Report on Cardiac Gross Pathologic Measurements of Sudden Cardiac Death in Adults.

OBJECTIVES: To analyze the gross pathological data of sudden cardiac death (SCD) with different causes, to provide data support for the identification of sudden cardiac death with unknown causes. METHODS: A total of 167 adult SCD cases in the archive of the Forensic Expertise Institute of Nanjing Medical University from 2010 to 2020 were collected. The gross pathological data of SCD cases were summarized and the characteristics of different causes of death were statistically analyzed. RESULTS: The ratio of male to female SCD cases was 3.4∶1. Coronary heart disease was the leading cause of SCD, and mainly distributed in people over 40 years old. SCD caused by myocarditis was mainly distributed in young people and the mean age of death was (34.00±9.55) years. By analyzing the differences in cardiac pathological parameters of SCD with different causes, it was found that the aortic valve circumference was significantly dilated in the SCD caused by aortic aneurysm or dissection (P<0.05). The heart weight of SCD caused by aortic aneurysm or dissection and combined factors was greater, and both pulmonary and tricuspid valvular rings were dilated in the SCD caused by combined factors in adult males (P<0.05). CONCLUSIONS: Various gross pathological measures of SCD with different causes are different, which has reference value in the cause of death identification of SCD.

Construction and Application of YOLOv3-Based Diatom Identification Model of Scanning Electron Microscope Images.

OBJECTIVES: To construct a YOLOv3-based model for diatom identification in scanning electron microscope images, explore the application performance in practical cases and discuss the advantages of this model. METHODS: A total of 25 000 scanning electron microscopy images were collected at 1 500× as an initial image set, and input into the YOLOv3 network to train the identification model after experts' annotation and image processing. Diatom scanning electron microscopy images of lung, liver and kidney tissues taken from 8 drowning cases were identified by this model under the threshold of 0.4, 0.6 and 0.8 respectively, and were also identified by experts manually. The application performance of this model was evaluated through the recognition speed, recall rate and precision rate. RESULTS: The mean average precision of the model in the validation set and test set was 94.8% and 94.3%, respectively, and the average recall rate was 81.2% and 81.5%, respectively. The recognition speed of the model is more than 9 times faster than that of manual recognition. Under the threshold of 0.4, the mean recall rate and precision rate of diatoms in lung tissues were 89.6% and 87.8%, respectively. The overall recall rate in liver and kidney tissues was 100% and the precision rate was less than 5%. As the threshold increased, the recall rate in all tissues decreased and the precision rate increased. The F1 score of the model in lung tissues decreased with the increase of threshold, while the F1 score in liver and kidney tissues with the increase of threshold. CONCLUSIONS: The YOLOv3-based diatom electron microscope images automatic identification model works at a rapid speed and shows high recall rates in all tissues and high precision rates in lung tissues under an appropriate threshold. The identification model greatly reduces the workload of manual recognition, and has a good application prospect.

Detection of cell-surface sialic acids and photodynamic eradication of cancer cells using dye-modified polydopamine-coated gold nanobipyramids.

A nanoprobe based on polydopamine-coated gold nanobipyramids surface modified with molecules of a phenylboronic acid-substituted distyryl boron dipyrromethene has been fabricated and characterised using various physical and spectroscopic methods. It serves as an ultrasensitive sensor for sialic acids on the surface of cancer cells based on its dual surface-enhanced Raman scattering and fluorescence response. This biomarker can also trigger the photodynamic activity of these nanobipyramids, effectively eradicating the cancer cells mainly through apoptosis as shown by various bioassays.

Novel insight from the first lung transplant of a COVID-19 patient.

BACKGROUND: To reveal detailed histopathological changes, virus distributions, immunologic properties and multi-omic features caused by SARS-CoV-2 in the explanted lungs from the world's first successful lung transplantation of a COVID-19 patient. MATERIALS AND METHODS: A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID-19-associated pulmonary fibrosis. RESULTS: The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+ CD4- T cells, neutrophils, NK cells, γ/δ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL-1ß and IL-6 were in the area of mild fibrosis. Multi-omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation. CONCLUSIONS: Our results provide novel insight that the significant neutrophil/ CD3+ CD4- T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID-19 patient and may contribute to a better understanding of COVID-19 pathogenesis.

Correction: Investigation of heart lipid changes in acute ß-AR activation-induced sudden cardiac death by time-of-flight secondary ion mass spectrometry.

Correction for 'Investigation of heart lipid changes in acute ß-AR activation-induced sudden cardiac death by time-of-flight secondary ion mass spectrometry' by Jia-Qian Lou, et al., Analyst, 2020, DOI: 10.1039/d0an00768d.

Investigation of heart lipid changes in acute ß-AR activation-induced sudden cardiac death by time-of-flight secondary ion mass spectrometry.

Sudden cardiac death (SCD), one of the most common causes of human death, has become a major health and social problem. The postmortem diagnosis and prevention of SCD remain primary challenges in the medical community due to the lack of reliable diagnostic biomarkers. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a sensitive surface analysis technique for analyzing tissue slices with high spatial resolution. Here, ToF-SIMS followed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were employed to study the SCD mouse myocardium samples and obtain high-resolution chemical mappings and mass spectra. Distinction between normal control (NC) and acute ß-adrenergic receptor (ß-AR) activation-induced SCD groups was primarily due to the changes of diacylglycerols (DAG), phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC) and sphingomyelin (SM) in positive mode. Meanwhile, chemical mapping of the myocardium showed different lipid distributions in the SCD mouse myocardium. The metabolite alterations in mouse models were further verified by analyzing the heart tissue sections of a 28-year-old woman that died from isoprenaline injection. This pilot study demonstrated the significance of ToF-SIMS in characterizing the lipid variations in SCD heart tissues and might contribute to the postmortem diagnosis of SCD, the discovery of molecule candidates to discriminate the progression of SCD and the understanding of the potential postmortem diagnostic significance of SCD.

A Gold Nanoparticle Bouquet held on plasma membrane: An ultrasensitive dark-field imaging approach for Cancer Cell Analysis.

Rational: p53 is suppressing tumor protein correlated with the cell cycle factors and apoptosis. Here, a gold nanoparticle bouquet is designed for an ultrasensitive dark-field imaging approach for cancer cell analysis. Methods: AuNP60/APBA is functionalized by a gold nanoparticle bouquet-plasmonic 60 nm gold nanoparticles. And consistent APBA can be held on the plasma membrane. After 13 nm gold nanoparticles are functionalized with mannose (AuNP13/MN), the AuNP60/APBA gold nanoparticles are captured. The absorption spectrum of aggregation gold nanoparticles (AuNPs) shifts to near-infrared (NIR) region which can be observed under dark-field microscopy (DFM) and is treated the subsequent with photothermal therapy. Results: The results that MCF-7 cells were successfully destroyed under the near-infrared (NIR) irradiation and the intracellular WTp53 increased while the MTp53 decreased. These results indicated that p53 is the key molecule in the apoptosis signaling pathway. Photothermal therapy can stimulate the MTp53 in the cell signal conductive pathway. Conclusion: This work offers a new method for intracellular p53 analysis and a potential targeted cancer treatment.

FKBP51 is associated with early postoperative cognitive dysfunction in elderly patients undergoing hip fracture surgery.

Enhanced inflammation response was increasingly reported in association with postoperative cognitive dysfunction (POCD). Glucocorticoid receptor (GR) signal plays a key role in suppression of inflammation. This prospective cohort study aimed to evaluate GR signaling in elderly patients undergoing selective operation.One hundred twenty-six elderly patients were scheduled for hip fracture surgery with general anesthesia. Plasma cortisol levels and the expression levels of GR and FK506 binding protein 51 (FKBP51) in leukocytes were determined at 1 day preoperatively and 7 days. Postoperatively postoperative pain was assessed following surgery using visual analog pain scale (VAS). Neuropsychological tests were performed before surgery and 1 week postoperation. A decline of 1 or more standard deviations in 2 or more tests was considered to reflect POCD.POCD incidence in participants was 28.3% at 1 week after surgery. POCD patients presented significantly higher cortisol and FKBP51 levels compared with non-POCD patients (P < .05). Compared with non-POCD patients, VAS scores at 12 hours after surgery were higher in POCD patients (P < .05). No significant difference in expression levels of GR was found between groups POCD and non-POCD patients.High expression of FKBP51 in leukocytes and glucocorticoid resistance were associated with POCD in aged patients following hip fracture surgery.

Identification of p90 Ribosomal S6 Kinase 2 as a Novel Host Protein in HBx Augmenting HBV Replication by iTRAQ-Based Quantitative Comparative Proteomics.

PURPOSE: The aim of this study was to screen for novel host proteins that play a role in HBx augmenting Hepatitis B virus (HBV) replication. EXPERIMENTAL DESIGN: Three HepG2 cell lines stably harboring different functional domains of HBx (HBx, HBx-Cm6, and HBx-Cm16) were cultured. ITRAQ technology integrated with LC-MS/MS analysis was applied to identify the proteome differences among these three cell lines. RESULTS: In brief, a total of 70 different proteins were identified among HepG2-HBx, HepG2-HBx-Cm6, and HepG2-HBx-Cm16 by double repetition. Several differentially expressed proteins, including p90 ribosomal S6 kinase 2 (RSK2), were further validated. RSK2 was expressed at higher levels in HepG2-HBx and HepG2-HBx-Cm6 compared with HepG2-HBx-Cm16. Furthermore, levels of HBV replication intermediates were decreased after silencing RSK2 in HepG2.2.15. An HBx-minus HBV mutant genome led to decreased levels of HBV replication intermediates and these decreases were restored to levels similar to wild-type HBV by transient ectopic expression of HBx. After silencing RSK2 expression, the levels of HBV replication intermediates synthesized from the HBx-minus HBV mutant genome were not restored to levels that were observed with wild-type HBV by transient HBx expression. CONCLUSION AND CLINICAL RELEVANCE: Based on iTRAQ quantitative comparative proteomics, RSK2 was identified as a novel host protein that plays a role in HBx augmenting HBV replication.