👤 Guangfeng Zhao

End-stage renal disease (ESRD) is associated with high morbidity and mortality. Identifying patients with stage 4 chronic kidney disease (CKD) at risk of short-term progression to ESRD remains challenging. Accurate prediction can improve advanced care planning and patient outcomes. This study aimed to develop and validate a machine learning (ML) model for predicting progression within 25 weeks (approximately six months) of ESRD in patients with stage 4 CKD. Electronic health records (EHRs) of patients with stage 4 CKD were analyzed. Nine ML models including Ridge regression (Ridge), random forest (RF), and eXtreme Gradient Boosting (XGBoost) were used to predict short-term progression to ESRD within 25 weeks. The models were trained and externally validated using the data of 346 and 105 patients. Of the 451 patients with stage 4 CKD, 219 developed ESRD. Among the evaluated models, XGBoost demonstrated the best overall performance. In the internal validation, it achieved an area under the curve (AUC) of 0.93, an accuracy of 0.90, and an F1 score of 0.89. In the external validation, XGBoost maintained the highest AUC (0.85), accuracy (0.79), and F1 score (0.79), along with the highest average precision (0.89) and a low log-loss (0.48), indicating strong discriminative ability and good generalizability. The top predictive features included high-density lipoprotein cholesterol, Alb, Cys C, ApoB, FGB, Bun, Neutrophil, and Total cholesterol. This study demonstrated the feasibility of ML for assessing ESRD prognosis based on easily accessible clinical features. XGBoost demonstrated superior performance in both internal and external validation, suggesting its potential for future patient screening. Show less

Mendelian randomization studies have identified that apolipoprotein B (ApoB) is the primary genetic determinant of ischemic stroke, rather than other lipid markers. However, its association with recurrent non-cardioembolic acute ischemic stroke (NCAIS) remains unclear. This study aimed to investigate this association. This study recruited 578 patients with acute ischemic stroke, excluding those with cardiogenic embolism. After a 3-year follow-up, a total of 428 patients completed the prospective cohort study. A Cox regression model was used to evaluate the association between ApoB levels at admission and the recurrence rate. Additionally, a nested case-control study was conducted by comparing blood samples collected at the time of recurrence from recurrent patients with those from non-recurrent patients. Binary logistic regression and ROC analysis were used to assess the association between serum ApoB, low-density lipoprotein cholesterol (LDL-C), and recurrent stroke at the time of recurrence. The Cox regression model demonstrated that ApoB levels at admission were independently associated with an increased risk of recurrent NCAIS (HR=6.697; 95%CI 2.581-17.374, P < 0.001). Recurrent stroke patients had significantly higher serum ApoB levels at admission than non-recurrent ones [0.85 g/L (IQR 0.21) vs. 0.63 g/L (IQR 0.15)]. In ROC analysis, ApoB (AUC = 0.732) showed a greater discriminatory ability for recurrent stroke than LDL-C (AUC = 0.685). Higher serum ApoB levels increased the risk of recurrence in patients with NCAIS, and ApoB demonstrated better discriminatory ability than LDL-C after therapy. These findings suggest that routine ApoB measurement may help improve secondary stroke risk assessment. Show less

The spleen is essential for immunity, mediating host defense against pathogens and regulating immunological homeostasis. Western-style diets commonly cause the aggregation of body fat and the emergence of obesity. This state might lead to damage to the spleen's functions. However, the effects of Western-style diets on gene expression and metabolic regulation in the spleen have not yet been fully explored. In this study, Show less

Increasing evidence underscores the driving role of coding and non-coding variants in cancer development. Analyzing gene sets in biological processes offers deeper insights into the molecular mechanisms of carcinogenesis. Here, we developed geMER to identify candidate driver genes genome-wide by detecting mutation enrichment regions within coding and non-coding elements. We subsequently designed a pipeline to identify a core driver gene set (CDGS) that broadly promotes carcinogenesis across multiple cancers. CDGS comprising 25 genes for 25 cancers displayed instability in DNA aberrations. Variants within the TTN enrichment region may influence the folding of the I-set domain by altering local polarity or side-chain chemistry properties of amino acids, potentially disrupting its antigen-binding capacity in LUAD. Multi-omics analysis revealed that APOB emerged as a candidate oncogene in LIHC, whose genetic alterations within the enrichment region may activate key TFs, upregulate DNA methylation levels, modulate critical histone modifications, and enhance transcriptional activity in the HepG2 and A549 cell lines compared to Panc1. Additionally, CDGS mutation status was an independent prognostic factor for the pan-cancer cohort. High-risk patients tended to develop an immunosuppressive microenvironment and demonstrated a higher likelihood of responding to ICI therapy. Finally, we provided a user-friendly web interface to explore candidate driver genes using geMER ( http://bio-bigdata.hrbmu.edu.cn/geMER/ ). Show less

Patients with schizophrenia (SCZ) face multiple health challenges due to the complication of chronic diseases and psychiatric disorders. Among these, cardiovascular comorbidities are the leading cause of their life expectancy being 15-20 years shorter than that of the general population. Identifying comorbidity patterns and uncovering differences in immune and metabolic function are crucial steps toward improving prevention and management strategies. A retrospective cross-sectional study was conducted using electronic medical records of inpatients discharged between 2015 and 2024 from a municipal psychiatric hospital in China. The study included patients diagnosed with Schizophrenia, Schizotypal, and Delusional Disorders (SSDs) (ICD-10: F20-F29). Comorbidity patterns were identified through latent class analysis (LCA) based on the 20 most common comorbid conditions among SSD patients. To investigate differences in peripheral blood metabolic and immune function, linear regression or generalized linear models were applied to 44 laboratory test indicators collected during the acute episode. The Benjamini-Hochberg method was used for p-value correction, and the false discovery rate (FDR) was calculated, with statistical significance set at FDR < 0.05. Among 3,697 inpatients with SSDs, four distinct comorbidity clusters were identified: SSDs only (Class 1), High-Risk Metabolic Multisystem Disorders (Class 2, n = 39), Low-Risk Metabolic Multisystem Disorders (Class 3, n = 573), and Sleep Disorders (Class 4, n = 205). Compared to Class 1, Class 2 exhibited significantly elevated levels of apolipoprotein A (ApoA; β = 90.62), apolipoprotein B (ApoB; β = 0.181), mean platelet volume (MPV; β = 0.994), red cell distribution width-coefficient of variation (RDW-CV; β = 1.182), antistreptolysin O (ASO; β = 276.80), and absolute lymphocyte count (ALC; β = 0.306), along with reduced apolipoprotein AI (ApoAI; β = -0.173) and hematocrit (HCT; β = -35.13). Class 3 showed moderate increases in low-density lipoprotein cholesterol (LDL-C; β = 0.113), MPV (β = 0.267), white blood cell count (WBC; β = 0.476), and absolute neutrophil count (ANC; β = 0.272), with decreased HCT (β = -9.81). Class 4 was characterized by elevated aggregate index of systemic inflammation (AISI; β = 81.07), neutrophil-to-lymphocyte ratio (NLR; β = 0.465), and systemic inflammation response index (SIRI; β = 0.346), indicating a heightened inflammatory state. The comorbidity patterns of patients with SCZ can be distinctly classified. During the acute episode, those with comorbid metabolic disorders exhibit a higher risk of cardiovascular diseases and immune system abnormalities, while patients with comorbid sleep disorders present a pronounced systemic inflammatory state and immune dysfunction. This study provides a basis for the chronic disease management and anti-inflammatory treatment, while also offering objective biomarker insights for transdiagnostic research. Show less

Phytosterols have been recommended as a lifestyle intervention for early lipid management-which has a significant impact on frailty. However, their effect on frailty remains unclear. Studies have shown that genetic proxied total blood phytosterol affects the development of cardiovascular disease through non-HDL-c and apolipoprotein B mediation, which makes phytosterol an underlying risk factor for frailty. The aim of this Mendelian randomization (MR) study was to investigate the genetic associations between phytosterols and frailty. We used univariate Mendelian randomization (UVMR) to assess the causal effects of blood phytosterols on the Frailty Index (FI) and Fried Frailty Score (FFS). We also employed multivariate Mendelian randomization (MVMR) and Two-step MR (TSMR) to evaluate the mediating role of blood lipids in the relationship between blood phytosterols and FI. We used the product of coefficients method to calculate the mediating effect. The inverse-variance weighted method was used as the primary analysis. Genetically proxied higher levels of blood total sitosterol were significantly associated with a higher risk of Frailty Index (OR = 1.035, 95% CI = 1.009-1.061, Show less

This study evaluated the efficacy and safety of tafolecimab in patients with type 2 diabetes (T2D) and hypercholesterolemia by a post-hoc analysis of pooled data from three phase 3 trials. Data from up to 12 weeks were analyzed to assess the effects of tafolecimab 450 mg every four weeks (Q4W) in patients with T2D and hypercholesterolemia. The primary endpoint was the percentage change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Secondary endpoints included the proportion of participants achieving LDL-C levels below 1.8 mmol/L at weeks 12, the proportion of patients achieving LDL-C ≥ 50% reduction and LDL-C < 1.4 mmol/L, as well as percentage changes from baseline to week 12 in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and triglyceride (TG) levels. The reduction in LDL-C from baseline was significantly greater in patients receiving tafolecimab than in those receiving placebo (estimated treatment difference: - 64.02%, 95% confidence interval: [- 68.08%, - 59.96%], P < 0.0001). The proportion of patients achieving a reduction of over 50% and an absolute LDL-C value below 1.4 mmol/L was significantly higher in the tafolecimab group than that in the placebo group (P < 0.0001). Furthermore, a significantly greater proportion of patients in the tafolecimab group achieved LDL-C levels below 1.8 mmol/L at week 12 compared to the placebo group (P < 0.0001). The tafolecimab group also showed significant reductions in TG, non-HDL-C, apo B, and Lp(a) from baseline to week 12 compared to the placebo group (all P < 0.001). The incidence of adverse events was generally similar between the two groups. Tafolecimab 450 mg Q4W demonstrated a superior lipid-lowering efficacy and favorable safety profile compared to placebo. This suggests it could be a promising new treatment option for Chinese patients with T2D and hypercholesterolemia. Show less

This study aimed to (1) evaluate small dense low-density lipoprotein cholesterol (sdLDL-C) dynamics from prediabetes to type 2 diabetes mellitus (T2DM) with complications, (2) validate existing sdLDL-C estimation formulas (Sampson’s, Srisawasdi’s, Han’s) in Chinese populations, and (3) develop a population-specific formula for enhanced accuracy. A multicenter study recruited 1,944 participants (216 controls, 70 with prediabetes, 212 with newly diagnosed T2DM, 164 with treated T2DM, and 1,286 in validation cohorts). Lipid profiles, including sdLDL-C (measured via enzymatic assays), were analyzed. Formula performance was assessed using spearman correlation, intraclass correlation coefficients (ICC), and multivariable linear regression. A novel formula was derived via multivariable regression. Atherogenic lipid triad manifestations emerged early: sdLDL-C was significantly elevated in participants with prediabetes (1.07 [0.73, 1.40] vs. 0.57 [0.44, 0.72] mmol/L in controls, P < 0.05) and further increased in those with T2DM, correlating strongly with triglycerides (TG; sdLDL-C elevation begins in prediabetes, highlighting its value for early atherosclerotic cardiovascular disease (ASCVD) risk assessment. Current formulas show population-specific limitations, whereas the new model provides improved accuracy for Chinese T2DM patients, enabling cost-effective sdLDL-C estimation and personalized lipid management. The online version contains supplementary material available at 10.1186/s12944-025-02636-0. Show less

Kelch-like protein 12 (KLHL12) has been shown to regulate coat complex II (COPII)-mediated endoplasmic reticulum (ER)-to-Golgi trafficking of large cargos carrying procollagen or apolipoprotein B-100 containing very-low-density lipoprotein (VLDL). It is known that lipid absorption and chylomicron metabolism in enterocytes are dependent on apolipoprotein B-48 (ApoB48) and COPII-mediated trafficking. This study aimed to investigate whether KLHL12 in the intestine regulates dietary lipid absorption, chylomicron assembly, and metabolic phenotypes in mice. We generated Show less

Whether serum lipids have an impact on breast cancer(BC) prognosis remains controversial and unstudied. We conducted this systematic review (SR) and meta-analysis (MA) to explore the impact of levels of various components of the lipid profile on multiple survival outcomes (OSs) of BC. We searched Pubmed, Embase, Cochrane Library, and Web of Science for relevant cohort studies to assess the impact of multiple lipids on the prognosis of BC patients. Included studies were subjected to quality assessment using the Newcastle-Ottawa scale (NOS). MA of extracted data was performed using StataSE 15.1. 17 studies in total were included, involving a sample size of 24,026. MA showed that high levels of low-density lipoprotein cholesterol (LDL-C ) (HR (hazard ratios) = 1.96, 95% confidence interva (CI): 1.03-3.73), apolipoprotein E (ApoE) (HR = 3.68, 95% CI: 1.71-7.94), and apolipoprotein B (ApoB) (HR = 1.93, 95% CI: 1.44-2.59) were associated with poorer OS, while high levels of low-density lipoprotein (LDL) (HR = 0.81, 95% CI. 0.74-0.88) and apolipoprotein D (ApoD) (HR = 0.44, 95% CI: 0.24-0.81) were associated with better OS. Both a high level of total cholesterol (TC) (HR = 1.60, 95% CI:1.08-2.37) and dyslipidemia (HR = 1.71, 95% CI:1.12-2.62) had a negative impact on disease-free survival (DFS) in BC patients. This MA showed that the levels of LDL-C, ApoE, and ApoB in serum were associated with OS, and the TC level in serum and dyslipidemia were associated with DFS. However, the levels of blood lipids were less associated with other prognostic outcomes. Other high-quality studies are needed to further elucidate this issue. PROSPERO CRD42024541755. Show less

Dehydroepiandrosterone (DHEA) and DHEA-sulfate (-s) fall with age and are implicated in aging. Observational studies suggest DHEA/DHEA-s could lengthen life in specifically older men. No trial has established the role of DHEA/DHEA-s in aging or lifespan. We assessed the role of DHEA-s in lifespan and key biological determinants, (blood pressure, Apolipoprotein B (ApoB), and haemoglobin A1C (HbA1c)), for men and women in a two-sample mendelian randomization (MR) study using naturally occurring genetic randomization to obviate confounding. We assessed associations of sex-specific DHEA-s from Life-Adult/Life-Heart (men = 4327, women = 3501) with lifespan, based on paternal (n = 415311) and maternal (n = 412937) attained age, and with blood pressure, ApoB and Hba1c (men = 167020, women = 194,174) from the UK Biobank. We used inverse variance weighted (IVW) estimates with sensitivity analysis. DHEA-s was unrelated to lifespan in women using IVW, 0.04 years per logged μmol/L DHEA-s, 95 % confidence interval (CI) -0.50 to 0.58, DHEA-s was associated with shorter lifespan in men (-1.15 years, 95 % CI -1.72 to -0.58) with a difference by sex (p = 0.0017), sensitivity analysis gave similar estimates. DHEA-s was unrelated to blood pressure in women and positively associated with systolic and diastolic blood pressure in men with a difference by sex for diastolic blood pressure. DHEA-s was possibly associated with lower ApoB in men. DHEA-s has different associations with lifespan and blood pressure in men and women. In settings where DHEA is an unregulated supplement, such as the United States, whether public health benefits might accrue from more regulation could be considered. Show less

This study aimed to evaluate the impact of combining high-intensity statins with CETP inhibitors on lipid levels, as well as to explore their potential clinical significance. We conducted a comprehensive search of relevant studies in the PubMed, Embase, Cochrane Library, and Web of Science databases. The Cochrane Risk of Bias Tool RoB 2.0 was employed to evaluate the quality of the included studies. Statistical analyses were carried out using STATA 15 software, with primary outcomes being high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Out of 2,552 records, 7 studies were included in the final analysis. The findings revealed that the combination of high-intensity statins with CETP inhibitors significantly raised HDL-C levels (SMD 2.47 [1.77, 3.18], p < 0.001) and lowered LDL-C levels (SMD -1.75 [-2.19, -1.31], p < 0.001). Compared to statin monotherapy, the combination of high-intensity statins and CETP inhibitors resulted in a more pronounced increase in HDL-C and ApoAI, while reducing LDL-C, triglycerides (TG), and ApoB levels, without increasing the incidence of adverse events. Show less

The incidence of Type 2 Diabetes Mellitus (T2DM) continues to rise steadily, significantly impacting human health. Early prediction of pre-diabetic risks has emerged as a crucial public health concern in recent years. Machine learning methods have proven effective in enhancing prediction accuracy. However, existing approaches may lack interpretability regarding underlying mechanisms. Therefore, we aim to employ an interpretable machine learning approach utilizing nationwide cross-sectional data to predict pre-diabetic risk and quantify the impact of potential risks. The LASSO regression algorithm was used to conduct feature selection from 30 factors, ultimately identifying nine non-zero coefficient features associated with pre-diabetes, including age, TG, TC, BMI, Apolipoprotein B, TP, leukocyte count, HDL-C, and hypertension. Various machine learning algorithms, including Extreme Gradient Boosting (XGBoost), Random Forest (RF), Support Vector Machine (SVM), Naive Bayes (NB), Artificial Neural Networks (ANNs), Decision Trees (DT), and Logistic Regression (LR), were employed to compare predictive performance. Employing an interpretable machine learning approach, we aimed to enhance the accuracy of pre-diabetes risk prediction and quantify the impact and significance of potential risks on pre-diabetes. From the China Health and Nutrition Survey (CHNS) data, a cohort of 8,277 individuals was selected, exhibiting a disease prevalence of 7.13%. The XGBoost model demonstrated superior performance with an AUC value of 0.939, surpassing RF, SVM, DT, ANNs, Naive Bayes, and LR models. Additionally, Shapley Additive Explanation (SHAP) analysis indicated that age, BMI, TC, ApoB, TG, hypertension, TP, HDL-C, and WBC may serve as risk factors for pre-diabetes. The constructed model comprises nine easily accessible predictive factors, which prove highly effective in forecasting the risk of pre-diabetes. Concurrently, we have quantified the specific impact of each predictive factor on the risk and ranked them based on their influence. This result may serve as a convenient tool for early identification of individuals at high risk of pre-diabetes, providing effective guidance for preventing the progression of pre-diabetes to T2DM. Show less

Patients with diabetic nephropathy (DN) often present with lipid profile abnormalities. While associations between these parameters and DN have been suggested, confounding factors obscure causal relationships. This study employed bidirectional Mendelian randomization (MR) to explore these links. Using genome-wide association study (GWAS) data, the primary analysis used the inverse-variance weighted (IVW) method, which was supported by MR-Egger regression and a weighted median estimator (WME). Sensitivity analyses, including heterogeneity, pleiotropy tests, leave-one-out, and reverse causality analyses, were conducted. The IVW model revealed the following: (1) causal relationships between triglycerides (TG) (OR: 1.5807, 95% CI: 1.2578-1.9865, P = 0.0001), high-density lipoprotein cholesterol (HDL-C) (OR: 0.7342, 95% CI: 0.5729-0.9409, P = 0.0146), and apolipoprotein A1 (ApoA1) (OR: 0.6506, 95% CI: 0.5190-0.8156, P = 0.0002) and DN; (2) causal relationships between TG (OR: 1.0607, 95% CI: 1.0143-1.1093, P = 0.0098), HDL-C (OR: 0.9453, 95% CI: 0.9053-1.9871, P = 0.0109), and apolipoprotein B (ApoB) (OR: 1.0672, 95% CI: 0.0070-1.1310, P = 0.0280) and the urinary albumin-creatinine ratio (UACR); (3) no causal relationship between total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ApoB and DN, or between TC, LDL-C, ApoA1 and UACR; (4) none of the results showed reverse causality. TG is a risk factor for DN and UACR; HDL-C is protective for both; ApoA1 protects against DN; and ApoB is a risk factor for UACR. To further explore the underlying mechanisms between TG, HDL-C, ApoA1, ApoB, and their associations with DN and UACR, and to provide reference for the selection of lipid management and treatment strategies for clinical DN patients. This study demonstrated that causal relationships between TG, HDL-C, and ApoA1 with DN and between TG, HDL-C, and ApoB with the UACR. Show less

To evaluate the efficacy and safety of siRNA drugs that lower Lp(a) in patients with dyslipidaemia. A network meta-analysis and systematic review were conducted to compare siRNA drugs targeting Lp(a), based on relevant randomized controlled trials (RCTs). A comprehensive search was performed in PubMed, Embase, Web of Science and the Cochrane Library (up to October 24, 2024). RCTs with an intervention duration of at least 12 weeks were included. Eligible studies compared siRNA drugs that reduce Lp(a), including both Lp(a)-targeted and non-targeted agents, with placebo or other siRNA drugs that reduce Lp(a). The primary outcomes were the percentage reduction and absolute reduction in Lp(a), percentage reduction in low-density lipoprotein cholesterol (LDL-C), percentage reduction in apolipoprotein B (apo(B)), adverse events and serious adverse events, including injection-site reactions. The risk of bias was assessed using the Cochrane Risk of Bias Tool (ROB2), and a random-effects network meta-analysis was performed using the frequentist approach. Confidence in effect estimates was evaluated using the Confidence In Network Meta-Analysis (CINeMA) framework. A total of 14 trials involving 5646 participants were included. Lp(a)-targeted siRNA agents, particularly Olpasiran, demonstrated strong efficacy in significantly reducing Lp(a) levels, with the greatest percentage reduction in Lp(a) (mean difference [MD]: -92.06%; 95% CI: -102.43% to -81.69%; P-score: 0.98). Olpasiran also showed the greatest absolute reduction in Lp(a) (MD: -250.70 nmol/L; 95% confidence interval [CI]: -279.89 to -221.50; P-score: 0.99). Certain non-Lp(a)-targeted siRNA agents, such as inclisiran and zodasiran, also showed modest reductions in Lp(a) levels, reducing Lp(a) by approximately 15%. Lp(a)-targeted siRNA agents reduced LDL-C by more than 20% and decreased apo(B) by approximately 15%. In terms of safety, most drugs exhibited favourable safety profiles with no significant differences compared to placebo. However, zerlasiran raised concerns regarding injection-site reactions and other adverse events when compared to placebo. Lp(a)-targeted siRNA agents have shown robust effectiveness in substantially reducing Lp(a) levels, including both percentage and absolute reductions, with moderate improvements in LDL-C and apo(B) concentrations. Non-Lp(a)-targeted siRNA agents also demonstrate modest reductions in Lp(a) levels. The safety profile is generally favourable, but zerlasiran and inclisiran may increase the incidence of injection-site reactions. Show less

Pre-eclampsia (PE) is a common complication of pregnancy and there is an urgent need for new drug targets. We performed whole proteome-wide Mendelian randomisation (MR) and colocalisation analyses to identify potential therapeutic targets for PE. A two-sample MR study was conducted using summary-level statistics of 734 plasma proteins retrieved from large genome-proteome-wide association studies. The summary statistics of PE or eclampsia were obtained from the FinnGen consortium. Wald ratio and Inverse variance weighted (IVW) were used to assess the causal association between proteins and PE. Colocalisation analyses were conducted to examine whether the identified proteins and PE shared incidental variants. Genetically predicted circulating levels of 42 proteins were associated with PE risk after Benjamini-Hochberg correction. Nineteen of the gene-predicted proteins showed evidence of increased PE risk (CRELD1, CPA4, AHSG, NFASC, QDPR, NTM, PZP, FAM171B, RTN4R, FLRT2, ADH4, ADM, SPINK5, LGALS4, CKM, SPON2, UROS, CXCL10 and APOBEC3G); 23 proteins reduced the risk of PE (CLIC5, NEO1, SWAP70, KLK8, VWA2, FSTL1, CXCL11, APOB, NPPB, CNTN4, IL12B, ACHE, TCN1, GFRA2, GNMT, HPGDS, DPT, MANBA, SPARCL1, ACE, FUT8, BST1 and ACP1). Bayesian colocalisation indicated that six proteins (VWA2, ACHE, CXCL10, PZP, AHSG and UROS) and PE, which were identified as high evidence of colocalisation with PE. This study provides evidence of the causal association between genetically predicted 42 proteins associated with PE risk, which might be promising drug targets for PE. Show less

This study aims to assess the impact of intravenous infusion of fospropofol disodium on lipid metabolism and the inflammatory response in individuals with hyperlipidemia. A total of 360 preoperative individuals with hyperlipidemia were selected and randomly assigned to either the treatment group or the control group, with 180 participants in each group. The treatment group received an induction dose of fospropofol disodium at 10 mg/kg intravenously, followed by maintenance at a rate of 10 mg/(kg·h). The control group was administered propofol intravenously at 2 mg/kg for induction and maintained at 4 mg/(kg·h). All other medications were consistent between the two groups. Blood samples (3 ml of venous blood) were collected from patients at four-time points: 1 day before surgery (T At T Compared with propofol, intravenous infusion of fospropofol disodium for more than 3 h during anesthesia has lesser impact on lipid metabolism in patients with hyperlipidemia and does not increase inflammatory factors levels. Show less

Lipoprotein subclasses and high-density lipoprotein (HDL) functions are associated with atherosclerotic cardiovascular disease (ASCVD), but researches on them in patients with nephrotic syndrome (NS) are limited. The aims of this study were (1) to analyze the changes in quantity and quality of lipoprotein in patients with idiopathic nephrotic syndrome (INS) and patients in remission from NS, and (2) to evaluate the lipid-related atherosclerotic risk in these patients. 51 patients with idiopathic nephrotic syndrome (NS group), 72 NS patients with complete remission (NS remission group), and 80 healthy controls (control group) were recruited. The levels of conventional lipids, lipoprotein subclasses, including VLDL, IDL (C, B, A), LDL (LDL1-7), HDL (large, intermediate, small) and HDL cholesterol efflux capacity (CEC), were measured and compared across the three groups. Conventional lipid parameters [TG, TC, LDL-C, apo-B and Lp(a)] and lipoprotein subclasses (VLDL, IDL-C, IDL-B, LDL-2 and sdLDL) were higher in NS group when compared to NS remission group and control group (P < 0.05). CEC in NS group was significantly lower than that in control group [21.0 (18.3-27.2) % vs 25.7 (23.3-28.9) %] (P < 0.001) and improved to 22.8 (20.6-23.7) % in NS remission group with the disease recovery. Proatherogenic changes in conventional lipid parameters, lipoprotein subclasses and HDL-CEC were observed in patients with NS, suggesting that more rigorous lipid regulation strategies may help reduce cardiovascular disease risk in patients with NS. Show less

Central obesity poses a significant health threat. Lutein-rich fruits and vegetables may help manage obesity. Limited evidence suggests that lutein exerts health effects by inhibiting advanced glycation end products (AGEs), but data on its effects in centrally obese individuals are sparse. Thus, we aimed to investigate the effects of lutein supplementation in subjects with central obesity. A double-blind, randomized controlled trial was conducted involving patients with central obesity. Anthropometric indices, dietary intake, metabolic parameters, carotenoid and AGEs levels were compared between those receiving a 32-week intervention of 10 mg d Show less

In preliminary research and literature review, we identified a potential link between chronic obstructive pulmonary disease (COPD) and lipid metabolism. Therefore, this study employed Mendelian randomization (MR) analysis to investigate the potential causal connection between blood lipids and COPD. A genome-wide association study (GWAS) on COPD was conducted, encompassing a total of 112,583 European participants from the MRC-IEU. Additionally, extensive UK Biobank data pertaining to blood lipid profiles within European cohorts included measurements for low-density lipoprotein cholesterol (LDL-C) with 440,546 individuals, high-density lipoprotein cholesterol (HDL-C) with 403,943 individuals, triglycerides (TG) with 441,016 individuals, total cholesterol (TC) with 187,365 individuals, apolipoprotein A-I (apoA-I) with 393,193 individuals, and apolipoprotein B (apoB) with 439,214 individuals. Then, MR analyses were performed for lipids and COPD, respectively. The primary analytical technique employed was the inverse-variance weighted (IVW) approach, which included a 95% confidence interval (CI) to calculate the odds ratio (OR). Additionally, a sensitivity analysis was conducted to assess the dependability of the MR analysis outcomes. MR analysis was primarily based on IVW, unveiled a causal link between COPD and LDL-C (OR=0.994, 95% CI (0.989, 0.999), P=0.019), TG (OR=1.005, 95% CI (1.002, 1.009), P=0.006), and apoA-I (OR=0.995, 95% CI (0.992, 0.999), P=0.008), in addition, no causal link was found with HDL-C, TC, apoB. Sensitivity analysis demonstrated the robustness of these causal relationships. However, through multivariate MR(MVMR) and multiple testing correction, LDL-C and TG had no causal effect on the outcome. ApoA-I remained a protective factor for the risk of COPD (OR=0.994, 95% CI (0.990-0.999), P=0.008). Through MR analysis, this study offers evidence of a causal link between apoA-I with COPD. This further substantiates the potential role of lipid metabolism in COPD, and has significant clinical implications for the prevention and management of COPD. Show less

Percutaneous coronary intervention (PCI) is a practical and effective method for treating coronary heart disease (CHD). This study aims to explore the influencing factors of major cardiovascular events (MACEs) and hospital readmission risk within one year following PCI treatment. Additionally, it seeks to assess the clinical value of Apolipoprotein B/Apolipoprotein A-I (ApoB/ApoA-I) in predicting the risk of one-year MACEs and readmission post-PCI. A retrospective study included 1938 patients who underwent PCI treatment from January 2010 to December 2018 at Shandong Provincial Hospital affiliated with Shandong First Medical University. Patient demographics, medications, and biochemical indicators were recorded upon admission, with one-year follow-up post-operation. Univariate and multivariate Cox proportional hazards regression models were utilized to establish the relationship between ApoB/ApoA-I levels and MACEs/readmission. Predictive nomograms were constructed to forecast MACEs and readmission, with the accuracy of the nomograms assessed using the concordance index. Subgroup analyses were conducted to explore the occurrence of MACEs and readmission. We observed a correlation between ApoB/ApoA-I and other lipid indices, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) (P < 0.001). Univariate and multivariate Cox regression analyses demonstrated that ApoB/ApoA-I is an independent risk factor for MACEs in post-PCI patients (P = 0.038). Within one year, the incidence of MACEs significantly increased in the high-level ApoB/ApoA-I group (ApoB/ApoA-I ratio ≥ 0.824) (P = 0.038), while the increase in readmission incidence within one year was not statistically significant. Furthermore, a nomogram predicting one-year MACEs was established (Concordance Index: 0.668). Subgroup analysis revealed that ApoB/ApoA-I was associated with the occurrence of both MACEs and readmission in male patients, those using CCB/ARB/ACEI, those without multivessel diseases, or those with LDL-C < 2.6 mmol/L. The ApoB/ApoA-I ratio serves as an independent risk factor for one-year MACEs in post-PCI patients and correlates closely with other blood lipid indicators. ApoB/ApoA-I demonstrates significant predictive value for the occurrence of MACEs within one year.Trial registration Chinese clinical trial registry: No.ChiCTR22000597-23. Show less

Cardiovascular diseases caused by atherosclerosis (AS) are the leading causes of disability and death worldwide. Apolipoprotein B (ApoB), the core protein of low-density lipoproteins, is a major contributor to cardiovascular disease-related morbidity and mortality, with apolipoprotein B (ApoB) playing a critical role in its pathogenesis. However, no bibliometric studies on the involvement of ApoB in AS have been published. This study aimed to conduct a comprehensive bibliometric analysis to explore the current and future trends regarding the role of ApoB in AS. Utilizing the Web of Science Core Collection, a thorough search was conducted for ApoB in AS-related papers related to research on ApoB in the field of AS during 1991-2023. The analysis focused on annual publication trends, leading countries/regions and institutions, influential authors, journal and key journals. CiteSpace and VOSviewer were employed to visualize reference co-citations, and keyword co-occurrences, offering insights into the research landscape and emerging trends. This bibliometric analysis employed network diagrams for cluster analysis of a total of 2105 articles and reviews, evidencing a discernible upward trend in annual publication volume. This corpus of research emanates from 76 countries/regions and 2343 organizations, illustrating the widespread international engagement in ApoB-related AS studies. Notably, the United States and the University of California emerge as the most prolific contributors, which underscores their pivotal roles in advancing this research domain. The thematic investigation has increasingly focused on elucidating the mechanistic involvement of ApoB in atherosclerosis, its potential as a diagnostic biomarker, and its implications for therapeutic strategies. This bibliometric analysis provides the first comprehensive perspective on the evolving promise of ApoB in AS-related research, emphasizing the importance of this molecule in opening up new diagnostic and therapeutic avenues. This study emphasizes the need for continued research and interdisciplinary efforts to strengthen the fight against AS. Furthermore, it emphasizes the critical role of international collaboration and interdisciplinary exploration in leveraging new insights to achieve clinical breakthroughs, thereby addressing the complexities of AS by focusing on ApoB. Show less

The intricate shared genetic architecture underlying halitosis and its related disorders-including salivary secretion disorders, chronic periodontitis, gastroesophageal reflux disease, dental caries, chronic sinusitis, helicobacter pylori infection, and porphyromonas genus abundance-remains incompletely characterized. Our study employed genomic structural equation modeling (Genomic SEM) to define the halitosis common factor (HCF) representing the shared genetic architecture of halitosis-related disorders. Coupled with diverse post-GWAS analytical methods, we aimed to discover susceptible loci and investigate genetic associations with external traits. Furthermore, we explored enriched genetic pathways, cellular layers, and genomic elements. Polygenic risk score analyses, leveraging our integrated GWAS data, were conducted to assess chromosomal-level risk associations for the HCF. A well-fitted genomic SEM integrated GWAS data, revealing the shared genetic architecture of halitosis-related disorders. We identified 23 independent genome-wide significant SNP loci, all previously unreported for this HCF relative to the input single-trait GWAS. Fine-mapping of variants and gene prioritization pinpointed numerous high-confidence putative causal variants and candidate susceptible genes. Subsequent analyses further illuminated the shared genetic architecture underlying HCF and multiple external traits, notably neuropsychiatric characteristics, cognitive function, and inflammatory or metabolic conditions. Notably, this study presents the first comprehensive genetic characterization of halitosis and its related disorders through a GWAS analysis of an unmeasured composite phenotype, providing novel insights into shared etiological pathways potentially linking oral health to systemic factors across these conditions. Show less

Earthworms are valued as a dietary protein source in many regions. Earthworm protein can yield bioactive peptides, but enzymatic hydrolysis is inefficient by commercial proteases, and bioactivity development is still inadequate. This study developed a novel efficient method for degrading earthworm protein and investigated the lipid-lowering activity and mechanism of earthworm peptides. It was found that combining autolysis and alcalase exhibited a higher hydrolysis degree of earthworm protein of 43.64 ± 0.78% compared to using autolysis or alcalase only. The hydrolysate significantly reduced lipid accumulation in steatotic hepatocytes. LC-MS/MS results showed that the primary lipid-lowering peptides (EWPs) in the hydrolysate were small molecule peptides with molecular weights of 500-1000 Da and chain lengths of 4-7 amino acid residues. Western blot results demonstrated that EWP regulated the expression of lipid metabolism-related proteins, including APOC3, HMGCR, PCSK9, SREBP1, C/EBP-α, NPC1L1, PPAR-γ, and CYP7A1. Transcriptomic analysis and validation experiments indicated that the lipid-lowering activity of EWP was associated with its suppression of inflammatory factors, such as IL-6. This study presents an efficient enzymatic hydrolysis strategy for earthworm protein utilization, laying the foundation for its application in functional foods such as protein supplements, nutraceutical capsules, hypoallergenic infant formulas, and sports nutrition products. Show less

Traumatic brain injury (TBI) is more common than ever and is becoming a global public health issue. A variety of secondary brain injuries occur after TBI, including ferroptosis characterized by iron-dependent lipid peroxidation. Gallic acid is a kind of traditional Chinese medicine, which has many biological effects such as anti-inflammatory and antioxidant. We further investigated whether Gallic acid can improve the neurological impairment caused by ferroptosis after TBI by targeting APOC3. Weighted gene coexpression network analyses (WGCNA) and 3 kinds of machine-learning algorithms were used to find the potential biomarkers. Then the HERB database was used to select the Chinese herb that acted on the target gene APOC3. Finally, we selected Gallic acid as a drug targeting APOC3 and verified by Western blotting. The effect of Gallic acid on the improvement of neurological function was studied by Nissl staining and FJB staining. Finally, the effect of Gallic acid on the cognitive ability of TBI mice was explored through behavioral experiments. Gallic acid can inhibit the expression level of APOC3 and thus inhibit the level of ferroptosis after TBI. It can also reduce the degeneration of nerve tissue by inhibiting ferroptosis and improve the neurological function deficit. The behavioral experiment proved that Gallic acid can alleviate the behavioral cognitive impairment caused by TBI. Gallic acid can reduce ferroptosis by inhibiting APOC3, and then alleviate neurological impairment after TBI. Show less

Type 2 diabetes (T2D) and mild cognitive impairment (MCI) are interrelated conditions that significantly impair quality of life. This study aimed to identify a feasible biomarker for assessing T2D-MCI risk and to evaluate a potential therapeutic strategy. We integrated data from the National Health and Nutrition Examination Survey (NHANES) with Mendelian randomization (MR) to investigate genetic causal relationships between T2D, MCI, and their shared biomarkers. Transcriptomic analysis identified T2D-associated genes. Clinical trials evaluated the short-term effects of modified fasting therapy (MFT) on glucose regulation and cognitive function. Cellular assays and patient samples were used to validate the regulatory roles of key genes in biochemical markers and downstream signaling pathways. Among 6,356 T2D and 1,138 MCI subjects, vitamin D, high-density lipoprotein cholesterol (HDL-C), globulin, and creatinine were associated with both conditions. MR analysis showed that higher HDL-C levels reduced T2D risk (0.9059, 95% CI: 0.8666-0.9470) but increased MCI risk (OR = 1.0482, 95% CI: 1.0216-1.0755). Nuclear factor I A ( HDL-C has divergent genetic effects on T2D and MCI. Show less

Although previous studies have reported associations between gonadotropins, testosterone, and Alzheimer's disease (AD), their longitudinal relationships with cognitive decline and temporal lobe atrophy remain insufficiently characterized. This study examined the association between baseline hormone levels and cognitive decline and temporal lobe volume loss trajectories, and whether these associations vary by sex or This study included 490 participants (378 MCI/112 AD; 311 men/179 women; mean age = 75.01 ± 7.52) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Baseline plasma levels of gonadotropins (FSH, LH) and total testosterone (TT) were measured using Luminex xMAP multiplex immunoassay. Cognitive decline was assessed longitudinally through MMSE and ADAS-Cog 13 scores. Temporal lobe atrophy was quantified using tensor-based morphometry of 1.5T MRI scans, with bilateral temporal lobe volumes scaled to a normalized reference (1,000 = baseline). Linear mixed effects models were employed to relate baseline plasma hormones to longitudinal cognitive performance and temporal lobe volume. Longitudinal analyses showed that higher baseline FSH levels were associated with faster cognitive decline (MMSE: β = -0.025, The results indicate that in individuals across the AD spectrum, elevated gonadotropin levels may exert deleterious, domain-specific effects on cognitive decline or temporal lobe atrophy. Women with lower TT levels may experience faster cognitive progression. Although future studies incorporating additional longitudinal hormone measurements and cognitive trajectories are warranted, our results underscore the importance of gonadotropins and testosterone in AD progression. Show less

CD11c+ microglia are a functionally specialized subpopulation of microglia that play a crucial role in the pathophysiological processes of various central nervous system diseases. This review synthesizes compelling evidence that CD11c+ microglia exhibit unique transcriptomic and phagocytic characteristics. These characteristics distinguish them from homeostatic microglia and support their specialized functions. During development, CD11c+ microglia are crucial for the maturation of oligodendrocytes and the integrity of white matter, particularly in regions such as the corpus callosum and cerebellum. In preclinical models of neurodegenerative diseases (such as Alzheimer's disease and amyotrophic lateral sclerosis) and central nervous system injuries (such as stroke and spinal cord injury), they are consistently associated with neuroprotective phenotypes. CD11c+ microglia exhibit enhanced phagocytic capacity near amyloid plaques and damaged neurons, helping to clear pathological protein aggregates and cell debris, thereby reducing neurotoxicity and promoting a repair environment. The current consensus is that specific microenvironmental cues, particularly hazard signaling molecules (DAMPs) and cytokines (such as interferon-γ), are the main drivers of the differentiation and activation of CD11c+ microglia. Among these, the TREM2-APOE signaling axis is a key and widely accepted regulatory pathway for their survival, proliferation, and functional status. The plasticity of CD11c+ microglia is regulated by multiple signaling pathways, including CSF1R, SIRPα-CD47, IFN-γ, and the complement cascade. Emerging therapeutic strategies aim to regulate their activities through gene targeting, metabolic intervention, and immune regulation using TREM2 agonists, CSF1R inhibitors, or nanopharmacological methods. However, challenges remain in defining specific CD11c+ biomarkers, understanding environment-dependent functions, and achieving targeted delivery. Future prospects depend on clearly addressing individual developmental issues, deciphering the molecular switches that control phenotypic plasticity, and developing highly specific therapeutic strategies to leverage their beneficial functions, thereby paving the way for new intervention methods for neurological diseases. Show less