This study aimed to comprehensively evaluate the clinical effectiveness and safety of acupuncture combined with repetitive transcranial magnetic stimulation (rTMS) in treating post-stroke cognitive im Show more
This study aimed to comprehensively evaluate the clinical effectiveness and safety of acupuncture combined with repetitive transcranial magnetic stimulation (rTMS) in treating post-stroke cognitive impairment (PSCI) through meta-analysis and trial sequential analysis (TSA), moreover to provide an evidence-based basis for the treatment of PSCI in clinical practice. The study conducted a comprehensive search of eight major domestic and international databases, including PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP and China Biology Medicine (CBM). Four English and four Chinese databases of randomized controlled trials of acupuncture combined with rTMS for the treatment of PSCI from inception until July 2025. Systematic reviews and meta-analyses were conducted based on the Cochrane systematic review method by using RevMan5.4 and Stata/MP 18.0, and trial sequential analyses were performed by TSA 0.9. Sixteen RCTs involving 1,058 patients were included, including 532 patients in the experimental group and 526 patients in the control group. Meta-analysis results showed that the experimental group had a higher clinical effectiveness rate in treating patients with PSCI compared to the control group [RR = 1.29, 95% CI (1.08, 1.55), Acupuncture combined with rTMS can improve cognitive function, regulate daily living ability, and regulate neurotransmitter levels in patients with PSCI, which is worthy recommended in the clinic. However, due to limitations in sample size, inclusion quality and incomplete reporting, it is worth noting that more rigorously designed and high-quality studies are needed to further validate these conclusions. Show less
This study focuses on the impacts of polystyrene/polylactic acid microplastics (PS/PLA-MPs) on ovarian reserve and oocyte maturation in female mice, along with the underlying mechanisms. 1 μm PS-MPs a Show more
This study focuses on the impacts of polystyrene/polylactic acid microplastics (PS/PLA-MPs) on ovarian reserve and oocyte maturation in female mice, along with the underlying mechanisms. 1 μm PS-MPs and PLA-MPs were prepared, with PLA-MPs having a rougher surface and broader size distribution. In vitro, PLA-MPs showed higher cytotoxicity to granulosa cells compared to PS-MPs. In vivo, MPs exposure disrupted the estrous cycle, and damaged ovarian reserve. Granulosa cell apoptosis and cytokine activation led to transzonal projection retraction, oocyte oxidative stress, meiotic abnormalities, and reduced oocyte retrieval and polar body extrusion rate, thus reducing litter size. PS-MPs induced more severe intestinal and ovarian impairment. Analysis of feces 16S rRNA, serum metabolomics, and ovarian RNA sequencing revealed that lipoprotein lipase (LPL) was suppressed by both MPs, linking gut microbiota, lipid metabolism, and ovarian injury. Fecal microbiota transplantation as a rescue strategy in MPs exposed mice upregulated LPL, alleviating ovarian reserve decline. In PLA-MPs exposed mice, ovarian reserve related indicators partially recovered after a two-week exposure cessation. These results clarify the similarities and differences in how PS-MPs and PLA-MPs impair ovarian function via gut-ovary axis and lipid metabolism dysregulation. Show less
Diabetic nephropathy (DN) is the most intractable complication of diabetes. Despite decades of research, accurate diagnostic markers and effective therapeutic drugs are still elusive. Abnormal copper Show more
Diabetic nephropathy (DN) is the most intractable complication of diabetes. Despite decades of research, accurate diagnostic markers and effective therapeutic drugs are still elusive. Abnormal copper metabolism is also implicated in diabetes and its complications. This study aims to identify copper metabolism-related biomarkers and potential drugs for DN. DN datasets and copper metabolism-related genes (CMGs) were obtained from Gene Expression Omnibus (GEO) and GeneCards. Differentially expressed CMGs (DE-CMGs) were identified using the limma package and the Venn algorithm. Functional enrichment analysis and protein-protein interaction (PPI) network were performed to identify candidate hub genes. The single gene with an area under the receiver operating characteristic (ROC) curve > 0.7 was identified as a potential diagnostic biomarker of DN. Finally, these biomarkers were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in high-glucose-treated human proximal tubular (HK-2) cells. These validated hub genes were used to construct a combined prediction model, confirmed by additional GSE30528 and GSE30529 datasets. The correlation analysis between the expression level of the hub genes and the estimated glomerular filtration rate (eGFR) was carried out. Additionally, immune cell infiltration and potential target drugs were investigated for these biomarkers. Five hub genes associated with copper metabolism, namely CD36, CCL2, CASP3, LPL, and APOC3, were identified as biomarkers for the early diagnosis of DN. Utilizing multiple biomarkers enhanced diagnostic accuracy and specificity. CD36, CCL2, and CASP3 correlated negatively with eGFR levels, while LPL and APOC3 correlated positively. Additionally, these hub genes were significantly linked to various immune cell types, including macrophages M1 and M2, T cells, gamma delta resting dendritic cells, neutrophils, and NK cells. Furthermore, 15 agents targeting these biomarkers were retrieved from the DrugBank database. Our study identified key genes possibly related to copper metabolism in the pathological mechanism of DN that could serve as novel targets for the diagnosis and therapy of DN. Show less
Autoantibodies hold promise for diagnosing lung cancer. However, their effectiveness in early-stage detection needs improvement. In this study, we investigated novel IgG and IgM autoantibodies for det Show more
Autoantibodies hold promise for diagnosing lung cancer. However, their effectiveness in early-stage detection needs improvement. In this study, we investigated novel IgG and IgM autoantibodies for detecting early-stage lung adenocarcinoma (Early-LUAD) by employing a multi-step approach, including Human Proteome Microarray (HuProtTM) discovery, focused microarray verification, and ELISA validation, on 1246 individuals consisting of 634 patients with Early-LUAD (stage 0-I), 280 patients with benign lung disease (BLD), and 332 normal healthy controls (NHCs). HuProtTM selected 417 IgG/IgM candidates, and focused microarray further verified 55 significantly elevated IgG/IgM autoantibodies targeting 32 tumor-associated antigens in Early-LUAD compared to BLD/NHC/BLD+NHC. A novel panel of 10 autoantibodies (ELAVL4-IgM, GDA-IgM, GIMAP4-IgM, GIMAP4-IgG, MGMT-IgM, UCHL1-IgM, DCTPP1-IgM, KCMF1-IgM, UCHL1-IgG, and WWP2-IgM) demonstrated a sensitivity of 70.5% and a specificity of 77.0% or 80.0% for distinguishing Early-LUAD from BLD or NHC in ELISA validation. Positive predictive values for distinguishing Early-LUAD from BLD with nodules ≤ 8 mm, 9-20 mm, and > 20 mm significantly increased from 47.27%, 52.00%, and 62.90% [low-dose computed tomography (LDCT) alone] to 79.17%, 71.13%, and 87.88% (10-autoantibody panel combined with LDCT), respectively. The combined risk score (CRS), based on the 10-autoantibody panel, sex, and imaging maximum diameter, effectively stratified the risk for Early-LUAD. Individuals with 10 ≤ CRS ≤ 25 and CRS > 25 indicated a higher risk of Early-LUAD compared to the reference (CRS < 10), with adjusted odds ratios of 5.28 [95% confidence interval (CI): 3.18-8.76] and 9.05 (95% CI: 5.40-15.15), respectively. This novel panel of IgG and IgM autoantibodies offers a complementary approach to LDCT in distinguishing Early-LUAD from benign nodules. Show less
This study aimed to identify heterogeneous patterns of medical coping modes (MCM) and to examine the moderating role of social support in the relationship between these patterns and social disability Show more
This study aimed to identify heterogeneous patterns of medical coping modes (MCM) and to examine the moderating role of social support in the relationship between these patterns and social disability in young and middle-aged patients after percutaneous coronary intervention (PCI). A cross-sectional study was conducted among 129 post-PCI patients from a single center in China. Participants completed the Medical Coping Modes Questionnaire (MCMQ), the Social Support Rating Scale (SSRS), and the Social Disability Screening Schedule (SDSS). Latent profile analysis (LPA) was used to identify distinct coping patterns. The moderation effect of social support was tested using the Johnson-Neyman technique. Two distinct coping profiles were identified via LPA: "Adaptive Copers" (55.1%), characterized by higher confrontation and lower avoidance/resignation, and "Maladaptive Copers" (44.9%), showing the opposite pattern. A counterintuitive finding emerged, with the Maladaptive Copers reporting significantly lower social disability scores. Furthermore, beyond this profile differentiation, social support demonstrated a significant U-shaped moderating effect in the coping-disability relationship. Its moderating role was statistically significant only at very low (<39.884) and very high (>52.924) levels of support. This study reveals two key findings: first, post-PCI patients are heterogeneous in coping, comprising adaptive and maladaptive subgroups; second, the impact of these coping styles on social disability is non-linearly moderated by social support. Clinicians should assess both coping profiles and social support levels to tailor interventions effectively. Show less
Mutations in the sarcomere protein, particularly in cardiac myosin binding protein C gene ( We used multi-omics approaches and super-resolution imaging to explore the effects of MyBPC3 P459fs mutation Show more
Mutations in the sarcomere protein, particularly in cardiac myosin binding protein C gene ( We used multi-omics approaches and super-resolution imaging to explore the effects of MyBPC3 P459fs mutation on humans and cells. HCM patients carrying MyBPC3 P459fs mutation (MyBPC3-P459fs HCMs) and healthy controls (HCs) were evaluated for myocardial function using both conventional and advanced echocardiography. In parallel, H9C2 myocardial cells infected with either MyBPC3 P459fs mutation (P459fs cells) or its wild type (WT cells) were investigated for myocardial fiber formation and the potential pathways behind this using super-resolution imaging and metabolomics and proteomics. First, conventional and advanced echocardiography showed that MyBPC3-P459fs HCMs exhibited left ventricular diastolic and systolic dysfunction. Subsequently, super-resolution imaging indicated that P459fs cells formed fewer and shorter myocardial fibers in the cytoplasm compared to WT cells. Moreover, our metabolomic and proteomic data suggested several key components of mitochondrial membrane integrity, myocardial remodeling, myocardial energy metabolism, oxidative stress, inflammation, and actin binding capacity were significantly altered in response to P459fs mutation. This investigation indicated myocardial dysfunction and myocardial fiber disarray in clinical HCMs with MyBPC3 P459fs mutation and added potential pathways underlying this. These findings provided a link between the observed structural and functional disorders in MyBPC3 P459fs mutation and its onset of HCM pathogenesis and might have a significant translational contribution to effective treatment in HCM patients with MyBPC3 P459fs mutation. Show less
Dyslipidemia is a central driver in the initiation and progression of atherosclerosis (AS). The chronic inflammation and endothelial injury triggered by dyslipidemia are key pathological events in AS Show more
Dyslipidemia is a central driver in the initiation and progression of atherosclerosis (AS). The chronic inflammation and endothelial injury triggered by dyslipidemia are key pathological events in AS development. Elucidating the molecular network underlying dyslipidemia and developing precise interventions are critical for achieving precision prevention and treatment of AS. Recent studies have demonstrated that sterol regulatory element-binding protein 1 (SREBP1) and lipoprotein(a) [Lp(a)] play pivotal roles in the regulation of lipid synthesis and transport. Additionally, gut microbiota-derived metabolites, such as trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), can activate inflammatory pathways and promote lipid deposition via inter-organ signaling axes, thereby accelerating the progression of AS. However, clinical studies have revealed that even when low-density lipoprotein cholesterol (LDL-C) levels are within the recommended range, a significant number of patients continue to experience cardiovascular events. This indicates the widespread presence of "residual risk". Such residual risk is primarily driven by elevated non-high-density lipoprotein cholesterol (non-HDL-C), abnormal levels of Lp(a), and imbalances in the triglyceride to HDL-C (TG/HDL-C) ratio, highlighting the limitations of traditional therapies in comprehensive lipid profile management. Emerging targeted therapies, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, small interfering RNA (siRNA)-based treatments, and Lp(a)-lowering agents like pelacarsen, represent promising strategies for more precise lipid modulation. With the continuous advancement of related research, the precise management of AS will increasingly rely on deeper mechanistic insights and individualized therapeutic strategies. Current strategies for AS prevention and treatment focus on understanding key pathways, including lipid metabolism, inflammation, and vascular dysfunction, to develop targeted therapies. The integration of the 2023 Chinese Guidelines for Lipid Management, imaging, and AI-assisted decision-making will promote data-driven, precision medicine. Personalized drug selection, efficacy monitoring, and long-term follow-up will optimize clinical outcomes and enhance prevention strategies for high-risk patients. Show less
A comprehensive understanding of protein corona (PC) composition is critical for engineering nanoparticles (NPs) with optimal safety and therapeutic performance, because the PC governs NP pharmacokine Show more
A comprehensive understanding of protein corona (PC) composition is critical for engineering nanoparticles (NPs) with optimal safety and therapeutic performance, because the PC governs NP pharmacokinetics, biodistribution, and cellular interactions. Yet systematic analyses are hampered by the absence of standardized, richly annotated data sets. Here, we introduce the Protein Corona Database (PC-DB), which compiles data from 83 studies (2000-2024) and integrates 817 NP formulations with quantitative profiles of 2497 adsorbed proteins. The PC-DB exposes pronounced heterogeneity in NP materials (metal 28.8%, silica 22.8%, lipid-based 14.8%), surface modifications, sizes (1-1400 nm), and ζ-potentials (-70 to +70 mV). Subsequent meta-analysis shows that silica, polystyrene, and lipid-based NPs smaller than 100 nm with moderately negative to neutral ζ-potentials preferentially bind the lipoproteins APOE and APOB-100, which are linked to receptor-mediated uptake and enhanced delivery efficiency. In contrast, metal and metal-oxide NPs carrying highly negative surface charge enrich complement component C3, indicating a greater likelihood of immune recognition and clearance. Interpretable machine learning models (LightGBM and XGBoost; ROC-AUC > 0.85) confirm NP size, ζ-potential, and incubation time as the most influential predictors of protein adsorption. These results delineate how physicochemical parameters dictate PC composition and illustrate the power of predictive modeling to guide rational NP design. Show less
Diabetes constitutes a risk factor for cognitive impairment, whereas insulin resistance serves as the shared pathogenesis underlying both diabetes and cognitive decline. The use of metformin for treat Show more
Diabetes constitutes a risk factor for cognitive impairment, whereas insulin resistance serves as the shared pathogenesis underlying both diabetes and cognitive decline. The use of metformin for treating cognitive impairment remains controversial. The present study found that hesperetin, a flavanone derived from citrus peel, enhanced metformin's efficacy in reducing blood sugar levels, improving insulin sensitivity, and ameliorating cognitive impairment in diabetic rats. Additionally, it reduced the required dosage of metformin to one-third of its conventional dose. Transcriptome analysis and 16S rRNA sequencing revealed that the activation of insulin and cyclic-adenosine monophosphate response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathways benefited from the regulation of gut microbiota and the promotion of short-chain fatty acid (SCFA) producers such as Show less
Qingyu Zhang, Zongliang Yu · 2025 · International journal of general medicine · added 2026-04-24
Heart failure with preserved ejection fraction (HFpEF) is becoming increasingly prevalent, yet clinical practice lacks specific biomarkers, early diagnostic tools, and reliable risk assessment methods Show more
Heart failure with preserved ejection fraction (HFpEF) is becoming increasingly prevalent, yet clinical practice lacks specific biomarkers, early diagnostic tools, and reliable risk assessment methods. Given the growing burden of HFpEF, identifying novel diagnostic markers is crucial. This study investigates the diagnostic potential of apolipoprotein C3 (ApoC3) in HFpEF and its correlation with ventricular structure. We analyzed data from HFpEF patients admitted to the Kunshan Branch of Gusu College of Nanjing Medical University and the First People's Hospital of Kunshan (March-December 2023). Controls included HFrEF+HFmrEF patients and healthy individuals. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of ApoC3 in all collected cases. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance of ApoC3 alone and combined with the fibrinogen-to-albumin ratio (FAR) in plasma, and the relative wall thickness (RWT) in echocardiography for HFpEF. After exclusions, 80 HFpEF patients (39 male, 41 female), 41 HFrEF+HFmrEF patients (27 male, 14 female), and 79 healthy controls (53 male, 26 female) were included. ApoC3 levels were significantly higher in HFpEF (63136.03±12,113.07 ng/mL) than in HFrEF+HFmrEF (55580.84±13,685.35 ng/mL) and controls (53090.31±5893.25 ng/mL, P<0.001). ROC analysis demonstrated that ApoC3 alone (AUC=0.836) and the combined index (ApoC3+FAR+RWT, AUC=0.891) effectively distinguished HFpEF. Both also aided in differentiating HFpEF from HFrEF+HFmrEF (AUC=0.702 vs 0.823). ApoC3 is a promising biomarker for HFpEF diagnosis, and the combined index (ApoC3+FAR+RWT) enhances diagnostic accuracy. These findings may improve early detection and clinical management of HFpEF. Show less
Yifei Dou, Ying Li, Meng Zhang · 2025 · Wei sheng yan jiu = Journal of hygiene research · added 2026-04-24
To explore the latent classes and their associated factors of sleep quality among police officers, and to analyze the potential heterogeneity in sleep quality within this population. A total of 1162 p Show more
To explore the latent classes and their associated factors of sleep quality among police officers, and to analyze the potential heterogeneity in sleep quality within this population. A total of 1162 police officers were selected using cluster random sampling in the Inner Mongolia Autonomous Region between September and December 2021. Participants completed a basic information questionnaire and the Pittsburgh sleep quality index(PSQI). Latent profile analysis(LPA) was employed to examine heterogeneity in sleep quality, and multinomial Logistic regression was used to identify associated factors of the latent profiles. The mean age of participants was(43.08±8.98) years. The sample comprised 920 males(79.2%) and 242 females(20.8%), 987(84.9%) were married and 175(15.1%) were single, 644(55.4%) had a high school education or below, and 518(44.6%) had college education or above. By department, 607(52.2%) worked in grassroots police stations, 200(17.2%) were criminal police, and 355(30.6%) served in other units. Significant heterogeneity in sleep quality was identified, revealing four distinct latent classes: good sleep group(n=821, 70.6%), moderate sleep group(n=46, 4.0%), sleep-disordered group(n=249, 21.4%), and medication-assisted sleep group(n=46, 4.0%). Using the good sleepers as the reference group, multinomial Logistic regression indicated that older age was a significant risk factor for belonging to the medication-assisted sleep group(OR=1.348, 95%CI 1.078-1.822). Higher education level was a protective factor against membership in the moderate sleep group(OR=4.101, 95%CI 1.304-12.893). Serving as a grassroots police station officer or criminal police officer was a significant risk factor for membership in both the moderate sleep group(OR = 3.329, 95%CI 1.338-8.284; OR=4.188, 95%CI 1.415-12.396) and sleep-disordered group(OR=1.701, 95%CI 1.196-2.420; OR=1.587, 95%CI 1.073-2.533). Sleep quality among police officers demonstrates significant heterogeneity. Age, police department assignment, and educational level are key associated factors of distinct latent classes of sleep quality. Show less
no PDFDOI: 10.19813/j.cnki.weishengyanjiu.2025.05.015
Sepsis is a severe systemic infection that can result in organ dysfunction and mortality. Dyslipidemia emerges as a key player in the intricate web of sepsis pathogenesis. Yet, the causal relationship Show more
Sepsis is a severe systemic infection that can result in organ dysfunction and mortality. Dyslipidemia emerges as a key player in the intricate web of sepsis pathogenesis. Yet, the causal relationship between blood lipid profiles and sepsis risk remains uncertain. This study aims to investigate the association between genetically predicted lipid traits, drug targets, and sepsis. The UK Biobank's Genome-wide association studies (GWAS) produced data on lipid and apolipoprotein characteristics. Four independent GWAS datasets were used to generate the sepsis statistics. The study utilized the two-sample Mendelian randomization (MR) approach, which incorporates multivariable (MVMR) models, to assess the correlations between sepsis risk and lipid-related parameters. To gain further insight, expression quantitative trait loci (eQTL) data were used to investigate the significant drug targets for lipid-lowering. Increasing ApoA-1 levels was associated with a diminished risk of sepsis (under 75) (OR 0.927, 95% CI 0.861-0.999; p = 0.047). This inverse correlation persevered even after performing multivariable MR. Elevated levels of HDL-C were associated with a decreased risk of sepsis (under 75) (OR 0.897, 95% CI 0.838-0.960; P = 0.002) and incidence of sepsis (OR 0.883, 95% CI 0.820-0.951; P = 0.001), which was consistent across sensitivity analyses. Furthermore, a decrease in total cholesterol exhibited a causal effect on sepsis in multivariable MR (OR 0.779, 95% CI 0.642-0.944; P = 0.01). The genetic variants related to lowering LDL-C, located near the HMGCR and LDLR genes, were predicted to elevate the risk of sepsis. Moreover, genetic mimicry near the ANGPTL3 and LPL gene suggested that reducing the activity of ANGPTL3 and LPL (mimicking antisense anti-ANGPTL3 and LPL agents) was forecasted to decrease sepsis risk. Genetically inferred elevated ApoA-1, total cholesterol, and HDL-C manifest a protective effect against sepsis. Within the 9 lipid-lowering drug targets investigated ANGPTL3 and LPL exhibit potential as candidate drug targets for sepsis. Show less
Discs large homolog 2 (DLG2) has been implicated in cancer development, yet its role in cervical cancer remains unclear. This study aims to explore the regulatory mechanism of DLG2 in cervical cancer Show more
Discs large homolog 2 (DLG2) has been implicated in cancer development, yet its role in cervical cancer remains unclear. This study aims to explore the regulatory mechanism of DLG2 in cervical cancer and its clinical implications. Quantitative reverse transcription polymerase chain reaction and western blotting assays were employed to detect RNA and protein expression, respectively. Colony formation assay, 5-Ethynyl-2'-deoxyuridine assay, flow cytometry, and transwell assays were conducted for cell functional analysis. A xenograft mouse model assay was performed to analyze tumor tumorigenesis in vivo. m6A RNA immunoprecipitation assay was used to analyze the association of METTL3 and DLG2. DLG2 was underexpressed in cervical cancer tissues and cells. Elevating DLG2 levels significantly suppressed cervical cancer cell proliferation, migration, and invasion, while promoting apoptosis. Additionally, DLG2 overexpression led to the deactivation of the Hippo/YAP signaling pathway. In vivo, DLG2 overexpression was shown to reduce tumor formation. We also discovered that METTL3 destabilized DLG2 mRNA through an m6A-dependent mechanism. Moreover, lowering DLG2 expression mitigated the effects of METTL3 silencing on cervical cancer cell malignancy. DLG2 acted as a tumor suppressor in cervical cancer by inhibiting the Hippo/YAP signaling pathway. The METTL3-dependent regulation of DLG2 mRNA stability could be a critical factor in cervical cancer progression. 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
Colorectal cancer (CRC) is a prevalent digestive system malignancy accompanied by peritoneal metastasis occurring in 7% of cases. Methyltransferase-like 3 (METTL3) promoted the progression of CRC wher Show more
Colorectal cancer (CRC) is a prevalent digestive system malignancy accompanied by peritoneal metastasis occurring in 7% of cases. Methyltransferase-like 3 (METTL3) promoted the progression of CRC whereas its function in peritoneal metastasis was incompletely understood. Here, we found that METTL3 was upregulated in peritoneal metastasis tissues of CRC patients compared with CRC tissues. By sequencing the mRNA of above tissues, we discovered that METTL3-mediated N6-methyladenosine (m6A) modification regulated the downstream target Show less
This study aimed to identify the latent profiles of cognitive function among community-dwelling and institutionalized older adults, and to examine their associated influencing factors, in order to inf Show more
This study aimed to identify the latent profiles of cognitive function among community-dwelling and institutionalized older adults, and to examine their associated influencing factors, in order to inform the development of targeted interventions. A convenience sampling method was used to select 6,708 elderly people aged 60 years and older from six communities and nine long-term care institutions across China, who were assessed using a general information questionnaire, Mini-Mental State Examination (MMSE), the Frailty Scale, the Anxiety Scale, the Depression Scale, and the Pittsburgh Sleep Quality Index. Latent profile analysis (LPA) was performed based on the MMSE scores, and multiple logistic regression was used to analyse the influencing factors of cognitive function categories. A total of three cognitive function profiles were identified: High cognitive Function group (41.2%), Moderate Cognitive Function Group (48.2%) and Low cognitive Function group (10.7%). Higher Frailty [odds ratio (ORs) = 1.070-1.246], higher depressive symptom scores (OR = 1.059-1.191) and poorer sleep quality (higher PSQI; OR = 1.088) were associated with higher odds of belonging to the Moderate/Low cognitive profiles, whereas adequate social support (Yes vs. No; OR = 0.530-0.696), selected middle-income categories versus ≥¥6,000 in per-capita monthly household income (OR = 0.462-0.735) and male sex (OR = 0.556-0.876) were associated with lower odds. Cognitive function among older adults can be classified into three distinct latent profiles, each associated with different influencing factors. These findings underscore the need for stratified and personalized interventions at the community level to support stratified screening and tailored community programs; given the cross-sectional design, these associations do not establish causality or intervention effects. Show less
Pancreatic cancer (PC), characterized by the absence of effective biomarkers and therapies, remains highly fatal. Data regarding the correlations between PC risk and individual plasma proteome known f Show more
Pancreatic cancer (PC), characterized by the absence of effective biomarkers and therapies, remains highly fatal. Data regarding the correlations between PC risk and individual plasma proteome known for minimally invasive biomarkers are scarce. Here, we analyzed 1,345 human plasma proteins using proteome-wide association studies, identifying 78 proteins significantly associated with PC risk. Of these, four proteins (ROR1, FN1, APOA5, and ABO) showed the most substantial causal link to PC, confirmed through Mendelian randomization and colocalization analyses. Data from two clinical cohorts further demonstrated that FN1 and ABO were notably overexpressed in both blood and tumor samples from PC patients, compared to healthy controls or para-tumor tissues. Additionally, elevated FN1 and ABO levels correlated with shorter median survival in patients. Multiple drugs targeting FN1 or ROR1 are available or in clinical trials. These findings suggest that plasma protein FN1 associated with PC holds potential as both prognostic biomarkers and therapeutic targets. Show less
This study aimed to explore the career adaptability status of cardiovascular specialist nurses (CSNs) through latent profile analysis (LPA), identify distinct subgroups and their demographic features, Show more
This study aimed to explore the career adaptability status of cardiovascular specialist nurses (CSNs) through latent profile analysis (LPA), identify distinct subgroups and their demographic features, and determine factors influencing different adaptability categories. CSNs play a vital role in treating and rehabilitating patients with cardiovascular conditions. However, the existing literature offers limited insights into the career adaptability of CSNs in China. A multicenter, cross-sectional survey involving 659 Chinese CSNs was conducted. LPA was utilized to classify career adaptability profiles based on responses to the Career Adaptation Abilities Scale Short Form (CAAS-SF). Influencing factors were assessed using the Conditions of Work Effectiveness Questionnaire-II (CWEQ-II) and the General Self-Efficacy Scale (GSES). Differences among identified profiles were analyzed through ANOVA, chi-square tests, and multinomial logistic regression to explore relevant socio-demographic characteristics and influencing variables. A four-profile model provided the best fit, identifying groups labeled as “high adaptability” (Class 4, These findings provide evidence to assist nursing administrators in developing training programs to enhance CSNs’ career adaptability. The variables identified as associated with profile membership may enable more tailored training strategies. Show less
Myeloid/lymphoid neoplasms with tyrosine kinase gene fusions (MLN-TK) are rare hematologic malignancies characterized by recurrent kinase rearrangements, including
To reveal the molecular basis of knee osteoarthritis (KOA) with Yang deficiency and blood stasis syndrome by analyzing the gene expression profiles in synovial fluid and blood of KOA patients with thi Show more
To reveal the molecular basis of knee osteoarthritis (KOA) with Yang deficiency and blood stasis syndrome by analyzing the gene expression profiles in synovial fluid and blood of KOA patients with this syndrome. A total of 80 KOA patients were recruited from October 2022 to June 2024, including 40 cases in the non- Logistic regression analysis showed that compared with KOA patients with non-Yang deficiency and blood stasis syndrome, those with Yang deficiency and blood stasis syndrome had increased BMI, LDL, fibrinogen, total cholesterol, and D-dimer, and decreased HDL, with a clear correlation between the two groups. There were 562 differential genes in the blood, among which 322 were up-regulated and 240 were down-regulated;755 differential genes were found in the synovial fluid, with 350 up-regulated and 405 down-regulated. KEGG signaling pathway analysis of synovial fluid revealed changes in lipid metabolism-related pathways, including cholesterol metabolism, fatty acid metabolism, and PPARG signaling pathway. Analysis of the involved differential genes identified 6 genes in synovial fluid that were closely related to lipid metabolism, namely LRP1, LPL, ACOT6, TM6SF2, DGKK, and PPARG. Subsequently, PCR and immunohistochemical verification were performed using synovial fluid and cartilage samples, and the results were consistent with those of microarray sequencing. This study explores the clinical and genomic correlation between traditional Chinese medicine syndromes and knee osteoarthritis from the perspective of lipid metabolism, and proves that abnormal lipid metabolism is closely related to KOA with Show less
Pentadecanoic acid (PEA), an odd-chain fatty acid derived from diet by the gut microbiome, has garnered increasing attention for its systemic health-promoting properties. Its potential role in bladder Show more
Pentadecanoic acid (PEA), an odd-chain fatty acid derived from diet by the gut microbiome, has garnered increasing attention for its systemic health-promoting properties. Its potential role in bladder cancer (BC) occurrence and invasion, however, remains unclear. Large-scale cohorts' analyses were performed to assess the association between dietary PEA and BC occurrence and invasion. In vitro and in vivo experiments, including EJ and T24 BC cell assays and a BBN-induced mouse model, were conducted to experimentally assess the impact of PEA on BC. Serum proteomics, gut microbiome, and targeted fecal lipidomics analyses were employed to explore the underlying mechanisms. Dietary PEA was negatively associated with BC occurrence and invasion in cohort analyses. PEA suppressed EJ and T24 BC cell migration, invasion, and proliferation, while inhibiting BC development in a BBN-induced mouse model. In vivo serum proteomics identified differentially expressed lipid-related proteins (e.g., Apoe and Apob) following PEA treatment, implicating its modulation of lipid metabolism pathways. Considering the essential role of the gut-bladder axis, the gut microbiome analysis exhibited that PEA markedly altered bacteria (e.g., g_Alistipes) and fungi (e.g., o_Erysiphales, g_Teberdinia, and g_Gibberella), with concomitant lipid metabolism changes. Furthermore, targeted fecal lipidomics demonstrated the shifts in key lipids, such as phosphatidylethanolamines (PE) involved in essential lipid clusters, suggesting regulation by gut microbiome linked to BC development. Collectively, our findings demonstrate that PEA mitigates BC by reshaping the gut microbiome and modulating lipid metabolism, providing new insights into its molecular and therapeutic potential. Show less
Sparstolonin B (SSNB) and Curcumin (Cur), from a pair of compatible herbs, were previously identified as anti-inflammation and T helper 17 (Th17) modulation reagents. However, their compatible roles i Show more
Sparstolonin B (SSNB) and Curcumin (Cur), from a pair of compatible herbs, were previously identified as anti-inflammation and T helper 17 (Th17) modulation reagents. However, their compatible roles in atherosclerosis (AS) and underlying mechanisms remain uninvestigated. In vivo, the apoE The gene-disease interaction and hub gene network reveals Th17-associated genes in the pathogenesis of atherosclerosis. In vitro, SSNB and Cur reduced oxLDL-induced BMDC activation by downregulating CD36. SSNB showed stronger inhibition to inflammatory activation of DC, while Cur more intensively suppressed co-stimulatory molecules. For the Th17/Treg bias in co-culture of BMDC and CD4 Our findings reveal, for the first time, that SSNB and Cur alleviate AS by modulating Th17-stromal cell interactions, with the IL-17RA-TAK1-NF-κB pathway as a related mediator. Notably, SSNB and Cur exhibit distinct anti-atherogenic roles. SSNB primarily targets TLR4/CD36 to inhibit DC activation, Th17 differentiation, VSMC inflammation and mainly inhibited TAK1 phosphorylation, while Cur more significant inhibited macrophage inflammation, and more directly inhibited NF-κB P65 phosphorylation. This study will be valuable for developing novel and precise adjuvant therapies for AS. Show less
To investigate the key regulatory genes and pathways related to growth traits in the Dongtingking crucian carp (Carassius auratus indigentiaus), the transcriptomes of brain, intestine, and muscle tiss Show more
To investigate the key regulatory genes and pathways related to growth traits in the Dongtingking crucian carp (Carassius auratus indigentiaus), the transcriptomes of brain, intestine, and muscle tissues were sequenced at early juvenile stage using RNA-Seq from two groups with extreme growth rates (fast-growing and slow-growing). A total of 65, 184, and 130 differentially expressed genes (DEGs) were detected in the brain, intestine, and muscle, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted that the PPAR signaling pathway, Insulin/PI3K/Akt/mTOR/FoxO/AMPK pathway, and Protein digestion and absorption pathways are crucial for growth in this species. Based on the transcriptome data, 32 key DEGs were identified, mainly participating in processes such as cell proliferation and differentiation, growth, development, and metabolism. Prominent examples are cyclic AMP-responsive element-binding protein 5 (creb5b), forkhead box protein O1-A (foxo1a), transcription factor AP-1-like (jun), lipoprotein lipase-like (lpl), angiopoietin-like 4 (angptl4), and egl nine homolog 3-like (egln3). This study enhances the understanding of the genetic factors and regulatory mechanisms responsible for variations in growth rates and provides a valuable basis for further studies on the regulatory mechanisms of growth in C. auratus indigentiaus. Show less
The deer antler is a fully regenerable and the fastest-growing osseous organ. Circular RNA (circRNA), a novel member of the non-coding RNA family, has significant research potential and crucial roles Show more
The deer antler is a fully regenerable and the fastest-growing osseous organ. Circular RNA (circRNA), a novel member of the non-coding RNA family, has significant research potential and crucial roles in biological processes. This study aims to explore the impact and mechanisms of circRNA505 on antler chondrocytes. Functional experiments demonstrated that m5C-modified circRNA505 inhibits antler chondrocyte proliferation, enhances osteogenic differentiation, and facilitates cellular glycolysis. Mechanistically, dual luciferase and AGO2-RIP assays revealed a direct binding relationship between circRNA505, miR-127, and p53. Rescue assays further showed that circRNA505 affects cell proliferation and differentiation through the miR-127/p53 axis. Meanwhile, RNA Antisense Purification (RAP) screening and analysis of related proteins binding to circRNA505 demonstrated that circRNA505 binds to LDHA and increases the level of LDHA phosphorylation through FGFR1 to promote cellular glycolysis by FISH-IF, RIP, and Western blot experiments. Additionally, Me-RIP assays confirmed the m5C methylation modification of circRNA505. NSUN2 mediates the m5C modification of circRNA505, affecting its stability, while the m5C reader ALYREF promotes the nuclear export of circRNA505 in an ALYREF-dependent manner. This study provides new insights into the regulatory mechanisms underlying rapid antler development. Show less
Lipid metabolism disorders have been confirmed to be closely related to kidney injury caused by adriamycin (ADR) and obesity, respectively. However, it has not been explored whether lipid metabolism d Show more
Lipid metabolism disorders have been confirmed to be closely related to kidney injury caused by adriamycin (ADR) and obesity, respectively. However, it has not been explored whether lipid metabolism disorders appear progressively more severe after ADR-based chemotherapy in the obese state, and the specific molecular mechanism needs to be further clarified. This study was designed to examine the role of p53-fibroblast growth factor 21 (FGF21) axis in ADR-induced renal injury aggravated by high-fat diet (HFD). We engineered Fgf21 KO mice and used long-term (4 months) and short-term (0.5 months) HFD feeding, and ADR-injected mice, as well as STZ-induced type 1 diabetic mice and type 2 (db/db) diabetic mice to produce an in vivo model of nephrotoxicity. The specific effects of p53/FGF21 on the regulation of lipid metabolism disorders and its downstream mediators in kidney were subsequently elucidated using a combination of functional and pathological analysis, RNA-sequencing, molecular biology, and in vitro approaches. Long-term HFD feeding mice exhibited compromised effects of FGF21 on alleviation of renal dysfunction and lipid accumulation following ADR administration. However, these impairments were reversed by p53 inhibitor (pifithrin-α, PFT-α). PFT-α sensitized FGF21 actions in kidney tissues, while knockout of Fgf21 impaired the protective effects of PFT-α on lipid metabolism. Mechanistically, p53 impaired the renal expression of FGF receptor-1 (FGFR1) and thereby developed gradually into FGF21 resistance via inhibiting hepatocyte nuclear factor 4 alpha (HNF4α)-mediated transcriptional activation of Fgfr1. More importantly, exogenous supplementation of FGF21 or PFT-α could not only alleviate ADR-induced lipid metabolism disorder aggravated by HFD, but also reduce lipid accumulation caused by diabetic nephropathy. Given the difficulties in developing the long-acting recombinant FGF21 analogs for therapeutic applications, sensitizing obesity-impaired FGF21 actions by suppression of p53 might be a therapeutic strategy for maintaining renal metabolic homeostasis during chemotherapy. Show less
To identify latent profiles of demoralization among older adults with disabilities, analyze their influencing factors, and examine their associations with active aging. From February to July 2025, a c Show more
To identify latent profiles of demoralization among older adults with disabilities, analyze their influencing factors, and examine their associations with active aging. From February to July 2025, a convenience sample of 411 older adults with disabilities was recruited from a tertiary hospital in Anhui Province, China. Data were collected using a general information questionnaire, the Chinese version of the Demoralization Scale, and the Active Aging Scale. Latent profile analysis (LPA) was performed based on demoralization subscale scores. Univariate and multinominal analyses were employed to investigate the influencing factors, and the Kruskal-Wallis The prevalence of demoralization syndrome was 49.1%. LPA identified three distinct profiles: the Well-Adapted Group (53.3%), the Disheartened-Helpless Group (23.8%), and the Fully Demoralized Group (22.9%). The Kruskal-Wallis Nearly half of the older adults with disabilities experienced demoralization, with heterogeneous subgroups identified. The active aging status of demoralized subgroups requires urgent attention. These findings suggest the need for targeted interventions tailored to the characteristics of each profile to improve mental health and promote active aging in this population. Show less
To evaluate the efficacy and safety of inclisiran in the treatment of hypercholesterolemia. Randomized controlled trials comparing inclisiran with a placebo were searched until April 2024. Overall, 8 Show more
To evaluate the efficacy and safety of inclisiran in the treatment of hypercholesterolemia. Randomized controlled trials comparing inclisiran with a placebo were searched until April 2024. Overall, 8 studies involving 4947 patients were included. Inclisiran reduced low-density lipoprotein cholesterol (mean difference [MD]: -46.95 %; 95 % confidence interval [CI]: -53.26 to -40.46; P < 0.05), proprotein convertase subtilisin/kexin type 9 (MD: -70.80 %; 95 % CI: -76.52 to -65.08; P < 0.05), serum total cholesterol (MD: -29.47 %; 95 % CI: -32.56 to -26.39; P < 0.05), non-high-density lipoprotein cholesterol (MD: -40.46 %; 95 % CI: -45.24 to -35.68; P < 0.05), apolipoprotein B (MD: -36.77 %; 95 % CI: -40.94 to -32.61; P < 0.05), and lipoprotein(a) (MD: -20.04 %; 95 % CI: -24.2 to -15.87; P < 0.05) levels but increased high-density lipoprotein cholesterol level (MD: 6.09 %; 95 % CI: 3.63 to 8.55; P < 0.05). The incidences of adverse events, serious adverse events, headache, nasopharyngitis, and muscular adverse reactions were not significantly different between the inclisiran and placebo groups. Inclisiran reduced the incidence of cardiovascular adverse reactions (odds ratio [OR] = 0.79; 95 % CI: 0.65 to 0.96; P = 0.02) and increased the incidence of injection-site reactions (OR = 4.79; 95 % CI: 2.18 to 10.52; P < 0.05). Inclisiran is effective in treating hypercholesterolemia and has a good safety profile. Show less
To investigate the regulatory role of MACF1 and its upstream transcriptional control in focal adhesion remodeling and tumor progression in lung adenocarcinoma (LUAD). We employed in vitro loss- and ga Show more
To investigate the regulatory role of MACF1 and its upstream transcriptional control in focal adhesion remodeling and tumor progression in lung adenocarcinoma (LUAD). We employed in vitro loss- and gain-of-function assays using shRNA-mediated knockdown and ectopic overexpression of MACF1 and NR2F1 in LUAD cell lines (H1299 and Calu-3). Cell proliferation, adhesion, and migration were assessed by CCK-8, EdU, crystal violet, and Transwell assays. In vivo tumor growth and metastasis were evaluated using subcutaneous and tail vein xenograft models in nude mice. RNA-seq and GSEA were performed to identify MACF1-regulated pathways, followed by nuclear-cytoplasmic fractionation, dual-luciferase reporter assays, and immunofluorescence to assess WNT/β-catenin activity. ChIP-qPCR and ChIP-seq data from ENCODE were used to validate NR2F1 binding to the MACF1 promoter. MACF1 knockdown significantly suppressed LUAD cell proliferation, DNA replication, adhesion, and migration, and reduced tumor burden and lung metastases in vivo. Mechanistically, MACF1 activated WNT/β-catenin signaling by promoting CTNNB1 nuclear translocation, which upregulated focal adhesion genes (Paxillin, FAK, ITGB1). CTNNB1 agonist TWS119 restored focal adhesion in MACF1-deficient cells. Bioinformatic prediction and ChIP validation identified NR2F1 as a transcription factor directly targeting the MACF1 promoter. NR2F1 deficiency reduced MACF1 expression and phenocopied its functional loss, while MACF1 overexpression rescued the impaired phenotype. Our study uncovers a previously unrecognized NR2F1-MACF1-WNT axis that drives focal adhesion formation and LUAD progression. Targeting this regulatory circuit may offer new avenues for anti-metastatic therapy in lung adenocarcinoma. 1. NR2F1 is identified as a direct upstream transcription factor that activates MACF1 expression in LUAD. 2. MACF1 promotes LUAD cell proliferation, adhesion, and migration by enhancing focal adhesion assembly. 3. MACF1 activates the WNT/CTNNB1 signaling cascade, facilitating CTNNB1 nuclear translocation and downstream target expression. 4. Loss of MACF1 impairs focal adhesion formation and metastatic potential both in vitro and in xenograft and tail vein models. 5. The NR2F1-MACF1-WNT axis represents a novel regulatory circuit driving LUAD metastasis and offers potential therapeutic targets. Show less