Jun Ma

BACKGROUND Solid fuel use for cooking and heating is a major environmental risk factor, yet its association with new-onset heart disease (HD) remains unclear. The aim of this study was to investigate the relationship between solid fuel exposure and new-onset HD in a large cohort. METHODS Multivariable logistic regression models assessed associations between cooking/heating fuel types (coal, crop residue/wood, liquefied petroleum gas, natural gas, and others) and new-onset HD. Subgroup analyses explored effect modification by age, sex, education, smoking, alcohol use, and region. RESULTS A prospective cohort study included 5915 participants, with 781 participants (13.2%) developing new-onset HD. Coal use for cooking showed an initial association with new-onset HD risk (OR = 1.41, 95% CI: 1.06–1.86, P = 0.02), which attenuated after full adjustment (OR = 1.28, 95% CI: 0.96–1.72, P = 0.10). Coal use for heating demonstrated robust associations across all models (OR = 1.86, 95% CI: 1.42–2.43, P < 0.001). Crop residue/wood burning for heating was also significant (Model 2: OR = 1.40, 95% CI: 1.06–1.86, P = 0.02). Subgroup analyses revealed stronger associations among females, non-smokers, non-drinkers, and less-educated participants. Geographic stratification showed significant associations in southern but not northern regions. CONCLUSIONS Solid fuel use, particularly coal for heating, is associated with increased new-onset HD risk. Reducing solid fuel exposure is crucial for HD prevention in low-resource settings.

Arterial stiffness is a critical factor in cardiovascular and cerebrovascular events, yet clinical practice lacks specific therapeutic targets and biomarkers for its assessment. Hyperlipidemia closely correlates with arterial stiffness, and we observed elevated CCAAT/enhancer-binding protein β (C/EBPβ) expression in atherosclerotic mouse arterial walls. As the arterial medial layer predominantly consists of vascular smooth muscle cells (VSMCs), C/EBPβ‘s role in VSMCs under hyperlipidemia remains unclear. Our findings demonstrate that cholesterol-induced phenotypic transition of contractile VSMCs to macrophage-like cells coincides with C/EBPβ upregulation and activation. The activation of C/EBPβ is closely related to cellular assembly and organization, regulating the cytoskeleton via Disheveled-associated activator of morphogenesis 1 (Daam1). Conditional knockout of C/EBPβ in VSMCs of ApoE^−/− mice alleviated hyperlipidemia-induced vascular remodeling and reduced the elevation of aortic pulse wave velocity. Additionally, C/EBPβ-regulated cytokine platelet-derived growth factor-CC (PDGF-CC) is correlated with brachial-ankle pulse wave velocity in humans. These results indicate that the activation of C/EBPβ promotes the transition of VSMCs from a contractile phenotype to a macrophage-like phenotype by regulating morphological changes, and C/EBPβ activation contributes to hyperlipidemia-induced arterial stiffness. PDGF-CC exhibited a significant association with arterial stiffness and may serve as a promising indicator of arterial stiffness in humans. Our study reveals molecular mechanisms behind hyperlipidemia-induced arterial stiffness and provides potential therapeutic targets and biomarkers.

Aims: This study aimed to identify potential therapeutic targets in the progression from non-alcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC), with a focus on genes that could influence disease development and progression. Background: Hepatocellular carcinoma, significantly driven by non-alcoholic fatty liver disease, represents a major global health challenge due to late-stage diagnosis and limited treatment options. This study utilized bioinformatics to analyze data from GEO and TCGA, aiming to uncover molecular biomarkers that bridge NAFLD to HCC. Through identifying critical genes and pathways, our research seeks to advance early detection and develop targeted therapies, potentially improving prognosis and personalizing treatment for NAFLD-HCC patients. Objective: Identify key genes that differ between NAFLD and HCC; Analyze these genes to understand their roles in disease progression; Validate the functions of these genes in NAFLD to HCC transition. Methods: Initially, we identified a set of genes differentially expressed in both NAFLD and HCC using second-generation sequencing data from the GEO and TCGA databases. We then employed a Cox proportional hazards model and a Lasso regression model, applying machine learning techniques to the large sample data from TCGA. This approach was used to screen for key disease-related genes, and an external dataset was utilized for model validation. Additionally, pseudo-temporal sequencing analysis of single-cell sequencing data was performed to further examine the variations in these genes in NAFLD and HCC. Results: The machine learning analysis identified IGSF3, CENPW, CDT1, and CDC6 as key genes. Furthermore, constructing a machine learning model for CDT1 revealed it to be the most critical gene, with model validation yielding an ROC value greater than 0.80. The single-cell sequencing data analysis confirmed significant variations in the four predicted key genes between the NAFLD and HCC groups. Conclusion: Our study underscores the pivotal role of CDT1 in the progression from NAFLD to HCC. This finding opens new avenues for early diagnosis and targeted therapy of HCC, highlighting CDT1 as a potential therapeutic target.

Background and aims: Coronary obstruction following plaque rupture is a critical pathophysiological change in the progression of stable angina (SAP) to acute coronary syndrome (ACS). The accumulation of platelets and various inflammatory cells on apoptotic endothelial cells is a key factor in arterial obstruction after plaque rupture. Through single-cell sequencing analysis (scRNA-seq) of plaques from SAP and ACS patients, we identified significant changes in the annexin V and P-selectin glycoprotein ligand 1 pathways. Staphylococcal superantigen-like 5 (SSL5) is an optimal antagonist P-selectin glycoprotein ligand 1 (PSGL1), while annexin V (AnxA5) can precisely detect dead cells in vivo. We constructed the SSL5-AnxA5 fusion protein and observed its role in preventing the interaction between apoptotic endothelial cells, platelets, and inflammatory cells. Methods: The scRNA-seq data were extracted from the Gene Expression Omnibus (GEO) database. Single-cell transcriptome analysis results and cell–cell communication were analyzed to identify the ACS and SAP cell clusters and elucidate the intercellular communication differences. Then, we constructed and verified a fusion protein comprising SSL5 and AnxA5 domains via polymerase chain reaction (PCR) and Western blot. The binding capacity of the fusion protein to P-selectin and apoptotic cells was evaluated by flow cytometry and AnxA5-FITC apoptosis detection kit, respectively. Furthermore, co-incubation and immunofluorescence allowed us to describe the mediation effect of it between inflammatory cells and endothelial cells or activated platelets. Results: Our analysis of the scRNA-seq data showed that SELPLG (PSGL1 gene) and ANNEXIN had higher information flowing in ACS compared to SAP. The SELPLG signaling pathway network demonstrated a higher number of interactions in ACS, while the ANNEXIN signaling pathway network revealed stronger signaling from macrophages toward monocytes in ACS compared to SAP. Competition binding experiments with P-selectin showed that SSL5-AnxA5 induced a decrease in the affinity of PSGL1. SSL5-AnxA5 effectively inhibited the combination of endothelial cells with inflammatory cells and the interaction of activated platelets with inflammatory cells. Additionally, this fusion protein exhibited remarkable capability in binding to apoptotic cells. Conclusions: The bifunctional protein SSL5-AnxA5 exhibits promising potential as a protective agent against local inflammation in arterial tissues, making it an excellent candidate for PSGL1-related therapeutic interventions.

Objectives Ascending aorta dilatation (AAD) has been suggested as a surrogate marker for vascular organ damage in the hypertensive population. However, limited data are available on AAD in normotensive individuals. This study aims to preliminarily explore the correlation between ascending aorta (AAO) and other established clinically significant target organ damage parameters and to investigate the possible risk factors of AAD in the non-diabetic normotensive individuals. Design Our study has a cross-sectional design. Setting All participants were recruited from the inpatient and outpatient departments of our hospital. Participants We recruited 634 normotensive participants (52.26±16.22 years, 39.43% male) who underwent both ambulatory blood pressure monitoring (ABPM) and echocardiography. The whole study population was divided into AAD and non-AAD groups according to age-gender-specific criteria. The baseline mean blood pressure (BP) of the two groups was 126.92/77.72 and 124.16/77.61 mm Hg, respectively. Primary and secondary outcome measures The relationship between AAO and other acknowledged cardiac damage indicators, as well as the associations of AAD with ABPM indexes in the non-diabetic normotensive individuals. Results We observed that AAO exhibited a significant correlation with left ventricular mass index (β=1.905, pConclusions We found that AAO was correlated with alterations in other acknowledged cardiac parameters, both structural and functional, in non-diabetic normotensive individuals, indicating AAD may be significant in these individuals. Notably, DBP, especially night-time DBP, showed a more significant correlation with AAD. Trial registration number ChiCTR2000030677.

Background: Sigmoid Ventricular Septum (SVS) is a type of hypertrophic cardiomyopathy characterized by a reduced angle between the basal interventricular septum and the ascending aorta, and SVS can lead to dynamic Left Ventricular Outflow Tract obstruction (LVOTO) during hypercontractile states. Patients experiencing LVOTO may manifest symptoms such as angina, syncope, etc. Radiofrequency ablation (RFA) has been utilized to treat patients with hypertrophic obstructive cardiomyopathy, but there is no reports on its use in treating LVOTO resulting from SVS. Our report describes two cases of SVS treated with endocardial ablation to improve LVOTO.Case report: Case 1: A 74-year-old female patient with angina and syncope was admitted to the hospital and diagnosed with SVS by transthoracic echocardiogram. The patient exhibited LVOTO and Systolic Anterior Motion (SAM) phenomena during the administration of the dobutamine stress test. After RFA was performed, the patient's symptoms significantly improved. Additionally, septum decreased from 16 to 13 mm after ten months, and the morphological changes associated with SVS also disappeared. Case 2: A 57-year-old female was admitted to the hospital due to recurrent chest pain after physical activity for more than four years. The transthoracic echocardiogram indicated that the patient met the diagnostic criteria for SVS, and LVOTO and SAM phenomenaoccurred following dobutamine stress test. The patient had significant improvement in symptoms after undergoing RFA treatment.Conclusions: These two cases represent the first documented instances where dynamic LVOTO caused by SVS could be effectively managed through endocardial RFA.

Hypertension is a global public health issue and the leading cause of premature death in humans. Despite more than a century of research, hypertension remains difficult to cure due to its complex mechanisms involving multiple interactive factors and our limited understanding of it. Hypertension is a condition that is named after its clinical features. Vascular function is a factor that affects blood pressure directly, and it is a main strategy for clinically controlling BP to regulate constriction/relaxation function of blood vessels. Vascular elasticity, caliber, and reactivity are all characteristic indicators reflecting vascular function. Blood vessels are composed of three distinct layers, out of which the endothelial cells in intima and the smooth muscle cells in media are the main performers of vascular function. The alterations in signaling pathways in these cells are the key molecular mechanisms underlying vascular dysfunction and hypertension development. In this manuscript, we will comprehensively review the signaling pathways involved in vascular function regulation and hypertension progression, including calcium pathway, NO-NOsGC-cGMP pathway, various vascular remodeling pathways and some important upstream pathways such as renin-angiotensin-aldosterone system, oxidative stress-related signaling pathway, immunity/inflammation pathway, etc. Meanwhile, we will also summarize the treatment methods of hypertension that targets vascular function regulation and discuss the possibility of these signaling pathways being applied to clinical work.

Brachial-ankle pulse wave velocity (baPWV) is an important clinical indicator of aortic stiffness and a risk predictor of cardiovascular disease and associated with obesity. However, whether body m...

Objective: The aim of this study was to compare the periprosthetic BMD changes around Tri‐Lock “Bone Preserving Stem” with the other two common and longer stems (Corail and Summit) after THA.Methods: It was a retrospective cohort study followed patients underwent the total hip arthroplasty from January 2013 to December 2015. They were selected and followed from January 2013 to Janaury 2020. Patients without osteoporosis underwent hip replacements with three aimed stems were included. Among the 138 patients included, 49 patients received the Tri‐Lock stem, 44 patients received the Corail stem, and 45 patients received the Summit stem. The periprosthetic BMD changes evaluated by the Dual energy X‐ray absorptiometry (iDXA) measurement according to the seven Gruen zones was the primary outcome. The Radiographic changes including spot welds, pedestal sign and grade of stress shielding was evaluated by the consecutive hip images. Einzel‐Bild‐Roentgen‐Analyze‐femoral component analysis (EBRA‐FCA) was used to measure the stem migration at 5 years postoperatively. Patient‐reported outcomes (PROMs) and adverse events were assessed and compared in three groups. Finally, the subgroups for the periprosthetic BMD changes, radiological and clinical outcomes were made based on the age, gender and length of follow‐up.Results: A total of 138 patients were retrospectively followed for an average of 4.66 years. Excepting the different stems used in three groups, the age, gender and other characteristics of patients included were similar between groups. There was no significant difference between the three groups in periprosthetic BMD changes over postoperative 5 years. The Summit stem shown more BMD loss in Gruen zone 1 compared with the Tri‐Lock and Corail stems without significant difference (7.49%, −1.89% and −2.62%, respectively, P = 0.42). And the most prominent BMD loss was found in Gruen zone 7 for all three stems (−12.60%, −11.84%, and −9.56%, respectively, P = 0.91). The spot weld was significantly more common around the Corail stem, while there was no difference in the stem migration between three groups. Patient reported outcomes (PROMs) were significantly improved compared with the preoperative values. Regarding the rate of postoperative complications, two patients underwent the dislocation and 25 patients sometimes felt mild to moderate thigh pain. Subgroup analysis showed that female patients older than 50 years lost more BMD and had lower clinical scores, while the stem stability was not good enough in male patients.Conclusions: The Tri‐Lock Bone Preserving Stem did not show significant difference in periprosthetic BMD changes compared with the other two conventional longer stems at 5 years after THA.

Physical exercise is an effective strategy for improving human health. Various organs, including the heart, lung and kidney, can benefit from exercise. However, the underlying molecular mechanisms by which exercise protects organs remain unknown. Irisin, a myokine secreted from muscle in response to exercise, has attracted increased attention from researchers. The role of irisin in multiorgan protection has been gradually revealed, and this muscle-derived circulating factor is regarded as an essential bridge linking exercise and organ health. The mechanisms by which irisin protects diverse organs are different. Here, we review the research progress on the multiorgan protective effects of irisin and discuss the underlying molecular mechanisms.