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Abstract Background In recent years, lead-induced tricuspid regurgitation (LITR) has attracted increasing attention. At present, there are two commonly used transvalvular methods for pacing lead wires to enter the right ventricle. The first transvalvular approach involves placing the tip of the pacing lead directly through the tricuspid valve into the right ventricle, including “direct-crossing” and “drop-down.” The second transvalvular approach is to bend the pacing lead so that the reflexed lead body crosses the tricuspid valve and then enters the right ventricle, which is “prolapsing.” However, there are no clinical trials to evaluate or compare the effects of the above two different pacing lead transvalvular approaches on tricuspid regurgitation. In this study, we will perform a randomized clinical trial to understand the effect of different transvalvular lead wire transversal techniques on the incidence of tricuspid regurgitation. Methods Three hundred seventy-six subjects with right ventricular single-chamber pacemaker implantation or dual-chamber pacemaker implantation were recruited in the First Affiliated Hospital of Shantou University Medical College. Participants will be randomized into the direct group (“direct-crossing” and “drop-down”) or the bending group (“prolapsing”). The primary objective will be new tricuspid regurgitation or exacerbation of existing tricuspid regurgitation within 1 year of follow-up. Discussion This study aims to verify whether different transvalvular approaches influence the incidence of LITR, and is expected to provide an optimized method for routine pacemaker surgery and improve the long-term prognosis and quality of life of patients. Trial registration Chinese Clinical Trials Registry ChiCTR2100045558. Registered on April 19, 2021.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an exceptionally contagious single-stranded RNA virus with a strong positive contagion. The COVID-19 pandemic refers to the swift worldwide dissemination of SARS-CoV-2 infection, which began in late 2019. The COVID-19 epidemic has disrupted many cancer treatments. A few reports indicate that the prevalence of SARS-CoV-2 has disrupted the treatment of breast cancer patients (BCs). However, the role of SARS-CoV-2 in the occurrence and prognosis of BC has not been elucidated. Here, we applied bioinformatics to construct a prognostic signature of SARS-CoV-2-related genes (SCRGs). Specifically, weighted gene co-expression network analysis (WGCNA) was utilized to extract co-expressed genes of differentially expressed genes (DEGs) in breast cancer and SCRGs. Then, we utilized the least absolute shrinkage and selection operator (LASSO) algorithm and univariate regression analysis to screen out three hub genes (DCTPP1, CLIP4 and ANO6) and constructed a risk score model. We further analyzed tumor immune invasion, HLA-related genes, immune checkpoint inhibitors (ICIs), and sensitivity to anticancer drugs in different SARS-CoV-2 related risk subgroups. In addition, we have developed a nomination map to expand clinical applicability. The results of our study indicate that BCs with a high-risk score are linked to negative outcomes, lower immune scores, and reduced responsiveness to anticancer medications. This suggests that the SARS-CoV-2 related signature could be used to guide prognosis assessment and treatment decisions for BCs.

Abstract Aims Depressive symptoms are comorbid with coronary heart disease (CHD). There is a controversial debate about whether screening and intervention for depressive symptoms could improve cardiovascular prognosis. This study characterizes the prevalence, characteristics, cardiovascular prognosis and management need of depressive symptoms among CHD patients. Methods CHD patients were recruited between November 18, 2020 and November 26, 2021. Depressive symptoms were evaluated with the Patient Health Questionnaire (PHQ-9). During the 12-month follow-up, cardiovascular disease (CVD) was the endpoint. Time-to-event data were estimated by Kaplan-Meier curves and Cox models. Results Of 582 patients (25% women), 21.0% had mild depressive symptoms, and 7.5% had moderate-to-severe depressive symptoms during hospitalization. Mild and moderate-to-severe depressive symptoms were risk factor-adjusted predictors of the primary composite endpoints (adjusted HR = 2.20; 95%CI 1.19–4.03, and adjusted HR = 2.70; 95%CI 1.23–5.59, respectively). Platelet count and low-density lipoprotein were higher in mild depressive symptoms compared to no depressive symptoms. Conclusion Depressive symptoms are prevalent in CHD patients. Mild and moderate-to-severe depressive symptoms are associated with higher risk of further CVD in CHD patients. Platelet function and behavioral mechanisms may contribute to this association. Trial registration This research was registered at https://www.chictr.org.cn . Full data of first registration is 11/09/2020. The registration number is ChiCTR2000038139.

Abstract Background Triglyceride-glucose (TyG) index is an emerging surrogate indicator of insulin resistance, which has been demonstrated as a risk factor for various cardiovascular diseases including coronary syndrome, in-stent restenosis, and heart failure. However, association of TyG index with incident aortic dissection (AD) and aortic aneurysm (AA) remains to be investigated. Methods This study included 420,292 participants without baseline AD/AA from the large-scale prospective UK Biobank cohort. The primary outcome was incident AD/AA, comprising AD and AA. Multivariable-adjusted Cox proportional hazards regression models and restricted cubic spline (RCS) analyses were applied to assess the relationship between TyG index and the onset of AD/AA. In addition, the association between TyG index and incident AD/AA was examined within subgroups defined by age, gender, smoking status, drinking status, diabetes, hypertension, and BMI. Results Over a median follow-up period of 14.8 (14.1, 15.5) years, 3,481 AD/AA cases occurred. The incidence of AD/AA rose along with elevated TyG index. RCS curves showed a linear trend of TyG index with risk of incident AD/AA. TyG index was positively associated with risk of incident AD/AA after adjusting for age, gender, smoking status, drinking status, BMI, hypertension, LDL-c, and HbA1c, with adjusted HRs of 1.0 (reference), 1.20 (95% CI 1.08–1.35), 1.21 (95% CI 1.08–1.35), and 1.30 (95% CI 1.16–1.45) for TyG index quartiles 2, 3, and 4, respectively. Especially, participants in the highest TyG index quartile had highest risk of developing AA, with an adjusted HR of 1.35 (95% CI 1.20–1.52). Conclusions TyG index is independently associated with a higher risk of incident AD/AA, indicating the importance of using TyG index for risk assessment of AD/AA, especially for AA.

BackgroundChina exited strict Zero-COVID policy with a surge in Omicron variant infections in December 2022. Given China’s pandemic policy and population immunity, employing Baidu Index (BDI) to analyze the evolving disease landscape and estimate the nationwide pneumonia hospitalizations in the post Zero COVID period, validated by hospital data, holds informative potential for future outbreaks.MethodsRetrospective observational analyses were conducted at the conclusion of the Zero-COVID policy, integrating internet search data alongside offline records. Methodologies employed were multidimensional, encompassing lagged Spearman correlation analysis, growth rate assessments, independent sample T-tests, Granger causality examinations, and Bayesian structural time series (BSTS) models for comprehensive data scrutiny.ResultsVarious diseases exhibited a notable upsurge in the BDI after the policy change, consistent with the broader trajectory of the COVID-19 pandemic. Robust connections emerged between COVID-19 and diverse health conditions, predominantly impacting the respiratory, circulatory, ophthalmological, and neurological domains. Notably, 34 diseases displayed a relatively high correlation (r > 0.5) with COVID-19. Among these, 12 exhibited a growth rate exceeding 50% post-policy transition, with myocarditis escalating by 1,708% and pneumonia by 1,332%. In these 34 diseases, causal relationships have been confirmed for 23 of them, while 28 garnered validation from hospital-based evidence. Notably, 19 diseases obtained concurrent validation from both Granger causality and hospital-based data. Finally, the BSTS models approximated approximately 4,332,655 inpatients diagnosed with pneumonia nationwide during the 2 months subsequent to the policy relaxation.ConclusionThis investigation elucidated substantial associations between COVID-19 and respiratory, circulatory, ophthalmological, and neurological disorders. The outcomes from comprehensive multi-dimensional cross-over studies notably augmented the robustness of our comprehension of COVID-19’s disease spectrum, advocating for the prospective utility of internet-derived data. Our research highlights the potential of Internet behavior in predicting pandemic-related syndromes, emphasizing its importance for public health strategies, resource allocation, and preparedness for future outbreaks.

Abstract Background Aortic dissection (AD) is a lethal cardiovascular emergency involving high mortality and disability. However, its specific pathogenesis remains to be elucidated. Methods A bibliometric analysis based on the Web of Science database, VOSviewer software and Citex platforms was conducted to have a knowledge of the development trends, frontiers and hot spots of AD. Subsequently, the top five AD‐related genes from the titles and abstracts of published literature were searched. Lastly, the roles of the top five genes and their encoded proteins in the onset of AD were reviewed. Results The bibliometrics showed that most studies are exploring the molecular drivers related to AD, especially gene mutations. The top five AD‐related genes were transforming growth factor‐β (TGFB)‐related genes, elastin (ELN), fibrillin‐1 (FBN1), angiotensinogen (AGT) and matrix metalloproteinase 9 (MMP9). In particular, regulation of the structure of elastic fiber by TGFB‐related genes, ELN and FBN1, appears to be the principal mechanism contributing to AD onset. Activation of the renin‐angiotensin system is the principal mechanism by which AGT triggers AD. MMP9 promotes the formation and development of AD by degrading extracellular matrix components. Conclusion TGFB, ELN, FBN1, AGT and MMP9 are the five top molecular drivers of AD, providing a comprehensive mechanistic insight into AD.

Background and objectivesAcute aortic syndrome (AAS) is a life-threatening condition in which there is a fracture in the integrity of the aortic wall. gamma-glutamyl transferase to lymphocyte ratio (GLR) is recognized as a risk factor for liver cirrhosis, fibrosis, and hepatocellular carcinoma. However, there are no clinical reports of GLR and AAS. We attempted to determine whether GLR level is associated with AAS in patients from the Chaoshan region of southern China.MethodsA total of 2,384 patients were recruited in this study and were divided into AAS and no-AAS groups according to the results of CT angiography of the thoracoabdominal aorta. Univariate and multivariate logistic regression was performed to identify risk factors for the occurrence of AAS. ROC was applied to assess the value of D-Dimer, GLR alone, or in combination for the diagnosis of AAS. And a 1:1 propensity score-matched analysis was performed.ResultsMultivariate logistics regression analysis indicated that male, age, hypertension, diabetes, creatinine, D-dimer, and GLR were independent risk factors of AAS patients in the before propensity score-matching cohort. After propensity score-matching, it showed that D-dimer, GLR [OR 3.558(1.891, 6.697); p

Abstract Background Recent studies have demonstrated a correlation between intestinal flora and the severity of myocardial infarction as well as post-myocardial infarction repair. However, few studies have investigated whether probiotics reduce mortality and improve cardiovascular outcomes in patients with acute myocardial infarction. In this study, we will conduct a randomized controlled trial (RCT) to evaluate the effect of probiotics on in-hospital mortality and the incidence of major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI). Methods This is an open-label, randomized, controlled, superiority clinical trial involving 2594 adult patients who were diagnosed with acute myocardial infarction. Patients will be randomized to (1) receive bifidobacteria triple viable capsule (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) 840 mg, twice a day, plus standard treatment strategy during the hospital stay, for a maximum of 30 days, or (2) receive the standard treatment strategy and will not take the bifidobacterium triple live capsule. The primary outcome was in-hospital all-cause mortality. Discussion The purpose of this clinical trial is to determine whether probiotics can reduce in-hospital mortality and improve prognosis in patients with AMI, and the results will provide evidence for probiotics as a complementary treatment for AMI. Trial registration Chinese Clinical Trials Registry ChiCTR2000038797. Registered on 2 October 2020.

IntroductionA high recurrence rate of atrial fibrillation was monitored after catheter ablation for persistent atrial fibrillation. Sacubitril/valsartan can improve outcomes for patients with heart failure and ventricular tachycardia, but few studies examined whether it can reduce recurrence or improve cardiovascular outcomes in patients with persistent atrial fibrillation after catheter ablation. In this study, we will assess the effect of sacubitril/valsartan on sinus rhythm maintenance and incidence of major adverse cardiovascular events (MACE) in patients with persistent atrial fibrillation after catheter ablation through a randomized controlled trial (RCT).MethodsThis is a multi-center, randomized, controlled, open-label, superiority clinical trial involving 462 patients without reduced ejection fraction heart failure after catheter ablation of persistent atrial fibrillation. Patients will be randomized to (1) receive the standard treatment strategy plus sacubitril/valsartan titration, or (2) receive the standard treatment strategy without taking sacubitril/valsartan. The primary outcome will be sinus rhythm maintenance rate over 12 months, monitored by random electrocardiogram and 24-h Holter electrocardiogram.DiscussionThis study is designed to evaluate the effect of sacubitril/valsartan on sinus rhythm maintenance and incidence of major adverse cardiovascular events (MACE) in patients with persistent atrial fibrillation after catheter ablation. The results will evaluate sacubitril/valsartan as a novel treatment for improving prognosis and a complement to conventional drug therapy. Trial RegistrationRegistered with Chinese Clinical Trials Registry on 27 August 2022, identifier: ChiCTR2200062995.

Background and Aims To evaluate the association of Chinese visceral adiposity index (CVAI) and its dynamic trends with risk of renal damage, and to compare its prediction performance with that of other obesity indices. Methods and Results A community-based population with 23 905 participants from Shantou city was included in the cross-sectional analysis. A total of 9,778 individuals from two separated cohort were included in the longitudinal portion. Five patterns of CVAI change were predefined (low-stable, decreasing, moderate, increasing, and persistent-high). Logistic and Cox regressions were used to evaluate the association between CVAI and renal damage. We explored potential mechanisms using the mediating effect method, and the prediction performance was determined by receiver operating characteristic curve analysis. Results from both cross-sectional and longitudinal data revealed a positive and linear association between CVAI and risk of renal damage. Pooled analysis of the two cohorts showed that per unit increase in Z score of CVAI induced 18% increased risk of renal damage (P = .008). Longitudinal trends of CVAI were also associated with renal damage, and the moderate, increasing, and persistent-high patterns showing a higher risk. Blood pressure and glucose had a mediating effect on renal damage induced by CVAI. Among several obesity indices, CVAI was the optimal for predicting renal damage. Conclusion A higher level of immediate CVAI and longitudinal increasing and persistent-high patterns of CVAI were independently associated with increased risk of renal damage. Monitoring immediate level and long-term trend of CVAI may contribute to the prevention of renal damage.

Prenatal depression and preeclampsia (PE) are well-known risk factors of maternal and fetal mortality and morbidity. In recent years, there are emerging evidence suggesting that prenatal depression and PE could be environmental risk factors for several neurodevelopment disorders of offspring. Prenatal depression and PE were also found to be risk factors of each other. At present, the mechanism (s) of how prenatal depression and PE affect one another and their roles in the development of maternal and fetal adverse outcomes are uncertain. In this review, we outline the most recent clinical studies on the effects of prenatal depression and PE on the neurodevelopmental outcomes of offspring, as well as the plausible mechanism(s) of how these two maternal conditions affect each other and their roles in the neurodevelopment of offspring, including inflammation, oxidative stress, and maternal immune activation. We postulate that the overproduction of pro-inflammatory cytokines and increased cortisol levels in maternal depression can alter fetal neurodevelopment, and the autonomic nervous system dysfunction caused by maternal depression may accelerate heart rate and elevate blood pressure in mothers. Similarly, in PE, the elevated inflammation and exaggerated oxidative stress in the mothers, placenta, and fetus could negatively affect maternal depression on and impair the neurodevelopment of offspring. Further studies are needed to examine the combined effects of prenatal depression and PE on the health outcomes of mothers and offspring, to explore the mechanism of maternal depression in the development of PE and to investigate their roles in the neurodevelopment of offspring.

BackgroundStrain analysis provides more thorough spatiotemporal signatures for myocardial contraction, which is helpful for early detection of cardiac insufficiency. The use of deep learning (DL) to automatically measure myocardial strain from echocardiogram videos has garnered recent attention. However, the development of key techniques including segmentation and motion estimation remains a challenge. In this work, we developed a novel DL-based framework for myocardial segmentation and motion estimation to generate strain measures from echocardiogram videos.MethodsThree-dimensional (3D) Convolutional Neural Network (CNN) was developed for myocardial segmentation and optical flow network for motion estimation. The segmentation network was used to define the region of interest (ROI), and the optical flow network was used to estimate the pixel motion in the ROI. We performed a model architecture search to identify the optimal base architecture for motion estimation. The final workflow design and associated hyperparameters are the result of a careful implementation. In addition, we compared the DL model with a traditional speck tracking algorithm on an independent, external clinical data. Each video was double-blind measured by an ultrasound expert and a DL expert using speck tracking echocardiography (STE) and DL method, respectively.ResultsThe DL method successfully performed automatic segmentation, motion estimation, and global longitudinal strain (GLS) measurements in all examinations. The 3D segmentation has better spatio-temporal smoothness, average dice correlation reaches 0.82, and the effect of target frame is better than that of previous 2D networks. The best motion estimation network achieved an average end-point error of 0.05 ± 0.03 mm per frame, better than previously reported state-of-the-art. The DL method showed no significant difference relative to the traditional method in GLS measurement, Spearman correlation of 0.90 (p < 0.001) and mean bias −1.2 ± 1.5%.ConclusionIn conclusion, our method exhibits better segmentation and motion estimation performance and demonstrates the feasibility of DL method for automatic strain analysis. The DL approach helps reduce time consumption and human effort, which holds great promise for translational research and precision medicine efforts.

Abstract Background Both DNA genotype and methylation of antisense non-coding RNA in the INK4 locus (ANRIL) have been robustly associated with coronary artery disease (CAD), but the interdependent mechanisms of genotype and methylation remain unclear. Methods Eighteen tag single nucleotide polymorphisms (SNPs) of ANRIL were genotyped in a matched case–control study (cases 503 and controls 503). DNA methylation of ANRIL and the INK4/ARF locus (p14 ARF , p15 INK4b and p16 INK4a ) was measured using pyrosequencing in the same set of samples (cases 100 and controls 100). Results Polymorphisms of ANRIL (rs1004638, rs1333048 and rs1333050) were significantly associated with CAD (p 0.05). Methylation levels of ANRIL were similar between the two studied groups (p > 0.05), but were different in the rs1004638 genotype, with AA and AT genotype having a higher level of ANRIL methylation (pos4, p = 0.006; pos8, p = 0.019). Further Spearman analyses indicated that methylation levels of ANRIL were positively associated with systolic blood pressure (pos6, r = 0.248, p = 0.013), diastolic blood pressure (pos3, r = 0.213, p = 0.034; pos6, r = 0.220, p = 0.028), and triglyceride (pos4, r = 0.253, p = 0.013), and negatively associated with high-density lipoprotein cholesterol (pos2, r = − 0.243, p = 0.017). Additionally, we identified 12 transcription factor binding sites (TFBS) within the methylated ANRIL region, and functional annotation indicated these TFBS were associated with basal transcription. Methylation at the INK4/ARF locus was not associated with ANRIL genotype. Conclusions These results indicate that ANRIL genotype (tag SNPs rs1004638, rs1333048 and rs1333050) mainly affects coronary atherosclerosis, but not MI/ACS. There may be allele-related DNA methylation and allele-related binding of transcription factors within the ANRIL promoter.

AimThe aim of this study is to evaluate the association between serum sodium concentrations at hospital admission and all-cause mortality within 365 days post-discharge in patients with atrial fibrillation (AF) without heart failure (HF).MethodsThe prospective cohort study enrolled 1,446 patients with AF without HF between November 2018 and October 2020. A follow-up was performed 30, 90, 180, and 365 days after enrollment through outpatient visits or telephone interviews. All-cause mortality was estimated in three groups according to serum sodium concentrations: hyponatremia (< 135 mmol/L), normonatremia (135–145 mmol/L), and hypernatremia (> 145 mmol/L). We estimated the risk of all-cause mortalities using univariable and multivariable Cox proportional hazards models with normonatremia as the reference.ResultsThe all-cause mortalities of hyponatremia, normonatremia, and hypernatremia were 20.6, 9.4, and 33.3% within 365 days post-discharge, respectively. In the univariable analysis, hyponatremia (HR: 2.19, CI 1.5–3.2) and hypernatremia (HR: 4.03, CI 2.32–7.02) increased the risk of all-cause mortality. The HRs for hyponatremia and hypernatremia were 1.55 (CI 1.05–2.28) and 2.55 (CI 1.45–4.46) after adjustment for age, diabetes mellitus, loop diuretics, antisterone, antiplatelet drugs, and anticoagulants in the patients with AF without HF. The association between serum sodium concentrations and the HRs of all-cause mortality was U-shaped.ConclusionDysnatremia at hospital admission was an independent factor for all-cause mortality in patients with AF without HF within 365 days post-discharge.

Abstract Background Dyslipidemia and local inflammation at sites of lipid deposition on blood vessel walls have been demonstrated to be risk factors for patients with acute aortic dissection (AAD). Statins have anti-inflammatory and lipid-lowering effects, which suggest that statins may play an important role in the prevention and treatment of AAD. Some retrospective studies show that statins can protect patients with aortic dissection. However, the effect of statins on the survival of AAD patients has been scarcely investigated, especially in randomized trials. In this study, we will perform a randomized clinical trial to understand whether statins can reduce in-hospital mortality of AAD patients. Methods A total of 384 subjects diagnosed with AAD in the First Affiliated Hospital of Shantou University Medical College will be recruited. Participants will be randomly divided into an atorvastatin-treated or control group. The primary outcome will be the in-hospital mortality at 30 days. Discussion This study is designed to verify the efficacy of atorvastatin on reducing in-hospital mortality of patients with AAD. The aim is to provide a new means of improving survival as a complement to conventional drug therapy. Trial registration Chinese Clinical Trials Registry ChiCTR1900023515 . Registered on 1 June 2019.

Abstract Because of the lack of sensitivity to radiotherapy and chemotherapy, therapeutic options for renal clear cell carcinoma (KIRC) are scarce. Long noncoding RNAs (lncRNAs) play crucial roles in the progression of cancer. However, their functional roles and upstream mechanisms in KIRC remain largely unknown. Exploring the functions of potential essential lncRNAs may lead to the discovery of novel targets for the diagnosis and treatment of KIRC. Here, according to the integrated analysis of RNA sequencing and survival data in TCGA-KIRC datasets, cyclin-dependent kinase inhibitor 2B antisense lncRNA (CDKN2B-AS1) was discovered to be the most upregulated among the 14 lncRNAs that were significantly overexpressed in KIRC and related to shorter survival. Functionally, CDKN2B-AS1 depletion suppressed cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, CDKN2B-AS1 exerted its oncogenic activity by recruiting the CREB-binding protein and SET and MYND domain-containing 3 epigenetic-modifying complex to the promoter region of Ndc80 kinetochore complex component (NUF2), where it epigenetically activated NUF2 transcription by augmenting local H3K27ac and H3K4me3 modifications. Moreover, we also showed that CDKN2B-AS1 interacted with and was stabilized by insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an oncofetal protein showing increased levels in KIRC. The Kaplan–Meier method and receiver operating curve analysis revealed that patients whose IGF2BP3, CDKN2B-AS1 and NUF2 are all elevated showed the shortest survival time, and the combined panel (containing IGF2BP3, CDKN2B-AS1, and NUF2) possessed the highest accuracy in discriminating high-risk from low-risk KIRC patients. Thus, we conclude that the stabilization of CDKN2B-AS1 by IGF2BP3 drives the malignancy of KIRC through epigenetically activating NUF2 transcription and that the IGF2BP3/CDKN2B-AS1/NUF2 axis may be an ideal prognostic and diagnostic biomarker and therapeutic target for KIRC.

Abstract Background The association between different ABO blood groups and mortality of aortic dissection (AD) remains controversial. This study aimed to examine whether different ABO blood groups affect the prognosis of AD. Methods Demographic and clinical data were collected from 877 patients diagnosed with AD from 2015 to 2019 in the First Affiliated Hospital of Shantou University Medical College. The association between in-hospital mortality of AD patients and ABO blood group was analyzed using Cox proportional hazards regression models. Results This retrograde cohort study demonstrated that for 877 patients, male gender, non-O blood group, Stanford type B AD (TBAD), higher presenting systolic and diastolic blood pressure, and being a recipient of aortic arch replacement surgery (surgery) or endovascular stent-graft implantation (stent-graft) were associated with decreased in-hospital mortality of AD. In Cox proportional hazards models, non-O blood group was associated with lower risk of early mortality regardless of adjustment (HR = 0.668, 95% confidence interval [CI] 0.473–0.944 before adjustment, HR = 0.662, 95% CI 0.468–0.935 after adjustment for age and sex, and HR = 0.641, 95% CI 0.453–0.906 after adjustment for AD types, SBP and surgery). Further analyses revealed that for patients diagnosed with type A AD (TAAD), non-O blood group renders a significant 34.3% decrease in the risk of in-hospital mortality compared with blood group O. Specifically, this difference in mortality risk was found among TAAD patients who did not undergo surgery (HR = 0.579, 95% CI 0.377–0.889), rather than those who did. There was no significant difference in early mortality for patients with TBAD, whether or not stent-grafts were implanted. Conclusions Non-O blood type decreases the risk of in-hospital mortality, especially for TAAD, in AD patients without surgical intervention. More attention must be paid to blood type O TAAD patients without surgical interventions, and early surgical intervention may be an effective means to decrease in-hospital mortality of TAAD.

Background: The association between impaired fasting glucose level (IFG) and coronary heart disease (CAD) remain controversial. In the present study, we sought to ascertain a relationship of IFG with the number of diseased coronary artery and occurrence of myocardial infarction, among CAD cases.Methods: We studied 1,451 consecutive no-diabetic patients who underwent coronary angiography at the First Affiliated Hospital of Shantou University Medical College in Southern China. Demographic, biochemical, clinical and angiographic data were collected.Results: The prevalence of IFG was higher in patients with angiographically confirmed CAD than in subjects without angiographic evidence of CAD (33.4 versus 28.2%, p = 0.034). Compared with CAD cases without IFG, CAD cases with IFG had a higher odds ratio (OR) of having triple-vessel disease as opposed to having single- or double-vessel disease [OR = 1.53, 95% confidence interval (CI) = 1.13–2.07]. Furthermore, the occurrence of MI was higher in CAD cases with IFG than in CAD cases without IFG (OR = 1.73, 95% CI = 1.27–2.36).Conclusions: There is an association between IFG and a predisposition to severe CAD indicated by triple vessel disease or myocardial infarction.

Background: We attempted to identify a regulatory competing endogenous RNA (ceRNA) network and a hub gene of Hypertrophic Cardiomyopathy (HCM).Methods: Microarray datasets of HCM tissue were obtained from NCBI Gene Expression Omnibus (GEO) database. The R package “limma” was used to identify differentially expressed genes. Online search databases were utilized to match the relation among differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs. Weighted correlation network analysis (WGCNA) was used to identify the correlations between key modules and HCM. STRING database was applied to construct PPI networks. Gene Set Enrichment Analysis (GSEA) was used to perform functional annotations and verified the hub genes.Results: A total of 269 DE-lncRNAs, 63 DE-miRNAs and 879 DE-mRNAs were identified in myocardial tissues from microarray datasets GSE130036, GSE36946 and GSE36961, respectively. According to online databases, we found 1 upregulated miRNA hsa-miR-184 that was targeted by 2 downregulated lncRNAs (SNHG9, AC010980.2), potentially targeted 2 downregulated mRNAs (LRRC8A, SLC7A5). 3 downregulated miRNAs (hsa-miR-17-5p, hsa-miR-876-3p, hsa-miR-139-5p) that were targeted by 9 upregulated lncRNAs, potentially targeted 21 upregulated mRNAs. Black and blue modules significantly related to HCM were identified by WGCNA. Hub gene IGFBP5 regulated by hsa-miR-17-5p, AC007389.5, AC104667.1, and AC002511.2 was identified. GSEA indicated that IGFBP5 might involve in the synthesis of myosin complex, participate in kinesin binding, motor activity and function via the regulation of actin cytoskeleton.Conclusion: The results provide a potential molecular regulatory mechanism for the diagnosis and treatment of HCM. IGFBP5 might play an important role in the progression of HCM.

Background: Low-dose rivaroxaban and low-intensity warfarin are widely used in Asia for patients with atrial fibrillation (AF). However, in Asians, it is unclear whether low-dose rivaroxaban and low-intensity warfarin can improve the prognosis of AF. In this study, we investigate the survival benefits of low-dose rivaroxaban and low-intensity warfarin in Asian patients with AF in clinical practice.Methods: This cohort study used medical records in a single tertiary hospital in China, between 2019 and 2020, to identify patients with AF who used rivaroxaban or warfarin, or had no anticoagulant therapy. Follow-ups were performed through telephone contact or medical record review. Cox proportional hazards models were used to compare the risk of mortality of patients in the anticoagulant-untreated group vs. warfarin-treated groups and rivaroxaban-treated groups.Results: A total of 1727 AF patients, discharged between 2019 and 2020, were enrolled in this cohort, of which 873 patients did not use any anticoagulant, 457 patients received warfarin and 397 patients used rivaroxaban. Multivariable analysis showed that, of all the warfarin groups, patients with an international normalized ratio (INR) below 2, good INR control, or poor INR control had a significantly lower risk of mortality compared with that of patients without anticoagulants (HR 0.309, p = 0.0001; HR 0.387, p = 0.0238; HR 0.363, p < 0.0001). Multivariable Cox proportional hazard analyses also demonstrated that, compared with the no anticoagulant group, all rivaroxaban dosage groups (≤10 mg, HR 0.456, p = 0.0129; 15 mg, HR 0.246, p = 0.0003; 20 mg, HR 0.264, p = 0.0237) were significantly associated with a lower risk of mortality.Conclusion: Despite effects being smaller than observed with recommended optimal anticoagulation, the use of warfarin with an INR below 2, poor INR control and the use of low-dose rivaroxaban may still provide survival benefits, suggesting viable alternatives that enable physicians to better resolve decisional conflicts concerning the risks and benefits of anticoagulant therapies, as well as for patients in need of but unable to receive standard anticoagulant therapy due to bleeding risk or other factors, such as financial burden, concerns of adverse outcomes, as well as low treatment compliance and persistence.

Background: Previous studies have reported that biomarkers of liver injury and renal dysfunction were associated with hypertensive disorders of pregnancy (HDP). However, the associations of these biomarkers in early pregnancy with the risk of HDP and longitudinal blood pressure pattern during pregnancy were rarely investigated in prospective cohort studies.Methods: A total of 1,041 pregnant women were enrolled in this prospective cohort study. BP was assessed in four stages throughout pregnancy. The following biomarkers were measured at early pregnancy before 18 weeks gestation: lactate dehydrogenase (LDH), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), uric acid (UA), and estimated glomerular filtration rate (eGFR). Linear mixed-effects and logistic regression models were used to examine the associations of these biomarkers with longitudinal BP pattern during pregnancy and HDP incidence, respectively.Results: In unadjusted models, higher serum UA, GGT, ALP, and LDH levels, as well as lower eGFR and AST/ALT, were associated with higher BP levels during pregnancy and an increased risk of HDP. After adjustment for maternal age, pre-pregnancy BMI and other potential confounders, UA, GGT, ALP, and LDH remained positively associated with both BP and HDP. However, eGFR and AST/ALT were not associated with HDP after adjusting for potential confounders. When including all 6 biomarkers simultaneously in multivariable analyses, increased UA, GGT, and ALP significantly associated with gestational hypertension and preeclampsia.Conclusion: This study suggests that increased UA, GGT, and ALP in early-pregnancy are independent risk factors of gestational hypertension and preeclampsia.

Background: Although mortality remains high in patients with atrial fibrillation (AF), there have been limited studies exploring machine learning (ML) models on mortality risk prediction in patients with AF.Objectives: This study sought to develop an ML model that captures important variables in order to predict all-cause mortality in AF patients.Methods: In this single center prospective study, an ML-based mortality prediction model was developed and validated using a dataset of 2,012 patients who experienced AF from November 2018 to February 2020 at the First Affiliated Hospital of Shantou University Medical College. The dataset was randomly divided into a training set (70%, n = 1,223) and a validation set (30%, n = 552). A total of 122 features were collected for variable selection. Least absolute shrinkage and selection operator (LASSO) and random forest (RF) algorithms were used for variable selection. Ten ML models were developed using variables selected by LASSO or RF. The best model was selected and compared with conventional risk scores. A nomogram and user-friendly online tool were developed to facilitate the mortality predictions and management recommendations.Results: Thirteen features were selected by the LASSO regression algorithm. The LASSO-Cox model achieved an area under the curve (AUC) of 0.842 in the training dataset, and 0.854 in the validation dataset. A nomogram based on eight independent features was developed for the prediction of survival at 30, 180, and 365 days following discharge. Both the time dependent receiver operating characteristic (ROC) and decision curve analysis (DCA) showed better performances of the nomogram compared to the CHA2DS2-VASc and HAS-BLED models.Conclusions: The LASSO-Cox mortality predictive model shows potential benefits in death risk evaluation for AF patients over the 365-day period following discharge. This novel ML approach may also provide physicians with personalized management recommendations.

Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD risk.

There are sex differences in many inflammatory and immune diseases, and the differences tend to diminish after menopause. The underlying reasons are unclear, but sex hormone levels are likely to be an important factor. Blood leukocyte count and composition provide an indicator of the inflammatory and immune status of an individual. We performed a cross-sectional analysis of blood leukocyte data from 46,879 individuals (26,212 men and 20,667 women, aged 18 to 93 years) who underwent a routine health checkup. In women aged around 50 years, neutrophil percentage (NE%) dropped whilst lymphocyte percentage (LY%) rose. Accordingly, women before age 50 had significantly higher NE%, lower LY%, and higher neutrophil-to-lymphocyte ratio (NLR) than women of 51-70 years of age (p = 1.35×10-82, p = 5.32×10-100, and p = 1.25×10-26, respectively). In age groups of 51 years, it was the reverse (p = 1.92×10-15, p = 1.43×10-84, and p = 1.51×10-48, respectively). These results show that blood leukocyte composition differs between women before and after menopausal age, with distinct sexual dimorphism.