Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

Objective:To explore the key components and mechanism of Qufeng Ningfei Powder in treating asthma through qualitative analysis of its blood components, combined with network pharmacology and molecular docking techniques.Methods:The blood components of Qufeng Ningfei Powder were qualitatively analyzed using UPLC-QE-Orbitrap-MS technology. R language was employed to analyze chip data from the GEO database, obtaining a list of differentially expressed genes. SwissTargetPrediction was utilized to predict the targets of drug components. Asthma-related targets were searched through databases such as OMIM, GeneCards, and TTD. The intersection of drug and disease targets was identified using Venn online analysis tool, constructing a "drug-component-target-disease" network to screen potential core components. A protein-protein interaction network (PPI) of core targets was constructed using STRING platform and Cytoscape software. GO function enrichment and KEGG pathway analysis were conducted using DAVID database to validate potential mechanism. Molecular docking was performed to verify the interaction between key components and core targets.Results:A total of 64 components were identified, from which 53 active components were screened, corresponding to 609 targets. Further searching disease databases revealed 96 target genes related to asthma, with an intersection of 6 genes between drug and asthma differential genes. Core target gene IL6 and its corresponding core compound were determined through network topology analysis. Molecular docking confirmed the binding of the main active components of Qufeng Ningfei Powder with the core target protein IL6.Conclusion:The blood components of Qufeng Ningfei Powder may regulate IL-17 through IL6, counteract airway remodeling, oxidative stress, and airway hyperresponsiveness, and thus treat asthma.

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Aged ; Animals ; Humans ; Aging/genetics* ; Forkhead Transcription Factors/metabolism* ; Myocytes, Cardiac/metabolism* ; Primates/metabolism* ; Repressor Proteins/metabolism* ; Transcriptome ; Macaca fascicularis/metabolism*

Objective:To evaluate the effectiveness and quality of ultrasound-based (BUS) process optimization in breast cancer screening.Methods:The program collected the first to fourth quarterly breast cancer screening statistic data and case report data from 30 provinces, autonomous regions and municipalities in 2015 by the online report system of national key service program of women and children′s public health. The call rate, mammography (MG) subsequent screen rate, biopsy rate, detection rate, early diagnosis rate, carcinoma in situ rate, missing detection rate, false positive rate and positive predictive value (PPV) of breast cancer were calculated.Results:A total of 1 501 753 rural women attended the BUS process optimization screening. The nationwide recall rate was 3.01%(45 156/1 501 753), and in the eastern and central area were 3.41%(17 173/503 130) and 3.56%(14 499/407 739), respectively, higher than 2.28% (13 484/590 884) of western area ( P<0.05). The nationwide MG subsequent screen rate was 2.78%(41 694/1 501 753), and in the eastern and central area were 3.19%(16 036/503 130) and 3.29% (13 421/407 739), respectively, higher than 2.07%(12 237/590 884) of western area ( P<0.05). The nationwide biopsy rate was 0.23%(3 462/1 501 753), and in the central area were 0.26%(1 078/407 739), respectively, higher than 0.21%(1 247/590 884) of western area and 0.23% (1 137/503 130) of eastern area ( P<0.05). The nationwide biopsy PPV was 37.00%(1 281/3 462). The biopsy PPV of eastern area was (34.30%, 390/1 137), lower than 39.33% (424/1 078) of central area ( P<0.05). A total of 1 281 cases of breast cancer were detected, the detection rate was 0.85‰(1 281/1 501 753), and the detection rates of central area was 1.04‰ (424/407 739), higher than 0.79‰(467/590 884) of western area and 0.78‰(390/503 130) of eastern area ( P<0.05). The BUS initiate screening positive rate from detected breast cancer cases was 96.96%(1 242/1 281), the MG subsequent screening positive rate was 2.42%(31/1 281). The nationwide early diagnosis rate was 85.25%(1 092/1 281), and in the eastern and central areas were 87.95%(343/390) and 88.21%(374/424), higher than 80.30%(375/467) of western area ( P<0.05). The screening rate of on or above stage Ⅱ breast cancer in eastern area was 55.64%(217/390), lower than 64.62%(374/424) of central area and 62.31%(291/467) of western area. The missing detection rate was 0.62%(8/1 281) and false positive rate was 1.20%(17 528/1 464 149). Conclusions:The BUS process optimization of breast cancer screening scheme is reasonable and applicable to China rural women. The effectiveness and quality of eastern area are superior to those of central and western area.

Objective:To evaluate the effectiveness and quality of ultrasound-based (BUS) process optimization in breast cancer screening.Methods:The program collected the first to fourth quarterly breast cancer screening statistic data and case report data from 30 provinces, autonomous regions and municipalities in 2015 by the online report system of national key service program of women and children′s public health. The call rate, mammography (MG) subsequent screen rate, biopsy rate, detection rate, early diagnosis rate, carcinoma in situ rate, missing detection rate, false positive rate and positive predictive value (PPV) of breast cancer were calculated.Results:A total of 1 501 753 rural women attended the BUS process optimization screening. The nationwide recall rate was 3.01%(45 156/1 501 753), and in the eastern and central area were 3.41%(17 173/503 130) and 3.56%(14 499/407 739), respectively, higher than 2.28% (13 484/590 884) of western area ( P<0.05). The nationwide MG subsequent screen rate was 2.78%(41 694/1 501 753), and in the eastern and central area were 3.19%(16 036/503 130) and 3.29% (13 421/407 739), respectively, higher than 2.07%(12 237/590 884) of western area ( P<0.05). The nationwide biopsy rate was 0.23%(3 462/1 501 753), and in the central area were 0.26%(1 078/407 739), respectively, higher than 0.21%(1 247/590 884) of western area and 0.23% (1 137/503 130) of eastern area ( P<0.05). The nationwide biopsy PPV was 37.00%(1 281/3 462). The biopsy PPV of eastern area was (34.30%, 390/1 137), lower than 39.33% (424/1 078) of central area ( P<0.05). A total of 1 281 cases of breast cancer were detected, the detection rate was 0.85‰(1 281/1 501 753), and the detection rates of central area was 1.04‰ (424/407 739), higher than 0.79‰(467/590 884) of western area and 0.78‰(390/503 130) of eastern area ( P<0.05). The BUS initiate screening positive rate from detected breast cancer cases was 96.96%(1 242/1 281), the MG subsequent screening positive rate was 2.42%(31/1 281). The nationwide early diagnosis rate was 85.25%(1 092/1 281), and in the eastern and central areas were 87.95%(343/390) and 88.21%(374/424), higher than 80.30%(375/467) of western area ( P<0.05). The screening rate of on or above stage Ⅱ breast cancer in eastern area was 55.64%(217/390), lower than 64.62%(374/424) of central area and 62.31%(291/467) of western area. The missing detection rate was 0.62%(8/1 281) and false positive rate was 1.20%(17 528/1 464 149). Conclusions:The BUS process optimization of breast cancer screening scheme is reasonable and applicable to China rural women. The effectiveness and quality of eastern area are superior to those of central and western area.

Objective To investigate the clinical efficacy of cyclosporine injection in subclinical or critical treatment of renal transplant patients，and to establish an individualized dosage regimen of cyclosporine injection by studying the effects of nine single nucleotide polymorphisms related to the pharmacokinetics of cyclosporine on the dose-adjusted trough concentration (C₀/D′) of cyclosporine injection. Methods Blood samples and clinical data of 144 adult renal transplant patients who used cyclosporine injection were collected and recorded, then, their genotypes of CYP3A4*18B, CYP3A5*3, ABCB1 (C1236T, G2677T/A, C3435T), POR*28, PXR (C5705T, C39823T) and NFKB1-94 ins/del ATTG were determined by Sequenom MassARRAY^® SNP methods. Then, the discrepancies of cyclosporine injection’s C₀/D′ among the patients with different genotypes was compared and an individualized dosage regimen based on gene polymorphism of cyclosporine injection was established by using multivariate regression analysis. Results Cyclosporine injection improved serum creatinine level by 68.8% in renal transplant patients with subclinical or critical rejection, and the steady-state plasma concentration was (189.50±38.56) ng/ml. The CYP3A4*18B gene polymorphism was significantly correlated to C₀/D' of cyclosporine injection, and the C₀/D' of patients with *1/*1 genotype was significantly higher than patients of *18B/*18B genotype; but CYP3A5*3, ABCB1(C1236T, G2677T/A, C3435T), PXR C5705T, PXR C39823T, NFKB1-94 ins/del ATTG and POR*28 gene polymorphisms were not significantly correlated to C₀/D' of cyclosporine injection. In the final regression model, hemoglobin and CYP3A4*18B gene polymorphisms were significantly correlated to C₀/D' of cyclosporine injection. Conclusion Cyclosporine injection can effectively improve the serum creatinine level in patients with subclinical or critical rejection; CYP3A4*18B gene polymorphism is significantly correlated to C₀/D' of cyclosporine injection.

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult

Asbestos is classified as a Class 1 carcinogen by the International Cancer Organization (IARC) , and almost all types of asbestos are carcinogenic. The clinical data of 30 asbestos-induced occupational tumor patients in Qingdao city from January 2002 to May 2019 were analyzed, including 24 cases of asbestos-induced lung cancer and 6 cases of asbestos-induced malignant mesothelioma. Mesothelioma was significantly worse than lung cancer in terms of malignancy, the survival time of patients is shorter, and the mortality rate was higher. Both its diagnostic methods and treatment methods should be improved. The high incidence of asbestos-caused tumors is coming. It is recommended that workers exposed to asbestos dust should undergo regular chest CT examinations for early detection, early diagnosis and early treatment.

Asbestos is classified as a Class 1 carcinogen by the International Cancer Organization (IARC) , and almost all types of asbestos are carcinogenic. The clinical data of 30 asbestos-induced occupational tumor patients in Qingdao city from January 2002 to May 2019 were analyzed, including 24 cases of asbestos-induced lung cancer and 6 cases of asbestos-induced malignant mesothelioma. Mesothelioma was significantly worse than lung cancer in terms of malignancy, the survival time of patients is shorter, and the mortality rate was higher. Both its diagnostic methods and treatment methods should be improved. The high incidence of asbestos-caused tumors is coming. It is recommended that workers exposed to asbestos dust should undergo regular chest CT examinations for early detection, early diagnosis and early treatment.