The maintenance of normal ovarian function depends on the presence of two structurally intact X chromosomes, which explains the high risk of premature ovarian insufficiency in individuals with Turner syndrome (TS). Most aneuploid germ cells undergo apoptosis during embryonic gonadal development, resulting in the formation of streak gonads in the majority of individuals with a 45,X karyotype. However, the role of X-monosomy in ovarian somatic cells, which provide the microenvironment essential for oocyte survival and development, remains poorly understood. To our knowledge, this is the first study to investigate the association between X chromosome aneuploidy in ovarian somatic cells and peripheral blood lymphocytes and ovarian function in adolescents with mosaic TS. The aim of this exploratory case-series study was to comprehensively evaluate the clinical, hormonal, ultrasonographic, morphological, morphometric, immunohistochemical, and molecular cytogenetic characteristics of the ovaries in adolescents with mosaic TS and spontaneous pubertal development.

Five adolescents with mosaic TS underwent assessment of ovarian reserve markers and ovarian tissue cryopreservation. Follicle density (FD), expression of oocyte-specific markers (GDF9, BMP15, and CD117), and X chromosome mosaicism in 2-6 oocytes, 50-300 granulosa cells (GCs), and 50 ovarian stromal cells per participant were evaluated.

Despite ongoing puberty and normal gonadotropin levels, reduced serum anti-Müllerian hormone (AMH) and inhibin B concentrations were observed in some participants. A normal X chromosome complement was identified in all analyzed oocytes. Ovarian stromal cells were predominantly monosomic for the X chromosome, whereas GCs demonstrated substantial intra- and inter-individual variability in X chromosome mosaicism. No clear relationship was observed between X chromosome mosaicism in peripheral blood lymphocytes and ovarian tissue. Age-appropriate FD was observed only in participants whose follicles contained more than 60% non-monosomic GCs (XX or XXX).

The findings suggest that ovarian function in adolescents with mosaic TS may be associated not only with the chromosomal status of oocytes but also with that of GCs. Peripheral blood karyotype did not reliably reflect ovarian tissue mosaicism in this exploratory series, highlighting the importance of comprehensive evaluation of ovarian reserve markers when counseling patients with TS regarding fertility preservation.

Atrial fibrillation (AF) is associated with increased cardiovascular mortality. Cardiac remodeling is a non-negligible pathological mechanism for the elevated risk of death in patients with AF. In addition, an elevated systemic inflammatory response is associated with adverse cardiac remodeling and increased mortality. However, it remains incompletely understood whether inflammation markers, such as the monocyte/lymphocyte ratio (MLR), are associated with adverse cardiac remodeling and clinical biochemical indexes in patients with AF. Therefore, this study investigated the association between MLR and clinical biochemical indexes and cardiac remodeling in elderly patients with AF.

In a single medical care center, a total of 1,154 elderly Chinese hospitalized patients (aged ≥ 65 years) with AF were collected retrospectively. The patients were divided into low (≤ 0.293), moderate (> 0.293 to ≤ 0.460), and high (> 0.460) MLR groups according to the MLR tertiles. A regression analysis of MLR (> 0.460) with clinical biochemical indexes and echocardiographic parameters was conducted.

The results revealed that high MLR (> 0.460) was independently associated with male sex, decreased estimated glomerular filtration rate (eGFR), lower plasma albumin level, cardiac ventricular dilatation, and cardiac dysfunction (all P < 0.05).

High MLR was linked to male sex, decreased eGFR, lower plasma albumin level, and adverse cardiac remodeling in elderly patients with AF.

Various studies have reported the clinical importance of psychological distress in patients with cardiovascular diseases (CVD). However, few studies have examined the psychological distress experienced by family caregivers of patients with CVD. This study aimed to examine how having to care for patients with CVD affects psychological distress among family members.

Data on patients with CVD requiring care and family caregivers living with them were extracted from a nationwide population-based study in Japan (2019 Comprehensive Survey of Living Conditions), conducted by the Ministry of Health, Labor, and Welfare. Psychological distress was assessed using the Kessler Psychological Distress Scale-6 item score (0-24 points) from the questionnaire, and a score ≥9 was defined as psychological distress.

Family caregivers of patients with CVD who required care in 1990 were analyzed. The proportion of family caregivers experiencing psychological distress was 12.9% (257 in 1990). Multivariate logistic regression analysis revealed that the patients themselves had psychological distress, younger family caregivers, female family caregivers, family caregivers and patients residing alone, family caregivers who were not working, and patients with CVD complicated with dementia were independent factors affecting psychological distress in family caregivers.

Multidisciplinary healthcare providers need to be aware of the mental health of not only patients with CVD requiring care but also their family caregivers and implement appropriate medical support.

Abdominal aortic aneurysm (AAA) is a progressive vascular disease characterized by chronic inflammation, extracellular matrix degradation, and aortic wall remodeling, yet effective pharmacological therapies remain lacking and how macrophage state heterogeneity contributes to disease progression and defective inflammation resolution remains incompletely understood.

We combined single-cell RNA sequencing of elastase-induced murine AAA with pathway, cell-cell communication, trajectory, and regulon analyses, and validated key findings in vivo by immunostaining and flow cytometry and in vitro by pharmacologic ERK inhibition, gene-expression analysis, and macrophage efferocytosis assays.

Single-cell transcriptomic analysis identified four macrophage subsets in AAA, comprising Thbs1⁺Spp1⁺ inflammatory macrophages, Mrc1⁺Gas6⁺ efferocytosis-associated macrophages, Cdca8⁺ proliferative macrophages, and Cd36⁺Lpl⁺ lipid-handling macrophages. AAA progression was characterized by expansion of Thbs1⁺Spp1⁺ macrophages and emergence of Cdca8⁺ macrophages, together with relative loss of Mrc1⁺Gas6⁺ and Cd36⁺Lpl⁺ macrophages. Thbs1⁺Spp1⁺ macrophages showed inflammatory, chemotactic, oxidative stress, and metabolic remodeling signatures, whereas Mrc1⁺Gas6⁺ macrophages were enriched for efferocytosis- and homeostasis-associated features but exhibited increased apoptosis-related signals and reduced expression of Mertk, Gas6, and Igf1 during AAA progression. ERK signaling was overactivated in AAA and associated with loss of these effectors and impaired macrophage efferocytosis, whereas ERK inhibition restored Mertk, Gas6, and Igf1 expression and enhanced uptake of apoptotic cells in macrophage-line models. Trajectory and regulon analyses further suggested that inflammatory and efferocytosis-associated macrophages follow distinct state trajectories, with Maf emerging as a candidate regulator of the Mrc1⁺Gas6⁺ program.

AAA is characterized by an imbalance between inflammatory and efferocytosis-associated macrophage states. ERK-associated dysfunction of Mrc1⁺Gas6⁺ macrophages may contribute to defective inflammation resolution and represents a potential therapeutic target in aneurysmal disease.

Up to now, Intracerebral hemorrhage (ICH) remains a type of cerebrovascular emergency with high incidence, mortality and disability rates. The secondary brain injury following ICH involves a series of complex pathophysiological mechanisms, including the space-occupying and edema effects of hematoma, abnormal mediation of multiple cell signaling pathways, intense inflammatory storms and immune responses, structural and functional damage to the blood-brain barrier(BBB), progressive increase in intracranial pressure, early hematoma expansion, and neurotoxic effects of blood decomposition product. Over the past few decades, although substantial progress has been made in the construction of risk prediction models, optimization of acute treatment strategies, and improvement of long-term prognosis assessment systems, and dues to the advancement of neuroimaging techniques, improvement in neurocritical care, and innovation in minimally invasive neurosurgery, the overall mortality and disability rates of patients have shown a downward trend. However, it is regrettable that the neurological function recovery of survivors is still generally poor, and the long-term functional improvement rate is very low. Despite extensive and in-depth exploration of the best drug intervention targets and optimal surgical methods for ICH through multiple basic research and clinical trials, these efforts have not yet translated into breakthroughs in clinical treatment outcomes or significant improvements in patient prognosis. This review aims to comprehensively summarize the epidemiological characteristics of spontaneous ICH, the mediation mechanisms of key signaling pathways, the dynamic process of BBB disruption, potential immune-related therapeutic targets, exploration directions of novel drug targets, core mechanisms of secondary brain injury, and key research directions in the future.

Antiplatelet medications remain essential in managing atherosclerotic cardiovascular disease. We assessed the adequacy of female representation in the antiplatelet medication literature, which informed the 2023 Canadian Antiplatelet Guidelines. Literature cited in the 2023 Canadian Antiplatelet Guidelines was systematically reviewed. Randomized controlled trials were included. Observational studies, systematic reviews, guidelines, consensus documents, studies missing demographic data, and research protocols were excluded. Extracted data included study titles, author, year, design, sample size, mean participant age, and proportion of female participants. Of 138 identified unique citations, 109 studies met the inclusion criteria. From the included evidence informing the 7 antiplatelet PICO (population, intervention, comparison, outcome) topics, the total sample size was 570,217 participants, with a mean age of 65.4 years. The mean percentage of female participants included across trials was 28.5%, and 21% of the included studies had a participation-to-prevalence ratio of 0.8-1.2 for female participants. Female patients were not adequately represented in nearly two-thirds of the evidence informing antiplatelet medication trials. Thus, the 2023 Canadian Antiplatelet Guidelines PICO topics are informed largely by evidence with inadequate female representation. A need remains for greater attention to adequately representing female patients in clinical trials for antiplatelet medications, which in turn inform clinical guidelines.

Vascular dementia (VD) is a common cognitive impairment syndrome, for which there is currently no effective treatment. As a distinctive acupuncture therapy founded by Professor Jin Rui, the intelligence three-needling (Zhisanzhen, a specific set of 3 acupuncture points) selects the acupoints Shenting (GV24) and bilateral Benshen (GB13), and has shown significant clinical efficacy in improving cognitive function in patients with vascular dementia. This article systematically reviewed the research progress of intelligence three-needling in treating vascular dementia from both clinical and mechanistic perspectives: (1) Clinically, intelligence three-needling, applied via manual acupuncture or electroacupuncture, either alone or in combination with medication and rehabilitation training, can effectively improve patients' scores on the Mini-Mental State Examination and Hasegawa Dementia Scale, as well as their daily living abilities. (2) Mechanistically, intelligence three-needling exerts multi-target and multi-pathway neuroprotective effects, including reducing neurotoxic substances such as homocysteine and β-amyloid, inhibiting neuroinflammatory responses, modulating synaptic plasticity-related proteins, improving cerebral blood flow perfusion, and promoting neuronal repair and functional recovery by regulating the Eph/ephrin signaling pathway and GABAergic system.

To observe the effect of electroacupuncture (EA) on the homeostasis of Th17/Treg cells and the expressions of key proteins of the janus kinase 1/signal transducer and activator of transcription 3 signaling pathway in myocardial tissue of rats with myocardial ischemia(MI), so as to explore its mechanisms underlying amelioration of inflammatory injury following MI.

SD rats were randomly divided into control, model, and EA groups, with 6 rats in each group. The MI model was established by subcutaneous injection of isoproterenol hydrochloride(5 mg·kg^-1·d^-1), once daily for 7 consecutive days. After successful modeling, the rats of EA group received EA stimulation (2 Hz/10 Hz, 2 to 3 mA) of unilateral "Neiguan" (PC6) and "Zusanli" (ST36) for 20 min, once daily for 21 d. The standard limb lead II electrocardiogram (ECG) was recorded to analyze the height of ST and amplitude of T wave for assessing the degree of ischemic myocardial injury. The hematoxylin-eosin (H.E.) staining was used to observe histopathological changes in the myocardial tissue, and the Masson staining performed to examine the collagen deposition of the myocardial cells. The concentrations of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-17, and IL-10 in the serum and myocardial tissue were detected using enzyme-linked immunosorbent assays (ELISA), and the proportions of Th17 cells and Treg cells in the myocardial tissue analyzed using flow cytometry. The expression levels of signal transducers and activators of transcription 3 (STAT3), phosphorylated (p)- STAT3, forkhead box protein 3 (Foxp3), Janus kinase 1 (JAK1), retinoic acid-related orphan nuclear receptor-α(RORα), suppressor of cytokine signaling 3 (SOCS3) proteins in the myocardial tissue were detected using Western blot.

Compared with the control group, the model group had a significant increase in the ST height and T-wave amplitude, myocardial collagen volume fraction (CVF), TNF-α and IL-17 contents in the serum and myocardial tissue, myocardial Th17/Treg ratio, and expression levels of myocardial JAK1, STAT3, p-STAT3, and RORα proteins (P<0.01, P<0.05), and a striking decrease in the proportion of Treg cells, contents of myocardial and serum IL-10, and expression levels of myocardial FOXP3 and SOCS3 (P<0.01, P<0.05). In contrast to the model group, both the increase and the decrease of the indexes mentioned above were reversed in the EA group (P<0.05, P<0.01). H.E. staining showed necrosis and dissolution of a large number of myocardial cells, with increased cell spacing and blurred boundaries, inflammatory infiltration and fibrous tissue hyperplasia in the model group, which was relatively and significantly milder in the degree of myocardial injury in the EA group.

EA at PC6 and ST36 can improve myocardial inflammation injury in rats with MI, which may be related to its function in regulating the homeostasis of Th17/Treg cells in myocardial tissue through JAK1/STAT3 signaling, balancing the secretion of pro-inflammatory factors TNF-α, IL-17 and anti-inflammatory factor IL-10.

Genetic testing is routinely recommended in dilated cardiomyopathy (DCM), yet the prevalence and implications of pathogenic/likely pathogenic (P/LP) variants in patients with DCM and left bundle branch block (LBBB) remain unclear. We therefore investigated the electromechanical profile of genotyped patients with DCM and LBBB, and its relationship with cardiac resynchronization therapy (CRT) response and clinical outcomes.

Patients with LBBB were selected from a multicenter cohort of 1206 consecutive DCM patients undergoing genetic testing. All underwent sequencing of 20 clinically validated DCM-related genes (ClinGen) and comprehensive electro- and echocardiographic phenotyping, including speckle-tracking strain analysis, categorizing septal strain curves into five stages (LBBB-0 to LBBB-4). CRT response was assessed as end-systolic volume (ESV) reduction and left ventricular ejection fraction (LVEF) improvement. The clinical endpoints were a composite of all-cause mortality, heart transplantation/left ventricular assist device implantation, and heart failure hospitalization (HFH).

Among 347 DCM patients with LBBB (median age 60[53-68], median LVEF 31%[23-39]), 22 (6%) exhibited P/LP variants. Genotype-positive patients less frequently fulfilled strict LBBB criteria (Strauss:P<0.001) and exhibited less mechanical dyssynchrony (predominantly LBBB-0/1;P<0.001). They showed attenuated reverse remodeling after CRT (ΔLVEF 1%[-6-6] vs. 14%[7-22];P<0.001) and worse clinical outcomes (both composite outcome and HFH;P<0.001). Conversely, advanced LBBB stages excluded an underlying rare genetic variant. P/LP variant status, LVEF, and LBBB stage independently predicted CRT response and composite outcome.

Genetic testing has a low diagnostic yield in patients with DCM and LBBB. Genotype-positive variants exhibit a distinct electromechanical profile, characterised by atypical electrocardiographic features and markedly reduced mechanical dyssynchrony, poor CRT response, and worse long-term outcomes. Integrating genetic and electromechanical phenotyping may improve individualized risk stratification and management.

Cardiometabolic disease (CMD) and cardiometabolic multimorbidity (CMM) are increasing rapidly, particularly among younger adults. This study aimed to quantify associations of age at CMD/CMM diagnosis with mortality risk and life expectancy.

A total of 684,218 participants from six cohorts (UK Biobank, US NHANES, SHARE, CHARLS, CMEC, and ELSA) were included. CMD was defined as the presence of cardiovascular disease (CVD), hypertension, or diabetes. Cox proportional hazard models were used to estimate hazard ratios (HRs) for all-cause and cause-specific mortality according to age at CMD diagnosis. Life expectancy reduction were further evaluated by age of diagnosis.

Earlier CMD diagnosis showed a clear dose-response association with higher mortality across cohorts. In the UK Biobank, the HR (95% CI) for all-cause mortality was 5.91 (4.95-7.06) for diagnosis before age 40, declining to 1.37 (1.33-1.41) at ≥70 years. Similar trends were observed in other cohorts. Earlier CMD diagnosis were also associated with greater life expectancy reduction. For instance, among 60-year-olds in the UK Biobank, those diagnosed before age 40, at 40-49, and at 50-59 years lost approximately 9.3, 5.4, and 3.2 years, respectively. For multimorbidity, mortality risk and years of life lost increased with the number of CMDs. Participants with coexisting CVD and hypertension diagnosed before age 40 had the highest mortality risk [7.36 (5.09-10.63)] and lost about 9.6 years of life at age 60.

Earlier diagnosis of CMD and CMM is strongly associated with elevated mortality and substantial reductions in life expectancy. These findings underscore the importance of early preventive intervention strategies to delay disease onset and mitigate premature mortality.