👤 Chongjing Shi

Calcific aortic valve disease (CAVD) involves pathological mineralization, but the roles of chemokine signaling and ferroptosis remain unclear. This study investigated the regulatory function of C-C motif chemokine ligand 5 (CCL5) in CAVD progression via the chemokine pathway and ferroptosis. Bioinformatics analysis and single-cell RNA sequencing analysis were performed to identify hub genes and potential cell types. Human aortic valve interstitial cells (VICs) were treated with osteogenic medium (OM) to induce calcification. Apoe CCL5 was identified as a key hub gene in CAVD. Knockdown of CCL5 significantly attenuated OM-induced VICs calcification, osteogenic differentiation, oxidative stress, and ferroptosis. Similar protective effects were observed in vivo, with reduced valve thickening and calcification in Apoe CCL5 promoted CAVD progression by activating the chemokine signaling pathway to induce ferroptosis. Targeting CCL5 may offer a novel therapeutic strategy for CAVD. Show less

Alport syndrome (AS) is the most common inherited glomerular disease among patients with chronic kidney disease. With exome sequencing now widely used in clinical practice, pathogenic variants in Alport-related genes (COL4A3/COL4A4/COL4A5) are increasingly identified in patients with diverse phenotypes, including proteinuria‑predominant disease and kidney failure of unknown etiology. Diagnostic complexity further increases when COL4A3/COL4A4/COL4A5 variants are co‑inherited with pathogenic variants associated with other genetic kidney disorders. We reported a 31‑year‑old male presenting with kidney failure, significant proteinuria, familial hematuria and hyperlipidemia. Whole‑exome sequencing (WES) identified two pathogenic variants: a hemizygous COL4A5 variant (c.2105G > A; p.Gly702Asp) and a heterozygous APOE Kyoto variant (c.127C > T; p.Arg43Cys). Given the potential dual diagnosis of AS and lipoprotein glomerulopathy (LPG), a kidney biopsy was performed. Histologic examination revealed uneven thickness of the glomerular basement membrane consistent with the diagnosis of AS, but no LPG-related lesions were observed, indicating incomplete penetrance of APOE Kyoto variant. Cascade family screening detected APOE Kyoto variant in the patient's father and elder sister, both of whom lacked proteinuria until follow-up period. This case highlights the complementary role of kidney biopsy alongside WES in AS with complex genetic mechanisms. It also illustrates the incomplete penetrance of APOE Kyoto, common among Chinese carriers. Show less

Conventional nanocarriers are readily cleared by macrophages in the liver, with only a minimal fraction reaching hepatocytes. This limitation has been effectively overcome in clinically approved lipid nanoparticles (LNPs) through the incorporation of ionizable lipids. Inspired by this property, we explored whether incorporating ionizable lipids into the lipid bilayer membrane of mesoporous silica nanoparticles (silicasomes) could similarly enhance their hepatic cellular uptake. We developed ionizable silicasomes (I-silicasomes) and systematically compared them with ionizable liposomes (I-liposomes), as well as their conventional counterparts (C-silicasomes and C-liposomes). Surprisingly, I-silicasomes did not enhance hepatocyte uptake Show less

Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have revolutionized cancer therapy, yet primary and acquired resistance remain major clinical obstacles. Dysregulated angiogenesis fuels the development of an immunosuppressive tumor microenvironment, while crosstalk between immunity and angiogenesis further propels tumor immune evasion and treatment resistance. The present study aimed to establish a penpulimab-resistant model, delineate anti-PD-1 resistance traits via single-cell RNA sequencing, and unravel the precise mechanisms through which anlotinib-an anti-angiogenic agent-mitigates penpulimab resistance. These findings offer insights to guide clinical management of immune-pretreated patients. Single-cell sequencing analyses demonstrated that anlotinib reverses penpulimab resistance by reprogramming the tumor immune microenvironment, thereby boosting PD-1 blockade efficacy via modulation of immune infiltration and tumor signaling pathways. Identifying Apoe⁺ M2 macrophages, Srgn⁺ M1 macrophages, and Cxcl2⁺ T cells provides key cellular and molecular targets for developing clinically actionable immunotherapies. Taken together, this work validates the preclinical potential of anlotinib combined with immunotherapy for immunotherapy-resistant tumors. Show less

We developed a viscosity-activated near-infrared (NIR) fluorescent probe, QV-S. This probe features a long emission wavelength (815 nm), a large Stokes shift (135 nm), high viscosity sensitivity (431-fold signal enhancement), and specific lysosome-targeting capability. QV-S allows for not only real-time monitoring of lysosomal viscosity changes in inflammatory and foam cells but also the precise imaging of atherosclerotic plaques in the aortas of ApoE Show less

Hemodynamic abnormalities within atherosclerotic plaque regions, particularly localized high shear stress and endothelial dysfunction, present novel targets for intervention by drug delivery systems. In this study, we designed a polysaccharide-based carrier (HF-AF) from fucoidan, featuring a dynamic supramolecular structure. A dynamic supramolecular network was established within this carrier via dynamic supramolecular interactions between hydroxypropyl-β-cyclodextrin and adamantane-methylamine. The anti-inflammatory compound tilianin, formulated into nanocrystals (Til NCs), was then encapsulated to create a shear-responsive nanosystem (HF-AF@Til NCs). The system's primary therapeutic strategy is its response to pathological hemodynamic forces: upon encountering high shear stress at a stenosis, the supramolecular network undergoes dissociation, triggering a mechanically-gated release of the encapsulated Til NCs. This shear-triggered function is complemented by the natural P-selectin affinity of the fucoidan backbone, which facilitates the anchoring of the nanocarrier at the inflamed lesion site. This sophisticated "anchor-and-release" mechanism enables superior drug accumulation precisely at plaque sites. In ApoE Show less

Precise toxicological mechanism of atherosclerosis (AS) induced by environmental hazardous substance nicotine exposure remains unclear, impeding its prevention strategies and antagonist development. Additionally, it is yet unknown whether Dendrobium officinale's active components can antagonize nicotine-induced AS. This study aimed to elucidate nicotine exposure-induced AS toxicological mechanisms and identify Dendrobium officinale's active components-derived antagonists. Firstly, using ApoE Show less

Pro-inflammatory macrophage function is linked to an increase in mitochondrial fission. Melatonin has a positive impact on atherosclerosis and has a significant effect on the control of mitochondrial fission and fusion. Nevertheless, it is still unclear how melatonin contributes to slowing the advancement of atherosclerosis. The ApoE The study found that melatonin treatment decreased the area of atherosclerotic plaque, decreased lipid deposition, suppressed inflammatory cytokine levels, inhibited macrophage pro-inflammatory differentiation, inhibited mitochondrial fragmentation, increased the level of Sirt3, and decreased Drp1 expression in atherosclerosis (AS) mice. However, Sirt3 inhibition abolished the protective affects of melatonin in AS mice. Melatonin therapy upregulated Sirt3 expression in RAW264.7 cells subjected to ox-LDL, blocked Drp1-mediated mitochondrial fission, and reduced inflammatory cytokine levels. On the other hand, melatonin's inhibitory effects on Drp1 expression and mitochondrial fission were lessened by Sirt3 inhibition. Additionally, DRP1 siRNA knockdown inhibited mitochondrial fission and pro-inflammatory differentiation of macrophages induced by ox-LDL. Melatonin inhibits the growth of atherosclerosis and the pro-inflammatory differentiation of macrophages by blocking the Sirt3-Drp1 pathway, which prevents mitochondria from fission. Melatonin's suppression of mitochondrial fission may be a viable strategy for postponing cardiovascular problems in atherosclerosis patients. Show less

The ability to permeate the blood‒brain barrier (BBB) remains a major challenge in treating neurological disorders. Molecularly imprinted polymeric nanocarriers (nanoMIPs) are emerging as versatile platforms that integrate antibody-mimetic recognition with exceptional stability, tunable physicochemical properties, and controlled drug release. This review summarizes recent advances in nanoMIP design, including template selection, polymerization strategies, and surface modifications, and explores their potential for targeted brain delivery. Particular emphasis is placed on surface engineering approaches, such as functionalization with apolipoprotein E (ApoE), transferrin, and angiopep-2 ligands, which exploit receptor-mediated transcytosis (RMT) to increase BBB permeation and drug accumulation in pathological brain regions. The therapeutic and diagnostic applications of nanoMIPs in neurodegeneration, brain tumors, and CNS infections are also highlighted. Finally, current limitations and future perspectives are discussed, including biocompatibility, large-scale production, and regulatory considerations, positioning nanoMIPs as a next-generation platform for overcoming BBB-associated barriers, and advancing precision brain therapeutics. Show less

Aging and age-related diseases share convergent pathways at the proteome level. Here, using plasma proteomics and machine learning, we developed organismal and ten organ-specific aging clocks in the UK Biobank (n = 43,616) and validated their high accuracy in cohorts from China (n = 3,977) and the USA (n = 800; cross-cohort r = 0.98 and 0.93). Accelerated organ aging predicted disease onset, progression and mortality beyond clinical and genetic risk factors, with brain aging being most strongly linked to mortality. Organ aging reflected both genetic and environmental determinants: brain aging was associated with lifestyle, the GABBR1 and ECM1 genes, and brain structure. Distinct organ-specific pathogenic pathways were identified, with the brain and artery clocks linking synaptic loss, vascular dysfunction and glial activation to cognitive decline and dementia. The brain aging clock further stratified Alzheimer's disease risk across APOE haplotypes, and a super-youthful brain appears to confer resilience to APOE4. Together, proteomic organ aging clocks provide a biologically interpretable framework for tracking aging and disease risk across diverse populations. Show less

Peripheral injury reprograms metabolism in spinal cord oligodendrocytes, initiating a molecular cascade that drives chronic pain via neuronal β-amyloid (Aβ) release. After injury, mouse spinal oligodendrocytes downregulate myelin protein synthesis and upregulate lipid biosynthesis-but reroute lipids toward neuroplastic remodeling and away from myelin maintenance. This metabolic reallocation disrupts myelin integrity and axonal function, causing neuronal accumulation of amyloid precursor protein, enhanced expression of its processing β-secretase BACE1, and local release of Aβ peptides. Blocking Aβ production or clearing Aβ deposits stops the transition to pain chronicity. Deleting the lysosomal lipid hydrolase NAAA in oligodendrocytes prevents both injury-induced Aβ production and chronic pain development. The findings identify an unexpected mechanistic link between chronic pain and Alzheimer's-like neurodegeneration, positioning Aβ as a target for therapeutic intervention. Show less

Congenital heart disease (CHD) is the most common birth defect worldwide, with over half of cases lacking a defined etiology. Maternal metabolic dysregulation has been implicated in CHD risk, but the specific metabolites and mechanisms involved in embryonic heart development remain poorly understood. Carbamoyl phosphate (CP), a key urea cycle intermediate, has not previously been linked to cardiac morphogenesis. This study aimed to identify maternal metabolites associated with offspring CHD risk and to elucidate the role of CP in regulating cardiac development. Untargeted metabolomic profiling was performed on early-pregnancy serum from 98 mothers of CHD offspring and 50 age-matched controls. Functional validation was performed using two pregnant mouse models: pharmacological inhibition of glutamine metabolism via BPTES and Cps1 heterozygous knockout (Cps1 Maternal serum CP levels were significantly reduced in CHD cases and negatively correlated with upstream nutrient levels. In mice, both BPTES treatment and maternal Cps1 knockdown increased CHD incidence in offspring. Conversely, NCG supplementation reduced CHD risk in Cps1 Maternal CP deficiency increases offspring CHD risk by disrupting TET2-mediated DNA demethylation through impaired lysine carbamylation. These findings highlight maternal CP and TET2 carbamylation as potential metabolic-epigenetic targets for CHD prevention. Show less

This study sought to identify neurotransmitter receptor-related genes (NR-RGs) that are critically involved in non-small cell lung cancer (NSCLC) through bioinformatics approaches. The TCGA-NSCLC dataset was utilized as the training cohort, while the GSE50081 dataset served as the validation cohort. NR-RGs were curated, and single-sample gene set enrichment analysis (ssGSEA) scores were computed. Subsequently, weighted gene co-expression network analysis (WGCNA) and functional enrichment analyses were conducted. A risk prediction model and a prognostic model were constructed based on identified gene signatures. Finally, a competing endogenous RNA (ceRNA) network was established, and gene expression levels were experimentally validated. 192 differentially expressed genes were identified as candidate NR-RGs. The risk model ultimately highlighted six genes: CPS1, CDH17, NIPAL4, SOX2, CALB2, and KREMEN2 as potential biomarkers. The prognostic model demonstrated robust predictive performance for patient outcomes. Immune infiltration analysis revealed a significant positive correlation between neutrophil abundance and the risk score. Expression analysis indicated that CPS1 and CALB2 were downregulated in NSCLC samples, whereas CDH17, NIPAL4, SOX2, and KREMEN2 were upregulated. The genes CPS1, CDH17, NIPAL4, SOX2, CALB2, and KREMEN2 were identified as prognostic biomarkers in NSCLC, providing insights into their potential roles in disease progression and therapeutic targeting. Show less

N-carbamylglutamate (NCG) is an activator of arginine biosynthesis, but its specific role in crustaceans remains poorly understood. This study aimed to investigate the effects of NCG on arginine biosynthesis capacity, metabolism, digestion, and the gene expression of the mTOR signaling pathway in Eriocheir sinensis. In Experiment 1, hepatopancreas was cultured in vitro with NCG medium (0, 65, 75, and 85 mg/L NCG). In Experiment 2, crabs were fed either regular feed or NCG feed (content: 302.96 ± 4.07 mg/kg) for 14 days. In Experiment 1, NCG significantly upregulated pyrroline-5-carboxylate synthase (p5cs) gene expression (P < 0.05), an enzyme that is related to arginine biosynthesis. Similarly, dietary NCG upregulated p5cs expression and significantly increased the activities of carbamoyl-phosphate synthase-1 (CPS-1) and P5CS in the hepatopancreas and intestine (P < 0.05). Metabolomics analysis indicated that NCG altered the metabolic profile of the hepatopancreas, promoting cholesterol metabolism, and arginine and proline metabolism. In the intestine, trypsin and α-amylase activities were significantly elevated (P < 0.05). NCG also altered the composition of intestinal microflora, with an increase in Proteobacteria and in the ratio of Firmicutes to Bacteroidota. Additionally, NCG increased the content of signaling molecule nitric oxide (NO) and upregulated the expression of genes in the mTOR signaling pathway (P < 0.05). In conclusion, NCG supplementation enhanced arginine biosynthesis capacity, stimulated intestinal enzymatic activities, and upregulated mTOR signaling pathway gene expression in Eriocheir sinensis, indicating the potential for improved metabolism and digestion. Show less

Primary resistance to chimeric antigen receptor (CAR) T-cell therapies has limited their widespread application. Our prior genome-wide CRISPR/Cas9 screening revealed that the loss of CD58, a crucial intrinsic resistance factor in tumors, resulted in insufficient immune synapse formation and impaired CAR T-cell activation and cytotoxicity. However, the specific signaling pathway and transcriptional changes associated with CAR T-cell dysfunction have not been addressed. Here, we revealed that AP-1-mediated activation was attenuated in CAR T cells impaired by tumor CD58 loss, driving a decrease in mitochondrial biogenesis, metabolic kinetic impairment, mitochondrial membrane potential loss and ROS accumulation. Moreover, this AP-1 attenuation triggered death receptor-independent apoptosis through the intrinsic mitochondrial pathway. In seeking therapeutic strategies, we pharmacologically and genetically blocked three distinct inhibitory phosphatases positioned upstream of AP-1 signaling. Multifaceted validation has demonstrated that dual specificity phosphatase 6 (DUSP6) blockade is an effective approach to supplement AP-1 signaling while notably reducing CAR T-apoptosis and enhancing mitochondrial fitness, proliferation and long-term cytotoxicity. The transcriptomic profiles of DUSP6-ablated CAR T cells revealed markedly upregulated T-cell activation signatures and enriched metabolic pathways. Clinically, bulk and single-cell RNA-seq analyses revealed that DUSP6 was downregulated in patients who responded to T-cell-based immunotherapy, implying its relevance to patient outcomes. Our findings repositioned CD58 not merely as an immune synapse component but also a metabolic checkpoint in CAR T-cell biology, the loss of which triggers AP-1-dependent mitochondrial derangement and creates a permissive landscape for intrinsic apoptosis, which can be ameliorated by ablation of the inhibitory phosphatase DUSP6. Crucially, DUSP6 ablation represents a promising engineering target to potentiate CAR T-cell efficacy in broader applications. Show less

There is a close connection between aging and osteoarthritis (OA), but the specific mechanisms are still unclear. This study aims to explore the potential connections and molecular mechanisms between OA and aging through multi-omics and genetics methods. Integrating single-cell RNA sequencing (scRNA-seq), bulk RNA-seq data, Mendelian randomization (MR), colocalization analysis, and cell function analysis, this study explores the correlation between OA and aging. Furthermore, it investigates the potential causal relationship between key marker genes and OA. Integrating and analyzing scRNA-seq data from OA, aging, and control groups revealed a significant increase in the proportion of the classical monocyte core subgroup. Differential expression analysis yielded 77 marker genes, and further MR analysis identified four key marker genes (DUSP6, CSTA, CD300E, and GPX1) as causally related to OA, which was confirmed in an independent validation cohort. Reverse MR and Steiger filtering indicated no evidence of reverse causality. DUSP6- and CSTA-classical monocytes may interact with other cell subgroups through the MIF-(CD74 + CD44) signaling pathway. This study revealed the heterogeneity of monocyte subgroups in OA and aging patients, identifying key marker genes with a causal relationship to OA through an integrated multi-omics approach, providing potential molecular targets for the diagnosis and treatment of OA from an aging perspective. Show less

Perioperative neurocognitive disorder (PND) is one of the most prevalent neurological complications in elderly surgical patients. Dysregulated lipid metabolism is a hallmark of aging and is strongly associated with cognitive dysfunction. This study aimed to investigate whether ω-6 polyunsaturated fatty acid (PUFA) metabolism contribute to PND and examined whether fatty acid desaturase 1 (FADS1) represents a key regulatory link between fatty acid metabolism and PND in aged mice. An anesthesia/surgery-induced cognitive dysfunction model was established Anesthesia/surgery significantly upregulated hippocampal FADS1 expression (1.91-fold [0.37] vs. 1.00-fold [0.43]; These findings highlight anesthesia/surgery could disrupt ω-6 PUFA metabolism, notably activating the PGD The online version contains supplementary material available at 10.1186/s12974-025-03678-y. Show less

The intramuscular fat content and the unsaturated fatty acid (UFA) composition are both critical indicators of buffalo meat quality. While microRNAs regulate fatty acid metabolism, their specific roles in buffaloes remain unclear. Our previous WGCNA identified bta-miR-30f as a hub miRNA positively correlated with UFA levels. In the present study, bta-miR-30f was found to be highly expressed in sternum subcutaneous adipose tissue and mature adipocytes. Functional studies indicated that bta-miR-30f increased lipid accumulation via enhanced adipogenesis and UFA levels, upregulating key genes including Show less

Scirrhous gastric cancer (SGC), including the Borrmann type IV subtype, is characterized by a desmoplastic stroma, rapid progression, and a poor prognosis with limited effective treatment options. While fibroblast growth factor receptor 2 (FGFR2) alterations are recognized therapeutic targets in some cancers, their clinical application in gastric cancer, particularly in SGC, remains underexplored. We present the case of a 47-year-old female with advanced, chemotherapy-refractory Borrmann type IV gastric cancer harboring FGFR2 rearrangement and amplification. Treatment with the selective FGFR1-3 inhibitor pemigatinib elicited a marked clinical and serological response; however, disease progression ensued after 3 months. Comprehensive genomic profiling revealed an acquired FGFR2 N549K mutation, a recognized on-target resistance mechanism. Subsequent administration of the irreversible FGFR1-4 inhibitor futibatinib was associated with a declining trend in tumor biomarkers, indicating preliminary antitumor activity against the resistant clone. This case underscores the clinical activity of FGFR inhibition in FGFR2-altered SGC and exemplifies the emergence of kinase domain mutations as a principal resistance pathway. It further suggests that irreversible FGFR inhibitors may represent a rational therapeutic strategy upon progression on prior FGFR-directed therapy, warranting further clinical investigation in this molecularly defined patient subset. Show less

Despite the rapid development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in recent decades, resistance remains a significant challenge in managing advanced non-small cell lung cancer (NSCLC). Elucidating the mechanisms underlying EGFR-TKI resistance and developing novel strategies are therefore crucial. In this study, we investigated the role of polo-like kinase 1 (PLK1) in EGFR-mutant NSCLC and evaluated the therapeutic potential of combining EGFR-TKIs with PLK1 inhibitors. We demonstrated that high PLK1 expression correlates with STAT3 signaling activation and decreased survival probability in EGFR-mutant NSCLC patients. Subsequent studies revealed that PLK1 inhibitors effectively reversed the activation of STAT3 induced by EGFR-TKIs. When used in combination with EGFR-TKIs, they promoted cell apoptosis, inhibited cell proliferation in vitro, and induced tumor regression in animal models. Mechanistically, our data demonstrated that PLK1 regulated STAT3 activity through protein-protein interactions and JAK1-mediated phosphorylation, while STAT3 reciprocally regulated PLK1 transcription, establishing a positive feedback loop between these signaling molecules. This PLK1/STAT3 loop was further reinforced by FGFR1 upregulation and directly linked to EGFR-TKI resistance. Targeting this axis with combinatorial inhibitors exerted synergistic anti-tumor effects, suppressing proliferation and migration in osimertinib-resistant models. In conclusion, concurrent inhibition of EGFR and FGFR1/STAT3/PLK1 signaling pathways provides a promising therapeutic strategy for NSCLC patients with EGFR mutations, enhancing efficacy and overcoming resistance. Show less

Community-acquired pneumonia (CAP) is still a leading cause of death due to infection globally, yet precise severity assessment remains a significant clinical problem. More than any other group of cytokines, interleukins are central to the regulation of inflammation and shed light on this intricate pathology. In the present review we summarize the biological and clinical characteristics of some of the principal interleukins (ILs) in CAP, classified primarily according to their physiological activity as pro-inflammatory (IL-2, IL-6, IL-8 and IL-12), anti-inflammatory (IL-7, IL-10 and IL-37), dual-action (IL-4 and IL-17), and emerging factors (IL-3, IL-27 and IL-33). Additionally, recent multimodal approaches are discussed such as combining cytokines with organ dysfunction parameters (MR-proADM) or revealing host-response patterns to inform antibiotic and corticosteroid management. We propose that the field needs to transition to immunological endotyping, multi-omics (integrating genetics and lung microbiome), and artificial intelligence (AI) models based on dynamic patient data to achieve precision medicine in CAP management. Show less

Acute respiratory distress syndrome (ARDS) induced by sepsis is a clinical syndrome characterized by high morbidity and mortality rates. This study aims to clarify the effects of recombinant mouse IL-27 protein on macrophage ferritinophagy, macrophage polarization, and its interventional role in sepsis-induced ARDS. This study utilized wild-type (WT) and IL-27 receptor knockout (IL-27R This study investigates the role of IL-27 in exacerbating ferritinophagy and ferroptosis in macrophages and septic lung injury, and explores the therapeutic potential of the NCOA4 degrader CV3. We found that IL-27 synergizes with LPS to enhance NCOA4-mediated ferritinophagy, leading to increased degradation of FTH1, upregulation of LC3A/B, and promotion of ferroptosis. Ferritinophagy amplification drove M1 macrophage polarization and inflammatory cytokine release. CV3, a PROTAC-based NCOA4 degrader, effectively disrupted the NCOA4-FTH1 interaction, inhibited ferritinophagy, and mitigated ferroptosis and inflammation. In murine models of sepsis-induced ARDS, CV3 alleviated lung injury, restored antioxidant defenses, and reduced ferroptosis. Notably, IL-27R These findings reveal a potential mechanistic link between NCOA4-mediated ferritinophagy and sepsis-associated ARDS pathogenesis. Targeting this pathway with CV3 may offer a novel therapeutic strategy, which warrants further investigation. Show less

Psoriasis and atopic dermatitis (AD) are two prevalent inflammatory skin disorders, each characterized by distinct adaptive immune responses. However, recent evidence suggests that these diseases may share overlapping immune mechanisms, especially concerning keratinocyte function. The specific cytokines that coordinate these inflammatory pathways remain largely undefined. The expression of IL-27 and its receptor was analyzed using data derived from GEO datasets. Imiquimod-induced psoriasis-like and MC903-induced AD-like skin inflammation models were established in wild-type and Il27ra knockout littermates. Skin inflammation was evaluated using clinical scoring, histology, and immunostaining. Flow cytometry was employed to characterize immune cell populations in skin. Expression of relevant cytokines and signaling molecules was assessed using quantitative PCR, bulk RNA sequencing, and Western blotting. We found significantly elevated expression of the IL-27 receptor in the lesional skin of patients with psoriasis or AD. IL-27 receptor-deficient mice exhibited markedly reduced skin inflammation in both psoriasis-like and AD-like murine models. Mechanistic investigations revealed that IL-27 induces tumor necrosis factor-α production via signal transducer and activator of transcription 1 activation in keratinocytes, thereby potentiating inflammatory responses. Our findings identify IL-27 signaling in keratinocytes as a pivotal regulator of skin inflammation in both psoriasis and AD. This highlights IL-27 as a promising therapeutic target for inflammatory skin diseases. Show less

In recent years, the impact of lipoprotein(a) (Lp(a)) on the prognosis of coronary heart disease has been increasingly recognized. Lp(a) is an independent risk factor for cardiovascular disease, and studies have shown that homocysteine (HCY) may influence the association between Lp(a) and the risk of recurrent cardiovascular events. This study investigates the association between Lp(a) levels and recurrent cardiovascular events in patients with varying HCY concentrations. We conducted a 36-month follow-up on 530 patients with coronary heart disease and divided them into low-Lp(a) and high-Lp(a) groups based on Lp(a) levels. The incidence rates of major adverse cardiovascular events (MACE) and acute coronary events (ACE) were compared between the two groups. The association between elevated Lp(a) and cardiovascular risk in different subgroups(based on HCY concentration) was analyzed using Kaplan-Meier curves and Cox proportional hazards models. Elevated Lp(a) remained a significant risk factor for both MACE (HR = 2.07, 95% CI = 1.37-3.12, P = 0.001) and ACE (HR = 2.83, 95% CI = 1.67-4.81, P = 0.001) overall. In subgroup analyses, elevated Lp(a) in patients with moderate-to-high HCY levels constituted a high-risk cohort for MACE and ACE occurrence (HR = 1.87, 95% CI = 1.01-3.46, P = 0.046;HR = 2.85, 95% CI = 1.32-6.18, P = 0.008). Among those with low HCY levels, elevated Lp(a) showed no association with either MACE or ACE (P > 0.05). When HCY is elevated, patients with increased Lp(a) experience amplified risk of recurrent cardiovascular events. This association shifts when HCY is at low levels. Future efforts should emphasize combined assessment of Lp(a) and HCY and explore targeted intervention strategies to reduce residual cardiovascular risk. Show less

The purpose of this study was to explore the latent profiles of ambivalence over emotional expression (AEE) in breast cancer patients and its influencing factors. From July 2024 to June 2025, breast cancer patients were recruited using a convenience sampling method from a tertiary hospital in China. A total of 388 participants completed demographic and clinical characteristic questionnaires, the Ambivalence Over Emotional Expression Questionnaire (AEQ), the Perceived Stress Scale-14 (PSS-14), the Social Support Rating Scale (SSRS), and the Irrational Beliefs Scale (IBS). Latent profile analysis (LPA) was used to identify AEE subgroups, followed by univariate analysis, ANOVA, and multinomial logistic regression to examine associated influencing factors. Based on the level of AEE, breast cancer patients were divided into 3 sub groups: "low conflict-active disclosure group " (34.5%), "moderate conflict-inhibition and regret group " (46.5%), and "high conflict-inhibition and regret group " (19.3%). The multivariate logistic regression analysis showed that retirement status, perceived stress, social support and irrational beliefs were factors influencing participants' AEE (P < .05). There was significant variability in AEE among 3 subgroups of breast cancer patients. Retirement status, perceived stress, social support, and irrational beliefs have an impact on AEE in breast cancer patients. It is crucial for healthcare professionals to promptly identify high-risk groups and implement targeted interventions to improve AEE. This study can help healthcare providers identify patients at high risk of AEE, enabling early intervention and targeted psychological nursing interventions. Healthcare providers can assist patients in establishing correct beliefs about their illness and alleviating perceived stress, thereby reducing the negative impact of AEE. Show less

Current genetic testing for coronary artery disease (CAD) primarily targets monogenic variants in individuals with severe hypercholesterolemia. Whether supplementing monogenic testing with polygenic risk scores for CAD and Lp(a; lipoprotein[a]) levels [PRS A genetic probability for CAD (GenProb In the UK Biobank development cohort, PVs, polygenic risk scores for CAD and PRS GenProb Show less

The quality of informal care for people with dementia (PwD) has gained increasing importance, as most PwD prefer home-based care over institutional placement. However, evidence-based intervention programs tailored to distinct care quality profiles remain limited. Additionally, the absence of clear thresholds to identify PwD receiving low-quality informal care poses a challenge for research and clinical practice. Thus, this study aimed to identify the profiles of quality of care (QoC) among informal caregivers of PwD, explore influencing factors of different profile, and determine the optimal cut-off score of the Exemplary Care Scale (ECS). A cross-sectional survey was conducted. A total of 213 dyads of PwD and their informal caregivers were recruited from memory clinic, rehabilitation clinic, and neurological clinic of a tertiary hospitals and communities in Wuhan, Hubei, China, between July 15, 2023, and July 14, 2024. Latent profile analysis (LPA) was employed to identify QoC profiles. Multinomial logistic regression was performed to explore influencing factors of profile membership. Receiver Operating Characteristic (ROC) analysis was conducted to determine the ECS cut-off score. Three distinct QoC profiles were identified: high (24.41%), moderate (44.60%), and low (30.99%). Among informal caregivers, lower monthly income, insufficient social support, and higher perceived overload were associated with low QoC profile, whereas, better quality of pre-illness relationship with PwD and greater activities of daily living (ADL) of PwD were associated with high QoC. ROC analysis yielded an optimal ECS cut‑off score of 15, with high sensitivity (0.993) and specificity (0.955). This study identified three distinct QoC profiles among caregivers of PwD, underscoring the heterogeneity of informal care quality. The identified predictors and the validated ECS cut‑off score of 15 provide an empirical basis for developing tailored screening tools and targeted interventions for high‑risk caregiver subgroups. Show less

In recent years, the global incidence of Non-Suicidal Self-Injury (NSSI) has risen, posing a significant challenge in public health. Adolescents are the main group affected. A cross-sectional study was conducted using a self-administered questionnaire to collect data from 6,311 adolescents in Hefei, China. This study employed the Compositional Isotemporal Substitution Model (CISM, a statistical method that estimates health effects of replacing time in one behavior with another while accounting for the interdependent, compositional nature of 24-h time-use data) to examine the impact of Screen Time (ST), Non-Screen-based Sedentary Time (NSST), Physical Activity, and Sleep Time on NSSI among adolescents. Compositional logistic regression analysis revealed that, relative to the remaining behavioral components, higher Light Physical Activity (LPA) ( The findings highlight those reasonably allocating adolescents' daily activities, reducing ST, can help lower the risk of NSSI among adolescents. Show less

Previous research on breast cancer patients has primarily examined singular behavioral indicators, often overlooking the coexistence and interaction between physical activity and sedentary behavior-particularly screen-based sedentary time. This study aims to identify the latent activity pattern categories among breast cancer patients during chemotherapy intervals and explore their associated factors to inform targeted behavioral interventions. A cross-sectional survey was conducted with 292 breast cancer patients undergoing chemotherapy intervals at four general hospitals in Foshan, Guangdong Province. Latent Profile Analysis (LPA) was applied as a person-centered analytic approach to identify distinct activity pattern profiles. Data were collected using a general information questionnaire, the Adult Sedentary Behavior Questionnaire (ASBQ), the Chinese version of the International Physical Activity Questionnaire (IPAQ-SC), the Exercise Self-Efficacy Scale (ESES), the Perceived Social Support Scale (PSSS), and the Hospital Anxiety and Depression Scale (HADS). The activity patterns of breast cancer patients were categorized into three groups: Moderate Activity-Dominant Group (37.33%), Screen-Sedentary High-Risk Group (8.22%), and Activity-Sedentary Coexistence Group (54.45%). Logistic regression analysis showed that, compared to the Moderate Activity-Dominant Group, patients with low exercise self-efficacy and higher anxiety and depression levels were more likely to be classified into the Screen-Sedentary High-Risk Group and Activity-Sedentary Coexistence Group. Higher education levels and being on medical leave were associated with a higher probability of belonging to the Activity-Sedentary Coexistence Group (all Activity patterns in breast cancer patients show significant heterogeneity. Healthcare providers should pay attention to the individual physical activity characteristics of patients and offer personalized physical activity guidance. Tailored interventions that meet the needs of breast cancer patients should be developed to improve health outcomes. Show less