Brucellosis is one of the most widespread zoonoses globally, which poses serious threats to both global public health and development of animal husbandry. Conventional brucellosis control measures suffer problems of surveillance coordination, regional joint prevention, and policy implementation, which are insufficient to address the challenges of ecological risks and crosshost transmission. The One Health approach allocates interdisciplinary and intersectoral collaborations to achieve systemic health of humans, animals, and environments, which provides new insights into brucellosis control programmes. This review describes the pathogenic biological characteristics, global epidemiological landscape, and transmission ecology of brucellosis, evaluates the main limitations of current control strategies, summarizes the experiences from successful One Health practices across countries at different stages of development, and proposes the brucellosis control strategy based on the One Health concept with adaptations to the current epidemiology of brucellosis in China, so as to provide the theoretical evidence and practical framework for the national brucellosis control programmes in China, thereby facilitating the effective control and the ultimate elimination of brucellosis.

Objective To investigate the epidemiological survey of pulmonary Aspergillus infection in a district of Hefei City, Anhui Province, from 2019 to 2023. Methods The data of 302 patients who attended and were treated in the respiratory department, thoracic surgery department, oncology department, tuberculosis department and RICU ward of Anhui Chest Hospital from January 2019 to September 2023 were selected, and patients with Aspergillus infections were taken as the observation group, patients with Candida infections were taken as the control group, and bacterial infections were taken as the blank group. The general information of patients, pre-treatment infection, underlying diseases, and use of antifungal drugs were analyzed. Compare the data of observation group and control group, and analyze the risk factors affecting pulmonary Aspergillus infection. Results Pulmonary Aspergillus infection 100 cases, accounting for 33.11%. Pulmonary Candida infection was 80 cases, accounting for 26.49%. The other 122 cases were other lung diseases, accounting for 40.40%. The most common causative agent of pulmonary Aspergillus infection was Aspergillus fumigatus (57.00%), cough, sputum and occasional blood were found in most of the patients (88.00%), most of the lesions were located in the right upper lobe of the lungs (55.00%), and most of the single or multiple cavities were seen on imaging (47.00%). Specimens mostly originated from the deep airways of hospitalized patients and there was a predominance of male patients. Risk factors for pulmonary Aspergillus infection were history of hospital transfer, ICU admission, mechanical ventilation, extracorporeal catheterization (intravenous catheter and urinary catheter), history of surgery within 15 days, history of diabetes mellitus, history of respiratory chronic disease, history of antifungal prophylaxis and abnormal serum indicators. History of hospital transfer (OR=2.951, P=0.008), history of diabetes mellitus (OR=5.073, P=0.018), history of chronic respiratory disease (OR=7.523 , P=0.028), extracorporeal catheterization (OR=3.142, P=0.022), and history of anti-fungal prophylaxis (OR=6.334, P<0.001) were Aspergillus pulmonaryis infection independent risk factors for infection. Conclusion Aspergillus fumigatus and Aspergillus flavus are the main pathogens of pulmonary Aspergillus infections in the region, and a history of nosocomial transfer, extracorporeal tubes, diabetes mellitus, chronic respiratory disease, and antifungal prophylaxis are independent risk factors for pulmonary Aspergillus infections.

BackgroundDepression has become a public health concern that affects the physical and mental health of college students. acute stress response is a risk factor of depression. Exploring the relationship and mechanism between acute stress response and depression is of great significance for preventing and intervening depression in college students. ObjectiveTo examine the relationship between acute stress response and depression among college students， and to analyze the mediating role of rumination and the moderated effect of perceived social support， so as to provide references for the prevention and intervention of depression in college student . MethodsFrom March to April 2020， a cluster sampling method was employed to select 1 355 college students from three universities in Hubei， Jiangxi and Guangxi Zhuang Autonomous Region. Participants were assessed with Acute Stress Disorder Scale （ASDS）， Ruminative Responses Scale （RRS）， Brief form of Perceived Social Support Questionnaire （F-SozU） and Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）. Pearson correlation analysis was adopted to examine the correlation between the scores of each scale. The mediating role of rumination between acute stress response and depression and the moderated role of perceived social support were examined respectively by using Model 4 and Model 14 in Macro Program Process 3.3. ResultsA total of 1 303 valid questionnaires were collected， yielding a valid response rate of 96.16%. The results of Pearson correlation analysis showed that ASDS score was positively correlated with RRS score and PHQ-9 score （r=0.649， 0.528， P<0.01） among college students. The mediation analysis results demonstrated that rumination played a partial mediating role between acute stress response and depression， with the mediating effect value of 0.273 （95% CI：0.222~0.328）， accounting for 68.59% of the total effect. Perceived social support played a moderated role in the latter path of the mediation model （rumination → depression） （β=-0.004， 95% CI： -0.017~-0.004， P<0.01）. ConclusionRumination played a partial mediating role between acute stress response and depression in college students， and perceptive social support played a moderated role between rumination and depression. ［Funded by Scientific Research Fund Project of Education Department of Yunnan Province （number， 2025J0437）］

Objective To explore the characteristics of the inhibitory effect of Evodiamine on the proliferation of activated T cells. Methods Mononuclear cells from peripheral blood (PBMCs) were obtained from healthy donors through density gradient centrifugation, and T cells were subsequently purified by using immunomagnetic bead separation. T cell activation was induced by employing anti-human CD3 and anti-human CD28 antibodies. T cells were treated with different concentrations of EVO (0.37, 1.11, 3.33, and 10)μmol/L. Flow cytometry was applied to evaluate the proliferation index, apoptosis rate, viability, CD25 expression levels, and cell cycle distribution of T cells. The expression levels of cytokines IL-2, IL-17A, IL-4, and IL-10 were quantified by using ELISA. Results 1.11, 3.33 and 10 μmol/L EVO effectively inhibited the proliferation of activated T cells, with an IC₅₀ of (1.5±0.3)μmol/L. EVO did not induce apoptosis in activated T cells and affect the survival rate of resting T cells. EVO did not affect the expression of CD25 and the secretion of IL-2 in activated T cells. EVO arrested the T cell cycle at the G2/M phase, resulting in an increase in G2/M phase cells, and exhibited a concentration-dependent effect. EVO did not affect the secretion of IL-4, IL-10 by activated T cells, but significantly inhibited the secretion of IL-17A. Conclusion EVO did not significantly affect the activation process of T cells but inhibited T cell proliferation by arresting the cell cycle at the G2/M phase and significantly suppressed the secretion of the pro-inflammatory cytokine IL-17A, which suggests that EVO has the potential to serve as a lead compound for the development of low-toxicity and high-efficiency immunosuppressants and elucidates the mechanisms underlying the anti-inflammatory and immunomodulatory effects of the traditional Chinese medicine Evodia rutaecarpa.
Humans ; Cell Proliferation/drug effects* ; Quinazolines/pharmacology* ; T-Lymphocytes/metabolism* ; Lymphocyte Activation/drug effects* ; Apoptosis/drug effects* ; Interleukin-4/metabolism* ; Interleukin-10/metabolism* ; Interleukin-2 Receptor alpha Subunit/metabolism* ; Interleukin-17/metabolism* ; Interleukin-2/metabolism* ; Cell Cycle/drug effects* ; Cells, Cultured

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

In the ever-evolving landscape of cancer therapy, while cancer treatments such as chemotherapy, radiotherapy, and targeted therapy aim to eradicate malignant cells, they also inadvertently trigger cellular senescence in both cancerous and microenvironmental tissues. Therapy-induced senescence (TIS) can act as a barrier against tumor growth by halting cell proliferation in the short term, but the long-term persistence of therapy-induced senescent (TISnt) cells may pose a significant challenge in cancer management. Their distinct characteristics, like senescence-associated secretory phenotype (SASP), metabolic dysregulation, and immune evasion, make them exhibit remarkable heterogeneity to orchestrate the tumor microenvironment (TME), resulting in therapy resistance. However, how these TISnt cells functioning differently in cancer progression, and the intricate mechanisms by which they remodel the senescence-associated immunosuppressive microenvironment present challenges for improving anticancer therapy. Therefore, this review summarizes the heterogeneous TISnt cell phenotypes contributing to an accumulated senescent state, outlines their multidimensional interactions in the senescent microenvironment, and discusses current senescence-targeting strategies. Building on the current understanding of TIS, we propose potential avenues for improving TIS-targeting methodologies in the context of head and neck cancer, a representative heterogeneous malignancy, which can substantially enhance the efficacy of the "one-two punch" sequential treatment approach for head and neck cancer.
Humans ; Cellular Senescence/drug effects* ; Tumor Microenvironment ; Neoplasms/pathology* ; Senescence-Associated Secretory Phenotype

ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.

Objective To investigate the ameliorative effect and potential mechanism of Cyclocaryae Paliuri Folium in sodium palmitate-induced lipid deposition in HepG2 cells.Methods The effect of sodium palmitate and lyophilized powder of Cyclocaryae Paliuri Folium on the viability of HepG2 cells was determined by the CCK-8 method to determine the subsequent dosage administered.The HepG2 cells were divided into blank group,model group,pioglitazone group and Cyclocaryae Paliuri Folium low-,medium-and high-dosage group,the lipid deposition model of HepG2 cells was established using 350 μmol/L sodium palmitate,the medication group were given pioglitazone and low-,medium-and high-dosage of Cyclocaryae Paliuri Folium(100,250,500 μg/mL)for 12 h respectively.The intracellular lipid deposition was observed by Nile red staining and BODIPY493/503 fluorescent probe staining,the content of TNF-α and IL-6 in supernatant of cell culture medium were detected by ELISA,Western blot was used to detect PI3K,Akt,sterol-regulatory element binding protein-1(SREBP-1),fatty acid synthase(FAS),Bcl-2,Bax protein expression,qPCR was used to detect the mRNA expression of adipose triglyceride lipase(ATGL)and CD36.Results Compared with the blank group,the lipid deposition of HepG2 cells in the model group increased,TNF-α and IL-6 contents in the supernatant of cell culture medium significantly increased(P<0.01),the protein expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax in cells significantly increased,while the protein expression of Bcl-2 significantly decreased(P<0.01),the mRNA expression of ATGL significantly decreased,and the mRNA expression of CD36 significantly increased(P<0.01).Compared with the model group,the intracellular lipid deposition of the pioglitazone group and Cyclocaryae Paliuri Folium groups improved to varying degrees,the contents of TNF-α and IL-6 in the cell supernatant decreased,the expressions of p-PI3K,p-Akt,SREBP-1,FAS and Bax proteins decreased,the expression of Bcl-2 protein increased,the expression of ATGL mRNA increased,and the expression of CD36 mRNA decreased,with statistical significance in pioglitazone group and Cyclocaryae Paliuri Folium high-dosage group(P<0.05,P<0.01).Conclusion Cyclocaryae Paliuri Folium may ameliorate sodium palmitate-induced lipid deposition in HepG2 model cells by modulating the PI3K/Akt/SREBP-1/FAS signaling pathway and affecting triacylglycerol metabolism.

Objective To observe changes of white matter function in adolescent smoker(AS)with resting-state functional MRI(rs-fMRI)fractional amplitude of low-frequency fluctuation(fALFF)technique.Methods Forty-five adolescents(AS group)and 45 control subjects(control group)were prospectively enrolled,and brain rs-fMRI were acquired.Brain regions with fALFF being different between groups were observed,and the correlations with clinical indicators were analyzed.Results Compared with that in control group,fALFF of the right superior longitudinal fasciculus significantly elevated in AS group(FDR correct Q＜0.05),in which the peak of the cluster was positively correlated with score of Fagerstr?m test for nicotine dependence(FTND)(r=0.294,P=0.049).Conclusion White matter function changed in AS,presenting as significantly increased fALFF in right superior longitudinal fasciculus,which was positively correlated with nicotine dependence.

Objective:To analyze the infiltration of immune cells in different molecular subtypes of endometrial cancer(EC)at the protein level and explore the correlation between immune infiltration and clinicopathological features.Methods:Clinical data from 75 mismatch repair-deficient(MMR-D)EC cases and 74 mismatch re-pair-proficient(MMR-P)EC cases with comparable differentiation levels,diagnosed at Sichuan Provincial People's Hospital between January 2013 and January 2021,were selected.Molecular classification of EC was con-ducted according to the ProMisE standard.Immunohistochemistry(IHC)staining and fluorescent multiplexed im-munohistochemistry(F-mIHC)techniques were used to quantify the distribution of CD8+T cells,regulatory T cells(Tregs),and macrophages.The clinicopathological features and immune infiltration characteristics of different subtypes were investigated.Results:Among 149 samples,75 were MMR-D,8 were POLE-mutated(POLEmut),13 were p53-mutated(p53abn),and 53 were p53 wild-type(p53wt).The infiltration characteristics of CD8+T cells,Tregs,and macrophages were no statistically significant differences correlated with age and pathological stage(P>0.05).Among the molecular subtypes of EC,MMR-D tumors demonstrated a significantly higher densi-ty of CD8+T cells and Tregs compared to MMR-P tumors(P<0.05).Further comparison across the four EC mo-lecular subtypes revealed that the MMR-D subtype,which had a favorable prognosis,displayed a significantly high density of CD8+T cells compared to the p53abn subtype and the p53wt subtype(P<0.05).Additionally,the Tregs density of the MMR-D tumors was significantly higher than that of the p53wt tumors,in both the tumor area(P<0.05)and the stroma area(P<0.05).The POLEmut type tumors,which had the best prognosis,showed a high infiltration of CD8+T cells and Tregs cells compared to the p53abn and p53wt types,although there was no signifi-cant statistical difference(P>0.05).The p53wt subtype,which had a moderate prognosis,exhibited low density of CD8+T cells(P<0.05)and Tregs(tumor area,P<0.01,stroma area,P<0.05)compared to MMR-D tumors.The p53abn subtype,which was associated with the worst prognosis,exhibited higher infiltration of M2-like macro-phages than the MMR-D subtype(P<0.05)and the p53wt subtype(P<0.05)in tumor region,and lower CD8+T cell density than the MMR-D subtype(P<0.05).No significant statistical difference was observed in the density of M1-like macrophages across the four molecular subtypes in either the tumor or stroma areae(P>0.05).Conclu-sions:There was no statistically significant relation found between infiltration characteristics of immune cells and clinicopathological features.The types and distribution of infiltrated immune cells were different across these EC molecular subtypes.This indicated that ECs with different molecular subtype exhibited different features of immune infiltration which is closely associated with patient prognosis.