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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

Understanding the time course of Alzheimer's disease biomarkers of amyloid and tau pathology and their temporal relation to clinical symptoms is key to identifying optimal windows for disease intervention and planning future drug trials. The goal of this work was to determine the extent to which Sampled Iterative Local Approximation (SILA), an algorithm extensively validated for amyloid PET, is capable of modeling longitudinal tau (T) PET trajectories and estimating person-level tau positivity onset ages in two commonly analyzed brain regions and two tracers from two different cohorts. 385 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI; mean (SD) age = 73.4 (7.3) years) with longitudinal flortaucipir tau PET and 288 participants from the Wisconsin Registry for Alzheimer's Prevention and Wisconsin Alzheimer's Disease Research Center (collectively referred to as WISC; mean (SD) age = 67.4 (6.7) years) with longitudinal MK-6240 tau PET were included in the study. Standard uptake value ratios (SUVRs) in the entorhinal cortex and a meta-temporal ROI were modeled with SILA separately, for each cohort and region. Forward and backward SUVR and T+/- prediction were characterized with ten-fold cross-validation and in-sample validation techniques. Accuracy of estimated T+ onset ages (ETOA) was characterized in T- to T+ converters. Differences in ETOA were tested between SILA was able to accurately estimate retrospective change in tau SUVR in the meta-temporal region regardless of age, sex, Our results suggest SILA can be used to accurately model longitudinal tau PET trajectories and retrospectively estimate individual T+ onset ages in the meta-temporal region. The accuracy of SILA time estimates in entorhinal cortex worsened amongst those with dementia in ADNI suggesting entorhinal cortex may only be suitable for studying the temporal progression of tau during the preclinical time frame. 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

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

Coronary artery calcification (CAC), a hallmark of coronary atherosclerosis, links closely to dysregulated lipid metabolism and chronic inflammation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors exert potent lipid-lowering and anti-inflammatory effects, holding translational potential for vascular calcification intervention. However, evidence on PCSK9 inhibition's impact on vascular calcification remains inconsistent. Here, we combined genetic causal analysis with First, we used two-sample Mendelian randomization (MR) and multivariable Mendelian randomization to identify lipid profiles genetically associated with coronary artery calcification. Subsequently, we investigated the value of the PCSK9 gene as a potential therapeutic target for CAC through drug target MR and colocalization analysis, and screened for potential inflammatory mediators via Mediation MR analyses. Following the completion of the aforementioned analyses, we verified the beneficial effect of PCSK9 inhibitors on delaying vascular calcification through animal experiments and cell experiments. MR analysis revealed that genetic proxies for apolipoprotein B (ApoB) (OR=1.64; 95%CI: 1.42-1.90; Inhibition of PCSK9 may effectively slow the progression of coronary artery calcification, with inflammatory mediators such as FGF23 playing key regulatory roles in this process. Show less

High-density and low-density lipoproteins (HDL and LDL) are established analytical targets for diagnosis and risk stratification of numerous chronic diseases. This study investigates potential sources of bias in lipoprotein particle counting (HDL-P and LDL-P), focusing on the most atheroprotective small-HDL and most pro-atherogenic small-LDL. Plasma samples were fractionated using asymmetric-flow field-flow fractionation (AF4), coupled with hydrodynamic size measurement and comprehensive liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of each fraction. Concentration-size profiles were deconvoluted into 10 HDL and 8 LDL Gaussian subspecies. Molecular volume ratios were used to evaluate proposed particle models, providing evidence for the presence of s-HDL disk and s-LDL dimers, as sources of bias in calculated HDL-P and LDL-P when spherical particle geometry is assumed. Matching apoA1/HDL-P and apoB/LDL-P to consensus values enabled correction of mass diameters (k*d 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

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

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

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

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

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

Cardiovascular diseases are the leading cause of death globally. Consequently, metabolomics studies have in recent years aimed at identifying relevant biomarkers, yet no studies have been performed in twin populations, which reduce confounding due to genetic and environmental factors. We included 11,217 twins (age at intake, 47-94 years (mean = 65)) from the Swedish Twin Registry, holding data on 173 nuclear magnetic resonance metabolomic biomarkers and nationwide register-based data on diagnoses of ischemic stroke, ischemic heart disease, myocardial infarction, angina pectoris, and coronary artery disease. Only incident cases (i.e., exclusively holding diagnosis after blood sampling) were included for statistical analyses, which were performed at the individual level and the twin-pair level by Cox regression analyses. Lastly, biomarkers significant in both analyses were inspected, hence conditioning on the twin pair design. Fifty-one biomarkers were found to be associated with myocardial infarction after correction for multiple testing, all showing a hazard ratio above 1. LASSO regression analysis of these biomarkers identified four biomarkers, all related to ApoB lipoprotein biology, potentially reflecting a pro-atherogenic effect. Investigation of biomarkers with p-values < 0.05 identified 20 biomarkers for ischemic heart disease, all showing hazard ratios below 1 and primarily related to ApoA1 lipoprotein biology, potentially reflecting an anti-atherogenic effect. Lastly, three biomarkers, i.e., acetoacetate, bOHbutyrate, and isoleucine, were found for ischemic stroke, all showing a hazard ratio above 1. Taken together, different biomarkers associated with the disease phenotypes indicate that their molecular profiles are different, despite their common basis. The ApoB stands out as a promising biomarker for myocardial infarction. Show less

Alzheimer's disease (AD) involves proteostasis dysregulation causing protein misfolding, but whether these structural changes manifest as plasma conformational biomarkers remains unclear. We profiled plasma protein structures from 520 participants including individuals with AD, individuals with mild cognitive impairment (MCI) and healthy controls. Using mass spectrometry and machine learning, we systematically characterized the structural proteome changes associated with ApoE variations and neuropsychiatric symptoms to identify AD-specific signatures. We developed a diagnostic panel using peptides from C1QA, CLUS and ApoB representing AD-associated structural changes. This three-marker panel achieved 83.44% accuracy in three-way classification (healthy versus MCI versus AD). Binary classification yielded area under the receiver operating characteristic curves of 0.9343 for healthy versus MCI and 0.9325 for MCI versus AD. Longitudinal samples were classified with 86.0% accuracy. This multi-marker panel based on plasma protein structural alterations represents a promising diagnostic approach that may enhance early AD detection and provide insights for clinical trials, improving therapeutic outcomes. 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Atherosclerosis, affecting the aorta, cervical, or intracranial arteries, is a common cause of stroke. Previous studies have shown a strong link between high Lp(a) levels and atherosclerotic stroke due to intracranial atherosclerotic disease, implicating Lp(a) in disease development and progression. The precise role of Lp(a) in stroke subtypes remains unclear, although smaller isoform sizes and oxidized phospholipids on Lp(a) are associated with the disease presence. To clarify Lp(a)'s connection with ischemic stroke subtypes, we evaluated various plasma biomarkers previously linked to Lp(a) and disease. We used stored plasma samples and data from 244 participants enrolled in an acute ischemic stroke registry at Columbia University Medical Center in New York. Plasma Lp(a) concentrations, apolipoprotein B100 (APOB), and oxidized phospholipids were measured via enzyme-linked immunosorbent assay. APO(a) isoform size was measured via gel electrophoresis. Stroke subtypes were classified based on etiologies using clinical and imaging data. Adjusted multivariate logistic regression models were built to assess associations between Lp(a)-related biomarkers and stroke subtype. In participants with acute ischemic stroke, high Lp(a) concentrations, percentage of APOB in Lp(a), and OxPL-APO(a) concentrations were significantly associated with the presence of atherosclerotic stroke compared to those with non-atherosclerotic strokes [OR = 1.30 ( In addition to Lp(a) concentrations, the percentage of APOB in Lp(a), and OxPL-APO(a) concentrations are positively associated with acute atherosclerotic ischemic stroke, specifically ECAD. Show less