Background Silicosis, an occupational lung disease induced by chronic silica (SiO₂) exposure, is pathologically defined by progressive pulmonary fibrosis, and its associated molecular mechanisms are not yet fully elucidated. Objective To understand the critical role of macrophage-derived vesicles in silicotic pulmonary fibrosis via their carried complement component 1r (C1R). Methods Through integrated analysis of human plasma vesicle proteomics and spatial transcriptomics in silicosis mouse models, the key molecular C1R was identified in silicotic fibrosis. Spatial transcriptomic data were further employed to analyze the expression distribution of C1R in lung tissues. In animal experiments, a mouse silicosis model was established via tracheal instillation of silica dust, followed by pulmonary fibrosis assessed by Sirius Red staining, and C1R expression levels in plasma and lung tissue vesicles examined by Western blot. In cellular experiments, an in vitro model was constructed by stimulating macrophages with silica. Extracellular vesicles isolated from this system were then co-cultured with mouse lung fibroblasts (MLG),followed by intervention with a C1R-neutralizing antibody. Results The proteomic analysis of human plasma vesicles revealed a significant upregulation of C1R in silicosis patients, confirmed by Western blot. The spatial transcriptomics in silicotic mice indicated elevated C1R expression in lung tissues after 56 d of SiO₂ exposure, colocalizing with fibrotic lesions. The results of Western blot further demonstrated increased C1R levels in both lung tissue-derived and peripheral blood-derived vesicles during silicosis progression, consistent with the findings in an ex vivo macrophage model. The results of functional assays demonstrated that macrophage-derived vesicles significantly increased the expression of fibrosis markers, including fibronectin 1 (FN1), collagen type I alpha 1 (COL1A1), and alpha-smooth muscle actin (α-SMA), as well as the migratory capacity of lung fibroblasts; these effects were blocked by the C1R-neutralizing antibody. Conclusion Macrophage vesicles drive fibroblast activation and migration through C1R. Since a C1R-neutralizing antibody blocks this pro-fibrotic effect, C1R represents a key mediator in silicosis and thus is considered a new potential therapeutic target.

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

Objective To analyze correlation of endolymphatic hydrops (EH) in the inner ear with age in Meniere’s disease (MD) patients. Methods A retrospective analysis were underwent in 101 definite unilateral MD patients. They were divided into young-age (＜18 years old) group, middle-age (18-45 years old) group and elder-age (＞45 years old) group. All patients underwent inner ear three-dimensional inversion-recovery with real reconstruction (3D-real IR) imaging 4 hours after intravenous gadolinium injection. EH rates among different groups were compared. Results The positive rates of EH in the young-age group, middle-age group and elder-age group were 68.2% (15/22), 54.5% (18/33) and 56.5% (26/46), respectively (P＝0.567). There was no difference in the positive rates of EH in vestibule and cochlea among three groups. There was no difference in the rates of mild and significant EH in vestibule and cochlea among three groups. Conclusions Age might not be related to the occurrence of EH in the inner ear in MD patients.

Icaritin(ICT)is an 8-isopentenylflavonoid,which is the main effective component of the tra-ditional Chinese medicine Epimedium.Previously,we found that Icaritin inhibits the growth of glioblasto-ma(GBM)cells.Herein we aim to study the in vivo anti-GBM effectiveness of Icaritin and explore its mechanism.The results of MTT assay,flow cytometry,comet assay and cellular immunofluorescence as-say in vitro showed that ICT inhibited the proliferation of four kinds of GBM cells,U87,U251,U118 and A172,induced early apoptosis(P＜0.001)and late apoptosis(P＜0.05)in U87 cells,induced DNA damage in U87 cells,and blocked the growth of U87 cells at the G0/G1 phase(P＜0.0001)in a concen-tration-time-dependent manner.In vivo subcutaneous tumor transplantation tumor experiments showed that feeding 200 mg/kg(P＜0.01)and 400 mg/kg(P＜0.001)ICT had a significant inhibitory effect on the growth of GBM subcutaneous tumors,and had no significant toxic effects on heart,liver,spleen,lung and kidney tissues.The results of network pharmacological analysis,molecular docking and cellular thermodynamic experiments showed that there were 26 possible target proteins between ICT and GBM,a-mong which the expression of p53 in GBM tissues was significantly(P＜0.001)higher than in normal tis-sues,and the binding energy of ICT and p53 was lower;cellular thermodynamic experiments verified that ICT significantly enriched the level of p53 in the living cells of GBM,which indicated that ICT could tar-get p53.The expression of key proteins in the DNA damage repair and apoptosis-associated FOXO signa-ling pathway was detected by ICT.The results showed that the expression of ATR(P＜0.01),P53(P＜0.001),P21(P＜0.05)and γ-H2AX(P＜0.05)was up-regulated,whereas the expression of Cyc-lin E1(P＜0.01),E2F1(P＜0.05),CDK2(P＜0.01),Rb(P＜0.001),p-Rb(P＜0.0001)and WRN(P＜0.0001)expression were down-regulated.There was no significant change in the expres-sion of FOXO 1 in the FOXO pathway or a significant down-regulation of its phosphorylation level.This study demonstrated that ICT could effectively inhibit the growth of GBM cells in vivo.It targets p53 to regulate the DNA damage repair pathway and FOXO signaling pathway to induce GBM cell cycle arrest and apoptosis.

ObjectiveThis study aims to observe the clinical effect of Danggui Liuhuang Tang （DGLHT） on patients with type 2 diabetes mellitus （T2DM） complicated by atherosclerotic cardiovascular disease （ASCVD） at high risk， focus on evaluating the influence of DGLHT on cardiovascular risk indicators such as flow-mediated dilation （FMD）， atherogenic index of plasma （AIP）， and triglyceride-glucose index （TyG）， and explore the regulatory effect of DGLHT on the myeloid differentiation factor 88/nuclear factor-kappa B （MyD88/NF-κB） signaling pathway. MethodsThe clinical study was a single-center， double-blind， and randomized controlled trial. A total of 68 patients with T2DM-ASCVD at high risk for cardiovascular events with Yin deficiency and fire excess syndrome were enrolled and randomly assigned to a treatment group and a control group. The treatment group was given atorvastatin calcium tablets and DGLHT， while the control group was given atorvastatin calcium tablets and placebos. The treatment course was 12 weeks， with a final study completion of 30 patients in the treatment group and 29 in the control group. Changes in cardiovascular risk indicators such as FMD， AIP， TyG， and small dense low-density lipoprotein cholesterol （sdLDL-C） index were compared. Human umbilical vein endothelial cells （HUVECs） were used to establish a vascular endothelial injury and inflammation model. The protective effect of DGLHT on endothelial injury was verified by reverse transcription polymerase chain reaction （Real-time PCR） and Western blot . ResultsAfter 12 weeks of treatment， the AIP in the treatment group significantly decreased compared with that before the treatment （P<0.05）. Compared with the control group， the treatment group showed significant improvements in FMD and TyG （P<0.05）. Additionally， the treatment group demonstrated significant reductions in two-hour postprandial glucose （2 hPG）， glycated albumin （GA）， triglycerides （TG）， apolipoprotein E （Apo E）， and sdLDL-C （P<0.05）. Analysis of traditional Chinese medicine （TCM） syndrome efficacy indicated that in the treatment group， Yin deficiency and fire excess syndromes， including dry throat and mouth （P<0.05）， excessive thirst （P<0.01）， tidal fever and night sweats （P<0.05）， and dry stools （P<0.05）， improved. Compared with the control group， the treatment group showed significant improvements in symptoms of dry throat and mouth （P<0.05） and excessive thirst （P<0.01）. TCM syndrome scores significantly decreased （P<0.01）， and the overall efficacy rate was 56.67%， significantly higher than the 10.34% observed in the control group （P<0.01）. At the cellular level， increasing concentrations of DGLHT led to decreased messenger ribonucleic acid （mRNA） levels of pro-inflammatory cytokines interleukin-6 （IL-6）， tumor necrosis factor-alpha （TNF-α）， and interleukin-1-beta （IL-1β） in lipopolysaccharide （LPS）-stimulated HUVECs （P<0.01）， with significant reductions in the high-concentration group （P<0.01）. DGLHT may inhibit the expressions of MyD88 and phosphorylated （p）-NF-κB p65 proteins in a concentration-dependent manner. ConclusionDGLHT shows significant effects in reducing cardiovascular risks and may exert an anti-inflammatory effect by inhibiting the MyD88/NF-κB signaling pathway. This finding provides a new perspective for the prevention and treatment of cardiovascular diseases in high-risk individuals with T2DM-ASCVD.

Objective To evaluate the prevention and control effectiveness of four major chronic diseases in Youyang County, and find the weak link of prevention and control, and to provide theoretical support for improving prevention and control strategies. Methods Based on the death data of permanent residents from 2012 to 2020 extracted from the cause-of-death registration and reporting system of Youyang County, a statistical analysis was conducted using SPSS19.0. The annual percentage change (APC) was tested by t-test. Results From 2012 to 2020, the mortality rate of and the standardized mortality rate of the four major chronic diseases and the premature mortality rate of diabetes in males showed an increasing trend (APC was 3.05%, 1.82% and 27.12%, respectively, P < 0.05). The mortality rate of the four chronic diseases in females increased (APC was 2.53%, P < 0.05), while the proportion of premature death of the four chronic diseases and the probability of premature death of cardiovascular and cerebrovascular diseases in females decreased (APC was -2.37%, -5.73%, P < 0.05). The standardized mortality rate and premature death rate of the four major chronic diseases were higher in males than those in females. The mortality rate of the four major chronic diseases and the premature death rate of diabetes in the whole population were on the rise (APC was 2.84% and 12.86%, P < 0.05). It was expected that the early death probability of the four major chronic diseases in Youyang County would be 12.65% in 2030, higher than the target value of 12.59% of ^“Healthy China 2030^”. Conclusion The future focus of Youyang County is to prevent and control malignant tumors and diabetes, especially to strengthen the prevention and control of male diabetes.

With the extended survival period of breast cancer patients and the increasing health demands, the concomitant diseases of breast cancer have gradually attracted the attention of both doctors and patients, and it is imperative to conduct comprehensive management of these diseases, in which the general practitioners, as the more comprehensive and complex medical talents, have not yet played their due roles. In this article, we report two cases of comprehensive management of concomitant diseases of breast cancer through collaboration of general practitioners and specialists (integrated general and specialist care). The role and function of general practitioners in this process were deeply analyzed, and the establishment of a consultation-liaison general practice model to further promote the role of integrated general and specialist care in integrated oncology care was advocated.

Objective To explore the role of secreted phosphoprotein 1(SPP1)and myeloid differentiation primary response 88(MYD88)in morphine-induced cardiomyocyte apoptosis.Methods A morphine addiction model was established in Sprague-Dawley(SD)rats.Twelve SD rats were randomly assigned to the normal saline(NS)group or the morphine-dependent(DAM)group.Histopathological analysis was employed to observe and compare myocardial tissue morphology between the two groups.Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining was performed to assess the number of apoptotic cells in each group.The expression levels of SPP1 and MYD88 were evaluated using immunohistochemistry.Quantitative real-time poly merase chain reaction(RT-qPCR)and Western blot were used to detect the mRNA and protein expression of SPP1,MYD88,Bax,Bcl2,Caspase-3,and Caspase-9.Simultaneously,Western blot analysis was used to detected the expression of Cleaved Caspase-3 and Cleaved Caspase-9 proteins.In vitro,SPP1 expression was knocked down in primary neonatal rat cardiomyocytes(NRCMs),and cells were divided into three groups:control(CON),morphine treated(DA),and shSPP1#3+DA.Cell viability was assessed using the CCK-8 assay,and apoptosis rates were determined by flow cytometry.Results HE and TUNEL staining of myocardial tissues from morphine-addicted SD rats revealed that,compared with the NS group,myofibrils in the DAM group exhibited partial disruption and a significant increase in apoptotic cells(P<0.05).Western blot and RT-qPCR analyses demonstrated that,relative to the NS group,the mRNA and protein levels of SPP1,MYD88,Bax,Caspase-3,and Caspase-9 were significantly upregulated in the DAM group(P<0.05),whereas Bcl2 expression was significantly downregulated at both mRNA and protein levels(P<0.05),and the protein expression levels of Cleaved Caspase-3 and Cleaved Caspase-9 were also increased.with all differences being statistically significant.In NRCMs following morphine intervention,cell viability in the DA group was markedly reduced compared to the CON group(P<0.05),accompanied by a signifi-cant increase in apoptosis rate(P<0.05).Consistently,Western blot and RT-qPCR results showed elevated mRNA and protein expression of SPP1,MYD88,Bax,Caspase-3,and Caspase-9 in the DA group(P<0.05),along with decreased Bcl2 expression(P<0.05).The protein expression levels of Cleaved Caspase-3 and Cleaved Caspase-9 were elevated simultaneously.In contrast,the shSPP1#3+DA group exhibited opposing trends compared to the DA group,with statistically sig nificant differences(P<0.05).Conclusion SPP1 and MYD88 play critical roles in mediating morphine-induced cardiomyocyte apoptosis,and silencing SPP1 has been shown to significantly reduce the extent of cardiomyocyte apoptosis following morphine exposure.

Objective This study applies Roy adaptation theory to deeply explore the experience of food avoid-ance behavior in patients with inflammatory bowel disease(IBD),offering insights for developing dietary management strategies.Methods A descriptive qualitative research method was employed.By purposive sampling,24 IBD pa-tients hospitalized in the gastroenterology department of a tertiary hospital in Nanjing from July 2022 to December 2024 were selected for semi-structured interviews.Data were analyzed using a directed content analysis approach.Results This study identified 4 main themes and 11 sub-themes,encompassing overattribution leading to inappro-priate avoidance(recurrent symptoms triggering overattribution,disease staging triggering inappropriate avoidance),negative self-perception leading management struggles(illness fear diminishing self-efficacy,disease trauma eroding self-identity,knowledge deficiency constraining self-determination),functional impairment intensifying role challenges(role internalization undermining social function,social roles relinquishing dietary management),and external con-straints amplifying practical difficulties(family and friend oversight heightening dietary stress,healthcare gaps foster-ing practical helplessness,traditional beliefs restricting dietary exploration,economic hardship limiting balanced nu-trition).Conclusion The interplay of overattribution,negative self-perception,functional impairment,and external constraints in IBD patients hinders their ability to adapt to disease fluctuations,ensnaring them in the adaptive predicament of food avoidance behavior.Healthcare professionals should comprehensively address these factors by fostering accurate perceptions,enhancing psychological support,guiding effective coping strategies,and optimizing ex-ternal resources,thereby improving patients' overall adaptive capacity and promoting their recovery.