• Bronchial epithelial-derived exosomal SLC6A14 promotes airway inflammation and mucus hypersecretion via the ZFP36L1/IL-8 axis.
    3 weeks ago
    SLC6A14 is an exosomal protein derived from bronchial epithelial cells. This study aims to investigate how exosomal SLC6A14 contributes to airway inflammation and mucus hypersecretion in chronic obstructive pulmonary disease (COPD).An in vitro COPD model was established by treating normal human bronchial epithelial cells (BEAS-2B) with 8% cigarette smoke extract (CSE) for 48 h. Interventions included SLC6A14 overexpression, ZFP36L1 overexpression, and exosome treatment. For the in vivo experiments, a COPD mouse model was induced by long-term cigarette smoke (CS) exposure for 6 months, and exosomes were administered during the final 2 weeks. Levels of inflammatory cytokines and mucin secretion were measured by RT-qPCR, ELISA, and Western blot. Lung tissue pathology, fibrosis, goblet cell hyperplasia, and mucus expression were analyzed using HE staining, Masson staining, immunohistochemistry, and multiplex immunofluorescence. An in vitro COPD model was established by treating normal human bronchial epithelial cells (BEAS-2B) with 8% cigarette smoke extract (CSE) for 48 h. Interventions included SLC6A14 overexpression, ZFP36L1 overexpression, and exosome treatment. For the in vivo experiments, a COPD mouse model was induced by long-term cigarette smoke (CS) exposure for 6 months, and exosomes were administered during the final 2 weeks. Levels of inflammatory cytokines and mucin secretion were measured by RT-qPCR, ELISA, and Western blot. Lung tissue pathology, fibrosis, goblet cell hyperplasia, and mucus expression were analyzed using HE staining, Masson staining, immunohistochemistry, and multiplex immunofluorescence. SLC6A14 expression was significantly upregulated in the lungs of CS-exposed mice and in CSE-treated BEAS-2B cells. Its overexpression triggered inflammatory responses and mucin expression in BEAS-2B cells irrespective of CSE treatment. Mechanistically, SLC6A14 could enhance IL-8 mRNA stability by suppressing the RNA-binding protein ZFP36L1. Comparatively, ZFP36L1 overexpression reduced CSE-induced inflammation and mucin expression in BEAS-2B cells by decreasing IL-8 mRNA. Exosomes released from CSE-treated BEAS-2B cells, which were enriched in SLC6A14, promoted inflammation and mucin secretion in recipient BEAS-2B cells. Importantly, exosomes isolated from the SLC6A14-silenced and CSE-treated BEAS-2B cells significantly alleviated airway inflammation, goblet cell hyperplasia, fibrosis, and mucus hypersecretion in CS-exposed mice. CSE stimulated bronchial epithelial cells to release exosomes enriched with SLC6A14, and these exosomes aggravated COPD-related airway inflammation and mucus hypersecretion by disrupting the ZFP36L1/IL-8 signaling axis.
    Chronic respiratory disease
    Care/Management
  • Hepatitis B Virus Infection and the Risk of Cardiovascular Disease: Findings From the China Kadoorie Biobank.
    3 weeks ago
    The existing evidence on the association of hepatitis B virus (HBV) infection with the risk of cardiovascular disease (CVD) is limited and mixed. Moreover, no epidemiological studies have been conducted to comprehensively investigate this association in China. Hence, we performed a nationwide prospective cohort study to address these issues. Our study included 477,126 adults without a history of CVD. Participants were recruited from 10 diverse areas in China during 2004-2008, and followed up through December 31, 2016. Adjusted hazard ratio (HR) for CVD incidence was calculated using Cox regression. Subgroup analyses were conducted to identify the potential effect modifiers. During a mean follow-up of 9.94 years, 32,841 ischemic heart disease events, 35,532 ischemic strokes, 5538 intracerebral haemorrhages, 3165 acute myocardial infarction events, and 2939 heart failure events were observed. HBsAg-positive participants had a lower risk of ischemic heart disease [HR: 0.91, 95% confidence interval (CI): 0.84, 0.98; p: 0.011] but a higher risk of intracerebral haemorrhage (HR: 1.25, 95% CI: 1.07, 1.46; p: 0.004) than HBsAg-negative participants. These associations could not be modified by age, sex, study area, body mass index, regular alcohol intake, regular smoking, and physical activity level, and remained in a series of sensitivity analyses. No significant associations were found for ischemic stroke, acute myocardial infarction, and heart failure in the whole study population. In conclusion, HBV infection confers a decreased risk of ischemic heart disease but an increased risk of intracerebral haemorrhage in this Chinese population. More studies are needed to clarify the corresponding mechanisms.
    Cardiovascular diseases
    Access
    Care/Management
    Advocacy
  • Ageing Through the Looking-Glass: The Different Flavours of Clonal Haematopoiesis.
    3 weeks ago
    Clonal haematopoiesis (CH) is the presence of acquired mutations in blood cells and is a consequence of ageing that is linked to malignancy, cardiovascular disease and other diseases of ageing. CH is a reflection of genomic instability with ageing; however, there is evidence that CH may exacerbate features of normal ageing, including inflammageing and immunosenescence, and more directly contribute to disease causation. CH can manifest as mosaic loss of X or Y, autosomal mosaic chromosomal rearrangements, or point mutations or small insertions or deletions. Until recently, little has been known about the relationship between different forms of CH and other biomarkers of ageing, including whether they are more likely to co-exist, whether they work synergistically to promote clonal expansion, and whether they have independent impacts on risk of clinical outcomes. Defining the overlap between different forms of CH and other markers of ageing is important to understand the biological processes involved in ageing, and the mechanisms underlying the associations with diseases of ageing. Here we provide an overview of the current literature on intersections of different forms of CH, the clinical implications of these, and a perspective on how CH enhances our understanding of the biology of ageing.
    Cardiovascular diseases
    Access
    Care/Management
  • Pre-pregnancy BMI, gestational weight gain trajectories, and new-onset hypertensive disorders in ART singleton pregnancies: a retrospective cohort study.
    3 weeks ago
    To investigate non-linear associations between pre-pregnancy BMI and new-onset hypertensive disorders of pregnancy (HDP), and the relationship between gestational weight gain (GWG) trajectories and HDP.

    Using data from the Ningbo Birth Cohort of Population Undergoing ART (NBart) cohort (June 2018-June 2024), we included women with singleton ART pregnancies. Restricted cubic splines, latent class mixed models, and logistic regression were applied.

    Of 4219 eligible pregnancies, 255 (6.0%) developed HDP. Risk increased when pre-pregnancy BMI exceeded 21.5 kg/m2 (∼6% higher per 0.5 kg/m2 gain). In stratified analyses, risk also increased below 16.6 kg/m2; the J-shaped relationship was evident in normal-weight women; a significant non-linear association was not detected within the overweight and obese subgroups alone. Advanced maternal age, nulliparity, primary infertility, and frozen embryo cycle amplified BMI-related risk. Exceeding recommended GWG guidelines at various pregnancy stages increased HDP risk; refined GWG thresholds were proposed for ART pregnancies. Two GWG patterns-concave negative (0-20 ± 1 weeks; aOR = 0.540, 95% CI: 0.290-0.944) and delayed acceleration (entire gestation period; aOR = 0.627, 95% CI: 0.380-0.996)-were inversely associated with HDP. Both featured minimal or negative early-pregnancy weight change followed by steady gain, occurred predominantly in overweight and obese women, and total GWG was lower compared with other patterns.

    Maintaining optimal pre-pregnancy BMI and adhering to the proposed, more conservative GWG thresholds for ART pregnancies may reduce HDP risk. Distinct GWG trajectories may further modulate this risk.
    Cardiovascular diseases
    Access
    Care/Management
    Advocacy
  • Postintubation Hemodynamic Collapse in Traumatically Injured Critical Care Transport Patients: A Retrospective Cohort Study.
    3 weeks ago
    Endotracheal intubation of trauma patients incurs risks including post-intubation hemodynamic collapse. Trauma patients are at increased risk of secondary harm related to hypotension. The aim of this study was to describe post-intubation hemodynamic collapse in traumatically injured CCT patients and investigate associations with in-hospital outcomes.

    Retrospective chart review of trauma patients ≥18 years admitted to a rural level one trauma center who were transported and intubated by the hospital-based CCT service between January 2017 and June 2024. Hemodynamic collapse was defined as cardiac arrest, systolic blood pressure (SBP) <65 mmHg at least once, SBP <90 mmHg for greater than 30 minutes, new vasopressor requirement, vasopressor dose increase, or fluid bolus of >15 mL/kg to maintain SBP. The primary outcome was the incidence of hemodynamic collapse. Secondary outcomes were identification of potentially modifiable patient risk factors and in-hospital outcomes including length of stay and mortality.

    One hundred forty-two trauma patients were included. Thirty-five (24.6%) patients experienced hemodynamic collapse and 2 (5.7%) had cardiac arrest. When controlled for ISS, patients with pre-intubation blood administration (OR 5.89, 95% CI 1.8-19.31), pre-intubation vasopressors (OR 11.21, CI 2.02-62.25), and first systolic blood pressure <90 mmHg (OR 7.66, CI 1.18-49.74) had higher odds of hemodynamic collapse after intubation. The median shock index and injury severity scores (ISS) were also higher: 1.07 (0.71-1.38) versus 0.68 (0.53-0.84) and 36 (14-43) versus 24 (17-34), respectively (p <0.05). When controlled for ISS there was no significant difference in hospital mortality (OR 1.78, 95% CI 0.73-4.36).

    Post-intubation hemodynamic collapse occurred in 1 in 4 patients in this cohort of traumatically injured patients. Patients with post-intubation hemodynamic collapse were more likely to have received blood, fluids, and vasopressors and they had higher ISS and in-hospital mortality. The risks and benefits of a definitive airway for these patients must be carefully weighed.
    Cardiovascular diseases
    Access
    Care/Management
    Advocacy
  • Detecting undiagnosed hypertension using repeated blood pressure measurements: a cross-sectional study in rural Sidama Region, Ethiopia.
    3 weeks ago
    To determine the prevalence of undiagnosed hypertension and its risk factors among adults in rural Sidama Region, Ethiopia, using a two-step diagnostic method.

    A community-based cross-sectional study was conducted from 1 April to 31 July 2024. Data were collected among adults aged 45 years and above using the World Health Organization STEPwise Approach to Surveillance questionnaire. The Demographic and Health Survey questionnaire was also used to collect data on household characteristics.

    Selected rural kebeles of Shebedino district, Sidama, Ethiopia.

    2875 adults aged ≥45 years identified via census.

    Undiagnosed hypertension was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg, in individuals with no history of the condition.

    The prevalence of undiagnosed hypertension ranged from 7.7% (95% CI: 6.7% to 8.7%) to 14.3% (95% CI: 13.0% to 15.6%). The previously diagnosed hypertensive cases were found in 3.3% (95% CI: 2.7% to 4.1%). Female sex (AOR 2.02; 95% CI: 1.44 to 2.82), age ≥ 65 years (AOR 1.48; 95%CI: 1.01 to 2.15), and history of alcohol drinking and khat chewing (AOR 2.94; 95%CI: 1.52 to 5.66) were significantly associated with undiagnosed hypertension. Lack of awareness of salt-related health risks (AOR 3.14; 95% CI: 2.30 to 4.30) and no prior blood pressure measurement (AOR 5.60; 95% CI: 1.73 to 18.07) were also associated with undiagnosed hypertension.

    Undiagnosed hypertension is common among adults aged ≥45 years in the rural Sidama Region. Female sex, older age, substance use, limited awareness of salt-related health risks, and lack of prior blood pressure measurement were the identified risk factors. Regular screening should be implemented to detect cases at an early stage.
    Cardiovascular diseases
    Access
    Advocacy
  • Blood pressure control rates among hypertensive patients managed in community health centres in Shenzhen, China: a megacity population-based observational study.
    3 weeks ago
    Hypertension represents a major public health challenge globally, with a rising prevalence in China. This study aims to explore the factors shaping blood pressure (BP) control among hypertensive patients managed in community health centres (CHCs), with a particular emphasis on the association with age.

    This was a population-based, observational study that used healthcare records from CHC in Shenzhen, covering the period from 1 January 2000 to 8 October 2024. Univariate and multivariate logistic regression analyses were employed to assess the independent associations of various factors with BP control rate. Additionally, the study evaluated the relationship between age and BP control across six distinct age subgroups.

    The study included 1 073 914 participants who met the eligibility criteria, with 955 415 (88.97%) patients achieving BP control. The median baseline age was 55.9 (IQR 18-109) years. Individuals aged 45 years and above demonstrated better BP control rates (46-55, OR 1.053, 95% CI 1.020 to 1.087; 56-65, OR 1.246, 95% CI 1.205 to 1.289; 66-75, OR 2.183, 95% CI 2.103 to 2.265; >75, OR 2.159, 95% CI 2.060 to 2.262). Among young adults aged 18-35 years, increasing age was consistently associated with poorer BP control across most subgroups. For the middle-aged groups (36-45 and 46-65 years), age had little impact on BP control. In the 66-75 years age range, older age was linked to better BP control in some groups.

    The association between age and BP control varied across age groups. Hypertension management strategies should be tailored to address the unique needs of different age groups, geographical regions and targeted populations.
    Cardiovascular diseases
    Access
    Care/Management
    Advocacy
  • Effect of preoperative liposomal bupivacaine single-injection pericapsular nerve group (PENG) block on lower extremity deep vein thrombosis in elderly patients with hip fractures: a randomised controlled, double-blind, prospective clinical study protocol.
    3 weeks ago
    Deep vein thrombosis (DVT) of the lower limbs has a significantly higher incidence among elderly populations than that observed in other types of fractures, prolonged immobilisation and the systemic inflammatory response triggered by preoperative pain are the main risk factors. Liposomal bupivacaine (LB) single-injection pericapsular nerve group (PENG) block has demonstrated effective analgesia both before and after surgery, while preserving motor function in patients with hip fracture. Although regional nerve block is a well-established component of preoperative multimodal analgesia, its potential role and underlying mechanisms in the prevention of DVT in elderly patients with hip fracture remain largely unexplored.

    This study will be conducted as a double-blind, randomised, sham-controlled, prospective clinical trial. On admission, a total of 132 participants will be randomly assigned using block randomisation to receive either treatment group (LB single-injection PENG block) or sham group (saline solution single-injection PENG block). The primary outcome was the incidence of DVT, while secondary outcomes included perioperative inflammatory and immune-related stress levels and functional-based pain scores.

    This study protocol complies with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 guidelines and has been approved by the Ethics Committee of Shunde Hospital, Guangzhou University of Traditional Chinese Medicine (Approval No KY-2025005). The raw data are planned to be made publicly available on the ResMan raw data-sharing platform (IPD sharing platform) of the Chinese Clinical Trial Registry in December 2027 and can be accessed at http://www.medresman.org.cn.

    ChiCTR2500100799.
    Cardiovascular diseases
    Access
    Care/Management
    Advocacy
  • Glucagon-like Peptide-1 Receptor Dependent Signaling in Cardiovascular Health and Disease: A Mini-review.
    3 weeks ago
    Glucagon-like peptide-1 (GLP-1) is a hormone mainly produced by intestinal L cells after meal, and its main functions include enhancing glucose-dependent insulin secretion, promoting insulin biosynthesis, inhibiting glucagon secretion, inhibiting gastrointestinal activity and regulating appetite. In recent years, GLP-1, besides its well-known hypoglycemic effects, has been shown to have beneficial effects in the cardiovascular field, but the precise molecular mechanism is not yet fully understood. GLP-1 receptor (GLP-1R) is a class B G-protein-coupled receptor (GPCR), which is widely distributed in the cardiovascular system. This review aims to summarize the GLP-1R dependent signaling pathways in GLP-1 cardiovascular protection and related researches, such as the GLP-1R structure, distribution and expression. Moreover, we also discussed the development of GLP-1R agonist (GLP-1RA) therapies in cardiovascular field.
    Cardiovascular diseases
    Care/Management