As the social pressure is increasing,the incidence of depression is growing.Testosterone is synthesized and secreted through the hypothalamic-pituitary-gonadal axis,which plays a regulatory role in men's mental health.Studies have shown that low testosterone levels,clinical hypogonadism,and androgen deprivation therapy-induced testosterone deficiency are significantly associated with male depression,while there are still many uncertainties about the mechanism of their effects.Given that low testosterone levels may serve as a characteristic biomarker of male depression risk,testosterone replacement therapy may have a good therapeutic effect on male depression.This article focuses on assessing the role of testosterone levels and related clinical therapies in mood regulation in men.
Humans ; Testosterone/physiology* ; Male ; Depression/etiology* ; Hormone Replacement Therapy

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Background and Aims:Chronic skin ulcers are a significant disease affecting patients'daily lives and psychological well-being.Abnormalities in the cells and extracellular matrix within the tissue may disrupt the balance of the microenvironment,hindering the normal skin repair process and leading to delayed healing of the ulcer.There is currently a lack of research on the mechanisms underlying the development of chronic ulcers and their diagnostic biomarkers.Single-cell sequencing,a newly developed high-throughput sequencing method in recent years,uses gene sequencing at the single-cell resolution to precisely reveal disease mechanisms and has been applied in various diseases.This study used single-cell transcriptome sequencing(scRNA-Seq)to investigate the cellular heterogeneity in chronic skin ulcer tissue to elucidate the potential molecular mechanisms behind delayed healing and provide new insights for clinical treatment.Methods:The scRNA-Seq technology was used to compare the differences in cell subpopulations and gene expression between chronic ulcer tissue and normal skin tissue.Single cells were sorted using a microfluidic platform,and cDNA libraries were constructed for subsequent differential gene analysis and functional enrichment analysis.Results:scRNA-Seq analysis revealed significant immune-metabolic remodeling features in chronic ulcer tissue:the number of B cells,monocytes,and macrophages in ulcer tissue increased by 2.1 to 3.5 times compared to the normal tissue control.This was accompanied by widespread activation of collagen synthesis genes(COL1A1/COL3A1)and synergistic suppression of immune regulators(e.g.,granzyme family GZMA/GZMB/H).Cross-cell subpopulation functional network analysis showed that hypoxia response mediated by the HIF-1 signaling pathway and PI3K/Akt pathway abnormalities formed a positive feedback loop,exacerbating the imbalance in the secretion of inflammatory factors(CXCL3/8,TGFBI)and compensatory upregulation of mitochondrial oxidative phosphorylation.Conclusion:Chronic skin ulcers exhibit significant differences in cellular heterogeneity and gene expression,suggesting that chronic ulcers are not simply tissue defects but a complex pathological process dominated by chronic inflammation and immune dysregulation.The coordinated dysregulation of multiple cell subpopulations in the ulcer microenvironment,along with persistent inflammatory responses and metabolic abnormalities,is interconnected through the HIF-1/TNF/MAPK pathway network.Downregulation of granzyme gene family members and abnormal histone modifications may contribute to immune clearance defects,providing a theoretical basis for developing novel therapies targeting epigenetic regulation or mitochondrial function.

OBJECTIVE: To prepare clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSC) with high expression of hematopoietic supporting factors and evaluate their stem cell characteristics. METHODS: Fetal umbilical cord tissues were collected from healthy postpartum women during full-term cesarean section. Wharton's jelly was mechanically separated and hUC-MSCs were obtained by explant culture method and enzyme digestion method in an animal serum-free culture system with addition of human platelet lysate. The phenotypic characteristics of hUC-MSCs obtained by two methods were detected by flow cytometry. The differences in proliferation ability between the two groups of hUC-MSCs were identified through CCK-8 assay and colony forming unit-fibroblast (CFU-F) assay. The differences in multilineage differentiation potential between the two groups of hUC-MSCs were identified through induction of adipogenic, osteogenic, and chondrogenic differentiation. The mRNA expression levels of hematopoietic supporting factors such as SCF, IL-3, CXCL12, VCAM1 and ANGPT1 in the two groups of hUC-MSCs were identified by real-time fluorescence quantiative PCR(RT-qPCR). RESULTS: The results of flow cytometry showed that hUC-MSCs obtained by the two methods both expressed high levels of CD73, CD90 and CD105, while lowly expressed CD31, CD45 and HLA-DR. The results of CCK-8 and CFU-F assay showed that the proliferation ability of hUC-MSCs obtained by explant culture method was better than those obtained by enzyme digestion method. The results of the triple lineage differentiation experiment showed that there was no significant difference in multilineage differentiation potential between the two grous of hUC-MSCs. The results of RT-qPCR showed that the mRNA expression levels of hematopoietic supporting factors SCF, IL-3, CXCL12, VCAM1 and ANGPT1 in hUC-MSCs obtained by explant cultrue method were higher than those obtained by enzyme digestion method. CONCLUSION Clinical-grade hUC-MSCs with high expression levels of hematopoietic supporting factors were successfully cultured in an animal serum-free culture system.
Humans ; Mesenchymal Stem Cells/metabolism* ; Umbilical Cord/cytology* ; Cell Differentiation ; Female ; Cell Proliferation ; Cells, Cultured ; Chemokine CXCL12/metabolism* ; Angiopoietin-1/metabolism* ; Vascular Cell Adhesion Molecule-1/metabolism* ; Stem Cell Factor/metabolism* ; Flow Cytometry ; Pregnancy

OBJECTIVE: To investigate the characteristics of central nervous system regulation in patients with refractory overactive bladder (rOAB) using resting-state functional magnetic resonance imaging (rs-fMRI), and to analyze the differences in brain function and connection between the patients and healthy population. METHODS: From May 1 to November 30, 2024, we performed rs-fMRI for 47 rOAB patients and another 47 matched healthy controls, documented relevant clinical data from all the participants and obtained their Overactive Bladder Symptom Scores (OABSS) and Overactive Bladder Questionnaire (OAB-Q) scores. Based on rs-fMRI, we compared the results of Independent Component Analysis (ICA), amplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo) and degree centrality (DC) between the rOAB patients and healthy controls. RESULTS: The rOAB patients, in comparison with the healthy controls, showed dramatically higher daytime urination frequency (11.64 ± 3.85) vs (5.76 ± 0.91), nighttime urination frequency (3.72 ± 1.64) vs (0.31 ± 0.47), OABSS (8.22 ± 2.21) vs (0.64±0.78), OAB-Q1 score (20.85 ± 5.28) vs (6.78 ± 1.04), and OAB-Q2 score (45.04 ± 12.11) vs (14.51 ± 1.66) (all P<0.01). No statistically significant differences were observed in the results of ICA and ALFF between the right superior frontal and right middle frontal regions in the rOAB patients (P>0.05), but fALFF, ReHo and DC were significantly decreased in the patients compared with those in the healthy controls (P<0.01). CONCLUSION Compared with healthy population, the functions and connection of the frontal superior right and frontal middle right brain regions in rOAB patients are significantly down-regulated, which may serve as new therapeutic targets.
Humans ; Urinary Bladder, Overactive/physiopathology* ; Magnetic Resonance Imaging ; Brain/physiopathology* ; Female ; Male ; Adult ; Surveys and Questionnaires ; Case-Control Studies ; Middle Aged ; Rest ; Brain Mapping

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

OBJECTIVE: This study examines the sequential mediating roles of body pain and self-reported health in the association between sleep duration and self-reported life satisfaction among elderly Chinese adults. METHODS: Data from the fifth wave of the China Health and Retirement Longitudinal Survey (CHARLS) were used to analyse the relationships between sleep duration and body pain, self-reported health, and life satisfaction through logistic regression and Restricted Cubic Spline (RCS) analyses. The sequential mediation effects of body pain and self-reported health status were examined via chain mediation analysis. RESULTS: Logistic regression analysis showed that sleeping fewer than 6 hours or 6-7 hours was linked to higher risks of body pain, poor health, and dissatisfaction with life compared to sleeping 7-8 hours (all P < 0.05). Additionally, those sleeping more than 9 hours also had increased risks of poor health and dissatisfaction with life compared to those sleeping 7-8 hours (all P < 0.05). Chain mediation analysis showed that body pain and self-reported health status sequentially mediated 46.15% of the association between sleep duration and life satisfaction. CONCLUSION Body pain and self-reported health may shape the relationship between sleep duration and life satisfaction in elderly Chinese adults.
Humans ; Male ; Female ; Aged ; Personal Satisfaction ; Sleep ; Health Status ; Self Report ; China ; Middle Aged ; Longitudinal Studies ; Pain/psychology* ; Sleep Duration