The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Aim To investigate the pharmacological mechanism of Ebselenin(Ebselen,EbSe)in the treat-ment of Escherichia coli(E.coli)infection,which had no significant inhibitory effect on Gram-negative bacte-ria,based on previous studies.Methods After EbSe intervention in E.coli infected Raw264.7 cells,the via-bility of Raw264.7 cells was determined by CCK-8 method,the morphology and structure of Raw264.7 cells were observed by electron microscope,and the in-tracellular bacterial load of Raw264.7 cells was calcu-lated by coated plate method.Polarization status of peritoneal macrophages,Raw264.7 intracellular NO and ROS content and intracellular HO-1 expression in Raw264.7 and E.coli acutely infected mice after E.co-li infection by flow cytometry.qPCR was used to detect the expression of related mRNAs in Raw264.7 cells.qPCR was used to detect the intracellular GSH content in Raw264.7 cells by spectrophotometric assay,and the state of cytoskeletal proteins was observed by immuno-fluorescence.Western blot assay was performed to de-tect the intracellular Txnrd1 expression level.Results Microtiter method,CCK-8,and electron microscopy observations showed that EbSe had no effect on the growth of E.coli and Raw264.7 cells in vitro.The re-sults of smear plate counting showed that EbSe reduced the intracellular bacterial load of Raw264.7 in the in-fected group.Flow cytometry results showed that EbSe upregulated the number of M2-type macrophages.The EbSe-treated infected group had reduced intracellular NO and ROS levels and increased GSH levels.The qPCR results showed that the expression of IL-6,IL-1β,and iNOS was decreased,and the expression of HO-1,Txnrd1,and Glut1 was increased in DHB4-in-fected Raw264.7 cells after EbSe treatment.Cytoskel-etal staining showed that the morphology of the EbSe-treated infected cells was similar to that of oxPAPC-in-duced cells.Western blot results showed the expres-sion of Txnrd1 protein in EbSe-treated infected cells in-creased.Conclusion EbSe exerts anti-E.coli acute infection effect by regulating macrophage polarization and inhibiting macrophage excessive inflammatory state.

Objective To analyze the changes in serum immunoglobulin E(IgE),interleukin-6(IL-6),high-mobility group protein B1(HMGB1),β2-microglobulin(β2-M),and T lymphocyte subsets in patients with secretory otitis media(SOM)and to evaluate their clinical significance.Methods A total of 185 patients with SOM admitted to Wuhan First Hospital between March 2023 and March 2025 were enrolled as the patient group,and 185 healthy individuals who underwent routine physical examinations at our hospital during the same period served as the control group.Serum levels of IgE,IL-6,HMGB1,and β2-microglobulin(β2-M),as well as peripheral blood T lymphocyte subsets,were compared between the two groups.Based on disease duration,the patients were further classified into acute(n=43),subacute(n=61),and chronic(n=81)subgroups.Levels of the serum markers and T lymphocyte subsets were compared across these three subgroups.The diagnostic value of the serum markers for SOM was evaluated,and their correlations with peripheral blood T lymphocyte subsets were analyzed.Results he levels of serum IgE,IL-6,HMGB1,β2-M,and peripheral blood CD8+were significantly higher in the disease group than in the control group,whereas the levels of peripheral blood CD4+and CD4+/CD8+were significantly lower(P<0.05).Across the acute,subacute,and chronic subgroups,the levels of serum IgE,IL-6,HMGB1,β2-M,and CD8+exhibited a progressive increasing trend,while CD4+and CD4+/CD8+levels showed a corresponding decreasing trend(P<0.05).The combined measurement of serum IgE,IL-6,HMGB1,and β2-M yielded a higher area under the curve(AUC)for diagnosing SOM compared to each marker alone(P<0.05),with a sensitivity of 88.65%and specificity of 76.76%.Furthermore,serum levels of IgE,IL-6,HMGB1,and β2-M were positively correlated with peripheral blood CD8+levels(r=0.618,0.578,0.622,0.549;P<0.05),and negatively correlated with CD4+and CD4+/CD8+ratios(r=-0.539,-0.573,-0.519,-0.559 for CD4+;r=-0.604,-0.618,-0.559,-0.649 for CD4+/CD8+;P<0.05).Conclusion The progression of SOM is associated with alterations in serum markers and peripheral blood T lymphocyte subsets.Furthermore,the combination of serum IgE,IL-6,HMGB1,and β2-MG demonstrates enhanced diagnostic value in patients with SOM,and a significant correlation exists between these four markers and the levels of peripheral blood T lymphocyte subsets.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence, particularly during the COVID-19 pandemic. It enables the population-level monitoring of illicit drug use, pathogen prevalence, and environmental pollutant exposure. In this perspective, we summarize the key challenges specific to the Chinese context: (1) Sampling inconsistencies, necessitating standardized 24-hour composite protocols with high-frequency autosamplers (≤ 15 min/event) to improve the representativeness of samples; (2) Biomarker validation, requiring rigorous assessment of excretion profiles and in-sewer stability; (3) Analytical method disparities, demanding inter-laboratory proficiency testing and the development of automated pretreatment instruments; (4) Catchment population dynamics, reducing estimation uncertainties through mobile phone data, flow-based models, or hydrochemical parameters; and (5) Ethical and data management concerns, including privacy risks for small communities, mitigated through data de-identification and tiered reporting platforms. To address these challenges, we propose an integrated framework that features adaptive sampling networks, multi-scale wastewater sample banks, biomarker databases with multidimensional metadata, and intelligent data dashboards. In summary, wastewater-based epidemiology offers unparalleled scalability for equitable health surveillance and can improve the health of the entire population by providing timely and objective information to guide the development of targeted policies.
China/epidemiology* ; Humans ; Wastewater/analysis* ; COVID-19/epidemiology* ; Public Health ; Wastewater-Based Epidemiological Monitoring ; SARS-CoV-2

Objective To analyze the changes in serum immunoglobulin E(IgE),interleukin-6(IL-6),high-mobility group protein B1(HMGB1),β2-microglobulin(β2-M),and T lymphocyte subsets in patients with secretory otitis media(SOM)and to evaluate their clinical significance.Methods A total of 185 patients with SOM admitted to Wuhan First Hospital between March 2023 and March 2025 were enrolled as the patient group,and 185 healthy individuals who underwent routine physical examinations at our hospital during the same period served as the control group.Serum levels of IgE,IL-6,HMGB1,and β2-microglobulin(β2-M),as well as peripheral blood T lymphocyte subsets,were compared between the two groups.Based on disease duration,the patients were further classified into acute(n=43),subacute(n=61),and chronic(n=81)subgroups.Levels of the serum markers and T lymphocyte subsets were compared across these three subgroups.The diagnostic value of the serum markers for SOM was evaluated,and their correlations with peripheral blood T lymphocyte subsets were analyzed.Results he levels of serum IgE,IL-6,HMGB1,β2-M,and peripheral blood CD8+were significantly higher in the disease group than in the control group,whereas the levels of peripheral blood CD4+and CD4+/CD8+were significantly lower(P<0.05).Across the acute,subacute,and chronic subgroups,the levels of serum IgE,IL-6,HMGB1,β2-M,and CD8+exhibited a progressive increasing trend,while CD4+and CD4+/CD8+levels showed a corresponding decreasing trend(P<0.05).The combined measurement of serum IgE,IL-6,HMGB1,and β2-M yielded a higher area under the curve(AUC)for diagnosing SOM compared to each marker alone(P<0.05),with a sensitivity of 88.65%and specificity of 76.76%.Furthermore,serum levels of IgE,IL-6,HMGB1,and β2-M were positively correlated with peripheral blood CD8+levels(r=0.618,0.578,0.622,0.549;P<0.05),and negatively correlated with CD4+and CD4+/CD8+ratios(r=-0.539,-0.573,-0.519,-0.559 for CD4+;r=-0.604,-0.618,-0.559,-0.649 for CD4+/CD8+;P<0.05).Conclusion The progression of SOM is associated with alterations in serum markers and peripheral blood T lymphocyte subsets.Furthermore,the combination of serum IgE,IL-6,HMGB1,and β2-MG demonstrates enhanced diagnostic value in patients with SOM,and a significant correlation exists between these four markers and the levels of peripheral blood T lymphocyte subsets.

Chronic stress triggers the imbalance of the homeostasis of the tumor immune microenvironment(TIME),which is a key factor driving the development of lung cancer.Based on the mapping relationship between the concept of"spirit"in traditional Chinese medicine and chronic stress,and between"qi"and"immunity",it is believed that the cross-linking mechanism of"chronic stress-TIME-lung cancer"aligns with the understanding of traditional Chinese medicine of disease as involving the interplay between the"body,qi and spirit".The disorganization of"spirit"and"qi"is not only the root of the change of the"form",but also the key to prevent and control it.The treatment principle of synergizing to improve the chronic stress of"regulating the spirit"and remodeling the TIME of"invigorating the qi"is further proposed,which emphasizes on grasping the core pathogenesis of lung cancer at each stage of its evolution in order to administer medicines,drawing on the clinical experience and pharmacological research results in order to accurately hit the target,and combining special therapies like acupuncture,Chinese kungfu,sound therapy to treat the change of"shape"by modulating neuro-endocrine-immune network homeostasis,so as to provide new ideas and accessible solutions for the comprehensive prevention and treatment system of lung cancer.

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

This study employed the "disease-medicine-dose" pattern to mine the medication rules of traditional Chinese medicine(TCM) prescriptions containing Astragali Radix in ancient Chinese medical books, aiming to provide a scientific basis for the clinical application of Astragali Radix and the development of new medicines. The TCM prescriptions containing Astragali Radix were retrieved from databases such as Chinese Medical Dictionary and imported into Excel 2020 to construct the prescription library. Statical analysis were performed for the prescriptions regarding the indications, syndromes, medicine use frequency, herb effects, nature and taste, meridian tropism, dosage forms, and dose. SPSS statistics 26.0 and IBM SPSS Modeler 18.0 were used for association rules analysis and cluster analysis. A total of 2 297 prescriptions containing Astragali Radix were collected, involving 233 indications, among which sore and ulcer, consumptive disease, sweating disorder, and apoplexy had high frequency(>25), and their syndromes were mainly Qi and blood deficiency, Qi and blood deficiency, Yin and Yang deficiency, and Qi deficiency and collateral obstruction, respectively. In the prescriptions, 98 medicines were used with the frequency >25 and they mainly included Qi-tonifying medicines and blood-tonifying medicines. Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Citri Reticulatae Pericarpium were frequently used. The medicines with high frequency mainly have warm or cold nature, and sweet, pungent, or bitter taste, with tropism to spleen, lung, heart, liver, and kidney meridians. In the treatment of sore and ulcer, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to promote granulation and heal up sores. In the treatment of consumptive disease, Astragali Radix was mainly used with the dose of 37.30 g and combined with Ginseng Radix et Rhizoma to tonify deficiency and replenish Qi. In the treatment of sweating disorder, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to consolidate exterior and stop sweating. In the treatment of apoplexy, Astragali Radix was mainly used with the dose of 7.46 g and combined with Glycyrrhizae Radix et Rhizoma to dispell wind and stop convulsions. Astragali Radix can be used in the treatment of multiple system diseases, with the effects of tonifying Qi and ascending Yang, consolidating exterior and stopping sweating, and expressing toxin and promoting granulation. According to the manifestations of different diseases, when combined with other medicines, Astragali Radix was endowed with the effects of promoting granulation and healing up sores, tonifying deficiency and Qi, consolidating exterior and stopping sweating, and dispelling wind and replenishing Qi. The findings provide a theoretical reference and a scientific basis for the clinical application of Astragali Radix and the development of new medicines.
Drugs, Chinese Herbal/history* ; Humans ; Medicine, Chinese Traditional/history* ; History, Ancient ; Astragalus Plant/chemistry* ; China ; Astragalus propinquus