The rising incidence of childhood metabolic disorders poses an increasingly serious public health challenge. The developmental programming of the gut microbiota during early life, shaped by perinatal and postnatal factors, establishes a functional trajectory that profoundly influences host metabolism, with microbiota-derived metabolites serving as critical bridging molecules that mechanistically link early-life exposures to metabolic outcomes in childhood. Key microbiota‒metabolite pathways underpin this process, including the fermentation of dietary fiber into short-chain fatty acids (SCFAs), the microbial metabolism of amino acids into both protective and detrimental products, the biotransformation of primary bile acids (BAs) into secondary BAs, and the generation of trimethylamine N-oxide (TMAO) from methylamine precursors. These metabolites exert their effects through diverse molecular mechanisms, spanning epigenetic regulation and receptor signaling (including farnesoid X receptor [FXR], G protein-coupled bile acid receptor 1 [TGR5], and other metabolite-sensing receptors). A deep understanding of these microbiota-derived metabolites in the context of developmental programming is therefore essential not only for advancing precise diagnosis and personalized treatment but also for informing early and targeted prevention strategies to reduce the burden of childhood metabolic diseases.
The ferroptosis of intestinal epithelial cells (IECs), an iron-dependent form of cell death driven by lipid peroxidation, has emerged as a critical pathogenic driver of ulcerative colitis (UC). This review summarizes the core hallmarks of IEC ferroptosis in UC—specifically, lipid peroxidation, iron overload, and antioxidant system dysregulation—and describes key regulatory signaling networks, including the Nrf2/HO-1, SLC7A11/GPX4, and AMPK/mTOR pathways. Furthermore, we systematically evaluated emerging therapeutic strategies targeting these mechanisms, categorized into antioxidant activation, iron and lipid metabolism regulation, immune and microbiota modulation, and multitarget interventions. Elucidating this complex ferroptotic regulatory network provides a vital theoretical foundation for the development of novel disease-stage-specific therapeutic paradigms for UC management.
Neurofilaments (NFs) are protein structures that form part of the neuronal cytoskeleton, providing structural support and facilitating axonal transport. Neurofilament light chain (NFL) has emerged as a promising biomarker for various neurological conditions, as it is released into the bloodstream following neuronal damage. The ability of NFL to differentiate between types of injury and enhance the accuracy of clinical prediction models makes it an asset in both clinical practice and research. Studies suggest that NFL can be employed to diagnose and monitor disease progression and aid in the prognosis of various neurological conditions, including ischemic stroke (IS). In IS, NFL serves as a predictor of severity, functional recovery, and the risk of complications. This review therefore synthesizes current preclinical and clinical studies on the use of NFL as a biomarker for prognosis, monitoring, and treatment in IS.
Diabetic kidney disease (DKD) is one of the most common microvascular complications of diabetes. It can be identified by thickening of the glomerular basement membrane, reduced glomerular filtration rate, and persistent proteinuria. Macrophages play a key role in the pathogenesis of DKD, and their phenotype (M1 and M2) is finely regulated by metabolic reprogramming. M1 macrophages exacerbate inflammatory damage and fibrosis in renal tissue by secreting pro-inflammatory mediators and reactive oxygen species (ROS). M2 macrophages (further subdivided into M2a, M2b, M2c and M2d subtypes) primarily exert anti-inflammatory and tissue-repairing effects. Of these, the M2a and M2c subtypes are particularly crucial for anti-inflammatory repair. This study aimed to systematically review the mechanisms by which glucose, lipid, amino acid, and mitochondrial function-related metabolism influence macrophage polarization. It further explored therapeutic strategies to mitigate renal inflammation and fibrosis by regulating macrophage polarization through targeted metabolic pathways, including inhibiting glycolysis, promoting fatty acid oxidation, modulating amino acid metabolism, and enhancing mitochondrial biogenesis and oxidative phosphorylation (OXPHOS). Several natural compounds and synthetic drugs exhibit the potential to induce M2 polarization and suppress M1 polarization through metabolic reprogramming, thereby offering new directions for optimizing therapeutic strategies for DKD.
Biguanides, especially metformin, are essential for managing type 2 diabetes, a major global health concern. They show favorable pharmacokinetic and pharmacodynamic profiles and have been in clinical use for decades, although their therapeutic mechanisms have yet to be fully elucidated beyond their primary role in hepatic glucose production. Recent investigations have highlighted the significant roles of the gastrointestinal tract, gut microbiota, and tissue-resident immune cells in modulating metformin efficacy. Metformin is of interest for repurposing across various disorders, including cancer, aging, inflammation, and microbial infections. These manifestations are a consequence of their pleiotropic molecular effects and of treatment benefit, which depend on dose or duration. Nevertheless, the associated lactic acidosis, as well as other rare and serious adverse effects, requires a full knowledge of their toxicity profile and organ responses. Novel nanotechnology-based strategies can provide new opportunities to improve the therapeutic index of biguanides by enhancing bioavailability, increasing tissue specificity, and reducing systemic toxicity. In this review, we have examined the complex pharmacology of biguanides, discussed organ-specific therapeutic and toxicological effects, and critically evaluated targeted delivery to optimize their clinical utility through nanotechnology interventions.
Thyroid cancer (TC) is a common endocrine malignancy with rapidly increasing global incidence. Clinical management remains challenging for advanced and radioiodine-refractory thyroid cancer (RAIR-TC). Metabolic reprogramming, especially enhanced aerobic glycolysis (the Warburg effect), is a core hallmark of TC that drives tumor progression and therapeutic resistance. This review systematically summarizes the molecular mechanisms of glucose metabolic reprogramming in TC, focusing on key oncogenic drivers including BRAF V600E mutation, RAS mutation, and RET/PTC rearrangement, as well as their downstream mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways. These pathways coordinately upregulate critical glycolytic regulators: glucose transporter 1 (GLUT1), hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA). We further discuss emerging therapeutic strategies targeting glucose metabolism and highlight challenges including isoform-specific regulation and biomarker-driven patient stratification. This review provides a conceptual framework for translating metabolic insights into improved diagnosis and therapy for TC.
Premature ovarian insufficiency (POI) is a harmful disease that leads to decreased fertility and osteoporosis and an increased risk of cardiovascular disease. POI seriously affects women’s physical and mental health. Currently, the incidence of POI is rising; however, the etiology of most cases remains unclear, and these cases are referred to as idiopathic POI. Understanding the risk factors for idiopathic POI is beneficial for preventing and recognizing POI early on, as well as for improving treatment outcomes. This paper describes the etiology and pathogenesis of idiopathic POI from five perspectives: genetic and familial factors; environmental factors (including endocrine-disrupting chemicals, persistent organic pollutants, and heavy metals); gut microbial disorders; lifestyle factors (including smoking, diet, physical activity, and pathological sleep); and psychological and social factors. Furthermore, this review discusses the interactions among these risk factors and provides clinical prevention recommendations. This study aims to improve clinical diagnosis and treatment of idiopathic POI and women’s health.
Lupus nephritis (LN) is a frequent and severe manifestation of systemic lupus erythematosus (SLE) that substantially affects renal outcomes and long-term survival. Notably, this disease remains a leading cause of SLE-related mortality. Glucocorticoids, hydroxychloroquine, immunosuppressive agents, and calcineurin inhibitors (CNIs) represent the standard therapy. As a next-generation CNI, the use of voclosporin represents a therapeutic advance for LN. This can be attributed to its optimized pharmacologic properties and dual mechanism of action, which involves potent inhibition of T-cell activation and direct stabilization of podocytes. In pivotal phase III trials, the addition of voclosporin to a background of mycophenolate mofetil and low-dose glucocorticoids significantly increased complete renal remission rates and produced a rapid, durable reduction in proteinuria. These findings support a “low steroid” treatment approach. Compared with conventional CNIs, voclosporin has more consistent pharmacokinetics, favorable metabolic safety, and lacks clinically meaningful drug–drug interactions with mycophenolate mofetil. Voclosporin is also cost effective, as suggested by economic evaluations conducted from multiple national health-system perspectives. The available evidence collectively indicates that voclosporin, through its efficacy, safety, and economic value, enables a more precise, efficient, and comparatively cost-effective treatment paradigm for LN.
Melanotic schwannoma (MS) is a rare peripheral nerve sheath tumor accompanied by melanin deposition and severe refractory pain. However, its molecular pathogenesis remains unclear. This study aimed to explore the histomorphological, transcriptomic, and proteomic characteristics of MS, and to identify key molecules related to melanin production, pain generation, and targeted therapy.
Histomorphological characteristics of MS were observed by Luxol Fast Blue (LFB) staining and hematoxylin and eosin (HE) staining in tumor tissues from 3 MS patients. Combined transcriptomic and proteomic analyses were performed to screen differentially expressed genes and proteins. The expression levels of tyrosinase-related protein 1 (TYRP1), transient receptor potential ankyrin 1 (TRPA1), and Bruton’s tyrosine kinase (BTK) were validated by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence staining.
Histomorphological examination revealed typical melanin deposition and prominent compression of adjacent nerve fibers in MS. Transcriptomic and proteomic analyses showed activation of the melanin synthesis pathway and transient receptor potential (TRP) channel-related neuroinflammatory pathway. The expression of TYRP1 and TRPA1 was significantly upregulated, suggesting that these related pathways are associated with melanin production and neuropathic pain in MS. In addition, the expression of BTK, a known molecular target of targeted drugs, was significantly increased, suggesting that BTK inhibitors have potential therapeutic effects on MS.
This study delineates the histomorphological features, transcriptomic and proteomic profiles of MS. TYRP1, TRPA1, and BTK are identified as key molecules involved in melanogenesis, pain generation, and targeted therapy, respectively. These findings provide novel insights into the pathogenesis and potential therapeutic strategies for MS.
This study aimed to develop a predictive model utilizing radiomics features and clinical characteristics to accurately differentiate low-grade (WHO grade I) from high-grade (WHO grade II/III) meningiomas preoperatively, thereby improving treatment planning and prognosis.
A retrospective analysis of 288 meningioma cases (191 low-grade and 97 high-grade) confirmed by histopathology was conducted. Radiomics features were extracted from contrast-enhanced T1-weighted MRI (CE-T1WI) using the pyradiomics package, followed by feature selection via LASSO regression. Predictive models (logistic regression, decision tree, support vector machine [SVM], adaptive boosting) were evaluated. Clinical variables (peritumoral edema index and monocyte count) were integrated to try to improve the predictive performance. Model efficacy was assessed using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis.
Four key radiomics features were identified as significant discriminators of tumor grade. The logistic regression model demonstrated superior predictive performance over decision trees, SVMs, and adaptive boosting methods. The inclusion of the peritumoral edema index and monocyte count increased the AUC to 0.801 (95% CI 0.753–0.869) in the training set. However, in the validation set, the radiomics model achieved the best performance, with an AUC of 0.770 (95% CI 0.670–0.869).
The radiomics-based model effectively predicts high-grade meningioma and demonstrates superior performance compared to the clinical and combined models. This study advances the precision of meningioma grading, offering significant implications for treatment planning and patient management.
Epilepsy is a common neurological disorder with high genetic heterogeneity and affects approximately 70 million people worldwide. Although several studies have combined Genome-Wide Association Studies (GWAS) with bulk expression quantitative trait loci (eQTLs) to explore epilepsy risk genes, the cellular context of genetic regulation remains insufficiently defined.
We integrated epilepsy GWAS data with brain bulk and single-cell eQTLs using summary-data-based Mendelian randomization (SMR) and Bayesian colocalization to identify causal genes. The identified genes were validated in an independent RNA-seq cohort of patients with refractory epilepsy. We then characterized cell-type specificity and intercellular signaling using single-cell RNA sequencing (scRNA-seq) and CellChat. Druggability and drug-repurposing analyses were performed using DSigDB to identify targeted therapeutic compounds for epilepsy.
Seven epilepsy causal genes (FGFR3, PM20D1, ZNF564, HAGH, CAPN15, CCDC117 and DARS1-AS1) were identified, with FGFR3 and HAGH identified as druggable targets. FGFR3 was predominantly expressed in astrocytes and involved in an astrocyte-centered FGF2–FGFR signaling loop, whereas HAGH was enriched in neurons. DSigDB analysis highlighted the FGFR inhibitor, Ro-4396686, as the top candidate compound.
Multi-scale integration of eQTL, GWAS and transcriptomic datasets reveals the genetic variants of epilepsy, with FGFR3-driven FGF signaling representing a principal molecular axis. This study reveals the cellular context of this disorder and highlights FGFR3 and HAGH as promising therapeutic targets.
While the RNA modification N6-methyladenosine (m6A) is known to influence immune cell function, its specific role in regulating macrophage migration and invasion remains poorly defined. This study aimed to elucidate the function and mechanism of the core m6A methyltransferase METTL3 in the migratory and invasive capacities of macrophages.
A macrophage-specific METTL3-knockdown model was established. The functional effects of METTL3 deficiency were systematically evaluated using migration, invasion, phagocytosis, and polarization assays. Subsequent transcriptome sequencing (RNA-seq) and methylated RNA immunoprecipitation-quantitative PCR (MeRIP-qPCR) were employed to identify the key differentially expressed gene, lysyl oxidase-like 2 (LOXL2). This mechanistic link was ultimately confirmed through functional rescue experiments and reconstitution assays.
METTL3 deficiency significantly increased the migratory and invasive capacities of macrophages but attenuated their phagocytic activity, promoting a shift toward an M2-like polarization state. Mechanistically, METTL3 knockdown reduced m6A modification at a specific site of LOXL2 mRNA, thereby decreasing its RNA stability and leading to decreased expression. Importantly, this phenotype was validated through functional inhibition assays. Reconstitution of LOXL2 in METTL3-deficient macrophages substantially reversed the enhanced migratory and invasive phenotypes.
This study reveals a novel METTL3–m6A–LOXL2 signaling axis that posttranscriptionally fine-tunes macrophage migration and invasion by regulating gene expression. These findings provide a mechanistic explanation for the functional dynamics of macrophage migration and invasion and underscore that m6A modification is a key regulator of innate immune cell behavior.
To investigate the mechanistic role of Sijunzi decoction (SJZD) in overcoming chemoresistance through the suppression of adaptive metabolic responses in non–small cell lung cancer (NSCLC).
Chemical profiling of SJZD-derived components in systemic circulation was conducted using liquid chromatography–tandem mass spectrometry (LC‒MS/MS) in Sprague–Dawley rats. Multiomics integration and network pharmacology were employed to identify convergent targets shared by the bioactive constituents of SJZD and genes associated with cisplatin resistance. In vitro functional assessments using cisplatin-resistant human lung adenocarcinoma (A549/DDP) cells included the following: quantification of cell viability via Cell Counting Kit-8 (CCK-8) assays; evaluation of mitochondrial bioenergetics through targeted metabolomic profiling; and ultrastructural characterization of ferroptotic morphology via transmission electron microscopy (TEM). Cellular redox homeostasis was dynamically monitored using fluorescent probes, including a DCFH-DA probe for reactive oxygen species (ROS) and a C11-BODIPY581/591 probe for lipid peroxidation. siRNA-mediated gene silencing and immunohistochemical analysis were performed to elucidate the functional hierarchy of the p62/Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant axis. Complementary in vivo validation was performed using BALB/c nude mice bearing A549/DDP xenografts, with longitudinal monitoring of tumor progression under SJZD treatment regimens.
Untargeted metabolomics of SJZD-medicated serum revealed 392 differentially abundant metabolites, with pathway enrichment revealing significant dysregulation of glutamine metabolism. Structural validation confirmed 55 bioactive components of SJZD in serum, including glycyrrhizin, ginsenoside Ro, liquiritigenin, and atractylenolide I. Integration of these components with disease targets yielded 355 overlapping genes associated with both SJZD activity and cisplatin-resistant NSCLC, with significant enrichment in oxidative stress response pathways. Experimental assays confirmed that SJZD induced ferroptosis in cisplatin-resistant A549/DDP cells, as evidenced by disrupted iron homeostasis, lipid peroxidation, and characteristic mitochondrial damage. These effects and subsequent cell death were specifically abrogated by the ferroptosis inhibitor ferrostatin-1 (Fer-1) but not by apoptosis inhibition, confirming that ferroptosis is the primary mechanism of cell death. Mechanistically, the inhibition of p62/Keap1/Nrf2 signaling was involved in the modulation of SJZD-induced ferroptosis both in vitro and in vivo.
SJZD counteracts metabolic adaptation through ferroptosis mediated by the inhibition of p62/Keap1/Nrf2 in cisplatin-resistant NSCLC.
DNA repair plays a critical role in the development of smoking-related cancers. We hypothesized that DNA repair capacity (DRC) and nucleotide excision repair (NER) mRNA expression are associated with increased head and neck squamous cell carcinoma (HNSCC) risk in the Chinese population.
We conducted a case-control study including 349 patients with HNSCC and 316 cancer-free controls. DRC and NER mRNA expression levels were measured in lymphoblastoid cells exposed to benzo[a]pyrene diol epoxide (BPDE). Correlations between DRC and NER mRNA expression were analyzed, and their associations with HNSCC risk were evaluated.
The mean DRC was significantly lower in patients with HNSCC (9.72% ± 2.25%) than in healthy controls (10.81% ± 2.63%, P < 0.001). Compared with individuals with higher DRCs, those with lower DRCs had a significantly greater risk of HNSCC (odds ratio [OR] = 2.23, 95% confidence interval [CI] = 1.60–3.10, P < 0.001; Ptrend < 0.001). Correlation analyses demonstrated significant associations between DRC and the expression of XPA and XPB. Moreover, predictive models combining DRC with XPA and/or XPB mRNA expression significantly improved risk prediction, as evidenced by increased area under the curve (AUC) values (P < 0.05).
Suboptimal DRC and reduced expression of key NER genes, particularly XPA and XPB, are associated with increased HNSCC risk. Integrating these two NER biomarkers may provide a novel and improved model for HNSCC risk assessment.
The high toxicity of current therapies and frequent relapse in mature B-cell non-Hodgkin lymphomas (B-NHLs) reveal a substantial unmet clinical need for more effective targeted treatment strategies. To address this gap, Gene Set Enrichment Analysis (GSEA) of B-NHL datasets was conducted, uncovering marked enrichment of E2F transcription factors and their target genes. Despite the central role of E2F signaling in cell cycle control and oncogenesis, its contribution to pediatric B-NHLs has not been systematically characterized. Accordingly, we performed a comprehensive analysis of E2F signaling and its downstream targets to identify potential therapeutic and prognostic biomarkers in pediatric B-NHLs.
The datasets used for this analysis were obtained from the Gene Expression Omnibus (GEO) database, and mRNA and protein expression levels were further validated via data from The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). Key bioinformatics findings were validated via quantitative PCR (qPCR) and cell proliferation assays. Survival analysis was conducted to evaluate the associations between gene expression levels and the prognosis of B-NHL patients. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA were employed to predict gene functions and associated pathways.
Childhood B-NHLs were markedly enriched for E2F gene set. The identified overlapping differentially expressed genes (DEGs) were linked to cell cycle regulation, DNA replication, and proliferative activity. E2F1 and hub genes such as POLD1, LIG1, MCM3, MCM6, and PCNA were markedly overexpressed in B-cell lymphoma. These genes demonstrated strong discriminatory potential as disease-associated signaling molecules. Moreover, the expression of POLD1 was closely associated with the proliferative capacity of B-NHLs.
E2Fs and their downstream target genes are significantly overexpressed in pediatric B-NHLs, driving tumor cell proliferation. These molecules may serve as biomarkers for therapeutic stratification, prognosis, and disease monitoring in pediatric B-NHLs.
Disruptions to trophoblast infiltration and placental implantation are recognized as pivotal early mechanisms underlying the pathogenesis of preeclampsia. Previous studies have reported the aberrant expression of PTPRN2 in preeclamptic placentas, yet its precise pathological role remains poorly defined. The present study investigated the functional involvement of PTPRN2 in regulating trophoblast invasion.
PTPRN2 expression was detected by qRT-PCR and Western blotting in normal and preeclamptic placentas, as well as in HTR-8/SVneo cells cultured under normoxic or hypoxic conditions. HTR-8/SVneo cells were then transfected with a PTPRN2 overexpression plasmid. Transwell assays were performed to evaluate trophoblast invasion ability. Additionally, the expression of key Wnt/β-catenin signaling components, including β-catenin and GSK-3β was analyzed in PTPRN2-overexpressing HTR-8/SVneo cells and preeclamptic placentas.
Our results demonstrated that PTPRN2 was significantly upregulated in preeclamptic placental tissues. In vitro experiments further revealed that hypoxic exposure induced PTPRN2 expression in HTR-8/SVneo cells and that overexpression of PTPRN2 markedly suppressed the invasive ability of these cells. Moreover, hypoxia decreased the protein levels of β‑catenin and GSK‑3β in HTR-8/SVneo cells, and these effects were further exacerbated by PTPRN2 overexpression.
Collectively, these findings indicate that hypoxia‑induced upregulation of PTPRN2 contributes to impaired trophoblast invasion via inhibition of the Wnt/β‑catenin signaling pathway.
Spontaneous abortion (SA) is a common adverse outcome of early pregnancy, yet its underlying pathophysiological mechanisms remain incompletely understood. Accumulating evidence suggests that dysregulated inflammatory responses at the maternal-fetal interface play a critical role in pregnancy loss. However, the potential associations between alterations in gut microbiota, metabolic disturbances, and localized decidual inflammation in patients with SA have not been systematically characterized.
Women with SA (n = 30) and those with normal early pregnancy (NP, n = 28) were enrolled in this study. Proinflammatory cytokines were quantified in decidual tissue homogenates, and histopathological and molecular analyses were performed to evaluate inflammatory activation at the maternal-fetal interface. The gut microbiota composition was profiled using shotgun metagenomic sequencing, while metabolic alterations in the feces were assessed by untargeted metabolomics. Integrated multi-omics analyses were conducted to explore associations among gut microbial dysbiosis, metabolic perturbations, decidual inflammatory signaling, and molecular alterations.
Compared with those from the NP group, the decidual tissues from the SA group exhibited significantly elevated levels of IL-1β and TNF-α (1.49-fold and 1.51-fold, both P < 0.0001), accompanied by pronounced histopathological abnormalities. Enhanced activation of the NF-κB signaling pathway was observed at the maternal–fetal interface in SA patients. Metagenomic analyses revealed distinct differences in the gut microbiota composition and community structure between the two groups, with differentially abundant bacterial taxa identified (LDA score > 2.0). Consistent with these findings, fecal metabolomic profiling clearly revealed differences between SA and NP patients, with differentially abundant metabolites (VIP > 1.0, adjusted P < 0.05) predominantly enriched in lipid metabolism, amino acid metabolism, and immune-related pathways. In addition, the expression of leucine-rich repeat-containing G protein-coupled receptor 6 was significantly upregulated (P < 0.0001) in the decidual tissue of SA patients.
These findings indicate that SA is associated with localized inflammatory activation at the maternal-fetal interface, dysregulation of decidual molecular activity, gut microbiota dysbiosis, and metabolic perturbations. Integrated multi-omics analyses suggest potential interactions among these factors that may be linked to decidual dysfunction during early pregnancy, providing new insights into the complex pathophysiology of SA.
Recent study links sarcopenia with lipid metabolism disorders. This study aimed to examine the associations between non-traditional lipid indices—specifically the lipoprotein combined index (LCI) and the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (non-HDL-C to HDL-C ratio, NHHR)—and incident sarcopenia in a Chinese population.
Participants aged ≥ 45 years were enrolled from the 2011–2015 waves of the China Health and Retirement Longitudinal Study (CHARLS). Multivariate logistic regression was applied in cross-sectional analyses (n = 3,161) to assess the associations between log-transformed LCI, NHHR and sarcopenia. Longitudinal analyses (n = 2,898) were performed using multivariate Cox proportional hazards models, restricted cubic splines, subgroup analyses, and receiver operating characteristic (ROC) curves. Sensitivity analyses were conducted to test the robustness of the results.
Higher quartiles of lnLCI and lnNHHR were inversely associated with sarcopenia in both cross-sectional (lnLCI Q4: OR 0.58, P = 0.015; lnNHHR Q3: OR 0.56, P = 0.005) and longitudinal analyses (lnLCI Q4: HR 0.57, P = 0.001; lnNHHR Q4: HR 0.46, P = 0.002), with linear trends observed in spline models. Alcohol intake modified the association between lnNHHR and sarcopenia (P = 0.017), whereas the association of lnLCI with sarcopenia remained consistent in alcohol intake subgroup. ROC analyses showed similar predictive ability (lnLCI AUC 0.599; lnNHHR AUC 0.603). Sensitivity analyses excluding participants with hypercholesterolemia further validated the findings.
Among Chinese adults aged ≥ 45 years, LCI and NHHR were inversely associated with sarcopenia, with NHHR demonstrating slightly superior diagnostic potential.
Growing evidence suggests that environmental pollutants may increase the risk of gestational diabetes mellitus (GDM). This study aimed to assess the association between blood concentrations of trihalomethanes (THMs) and GDM, and to explore the mediating role of Homeostatic Model Assessment of β-Cell Function (HOMA-β).
This cross-sectional study analyzed data from 2,592 participants in the National Health and Nutrition Examination Survey (NHANES, 2007–2018). Weighted multivariate logistic regression and weighted quantile sum (WQS) regression were used to evaluate the individual and combined effects of blood THMs on GDM. Mediation analysis was conducted to assess the intermediary role of HOMA-β.
Higher blood concentrations of chloroform (TCM), bromodichloromethane (BDCM), brominated THMs (BTHM), chlorinated THMs (CTHM), and total THMs (TTHM) were significantly associated with increased odds of GDM, with adjusted odds ratios (highest vs. lowest group) ranging from 1.58 (95% CI: 1.01–2.49) for BDCM to 2.00 (95% CI: 1.24–3.23) for CTHM. WQS analysis identified BDCM as the primary contributor to this risk. Mediation analysis revealed that HOMA-β significantly mediated 14.73%, 10.95%, 11.16%, and 10.94% of the effects of BDCM, BTHM, CTHM, and TTHM on GDM, respectively.
This nationally representative cross-sectional study reveals a positive association between blood THM concentrations and GDM, with BDCM as the main contributor. The association was partially mediated by reduced pancreatic β-cell function (HOMA-β). These findings suggest a potential environmental risk pathway for gestational health, warranting validation in prospective cohort studies.
Viral hepatitis remains a major global health threat, causing approximately 1.3 million deaths in 2022. Despite substantial advances in vaccination and clinical treatment, it continues to impose a heavy disease burden across China. Existing studies have largely focused on single hepatitis subtypes and national epidemiological trends, with limited evidence on provincial heterogeneity. To fill this research gap, this study aimed to conduct a refined, region-specific epidemiological assessment of viral hepatitis in China.
Data were extracted from the Global Burden of Disease Study 2021 (GBD 2021) and the China Public Health Science Data Center to systematically analyze the epidemiological characteristics and spatiotemporal trends of viral hepatitis in China over the past three decades.
The overall burden of viral hepatitis in China decreased substantially over the study period, with obvious regional heterogeneity. Acute hepatitis A, B and E, as well as chronic hepatitis B and C, all presented prominent downward trends. The fastest declines in incidence were observed in acute hepatitis B (estimated annual percentage change [EAPC] = −3.03) and chronic hepatitis B (EAPC = −4.74). Notably, males suffered a higher disease burden for nearly all outcomes, except for HCV-related hepatocellular carcinoma, which predominantly affected females. Furthermore, provincial-level analysis indicated marked regional disparities: Xizang maintained a high incidence rate, while Beijing exhibited low incidence accompanied by strikingly high hepatitis-related mortality, suggesting a notable decoupling between infection prevalence and mortality.
China has achieved remarkable reductions in the overall burden of viral hepatitis, attributable to comprehensive public health interventions such as universal vaccination, standardized screening and improved sanitation conditions. Nevertheless, residual burdens in vulnerable populations and striking regional inequalities warrant targeted prevention and control strategies to reduce disease disparities nationwide.
Complete removal of filling material from complex anatomies such as the mesiobuccal isthmus remains a challenge in endodontic retreatment. This study aimed to compare the efficacy of XP-endo Shaper (XPS), Reciproc (REC), and WaveOne Gold (WOG) in removing root canal filling material during the retreatment of 3D-printed maxillary first molars, as quantified by micro-CT.
Fifteen standardized 3D-printed resin teeth with Vertucci type II mesiobuccal canals were prepared, obturated, and randomly assigned to retreatment using XPS, REC, or WOG (n = 5 per group). Micro-CT scans were acquired before and after retreatment to analyze residual filling material volume in the coronal, middle, and apical thirds. Statistical analysis was performed using the Kruskal‒Wallis H test with post hoc Mann‒Whitney U tests (Bonferroni corrected).
While all the systems achieved near-complete coronal debridement (> 97%), REC demonstrated significantly greater removal in the middle third (99% ± 1% vs. 97% WOG and 94% XPS; P < 0.05). Crucially, in the apical isthmus region, both XPS (95% ± 3%) and REC (90% ± 7%) significantly outperformed WOG (76% ± 3%) (P < 0.05). No significant difference was detected between XPS and REC in the apical third.
Residual filling material persisted in all the samples. REC showed the highest overall efficiency, whereas XPS achieved comparable apical debridement to REC. These quantitative, region-specific findings support the preferential use of XPS or REC over WOG for retreatment cases involving complex apical anatomy or isthmus configurations.
To elucidate the therapeutic mechanism of Yudantong decoction (YDTD) in cholestatic liver disease (CLD), focusing on the gut microbiota-bile acid-intestinal farnesoid X receptor (FXR) axis.
A CLD mouse model induced by α-naphthylisothiocyanate was treated with YDTD. Hepatic injury, gut microbiota composition (16S rRNA sequencing), bile acid profiles (high-performance liquid chromatography–tandem mass spectrometry, HPLC-MS/MS), intestinal FXR/NLRP3 signaling, and barrier function were assessed. Fecal microbiota transplantation, bile salt hydrolase (BSH) inhibition, and FXR antagonism were employed for mechanistic validation.
CLD mice exhibited hepatocellular steatosis, lobular necrosis, and elevated serum markers. These pathological changes were associated with gut dysbiosis, impaired bile acid metabolism via bile salt hydrolase (BSH) suppression, FXR signaling inhibition, and NLRP3 inflammasome activation. YDTD restored BSH activity and bile acid homeostasis, upregulated FXR expression, suppressed NLRP3 inflammasome activation, and improved intestinal barrier integrity. Fecal microbiota transplantation experiments confirmed that YDTD-modified microbiota mediated these therapeutic benefits, whereas pharmacological inhibition of BSH or FXR attenuated YDTD’s therapeutic effects.
YDTD alleviates CLD, at least in part, by targeting the gut microbiota-bile acid-FXR signaling pathway, highlighting the gut microbiota as a promising therapeutic target for CLD.