Review and Thinking on Forensic Pathological Changes of Coronavirus-Infected Diseases.

Since the beginning of this century, three types of coronavirus have widely transmitted and caused severe diseases and deaths, which strongly indicates that severe infectious diseases caused by coronavirus infection are not accidental events. Coronavirus-infected diseases are mainly manifested by respiratory symptoms, with multiple organ dysfunctions. Precisely investigating the pathological process, characteristics and pathogenesis of coronavirus-infected diseases will be beneficial for us to understand clinical manifestations and provide targeted suggestions on prophylaxis and treatment. This paper briefly reviews the pathological findings of three known coronavirus-infected diseases, and attempts to construct the pathological spectrum of coronavirus-infected diseases, aiming to provide reference and thinking for autopsy, histopathological examination and animal infection model study of coronavirus-infected diseases.

Review and Thinking on Forensic Pathological Changes of Coronavirus-Infected Diseases / 法医学杂志

Since the beginning of this century, three types of coronavirus have widely transmitted and caused severe diseases and deaths, which strongly indicates that severe infectious diseases caused by coronavirus infection are not accidental events. Coronavirus-infected diseases are mainly manifested by respiratory symptoms, with multiple organ dysfunctions. Precisely investigating the pathological process, characteristics and pathogenesis of coronavirus-infected diseases will be beneficial for us to understand clinical manifestations and provide targeted suggestions on prophylaxis and treatment. This paper briefly reviews the pathological findings of three known coronavirus-infected diseases, and attempts to construct the pathological spectrum of coronavirus-infected diseases, aiming to provide reference and thinking for autopsy, histopathological examination and animal infection model study of coronavirus-infected diseases.

The Rhinolophus affinis bat ACE2 and multiple animal orthologs are functional receptors for bat coronavirus RaTG13 and SARS-CoV-2

Bat coronavirus (CoV) RaTG13 shares the highest genome sequence identity with SARS-CoV-2 among all known coronaviruses, and also uses human angiotensin converting enzyme 2 (hACE2) for virus entry. Thus, SARS-CoV-2 is thought to have originated from bat. However, whether SARS-CoV-2 emerged from bats directly or through an intermediate host remains elusive. Here, we found that Rhinolophus affinis bat ACE2 (RaACE2) is an entry receptor for both SARS-CoV-2 and RaTG13, although RaACE2 binding to the receptor binding domain (RBD) of SARS-CoV-2 is markedly weaker than that of hACE2. We further evaluated the receptor activities of ACE2s from additional 16 diverse animal species for RaTG13, SARS-CoV, and SARS-CoV-2 in terms of S protein binding, membrane fusion, and pseudovirus entry. We found that the RaTG13 spike (S) protein is significantly less fusogenic than SARS-CoV and SARS-CoV-2, and seven out of sixteen different ACE2s function as entry receptors for all three viruses, indicating that all three viruses might have broad host rages. Of note, RaTG13 S pseudovirions can use mouse, but not pangolin ACE2, for virus entry, whereas SARS-CoV-2 S pseudovirions can use pangolin, but limited for mouse, ACE2s enter cells. Mutagenesis analysis revealed that residues 484 and 498 in RaTG13 and SARS-CoV-2 S proteins play critical roles in recognition of mouse and human ACE2. Finally, two polymorphous Rhinolophous sinicus bat ACE2s showed different susceptibilities to virus entry by RaTG13 and SARS-CoV-2 S pseudovirions, suggesting possible coevolution. Our results offer better understanding of the mechanism of coronavirus entry, host range, and virus-host coevolution.

Guide to the Forensic Pathology Practice on Death Cases Related to Corona Virus Disease 2019 （COVID-19） （Trial Draft） / 法医学杂志

Autopsy is of great significance to the elucidation of the pathological changes, pathogeneses and causes of death of corona virus disease 2019 （COVID-19） and can provide theoretical basis for more scientific and accurate prevention and control of the outbreak. Based on related laws and regulations, such as the Law of the People's Republic of China on Prevention and Control of Infectious Diseases, the clinical manifestations and epidemiological characteristics of COVID-19, and the related guidelines on the prevention and control of the outbreak, combined with the practical work of forensic pathology examination, the Guide to the Forensic Pathology Practice on Death Cases Related to Corona Virus Disease 2019 （COVID-19） （Trial Draft） has been developed. This guide includes information on the background investigation of the cases, autopsy room requirements, personal prevention and protections, external examinations, autopsy, auxiliary examinations, and so on. This guide can be used as a reference by forensic and pathological examination institutions, as well as examination staff.

Eye-acupuncture intervention reduces cerebro-cortical apoptosis of neurovascular unit in cerebral ischemia-reperfusion injury rats / 针刺研究

OBJECTIVE: To observe the effect of eye-acupuncture intervention on cerebro-cortical apoptosis of microvascular endothelial cells, neurons and astrocytes (main components of neurovascular unit) and the expression of Bad (an apoptosis promoter) and B-cell lymphoma-extra large(Bcl-xL) proteins in focal cerebral ischemia-reperfusion injury (CIRI) rats, so as to explore its mechanisms underlying improvement of CIRI. METHODS: SD rats were randomly divided into control, sham-operation, model 3 h, model 24 h, model 72 h, eye-acupuncture 3 h, eye-acupuncture 24 h and eye-acupuncture 72 h groups(n＝12 in each group). The CIRI model was established by middle cerebral artery occlusion/reperfusion (MCAO/R). Eye-acupuncture was applied to bilateral "Gan" (Liver) regions, "Shen" (Kidney) regions, "Shangjiao" (Upper-energizer) and "Xiajiao" (Lower-energizer) for 20 min, once 3 h and every 12 h after modeling. The expression levels of Bad and Bcl-xL in the ischemic cerebral cortex tissue were detected by Western blot. The apoptotic neurons, microvascular endothelial cells and astrocytes were assayed by immunofluorescence double labeling (Nestin/TUNEL, CD34/TUNEL and glial fibrillary acidic protein [GFAP]/TUNEL) separately. RESULTS: After modeling, the numbers of apoptotic neurons, microvascular endothelial cells and astrocytes in the ischemic cerebral cortex tissue were significantly increased in the model 72 h group than in the sham-operation group (P<0.01). Following the treatment, the numbers of the 3 types of apoptotic cells were markedly lower in the eye-acupuncture 72 h group than in the model 72 h group(P<0.01). The expression levels of Bad and Bcl-xL proteins were notably up-regulated in the model 3 h, model 24 h and model 72 h groups than in the sham operation group(P<0.01). Following eye-acupuncture intervention, modeling induced increase of the Bad expression were obviously reversed in eye-acupuncture 24 h and eye-acupuncture 72 h groups than those in the 2 model groups(P<0.05). And the increase of Bcl-xL expression levels were further increased in the eye-acupuncture groups in comparison with those in the 3 model groups (P<0.01). CONCLUSION: Eye-acupuncture can down-regulate the expression of Bad protein, and up-regulate the expression of Bcl-xL protein in the ischemic cerebral cortex in CIRI rats, which may contribute to its function in reducing apoptotic neurons, microvascular endothelial cells and astrocytes, suggesting a protective effect of eye-acupuncture intervention on neurovascular unit.