ObjectiveTo investigate the effects of lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1） gene G501C on brain structure and cognitive function in patients with white matter hyperintensities （WMH）. MethodsA total of 118 patients with WMH were enrolled. All participants underwent T1-weighted and T2-fluid-attenuated inversion recovery （T2-FLAIR） MRI to assess gray matter structure and WMH burden， and completed the mini-mental state examination （MMSE） and Montreal cognitive assessment （MoCA）. Partial correlation and mediation analyses were performed to explore the impact of LOX-1 polymorphism on cognitive function. ResultsParticipants were divided into GG+GC group （n = 35） and CC group （n = 83）. The GG+GC group showed lower MMSE and MoCA scores （MMSE： P=0.003； MOCA： P=0.015）， as well as greater WMH burden （all P0.001）， compared with the CC group. Voxel-based morphometry （VBM） analysis revealed reduced left thalamic volume in the GG+GC group， which was correlated with cognitive scores （all P0.05）. Subregional thalamic analysis further showed volume reductions in the lateral， ventral， medial， and pulvinar thalamic regions （all P0.05） in the GG+GC group， all positively associated with cognitive performance （all P0.05）. Mediation analyses indicated that volumes of the medial and pulvinar thalamic regions mediated the association between genotype and cognitive function （MMSE， MoCA）， and that WMH volume mediated the effect on MoCA scores. ConclusionThe LOX-1 G501C polymorphism may indirectly affect cognitive function by influencing specific thalamic subregional volumes and white matter damage， suggesting a potential mediating role of thalamic structures between genetic background and cognitive impairment.

OBJECTIVE To investigate the current status of informatization tools applied to antimicrobial stewardship in county hospitals in China， and to provide a reference for promoting the informatization development of antimicrobial stewardship in county hospitals.METHODS From August to September 2025， an online questionnaire survey was conducted among 1 007 county hospitals across 31 provinces（autonomous regions， and municipalities） in China. The survey focused on the application of four types of informatization tools：the real-time monitoring system for antimicrobial use， the pre-prescription review system， the irrational use warning system， and the electronic prescription evaluation system（hereinafter referred to as the “monitoring system”“review system”“warning system”“evaluation system”，respectively）. Correlation analysis and binary Logistic regression analysis were employed to explore the influencing factors.RESULTS Of the county hospitals， 80.83% were equipped with at least one type of informatization tool for antimicrobial stewardship， while 19.17% had no relevant tool. Only 18.87% of the hospitals were equipped with all four types of tools. The monitoring system exhibited the highest equipped rate （70.80%）， whereas the warning system was equipped in only 33.96% of the hospitals. Four types of tools are evenly and adequately deployed in the eastern region， the central and western regions have far lower deployment rates of intervention tools including review system and warning system， accompanied by prominent intra-provincial gaps. The total number of the health technicians， hospital grade， and prescription review rate of outpatient antibacterial drug were significantly and positively correlated with the deployment rates of the four informatization tools （ P ＜0.05）. The results of the Logistic regression model fitting indicated that the model of the review system was rated “excellent” [area under the receiver operating characteristic curve （AUC）＝0.81]， and the model of the warning system was rated “further improvement” （AUC＝0.67）. The total number of health technicians was significantly positively correlated with the deployment rates of all four types of informatization tools （all P ＜0.05）.CONCLUSIONS The informatization of antimicrobial stewardship in county hospitals in China remains in the initial stage of transitioning from “passive statistics” to “active prevention and control”， with challenges such as structural imbalance and regional disparities. In the future， differentiated support strategies should be implemented， the allocation of resources should be optimized， to enhance the level of refined antimicrobial stewardship.

BACKGROUND: The combination of immune checkpoint inhibitors and chemotherapy (ICI + Chemo) shows promise in treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), but some patients received limited benefit and the prognostic factors of the treatments remain unclear. Furthermore, ICIs efficacy in subsequent treatments needs further evaluation. METHODS: A systematic search on PubMed, Embase, the Cochrane Library, and major conference proceedings was conducted to identify relevant studies for meta-analysis. The study was designed to compare ICI + Chemo with chemotherapy in first-line treatment and identify efficacy predictors, and to evaluate ICIs alone in subsequent-line treatment for RM-NPC, with a focus on progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (AEs). RESULTS: Fifteen trials involving 1928 patients were included. Three trials compared ICI + Chemo with chemotherapy as a first-line treatment, while 12 trials evaluated ICIs alone in subsequent-line treatment of RM-NPC patients. First-line ICI + Chemo showed superior PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.43-0.63; P <0.001) and ORR (risk ratio [RR] = 1.14, 95% CI, 1.05-1.24; P <0.001) compared to chemotherapy, without increased AEs (RR = 1.01, 95% CI, 0.99-1.03; P = 0.481). Neither programmed death-ligand 1 (PD-L1) nor other factors predicted the efficacy of ICI + Chemo vs . chemotherapy. Subsequent-line ICIs alone had a median PFS of 4.12 months (95% CI, 2.93-5.31 months), an ORR of 24% (95% CI, 20-28%), with grade 1-5/grade 3-5 AEs at 79%/14%. However, ICIs alone were associated with significantly shorter PFS (HR = 1.31, 95% CI, 1.01-1.68; P = 0.040) than chemotherapy alone. CONCLUSIONS ICI + Chemo confers superior survival benefits compared to chemotherapy in first-line RM-NPC treatment, independent of PD-L1 expression or other factors. However, ICIs alone demonstrate a manageable safety profile but do not surpass chemotherapy in efficacy for subsequent-line treatment.
Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Nasopharyngeal Carcinoma/drug therapy* ; Nasopharyngeal Neoplasms/drug therapy* ; Neoplasm Recurrence, Local/drug therapy*

Objective To investigate the common molecular features of immunothrombosis, thus enhancing the comprehension of thrombosis triggered by immune and inflammatory responses and offering crucial insights for identifying potential diagnostic and therapeutic targets. Methods Differential gene expression analysis and functional enrichment analysis were conducted on datasets of systemic lupus erythematosus (SLE) and venous thromboembolism (VTE). The intersection of differentially expressed genes in SLE and VTE with those of neutrophil extracellular traps (NET) yielded cross-talk genes (CG) for SLE-NET and VTE-NET interaction. Further analysis included functional enrichment and protein-protein interaction (PPI) network assessments of these CG to identify hub genes. Venn diagrams and receiver operating characteristic (ROC) curve analysis were employed to pinpoint the most effective shared diagnostic CG, which were validated using a graft-versus-host disease (GVHD) dataset. Results Differential expression genes in SLE and VTE were associated with distinct biological processes, whereas SLE-NET-CG and VTE-NET-CG were implicated in pathways related to leukocyte migration, inflammatory response, and immune response. Through PPI network analysis, several hub genes were identified, with matrix metalloproteinase 9 (MMP9) and S100 calcium-binding protein A12 (S100A12) emerging as the best shared diagnostic CG for SLE (AUC: 0.936 and 0.832) and VTE (AUC: 0.719 and 0.759). Notably, MMP9 exhibited good diagnostic performance in the GVHD dataset (AUC: 0.696). Conclusion This study unveils the common molecular features of SLE, VTE, and NET, emphasizing MMP9 and S100A12 as the optimal shared diagnostic CG, thus providing valuable evidence for the diagnosis and therapeutic strategies related to immunothrombosis. Additionally, the expression of MMP9 in GVHD highlights its critical role in the risk of VTE associated with immune system disorders.
Humans ; Computational Biology/methods* ; Lupus Erythematosus, Systemic/immunology* ; Protein Interaction Maps/genetics* ; Venous Thromboembolism/therapy* ; Matrix Metalloproteinase 9/genetics* ; Extracellular Traps/metabolism* ; Gene Regulatory Networks ; Thrombosis/immunology* ; Graft vs Host Disease/genetics* ; Gene Expression Profiling

OBJECTIVE To screen and obtain nanobodies with neutralizing activity against granulo-cyte-macrophage colony stimulating factor(GM-CSF)to contribute to investigations into the mecha-nism of inflammation interventions and the development new drugs.METHODS Recombinant human GM-CSF was subcutaneously injected to immunize camels.Peripheral blood was collected after five immunizations,and mononuclear cells were isolated.Total mRNA was extracted,and the variable domains of the heavy chain of heavy-chain antibody(VHH,also called nanobody)genes were obtained by PCR amplification after reverse transcription.The genes were cloned into the pADSCFV-S phage display vector and electrotransformed into TG1 competent cells to construct a nanobody immune library that was screened with recombinant human GM-CSF immobilized on a solid phase.The VHH genes specifi-cally binding to human GM-CSF were cloned into the pABG eukaryotic expression vector before VHH-Fc samples were prepared by using the human embryonic kidney 293 fibroblast expression system.The binding activity of candidate VHH-Fc molecules to GM-CSF was investigated through ELISA response curves,and binding colorimetric values with different antigens were detected to determine their specificity.The binding affinity between VHH-Fc candidates and GM-CSF was measured using biolayer interferom-etry(BLI).The inhibition rate curve of VHH-Fc candidates on GM-CSF was detected through cell prolif-eration assays to determine its neutralization activity.The Uncle system was used to investigate its thermal stability.100 μg of VHH-Fc was injected into mice via the tail vein,and the serum concentration of VHH-Fc was quantitatively detected by ELISA to examine its pharmacokinetic curve in mice.RESULTS The camel serum titer of anti-human GM-CSF antibodies was higher than 1:800 000 after the fifth immuni-zation,and the capacity of the constructed nanobody library was about 5.55×107.Following the screening process,five candidate VHH-Fc molecules specifically binding to human GM-CSF were obtained.Among these,22N10 effectively neutralized the cell proliferation-promoting activity of GM-CSF(the IC50 value was 17.23 nmol·L-1).Subsequent studies revealed that 22N10 interacted with human GM-CSF with an affinity of 1.97×10-8 mol·L-1,blocked the binding of GM-CSF to its receptor CSF2Rα,exhibited good thermal stability(Tm1=59.2℃),and showed favorable metabolic characteristics in mice.CONCLU-SION A new candidate nanobody molecule 22N10 targeting human GM-CSF is obtained which is expected to facilitate the drug development and mechanism investigations.

Objective To evaluate the efficacy and safety of Qixian Tongluo Formula in the treatment of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome,and to preliminarily explore the molecular mechanism of Qixian Tongluo Formula in improving impaired motor function from the perspective of cross-kingdom regulation of Chinese medicine microRNA(miRNA).Methods A pragmatic randomized controlled trial was conducted with 102 patients in the recovery period of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome in our hospital.Patients were randomly divided into trial group and control group,with 51 cases in each group.The control group received standard Western medicine standard treatment,while the trial group received Qixian Tongluo Formula in addition to the standard treatment,with one dose per day,boiled in water,and taken warm after breakfast and dinner for a course of 2 months.The disability rate was used as the main efficacy indicator,and the incidence of adverse reactions was used as a safety indicator.miRNA from patient serum and Qixian Tongluo decoction were extracted respectively,and high-throughput sequencing was performed.The two sequences were compared to screen out the cross-kingdom gene transfer of Chinese medicine miRNA.Finally,its target genes of miRNA were predicted,and GO function and KEGG pathway enrichment analysis were carried out.Results A total of 67 patients completed the clinical trial,including 36 cases in the trial group and 31 cases in the control group;The disability rate in the trial group(13.9%)was lower than that in the control group(35.5%)(P<0.05);The incidence of adverse reactions was similar between the trial group(7.69%)and the control group(6.06%)(P>0.05);A total of 9530 Qixian Tongluo decoction miRNA sequences were screened,with 150 potentially involved in cross-kingdom gene transfer,including families such as miR-15 and miR-17;According to the target gene prediction of the top 10 miRNAs in cross-kingdom gene transfer of Chinese medicine,345 overlapping target genes were obtained;GO functional enrichment analysis revealed 16 biological processes,7 cellular components,and 2 molecular functions among the top 25 enriched functions,while KEGG pathway analysis mainly focused on the transforming growth factor-βsignaling pathway,neurotrophin signaling pathway,which are closely related to neural repair and functional recovery processes such as glial scar formation and synaptic plasticity after cerebral ischemia.Conclusion Qixian Tongluo Formula can significantly improve the functional independence level of patients with kidney deficiency and blood stasis syndrome in the recovery period of paralysis after cerebral infarction,offering a safe and effective treatment option for these patients;There were a large number of miRNAs in Qixian Tongluo decoction,some of which could cross-kingdom transferred into the human blood circulation,and promote the recovery of motor function in patients with cerebral infarction through multi-target,multi link and multi pathway gene network regulation.This study provides a new idea for subsequent clinical and basic research.

Objective To understand the status of medical laboratories participating in external quality assessment(EQA)program in China.Methods The test covered by an EQA control rate and acceptable performance rate of theinformation collection and data analy-sis systems in the EQA program developed by National Center for Clinical Laboratories in medical laboratories of nationwide various re-gions were evaluated descriptively and analyzed statistically.Forty analytes in various disciplines were selected to analyze statistically the implementation of the testing items and participation retes of EQA program.Results The number of medical laboratories participat-ing in EQA program increased yearly from 592 in 2019 to 1 169 in 2023.The nationwide median test covered by an EQA control rate and acceptable performance rate of EQA program reached over 91％and 98％,respectively.In 2023,the median test covered by an EQA control rate of EQA program in the medical laboratories of nationwide regions showed that the median test covered by an EQA con-trol rate reached 100％in Gansu and Hainan regions,and the medians of acceptable performance rate reached 100％in Beijing,Guangdong,Hubei,Jiangsu,Shandong,Shanxi,Shanghai,Tianjin,Xinjiang,and Zhejiang regions.Among the 40 analytes,the test covered by an EQA control rate of only 6 EQA items were greater than 80％in nationwide medical laboratories,i.e.,rheumatoid factor,neonatal deafness gene detection,high throughput sequencing of peripheral fetal chromosome aneuploidy(T21,T18 and T13)by high throughput sequencing,thalassemia gene typing,hepatitis C virus RNA quantification,and EGFR gene mutation,and the acceptable performance rates of only 3 EQA items were 100％,i.e.,HbA2,urine microalbumin,and non-invasive prenatal testing(NIPT).Thir-ty-six analytes exhibited acceptable performance rate above of 80％,while that of troponin I was below 80％.Conclusion The medical laboratories in China should further increase their test covered by an EQA control rate and acceptable performance rate of EQA pro-gram,and consistantly improve testing quality by utilizing EQA programs adequately.

Background::Atopic dermatitis (AD) is a chronic inflammatory skin disorder impacting populations worldwide, although its clinical characteristics and patient demographics remain uncharacterized in China. The aim of this study was to investigate the demographics, comorbidities, aggravating factors, and treatments in AD patients across different age groups in China.Methods::This cross-sectional study included Chinese AD patients from 205 hospitals spanning 30 provinces. Patients completed dermatologist-led surveys of general medical history, comorbidities, AD-related aggravating factors, and medications. Two-level mixed-ordered logistic regression was used to evaluate aggravating factors.Results::Overall, 16,838 respondents were included in the final analysis (aged 30.9 ± 24.1 years). The proportion of severe AD was the highest in patients with AD onset at ≥60 years (26.73%). Allergic rhinitis and hypertension were the most common atopic and metabolism-related non-atopic comorbidities, respectively. AD severity was significantly associated with chronic urticaria, food allergies, and diabetes. Aggravating factors including foods, seasonal changes, and psychological factors were also linked to AD severity. The cross-sectional survey implied that severe AD may be related to the undertreatment of effective systemic or topical interventions.Conclusion::To enhance the management of AD, it is crucial to consider both aggravating factors and the increased utilization of systemic immunotherapy.Registration::ClinicalTrials.gov, NCT05316805

Intricate nature of Immunology teaching,characterized by diverse cellular types,complex molecular mechanisms,and highly dynamic immune responses,poses significant challenges.Utilization of artificial intelligence(AI)technology to provide personalized learning pathways and resources for Immunology education has emerged as a critical direction in contemporary educational reform.By examining current domestic application status and specific teaching practices,this article explores gap between AI technology and traditional teaching theories,analyzes issues such as deep integration and transformation of teacher's role.Special attention is also given to ethical considerations,including privacy protection,fairness and accessibility,and ethical implications of data processing.In response to these issues,authors propose a set of comprehensive recommendations,including establishing a student-centered learning model,strengthening teaching staff capabilities,improving privacy protection and algorithmic transparency,promoting educational equity,and reinforcing ethical education,aiming to support healthy and sustainable development of AI technology within Immunology education,offering valuable insights for reform and innovation of Immunology education.

Objective:To explore the influence of human induced pluripotent stem cell (iPSC) derived skin organoid-conditioned culture medium (SO-CM) on the function of human dermal fibroblasts (Fbs) induced by high glucose, with the aim of providing treatment ideas for diabetic wounds.Methods:This study was an experimental research. Human iPSCs were induced into skin organoids. Human iPSC-derived skin organoids and human dermal Fbs were seeded into skin organoid culture medium (SOM) and cultured for three days, respectively. Then the cell culture supernatants were collected as SO-CM and Fb-conditioned culture medium (Fb-CM), respectively. The content of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), IL-18, C-C motif chemokine ligand 2 (CCL-2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), epidermal growth factor (EGF), and VEGF-β in SOM, Fb-CM, and SO-CM was detected by enzyme-linked immunosorbent assay. Human Fbs of passage 8 and 9 induced by high glucose were divided into SOM group, Fb-CM group, and SO-CM group according to the random number table method, and were cultured with SOM, Fb-CM, and SO-CM all containing glucose at final molarity of 35 mmol/L, respectively. After 24 hours of culture, the Ki67 positive ratio of cells was calculated after immunofluorescence staining, and the cell absorbance value was detected by using cell counting kit-8, representing cell proliferation activity. The cell scratch test was performed to calculate the cell migration rate at 13 hours after scratching. After 48 hours of culture, the expression of reactive oxygen species in cells was detected by fluorescent probe method, and the rate of β-galactosidase-positive staining of cells was detected by β-galactosidase staining kit, representing cellular senescence. The sample size was three.Results:There was no statistically significant difference in the content of TNF-α, PDGF, and TGF-β among the three culture media ( P>0.05). Compared with that in SOM, the content of IL-10 and EGF in Fb-CM and SO-CM was significantly decreased ( P<0.05), while the content of CCL-2 in FB-CM and VEGF in SO-CM was significantly increased ( P<0.05). After 24 hours of culture, the Ki67 positive ratio ((45.2±6.0)% and (57.4±4.0)%) and absorbance values (124±5 and 158±12) of cells in the Fb-CM group and the SO-CM group were significantly higher than those in the SOM group ((29.6±2.1)% and 100±6, P<0.05), and the Ki67 positive ratio and absorbance value of cells in the SO-CM group were significantly higher than those in the Fb-CM group ( P<0.05). At 13 hours after scratching, the cell migration rates in the Fb-CM group and the SO-CM group were significantly higher than that in the SOM group ( P<0.05). After 48 hours of culture, the level of reactive oxygen species in the SO-CM group was significantly higher than that in the SOM group and the Fb-CM group (with both P values <0.05). After 48 hours of culture, there was no statistically significant difference in the rate of β-galactosidase-positive staining of cells among the three groups ( P>0.05). Conclusions:The SO-CM has high content of VEGF and can significantly promote the proliferation, migration, and expression of reactive oxygen species in human dermal Fbs induced by high glucose, but has no significant effect on cell senescence.