BACKGROUND:The triglyceride-glucose (TyG) index is a simple surrogate marker of insulin resistance (IR) and has been associated with coronary artery disease (CAD). However, the association between the TyG index and coronary chronic total occlusion (CTO) remains limited. METHODS:In this retrospective study, 1157 patients who underwent coronary angiography at Beijing Chaoyang Hospital from January 2024 to January 2026 were enrolled and classified into the CTO group (n = 317) and the non-CTO group (n = 840). Multivariable logistic regression analyses were performed to assess the association between the TyG index and CTO. Restricted cubic spline analysis was used to examine the linear dose-response relationship. Subgroup analyses were conducted according to age, sex, smoking status, hypertension, and diabetes mellitus. RESULTS:Patients with CTO had a significantly higher TyG index than those without CTO (8.98 [8.46, 9.45] vs. 8.79 [8.41, 9.26], p = 0.003). In the multivariable logistic regression analysis, the TyG index was independently associated with the presence of CTO (OR = 1.377, 95% CI 1.082-1.752, p = 0.009). In a sensitivity analysis further adjusted for diabetes mellitus, the association remained significant (OR = 1.356, 95% CI 1.052-1.747, p = 0.018). Restricted cubic spline curve analysis showed a nonlinear dose-response relationship (p for nonlinear = 0.005) between the TyG index and CTO risk. In the subgroup analyses, the association was directionally consistent across subgroups. Nominally significant associations were observed in elderly participants (OR 1.68, 95% CI 1.20-2.37, p = 0.003), men (OR 1.40, 95% CI 1.06-1.86, p = 0.018), and patients with hypertension (OR 1.55, 95% CI 1.14-2.11, p = 0.005). CONCLUSIONS:An elevated TyG index was independently associated with the presence of CTO. The association was generally consistent across major clinical subgroups, with no significant interactions observed.

A growing body of research demonstrates the critical involvement of gut microbiota in the initiation and progression of central nervous system disorders. Notably, gut dysbiosis has been shown to impair immune responses, metabolic pathways, and behavioral phenotypes, positioning it as a key focus in contemporary central nervous system disease research. In this study, we aimed to elucidate the pathological and physiological processes by which microbiota-gut-brain communication mediates neural repair, particularly in the context of secondary injury after spinal cord injury. We established a traumatic spinal cord injury model at thoracic level 10 in mice. Neurological restoration in spinal cord injury mice was evaluated using behavioral testing and histopathological analysis in a time-dependent manner. The gut microbiota and short-chain fatty acids were analyzed via 16S rDNA sequencing and gas chromatography-mass spectrometry, respectively. Gene expression profiling of the colon was conducted through transcriptome sequencing. The expression levels of short-chain fatty acid-related receptors and transporters were detected via quantitative polymerase chain reaction. Serum cytokine profiles were analyzed via a cytometric bead array. 16S rDNA sequencing showed dynamic alterations in the gut microbiota at different stages after spinal cord injury, and indicated a lack of gut microbial recovery following injury. Moreover, targeted metabolomic analysis demonstrated that the levels of major short-chain fatty acids (acetic acid, propionic acid, and butyric acid) fluctuated across different phases after spinal cord injury, exhibiting a trend consistent with observed behavioral changes. Transcriptome sequencing showed that the gut exhibited different types of immune responses at different phases following injury and that the humoral immune response, innate immune response, and adaptive immune response dominated during the acute, subacute, and chronic phases, respectively. These responses were accompanied by alterations in short-chain fatty acid receptor and transporter profiles in the colon and cytokine profiles in the serum. Integrated spearman correlation analysis showed that changes in the gut microbiota and metabolite-short-chain fatty acid interactions were significantly correlated with behavioral outcomes, which suggests that gut dysbiosis might have crucial effects on neural repair through short-chain-fatty-acid-mediated secondary injury. The findings of this study provide a comprehensive map of microbiota-gut-spinal cord axis alterations after spinal cord injury, and suggest novel therapeutic strategies for mediating secondary injury, including alterations in the gut microbiota and metabolites.

Objective:This study aims to investigate the association between the triglyceride-glucose (TyG) index and Phlegm-dampness constitution (PDC), as well as their joint association, on subclinical carotid atherosclerosis (SCAS) in an overweight and obese population. Methods:In this cross-sectional study, 217 overweight or obese participants were enrolled. The TyG index was categorized at the median into high and low TyG groups, and a four-category joint exposure variable was developed based on PDC status. Multivariable logistic regression was employed to assess the relationship between joint exposure and SCAS, with a stratified analysis conducted by PDC. Results:SCAS was identified in 67 of 217 participants (30.9%). The TyG index (AUC 0.681) demonstrated superior performance compared to HOMA-IR (0.585) and BMI (0.515) in distinguishing SCAS. The AUC increased from 0.704 (base model: age, sex, BMI) to 0.779 after adding the TyG index (DeLong P = 0.005) and remained essentially unchanged after further adding PDC (0.783, DeLong P = 0.220). Among the four groups, the highest prevalence of SCAS was noted in the high TyG/PDC group (50.0%), while the lowest prevalence occurred in the low TyG/PDC group (12.0%). After adjusting for age, sex, and BMI, the odds of SCAS were significantly increased in the high TyG/PDC group (OR=4.83, 95% CI: 1.67-13.95). In stratified analysis, the TyG-SCAS association was numerically stronger in the PDC subgroup (OR=11.81) than in the non-PDC subgroup (OR=2.88), although the interaction was not significant (P = 0.252). Conclusion:The coexistence of a high TyG index and PDC was associated with markedly higher odds of SCAS. The finding that the TyG-SCAS association appeared stronger in the PDC subgroup is exploratory and requires validation in larger prospective studies.

BackgroundSpinal cord injury (SCI) leads to irreversible neurological deficits, with emerging evidence highlighting the pivotal regulatory role of gut microbiota in neural repair through the bidirectional gut-brain axis. This study investigates age-related differences in SCI progression by longitudinally profiling multi-omics signatures in young versus aged mice, integrating spinal cord transcriptomics with gut microbiome analysis.MethodsA traumatic SCI model was established at the thoracic level 10 in mice. The gut microbiota was analyzed through 16S rRNA sequencing. Spinal cord gene expression was profiled using transcriptome sequencing. Correlation analysis was performed to evaluate associated between gut microbiota shifts and differential cytokines expression.ResultsAging significantly altered spinal cord gene expression profiles after SCI, KEGG pathway analysis revealed that differentially expressed genes (DEGs) in young and aged SCI mice were highly similar, predominantly involving immune and inflammatory response pathways. The age-dependent upregulation of inflammatory cytokines were observed under both sham and post-SCI conditions. Additionally, aging was associated with distinct shifts in gut microbiota composition across different phases of SCI. The abundance of certain bacterial genera, such as Lactobacillus and Dubosiella, which was significantly reduced in the acute phase, continued to decline in an age-dependent manner during the chronic phase. Correlation analysis indicated that alterations in the abundance of the gut microbiota were closely associated with variations in spinal cord inflammatory cytokine levels.ConclusionThis study delineates host-microbiome interactions in SCI and sheds light on potential mechanisms underlying age-related impairment of neural repair capacity.

Probiotics exert neuroprotective effects against Alzheimer’s disease (AD) by modulating gut-brain axis pathways, though disease-modifying therapies remain unavailable. Our study revealed that Escherichia coli (E. coli) strain HB101 ameliorated AD-related phenotypes in Caenorhabditis elegans‌ (C. elegans) models, including learning deficits, neurodegeneration, and paralysis. Mechanistically, HB101 reduced amyloid-β (Aβ) aggregation by enhancing lysosomal activity, autophagy, and mitochondrial/endoplasmic reticulum unfolded protein responses (UPRmt/UPRer). Specifically, HB101 activated UPRmt via atfs-1 and sphk-1, and UPRer through pek-1. Metabolomic screening pinpointed glutarate as a bioactive metabolite that mitigates AD-related pathology through lysosomal activation and autophagy promotion.

We sought to investigate whether remnant cholesterol (RC) modified the effect of intensive blood pressure (BP) lowering treatment. This study was a post hoc analysis of ESPRIT. In this trial, hypertensive patients with high cardiovascular risk were randomly assigned to intensive (systolic BP < 120 mmHg) or standard (systolic BP < 140 mmHg) treatment. Cox regression analysis was used to examine heterogeneity of treatment effect on the primary composite outcome (myocardial infarction, heart failure, stroke, coronary or non-coronary revascularization, or death from cardiovascular causes), individual components, and death from any cause in participants grouped by RC tertiles or the cut-off value (0.8 mmol/L). A total of 11,221 participants with complete data of baseline RC were included for analysis (females 41.3%, mean age 64.6 years). During a median follow-up of 3.3 years, 1163 primary outcomes occurred, and hazard ratios (HR) for the primary outcome were 0.98 (95% CI 0.80-1.20), 0.90 (95% CI 0.74-1.11), and 0.77 (95% CI 0.64-0.94) in the lowest, middle, and highest RC tertiles, respectively (P for interaction: 0.11). Additionally, intensive treatment only reduced the risk of myocardial infarction in the highest RC tertile (HR 0.56, 95% CI 0.36-0.89, P for interaction: 0.01). When grouping by RC level of 0.8 mmol/L, significant interactions were also noted for the primary outcome, myocardial infarction, death from cardiovascular causes, and death from any cause (all P for interaction <0.05). These results showed that effects of intensive treatment were shown to be modified by baseline RC level, and further research is needed to confirm our findings.

BACKGROUND:Fragile X syndrome (FXS) is a common inherited intellectual disability. In this study, long-read sequencing was used for the FMR1 gene detection. METHODS:Men with familial inherited intellectual disability and women with indications for FXS screening were defined as high-risk populations and were included in this study along with non-high-risk reproductive-aged women. PCR-capillary electrophoresis was used for preliminary screening of non-high-risk reproductive-aged women, and long-read sequencing was performed on abnormal samples and samples from high-risk populations. Prenatal diagnosis using long-read sequencing was performed for pregnant women in need. RESULTS:The prevalence of mutation in high-risk females was 3.10% (7/226). 3 mutations were detected in male samples, with a mutation ratio of approximately 8.3% (3/36). The three most common CGG repeats were 29, 30, and 36, respectively. Analysis of AGG interruption pattern in 242 samples identified 908 AGG interruptions, involving 67 different patterns. The most frequent AGG interruption pattern was (CGG)9AGG(CGG)9AGG(CGG)9. Furthermore, long-read sequencing was successfully applied for prenatal diagnosis in two pregnant women, and dynamic mutation of CGG repeat was detected within one family. CONCLUSION:Long-read sequencing-based assay cannot only accurately detect CGG repeat and AGG interruption, but also simultaneously identify other abnormalities of the FMR1 gene. Long-read sequencing offers a broader detection scope and better characterization of FXS-related genetic features.

ABSTRACT Adherence to antihypertensive medications is essential for blood pressure (BP) control, influencing long‐term outcomes in hypertensive patients. This study examines the association between visit‐to‐visit variability in BP and heart rate (HR) and its effect on adherence to beta‐blocker therapy among outpatients. Conducted across 160 hospitals in China from January 1, 2011, to December 31, 2011, this study included 9225 hypertensive outpatients prescribed metoprolol succinate. BP and HR variability were assessed over three visits (baseline, 1‐month, and 2‐month follow‐up) using standard deviation (SD) and mean‐independent parameters. Nonadherence was defined as medication discontinuation or treatment regimen changes by the 2‐month follow‐up. Among the 9037 patients analyzed, the mean age was 58.85 years (±12.54), and 52.9% were male. Visit‐to‐visit variability in the rate–pressure product (RPP; SBP×HR) was a significant predictor of nonadherence, with an odds ratio (OR) of 1.26 (95% confidence interval [CI]: 1.04–1.53, p < 0.05) for the top‐decile SD of RPP, independent of mean RPP. Variability in diastolic blood pressure (DBP) and pulse pressure (PP) were also associated with nonadherence, with ORs of 1.65 (95% CI: 1.35–2.00, p < 0.001) for DBP and 1.66 (95% CI: 1.39–1.99, p < 0.001) for PP, independent of their mean values. Patients with fluctuations in PP or HR had a higher risk of nonadherence compared to those with consistent reductions in these measures. Visit‐to‐visit variability in RPP, DBP, and PP is a significant predictor of nonadherence to beta‐blockers, regardless of mean levels. Addressing this variability is critical for improving adherence to antihypertensive treatments and optimizing patient outcomes.

Accumulating data suggest that remodeling aged gut microbiota improves aging-related imbalance in intestinal homeostasis. However, evidence in favor of the beneficial effect of remodeling gut microbiota on intestinal stress and immune responses during aging is scarce. The current study revealed that old mice presented impaired gut barrier integrity. Transcriptome sequencing coupled with bioinformatics analysis revealed that aging altered gene expression profiles of the colon and mesenteric lymph nodes, which are involved mainly in stress and immune responses, respectively. Notably, gut microbiota was closely related to the differentially expressed genes. Microbiota depletion in old mice ameliorated gut barrier integrity and partially reversed the inflammatory factors upregulated in aging mice. Furthermore, fecal microbiota transplantation from young mice to old mice resulted in a significant improvement in intestinal barrier integrity and immune homeostasis. These findings highlight the potential of microbiota-targeted interventions on aging-related physiological processes and call for further investigation.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by dysbiosis of nasal microbiota and dysregulation of the immune system. Macrophages are essential for protecting against infections, but their roles and mechanisms in CRSwNP are not fully understood. To date, we gradually recognize the heterogeneity of macrophages, and new subsets of macrophages have been identified at transcriptional level due to the development of single cell RNA-sequencing. In this review, we summarize the generation, polarization, phenotype identification, and function of macrophages in CRSwNP, providing a comprehensive understanding of macrophages in CRSwNP. Additionally, we also explore how macrophages interact with other cells, including epithelial cells, immune cells, and neurons, which can worsen inflammation. A better understanding of the role of macrophages could improve their ability to clear bacteria and reduce chronic inflammation in CRSwNP, which might be clinically beneficial for CRSwNP patients.

Objectives To compare physical information, such as age, sex, height, weight, body mass index (BMI) and pulmonary function test (PFT) results, between cough variant asthma (CVA) and chronic cough (CC) and establish a diagnostic model of CVA.Design A case–control study of patients with suspected CVA enrolled at The First Affiliated Hospital of Zhejiang Chinese Medical University.Setting One leader unit of the National Key Specialised Pulmonary Disease Cooperation Group in China.Participants Enrolled 545 patients who underwent PFT and bronchial provocation tests.Outcome measures We obtained physical information and pulmonary test data and established the model using logistic regression analysis. The Hosmer-Lemeshow goodness-of-fit test, area under the receiver operating characteristic curve (AUC), calibration plot and decision curve analysis were used to evaluate this model. All data were analysed using SPSS V.27 and RStudio software.Results The CVA group had more female patients (%) (68.12% vs 51.48%, p value<0.001) and lower height (m) (1.61 (0.40) vs 1.65 (3.26), p value<0.001), weight (kg) (60 (56) vs 63 (85), p value<0.001) and BMI (kg/m2) (22.59 (17.91) vs 23.28 (21.81), p value=0.016) than the CC group. Differences between CVA and CC in forced vital capacity (FVC) in percent predicted values (FVC% pred)(94.4 (57.3) vs 91.60 (94.10), p value=0.006), forced expiratory volume in 1 s/FVC (FEV1/FVC) (%) (84.65±6.82 vs 86.91±6.71, p value<0.001), peak expiratory flow in per cent predicted values (PEF% pred) (93.00 (81.10) vs 98.00 (108.00), p value=0.005), maximal mid-expiratory flow in percent predicted values (MMEF% pred) (74.50 (100.60) vs 90.85 (170.30), p value<0.001), forced expiratory flow (FEF) at 50% of FVC in per cent predicted values (FEF50% pred) (78.9(113.50) vs 93.10(169.80), p value<0.001) and FEF at 75% of FVC in per cent predicted values (FEF75% pred) (69.70 (137.60) vs 85.60 (225.80), p value<0.001) were significant. Patients with CVA were more in number compared with patients with CC at a lower degree (<65%) of MMEF% pred (32.37% vs 14.50%, p value<0.001), FEF50% pred (26.09% vs 13.02%, p value<0.001) and FEF75% pred (39.13% vs 23.67%, p value<0.001). FVC% pred, FEV1/FVC, BMI and MMEF% pred aided in establishing a model with an AUC of 0.733 (95% CI: 0.6829 to 0.7831). The model was tested using internal and external data (p value=0.2865 and p value=0.3197, respectively).Conclusion BMI, FVC% pred, FEV1/FVC (%) and MMEF% pred were used to establish the diagnostic model. Our model potentially indicates CVA.Trial registration number NCT06199830.

Group 2 innate lymphoid cells (ILC2s) directly contribute to local inflammation in type 2 inflammatory airway diseases. Here, we identify ILC2 subsets by single cell RNA sequencing in chronic rhinosinusitis with nasal polyps (CRSwNP) and in a memory inflammatory mouse model. We find that toll-like receptor 4 (TLR4)+ILC2s, with similar markers to their human counterparts, expresse memory cell markers, persist over time, and respond more vigorously to a secondary unrelated antigen challenge in the mouse model. Genetic ablation of TLR4 or blockade by anti-TLR4 antibodies leads to the reduction of IL-13 expression from ILC2s and mucus production in mice. The assay for transposase-accessible chromatin sequencing further confirms the importance of accessible TLR4 gene loci and its down-stream signaling pathway in maintaining trained immunity of TLR4+ILC2s after repeated stimulation by HDM. Taken together, TLR4 has a function in trained immunity maintenance within ILC2s, which may contribute to disease chronicity through a non-specific immunological memory.

BackgroundCentral obesity in children represents a significant public health concern due to its strong association with an elevated risk of metabolic and cardiovascular disorders. The systemic immune inflammation index (SII) has been implicated in the pathophysiology of obesity-related chronic inflammation. Despite its potential relevance, the specific relationship between central obesity and SII in the pediatric population remains insufficiently explored. The objective of this study was to examine the relationship between SII and central obesity, with a particular focus on the potential of SII as a predictor of central obesity and a means of preventing obesity at an early stage of life.MethodsWaist-to-height ratio (WHtR), subcutaneous fat, and visceral fat were employed as obesity proxies. Central obesity was defined according to WHtR with a cutoff value of 0.46. The implications of SII on central obesity were examined in a sample of 4,730 individuals in 2021 and validated through a prospective study involving 1,425 subjects in 2023. Cross-sectional associations between SII and central obesity were examined using binomial logistic regression models and generalized linear models. The restricted cubic spline regression was used to explore the non-linear relationship between SII and obesity indicators. In a prospective study, we employed a modified Poisson regression model to investigate the potential causal relationship between SII and central obesity.ResultsCross-sectionally, adolescents in the highest quartile of SII levels exhibited the greatest risk for central obesity(OR=3.07, 95% CI:2.45~3.87) when compared to those in the lowest quartile. Subgroup analyses showed that higher SII was associated with central obesity. Longitudinally, individuals in the highest SII quartile were found to have the highest risk of developing central obesity (RR=1.83, 95% CI:1.18~2.83) over time.

We report a rare case of IgG4-related lung disease (RLD) with pulmonary lesions and recurrent pleural effusion to improve the diagnosis and treatment of this disease. A 60-year-old man was admitted to hospital for cough and dyspnea. CT scan showed a right lower lobe intrapulmonary mass with unilateral right-sided pleural effusion. Histology revealed no malignant findings. After 1 year, the patient re-admitted to our hospital with high serum level of IgG4 and IgE concentrations. CT scan demonstrated partial resolution of intrapulmonary mass and right-sided pleural effusion, while concurrently revealing interval development of substantial left-sided pleural effusion. The patient was diagnosed with IgG4-RLD by biopsy finally. This is a first case report of IgG4-RLD with intrapulmonary lesions accompanied by asynchronous, rapidly accumulating bilateral pleural effusions. Clinicians should consider the possibility of IgG4-RLD with intrapulmonary lesions accompanied by asynchronous, rapidly growing bilateral pleural effusion, particularly after rigorously excluding common diseases.

BACKGROUND:The mediating role of inflammatory biomarkers in the causal relationship between body composition and hypertension remains unclear and requires further investigation. METHODS:This study used a combination of retrospective observational analysis and Mendelian randomization approaches. Observational data were derived from 4717 Chinese children and adolescents aged 6 to 18 years who underwent dual-energy X-ray absorptiometry to assess body composition. Mendelian randomization analyses utilized summary statistics from large-scale data sets, including UK Biobank, deCODE2021, International Consortium of Blood Pressure, FinnGen, and other consortia. The inflammatory biomarkers included leptin, insulin, adiponectin, osteocalcin, FGF23 (fibroblast growth factor 23), and PTH (parathyroid hormone). RESULTS:The observational analysis revealed that increased fat mass positively influenced diastolic blood pressure through osteocalcin, while fat-free mass had an inverse effect. Insulin mediated the association between fat mass and systolic blood pressure, diastolic blood pressure, and hypertension, with additional indirect effects observed for PTH (all P<0.05). The Mendelian randomization analyses demonstrated a causal relationship between childhood body mass index and hypertension mediated by insulin (indirect effect: odds ratio, 0.87 [95% CI, 0.78-0.97]) and adiponectin (odds ratio, 1.13 [95% CI, 1.04-1.23]). Adiponectin mediated the effects of fat-free mass (odds ratio, 0.81 [95% CI, 0.71-0.93]) and fat mass (odds ratio, 1.30 [95% CI, 1.11-1.51]) on hypertension. Leptin, adiponectin, and insulin also mediated the causal effects of body composition on systolic blood pressure, diastolic blood pressure, and hypertension. CONCLUSIONS:These findings indicate that body composition influences blood pressure through distinct inflammatory biomarkers. Targeting inflammatory biomarkers may provide tailored strategies for managing body composition and hypertension.

BACKGROUND:Elevated systolic blood pressure (SBP) accounts for one-half of the population attributable fraction for stroke, so lowering SBP is the most important treatment for preventing stroke. OBJECTIVES:In this study, the authors sought to assess the effects of intensive treatment targeting SBP <120 mm Hg on stroke compared with standard treatment targeting SBP <140 mm Hg. METHODS:In the ESPRIT trial, hypertensive patients with high cardiovascular risk were randomly assigned to intensive treatment or standard treatment and followed for 3.4 years. We fitted Cox proportional hazards regression models to examine the effects on the incidence of stroke, one of the prespecified secondary outcomes. In addition, we performed post hoc analyses including effects on stroke subtypes and the landmark analyses about stroke and stroke subtypes. RESULTS:We randomized 11,255 participants (3,022 with previous stroke). Their mean age was 64.6 ± 7.1 years, and 4,650 (41.3%) were female. During the follow-up, the mean SBP was 119.1 ± 11.1 mm Hg in the intensive arm and 134.8 ± 10.5 mm Hg in the standard arm. Stroke occurred in 262 participants (4.7%) in the intensive arm and 303 (5.4%) in the standard arm (HR: 0.86; 95% CI: 0.73-1.02; P = 0.083), ischemic stroke in, respectively, 243 (4.3%) vs 261 (4.6%) (HR: 0.93; 95% CI: 0.78-1.11; P = 0.423), and hemorrhagic stroke 23 (0.4%) vs 45 (0.8%) (HR: 0.51; 95% CI: 0.31-0.85; P = 0.009). Landmark analysis showed that the risk difference in stroke emerged after 1 year, and the HR for the period of longer than 1 year was 0.75 (95% CI: 0.60-0.94; P = 0.011). There were no interactions across all subgroups of baseline characteristics, including demographics, region, lifestyle, diastolic blood pressure, orthostatic hypotension, and comorbidities (all P interaction >0.05). CONCLUSIONS:Compared with targeting <140 mm Hg, targeting <120 mm Hg halved the risk of hemorrhagic stroke and did not increase that of ischemic stroke. The stroke-preventing effect emerged after 1 year of intervention. Future studies are needed to confirm these findings.

Background: Previous studies have presented conflicting results on the correlation between metabolic syndrome (MetS) and subclinical atherosclerosis. However, the binary MetS definition cannot reflect the severity of metabolic disorders continuously and dynamically. The present study calculated the MetS score and explored the association between MetS score and subclinical atherosclerosis. Methods: A total of 840 participants were included in this observational, cross-sectional study; 66.55% of participants were men, and the median age was 61.00 years (53.00, 67.00). Brachial–ankle pulse wave velocity (baPWV) and brachial flow-mediated dilation (bFMD) values were measured from October 2016 to January 2020. Spearman’s correlation and multiple linear regression analyses were conducted to explore the correlation between the MetS score and baPWV and bFMD. Arterial stiffness was defined as baPWV ≥1400 cm/s, while endothelial dysfunction was described as bFMD >6%. Multiple logistic regression was performed to explore the effects of MetS and MetS score on arterial stiffness and endothelial dysfunction. Results: The MetS score was significantly associated with baPWV (β = 73.59, 95% CI (42.70, 104.48); p < 0.001) and bFMD (β = –0.43, 95% CI (–0.75, –0.10); p = 0.010) after adjusting for covariates. Compared with the binary definition of MetS, the MetS score was a more significant predictor for arterial stiffness (odds ratio, OR = 2.63, 95% CI (1.85, 3.74); p < 0.001) and endothelial dysfunction (OR = 1.33, 95% CI (1.01, 1.76); p = 0.040). Leukocyte count (r = 0.32; p < 0.001) and high-sensitivity C-reactive protein (hs-CRP) (r = 0.17; p < 0.001) values were related to the MetS score. Conclusions: The MetS score is a clinically accessible assessment of metabolic status that can identify individuals at higher risk of subclinical atherosclerosis.

AIM:To investigate the effects of pharmacological PLD inhibition and astrocyte-specific PLD1 deletion on functional recovery and tissue pathology after SCI. MAIN METHODS:A contusion SCI model was established in transgenic mice with conditional astrocytic PLD1 deletion, as well as in wild-type animals treated with Five-Fluoro-2-Indolyl Des-Chlorohalopemide (FIPI), a pharmacological PLD inhibitor. Motor function recovery, tissue preservation, and astrocytic activity were assessed. In addition, lipidomic profiling was performed to evaluate metabolic alterations associated with SCI and PLD inhibition. KEY FINDINGS:Both PLD inhibition and astrocytic PLD1 deletion significantly improved motor function recovery and reduced astrocytic reactivity, partly through suppression of neurotoxic astrocyte populations. Lipidomic analysis revealed SCI-associated alterations, including increases in cholesteryl esters and free fatty acids and decreases in phosphatidylcholine and phosphatidylethanolamine. Notably, FIPI treatment partially restored lipid imbalances, particularly normalizing phosphatidylcholine and phosphatidylethanolamine levels. SIGNIFICANCE:These findings demonstrate that genetic deletion of astrocytic PLD1 or pharmacological PLD inhibition can mitigate astrocytic neurotoxicity and enhance functional recovery after SCI. Targeting PLD1 therefore represents a promising therapeutic strategy to improve outcomes in SCI.