This study aimed to investigate the therapeutic effects of minocycline on neuropathic pain by examining its regulatory influence on hippocampal proinflammatory cytokines and brain-derived neurotrophic Show more
This study aimed to investigate the therapeutic effects of minocycline on neuropathic pain by examining its regulatory influence on hippocampal proinflammatory cytokines and brain-derived neurotrophic factor (BDNF) levels, given the established involvement of neuroinflammation and BDNF dysregulation in the pathogenesis of neuropathic pain and associated neurological dysfunctions. This study used a rat model of neuropathic pain induced by L5 spinal nerve transection (L5-SNT). Forty-eight male Sprague-Dawley rats were divided into four groups: naive, sham-operated, model + saline, and model + minocycline. Minocycline was administered intraperitoneally at 40 mg/kg daily. Mechanical allodynia was assessed using the von Frey test, while real-time reverse transcription and ELISA were employed to quantify hippocampal expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and BDNF at various time points postsurgery. L5-SNT induced significant mechanical allodynia in the model + saline group, which was significantly attenuated by minocycline treatment in the model + minocycline group on days 3, 7, and 11 postsurgery (P < 0.05). Minocycline significantly reduced TNF-α, IL-6, and BDNF levels in the hippocampus, particularly on day 7 post-SNT (P < 0.05); however, minocycline did not significantly affect IL-1β levels. These findings suggest that minocycline's analgesic effects may be mediated through the downregulation of key proinflammatory cytokines and BDNF in the hippocampus. Minocycline administration significantly mitigates mechanical allodynia and modulates hippocampal neuroinflammatory markers in a rat model of neuropathic pain. These results highlight minocycline's potential as a therapeutic option for neuropathic pain, particularly in targeting neuroinflammation within the hippocampus. Show less
Cellular senescence is a hallmark for cancers, particularly in lung adenocarcinoma (LUAD). This study developed a risk model using senescence signature genes for LUAD patients. Based on the RNA-seq, c Show more
Cellular senescence is a hallmark for cancers, particularly in lung adenocarcinoma (LUAD). This study developed a risk model using senescence signature genes for LUAD patients. Based on the RNA-seq, clinical information and mutation data of LUAD patients collected from the TCGA and GEO database, we obtained 102 endotheliocyte senescence-related genes. The "ConsensusClusterPlus" R package was employed for unsupervised cluster analysis, and the "limma" was used for the differentially expressed gene (DEG) analysis. A prognosis model was created by univariate and multivariate Cox regression analysis combined with Lasso regression utilizing the "survival" and "glmnet" packages. KM survival and receiver operator characteristic curve analyses were conducted applying the "survival" and "timeROC" packages. "MCPcounter" package was used for immune infiltration analysis. Immunotherapy response analysis was performed based on the IMvigor210 and GSE78220 cohort, and drug sensitivity was predicted by the "pRRophetic" package. Cell invasion and migration were tested by carrying out Transwell and wound healing assays. According to the results, a total of 32 genes related to endotheliocyte senescence were screened to assign patients into C1 and C2 subtypes. The C2 subtype showed a significantly worse prognosis and an overall higher somatic mutation frequency, which was associated with increased activation of cancer pathways, including Myc_targets2 and angiogenesis. Then, based on the DEGs between the two subtypes, we constructed a five-gene RiskScore model with a strong classification effectiveness for short- and long-term OS prediction. High- and low-risk groups of LUAD patients were classified by the RiskScore. High-risk patients, characterized by lower immune infiltration, had poorer outcomes in both training and validation datasets. The RiskScore was associated with the immunotherapy response in LUAD. Finally, we found that potential drugs such as Cisplatin can benefit high-risk LUAD patients. In-vitro experiments demonstrated that silencing of Angiopoietin-like 4 (ANGPTL4), Gap Junction Protein Beta 3 (GJB3), Family with sequence similarity 83-member A (FAM83A), and Anillin (ANLN) reduced the number of invasive cells and the wound healing rate, while silencing of solute carrier family 34 member 2 (SLC34A2) had the opposite effect. This study, collectively speaking, developed a prognosis model with senescence signature genes to facilitate the diagnosis and treatment of LUAD. Show less
Residual feed intake (RFI) has recently gained attention as a key indicator of feed efficiency in poultry. In this study, 800 slow-growing ducks with similar initial body weights were reared in an exp Show more
Residual feed intake (RFI) has recently gained attention as a key indicator of feed efficiency in poultry. In this study, 800 slow-growing ducks with similar initial body weights were reared in an experimental facility until they were culled at 42 d of age. Thirty high RFI (HRFI) and 30 low RFI (LRFI) birds were selected to evaluate their growth performance, carcass characteristics, and muscle development. Transcriptome and weighted gene co-expression correlation network analyses of pectoral muscles were conducted on six LRFI and six HRFI ducks. The results revealed that selecting for LRFI significantly reduced feed consumption (P < 0.05) and improved feed efficiency without affecting the growth performance, slaughter rate, or meat quality of ducks (P > 0.05). Moreover, compared with HRFI ducks, LRFI ducks had a lower pectoral muscle fat content (P < 0.05), larger muscle fiber diameter and area (P < 0.05), and lower muscle fiber density (P < 0.05). There were significant differences in gene expression between LRFI and HRFI ducks, with 102 upregulated and 258 downregulated genes, which were enriched in the PPAR signaling pathway, adipocytokine signaling pathway, actin cytoskeleton regulation, ECM-receptor interaction, and focal adhesion. The expression of genes associated with fat and energy metabolism, including ACSL6, PCK1, APOC3, HMGCS2, PRKAG3, and G6PC1, was downregulated in LRFI ducks, and weighted gene co-expression correlation network analysis identified PRKAG3 as a hub gene. Our findings indicate that reduced mitochondrial energy metabolism may contribute to the RFI of slow-growing ducks, with PRKAG3 playing a pivotal role in this biological process. These findings provide novel insights into the molecular changes underlying RFI variation in slow-growing ducks. Show less
Xiang Lian, Xiaoyan Li, Kexin Wang+3 more · 2025 · Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics · added 2026-04-24
To investigate the gene detection results of 2 patients with familial hypercholesterolemia (FH) caused by complex heterozygous variation, and to clarify the relationship between clinical manifestation Show more
To investigate the gene detection results of 2 patients with familial hypercholesterolemia (FH) caused by complex heterozygous variation, and to clarify the relationship between clinical manifestations and gene variation. Two patients (patient 1 and 2) with FH who visited Beijing Anzhen Hospital Affiliated to Capital Medical University in 2018 were selected as research subjects. A retrospective study method was used to collect clinical and family history data of the two patients. And 2 mL of peripheral venous blood from each of the two patients was collected, and genomic DNA extraction was performed on the blood samples. Sanger sequencing was used to validate the variant sites of the two patients detected by whole-exome sequencing (WES). Pathogenicity of variants was classified based on the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Classification of Genetic Variants (hereinafter referred to as the "ACMG Guidelines"), and the impact of variant was analyzed using multiple bioinformatics tools including SIFT, PolyPhen-2, and SWISS-MODEL. This study has been approved by Beijing Anzhen Hospital Affiliated to Capital Medical University (Ethics No. 2024215X). Patient 1 initially presented with early-onset coronary heart disease, with initial lipid levels of serum total cholesterol (TC) 9.86 mmol/L (normal reference value: 3.10~5.20 mmol/L) and serum low-density lipoprotein cholesterol (LDL-C) 8.37 mmol/L (normal reference value: 1.27~3.12 mmol/L) on admission. Patient 1 initially underwent treatment with rosuvastatin combined with ezetimibe for one month, but the lipid-lowering effect was not significant. The lipid-lowering therapy was then adjusted to atorvastatin combined with ezetimibe and probucol. After one year of treatment, the patient developed paroxysmal chest pain symptoms. A follow-up lipid profile showed a serum TC level of 4.50 mmol/L and a LDL-C level of 3.55 mmol/L. The lipid-lowering regimen was continued, and the serum LDL-C levels were maintained between 2.65 and 3.66 mmol/L. Patient 2 was found to have an abnormally high blood lipid level and carotid artery hardening during physical examination, with an initial blood lipid level of serum TC 11.82 mmol/L and serum LDL-C 9.63 mmol/L. After receiving rosuvastatain therapy, the lipid-lowering effect was significant. WES revealed that patient 1 carried the heterozygous variants c.1871₁₈₇₃del(p.Ile624del) and c.1747C>T (p.His583Tyr) in the LDLR gene (NM₀₀₀₅₂₇.4), while patient 2 carried the heterozygous variants c.1747C>T (p.His583Tyr) in the LDLR gene and c.6936₆₉₃₇inv (p.Ile2313Val) in the APOB gene (NM₀₀₀₃₈₄₎. According to the ACMG Guidelines, the LDLR gene c.1747C>T (p.His583Tyr) was classified as a pathogenic variant (PS3+PM1+PM2_supporting+PM5+PP2+PP3), and c.1871₁₈₇₃del (p.Ile624del) was classified as a pathogenic variant (PS3+PS4+PM2_supporting+PM1+PM4); the APOB gene c.6936₆₉₃₇inv (p.Ile2313Val) was classified as a variant of uncertain clinical significance (PM2_supporting BP4). Patients 1 and 2 in this study were patients with complex heterozygous variant FH, and their genotypic differences may be related to the differences in clinical serum LDL-C levels and the efficacy of hypolipidemic agents. Show less
Cyclophosphamide (CTX), a cornerstone in breast cancer combination chemotherapy, frequently induces adverse effects including myelosuppression, gastrointestinal disturbances, hepatic impairment, and a Show more
Cyclophosphamide (CTX), a cornerstone in breast cancer combination chemotherapy, frequently induces adverse effects including myelosuppression, gastrointestinal disturbances, hepatic impairment, and alopecia. Chemotherapy-induced alopecia severely impacts patients' quality of life and psychological well-being. Modified Huanjingjian (MHJJ), a traditional Chinese herbal formula, demonstrates clinical efficacy in alleviating chemotherapy-related side effects, yet its mechanisms against CTX-induced alopecia remain uncharacterized. And our main aim was to explore the efficacy and the mechanism of MHJJ in mice. UPLC-QE-Orbitrap-MS characterized MHJJ's chemical composition. A CTX-induced alopecia murine model was established. Systemic toxicity was evaluated through body weight monitoring, automated biochemical analysis (ALT/AST levels), and hematological profiling (WBC/PLT counts). Hair follicle histopathology was assessed via H&E staining. IHC and IF staining quantified proliferation markers and hair follicle stem cell (HFSC) biomarkers. Reduced representation bisulfite sequencing (RRBS) was used to map DNA methylation patterns. Wnt pathway dynamics were analyzed through qRT-PCR and IF staining. We identified 110 bioactive compounds in MHJJ. MHJJ intervention attenuated alopecia severity, restored follicular architecture, and increased follicular density compared to CTX monotherapy (p<0.05). HFSC proliferation markers (Ki67/CD34) showed significant upregulation, while apoptosis markers (Caspase-3) were suppressed. RRBS revealed MHJJ-mediated hypomethylation in differentially methylated regions, with gene body methylation constituting 60% of total methylation changes. Methylation-modulated genes predominantly localized to Wnt signaling pathways: MHJJ enhanced Wnt3/Wnt10a expression while suppressing Cer1/Axin1. Corresponding methylation reductions at promoter and gene body regions were confirmed at mRNA and protein levels. MHJJ mitigates CTX-induced alopecia through epigenetic regulation of HFSCs, specifically via DNA hypomethylation-mediated activation of Wnt3/Wnt10a and suppression of Cer1/Axin1. This mechanism promotes follicular regeneration by restoring Wnt signaling homeostasis, positioning MHJJ as a promising adjuvant for chemotherapy-induced alopecia management. Show less
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, with current therapies offering only limited symptomatic relief and lacking disease-modifying ef Show more
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, with current therapies offering only limited symptomatic relief and lacking disease-modifying efficacy. Addressing this critical therapeutic gap, natural multi-target compounds like mulberroside A (MsA)-a bioactive glycoside from Show less
Deep brain stimulation (DBS) has emerged as a prospective treatment for psychiatric disorders; for example, DBS targeting the nucleus accumbens (NAc) abolishes addictive behaviors. However, neither th Show more
Deep brain stimulation (DBS) has emerged as a prospective treatment for psychiatric disorders; for example, DBS targeting the nucleus accumbens (NAc) abolishes addictive behaviors. However, neither the core pathway nor the cellular mechanisms underlying these therapeutic effects are known. Here, morphine-induced conditioned place preference (CPP) in mice as an addiction model and NAc-DBS combined with adeno-associated virus gene delivery for activity-dependent tagging, transgenic and chemogenetic manipulation of recruited neuronal networks are used. It is reported that a cortical-accumbal pathway and local fibroblast growth factor 1 (FGF1) signaling in the medial prefrontal cortex (mPFC) are critical for NAc-DBS to be effective in altering morphine CPP. It is shown that NAc-DBS retrogradely activates mPFC neurons projecting to the NAc, and chemogenetic activation/inhibition of these DBS-activated neuron ensembles in the mPFC reproduces the NAc-DBS effects on CPP. Sustained therapeutic effects accompany reductions in local FGF1 binding to fibroblast growth factor receptor 1 (FGFR1) in these neurons. Additionally, overexpressing FGF1 in the mPFC-NAc pathway abolishes the therapeutic effects of NAc-DBS. These results demonstrate that the mPFC-NAc pathway forms a top-down motif to regulate the therapeutic effects of subcortical DBS on addiction. These results support the potential for addiction treatments involving FGF1 signaling and highlight the mPFC as a target for noninvasive brain stimulation. Show less
Yan Huang, Bo-Wen Yue, Yue-Qin Hu+5 more · 2025 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · added 2026-04-24
Anxiety disorder is a highly prevalent psychological illness, and research has shown that obesity is a significant risk factor for its development. This study explored the ameliorative effects and mec Show more
Anxiety disorder is a highly prevalent psychological illness, and research has shown that obesity is a significant risk factor for its development. This study explored the ameliorative effects and mechanisms of saponins from Panax japonicus(SPJ) on anxiety disorder in mice fed a high-fat diet(HFD). Fifty C57BL/6J mice were randomly divided into normal control diet(NCD) group, HFD group, and low-and high-dose SPJ groups. At week 12, six mice from the HFD group were further divided into a control group(treated with DMSO) and an exogenous fibroblast growth factor 21(FGF21) group(administered rFGF21). The anxiety-like behavior of the mice was assessed using the open field test and elevated plus maze test. Hematoxylin-eosin(HE) staining and oil red O staining were performed to observe pathological changes in the liver and adipose tissue. Glucose metabolism was evaluated through the glucose tolerance test(GTT) and insulin tolerance test(ITT). Western blot analysis was performed to detect the expression of FGF21 and its downstream-related proteins in the liver and cortex, along with the expression of brain-derived neurotrophic factor(BDNF), disks large homolog 4(DLG4), and synaptophysin(SYP) in the cortex. Real-time quantitative fluorescent PCR(qPCR) was used to detect the expression of FGF21 and its receptor genes in the liver and cortex. Immunofluorescence staining was employed to examine the expression of neuronal activator c-Fos, FGF21, and the FGF21 co-receptor β-klotho in the cerebral cortex. The results showed that SPJ significantly improved the frequency of activity in the open arms of the elevated plus maze and the central area of the open field in HFD mice, up-regulated the expression of BDNF, DLG4, and SYP, and effectively alleviated anxiety-like behaviors in HFD mice. Compared with the NCD group, HFD mice exhibited up-regulated expression of FGF21 in the liver and cerebral cortex, while the expression of fibroblast growth factor receptor 1(FGFR1) and β-klotho was significantly down-regulated, suggesting that HFD mice exhibited FGF21 resistance. SPJ markedly up-regulated the β-klotho levels in HFD mice, reversing FGF21 resistance. Further comparison with exogenously administered FGF21 revealed that SPJ activates brain cortical regions in a consistent manner, and additionally, SPJ promotes the number and colocalization of c-Fos and β-klotho positive cells in the brain cortex. In summary, SPJ effectively alleviates anxiety-like behaviors in HFD mice. Its mechanism is associated with up-regulation of β-klotho expression in the brain, reversal of FGF21 resistance, and subsequent activation of neurons in the cerebral cortex and amygdala. Show less
Dysregulation of macrophage autophagy plays a critical role in sepsis-induced acute lung injury (ALI); however, its underlying mechanism remains unclear. In this study, we aimed to identify the regula Show more
Dysregulation of macrophage autophagy plays a critical role in sepsis-induced acute lung injury (ALI); however, its underlying mechanism remains unclear. In this study, we aimed to identify the regulatory pathway involving the PIK3C3-MAPK14 signaling axis that drives ALI progression by controlling autophagy and macrophage polarization. Using machine learning transcriptomic analysis, MAPK14 was identified as a core gene associated with ALI, and multi-omics integration confirmed its upregulated expression in ALI tissues. MAPK14 localization to pro-inflammatory macrophages was determined using single-cell sequencing. Furthermore, we observed a significant positive correlation between MAPK14 and autophagy-related genes. Molecular docking and kinetic simulations revealed high-affinity interactions between PIK3C3 and MAPK14 (ΔG-bind = -127.722 ± 33.269 kJ/mol). In vitro experiments followed by Western Blot(WB) and RT-q polymerase chain reaction (PCR) assays demonstrated that lipopolysaccharide stimulation upregulated MAPK14 expression through downregulation of PIK3C3 expression, resulting in impaired autophagic flux (LC3-II/Ⅰ↓, TOM20↑, P62↑, HSP60↑). Flow cytometry and enzyme-linked immunosorbent assay (ELISA) confirmed a shift toward pro-inflammatory (M1) macrophage polarization. RNA pull-down assay directly captured the PIK3C3-MAPK14 complex, and functional validation showed that PIK3C3 overexpression significantly inhibited MAPK14 protein expression, whereas PIK3C3 knockdown enhanced it. In conclusion, targeting the PIK3C3-MAPK14 axis is a promising therapeutic strategy for ALI. Show less
Atherosclerosis is a primary contributor to worldwide morbidity and mortality. Failure to timely clear apoptotic cells can trigger a cascade reaction, where the necrotic core expands until the fibrous Show more
Atherosclerosis is a primary contributor to worldwide morbidity and mortality. Failure to timely clear apoptotic cells can trigger a cascade reaction, where the necrotic core expands until the fibrous cap is ruptured, and atherosclerotic plaques become vulnerable. Efferocytosis is an important method for recognizing and eliminating apoptotic cells. Nevertheless, the specific effect of efferocytosis on atherosclerosis remains uncertain. This study aimed to identify and verify the relevant characteristics of efferocytosis for detecting atherosclerosis. The data of gene expression patterns of atherosclerosis were sourced from the Gene Expression Omnibus (GEO) database, and the differential expression analyses of efferocytosis-related genes (EFRGs) were performed between the atherosclerosis samples and the control samples. Subsequently, protein-protein interaction (PPI), correlation analysis, and functional enrichment analysis were performed to reveal the interaction between molecules as well as their pathways. Machine learning (ML) was employed to determine hub genes to construct a clinical prediction model. At the same time, immune infiltration, single-cell transcriptome analysis, and cell experiments were conducted in both atherosclerosis and control samples to provide a reference for the immune cell landscape and the cell heterogeneity under this condition. The study revealed that 14 genes were closely related to efferocytosis in atherosclerosis. Among them, an ML model was used to screen 5 potential diagnostic biomarkers, including tumor necrosis factor (TNF), apolipoprotein E (ApoE), neutrophil cytosolic factor 1 (NCF1), triggering receptor expressed on myeloid cells 2 (TREM2), and chitinase-3 like-protein-1 (CHI3L1). Subsequent external validation indicated that, except for TNF, the other 4 genes were all upregulated. From the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) analysis, those 5 genes were all significantly associated with various immune cells. Further single-cell RNA sequencing (scRNA-seq) analysis demonstrated that those 5 genes were selectively upregulated in the macrophages of atherosclerosis lesions, which was supported by mRNA levels in cell experiments. This study clarified the association between atherosclerosis and efferocytosis, and established an effective diagnostic model. Moreover, potential treatment targets for atherosclerosis were identified, offering new insights into the potential mechanism of atherosclerosis. Show less
SLC35B4, a nucleotide sugar transporter that mediates the transport of UDP-GlcNAc and UDP-xylose, was found to be required for the replication of influenza A virus (IAV) of the H5N1 subtype in our gen Show more
SLC35B4, a nucleotide sugar transporter that mediates the transport of UDP-GlcNAc and UDP-xylose, was found to be required for the replication of influenza A virus (IAV) of the H5N1 subtype in our genome-wide siRNA library screen. We found that defective IAV replication in SLC35B4-deficient A549 cells was independent of virus strain specificity, and the virulence of IAV in Slc35b4 knockdown mice was also decreased. By examining the individual stages of the IAV replication cycle, we discovered that the amount of internalized IAV was significantly reduced in SLC35B4-knockout A549 cells. Mechanistically, SLC35B4 facilitated IAV replication by transporting UDP-xylose, which attaches to the serine residue of heparan sulfate proteoglycans (HSPGs) in the heparan sulfate (HS) biosynthesis pathway. Knockdown of associated host factors (i.e., XYLT2, B4GALT7, EXT1, and EXT2) in the HS biosynthesis pathway also impaired IAV replication. Furthermore, we revealed that AGRN, a unique HSPG family member, was important for the endocytosis of IAV in A549 cells. Moreover, we found that the homeostasis of the AGRN protein was regulated by HS modification mediated by the initial UDP-xylose transporter SLC35B4, thereby affecting the expression level of endocytic adapter AP2B1 to influence IAV internalization. Collectively, these findings establish that SLC35B4 is an important regulator of IAV replication and uncover the underlying mechanisms by which SLC35B4 employs UDP-xylose transport activity to promote IAV internalization.IMPORTANCEThe entry process of IAV represents a favorable target for drug development. In this study, we identified SLC35B4 as an important host factor for the efficient replication of different subtypes of IAV Show less
Metastatic spread of cancer is the leading cause of death in patients with epithelial ovarian cancer (EOC), and elucidation of the molecular mechanisms underlying this process is a major focus of canc Show more
Metastatic spread of cancer is the leading cause of death in patients with epithelial ovarian cancer (EOC), and elucidation of the molecular mechanisms underlying this process is a major focus of cancer research. Fibroblast growth factor-inducible 14 (Fn14) has been shown to regulate wound repair, inflammation, angiogenesis, and chemoresistance, but its functional role in metastasis in EOC is still unknown. Here it is reported that Fn14 is identified as a cancer metastasis suppressor that inhibits the migratory and invasive potential of EOC cells by down-regulating epithelial-mesenchymal transition (EMT). Mechanistically, it is identified that Fn14 promotes acetylation-dependent protein degradation of Slug, a key transcriptional factor associated with EMT. The deacetylase Sirtuin 2 (SIRT2) has been reported to be involved in the deacetylation of Slug protein to stabilize it and then prevent its degradation in the nucleus. The results showed that Fn14 alters the subcellular localization of (SIRT2) by interacting with SIRT2, leading to reduced SIRT2 shuttling into the nucleus and subsequently promoting the acetylated degradation of Slug. Collectively, the work has demonstrated for the first time that Fn14 inhibits EOC metastasis by regulating SIRT2-mediated Slug deacetylation, providing a new perspective and method for the development of future novel therapeutic strategies for the treatment of EOC metastasis. Show less
The Wnt signaling pathway plays important roles in cardiomyocyte proliferation and cardiac regeneration after heart injury. Abnormal activation of the Wnt pathway causes a reduction in cardiomyocyte f Show more
The Wnt signaling pathway plays important roles in cardiomyocyte proliferation and cardiac regeneration after heart injury. Abnormal activation of the Wnt pathway causes a reduction in cardiomyocyte function, leading to hypertrophy, fibrosis, and heart failure. However, the mechanism through which Wnt signaling affects cardiomyocyte function during cardiac diseases is still unclear. In this study, we observed that activation of the Wnt/β-catenin pathway, but not the Wnt/Ca2+ pathway, leads to significant cytosol calcium enrichment. Such an effect can be inhibited by cycloheximide that blocks the downstream gene expression. By analyzing the transcriptome data, we found that activation of the Wnt/β-catenin pathway significantly upregulates the expression level of muscle-selective A kinase anchoring protein (mAKAP, also called AKAP6), a scaffold protein that can improve the interaction between protein kinase A (PKA) and its substrate ryanodine receptor 2 (RyR2) in cardiomyocytes. We further identified that AKAP6 is a target gene of the canonical Wnt pathway and increasing AKAP6 expression can enhance RyR2 phosphorylation by PKA, causing the sarcoplasmic reticulum calcium leakage and finally heart dysfunction. Our finding that the Wnt/β-catenin pathway affects cardiac calcium regulation via AKAP6 and RyR2 provides profound insights into heart diseases and sheds light on potential therapeutic strategies. Show less
Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea-cycle disorder, results in hyperammonemia initiating a sequence of adverse events that can lead to coma and death if not treated rapidly. The Show more
Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea-cycle disorder, results in hyperammonemia initiating a sequence of adverse events that can lead to coma and death if not treated rapidly. There is a high unmet need for an effective therapeutic for this disorder, especially in early neonatal patients where mortality is excessive. However, development of an adeno-associated virus (AAV)-based approach is hampered by large cDNA size and high protein requirement. We developed an oversized AAV vector as a gene therapy to treat Show less
To explore the optimal row-ratio in mechanized hybrid rice seed production, a field experiment was conducted in 2024 at Qionglai and Mianzhu using 'Tiantai A' × 'Taihui 808'. Three row-ratio treatment Show more
To explore the optimal row-ratio in mechanized hybrid rice seed production, a field experiment was conducted in 2024 at Qionglai and Mianzhu using 'Tiantai A' × 'Taihui 808'. Three row-ratio treatments (H1: 18:6, H2: 24:6, and H3: 30:6) were tested using agricultural unmanned aerial vehicles (AUAVs) for pollination assistance. The results showed that row-ratio had little effect on sterile line flowering dynamics. The index of flowers meeting (IFM) was 0.71-0.72 at Qionglai and 0.81-0.86 at Mianzhu, with 11 to 12 days of flowering duration. As the row-ratio increased, total pollen quantity in the panicle layer and grain filling rate (GFR) decreased, while grain infection rate (GIR) increased. The responses of grain blighted rate (GBR), grain empty rate (GER), and fertilization success rate (FSR) to row-ratio varied between sites. Pollen density and GFR followed the pattern of near region (NR) > central region (CR) > far region (FR). Within the panicle, pollen density was generally highest in the upper panicle layer (UPL), followed by the middle (MPL) and lower (LPL) layers, with partial exceptions observed in the H2 and H3 treatments at Mianzhu. The vertical distribution of GFR varied by site: at Qionglai, it was apical parts of panicle (APP) > median parts (MPP) > basal parts (BPP), whereas at Mianzhu the order was MPP > APP > BPP. With wider row-ratios, yield per unit area (YUA) and GFR declined (H1 > H2 > H3), while 1,000-grain weight increased or decreased and then increased. Under H1, yields reached 2,107.50 kg ha Show less
The beak bean, found only in waterfowl and Galliformes, aids in foraging, self-defense and pecking hard objects. Its rich coloration results from prolonged evolutionary adaptation. This study analyzed Show more
The beak bean, found only in waterfowl and Galliformes, aids in foraging, self-defense and pecking hard objects. Its rich coloration results from prolonged evolutionary adaptation. This study analyzed beak bean phenotypes of duck at 10, 20, 30 and 40 days of age, revealing that the most common type is the black beak bean, characterized by melanin deposition on the beak surface. This study performed single nucleotide polymorphism (SNP)-based genome-wide association studies (GWASs) to investigate the genetic basis of beak bean color, identifying signals on chromosome 1. The copy number variation region-based GWAS revealed a consistent candidate region overlapping with the SNP-based GWAS signals, further supporting the importance of this genomic region. Locus zoom analysis further refined the candidate regions to 48.5-50.5 and 50.8-52.8 Mb. Functional enrichment analysis highlighted six candidate genes within these regions: KITLG, DUSP6, GALNT4, MGAT4C, ATP2B1 and NTS. Notably, KITLG and DUSP6, which are linked to melanin production, were identified as key candidate genes for beak bean color. Our finding revealed the genetic basis of the bean color traits for the first time in ducks, providing a theoretical foundation and technological framework for enhancing duck beak coloration. Show less
Yuwen Guo, Huai Bai, Linbo Guan+4 more · 2025 · Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics · added 2026-04-24
To assess the association between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 of the fatty acid desaturase 2 (FADS2) gene and gestational diabetes mellitus (GDM). A total of 1 514 Show more
To assess the association between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 of the fatty acid desaturase 2 (FADS2) gene and gestational diabetes mellitus (GDM). A total of 1 514 pregnant women who visited West China Second University Hospital of Sichuan University between January 1, 2013 and December 31, 2021 were enrolled in this study. Among them, 583 were diagnosed with gestational diabetes mellitus (GDM group), and 931 had normal pregnancies (control group). The SNPs rs174575 and rs2845574 of the FADS2 gene were analyzed using Sanger DNA sequencing. Plasma levels of insulin (INS), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB) were measured using enzymatic methods, chemiluminescence and immunoturbidimetry. This study was approved by the Medical Ethics Committee of the West China Second University Hospital of Sichuan University (Ethics No.: 2020-036). The main genotype at the rs174575 C/G and rs2845574 C/T loci were CC in both GDM and control groups. No significant difference was found between the GDM and control groups regarding the genotypic or allelic frequencies of rs174575 and rs2845574 sites (P > 0.05). Among the GDM group, individuals with the GG genotype at the rs174575 site had lower plasma HDL-C levels compared to those with the CC genotype (P < 0.05), and had higher atherogenic indices (AI) compared with the CC and CG genotype (P < 0.05; P < 0.05). Individuals with the TT genotype at the rs2845574 site had higher AI compared with the CT genotype (P < 0.05). Among the control group, individuals with the GG genotype had lower diastolic blood pressure (DBP) compared to those with the CC genotype (P < 0.05). Additional subgroup analysis demonstrated that the rs174575 polymorphism was associated with AI levels in obesity subgroup of GDM, TG levels in non-obese subgroup of control and DBP levels in the obese subgroup of control (P < 0.05; P < 0.05; P < 0.05). The FADS2 rs174575 and rs2845574 polymorphisms in GDM patients are associated wit HDL-C and AI levels, and the FADS2 rs174575 polymorphisms was also associated with DBP levels in normal pregnant women. The AI and DBP levels have a BMI-dependent effect. Show less
Coronary heart disease (CHD) has a significant co-morbid association with chronic kidney disease (CKD), but identification tools for the risk of concomitant CKD in patients with CHD are still lacking. Show more
Coronary heart disease (CHD) has a significant co-morbid association with chronic kidney disease (CKD), but identification tools for the risk of concomitant CKD in patients with CHD are still lacking. The purpose of this research was to construct machine learning (ML) models for identifying undetected CKD in CHD patients. 1786 CHD patients undergoing coronary intervention were retrospectively included. Lasso regression and multifactor logistic regression were used to screen feature variables. Five ML models, ie, logistic regression (LR), support vector machine (SVM), random forest (RF), gradient boosting machine (GBM), and extreme gradient boosting (XGBoost), were constructed. Participants were divided into the training set and validation set in a 7:3 ratio. The evaluation metrics included the area under the curve, calibration curve, and decision curve. Totally, 1786 CHD patients were enrolled and split into training (70%) and validation (30%) sets. The prevalence of CKD was 21.8% (390/1786). Multivariate logistic regression analysis showed that men, advanced age, hypertension, diabetes mellitus, history of atrial fibrillation (AF), high Gensini, low hemoglobin, low plateletcrit (PCT), high triglycerides (TG), high lipoprotein(a) (Lp(a)), hyperkalemia, high uric acid to albumin ratio (UAR), high systemic inflammation response index (SIRI), low lymphocyte to monocyte ratio (LMR), and high apolipoprotein B to apolipoprotein A1 (ApoB/ApoA1) ratio were the key clinical and laboratory test indicators of CKD. The XGBoost model performed optimally in the validation set (AUC=0.909, 95% CI 0.881 -0.937). SHapley Additive explanation analysis identified UAR, hypertension, Gensini score, age, and SIRI as the top 5 key features. The XGBoost model constructed on routine clinical data was effective in identifying CKD risk in CHD patients, with UAR as a novel strong predictor. Decision curve analysis confirmed the clinical utility of the model, indicating that it may be used to guide decisions for enhanced monitoring and early intervention over a wide range of risk thresholds. Show less
Adipogenic differentiation of adipose-derived stem cells (ADSCs) is fundamental to both adipose tissue homeostasis and clinical applications, particularly fat grafting. However, the global and stage-s Show more
Adipogenic differentiation of adipose-derived stem cells (ADSCs) is fundamental to both adipose tissue homeostasis and clinical applications, particularly fat grafting. However, the global and stage-specific transcriptional regulatory networks underlying ADSC adipogenesis remain incompletely elucidated. In this study, we integrated bulk and single-cell RNA-seq datasets across multiple time points of ADSC adipogenesis to identify core regulators of differentiation and maturation. A total of 41 genes were consistently upregulated during early differentiation, among which eight hub genes (FABP4, FASN, FABP5, ADIPOQ, PLIN1, LPL, CIDEC, and ACSL1) formed a tightly connected protein-protein interaction (PPI) module associated with lipid metabolism, lipid droplet formation, and adipocyte maturation. Further integration of differentially expressed lncRNAs and miRNAs led to the construction of a ceRNA network involving 7 mRNAs, 9 miRNAs, and 4 lncRNAs, comprising 34 predicted lncRNA-miRNA-mRNA regulatory axes. To identify temporal transcriptional regulators, we defined five genes (TTC14, MBNL2, UBR3, ABCD2, and SORT1) as early-stage inducers of adipogenesis, and four genes (UQCR11, NDUFB4, S100A10, and PRDX3) as late-stage regulators involved in maintaining the mature phenotype. These stage-specific regulators showed distinct temporal expression patterns and were validated by qPCR. GeneMANIA network analysis further revealed that early-stage regulators were enriched in lipid transport and lipase activity regulation, while late-stage regulators were associated with mitochondrial electron transport and energy metabolism. These findings highlight the stage-dependent transcriptional landscape of ADSC adipogenesis and provide candidate regulatory targets for modulating adipocyte differentiation and stability. Show less
Oxymatrine is an alkaloid with the property of immunomodulation. Recent studies have demonstrated that oxymatrine inhibits experimental autoimmune encephalomyelitis (EAE), an animal model of multiple Show more
Oxymatrine is an alkaloid with the property of immunomodulation. Recent studies have demonstrated that oxymatrine inhibits experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by promoting the production of interferon-β (IFN-β). However, the mechanism through which oxymatrine regulates the production of IFN-β remains unclear. The aim of this study was to investigate the pharmacological effects and related molecular mechanisms of oxymatrine in the treatment of EAE through in vivo and in vitro experiments. Oxymatrine alleviated neurological dysfunction, demyelination, and inflammation in EAE mice. It reduced microglia/macrophage infiltration and polarization, lowered pro-inflammatory cytokine levels (iNOS, TNF-α), and enhanced the expression of IL-10 and IL-27. Additionally, oxymatrine upregulated the STING/TBK1/IRF3 signaling pathway in EAE mice, promoting IFN-β production by microglia. Similarly, in LPS-induced BV2 cells, oxymatrine suppressed inflammatory factors and activated the STING/TBK1/IRF3 pathway to enhance IFN-β production. Notably, treatment with the STING inhibitor, C176, reversed these effects in both EAE mice and LPS-induced BV2 cells, confirming the pathway's critical role in the mechanism of oxymatrine therapy. Oxymatrine promotes IFN-β production in microglia by upregulating the STING/TBK1/IRF3 signaling pathway, thereby alleviating the neurological dysfunction of EAE and reducing pathological and inflammatory events. This study identifies a novel anti-EAE mechanism of oxymatrine: promoting IFN-β production in microglia by activating the STING/TBK1/IRF3 pathway. However, it lacks clinical sample verification. If validated later, oxymatrine may provide a more economical, convenient endogenous IFN-β induction regimen for MS patients. Show less
Carbamoyl phosphate synthetase I (CPS1) deficiency is a rare autosomal recessive metabolic abnormality cause by dysfunctionality of CPS1 and often result in unfavorable outcome. In this study, we pres Show more
Carbamoyl phosphate synthetase I (CPS1) deficiency is a rare autosomal recessive metabolic abnormality cause by dysfunctionality of CPS1 and often result in unfavorable outcome. In this study, we presented the detailed laboratory features and genetic analysis of two patients with heterozygous variants of CPS1, c.1927 A > G (p.Asn643Asp), c.2375 T > G (p.Met792Arg), c.3443 T > A (p.Met1148Lys) in patient 1; c.3784C > T (p.Arg1262Ter), c.3734 T > A (p.Leu1245His) in patient 2, respectively. c.1927 A > G (p.Asn643Asp) and c.2375 T > G (p.Met792Arg) are novel out of 5 variants and classified as variants of uncertain significance (VUS) under the guidelines of ACMG/AMP-ClinGen. Structure-based analysis of 4 missense variants indicates deleterious alterations to the protein. Since the employment of genetic testing as a clinical diagnostic tool, distinguishing pathogenic from polymorphic changes poses significant problems for geneticists. As recommendation for PP3/BP4, the computational tools for missense variant have been published, we performed a comparative evaluation for pathogenicity interpretation in our patients and in ClinVar database regarding CPS1 missense variants under the updated guidelines of ACMG/AMP-ClinGen. The application of computational tools under the ACMG/AMP-ClinGen criteria revealed an increased sensitivity for pathogenicity evaluation, from variants of uncertain significance (VUS) to likely pathogenic (LP) in previously reported cases; while for variants without clinic information in the ClinVar database, the pathogenicity assessment of VUS remained, and shows a more optimistic and reliable clinical application in molecular diagnosis. Show less
Calcified chondroid mesenchymal neoplasm (CCMN) is a recently identified category of soft tissue neoplasms defined by cartilage or cartilaginous matrix formation and We conducted a clinicopathological Show more
Calcified chondroid mesenchymal neoplasm (CCMN) is a recently identified category of soft tissue neoplasms defined by cartilage or cartilaginous matrix formation and We conducted a clinicopathological analysis of five newly identified CCMN cases and reviewed 87 cases documented in PubMed. Next-generation sequencing was used to detect molecular alterations, while clinical, radiological and histopathological features were extensively reviewed. CCMN typically affects adults, presenting as a slow-growing, painless mass in soft tissue. Histologically, CCMN exhibits a chondroid matrix with variable calcification. Molecular analyses in our cases identified CCMN should be considered in the differential diagnosis of soft tissue tumours with chondroid and calcified components. Detecting Show less
Natriuretic peptides (NPs) have an important role in lipid metabolism in skeletal muscle and adipose tissue in animals. C-type natriuretic peptide (CNP) is an important NP, but the molecular mechanism Show more
Natriuretic peptides (NPs) have an important role in lipid metabolism in skeletal muscle and adipose tissue in animals. C-type natriuretic peptide (CNP) is an important NP, but the molecular mechanisms that underlie its activity are not completely understood. Treatment of intramuscular fat (IMF) and subcutaneous fat (SCF) adipocytes with CNP led to decreased differentiation, promoted proliferation and lipolysis, and increased the expression of natriuretic peptide receptor B (NPRB) mRNA. Silencing natriuretic peptide C (NPPC) had the opposite results in IMF and SCF adipocytes. Transcriptome analysis found 665 differentially expressed genes (DEGs) in IMF adipocytes and 991 in SCF adipocytes. Seven genes in IMF adipocytes (FABP4, APOA1, ACOX2, ADIPOQ, CD36, FABP5, and LPL) and eight genes in SCF adipocytes (ACOX3, ACSL1, APOA1, CPT1A, CPT2, FABP4, PDPK1 and PPARα) are related to fat metabolism. Fifteen genes were found to be enriched in the peroxisome proliferator-activated receptor (PPAR) pathway. Integrated analysis identified 113 intersection genes in IMF and SCF adipocytes, two of which (APOA1 and FABP4) were enriched in the PPAR pathway. In conclusion, CNP may regulated lipid metabolism through the NPRB-PPAR pathway in both IMF and SCF adipocytes, FABP4 and APOA1 may be the key genes that mediated CNP regulation of fat deposition. Show less
To date, glucocorticoids remain the mainstay of treatment of nephrotic syndrome (NS). However, serious side effects and development of drug-resistance following long-term use limit the application of Show more
To date, glucocorticoids remain the mainstay of treatment of nephrotic syndrome (NS). However, serious side effects and development of drug-resistance following long-term use limit the application of glucocorticoids. Protopanaxadiol (PPD) possesses activity of dissociating transactivation from transrepression by glucocorticoid receptor (GR), which may serve as a potential selective GR modulator. However, steroid-like effects of PPD in vivo are unclear and not defined. How to translate PPD into clinical practice remains to be explored. The current study explored the renoprotection and potential mechanism of PPD and its combination with steroid hormones using adriamycin-induced NS rats. Adriamycin was given intravenously to rats to induce nephropathy. The determination of proteinuria, biochemical changes and inflammatory cytokines were performed, and pathological changes were examined by histopathological examination. Immunostaining and PCR were used to analyze the expression of interesting proteins and genes. The results showed that PPD, alone and in combination with prednisone, efficiently alleviate the symptoms of NS, attenuate nephropathy, improve adriamycin-induced podocyte injury by reducing desmin and increasing synaptopodin expression. In addition, the combined treatment reduced the expression of NF-κB protein and mRNA, as well as cytokine levels, and yet increased the expression of GR protein and mRNA. PPD modulated the transactivation of GR, manifested as repressing TAT, PEPCK and ANGPTL4 mRNA expressions mediated by GR. Meanwhile, PPD inhibited elevation of blood glucose and immune organ atrophy induced by prednisone. In summary, PPD increases the therapeutic effect of prednisone in NS while effectively prevents or decreases the appearance of side effects of glucocorticoids. Show less
Existing evidence suggests that elevated 1-hour post-load plasma glucose (1-h PG ≥ 8.6 mmol/L) during an oral glucose tolerance test (OGTT) is associated with atherogenic lipid parameters which are li Show more
Existing evidence suggests that elevated 1-hour post-load plasma glucose (1-h PG ≥ 8.6 mmol/L) during an oral glucose tolerance test (OGTT) is associated with atherogenic lipid parameters which are linked to an increased risk of cardiovascular disease (CVD). However, it remains unclear whether normal glucose tolerance (NGT) individuals with elevated 1-h PG (NGT-1hPG-high) should still be considered low-risk. Therefore, this study aims to demonstrate comprehensive lipid characteristics in individuals with different glycemic status stratified by 1-h PG, with a particular focus on those with NGT-1hPG-high. This cross-sectional study included individuals aged 25-55 years with high-risk of diabetes from the Daqing Diabetes Prevention Study II (Daqing DPS-II). Individuals were categorized into different glycemic status based on the World Health Organization's 1999 criteria and the International Diabetes Federation's 2024 position statement on 1-h PG. Traditional (TC, TG, HDL-C, LDL-C) and non-traditional lipid parameters [ApoA-1, ApoB, sdLDL-C, Lp(a), non-HDL-C, remnant cholesterol (RC), ApoB/ApoA-1, LDL-C/ApoB] were measured. Dyslipidemia was defined according to the 2023 Chinese Guidelines for Lipid Management. The China-PAR equation was used to estimate 10-year CVD risk. Spearman's correlation coefficients were calculated to evaluate the correlation between lipid parameters and 10-year CVD risk. Logistic and multiple linear regression models were performed to assess the association between 1-h PG and dyslipidemia as well as lipid parameters adjusting for covariates. Among 2 469 individuals, 22.7% had NGT with normal 1-h PG (NGT-1hPG-normal), 19.9% had NGT-1hPG-high, 2.6% had prediabetes with normal 1-h PG (PDM-1hPG-normal), 34.2% had prediabetes with elevated 1-h PG (PDM-1hPG-high), and 20.6% had newly diagnosed diabetes. The prevalence of dyslipidemia did not significantly differ between NGT-1hPG-high and PDM-1hPG-high (OR = 1.13, 95%CI: 0.88-1.44, P > 0.05). Higher 1-h PG levels were consistently associated with an atherogenic lipid profile, characterized by increased TC, TG, LDL-C, ApoB, sdLDL-C, non-HDL-C, RC and ApoB/ApoA-1, along with decreased ApoA-1, HDL-C and LDL-C/ApoB (all P < 0.05). Among lipid parameters, TG, sdLDL-C, RC, ApoB/ApoA-1, LDL-C/ApoB and HDL-C showed the strongest correlation with 10-year CVD risk, with Spearman's correlation coefficients of 0.41, 0.38, 0.35, 0.31, - 0.37 and - 0.36, respectively. In the NGT-1hPG-high, TG, sdLDL-C, and ApoB/ApoA-1 levels were significantly higher, while HDL-C and LDL-C/ApoB levels were significantly lower compared to counterparts with NGT-1hPG-normal (all P < 0.05). Moreover, except for TG and RC (both P < 0.01), the majority of lipid parameter levels in NGT-1hPG-high did not significantly differ from those in PDM (all P > 0.05). NGT-1hPG-high exhibited a similar atherogenic lipid profile to that observed in PDM. 1-h PG could serve as a potential indicator for the early identification of at-risk individuals who may otherwise go undetected among NGT population. Show less
To explore the potential categories of fear of falling in elderly stroke patients and analyze the differences in characteristics and influencing factors among patients in different categories. AA tota Show more
To explore the potential categories of fear of falling in elderly stroke patients and analyze the differences in characteristics and influencing factors among patients in different categories. AA total of 386 elderly stroke patients hospitalized in the Department of Neurology of a tertiary grade A general hospital in Jilin Province from March 2024 to June 2024 were selected as research subjects using the convenience sampling method. A general information questionnaire, Modified Falls Efficacy Scale (MFES), Simplified Coping Style Questionnaire (SCSQ), and Social Support Rating Scale (SSRS) were used for the survey. Mplus 8.3 software was applied to conduct latent profile analysis (LPA) on fear of falling in elderly stroke patients to identify potential categories, and multivariate logistic regression was used to further explore the influencing factors of each category. There were 3 potential categories of fear of falling in elderly stroke patients: the high fear of falling group (21.8%), moderate fear of falling group (38.3%), and low fear of falling group (39.9%). Multivariate logistic regression analysis showed that gender, age, type of stroke diagnosis, visual status, hearing status, limb strength, coping style, and social support were the influencing factors for the potential categories of fear of falling in elderly stroke patients. Fear of falling in elderly stroke patients has obvious categorical characteristics. Medical staff should implement targeted interventions based on the characteristics and influencing factors of different potential categories to reduce patients' fear of falling. Show less
Familial Hypercholesterolaemia (FH) is characterised by high cholesterol and premature cardiovascular disease. While hypercholesterolaemia and inflammation are both key drivers in the formation of ath Show more
Familial Hypercholesterolaemia (FH) is characterised by high cholesterol and premature cardiovascular disease. While hypercholesterolaemia and inflammation are both key drivers in the formation of atherosclerotic plaques, inflammation remains understudied in FH. Inflammatory (M1) macrophages contribute to plaque destabilisation and macrophage precursors, monocytes, can be skewed towards an inflammatory state. Aims: Determine; whether monocytes of FH individuals are inflammatory, if they readily form inflammatory macrophages, and whether this remains so in statin-treated individuals. Blood samples were collected from people with FH (statin-treated and untreated) and healthy controls. Lipid profile was obtained and monocyte inflammatory marker expression was determined by whole blood flow cytometry. Monocytes were cultured with autologous serum and resultant macrophage profile determined by flow cytometry. Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were higher in the Untreated-FH group compared to the Treated-FH group and controls. In both Treated-FH and Untreated-FH groups, monocytes were inflammatory with high CD86 (M1). The ratio of inflammatory/anti-inflammatory markers (CD86/CD163) significantly correlated with LDL-C and ApoB/ApoA1 ratio across the cohort, indicating the high LDL-C of FH may promote an inflammatory monocyte profile. Monocyte-derived-macrophages from (Treated) FH individuals also had a more inflammatory profile (CD86 and CD86/CD163). Overall, monocytes show inflammatory skewing in FH individuals, even those with moderately-reduced cholesterol levels. These monocytes readily become inflammatory macrophages. This, along with subsequent inflammatory macrophage formation, could contribute to plaque destabilisation and downstream clinical events. This supports inflammatory monocyte targeting as a potential approach to reduce residual risk in FH individuals. Show less
Atherosclerosis is the leading cause of cardiovascular disease-related morbidity and mortality. The traditional Chinese medicine Qingre Sanjie Formula (QRSJF), composed of Prunellae Spica, Sargassum, Show more
Atherosclerosis is the leading cause of cardiovascular disease-related morbidity and mortality. The traditional Chinese medicine Qingre Sanjie Formula (QRSJF), composed of Prunellae Spica, Sargassum, Fritillariae Thunbergii Bulbus, Leonuri Herba, and Forsythiae Fructus, has shown efficacy in treating cardiovascular diseases, although its mechanisms are unclear. This study aimed to explore the protective effects of QRSJF against atherosclerosis and the mechanisms involved. The composition of QRSJF was analyzed using Ultra Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry. An 8-week high-fat diet (HFD)-induced atherosclerosis model was established in ApoE Both low- and high-dose QRSJF effectively attenuated dyslipidemia and decreased serum inflammatory cytokine levels in HFD-fed ApoE QRSJF improves dyslipidemia and reduces atherosclerotic plaque in ApoE Show less