AIM: To investigate the specific molecular mechanism of Yinqiao Powder in affecting macrophage polarization in herpes simplex keratitis(HSK)through the cyclic GMP-AMP synthetase(cGAS)-stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)molecular pathway.METHODS:Human corneal epithelial cells(HCE-T)were divided into control, HSK, and HSK + Yinqiao Powder groups. M0 macrophages were grouped as Ctrl, HSV-1, HSV-1+oe-cGAS, HSV-1+Yinqiao Powder, and HSV-1+oe-cGAS+Yinqiao Powder. Conditional medium(CM)from each group of M0 macrophages was collected to intervene in HCE-T cells and divided into Ctrl-CM, HSV-1-CM, HSV-1+oe-cGAS-CM, and HSV-1+Yinqiao Powder-CM groups. Cell viability was detected by MTT assay, and apoptosis was detected by TUNEL assay. ELISA was used to detect the concentrations of Arg-1 and iNOS in cell supernatants, and Western blotting was used to detect the relative protein expressions of cGAS, STING, and IRF3. Balb/c mice were divided into control, model, and drug groups. The model and drug groups were inoculated with HSV-1 on the cornea of Balb/c mice using the corneal scratch method to construct an HSK mouse model, and the drug group was treated with Yinqiao Powder. The incidence and mortality of the three groups were compared on days 1, 3, 5, 7, and 14 after modeling.RESULTS:Compared with the control group, the HCE-T cell viability in the HSK group was decreased but apoptosis was increased, which was reversed by Yinqiao Powder intervention. Compared with the Ctrl group, the Arg-1 concentration in the cell supernatant of the HSV-1 group was decreased, the iNOS concentration was increased, and the protein expressions of cGAS, STING, and IRF3 were decreased. Compared with the HSV-1 group, the Arg-1 concentration was increased, the iNOS concentration was decreased, and the protein expressions of cGAS, STING, and IRF3 were enhanced in the HSV-1+oe-cGAS group and the HSV-1+Yinqiao Powder group, and the same results were obtained in the HSV-1+oe-cGAS+Yinqiao Powder group. Compared with the Ctrl-CM group, the HCE-T cell viability was decreased and apoptosis was increased in the HSV-1-CM group, which was reversed by overexpressing cGAS in macrophages or intervening with Yinqiao Powder. In vivo experiments found that Yinqiao Powder intervention could improve the pathological progression of keratitis.CONCLUSION:Yinqiao Powder inhibits M1 polarization of macrophages through the cGAS-STING-IRF3 molecular pathway, thereby delaying the progression of HSK.

The prevalence of female pelvic floor dysfunction (PFD) ranges from 17.8% to 74.07%, with approximately 30% of patients experiencing comorbid anxiety, depression, or other psychological disorders, severely impairing their quality of life. Current assessment methods for PFD are primarily based on clinical techniques such as the pelvic organ prolapse quantification and two-dimensional ultrasound. But they are limited by high subjectivity, operational complexity, and the inability to provide real-time dynamic evaluation. In recent years, emerging technologies including high-density electromyography, three-dimensional ultrasound, specific biomarkers, and artificial intelligence have complemented conventional clinical methods by providing dynamic functional data and molecular-level evidence, achieving multidimensional “structure-function-molecular”assessment of PFD. The relevant literature on PFD assessment published in CNKI, PubMed, and other databases from 2019 to 2024 were retrieved. The current application status and value of commonly used clinical techniques, the core characteristics of emerging technology assessments, and the integration path between the two were reviewed, so as to provide the evidence for individualized diagnosis and treatment of PFD.

BACKGROUND: Inflammation plays a critical role in severe cerebral venous thrombosis (CVT) pathogenesis, but the benefits of anti-inflammatory therapies remain unclear. This study aimed to investigate the association between steroid therapy combined with anticoagulation and the prognosis of acute/subacute severe CVT patients. METHODS: A prospective cohort study enrolled patients with acute/subacute severe CVT at Xuanwu Hospital (July 2020-January 2024). Patients were allocated into steroid and non-steroid groups based on the treatment they received. Functional outcomes (modified Rankin scale [mRS]) were evaluated at admission, discharge, and 6 months after discharge. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), cerebrospinal fluid (CSF) IL-6, and intracranial pressure were measured at admission and discharge in the steroid group. Fundoscopic Frisén grades were assessed at admission and 6 months after discharge. Univariate and multivariate logistic regression were used to evaluat associations between steroid use and favorable outcomes (mRS ≤2) at the 6-month follow-up. Paired tests assessed changes in hs-CRP and other variables before and after treatment, and Spearman's correlations were used to analyze relationships between these changes and functional improvements. RESULTS: A total of 107 and 58 patients in the steroid and non-steroid groups, respectively, were included in the analysis. Compared with the non-steroid group, the steroid group had a higher likelihood of achieving an mRS score of 0-2 (93.5% vs . 82.5%, odds ratio [OR] = 2.98, P  = 0.037) at the 6-month follow-up. After adjusting for confounding factors, the result remained consistent. Pulsed steroid therapy did not increase mortality during hospitalization or follow-up, nor did it lead to severe steroid-related complications (all P  >0.05). Patients in the steroid group showed a significant reduction in serum hs-CRP, IL-6, CSF IL-6, and intracranial pressure at discharge compared to at admission, as well as a significant reduction in the fundoscopic Frisén grade at the 6-month follow-up compare to at admission (all P  <0.001). A reduction in serum inflammatory marker levels during hospitalization positively correlated with improvements in functional outcomes ( P  <0.05). CONCLUSION: Short-term steroid use may be an effective and safe adjuvant therapy for acute/subacute severe CVT when used alongside standard anticoagulant treatments, which are likely due to suppression of the inflammatory response. However, these findings require further validation in randomized controlled trials. TRAIL REGISTRATION ClinicalTrials.gov , NCT05990894.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Anticoagulants/therapeutic use* ; C-Reactive Protein/metabolism* ; Interleukin-6/metabolism* ; Intracranial Thrombosis/drug therapy* ; Prospective Studies ; Steroids/therapeutic use* ; Venous Thrombosis/drug therapy*

Objective To investigate the gene expression and regulatory mechanisms of mouse embryonic fibroblasts (MEFs) under inflammatory conditions, aiming to elucidate the role of MEFs in inflammatory responses and provide a foundation for discovering anti-inflammatory drugs that act by modulating MEF function. Methods MEFs cultured in vitro were divided into the following groups: lipopolysaccharides (LPS)-treated group, inflammatory conditioned medium (CM)-treated group, and control group, which were treated with LPS, CM, and equal volume solvent, respectively. Transcriptome sequencing was used to analyze the effects of two stimuli on gene expression profile of MEFs. Real time fluorescence quantitative PCR (RT-qPCR) was employed to verify the transcription levels of highly expressed genes of MEFs induced by CM. ELISA was performed to determine the concentrations of cytokines in cell supernatants. Finally, the regulatory effects of CM on the activation of signaling pathways in MEFs were analyzed by immunoblotting. Results Transcriptome analysis showed that both LPS and CM induced the transcription of a large number of genes in MEFs. Compared with LPS, CM potentiated the mRNA transcription of some acute phase proteins, inflammatory cytokines, chemokines, matrix metalloproteinases (MMP), prostaglandin synthetases, and colony-stimulating factors. The transcriptome analysis was verified by RT-qPCR. The results of ELISA showed that CM treatment significantly increased the secretion of interleukin 6 (IL-6), C-C motif chemokine ligand (CCL2), and C-X-C motif chemokine ligand (CXCL1) by MEFs compared with LPS. Mechanism study showed that both LPS and CM induced the phosphorylation of nuclear factor-κB p65 (NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), extracellular regulated protein kinases 1/2 (ERK1/2), and TANK-binding kinase (TBK) in MEFs, and CM strongly stimulated the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in MEFs. Conclusion Both LPS and CM can induce transcription and protein secretion of various inflammation-related genes in MEFs. CM can partly enhance LPS-induced activation of MEFs, and the mechanism may be related to the enhancement effect of CM on the activation STAT3 signaling pathway.
Animals ; Fibroblasts/immunology* ; Mice ; Lipopolysaccharides/pharmacology* ; Inflammation/metabolism* ; Signal Transduction/drug effects* ; Gene Expression Regulation/drug effects* ; Cytokines/genetics* ; Culture Media, Conditioned/pharmacology* ; Cells, Cultured

Invasive angiomyxoma（AAM） is characterized by unclear boundaries, non enveloped glial growth, high recurrence rate, and belongs to a benign tumor, but it is invasive and grows slowly. A patient with recurrent left vestibular invasive angiomyxoma was admitted to the Otorhinolaryngology ward of Beijing Traditional Chinese Medicine Hospital Affiliated with Capital Medical University. The patient underwent two repeated surgeries and underwent a combined internal and external nasal approach for the removal of the nasal vestibular angiomyxoma. The patient recovered well after the surgery and has not recurred since follow-up.
Humans ; Myxoma/pathology* ; Neoplasm Recurrence, Local ; Nose Neoplasms/pathology*

Objective:To investigate the consistency and sensitivity of minimal residual disease (MRD) detected by multicolor flow cytometry (FCM) and real-time quantitative polymerase chain reaction (RQ-PCR) in patients with acute myeloid leukemia (AML) accompanied by monocytic differentiation after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective case series study was conducted. A total of 218 patients diagnosed with AML accompanied by monocytic differentiation who underwent allo-HSCT in Peking University People's Hospital between January 2017 and December 2021 were included. MRD was detected by using bone marrow FCM and RQ-PCR at predefined intervals (at 1-, 2-, 3-, 4.5-, 6-, 9-, and 12-month before and after transplantation). Patients were grouped based on AML-related specific genes, and dynamic changes in MRD results detected by FCM and RQ-PCR after transplantation were analyzed to evaluate the correlation with post-transplant relapse.Results:A total of 218 enrolled patients included 114 males and 106 females, with the median age of 32 years (1-65 years). The median follow-up duration was 218 d (21-1 541 d). Hematologic relapse occurred in 26 patients (12.7%), with a median relapse time of 272 d (83-934 d); 35 patients (15.9%) died, including 15 (6.9%) due to leukemia relapse and 20 (9.2%) due to transplant-related mortality. Predictive markers for relapse included once WT1 positive (WT1+once), twice WT1 positive (WT1+twice), CBFβ::MYH11 fusion genes positive, mixed-lineage leukemia (MLL)-related fusion genes positive, AML1::ETO fusion genes positive, and once FCM positive (FCM+once), twice FCM positive (FCM+twice). The overall consistency rate between FCM and RQ-PCR for MRD detection in AML patients accompanied by monocytic differentiation after transplantation was 75.7% (165/218). The consistency rate of MRD detection results in WT1+once, WT1+ twice, MLL-related fusion gene positive, and NPM1 gene mutation positive with FCM was higher than the average value (>75.7%), while the consistency rate of MRD detection results in AML1::ETO and CBFβ::MYH11 fusion gene positive with FCM was lower than the average value (<75.7%). Notably, persistent low-level positivity without relapse after transplantation occurred in cases with WT1 (15 patients), NPM1 (2 patients), CBFβ::MYH11 (11 patients), or AML1::ETO (2 patients); in contrast, MLL-related fusion genes (particularly MLL::AF6 and MLL::AF9) positive after transplantation indicated relapse in patients. The sensitivity and specificity of RQ-PCR for MRD monitoring varied by genetic markers: WT1+once and WT1+twice (sensitivity: 66.7%, 50.0%; specificity: 84.5%, 91.1%, respectively), AML1::ETO (sensitivity: 100.0%; specificity: 50.0%), CBFβ::MYH11 (sensitivity: 100.0%; specificity: 58.6%), MLL-related fusion genes (sensitivity: 75.0%; specificity: 96.4%), and NPM1 (sensitivity: 75.0%; specificity: 91.7%).Conclusions:The sensitivity and specificity of AML-related genetic markers for recurrence prediction show differences. Discrepancies between RQ-PCR and FCM in MRD detection are notable in AML with monocytic differentiation after transplantation. FCM exhibits relatively lower sensitivity for MRD monitoring in this subtype, while RQ-PCR based on AML-related genes may compensate for FCM limitations.

Objective To analyze the changes in serum levels of cancer-associated fibroblast-re-lated factors[vascular endothelial growth factor(VEGF),transforming growth factor-β1(TGF-β1)]and inflammatory mediators[interleukin-1(IL-1),interleukin-6(IL-6)]in patients with endometrial cancer(EC)and their relationship with clinicopathological features.Methods A total of 180 pa-tients with EC were selected as EC group,and 100 patients with benign endometrial lesions who visi-ted the hospital during the same period were selected as control group.The serum levels of VEGF,TGF-β1,IL-1 and IL-6 were compared between the two groups,as well as among EC patients with different clinicopathological features.Spearman correlation analysis was used to examine the relation-ship between the above-mentioned serum indicators and clinicopathological features in EC patients.Results The serum levels of VEGF,TGF-β1,IL-1 and IL-6 in the EC group were higher than those in the control group,with statistically significant differences(P＜0.05).The serum levels of VEGF,TGF-β1,IL-1 and IL-6 in EC patients with a myometrial invasion depth ≥ 1/2 and lymph node metas-tasis were higher than those in EC patients with a myometrial invasion depth＜1/2 and no lymph node metastasis(P＜0.05).Spearman correlation coefficient analysis showed that the serum levels of VEGF,TGF-β1,IL-1 and IL-6 in EC patients were positively correlated with myometrial invasion depth and lymph node metastasis status,respectively(P＜0.05).Conclusion The serum levels of VEGF,TGF-β1,IL-1 and IL-6 are significantly elevated in EC patients.These indicators are sig-nificantly correlated with clinicopathological features and have potential value in the early diagnosis,prognosis assessment,and targeted therapy of EC.

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Allergic conjunctivitis is the most common type of allergic eye disease, and the incidence in children and adolescents is increasing year by year. Drug therapy can only relieve some symptoms and only in a short period, while allergen immunotherapy is currently a therapy that can significantly improve the symptoms of chronic allergy and the course of the disease. This method has been used abroad for many years but has yet to be reported in China. The author reviews the effective mechanism and clinical efficiency of allergen immunotherapy and provides a reference for the further clinical application in China.

ObjectiveTo investigate the effects of Bushen Huoxue prescription on the cardiac function， inflammation， and quality of life of the patients with chronic heart failure resistant to diuretics. MethodA total of 78 patients who met the inclusion criteria were randomized into observation and control groups （39 cases）. Both groups received standardized treatment for diuretic resistance in accordance with the guidelines. In addition， the observation group received Bushen Huoxue prescription. The cardiac function indicators， total response rate regarding symptom alleviation， exercise endurance， urine volume， body mass， quality of life， and levels of inflammatory cytokines were compared between the two groups before and after treatment. ResultBefore treatment， the two groups of patients showed no significant differences in terms of 24 h urine volume， body mass， 6 minute walk test （6MWT）， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP） level， left ventricular ejection fraction （LVEF）， stroke volume （SV）， and serum levels of interleukin-6 （IL-6）， interleukin-4 （IL-4）， and tumor necrosis factor-alpha （TNF-α）. After treatment， the observation group outperformed the control group in terms of the response rates regarding traditional Chinese medicine symptom scores and New York Heart Association （NYHA） grading of cardiac function （P<0.05）. After treatment， the body mass， MLHFQ score， and IL-6， TNF-α， and NT-proBNP levels decreased in both groups （P<0.05， P<0.01）， and the observation group showed more significant decreases than the control group （P<0.05， P<0.01）. Both groups showed increases in 24-h urine volume， 6MWT， LVEF， SV， and IL-4 after treatment （P<0.05， P<0.01）， and the observation group showed more significant increases than the control group （P<0.05， P<0.01）. ConclusionThe combination of Bushen Huoxue prescription with standardized treatment is effective in ameliorating the clinical symptoms of the patients with chronic heart failure resistant to diuretics. Moreover， it alleviates diuretic resistance and improves the cardiac function without causing obvious adverse reactions.