Shen-Jiang Hu

Background: The rarity of right heart masses challenges diagnostic proficiency, while reproducibility is affected by the echocardiography operator. Artificial intelligence (AI)-based imaging tools may help address these limitations. Methods: In this retrospective study (2013–2024), we enrolled surgical patients with right heart masses and obtained preoperative transthoracic (TTE) and transesophageal (TEE) echocardiographic images. Two-dimensional (2D) TTE ( n = 98) and TEE ( n = 87) images underwent radiomics analysis. Binary classification models were developed to differentiate benign from non-benign lesions using five machine-learning (ML) algorithms (decision trees, logistic regression, random forests, support vector machines (SVMs), extreme gradient boosting (XGBoost)). ML performance was compared with that of a deep-learning model based on the residual network (ResNet)-18 architecture using standard evaluation metrics such as the area under the curve (AUC). Results: In 2D TTE analysis, ResNet-18 achieved the highest AUC (0.889), followed by XGBoost (0.836) and decision tree (0.815). ResNet-18 significantly outperformed SVM ( P = 0.013) and logistic regression ( P = 0.028), but showed no significant differences versus XGBoost ( P = 0.408), decision tree ( P = 0.429), or random forest ( P = 0.053). In 2D TEE analysis, SVM achieved the highest AUC (0.959), followed by XGBoost (0.924) and random forest (0.906), with no significant differences among these models (all P > 0.05). ResNet-18 (AUC = 0.900) significantly outperformed only the decision tree ( P = 0.027). Conclusion: ResNet-18 showed the highest TTE AUC and outperformed SVM and logistic regression, but was comparable to other ML models. SVM achieved the highest TEE AUC, with no significant differences among top models. These findings provide a preliminary AI benchmark for right heart mass diagnosis, though external validation is needed.

Background: Cardiac arrhythmia is a common disease associated with high mortality and morbidity. Circulating leukocyte counts, which serve as a biomarker for assessing systemic immune status, have been linked to arrhythmias in observational studies. However, observational studies are plagued by confounding factors and reverse causality, whether alterations in circulating leukocyte components are causally associated with arrhythmias remains uncertain. The present study explored this question based on genetic evidence.Methods and findings: We performed Mendelian randomization (MR) analysis to evaluate whether alterations in leukocyte counts affect aggregated risk of all types of arrhythmia or risk of five specific types of arrhythmia. Single-nucleotide polymorphisms serving as proxies for leukocyte differential counts were retrieved from the Blood Cell Consortium, and statistical data on arrhythmias were obtained from the UK Biobank), FinnGenand a meta-analysis of genome-wide association studies for atrial fibrillation. We applied inverse variance-weighted method as the primary analysis, complemented by a series of sensitivity analyses. Bidirectional analyses were conducted to assess reverse causality. Finally, multivariable MR was performed to study the joint effects of multiple risk factors. We found that genetically predicted differential leukocyte counts were not significantly associated with aggregated occurrence of all types of arrhythmia. In contrast, each 1-standard deviation increase in lymphocyte count was associated with 46% higher risk of atrioventricular block (OR 1.46, 95% CI 1.11–1.93, p=0.0065). A similar effect size was observed across all MR sensitivity analyses, with no evidence of horizontal pleiotropy. Reverse MR analysis suggested that atrioventricular block was unlikely to cause changes in lymphocyte count. Primary MR analysis based on the inverse-variance weighted method suggested that changes in neutrophil count alter risk of right bundle branch block, and changes in basophil count alter risk of atrial fibrillation. However, these causal relationships were not robust in sensitivity analyses. We found no compelling evidence that neutrophil or lymphocyte counts cause atrial fibrillation.Conclusion: Our data support higher lymphocyte count as a causal risk factor for atrioventricular block. These results highlight the importance of immune cells in the pathogenesis of specific cardiac conduction disorders.

A large number of studies suggest that uric acid (UA) is related to the occurrence, complications, and prognosis of atrial fibrillation (AF). However, the guidelines did not clearly elaborate on this issue. The current research results need to be summarized to analyze the association between UA and AF. This study found that in the current clinical research on the relationship between UA and AF, studies mainly focus on the development or complications of AF. A lot of repetitive work does not deepen awareness of this question. In contrast, studies investigating the effects of UA-lowering therapy on the management of AF are limited. The only reports deny the protective effect of UA-lowering therapy. For now, we suggest that UA is close to the occurrence and progression of AF; therefore, it may have important significance as a clinical marker. The role of UA-lowering therapy in the management of AF is one of the next key issues to be explored. It will be a meaningful topic to focus on the latest research on AF ablation and to conduct a secondary analysis to explore the prognostic impact of UA on the latest treatment methods for AF. Multiomics techniques may allow us to have a deeper understanding of the role of UA in AF management in the future.

Purpose: This study aimed to explore relationships between whole blood copper (Cu), zinc (Zn) and Cu/Zn ratio and cardiac dysfunction in patients with septic shock. Subjects and Methods: Between April 2018 and March 2020, septic shock patients with sepsis-induced left ventricular systolic dysfunction (SILVSD, left ventricular ejection fraction, LVEF< 50%) and with no sepsis-induced myocardial dysfunction (non-SIMD, septic shock alone and LVEF> 50%) and controls were prospectively enrolled. Whole blood Cu and Zn levels were measured using flame atomic absorption spectrophotometry. Results: Eighty-six patients with septic shock including both 41 SILVSD and 45 non-SIMD and 25 controls were studied. Whole blood Cu levels and Cu/Zn ratio were significantly higher and Zn levels were lower in SILVSD compared with non-SIMD and controls (Cu, p=0.009, < 0.001; Zn, p=0.029, < 0.001; Cu/Zn ratio, p=0.003, < 0.001). Both increased whole blood Cu and Cu/Zn ratio and reduced Zn were associated with lower LVEF (all p< 0.001) and higher amino-terminal pro-B-type natriuretic peptide (NT-proBNP) (Cu, p=0.002; Zn, p< 0.001; Cu/Zn ratio, p< 0.001) and had predictive values for SILVSD (Cu, AUC=0.666, p=0.005; Zn, AUC=0.625, p=0.039; Cu/Zn ratio, AUC=0.674, p=0.029). Whole blood Cu levels and Cu/Zn ratio were increased but Zn levels were reduced in non-survivors compared with survivors (Cu, p< 0.001; Zn, p< 0.001; Cu/Zn ratio, p< 0.001). Whole blood Cu and Zn displayed the value of predicting 28-day mortality (Cu, AUC = 0.802, p< 0.001; Zn, AUC=0.869, p< 0.001; Cu/Zn ratio, AUC=0.902, p< 0.001). Conclusion: Findings of the study suggest that whole blood Cu levels and Cu/Zn ratio are increased in SILVSD patients and positively correlated with cardiac dysfunction, while whole blood Zn levels are reduced and negatively associated with cardiac dysfunction. Moreover, both whole blood Cu, Zn and Cu/Zn ratio might distinguish between SILVSD and non-SIMD in septic shock patients and predict 28-day mortality. Trial Registration: Registered at http://www.chictr.org.cn/ChiCTR1800015709.

Dilated cardiomyopathy (DCM) is a relatively common cause of heart failure and the leading cause of heart transplantation. Aberrant changes in long non-coding RNAs (lncRNAs) are involved in DCM disorder; however, the detailed mechanisms underlying DCM initiation and progression require further investigation, and new molecular targets are needed. Here, we obtained lncRNA-expression profiles associated with DCM and non-failing hearts through microarray probe-sequence re-annotation. Weighted gene co-expression network analysis revealed a module highly associated with DCM status. Then eight hub lncRNAs in this module (FGD5-AS1, AC009113.1, WDFY3-AS2, NIFK-AS1, ZNF571-AS1, MIR100HG, AC079089.1, and EIF3J-AS1) were identified. All hub lncRNAs except ZNF571-AS1 were predicted as localizing to the cytoplasm. As a possible mechanism of DCM pathogenesis, we predicted that these hub lncRNAs might exert functions by acting as competing endogenous RNAs (ceRNAs). Furthermore, we found that the above results can be essentially reproduced in an independent external dataset. We observed the localization of hub lncRNAs by RNA-FISH in human aortic smooth muscle cells and confirmed the upregulation of the hub lncRNAs in DCM patients through quantitative RT-PCR. In conclusion, these findings identified eight candidate lncRNAs associated with DCM disease and revealed their potential involvement in DCM partly through ceRNA crosstalk. Our results facilitate the discovery of therapeutic targets and enhance the understanding of DCM pathogenesis.

Background: The dyshomeostasis of trace elements is associated with multiple organ dysfunction in patients with septic shock. However, it remains unclear whether the change of whole blood copper (Cu) and zinc (Zn) levels influence cardiac function in patients with septic shock. Here, we sought to explore relationship between whole blood Cu and Zn and cardiac dysfunction in septic shock. Methods: Between April 2018 and March 2020, septic shock patients with sepsis-induced left ventricular systolic dysfunction (SILVSD, left ventricular ejection fraction, LVEF ＜ 50%) and with no sepsis-induced myocardial dysfunction (non-SIMD, septic shock alone and LVEF＞ 50%) on an intensive care unit (ICU) in south China and healthy controls were prospectively enrolled. whole blood Cu and Zn levels were measured using flame atomic absorption spectrophotometry.Results: 86 patients with septic shock including 41 SILVSD and 45 non-SIMD and 25 healthy controls were studied. Whole blood Cu levels were significantly higher and Zn were significantly lower in SILVSD compared with non-SIMD and controls [Cu, (16.34±1.93) vs. (15.23±2.07) vs. (14.02±1.65) µmol/L, p = 0.009, < 0.001; Zn, (78.45±12.18) vs. (85.07±14.80) vs. (94.90±14.78) µmol/L, p = 0.029, < 0.001]. Both increased whole blood Cu and reduced Zn were associated with lower LVEF ( all p < 0.001) and higher amino-terminal pro-B-type natriuretic peptide (NT-proBNP) (Cu, p = 0.002, Zn, p = 0.001), and had predictive values for SILVSD [Cu, (AUC = 0.666; p = 0.005) ; Zn, (AUC = 0.625; p = 0.039)]. Whole blood Cu levels were increased but Zn were reduced in non-survivors compared with survivors[Cu, (17.20 ±2.25) vs. (14.99 ±1.49) µmol/L, p < 0.001; Zn, (71.17 ±11.98) vs. (87.67±11.30) µmol/L, p < 0.001],. Whole blood Cu and Zn displayed the value of predicting 28-day mortality [Cu (AUC = 0.802, p < 0.001); Zn (AUC = 0.869, p < 0.001)].Conclusions: Whole blood Cu levels were increased in SILVSD patients and positively correlated with the cardiac dysfunction while Whole blood Zn were reduced and negatively associated with the cardiac dysfunction. Moreover, both whole blood Cu and Zn could distinguish between SILVSD and non-SIMD in septic shock patients and predict 28-day mortality.Trial registration: ChiCTR1800015709. Registered 16 April 2018, http://www.chictr.org.cn/edit.aspx?pid=26746&htm=4.

Farnesyltransferase (FTase) is an important enzyme that catalyses the modification of protein isoprene downstream of the mevalonate pathway. Previous studies have shown that the tissue of the heart in the suprarenal abdominal aortic coarctation (AAC) group showed overexpression of FTaseβ (FNTB) and the activation of the downstream protein Ras was enhanced. FTase inhibitor (FTI) can alleviate myocardial fibrosis and partly improve cardiac remodelling in spontaneously hypertensive rats. However, the exact role and mechanism of FTase in myocardial hypertrophy and remodelling are not fully understood. Here, we used recombinant adenovirus to transfect neonatal rat ventricular cardiomyocytes to study the effect of FNTB overexpression on myocardial remodelling and explore potential mechanisms. The results showed that overexpression of FNTB induces neonatal rat ventricular myocyte hypertrophy and reduces the survival rate of cardiomyocytes. FNTB overexpression induced a decrease in mitochondrial membrane potential and increased apoptosis in cardiomyocytes. FNTB overexpression also promotes autophagosome formation and the accumulation of autophagy substrate protein, LC3II. Transmission electron microscopy (TEM) and mCherry‐GFP tandem fluorescent‐tagged LC3 (tfLC3) showed that FNTB overexpression can activate autophagy flux by enhancing autophagosome conversion to autophagolysosome. Overactivated autophagy flux can be blocked by bafilomycin A1. In addition, salirasib (a Ras farnesylcysteine mimetic) can alleviate the hypertrophic phenotype of cardiomyocytes and inhibit the up‐regulation of apoptosis and autophagy flux induced by FNTB overexpression. These results suggest that FTase may have a potential role in future treatment strategies to limit the adverse consequences of cardiac hypertrophy, cardiac dysfunction and heart failure.

Hyperglycemia contributes to the excessive proliferation and migration of vascular smooth muscle cells (VSMC), which are closely associated with atherosclerosis. MicroRNAs (miRNAs/miRs) constitute a novel class of gene regulators, which have important roles in various pathological conditions. The aim of the present study was to identify miRNAs involved in the high glucose (HG)‑induced VSMC phenotype switch, and to investigate the underlying mechanism. miRNA sequencing and reverse transcription‑quantitative PCR results indicated that inhibition of miR‑125a expression increased the migration and proliferation of VSMCs following HG exposure, whereas the overexpression of miR‑125a abrogated this effect. Furthermore, dual‑luciferase reporter assay results identified that 3‑hydroxy‑3-methyglutaryl‑coA reductase (HMGCR), one of the key enzymes in the mevalonate signaling pathway, is a target of miR‑125a. Moreover, HMGCR knockdown, similarly to miR‑125a overexpression, suppressed HG‑induced VSMC proliferation and migration. These results were consistent with those from the miRNA target prediction programs. Using a rat model of streptozotocin‑induced diabetes mellitus, it was demonstrated that miR‑125a expression was gradually downregulated, and that the expressions of key enzymes in the mevalonate signaling pathway in the aortic media were dysregulated after several weeks. In addition, it was found that HG‑induced excessive activation of the mevalonate signaling pathway in VSMCs was suppressed following transfection with a miR‑125a mimic. Therefore, the present results suggest that decreased miR‑125a expression contributed to HG‑induced VSMC proliferation and migration via the upregulation of HMGCR expression. Thus, miR‑125a‑mediated regulation of the mevalonate signaling pathway may be associated with atherosclerosis.

Background: High risk of embolic events exists in both patients with chronic atrial fibrillation (AF) and patients in the perioperative period of ablation (effective treatment for AF). Therefore, anticoagulant therapy is important. Oral anticoagulants can be divided into two major categories: vitamin K antagonists (VKAs) and non-vitamin K antagonist oral anticoagulants (NOACs). VKAs, represented by warfarin, have been widely used as traditional anticoagulants, whereas NOACs have been used in clinical practice, but their anticoagulant effects and side effects are still the focus of research. We used a meta-analysis to compare the incidence of left atrial thrombi (LAT) between different anticoagulants. Methods: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library databases for observational studies that compared the transesophageal echocardiography (TEE) findings for patients treated with NOACs and VKAs. The incidence of LAT and dense spontaneous echocardiographic contrast (dense SEC) were extracted as the basis of the meta-analysis. Results: Fifteen studies were included in the meta-analysis. We found that patients anticoagulated with NOACs and VKAs had similar incidence of LAT (OR = 0.74, 95%CI: 0.55–1.00). After excluding the heterogeneous article by sensitivity analysis, we found the incidence of LAT in patients anticoagulated with NOACs is lower than VKAs (OR = 0.59, 95%CI: 0.42–0.84). The results of subgroup analysis showed that the incidence of LAT among three types of NOACs have no significant difference (dabigatran vs. rivaroxaban, OR = 1.16 [0.75, 1.81]; rivaroxaban vs. apixaban, OR = 0.97 [0.54, 1.74]; dabigatran vs. apixaban, OR = 1.09 [0.55, 2.16]). Conclusion: Patients anticoagulated with NOACs may have lower incidence of LAT than VKAs. The incidence of LAT among different type of NOACs are similar.