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Seasonal variation in cardiovascular disease (CVD) is well documented. Data on seasonal fluctuations in cardiovascular risk markers are relatively sparse but may be relevant for CVD risk classification and treatment. We aimed to quantify the presence, magnitude, and timing of seasonality across various cardiovascular risk markers in patients referred to coronary angiography. In this retrospective, cross-sectional study, we analysed cardiovascular risk markers in 3316 patients referred to coronary angiography between July 1997 and January 2000 from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Seasonal patterns were assessed using robust cosinor regressions, while correcting for age and sex. For each cardiovascular risk marker, we evaluated seasonality, peak date and magnitude (difference between peak and nadir) of seasonal fluctuations. Accordingly, we analysed 24 different cardiovascular risk markers and corrected for the false discovery rate (FDR). Overall, 16 cardiovascular risk markers showed significant seasonal dependency, of which the following had Cohen's d higher than 0.2 (peak-nadir difference): 25-hydroxyvitamin D (10.28 ng/mL), LDL cholesterol (15.36 mg/dL), HbA1c (0.31%), Omega-3 Index (0.45%), HDL (3.18 mg/dL), HOMA Index (0.54), calcium (0.03 mmol/L), and ApoB (5.6 mg/dL). Timing of peaks varied starkly. The seasonality in cardiovascular risk markers of patients referred to coronary angiography indicates that diagnostic and therapeutic thresholds for these markers should consider the date of assessment. Diverse seasonality timings suggest that the underlying mechanisms for seasonal fluctuations are likely multifactorial. Further research should evaluate the individual and environmental factors that may cause these seasonal fluctuations. Show less

Dyslipidemia was a hallmark of metabolic disturbances in coronary heart disease (CHD), metabolic syndrome (MetS), and nephrotic syndrome (NS), yet the specific lipid profile patterns characteristic of each disease remained insufficiently defined. This study aimed to clearly characterize and compare the qualitative features of lipid profiles across patients with CHD, MetS, and NS, and to identify key lipid markers associated with disease classification using multinomial logistic regression. A total of 180 patients were enrolled and classified into three groups (CHD, MetS, NS) based on established diagnostic criteria. 60 healthy controls were concurrently enrolled. Lipidomic profiles and additional laboratory parameters were measured using validated analytical methods. Multinomial logistic regression was used to evaluate the associations between lipid parameters and disease categories. Lipid profile analysis revealed distinct qualitative trends across the disease groups. The CHD group demonstrated notably higher levels of TC and sdLDL, the MetS group exhibited prominent increases in TG and ApoE, while the NS group showed a broad and pronounced elevation across most measured lipid parameters. By contrast, the healthy control group consistently presented uniformly lower lipid levels. LASSO-guided multinomial logistic regression identified TC, TG, ApoB, ApoE, and sdLDL-C as independent predictors of disease classification. Distinct patterns of dyslipidemia were observed in CHD, MetS, and NS. TC and sdLDL-C might serve as robust markers for CHD, while ApoB demonstrated disease-specific variability with diagnostic potential. These findings underscored the importance of detailed lipid profiling for improved risk stratification and targeted management. Show less

Psoriasis patients face a significantly elevated risk of cardiovascular diseases (CVD), necessitating early and accurate risk prediction tools. This study developed and validated a machine learning model to predict CVD risk in psoriasis patients using clinical and biochemical data from 2685 individuals. After preprocessing and addressing class imbalance with SMOTE-NC, six machine learning models (Logistic Regression as baseline, XGBoost, LightGBM, CatBoost, GradientBoosting, AdaBoost) were evaluated using a completely leak-free nested cross-validation framework (outer k = 10, inner k = 3) with randomized hyperparameter search (n_iter = 50). Feature selection via the Boruta algorithm was performed separately within each training fold to prevent data leakage. The Boruta algorithm identified 21 key predictors, including age, systolic blood pressure (SBP), apolipoprotein B (apoB), fasting blood glucose (FBG), and complement C1q. CatBoost emerged as the top-performing model (OOF ROC-AUC = 0.908, 95% CI [0.892-0.924]; PR-AUC = 0.509, 95% CI [0.448-0.578]; F1 = 0.540; MCC = 0.498; Brier = 0.078), while the Logistic Regression baseline achieved ROC-AUC = 0.909 but was eliminated due to poor calibration (Brier = 0.114 > 0.10). All metrics were evaluated with 95% bootstrap confidence intervals ( Show less

To explore the correlation between lipid metabolism profile, clinical indicators and prognosis of corticosteroid treatment in sudden sensorineural hearing loss (SSNHL) patients, and construct/verify a prognostic assessment model based on lipid metabolism profile for clinical individualized treatment. A retrospective study enrolled 446 SSNHL patients (divided into training set, Poor prognosis group had higher age, diabetes/hypertension rates, ApoB/ApoB/ApoA ratio, non-HDL-C, disease duration, total deafness rate, and lower HDL-C/ApoA (all Age, diabetes, HDL-C, ApoB/ApoA ratio and disease duration are key factors for SSNHL corticosteroid treatment prognosis. The nomogram based on these indicators has reliable predictive efficacy, serving as an effective tool for clinical prognosis assessment and individualized treatment. Show less

Atherosclerotic cardiovascular disease (ASCVD) risk assessment relies heavily on low-density lipoprotein cholesterol (LDL-C), arterial blood pressure, and population-based risk calculators. Although effective for population screening, these approaches may underestimate risk in individuals with discordant lipid profiles when atherogenic particle burden is not captured by conventional testing. We report a 55-year-old male Ironman triathlete who suffered an acute myocardial infarction during competition. Evaluation showed posterior ST-segment changes, metabolic acidosis, transient hyperglycemia, and acute kidney injury. Coronary angiography revealed chronic total occlusion of the right coronary artery, complete occlusion of the left circumflex artery, and severe distal left anterior descending artery stenosis requiring multivessel percutaneous coronary intervention. Longitudinal outpatient testing demonstrated unremarkable risk factors, including mildly elevated total cholesterol and LDL-C, normal apolipoprotein B (apoB), and normal glycemic markers suggestive of low 10-year ASCVD risk. Advanced lipid testing after discharge showed markedly elevated LDL particle number (LDL-P) and increased small dense LDL (sdLDL), consistent with LDL pattern B. This case highlights how particle-based abnormalities may contribute to accelerated atherosclerosis despite reassuring conventional risk assessment and absence of guideline-defined lipid risk-enhancing factors. Show less

Apolipoprotein B [apoB] and lipoprotein(a) [Lp(a)] concentrations are the two prime lipoprotein indices recommended by some expert consensus to assess and manage cardiovascular risk. However, their distributions, associations, inter-relationships, and clinical relevance remain un-investigated in the majority of Asian populations, particularly among healthcare workers. The distributions and relationships of serum Lp(a), apoB, and other lipid biomarker concentrations in 1,927 Asian consenting healthcare workers across ethnicities, sexes, and body mass index (BMI) were analysed. The percentage of apoB content of Lp(a) relative to apoB particle concentrations (Lp(a)-to-apoB proportion) was calculated. Participants’ mean age was 39.4 years, mostly females (79.7%). Ethnicities were Chinese (57.2%), Malay (16.9%), Indian (9.2%), Filipino (12.8%) and others (3.8%). Distribution of Lp(a) was positively skewed to the right for all ethnicities. The median Lp(a) was 16.4 nmol/L (IQR 7.9, 41.8) and ranged between < 7 to 470 nmol/L. The proportion of participants with Lp(a) ≥ 75 nmol/L was 13.9%, and with Lp(a) ≥ 125 nmol/L was 7.8%. Multivariable linear regression analysis showed that being female, older age, and Indian ethnicity were associated with higher Lp(a) levels, whereas being male, older age, Indian ethnicity, and higher BMI were associated with higher mean apoB levels. In this cohort, 11.4% of individuals had Lp(a)-to-apoB proportion > 5%, whilst 3.3% had Lp(a)-to-apoB proportion of > 10%. Among individuals with Lp(a) ≥ 250 nmol/L, the median Lp(a)-to-apoB proportion was 14.9% (IQR 12.6,19.7). Across Lp(a) deciles, the Lp(a)-to-apoB proportions were inversely correlated with LDL-C, non-HDL-C, remnant cholesterol, and triglyceride concentrations. Abnormal Lp(a) (≥ 75 nmol/L) was found in 13.9% of a predominantly female Asian healthcare cohort. In individuals with Lp(a) ≥ 250 nmol/L, Lp(a) particles contributed to the circulating apoB levels by a median of 15%. These findings support the notion that Lp(a) should be integrated into routine lipid assessment in Asian populations, including healthcare workers. clinicaltrial.gov NCT06304415. The online version contains supplementary material available at 10.1186/s12944-026-02912-7. Show less

Acute alcohol consumption is known to exert widespread physiological effects, yet the immediate impacts on metabolic biomarkers remain incompletely understood. The present randomized controlled trial was conducted to investigate the acute effects of a single episode of alcohol ingestion on various biomarkers in healthy individuals. A total of 45 male participants were recruited and randomized into an alcohol group (n = 40) and a control group (n = 5) at an 8:1 ratio. Volunteers in the alcohol group ingested 40% Absolut vodka within 15 min. Blood pressure, heart rate, and blood oxygen saturation were measured at 0 h, 1 h, 3 h, 5 h, 12 h, and 24 h. Venous blood samples were drawn at 0 h, 1 h, 5 h, 12 h, and 24 h after alcohol intake. Our results showed that levels of liver function markers, including α-fucosidase (AFU), albumin (ALB), and alkaline phosphatase (ALP), were significantly increased in the alcohol group compared to the control group. The 24-h area under curve (AUC) of AFU, ALB, and ALP were significantly higher in the alcohol group. The liver fibrosis maker collagen type Ⅳ (Ⅳ-C) tended to be higher at 1 h and 12 h in the alcohol group compared to the control group. Lipid levels, including triglycerides (TG), apolipoprotein A1 (APOA1), and the APOA1/APOB, were significantly elevated after alcohol ingestion, particularly at 5 h and 12 h. The 24 h-AUC of TG, APOA1, and APOA1/APOB were higher in the alcohol group than in the control group. Additionally, cardiac function indicators, including heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP), were significantly elevated in the alcohol group. SBP and DBP remained higher 24 h after alcohol ingestion compared to the control group. This study demonstrated that even a single episode of binge drinking could induce significant alterations of biomarkers related to liver function, cardiac function, and lipid profiles. These findings provided valuable insights into the short-term impact of alcohol on health and highlighted the importance of further research to explore the long-term implications of repeated acute alcohol exposure. Given the very small control group, these results should be interpreted as preliminary and confirmed in larger, more balanced randomized trials. The online version contains supplementary material available at 10.1038/s41598-026-40028-1. Show less

Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disorder. Notably, the differences in lipid metabolism between bulbar- and limb-onset subtypes of ALS remain unclear, particularly in non-Western populations. The present study investigated serum lipid profiles in a Chinese cohort of patients with ALS to explore their associations with disease severity and clinical subtypes. A retrospective, cross-sectional study was conducted, involving 158 patients with ALS and 62 matched healthy controls. Serum lipid parameters, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), small dense LDL cholesterol (sdLDL-c), apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB) and the TG/HDL ratio, were compared between the groups. Correlation analyses and multivariable linear regression models incorporating phenotype x lipid interaction terms were conducted after adjusting for age, sex, body mass index and disease duration. Patients with ALS exhibited significantly higher TC, TG, LDL, sdLDL-c, ApoA1, ApoB and TG/HDL ratios than controls. Subtype-specific analyses revealed different associations; in bulbar-onset ALS, higher sdLDL-c and TG/HDL ratios were associated with better functional status, whereas higher HDL and ApoA1 levels were negatively correlated with functional status. By contrast, in limb-onset ALS, higher sdLDL-c and ApoB levels were associated with worse function. Interaction analyses confirmed significant phenotype modification for sdLDL-c, TG/HDL ratio, HDL and ApoA1. These results suggest that lipid-severity relationships in ALS vary by subtype, indicating metabolic heterogeneity across phenotypes and supporting the potential of specific lipid parameters as exploratory markers for disease monitoring. Show less

Chronic low-grade inflammation plays a central role in cardiometabolic disease, yet the associations between lipid metabolism and inflammatory biomarkers in generally healthy individuals remain incompletely understood. This study aimed to investigate the relationship between blood lipids, high-sensitivity C-reactive protein (hsCRP), and a broad panel of inflammatory cytokines in a healthy adult population. A total of 165 healthy participants aged 18-44 years were recruited at the Falun County Hospital, Sweden. Blood samples were analyzed for a full lipid profile, blood counts, cytokines, and hsCRP. Plasma inflammatory protein levels were quantified using the Olink Proseek Multiplex Inflammation panel, including 92 cytokines. Statistical analysis included Spearman rank correlations and multiple testing correction using the Benjamini-Hochberg false discovery rate (FDR < 0.10). hsCRP showed significant correlations with several lipid parameters, particularly remnants, triglycerides, apolipoprotein B (ApoB), and non-HDL cholesterol, as well as with BMI and specific leukocyte counts. Additionally, hsCRP was significantly associated with multiple cytokines, including IL-6, TNF, IL-10, and CXCL10, highlighting a complex pro- and anti-inflammatory milieu. This study demonstrates correlations between hsCRP, lipid-related biomarkers, and inflammatory cytokines in healthy adults, underscoring the interplay between lipid metabolism and subclinical inflammation. The significant correlations between hsCRP and remnants, ApoB, and cytokines such as IL-6 support the role of these factors as early indicators of cardiometabolic risk, even in the absence of overt disease. Show less

Adolescent Idiopathic Scoliosis (AIS) is the most common form of spinal deformity among adolescents. To explore its etiology of progression and scoliosis-modifying drugs, chondrocytic senescence was confirmed in AIS facet joint cartilage by analyzing clinical specimen. Furthermore, through 4D/480 label-free proteomics analysis, we identified an exosome-mediated positive feedback loop during scoliosis progression, which driving the elevation of cholesterol flow between spinal cartilage and vertebra. To further investigate the pathological significance of the loop in vivo, high-cholesterol flow was reconstructed in C57BL/6 J mice by injecting with recombinant adeno-associated virus rAAV9-Runx2-HMGCR. Our results confirmed the important role of the positive feedback loop in the development of scoliosis. Meanwhile, Avasimibe or/and Corylin were used to delay the scoliosis progression by targeting the key exosomal proteins APOB (Apolipoprotein B-100) or/and HSP90β (Heat Shock Protein 90-beta). This research extends the etiology of scoliosis progression and provides an alternative perspective for scoliosis non-surgical treatment. Show less

Lipoprotein(a)-targeted therapies are emerging approaches for lowering lipoprotein(a) [lp(a)]. We conducted a systematic review and network meta-analysis to evaluate the efficacy and safety of lipoprotein(a)-targeted therapies in patients. We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to May 6, 2025, for randomized controlled trials (RCTs) with intervention duration of at least 12 weeks. The primary outcomes were percentage and absolute changes in Lp(a). Secondary outcomes included changes in low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB), and safety outcomes including adverse events (AEs), serious adverse events (SAEs), and injection-site reactions. A frequentist framework network meta- analysis was performed. Nine studies involving 1,432 participants were included. All six Lp(a)-targeted therapies significantly reduced Lp(a) levels. Compared with placebo, Olpasiran was the most effective therapy for both percentage [mean difference: -92.06, 95% (-109.80; -74.32), Lp(a)-targeted therapies achieved substantial reductions in Lp(a). Olpasiran was the most effective agent in lowering Lp(a) levels. These therapies also improved LDL-C and apoB. The majority of Lp(a)-targeted therapies demonstrate generally favorable safety profiles; However, injection-site reactions, particularly with Zerlasiran, warrant careful consideration. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251069288, PROSPERO CRD420251069288. Show less

Copper overload has been implicated in impaired A total of 117 patients with T2DM (mean age 55.15 ± 10.70 years; 62.4% male) were included. Whole blood copper concentration was measured using inductively coupled plasma mass spectrometry. Associations between blood copper and glycemic indicators, including glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG), were evaluated using multivariable linear regression models. Stratified and interaction analyses were performed according to apoB and other lipid-related parameters. After adjustment for potential confounders, a significant interaction between blood copper and apoB was observed in relation to HbA1c (P for interaction< 0.001). Stratified analyses showed that higher blood copper concentration was significantly associated with higher HbA1c levels among patients with lower apoB levels below the study median, whereas no significant association was observed among those with higher apoB levels. Exploratory analyses further indicated that apoB also influenced the association between blood copper and FPG (P for interaction< 0.05), showing a consistent pattern. In patients with T2DM, a significant association between blood copper concentration and glycemic control was observed among individuals with lower apoB levels, whereas no such association was found among those with higher apoB levels. These findings suggest that apoB status may influence the relationship between blood copper and glycemic control and merit further investigation in longitudinal studies. Show less

To investigate the connection betweenischemic stroke (IS) patients' risk of dying after being discharged and their residual cholesterol (RC) levels uponadmission. 2021 IS patients between the ages of 35 and 80were chosen as the study's subjects, and data on deathendpoints following discharge were gathered. The doseresponse association between the risk of death and the RCat admission was examined using restricted cubic spline(RCS) regression. The hazard ratio (HR) and 95% CI werecalculated via Cox regression to analyse the associationbetween the RC level at admission and the risk of deathafter discharge in patients with IS. According to the RCS model, RC levels were nonlinearly associated with deaths from IS and other causes(P<0.001). With the median RC level as the cutoff value,the subjects were divided into two groups: a low RC group(RC<0.72 mmol/L) and a high RC group (RC≥0.72mmol/L). Compared with those in the high RC group, theage and male ratio in the low RC group were significantlygreater. The fasting blood glucose (GLU), total cholesterol(TC), triglyceride (TG), low-density lipoprotein cholesterol(LDL-C), non-high-density lipoprotein cholesterol (nonHDL-C), apolipoprotein A-1 (ApoA-1), and apolipoproteinB (ApoB) levels, as well as diabetes rates, were lower (P=0.01). Cox regression analysis revealed that withoutadjusting for covariates, the high-level RC group presenteda lower risk of all-cause death than the low-level RC group(HR=0.765, 95% CI: 0.619~0.946, P=0.013) and alower risk of death from IS (HR = 0.638, 95% CI:0.435~0.936, P=0.022). After adjusting for sex, age,smoking status, drinking status, hypertension status, anddiabetes status, the high-level group still had a lower risk ofall-cause death (HR = 760, 95% CI: 0.614~0.941,P=0.012) and a lower risk of death from IS (HR=0.653,95% CI: 0.444-0.961, P=0.031). Male sex (HR=0.753,95% CI: 0.572~0.990, P=0.042). Age ≥65 years (HR=0.598, 95% CI: 0.391~0.916, P=0.018), nonsmokingstatus (HR=0.628, 95% CI: 0.408~0.967, P=0.035),nonalcoholic status (HR=0.656, 95% CI: 0.439~0.979,P=0.039), not complicated with hypertension (HR=0.321, 95% CI: 0.108~0.957, P=0.041), no diabetesmellitus (HR=0.607, 95% CI: 0.389~0.947, P=0.028).Compared with those in the high RC group, the IS patientsin the low RC group had a lower incidence of all-causedeath, IS death and other causes of death and a higher survival rate. An RC<0.72 mmol/L at admission is associated with an increased risk of all-cause death and longterm IS death after discharge. Show less

Apolipoprotein B (ApoB) is a key marker of atherogenic lipoprotein burden, but conventional plasma-based testing requires venous sampling and centralized laboratory infrastructure. Dried blood spot (DBS) sampling offers a minimally invasive alternative suitable for decentralized settings. This study evaluated the analytical performance of a DBS-based ApoB assay on the Chem7 semi-automated analyser and compared it with the Abbott ARCHITECT ci4100 plasma reference method. DBS samples prepared from 50 de-identified EDTA whole-blood specimens were extracted in saline and analysed using an immunoturbidimetric ApoB assay on the Chem7 analyser with a correction factor of 2 applied for haematocrit dilution. Paired plasma specimens were analysed on the ARCHITECT ci4100. Method comparison included Passing-Bablok and Deming regression and Bland-Altman analysis. Potential outliers were assessed using Grubbs' test ( Show less

Through the selective breeding of superior strains, livestock and poultry can achieve enhanced disease resistance and production performance, thereby improving farming efficiency and increasing chicken meat yield. This study analyzed the expression of gut health-related genes, cecal microbiota, and untargeted serum metabolomics in Wenchang chickens from the NS strain (Normal strain) and the AFS strain (Antibiotic-free strain), and explored the relationships between their cecal microbiota and serum metabolites. Our results show that in the ileum, antioxidant-related indicators T-AOC (P < 0.05), T-SOD (P < 0.05), and GSH-PX (P < 0.05) were significantly higher in the AFS strain than in the NS strain, while MDA (P < 0.05) was significantly lower in the AFS strain than in the NS strain. The mRNA expression level of RORγt/FoxP3, which is related to immune regulation, was significantly lower in the AFS strain than in the NS strain (P < 0.05). The differential microorganisms in the cecum primarily included Muribaculum, Cryptobacteroides, Blautia, Enterocloster, Lachnoclostridium, Hydrogenoanaerobacterium, Ruminococcus, Subdoligranulum, Clostridioides, and Evtepia. The main differential metabolites in serum included folinic acid, biotin, lysophosphatidic acid (LPA), 3-hydroxy-3-methylbutanoic acid, 3-hydroxybutyric acid, and others. The differential metabolites are primarily enriched in the following metabolic pathways: gap junction, glycolipid metabolism, and fatty acid biosynthesis. In addition, the Pearson correlation analysis between the gut microbiota and serum metabolites showed that Blautia was positively correlated with folinic acid (P < 0.05) and biotin (P < 0.05); Lachnoclostridium was positively correlated with biotin (P < 0.01); and Ruminococcus was positively correlated with 3-hydroxybutyric acid (P < 0.05). This study mainly elucidates the metabolic characteristics of the antibiotic-free Wenchang chicken strain by analyzing gut microbiota and serum metabolites. Show less

Chemokines C-X-C Motif Chemokine Ligand 9 (CXCL9) and C-C Motif Chemokine Ligand 2 (CCL2) were previously linked to incident cognitive impairment and dementia in the Northern Manhattan Study (NOMAS). We investigated whether circulating CXCL9 and CCL2 are independently associated with the cerebral white matter disease (WMD) burden and whether WMD mediates their association with prospective cognitive outcomes. In the stroke-free, prospective, community-dwelling NOMAS cohort (age≥50) we examined white matter hyperintensity volume (WMHV) on brain MRI and serum chemokine levels. WMHV was normalized, log-transformed, and standardized. Cognitive status was assessed at MRI and again 12.2±1.3 years later to adjudicate incident cognitive decline and dementia. Multivariable linear regression models with either CXCL9 or CCL2 (in quartiles) as exposures and WMHV as the outcome were adjusted for socio-demographics and key contributors to WMD, including vascular risk factors (Model 1), kidney function (2), and APOE ε4 status (3). Mediation of the CXCL9-cognitive outcome association by WMHV was tested using Monte Carlo integration. Among 1,179 participants (mean age 70±9 years; 60% female), elevated CXCL9 (Q4 vs. Q1) was associated with greater WMHV (Model 1: β=0.20, 95%CI 0.06-0.34). This association persisted even after adjusting for kidney function (Model 2: β=0.17, 95%CI 0.03-0.34) and APOE ε4 status (Model 3: β=0.19, 95%CI 0.04-0.33). CXCL9 (Q4 vs. Q1) effect magnitude in Model 3 approximated ~4 years of aging (β=0.05/year, 95%CI 0.04-0.06), exceeding that of hypertension (β=0.16, 95%CI 0.05-0.27), with a stepwise trend present across quartiles (β/quartile increase=0.07, 95%CI 0.02-0.12, p=0.003). Among 1,166 participants (dementia-free at MRI), the indirect, WMHV-mediated pathway was statistically significant for the association of CXCL9 with incident cognitive decline (ACME 0.009, 95%CI 0.002-0.018, p=0.016) and with dementia (ACME 0.008, 95%CI 0.003-0.016, p=0.004). CCL2 showed no association with WMHV. Greater CXCL9 levels were associated with greater white matter lesion load, independent of vascular, renal, and genetic factors, suggesting a role in WMD pathogenesis. WMHV mediated CXCL9's association with cognitive decline and dementia risk. This IFN-γ-induced monokine (MIG) warrants further evaluation as a biomarker of white matter and cognitive health as well as a potentially modifiable therapeutic target. Show less

We report the case of a 47-year-old woman with severe hypertriglyceridemia due to a homozygous APOA5 c.553G>T (p.Gly185Cys) mutation. She presented with markedly elevated triglyceride levels (TG, 1,047 mg/dL) that were unresponsive to lifestyle modifications. Lipoprotein fractionation revealed increased chylomicrons (CMs, 21%) and very-low-density lipoprotein (35%), consistent with type V hyperlipoproteinemia. Secondary causes, such as diabetes, alcohol intake, and hypothyroidism, were excluded. The post-heparinization lipoprotein lipase (PH-LPL) level was reduced (104 ng/mL), indicating impaired lipolysis. Genetic testing revealed no pathogenic variants in LPL or other major genes related to triglyceride metabolism. A homozygous APOA5 c.553G>T variant was identified. Pemafibrate (0.2 mg/day), a selective PPARα modulator (SPPARMα), was initiated. After 2 months, the blood lipid levels had markedly improved, with the complete disappearance of CMs, and the PH-LPL level had normalized to 173 ng/mL. This case highlights the potential pathogenic role of APOA5 mutations in LPL-related hypertriglyceridemia. Furthermore, it demonstrates the multifaceted therapeutic effects of pemafibrate, suggesting a potential role for SPPARMα therapy in the management of hereditary hypertriglyceridemia. Homozygous APOA5 mutations can cause reduced LPL protein levels, leading to severe hypertriglyceridemia with elevated CMs and VLDL. Pemafibrate may improve both LPL levels and lipid profiles, even in cases with reduced LPL protein and chylomicronemia. ApoA5-related chylomicronemia can resemble familial chylomicronemia syndrome but may respond to therapies such as pemafibrate, highlighting the importance of accurate genetic diagnosis. Show less

To investigate changes in serum lipid profile parameters combined with tumor markers in gastric cancer (GC) patients and their value in GC screening. A total of 100 patients diagnosed with GC at Renji Hospital (West) between May and September 2025 were consecutively enrolled as the GC group (54 cases in stage Ⅰ/Ⅱ and 46 cases in stage Ⅲ/Ⅳ). Additionally, 100 age- and sex-matched healthy individuals undergoing routine physical examinations were included as the healthy control (HC) group. The serum levels of nine lipid indicators (high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC], triglycerides [TG], small and dense low-density lipoprotein cholesterol [sdLDL-C], apolipoprotein [Apo] A1, ApoB, ApoC2, and ApoC3) and five tumor markers (carcinoembryonic antigen [CEA], carbohydrate antigen [CA] 19-9, CA50, CA242, and CA72-4) were measured using an automatic biochemical analyzer and an electrochemiluminescence instrument. Intergroup differences were analyzed using the Mann-Whitney Compared with the HC group, the GC group showed significantly lower levels of ApoA1, ApoC3, TC, HDL-C, LDL-C, and sdLDL-C ( The combined panel of ApoA1, ApoC3, HDL-C, LDL-C, TC, sdLDL-C, CEA, CA50 and age offers a potential auxiliary tool for detecting gastric cancer. Show less

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by severe hypertriglyceridemia and caused by mutations in genes involved in chylomicron metabolism. Dietary management includes a very-low-fat diet, restriction of simple carbohydrates and alcohol, supplementation with medium-chain triglycerides, essential fatty acids, and fat-soluble vitamins; however, long-term adherence is often poor and nutritional therapy alone is insufficient. We report two adult Chilean sisters with FCS caused by the homozygous Q97X mutation in the APOA5 gene. Both patients experienced severe hypertriglyceridemia (>5,000 mg/dL) and recurrent episodes of acute pancreatitis. One sister was treated with volanesorsen, an antisense oligonucleotide, receiving a weekly dose of 285 mg, which was repeated every 3 weeks due to thrombocytopenia. When combined with structured nutritional counseling, pharmacological treatment achieved a marked reduction in plasma triglycerides to <250 mg/dL and a substantial improvement in quality of life. The other sister was managed with conventional therapy due to a lack of health insurance coverage for volanesorsen. She presented persistent hypertriglyceridemia and recurrent hospitalizations, underscoring the challenges of access to advanced therapies in limited-resource settings. While volanesorsen offers a promising therapeutic alternative, equitable access remains a critical issue, particularly in health systems of low-to middle-income regions. Show less

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality in individuals with diabetes, partly driven by dyslipidemia. While low-density lipoprotein cholesterol (LDL-C) reduction is the primary target of lipid management, many patients with diabetes exhibit mixed dyslipidemia characterised by elevated triglycerides and increased concentrations of atherogenic remnant lipoproteins, which are more comprehensively captured by non-high-density lipoprotein cholesterol (non-HDL-C). Current guidelines from international societies, including the American Diabetes Association (ADA), the American Association of Clinical Endocrinology (AACE), and the European Society of Cardiology (ESC), recommend LDL-C and non-HDL-C targets based on individual cardiovascular risk profiles. Despite clear therapeutic algorithms, lipid target attainment remains suboptimal in routine clinical practice, necessitating more intensive and individualised treatment strategies. Lipid-lowering therapies, including statins, ezetimibe, bempedoic acid and PCSK9 inhibitors, effectively reduce LDL-C and non-HDL-C, significantly lowering cardiovascular risk. Triglyceride-lowering therapies, including omega-3 fatty acids and fibrates, have demonstrated substantial reductions in triglyceride levels, but their impact on cardiovascular outcomes remains uncertain. Given the heterogeneity of dyslipidemia in diabetes, non-HDL-C and apolipoprotein B (apoB) have emerged as superior markers for assessing atherogenic burden. While LDL-C reduction remains central, additional efforts are needed to optimise the management of residual atherogenic lipoprotein particles in diabetes. Future research should focus on refining risk stratification, improving lipid target attainment, and integrating novel lipid-modifying agents to enhance cardiovascular outcomes in this high-risk population. Show less

GLP-1 RAs are effective in treating obesity; however, they typically result in significant loss of skeletal muscle mass. Real-world evidence to inform systematic guidelines and clinical implementation for preserving skeletal muscle mass and reducing cardiometabolic risk with lifestyle modifications on GLP-1 RAs remains limited. This study evaluated the effectiveness of the TouchCare Method, a lifestyle intervention incorporating nutrition and exercise with GLP-1 RAs, for improving body composition and cardiometabolic risk. A retrospective chart review included patients enrolled in Bucks Health and Wellness between February 2024 and September 2025, for at least 12 month ( Patients adherent to the TouchCare Method for 12 months were included in the final analysis ( The TouchCare Method may improve GLP-1 RA treatment outcomes by providing comprehensive structured lifestyle interventions supporting clinically significant weight loss while preserving skeletal muscle mass and improving cardiometabolic risk factors. Show less

Postprandial metabolic impairments play a key role in the pathophysiology of cardiometabolic diseases. While liver fat content has been linked to distinct fasting metabolite profiles, its relationship with postprandial metabolite profiles remains unexplored. In this study, we aimed to (1) examine to what extent liver fat content is associated with the postprandial metabolomic profile beyond fasting metabolites; and (2) investigate whether diet-induced changes in liver fat content are associated with changes in plasma metabolites identified in objective 1. In a subpopulation (n = 1986) of an existing cohort study and a 12-week dietary intervention study (n = 80), liver fat content was measured by proton magnetic resonance spectroscopy and categorized as low (< 2.5%), middle (2.5-5.5%), or high (> 5.5%). In the cohort study, plasma metabolomic profiles were quantified by NMR spectroscopy at fasting (T High liver fat group was characterized by higher fasting and postprandial levels of triglycerides, all VLDL and the small LDL/HDL subclasses, ApoB, fatty acids, glycoprotein acetyls, and BCAAs, and lower medium/larger HDL subclasses, and acetate compared to the low liver fat group. In the high vs. low liver fat group, postprandial responses of cholesterol content of S-LDL, IDL, and S-HDL, glutamine and histidine, omega-3% and DHA % were lower. Diet-induced reductions in liver fat were associated with reductions in 40 fasting plasma metabolites, including VLDL-TG, tyrosine, isoleucine, fatty acid ratios, and most of the VLDL subclasses. Postprandial metabolomic profiling revealed additional associations between liver fat content and plasma metabolites beyond fasting measures, particularly in lipoprotein cholesterol and fatty acid composition. Diet-induced reductions in liver fat were associated with favorable changes in fasting metabolites, but not postprandial metabolite responses. Future studies with harmonized postprandial assessment are needed to further elucidate the postprandial observations and the underlying mechanisms. The trials in this study were registered at clinicaltrials.gov as NL21981.058.08/P08.109 and NCT02194504. Show less

Environmental exposure to toxic and essential metals can disrupt host immune function through mechanisms involving epigenetic, transcriptional, and post-transcriptional regulation. Although numerous studies have investigated these regulatory layers separately, integrative analyses across molecular levels in relation to metallome is missing. In this study, we performed a targeted multi-omics analysis of six immune-associated genes (NFKB1, CDKN2A, IGF2, H19, ESR1, and APOA5) and corresponding proteins in healthy residents from a long-term mining region (MRR, n = 46) and a non-mining region (NMR, n = 48). Transcriptome data were generated by mRNA sequencing, while DNA methylation data were obtained using targeted bisulfite sequencing by analyzing previously identified differentially methylated positions. Plasma protein levels were measured by enzyme-linked immunosorbent assay, and plasma metal concentrations were quantified using inductively coupled plasma mass spectrometry. We observed significantly higher plasma levels of NFKB1 and CDKN2A proteins, along with lower ESR1 transcript levels, in residents of the mining region compared to the non-mining region. NFKB1 protein levels were associated with both promoter methylation and residence in mining region, suggesting a regulatory cascade from DNA methylation to protein expression. IGF2 protein levels were higher in males and showed positive associations with age and the cumulative Z-score of essential metal mixture burden. Our results show that long-term residence in mining regions is associated with changes in NFKB1 at both the DNA methylation and protein levels, which may serve as a sensitive biomarker of metal exposure. Show less

This study aimed to evaluate the association between the LDL-c/ApoB ratio (LAR) and the prevalence of gallstones in regional Chinese adults. We conducted a cross-sectional study involving patients with gallstones who underwent surgical treatment at our hospital from March 2021 to September 2023, as well as e-cases from our medical check-up center during the same period. Participants were divided into gallstone and non-gallstone groups. Data on routine blood and biochemical tests, hypertension, and diabetes mellitus history were collected. The differences between the two groups were analyzed using the chi-square test or Kruskal-Wallis rank sum test. Logistic regression analysis, subgroup analysis, and propensity-matched analysis were performed to assess the relationship between LAR and the prevalence of gallstones. The study included 801 participants aged over 18 years, of whom 259 had gallstones. After adjusting for relevant confounders, LAR was found to be negatively associated with gallstone prevalence (OR = 0.67, 95% CI: 0.48, 0.95). Propensity-matched analyses confirmed that an elevated LAR remained negatively associated with gallstone prevalence (OR = 0.65, 95% CI: 0.43, 0.98). The dose-response curve indicated a linear negative correlation between LAR and gallstone prevalence. LAR is negatively associated with the prevalence of gallstones. Although a causal relationship cannot be established, these findings may provide preliminary insights for gallstone prediction in regional Chinese adult populations. Show less

We previously reported that triazine thiols reduce apolipoprotein B (ApoB) secretion from human iPSC-derived hepatocytes (HLCs) and from humanized mice. To determine whether these compounds affected hepatocyte mRNA levels, we performed bulk RNA sequencing of HLCs treated with the triazine thiol DL-1 or with vehicle (DMSO) for 24 hours. Analyses revealed that in triazine thiol-treated cells, 145 mRNAs were reduced and 37 increased by ≥ 2-fold.  Several mRNAs encoding cysteine-rich metallothionines were upregulated, implying that HLCs respond to treatment by mounting a protective response through metal buffering. Show less

Many randomised controlled trials (RCTs) have revealed the benefits of walnut on apolipoproteins and blood pressure, but the results are inconclusive. This meta-analysis of RCTs aimed to assess the effects of walnut on Apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1) and blood pressure. A systematic review of PubMed, Scopus, Web of Science, Cochrane and Embase databases was conducted, and the search time frame was from the establishment of the database up to January of 2025. A random effects model was applied to estimate weighted mean differences (WMDs) and 95% confidence intervals (CIs). Twenty-five RCTs comprising 26 intervention arms with 2155 patients were included. Walnut significantly decreased ApoB (WMD = -0.06; 95% CI: -0.10, -0.01, p = 0.002), but did not affect ApoA1 (WMD = -0.50; 95% CI: -1.34, 0.33, p = 0.249), systolic blood pressure (SBP) (WMD = -1.20; 95% CI: -4.02, 1.61, p = 0.401) and diastolic blood pressure (DBP) (WMD = -0.44; 95% CI: -2.55, 1.67, p = 0.682). Walnut intake was associated with reduced ApoB levels, with no significant effects observed on ApoA1, SBP, or DBP. Future research involving large-scale, international RCTs is essential to validate its therapeutic potential further. Show less

Hypertriglyceridaemia-induced pancreatitis in pregnancy (HTG-IPP) is a rare but serious condition. There is a paucity of evidence-based guidelines and recommendations for screening and management of HTG-IPP. Individual genomics can predispose certain populations to a higher risk of developing HTG-IPP. To report on a case series of the management of four individual pregnancies complicated by HTG-IPP, subsequently found to be associated with pathogenic genetic variants involved in triglyceride (TG) metabolism. The medical records of four individual pregnancies from two metropolitan hospitals in Australia were reviewed regarding the management of their HTG-IPP and genetic testing for hypertriglyceridaemia (HTG). A literature review of previous cases of HTG-IPP with an identified pathogenic variant was performed. The identified genetic variants resulting in a diagnosis of HTG and HTG-IPP were within glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 (GPIHBP1), lipoprotein lipase (LPL) and apolipoprotein A5 (APOA-5). All patients had co-morbid gestational diabetes mellitus (GDM) and were of South Asian or Asian ethnicity. All four patients were effectively managed with fasting, intravenous insulin, omega-3 fatty acids (O3FAs) and very low-fat diet (VLFD) with supplementation with medium-chain TG (MCT) oil. Further genomics research is needed to increase our understanding for its use in predicting risk of severe gestational HTG. With additional case identification, particular variants of pathogenic interest can be identified and screened for antenatally in patients with a moderate fasting HTG of more than 200 mg/dL (11.1 mmol/L) in the absence of other causative factors. Pre-conception optimisation of TGs and regular monitoring in pregnancy can reduce the incidence and disease burden associated with HTG-IPP and HTG. Show less

In order to address the challenge of early detection of ascending aortic dilation (AAD) in patients with bicuspid aortic valve (BAV), a machine learning prediction model integrating ultrasound hemodynamics and serum markers was developed to break through the limitations of traditional anatomical indicators. A total of 51 patients with BAV were prospectively enrolled and divided into ascending aortic dilation group (BAV-D, AAoV, AAoMPG and HDL-C in the BAV-D group were significantly higher than those in the BAV-ND group (all The machine learning model constructed by integrating hemodynamics (AAoV) and metabolic markers (HDL-C and ApoB) for the first time can accurately quantify the risk of AAD in BAV patients, and its performance is significantly better than that of a single anatomical parameter, providing a visual decision-making tool for early intervention. Show less

Familial hypercholesterolemia (FH) is characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels and an increased risk of premature cardiovascular disease. The present study aimed to investigate the genetic background, associated biochemical profiles, clinical manifestations, and therapeutic response in patients with clinically suspected FH in Serbia. A total of 101 patients with clinically suspected FH were recruited from the Clinic for Endocrinology, Diabetes and Metabolic Diseases in Serbia between 2015 and 2023. Clinical diagnosis was established using the Dutch Lipid Clinic Network (DLCN) criteria. Genetic profiles of all patients were previously determined using next-generation sequencing. Fasting serum lipids, apolipoprotein A-I [ApoA-I], apolipoprotein B [ApoB], and lipoprotein(a) (Lp(a)) were measured enzymatically. Levels of serum lipids were compared between genetically FH-positive (carriers of variants in LDLR, APOB, PCSK9 and LDLRAP1 genes) and FH-negative patients. Therapeutic response was assessed by achieving the LDL-C target level. Statistical analyses were conducted in SPSS (version 30.0). Genetically confirmed FH patients exhibited significantly higher levels of ApoB (p=0.001) compared with variant-negative individuals, while ApoA-I (p=0.413) and Lp(a) (p=0.421) levels did not differ significantly between groups. Patients with pathogenic FH-associated variants were less likely to reach target LDL-C levels after therapy than those without identified variants. This study demonstrates biochemical diversity in familial hypercholesterolemia associated with genetic background in the Serbian population. Pathogenic FH mutations were associated with higher ApoB levels, underscoring the importance of combining genetic testing with lipid profiling for precise diagnosis and management. Show less

PCSK9 inhibitors (PCSK9is) have been developed as an add-on therapy to maximally tolerated statin therapy. To date, high prices have precluded their use as first-line agents but, in the near future, PCSK9is will go off patent protection, reducing cost barriers and making them first-line agent candidates before statins. This study's objective was to evaluate the lipid lowering efficacy of PCSK9i monotherapy compared with high intensity statin monotherapy as a first line agent. This meta-analysis adhered to PRISMA guidelines. A systematic literature review identified all RCTs of: 1) PCSK9i vs. control in which data were available on a patient subgroup receiving PCSK9i monotherapy (predominantly due to total statin intolerance); and 2) high-intensity statins vs. control, with high-intensity statins defined as atorvastatin 40 or 80 mg daily or rosuvastatin 20 or 40 mg daily. The primary outcome was mean percent change in serum low density lipoprotein cholesterol (LDL-C). Secondary outcomes evaluated high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides (TG), and apolipoprotein B (ApoB). Five trials (766 patients) were identified for PCSK9is and 49 trials (19,603 patients) for statins. The mean age (±SD) was 57.5 ± 5.1 years in PCSK9i trials and 60.2 ± 2.3 years in statin trials, with a higher proportion of women enrolled in the PCSK9i group (54.3% vs. 39.9%). Compared to all high-intensity statin regimens combined, PCSK9is showed significantly greater reductions in LDL-C (-52.4% vs. -46.6%, PCSK9i monotherapy is superior to atorvastatin and comparable to rosuvastatin in improving LDL-C, HDL-C, TC, and ApoB, though inferior in reducing TG. These findings confirm that PCSK9is are currently highly useful second-line agents in patients with total statin intolerance and in the near future, after expiration of patent protection, will be useful first line agents for hyperlipidemia. Show less