Sudden cardiac death (SCD) is a leading cause of global mortality, with coronary artery disease (CAD) being the primary etiology. Vascular smooth muscle cell (VSMC) migration and proliferation, regulated by actin cytoskeletal dynamics, are pivotal to CAD pathogenesis. The integrin-focal adhesion-cytoskeleton signaling axis modulates these processes; however, its genetic contribution to SCD-CAD remains poorly understood. In this case-control study of a southern Chinese Han population (239 SCD-CAD cases; 594 healthy controls), we investigated 10 insertion-deletion (indel) polymorphisms across eight key genes within this axis. Using multiplex fluorescent PCR and capillary electrophoresis (CE), followed by logistic regression and haplotype analyses, we identified three protective variants: rs10599004 (OR = 0.78, p = 0.018), rs143263543 (OR = 0.70, p = 0.024), and rs58213835 (OR = 0.80, p = 0.046). Additionally, a significant risk haplotype was identified in BCAR1 (ins-rs149617239-ins-rs58213835, p = 0.007). Mendelian randomization (MR) analysis further supported the causal roles of genetically predicted BCAR1, CRK, and DOCK1 expression in cardiovascular risk. These findings underscore the involvement of this signaling axis in SCD-CAD susceptibility and suggest these genetic markers as potential tools for cardiovascular risk assessment as well as forensic molecular autopsy. Further validation through large-scale cohort studies and functional assays is essential to fully elucidate the underlying molecular mechanisms.

Background and Purpose:While our previous cross-sectional study linked the lymphocyte-to-monocyte ratio (LMR) to symptomatic ICAS and plaque inflammation, its prospective value for predicting stroke recurrence remained unexplored. This study aimed to validate the association between LMR and plaque instability in a larger cohort and, critically, to determine whether baseline LMR predicts future ischemic events. Methods:We prospectively enrolled adult patients with radiologically confirmed ICAS from April 2018 to July 2024 at our tertiary cerebrovascular center. Comprehensive datasets, including clinical characteristics, laboratory markers (LMR and full inflammatory profiles), and neuroimaging features, were systematically collected and analyzed. Hematologic markers were compared between patients with ICAS with and without plaque enhancement and between those with and without symptoms. Receiver operating characteristic analysis was used to assess the discriminative value of LMR for plaque instability and determine optimal cutoff points. A follow-up was conducted to record stroke recurrence and evaluate the predictive role of baseline LMR. Results:We included 132 patients with confirmed ICAS. LMR emerged as an independent predictor of both plaque enhancement and symptomatic ICAS. An LMR cutoff of 4.0 effectively distinguished symptomatic from asymptomatic plaques. In 120 patients with ICAS with follow-up data, those with LMR of ≤ 4.0 had significantly higher recurrence (32.1% vs 15.6%, P = 0.026) and shorter median recurrence time (P = 0.049) than those with an LMR of > 4.0. Kaplan-Meier analysis showed a significantly lower recurrence-free survival rate in the LMR ≤ 4.0 group than in the LMR > 4.0 group (P = 0.011). Conclusion:A low LMR is associated with plaque instability in ICAS, and an LMR ≤ 4.0 may serve as a practical and accessible hematologic marker that could help identify patients at increased short-term risk of stroke recurrence.

Background and purpose: Short-term external counterpulsation (ECP) noninvasively augments cerebral blood flow by elevating blood pressure in ischemic stroke. The current retrospective case-control study examined the effect of long-term ECP treatment on blood pressure and beat-to-beat blood pressure variability (BPV) in patients with recent ischemic stroke. Method: The ECP group included data from 20 recent ischemic stroke patients who received five daily 1 h sessions each week for seven weeks, for a total of 35 sessions of ECP treatment from our ECP registry. An equivalent comparative control group without ECP treatment was composed from the same pool of patients and matched with cases by sex and age. Beat-to-beat heart rate and blood pressure were monitored before and after the long-term intervention. Power spectral analysis calculated the beat-to-beat BPV oscillations at very low frequency (VLF; <0.04 Hz), low frequency (LF; 0.04-0.15 Hz), high frequency (HF; 0.15-0.40 Hz), and the total power spectral density (TP; <0.40 Hz) and LF/HF ratio. Result: There was a significant reduction in systolic blood pressure (SBP) after the intervention compared with that before intervention in both groups (p < 0.05), but only the ECP group displayed a statistically significant reduction in diastolic blood pressure (DBP) (p = 0.023). The changes in SBP and DBP (delta SBP and delta DBP) from pre-intervention to completion showed no significant differences between the two groups (all p > 0.05). The ECP group exhibited a more pronounced and significant decrease in each spectral component of BPV after the intervention than at pre-intervention, with a substantial decrease in systolic BPV at TP (p = 0.048) and in the LF/HF ratios (p = 0.021 in diastolic BPV and p = 0.004 in systolic BPV, respectively) compared to the control group. Conclusions: A standard 35-session ECP treatment decreases beat-to-beat BPV but does not change SBP and DBP in patients with recent ischemic stroke. This implies that long-term ECP treatment may enhance autonomic regulation to benefit post-stroke clinical outcomes.

Ischemic stroke caused by ischemia-reperfusion (I/R) injury remains a major clinical challenge because the secondary pathological cascade involves oxidative stress, inflammation, endothelial dysfunction, neuronal loss, and mitochondrial injury. In this study, we developed a polydopamine-based nanodrug, CeO2@PDA-curcumin, and systematically evaluated its therapeutic potential in vitro and in vivo. Material characterization confirmed successful preparation of the composite nanoplatform, pH-responsive curcumin release, favorable colloidal stability, and potent radical-scavenging activity. In HUVECs exposed to H2O2-induced oxidative stress, CeO2@PDA-curcumin improved cell viability, reduced intracellular reactive oxygen species, regulated Bax/Bcl-2-related apoptotic signaling, and alleviated mitochondrial membrane potential loss. The inclusion of a free-curcumin group in all cell-based experiments further showed that curcumin contributed independently at the cellular level, although its individual radical-scavenging activity was not directly evaluated in the cell-free DPPH and hydroxyl-radical assays. In the MCAO rat model, CeO2@PDA-curcumin improved cerebral blood flow recovery, reduced infarct size and brain edema, alleviated histopathological injury and apoptosis, promoted angiogenesis and neuronal recovery, and improved neurobehavioral outcomes. Additional in vivo immunofluorescence analyses of PGC-1α, NRF1, and TFAM further supported a mitochondria-associated protective effect in the injured brain. Collectively, these results indicate that CeO2@PDA-curcumin is a promising antioxidant and neuroprotective nanotherapeutic candidate for ischemic stroke associated with I/R injury.

Cerebrovascular computational fluid dynamics (CFD) models often rely on generic boundary conditions, which may limit their ability to represent subject-specific hemodynamics and cerebral autoregulation (CA). We propose a multimodal data-driven boundary calibration (MDBC) framework integrating transcranial color-coded Doppler and continuous blood pressure monitoring to optimize individualized outlet resistances. As a proof-of-concept, we evaluated the MDBC framework in a single healthy volunteer at resting baseline and enhanced external counterpulsation (EECP)-a hemodynamic perturbation potentially triggering CA. Compared with conventional open boundary (OB) and static Murray allocation boundary (SMAB) strategies, MDBC achieved closer agreement with in vivo middle cerebral artery (MCA) velocity waveforms under both states. At rest, MDBC's left MCA relative root mean square error (rRMSE) was 7.19%, versus 22.85% (OB) and 30.89% (SMAB). During EECP, conventional models yielded rRMSEs > 32%, whereas MDBC maintained 11.24%. Meanwhile, MDBC reproduced inter-hemispheric perfusion imbalance, an EECP-induced flow surge in the right MCA, and pronounced wall shear stress increases that were masked by generic boundary strategies. Moreover, MDBC estimated a 25.8% increase in global cerebrovascular resistance during EECP, suggesting the capability of the framework to characterize subject-specific impedance adaptations potentially associated with CA during intervention. These single-subject findings support the technical feasibility of integrating multimodal physiological measurements into cerebrovascular CFD boundary calibration and warrant further validation in larger cohorts and patient populations.

The biological significance of aneurysmal wall enhancement (AWE) on high-resolution vessel wall imaging (HR-VWI) and its relationship with peripheral inflammation in intracranial fusiform aneurysms (IFA) remain incompletely understood. This study aims to investigate the association between circumferential AWE (CAWE) and peripheral immunoinflammatory indices in IFA, and to compare these features in different subtypes of unruptured intracranial aneurysm (UIA). In this retrospective study, 196 patients with UIA (38 fusiform, 158 saccular) were included. Peripheral blood samples collected at admission were used to calculate immunoinflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and platelet–lymphocyte ratio (PLR). AWE was assessed and categorized by blinded readers. Clinical characteristics and inflammatory markers were compared, and multivariate logistic regression was used to identify variables associated with CAWE in patients with IFA. Patients with CAWE in the IFA cohort showed differences in peripheral blood-derived immunoinflammatory indices, with higher monocyte counts and NLR but a lower LMR (all P < 0.05). NLR remained associated with CAWE in a multivariable model (OR: 4.78, 95

The clinical prevention and forensic diagnosis of sudden cardiac death (SCD) remain challenging due to the absence of standardized quantitative criteria for evaluating cardiac morphological and histopathological alterations. We aimed to develop a machine learning-driven cardiac lesion evaluation system to facilitate quantitative diagnosis and risk stratification of SCD. A total of 2284 adult autopsy cases from the forensic center at Sun Yat-sen University and 1883 external cases from five independent centers were enrolled to develop and validate an autopsy-based diagnostic model. Eight machine learning algorithms were employed, with the optimal model further tested in human–machine collaborative experiments. The model was subsequently transformed to identify myocardial infarction in a prospective clinical cohort of 204 patients presenting with chest pain. SCD cases exhibited significantly greater right ventricular wall thickness (OR: 1.17 [95

Sudden cardiac death (SCD) is a major cause of cardiovascular mortality, with coronary artery disease-related SCD (SCD-CAD) being the most prevalent form. Genetic factors and mitochondrial dysfunction, particularly in calcium homeostasis, are critical in SCD-CAD. However, the specific genetic factors linked to mitochondrial dysfunction in SCD-CAD remain poorly understood. In this case-control study, we analyzed 229 SCD-CAD cases and 598 controls from a Southern Han Chinese population, focusing on 12 insertion-deletion (indel) variants across six mitochondrial calcium uniporter (MCU) complex genes. We used capillary electrophoresis-based multiplex genotyping and performed logistic regression and haplotype analyses to assess the association of these variants with SCD-CAD susceptibility. Four significant indel variants and three risk-associated haplotypes were identified. Two of these indels were previously validated in the GWAS catalog as strongly linked to cardiac disorders. Additionally, Mendelian randomization (MR) analysis revealed a causal relationship between elevated levels of the SMDT1-encoded MCU regulator and increased risks of cardiovascular diseases, including coronary atherosclerosis, myocardial infarction, and cardiomyopathy. These findings highlight the role of MCU complex variants in SCD-CAD susceptibility and suggest their potential as biomarkers for cardiovascular risk stratification. Further research with larger cohorts is needed to confirm these results and explore underlying mechanisms.

BackgroundMyocardial infarction (MI) complicated by heart failure (HF) is a common and severe clinical condition associated with poor outcomes. Estimated plasma volume status (ePVS), a marker of congestion derived from hemoglobin and hematocrit, has shown promise in predicting outcomes in various cardiovascular diseases. This study aimed to investigate the relationship between ePVS and both short-term and long-term prognosis in patients with MI complicated by HF.MethodsA retrospective cohort study was conducted using data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, including 3,238 patients with MI complicated by HF. Patients were stratified into quartiles based on ePVS values. The primary outcomes were in-hospital mortality, 180-day mortality, and 1-year mortality. Kaplan–Meier curves, multivariate Cox regression analysis, and subgroup analyses were performed to assess the relationship between ePVS and outcomes.ResultsKaplan–Meier analysis showed significant differences in survival rates across ePVS quartiles for all outcomes (P < 0.001). Multivariate logistic regression analysis revealed that patients in the highest quartile of ePVS (Q4 vs. Q1) had an independently increased risk of in-hospital mortality (OR 1.58, 95% CI 1.16–2.13, P = 0.003). Cox regression analysis further demonstrated that higher ePVS (Q4 vs. Q1) was associated with an increased risk of 180-day mortality (HR 1.45, 95% CI 1.19–1.75, P < 0.001) and 1-year mortality (HR 1.51, 95% CI 1.27–1.80, P < 0.001). Both Kaplan–Meier survival curves and restricted cubic spline models confirmed a positive association between ePVS and long-term mortality risks.The association between ePVS and long-term outcomes was stronger than for in-hospital mortality. Subgroup analyses revealed that the relationship between ePVS and long-term mortality was more pronounced in patients with systolic blood pressure below 140 mmHg, lower LODS and OASIS scores, and those without hemorrhagic disorders or anemia (P for interaction <0.05).ConclusionePVS was an independent predictor of both short-term and long-term mortality in patients with MI complicated by HF. Its prognostic value was particularly significant for long-term outcomes, suggesting its potential utility in risk stratification and guiding treatment strategies for this high-risk population.

Background and Purpose:Peripheral inflammatory markers and aneurysm wall enhancement (AWE) on high-resolution vessel wall MRI (HR-VWI) may reflect inflammation in unruptured intracranial aneurysms (UIAs). We assessed cognitive function and its association with inflammatory markers in UIA patients. Methods:The study included 120 consecutive patients with UIAs diagnosed between September 2018 and December 2023 and a control group of 27 healthy adults at our institution. Neuropsychological function in these patients was evaluated using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton Anxiety Scale (HAMA), and Self-Rating Depression Scale (SDS). A MoCA score of <23 was classified as cognitive decline, while scores of ≥23 indicated normal cognitive function. The peripheral blood inflammatory markers and radiological characteristics were compared between the patients with cognitive decline and those with normal cognitive function. The presence of AWE and white matter hyperintensities (WMH) in UIA was identified through HR-VWI. Results:UIA patients demonstrated significantly poorer cognitive performance than controls, with lower MMSE (27.0 vs 29.0, P < 0.001) and MoCA scores (23.0 vs 25.0, P = 0.020). Patients with cognitive decline were older and exhibited elevated inflammatory markers (NLR, SII, hsCRP; all P < 0.05), along with higher rates of AWE and white matter hyperintensities (WMH) (both P < 0.001). Multivariate analysis identified AWE (OR = 5.33, 95% CI:1.82-15.59), WMH (OR = 4.26, 95% CI:1.58-11.49), and age (OR = 1.07, 95% CI:1.02-1.12) as independent predictors of cognitive decline (all P ≤ 0.01). Moreover, the cognitive decline group also showed higher SDS and HAMA scores (P < 0.05), suggesting a correlation between emotional distress and cognitive impairment. Conclusion:Untreated UIA patients exhibit cognitive decline associated with systemic inflammation (NLR, SII, hs-CRP). AWE, WMH and age are independent risk factors, suggesting vascular inflammation contributes to cognitive dysfunction.

BACKGROUND Intracranial aneurysms (IAs) coexisting with chronic-phase cerebral infarction (CI) present unique therapeutic challenges. Antiplatelet therapy for infarction increases bleeding risks during aneurysm treatment, whereas delayed intervention may raise rupture risks. Flow diverters (FDs) have transformed IA management, but evidence regarding their safety and efficacy in patients with concomitant chronic CI remains scarce. CASE REPORT A 56-year-old man presented with slurred speech and right-sided weakness caused by subacute CI in the left basal ganglia. Imaging identified a small, unruptured IA (2.50×1.74×1.54 mm) in the left internal carotid artery ophthalmic segment. The aneurysm was asymptomatic, without corresponding neurological deficits or headaches. Dual antiplatelet therapy (DAPT: aspirin 100 mg/day and clopidogrel 75 mg/day) and atorvastatin (20 mg/day) were initiated on Day 1. By Day 25 (chronic infarction phase, ≥21 days post-onset, with stabilized neurological symptoms), an FD (Pipeline™ Flex, 4.25×16 mm; Medtronic, USA) was implanted. Postoperatively, DAPT was maintained for 6 months to mitigate FD-related thromboembolic risk and prevent CI recurrence, after which single antiplatelet therapy (aspirin 100 mg/day) was continued. Follow-up at 12 and 36 months demonstrated complete aneurysm obliteration and full recovery of motor and speech functions without recurrent ischemia or hemorrhage. CONCLUSIONS FD implantation was safely performed and resulted in favorable outcomes for an unruptured IA in a patient with chronic-phase CI. Appropriate timing during the chronic phase and individualized antiplatelet management appeared to balance infarction control and aneurysm occlusion. Further research is warranted to determine broader applicability of these findings.

Vascular calcification is a pathological consequence of chronic inflammation and phenotypic switching in smooth muscle cells (SMCs). However, the mechanisms underlying vascular calcification remain unclear. The present study explores the role of the mechanosensor channel, Piezo1, in regulating vascular SMC (VSMC) death and vascular calcification. The findings of the present study demonstrated that Piezo1 expression is upregulated in the atherosclerotic plaques of both mice and patients. In vitro experiments revealed that calcifying medium (CM) induced an increase in Piezo1 and runt‑related transcription factor 2 (RUNX2) expression, triggered pyroptosis in cultured VSMCs and promoted calcium deposition in arterial rings. These effects were mitigated by a Piezo1 inhibitor and exacerbated by a Piezo1 agonist. Furthermore, gene deletion of NLR family pyrin domain containing 3 (NLRP3), caspase1 or gasdermin D also reduced CM‑induced pyroptosis and calcium deposition in VSMCs. Immunoprecipitation assays showed that calcium/calmodulin dependent protein kinase II (CaMKII), a downstream effector of Piezo1, interacted with RUNX2, and CaMKII inhibition attenuated both pyroptosis and calcification in VSMCs exposed to CM. The role of Piezo1 in mediating VSMC pyroptosis and vascular calcification was confirmed in a mouse model, where VSMC‑specific deletion of Piezo1 inhibited arterial calcification in chronic kidney disease. In conclusion, Piezo1 is a key regulator of vascular calcification via Ca2+‑CaMKII‑mediated activation of the NLRP3 inflammasome and subsequent VSMC pyroptosis.

Morphology of right ventricular outflow tract (RVOT) is potentially related to cardiovascular outcomes. However, this relationship still remains to be verified with direct evidence. We retrospectively reviewed cases from the autopsy specimen library in the Center of Forensic Medicine in Sun Yat-sen University from 2017 to 2023. Six RVOT morphological characteristics were measured and their association with cardiovascular diseases (CVDs), sudden cardiac death (SCD) and age at death was evaluated. Relationship between myocardial fibrosis in RVOT and CVDs was investigated. RVOT characteristics were recruited by machine learning algorithms for diagnosing CVDs. A total of 2370 cases were finally recruited. Perimeter of sub-valve plane (pSBV) in RVOT was positively associated with risk of CVDs and SCD (OR: 1.21, 95%CI: 1.07-1.37, p = 0.003; OR: 1.33, 95%CI: 1.16-1.52, p < 0.001). Compared with thickness of septum (tS) < 3.0 mm, tS >= 3.0 mm was associated with premature death in disease-dominant death (beta=-0.16, 95%CI: -0.20 to -0.11, p < 0.001) and SCD (beta=-0.15, 95%CI: -0.21 to -0.10, p < 0.001). Degree of myocardial fibrosis in the posterior septum was increased in coronary atherosclerosis (6.86%+/- 2.48% vs. 4.91%+/- 2.14%, p = 0.011) and cardiomyopathies (8.11%+/- 3.24% vs. 4.88%+/- 3.11%, p = 0.005). A logistic regression model, recruiting age, left and right ventricular wall thickness, pSBV, circumference of pulmonary annulus and aortic annulus, was elected as an optimal diagnostic model of CVDs, yielding AUC of 0.734 (95%CI: 0.705-0.763), 0.781 (0.740-0.821) and 0.763 (0.725-0.800) in training, validation and test sets. Increased pSBV significantly correlates with higher risk of CVDs and SCD. And tS >= 3.0 mm is an independent risk factor of premature death regardless of diseases.

The effect of continuous positive airway pressure (CPAP) on resistant hypertension in patients at high risk with obstructive sleep apnea (OSA) needs further investigation. We aimed to determine the effect of CPAP on blood pressure in patients with resistant hypertension and OSA. Databases including PubMed, EMBASE, MEDLINE, the Cochrane Library, and CMB were searched. Data were pooled using a random-effects or fixed-effects model to derive weighted mean differences (WMDs) and 95

The objective of this study is to investigate whether common genetic variants of the LTBP4 gene are linked to the susceptibility of sudden cardiac death in individuals who have atherosclerotic coronary artery disease (SCD-CAD) in Chinese populations. A total of 208 SCD-CAD cases and 638 controls were included in the analysis, and logistic regression was employed to assess the association between a 4-bp insertion/deletion polymorphism (rs34005443) within LTBP4 and the susceptibility to SCD-CAD among Chinese individuals. Logistic regression analysis demonstrated a notable association between the insertion allele of rs34005443 and an escalated susceptibility to SCD-CAD [odds ratio (OR) = 1.434; 95 % confidence interval:1.14-1.80; P = 1.79 x 10-3]. Genotype-phenotype correlation analysis was performed using Genotype-Tissue expression (GTEx) database and further validated by human myocardium using qPCR. Correlation analysis revealed that LTBP4 expression level was lower in samples with the insertion allele. Furthermore, the dual-luciferase activity assays indicated that rs34005443 may play a regulatory role. Additionally, we predicted 30 transcription factors that are likely to bind to rs34005443 and its highly linked genetic variants via 3DSNP database. Subsequent GO and KEGG analysis indicated that these transcription factors have a significant function in regulating gene expression. Finally, PPI network analysis suggested a tight connection between LTBP4 proteins and TGF8s, highlighting these genes as potential hub genes in the context of SCD-CAD. In summary, our study revealed that rs34005443 might contribute to SCD-CAD susceptibility by regulating LTBP4 expression. These findings revealed that this indel could be a potentially functional marker for molecular diagnosis and risk stratification of SCD-CAD.

Ischemic stroke is a significant burden on human health worldwide. Carotid Atherosclerosis stenosis plays an important role in the comprehensive assessment and prevention of ischemic stroke patients. High-resolution vessel wall magnetic resonance imaging has emerged as a successful technique for assessing carotid atherosclerosis stenosis. This advanced imaging modality has shown promise in effectively displaying a wide range of characteristics associated with the condition, leading to a comprehensive evaluation. High-resolution vessel wall magnetic resonance imaging not only enables a comprehensive evaluation of the instability of carotid atherosclerosis stenosis plaques but also provides valuable information for understanding the pathogenesis and predicting the prognosis of ischemic stroke patients. The purpose of this article is to review the application of high-resolution magnetic resonance imaging in ischemic stroke and carotid atherosclerotic stenosis.

AbstractLysophosphoglycerides (LPLs) have been reported to accumulate in myocardium and serve as a cause of arrhythmias in acute myocardial ischemia. However, in this study we found that LPLs level in the ventricular myocardium was decreased by the onset of acute myocardial ischemia in vivo in rats. Decreasing of LPLs level in left ventricular myocardium, but not right, was observed within 26 min of left myocardial ischemia, regardless of whether arrhythmias were triggered. Lower LPLs level in the ventricular myocardium was also observed in aconitine-simulated ventricular fibrillation (P < 0.0001) and ouabain-simulated III° atrioventricular block (P < 0.0001). Shot-lasting electric shock, e.g., ≤ 40 s, decreased LPLs level, while long-lasting, e.g., 5 min, increased it (fold change = 2.27, P = 0.0008). LPLs accumulation was observed in long-lasting myocardial ischemia, e.g., 4 h (fold change = 1.20, P = 0.0012), when caspase3 activity was elevated (P = 0.0012), indicating increased cell death, but not coincided with higher frequent arrhythmias. In postmortem human ventricular myocardium, differences of LPLs level in left ventricular myocardium was not observed among coronary artery disease- and other heart diseases-caused sudden death and non-heart disease caused death. LPLs level manifested a remarkable increasing from postmortem 12 h on in rats, thus abolishing the potential for serving as biomarkers of sudden cardiac death. Token together, in this study we found that LPLs in ventricular myocardium were initially decreased by the onset of ischemia, LPLs accumulation do not confer arrhythmogenesis during acute myocardial ischemia. It is necessary to reassess the roles of LPLs in myocardial infarction.

ObjectiveTo analyze the independent influencing factors of intimate partner homicide （IPH） cases, construct an IPH prediction model, and provide a basis for criminal profiling.MethodsA total of 476 convicted homicide cases in Guangdong Province from January 1, 2014, to December 31, 2020, were collected as modeling dataset. They were divided into the IPH group （n=180） and the non-intimate partner homicide （N-IPH） group （n=296） based on whether the offender and victim were intimate partners. Logistic regression was used to build the model, the model was evaluated through the receiver operating characteristic （ROC） curve analysis and a nomogram was drawn. Internal validation was conducted using ten-fold cross-validation method. A total of 126 court judgments from outside Guangdong Province from January 1, 2011, to December 31, 2020, were randomly collected for external validation.ResultsThrough multi-factor Logistic regression analysis, 7 variables were ultimately selected for inclusion in the model. The Hosmer-Lemeshow goodness of fit test result of the model was χ2=13.158, P=0.068. The ROC area under the curve （AUC） of the model was 0.939 （95% CI: 0.919-0.959）, the cut-off value was 0.292, the sensitivity was 0.900, and the specificity was 0.865. The calibration curve was close to the ideal curve. The ten-fold cross-validation showed the accuracy of 0.863 and a Kappa value of 0.708. The external validation results showed an AUC of 0.922 （95% CI: 0.872-0.971）, a cut-off value of 0.292, a sensitivity of 0.890, and a specificity of 0.886. The calibration curve tended to the ideal curve.ConclusionThe IPH prediction model based on forensic field indicators has good predictive ability, reliable accuracy and stability, and can provide a scientific method for criminal profiling.

Sudden cardiac death represents a significant diagnostic challenge for forensic pathologists, particularly in inherited arrhythmia syndromes or cardiomyopathies resulting from genetic defects. Molecular autopsies can reveal the underlying molecular etiology in such cases. In this study, we investigated a family with a history of sudden cardiac death to elucidate the molecular basis responsible for sudden cardiac death. The proband underwent a comprehensive forensic examination. Family members received thorough clinical evaluations, including electrocardiogram, Holter monitoring, echocardiography, and cardiac magnetic imaging. Whole exome sequencing and genetic analysis were performed on the deceased and her parents. In addition, Western blotting and patch-clamp recordings were employed to evaluate the expression and function of the mutant protein in vitro. Forensic examination diagnosed arrhythmogenic right ventricular cardiomyopathy (ARVC) as the cause of sudden death. Genetic analysis identified a novel missense mutation in SCN5A (p.V1323L), which was assessed as likely pathogenic by the ACMG guideline. Another family member carrying the mutation manifested long QT syndrome and mild cardiac fibrosis. The cellular electrophysiological study demonstrated that the mutation resulted in an enhanced late sodium current, suggesting it was a gain-of-function mutation. This study characterizes a novel SCN5A mutation that putatively causes long QT syndrome and may contribute to the development of ARVC. Our work expands the pathogenic spectrum of SCN5A variants and underscores the importance of molecular autopsy in sudden death cases, especially in those with suspected genetic disorders.