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

OBJECTIVES: To investigate the impact of prenatal fear stress on placental amino acid transport and emotion and cognition development in offspring rats. METHODS: Thirty pregnant Wistar rats were randomized equally into control and fear stress (induced using an observational foot shock model) groups. In each group, placental and serum samples were collected from 6 dams on gestational day 20, and the remaining rats delivered naturally and the offspring rats were raised under the same conditions until 8 weeks of age. Emotional and cognitive outcomes of the offspring rats were assessed with behavioral tests, and placental structure was examined using HE staining. Bioinformatics analysis was used to identify differentially expressed placental transporter genes under fear stress. The expressions of system A and system L amino acid transporters, along with other specialized transporters, were detected using qRT-PCR and Western blotting. Fetal serum amino acid concentrations were determined by HPLC. The correlations between fetal amino acid levels and behavioral outcomes of the offspring rats were analyzed. RESULTS: The dams with fear stress showed reduced open-field activity and increased freezing behavior with significantly decreased placental weight, fetal weight, and fetal-to-placental ratio. Bioinformatics analysis revealed 28 differentially expressed transporter genes involved mainly in amino acid transport. In the fear stress group, fetal serum amino acid levels were significantly lowered and Slc38a1, Slc43a1, Slc43a2, Slc7a8, Slc6a6, Slc1a1 and Slc6a9 mRNA and protein expressions were all downregulated. The offspring rats in fear stress group exhibited decreased novel object preference and spontaneous alternation with reduced open arm exploration and increased immobility in emotional tests. Lower early-life amino acid levels was found to correlate with impaired adult cognition. CONCLUSIONS Prenatal fear stress in rats impairs placental amino acid transporter expression and reduces fetal serum amino acid levels, potentially contributing to long-term cognitive deficits in the offspring rats.
Animals ; Female ; Pregnancy ; Placenta/metabolism* ; Fear ; Rats ; Rats, Wistar ; Cognition ; Prenatal Exposure Delayed Effects ; Stress, Psychological ; Amino Acids/blood* ; Amino Acid Transport Systems/metabolism*

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.

The aim of this study is to establish an gene editing method of Mesomycoplasma hyo-pneumoniae(Mhp)based on the homologous recombination principle.The restriction enzyme di-gestion and ligation method combined with gene synthesis were used to construct a shuttle plasmid to achieve replication in both Mhp and Escherichia coli(E.coli).The pGEM?-T vector was used as the skeleton.The oriC sequence of Mhp which can achieve the replication of the plasmid in Mhp was inserted into the vector.Sequences of the Spiroplasma promoter and puromycin resistance gene were then inserted into the above constructed plasmid to screen recombinant clones.The up-stream and downstream homologous arms of p97 were constructed to initiate homologous recombination.The recA gene of E.coli is inserted to improve the efficiency of homologous recom-bination.The obtained shuttle plasmid was then delivered into Mhp by electro-transformation or chemical transformation.A shuttle plasmid,pGEM?-Mhp-oriC-p 97,which can replicate in both Mhp and E.coli was constructed.With the transformation of this plasmid,the carried puromycin gene and recA gene can be expressed,the p97 gene can be edited.Finally,the genetically unstable p97 gene mutant was initially obtained.In this study,a tool for Mhp gene editing based on the principle of homologous recombination was established,which laid a foundation for the develop-ment of tools for studying the pathogenesis of Mhp.

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 explore the prognosis-related genes of lung adenocarcinoma(LUAD)and establish a prognostic prediction model for LUAD.Methods The differentially expressed genes of LUAD tissues and adjacent normal tissues in the GSE43458,GSE7670,and GSE140797 datasets were screened.The protein-protein interaction(PPI)network analysis,gene ontology(GO)function,Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analyses,least absolute shrinkage and selection operator for prognosis coefficient screening,disease-specific survival analysis,Cox regression analysis,and gene correlation analysis were performed.Independent prognostic genes of LUAD were screened from the differential genes,and a prognostic prediction model of LUAD was established.The expression of independent prognostic genes was analyzed,and the predictive model was evaluated by receiver operating characteristic(ROC)curve.The GSE68465 data set was used as an external validation set to verify the predictive model.Results There were 197 up-regulated differential genes and 77 down-regulated differential genes in LUAD and adjacent normal tissues common to the three datasets.Through stepwise screening,two genes,IL7R and SLC2A1,were identified as independent prognostic factors for LUAD.IL7R was an independent protective factor,while the SLC2A1 was an independent risk factor.A prediction model for curve was built with IL7R and SLC2A1.The prediction model for LUAD constructed with IL7R and SLC2A1 is as follows:Risk score=(-0.694)×expression level of IL7R+0.763×expression level of SLC2A1.Conclusion This study screened out IL7R as an independent prognostic protective factor for LUDA,and SLC2A1 as an independent prognostic risk factor for LUAD.The LUDA prediction model constructed based on these two genes has good predictive ability and generalization ability,which can provide references for the research and clinical individualized treatment of LUAD.

Objective:To evaluate the application potential of the bimodal ultrasound/near-infrared (NIR) composite nanoscale probe Arg-Gly-Asp (RGD)/Ag 2Te/perfluoropentane (PFP) @ mesoporous silica nanoparticles (MSN) in the diagnosis and treatment of microvascular diseases. Methods:Nanoprobes loaded with RGD, PFP and Ag 2Te were prepared by ultrasound sonication and carbodiimide method. The characterization of the nanoprobes was determined. The imaging performance, photothermal response, and target-seeking ability of the nanoprobes under NIR irradiation were verified. The biosafety of the nanoprobes was examined, and the thrombolytic ability of the nanoprobes was evaluated. The mice were observed to visualize microvessels of the abdominal wall under the NIR-Ⅱ imaging, and the microvascular visualization ability of the nanoprobes was evaluated. Results:The particle size of nanoprobes was (205.3±2.9) nm and the potential was (2.05±0.58) mV. The coupling rate of the RGD was (82.27±0.36)%, the encapsulation rate of the quantum dots was (80.80±3.26)%, and the photostability of the quantum dots was good. The fluorescence intensity was enhanced with the increase of the mass concentration of RGD/Ag 2Te/PFP@MSN, and the warming effect was more obvious. After ultrasound and NIR irradiation, the thrombolysis rate was significantly increased. RGD/Ag 2Te/PFP@MSN successfully realized NIR-Ⅱ fluorescence imaging of mice microvessels. The cytotoxicity assay and hemolysis assay showed that the probe had a good biosafety. Conclusion:The RGD/Ag 2Te/PFP@MSN nanoprobe is a potential strategy for targeted therapy of thrombotic diseases, combining dual-modality therapy of ultrasound and NIR to offer new possibilities for non-invasive and visual diagnosis and treatment of microvascular embolism.

Objective:To investigate the clinical-epidemiological characteristics of connective tissue diseases (CTD) complicated with pulmonary hypertension in Shanxi province from 2018 to 2021.Methods:This was a cross-sectional study. Data of CTD patients with pulmonary hypertension from 2018 to 2021 were collected from the Shanxi Provincial Health Statistics Direct Reporting System based on inpatient medical records. The demographic and clinical data of patients with different CTD types were analyzed.Results:A total of 1 697 CTD patients with pulmonary hypertension were included, among whom there were 451 cases (26.58%) of Sj?gren′s syndrome, 392 cases (23.10%) of systemic lupus erythematosus, 289 cases(17.03%) of systemic sclerosis, 109 cases (6.42%) of mixed CTD, 69 cases (4.07%) of Takayasu arteritis, and 387 cases (22.80%) of other CTD. The majority of patients were female (1 410 (83.09%)), and 783 cases (46.14%) were aged between 41 and 65 years, and 6 cases (0.35%) were performed right heart catheterization. The prevalence of CTD with pulmonary hypertension increased from 0.06/10 4 in 2018 to 0.20/10 4 in 2021. There were significant differences in the severity of pulmonary hypertension, New York Heart Association (NYHA) functional class, length of hospital stay, medical costs, and clinical outcomes among patients with different CTD subtypes (all P<0.001). Patients with systemic sclerosis had the highest proportion of NYHA functional class Ⅲ/Ⅳ(65.1%(188/289)), the longest length of hospital stays (13 (9, 18) days), the highest average medical costs (13 622.67 (8 636.38, 20 597.75) ￥(RMB)), and the lowest rate of improvement and discharge (51.90%(150/289)). Conclusions:Between 2018 and 2021, Shanxi province, where CTD is more common in Sj?gren′s syndrome, has a high proportion of women, a high proportion of people aged 41-65 years, and a low prevalence of right ventricular catheterization in patients with CTD complicated with pulmonary hypertension. The prevalence of CTD complicated with pulmonary hypertension shows a rising trend in Shanxi province from 2018 to 2021, while patients with systemic sclerosis exhibit the most severe cardiac impairment and poorer clinical outcomes compared to other subtypes.

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