Background Sudden cardiac death (SCD) remains a great health threat and diagnostic challenge, especially those cases without positive autopsy findings. Molecular biomarkers have been urgently needed for the diagnosis of SCD displaying negative autopsy results. Due to their nature of stability, microRNAs (miRNAs) have emerged as promising diagnostic biomarkers for cardiovascular diseases. Methods This study investigated whether specific cardio-miRNAs (miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p) could serve as potential biomarkers for the diagnosis of SCD. Thirty-four SCD cases were selected, 18 categorized as SCD with negative autopsy (SCD-negative autopsy) findings and 16 as SCD with positive autopsy (SCD-positive autopsy) findings such as coronary atherosclerosis and gross myocardial scar. Carbon monoxide (CO) intoxication (n = 14) and fatal injury death (n = 14) that displayed no pathological changes of myocardium were selected as control group, respectively. Histological analyses were performed to reveal the pathological changes and real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of those miRNAs. Results It showed that heart samples from the SCD-negative autopsy group displayed no remarkable difference with regard to the expression of cleaved-caspase3, CD31, and CD68 and the extent of fibrotic tissue accumulation when compared with control samples. The four cardio-miRNAs were significantly up-regulated in the SCD samples as compared with control. When discriminating SCD from controls, receiver operating characteristic (ROC) curve analysis revealed that the areas under the curve (AUC) of these 4 miRNAs were from 0.7839 to 0.9043 with sensitivity of 64.71–97.06% and specificity of 70–100%. Moreover, when discriminating the specific causes of SCD, the four miRNA expressions increased in the heart from the SCD-negative autopsy group as relative to that from the SCD-positive autopsy group, and a combination of two miRNAs presented higher diagnostic value (AUC = 0.7407–0.8667). Conclusion miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p may serve as independent diagnostic biomarkers for SCD, and a combination of two of these miRNAs could further discriminate detailed causes of SCD.

BackgroundIschemia/reperfusion (I/R) injury of heart is one of the major causes of acute cardiac injury, which may result in worsening or even loss of heart function. With novel microRNAs being evolutionarily discovered, numbers of them remained functionally unknown. We aimed to discover novel microRNAs with therapeutic or diagnostic potential in the setting of early cardiac I/R injury.MethodsCardiac electrical activity, biochemical detection and histopathology analysis were performed to reveal early changes of cardiac I/R injury. A microRNA array was performed to screen differential microRNAs in the mouse model of cardiac I/R injury. The differentially expressed microRNAs were validated in cardiac tissues and in serum samples.ResultsThe abnormality in electrocardiogram and increases in serum cTnI levels suggested the successful establishment of cardiac I/R injury in mice. A total of 1882 microRNAs were identified, of which 11 were significantly down-regulated and 41 were significantly up-regulated at 3 h post reperfusion. microRNA 223-3p and microRNA 3113-5p were among the mostly altered microRNAs and were validated to be up-regulated within the early hours of I/R injury in heart tissues. In the circulating system, cTnI, a sensitive marker of cardiac injury, or microRNA 223-3p only increased within the first 6 h post I/R injury. However, microRNA 3113-5p stably increased in the serum, keeping an increase of 2.5-fold throughout the 24 h. In the human serum samples, microRNA 3113-5p was detected to be significantly upregulated as soon as 3 h after I/R stimuli and kept significantly higher levels within the 48 h.ConclusionThis is the first study that reported the functional roles of microRNA 3113-5p in cardiovascular system. Our data suggested that cardiac microRNA 3113-5p might be a useful target for therapeutic purposes and circulating microRNA 3113-5p might serve as a stable marker for early diagnosis of cardiac I/R injury.

Schizophrenia is a severe mental disorder that is often comorbid with heart dysfunction and even sudden cardiac death (SCD). Clinical studies of SCD in schizophrenia have been largely reported, while there are limited autopsy studies that directly showed whole-scale information of such events. In this study, we present nine autopsy-based SCD cases in schizophrenia patients who died suddenly during hospitalization. Their medical records before and during hospitalization, and postmortem autopsy findings were summarized. These decedents had an average duration of schizophrenia for 6.83 ± 3.75 years with a male/female ratio of 4:5. They were all on intermittent antipsychotics medication before hospitalization and died within 15 days after hospitalization. Seven of the nine cases (77.8%) died of organic heart diseases such as severe coronary artery atherosclerosis (n = 4), myocarditis (n = 1), cardiomyopathy (n = 1), and pulmonary thromboembolism (n = 1). Two cases remained unexplained after systemic autopsy and toxicological examinations. Postmortem autopsy identified hepatic steatosis (n = 6) and respiratory inflammation (n = 3) as the most common associate extra-cardiac lesions. Our data provided autopsy-based data of SCD cases in schizophrenia and highlighted an intensive care of such patients during hospitalization.

Epilepsy is a common neurological disorder that is associated with increased morbidity and mortality. Sudden unexpected death in epilepsy (SUDEP) is one of the most common causes for epilepsy-related deaths and its characteristics remain largely unknown, particularly from a forensic autopsy perspective. The present study aimed to investigate the neurological, cardiac, and pulmonary findings for a total of 388 SUDEP decedents, encompassing three cases from our forensic center during 2011–2020 and 385 literature-reported autopsy cases. In the cases mentioned in this study, two of them presented with only mild cardiac abnormalities, such as focal myocarditis and mild coronary atherosclerosis of the left anterior coronary artery. The third one was negative of any pathological findings. After pooling together these SUDEP cases, we found that neurological changes (n = 218 cases, 56.2%) were the most common postmortem findings associated with SUDEP, with cerebral edema/congestion (n = 60 cases, 15.5%) and old traumatic brain injury (n = 58 cases, 14.9%) being the major findings. Interstitial fibrosis, myocyte disarray/hypertrophy, and mild coronary artery atherosclerosis were the most common findings related to primary cardiac pathology, documented in 49 (12.6%), 18 (4.6%), and 15 (3.9%) cases, respectively. Non-specific pulmonary edema was the major finding in the lungs. This is an autopsy-based study that reports the scenario of postmortem findings for SUDEP cases. Our study paves the way for understanding the pathogenesis of SUDEP and the interpretation of death.

BackgroundSudden cardiac death (SCD) remains a great health threat and diagnostic challenge, especially those cases without positive autopsy findings. Molecular biomarkers have been urgently needed for the diagnosis of SCD displaying negative autopsy results. Due to their nature of stability, microRNAs (miRNAs) have emerged as promising diagnostic biomarkers for cardiovascular diseases. MethodsThis study investigated whether specific cardio-miRNAs (miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p) could serve as potential biomarkers for the diagnosis of SCD. Thirty-four SCD cases were selected, 18 categorized as acute myocardial infarction (AMI) without positive autopsy findings and 16 as atherosclerotic cardiovascular diseases (ASCVD) with gross myocardial scar. Carbon monoxide (CO) intoxication (n=14) and fatal injury death (n=14) that displayed no pathological changes of myocardium were selected as control group, respectively. Histological analyses were performed to reveal the pathological changes and real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of those miRNAs. Resultsit showed that heart samples from the AMI group displayed no remarkable difference with regard to the expression of cleaved-caspase3, CD31, and CD68 and the extent of fibrotic tissue accumulation when compared with control samples. The four cardio-miRNAs were significantly up-regulated in the SCD samples as compared with control. When discriminating SCD from controls, ROC curve analysis revealed that the areas under the curve (AUC) of these 4 miRNAs were from 0.7839 to 0.9043 with sensitivity of 64.71-97.06% and specificity of 70-100%. Moreover, when discriminating the specific causes of SCD, the four miRNA expressions increased in the AMI heart as relative to ASCVD, and a combination of two miRNAs presented higher diagnostic value (AUC=0.7407-0.8667). ConclusionmiR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p may serve as independent diagnostic biomarkers for SCD, and a combination of two of these miRNAs could further discriminate detailed causes of SCD.