8例)、头晕或头痛(3例)、意识丧失(4例)、腰痛或下肢不适(2例);97％(31例)的被鉴定人在急性期死亡;27例合并高血压或心脏肥大,24例合并动脉粥样硬化症.结论 法医鉴定创伤性AD案件时应进行伤病关系分析,先检查被鉴定人的自身基础疾病,再评估外伤的作用力,最后考虑医疗等中介因素对死亡或损伤的影响.

The increasing number of clinical trials of new drugs in China has brought huge benefits to the society, but also implied huge risks. This is particularly evident in experimental medicine. Germany has achieved good results in regulating experimental medical behaviors through the model of legislative norms. China should learn from Germany's beneficial experience to promote the orderly development of experimental medical behavior in China. Specifically, the crime of illegal human experiment should be added to the criminal law; Adopt special legislation model to regulate experimental medical behavior; Establish a no fault medical liability system to share experimental medical risks;Absorb and learn from the relevant norms of the international community on human experiment.

Epilepsy is a common neurological disorder with a complex etiology. Ferroptosis, a new form of programmed cell death, is characterized by the accumulation of lipid peroxides and associated with seizures. However, the underlying mechanism of ferroptosis in epilepsy remains elusive. Here, we found that GPX4-GSH-dependent neuronal ferroptosis was detected in epileptic mice, which was attenuated with ferroptosis inhibitors. Moreover, activated neurotoxic A1 astrocytes facilitated seizure-related neuronal ferroptosis in epileptic brains. Inhibition of ferroptosis blocked A1 astrocyte-induced neurotoxicity. A1 astrocyte-secreted CXCL10 enhanced STAT3 phosphorylation but suppressed SLC7A11 in neurons via CXCR3, leading to ferroptosis-associated lipid peroxidation in a GPX4-dependent manner. This was in line with clinical findings, showing a significant correlation between neuronal ferroptosis and A1 astrocytes in epileptic patients. In summary, the present data show that A1 astrocyte-induced neuronal ferroptosis contributes to the pathogenesis of epilepsy, which offers a novel therapeutic target for precision medicine.

Astrocytes are critical regulators of the immune/inflammatory response in several human central nervous system (CNS) diseases. Emerging evidence suggests that dysfunctional astrocytes are crucial players in seizures. The objective of this study was to investigate the role of transient receptor potential vanilloid 4 (TRPV4) in 4-aminopyridine (4-AP)-induced seizures and the underlying mechanism. We also provide evidence for the role of Yes-associated protein (YAP) in seizures. 4-AP was administered to mice or primary cultured astrocytes. YAP-specific small interfering RNA (siRNA) was administered to primary cultured astrocytes. Mouse brain tissue and surgical specimens from epileptic patient brains were examined, and the results showed that TRPV4 was upregulated, while astrocytes were activated and polarized to the A1 phenotype. The levels of glial fibrillary acidic protein (GFAP), cytokine production, YAP, signal transducer activator of transcription 3 (STAT3), intracellular Ca2+([Ca2+]i) and the third component of complement (C3) were increased in 4-AP-induced mice and astrocytes. Perturbations in the immune microenvironment in the brain were balanced by TRPV4 inhibition or the manipulation of [Ca2+]i in astrocytes. Knocking down YAP with siRNA significantly inhibited 4-AP-induced pathological changes in astrocytes. Our study demonstrated that astrocytic TRPV4 activation promoted neuroinflammation through the TRPV4/Ca2+/YAP/STAT3 signaling pathway in mice with seizures. Astrocyte TRPV4 inhibition attenuated neuroinflammation, reduced neuronal injury, and improved neurobehavioral function. Targeting astrocytic TRPV4 activation may provide a promising therapeutic approach for managing epilepsy.

1 案例资料 1.1 简要案情 某年1月28日中午12时许,卢某在武汉市某钢管租赁站内,与死者周某因纠纷发生打斗后被他人劝开.劝开后双方仍进行争吵,争吵过程中周某突然瘫软在地.卢某见状赶紧上前查看并拨打120急救电话,卢某在120电话的指导下对周某进行了胸外按压,一直持续到120救护车赶到现场.周某被送至医院后,经胸外按压等抢救无效,约25min后宣布死亡.

1 案 例 1.1 简要案情和病史摘要 某男,47岁,农民(农闲季节间断外出务工),某年6月3日07:47因"反复腹痛、腹泻伴发热3 d"入住某医院,空腹血糖19.3 mmol/L,诊断为"急性胃肠炎伴中度脱水,2型糖尿病伴血糖控制不佳".入院后血常规示:白细胞计数16.44×109/L,血红蛋白191 g/L,血小板计数52×109/L,红细胞计数6.18×1012/L,红细胞压积56.2％,中性粒细胞百分比89.0％,中性粒细胞绝对值14.64×109/L.甲型流感病毒抗原检测阴性,乙型流感病毒检测阴性.

在新型冠状病毒疫情中法医发挥专业优势,通过尸检为新型冠状病毒肺炎的诊疗提供了重要参考依据,在新冠肺炎的诊疗和减少恐慌、维持社会稳定中发挥了"侦察兵"作用。但我国法医学科体系也存在问题,专业设置、教育培训和鉴定管理体系存在不合理的现状和困境。后疫情时代,随着法制社会发展、公共卫生和健康社会需求,法医学科也面临挑战和发展机遇,需要重构法医学科体系,建立集约化现代法医中心管理体系,推进法医学科更好地服务于国家法制建设和人类健康,推进"健康中国2030"实施和"全健康"社会治理。

法医学；司法鉴定；全健康；法医科学技术体系；新型冠状病毒疾病

混合痔在临床上广泛采用吻合器痔上粘膜环切钉合术(procedure for prolapse and hemorrhoids,PPH)治疗,PPH术后尿潴留是较常见的并发症之一,多数经过心理疏导、物理疗法等干预措施后缓解,少数经导尿处理后恢复,因术后尿潴留导致膀胱憩室者罕见.尿潴留行导尿操作是临床上非常普通且安全的诊疗措施,虽然导尿操作的刺激、牵拉或疼痛可诱发心脑血管不良反应,但也罕见报道;因PPH术后并发尿潴留并膀胱憩室,行导尿操作后发生猝死的案例更是未见报道.本文报道1例此类法医病理学检验案例,以期引起临床和法医鉴定中重视和警惕.

Medical disputes in China are historically poorly documented. In particular, autopsy-based evaluation and its impact on medical malpractice claims remain largely unstudied. This study aims to document autopsy findings and medical malpractice in one of the largest cities of China, Wuhan, located in Hubei Province. A total of 519 autopsies were performed by the Department of Forensic Medicine, Wuhan University School of Medicine, Wuhan, China, over a 10-year period between 2004 and 2013. Of these cases, 190 (36.6%) were associated with medical malpractice claims. Joint evaluation by forensic pathologists and clinicians confirmed that 97 (51.1%) of the 190 claims were approved medical malpractice cases. The percentage of approved malpractice cases increased with patient age and varied according to medical setting, physician specialty, and organ system. The clinico-pathological diagnostic discrepancy was significantly different among various physician specialties (P = 0.031) and organ systems (P = 0.000). Of those cases involved in malpractice claims, aortic dissection, coronary heart disease, and acute respiratory infection were most common. Association between incorrect diagnosis and malpractice was significant (P = 0.001). This is the first report on China's medical malpractice and findings at autopsy which reflects the current state of health care services in one of the biggest cities in China.

Acute aortic dissection (AAD) is the most common cause of sudden unexpected death related to aortic diseases. A retrospective study of 31 sudden unexpected deaths caused by AAD was conducted at Xi'an Jiaotong University Forensic Center from 2001 to 2012. We summarized the forensic characteristics of AAD and assessed the clinically diagnostic accuracy of AAD. The characteristics of sudden unexpected death due to AAD were male predominant (male: female=6.7:1), relatively young with the mean age of 44, and predominance of type A dissection (77.4%). Cardiac tamponade was the most frequent cause of sudden death (87.1%). Of the 31 cases, 26 (83.9%) patients were not recognized clinically and were misdiagnosed with acute myocardial infarction, coronary artery disease, cholecystitis, acute gastroenteritis, renal/urinary lithiasis, or acute pancreatitis. In summary, AAD can be difficult to recognize, diagnosis is therefore sometimes delayed or missed. The medicolegal death investigation can help physicians have a better understanding of AAD.

Medical disputes in China are historically poorly documented. In particular, autopsy-based evaluation and its impact on medical malpractice claims remain largely unstudied. This study aims to document autopsy findings and medical malpractice in one of the largest cities of China, Wuhan, located in Hubei Province. A total of 519 autopsies were performed by the Department of Forensic Medicine, Wuhan University School of Medicine, Wuhan, China, over a 10-year period between 2004 and 2013. Of these cases, 190 (36.6%) were associated with medical malpractice claims. Joint evaluation by forensic pathologists and clinicians confirmed that 97 (51.1%) of the 190 claims were approved medical malpractice cases. The percentage of approved malpractice cases increased with patient age and varied according to medical setting, physician specialty, and organ system. The clinico-pathological diagnostic discrepancy was significantly different among various physician specialties (P=0.031) and organ systems (P=0.000). Of those cases involved in malpractice claims, aortic dissection, coronary heart disease, and acute respiratory infection were most common. Association between incorrect diagnosis and malpractice was significant (P=0.001). This is the first report on China's medical malpractice and findings at autopsy which reflects the current state of health care services in one of the biggest cities in China.

Objective:To analyze the distribution of age and cause of death in medical tangles,and to compare the accuracy of clinical diagnosis.Methods:A total of 123 forensic autopsy cases of medical tangles during January 2004 to December 2009 from forensic medicine department of medical school of Wuhan University were analyzed and compared retrospectively.Methods:The ratios of autopsy in county and city hospitals or clinics were higher;most cases were 30-50 years old;cardiovascular diseases and pneumonia was the most common in the adult and underage cases respectively,and misdiagnosis and miss-diagnosis rates in these cases were also the highest;drug adverse reaction rate was the highest in clinic.Conclusion:The autopsy results are helpful for evaluating the final diagnosis in medical tangle cases.Diseases of cardiovascular system for adult and pneumonia for children are the most fatal causes and tend to be misdiagnozed,and the diagnosis and treatment for these diseases should be cautious.

肾癌是常见的泌尿系肿瘤,发病率仅次于膀胱肿瘤.自杀基因治疗在晚期肿瘤的综合治疗中发挥了重要作用.单纯疱疹病毒胸苷激酶(HSV-TK)基因/无环鸟昔(GCV)及大肠杆菌胞嘧啶脱胺酶(CD)基因/5-氟胞嘧啶(5-FC)系统治疗机制不同,联合可产生协同效应.本研究旨在探讨联合TK/GCV、ClD/5-FC系统在肾癌治疗中的价值。

Objective To evaluate the value of detecting chlorophyll related genes of plankton in the diagnosis of drowning. MethodsEighteen rabbits were divided randomly into three groups: death by drowning (n=10), postmortem submersion (n=6) and control (n=2). The heart blood, lung, liver, kidney and brain tissues were taken from every rabbit. After isolated plankton from tissues with percoll and extracted their DNA, the chlorophyll-related genes, including EG (EG1 and EG2) and SK (SK1 and SK2), were detected using PCR technique. Meanwhile, diatom test was also performed from lung and liver tissues by nitric acid digestion method. ResultsFor the drowning group, the specific amplification products for EG1 were detected from 9 samples in heart blood, 10 samples in lung, 9 samples in liver, 7 samples in kidney and 8 samples in brain. The products for EG2 were detected from 8 samples, 10 samples, 7 samples, 5 samples and 7 samples accordingly. There were a small number of positives in heart blood, lung and kidney with SK1 and SK2 (≤2). For the postmortem submersion group, only one case was positive from heart blood and lung tissue respectively for EG1. No amplified product was detected for EG1 and EG2 in various tissues in control group, and also no product was detected for SK1and SK2 in other groups. In addition, diatoms were detected from 9 lung and 3 liver tissues in drowning group with the nitric acid digestion, and only one sample of lung was positive in the postmortem submersion group. ConclusionThe detection rate of the chlorophyll-related gene EG with PCR method was higher than that of diatom with nitric acid digestion method in drowning victims, and it can be used as a potentially useful tool for diagnosing drowning.

The diagnosis of drowning is one of the most difficult issues in forensic practice. We have developed a sensitive and specific PCR and DGGE method for identifying the 16S rDNA of plankton, which exists ubiquitously in all types of water. In order to evaluate the usefulness of this method for diagnosis of drowning, we used this method for detection of plankton 16S rDNA in drowned rabbits and non-drowned rabbits submerged after death, as well as two human drowning cases. Plankton DNA was identified from lung, liver, kidney, blood and brain of the drowned victims, and the DGGE patterns were helpful in indicating the site of drowning. Plankton DNA was also identified from two lung samples obtained from non-drowned rabbits. The results show that the new PCR–DGGE-based method is a potentially useful tool for diagnosing drowning.

Objective To experimentally evaluate the effect of different density gradient centrifugation on plankton separation from tissues with Percoll.Methods Mixture of three algae species with the homogenate of rabbit liver were divided into 5 centrifugation groups: well-mixed homogenate at high-speed centrifugation,well-mixed homogenate at low-speed centrifugation,overlaying homogenate at high-speed centrifugation,overla ying homogenate at low-speed centrifugation,and mixted homogenate centrifugated at 12 000r/min as control group.The planktons were separated from the mixture by density gradient centrifugation with Percoll.After separation,the sediment of different layer was detected under microscope,and DNA was extracted.The specific fragment of algae 16S rDNA and chlorophyll-related gene were subsequently amplified by PCR.Results In well-mixed homogenate at high-speed centrifugation,the algae were localized in the middle of tube as stratified layers.In overlaying homogenate at high-speed centrifugation,algae were detected beneath the tissue layer.In homogenate at low-speed centrifugation,less algae were found closely under the layer of tissue,and for the control,algae was in the bottom of tube.With DNA analysis,a 447bp fragment of 16S rDNA and a 194bp fragment of chlorophyll-related gene were detected in sediments separated from all group with Percoll.However,in control homogenate mixed with algae,no amplified product was detected with darker background of electrophoresis gel because of the interference of tissue DNA.Conclusion It is recommended that tissues homogenate should be centrifugated at high-speed density gradient centrifugation with Percoll,and sediments beneath the tissue layer should be collected for plankton isolation.