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关键词： EB   VCA-IGM病毒抗体   异型淋巴细胞   传染性单核细胞增多症   儿童   联合诊断  

摘要： 本研究对EB病毒抗体和外周血中的非典型淋巴细胞进行了深入的探讨,此诊断手段在儿童传染性单核细胞增多症的鉴别上具有显著价值。方法 本研究的观测窗口定在2024年12月至2025年2月,三十位小患者荣幸地成为研究样本的伙伴。本实验将儿童分成IM组(确诊传染性单核细胞增多症)和未确诊的非IM组(发热、咽喉痛、淋巴结肿大症状)。每组15例。分别检测两组患儿外周血异型淋巴细胞比例及EB病毒VCA-IgM抗体指标,比较两组间指标差异。结果 IM组外周血异型淋巴细胞比例显著升高(平均值为19.7%±11.4%),显著高于非IM组(4.5%±2.2%)(P<0.01);IM组EBVVCA-IgM阳性率为66.7%高于非IM组(为0.0%)(P<0.01)。结论 核实儿童是否患有传染性单核细胞增多症,同步对外周血中的异常淋巴细胞和EB病毒抗体进行分辨,诊断准确度大幅进步。提高临床实用价值。

关键词： 输卵管妊娠   腹腔内出血   腹腔镜手术  

摘要： 评价经腹腔镜途径治疗输卵管异位妊娠所致腹腔内出血的临床效果。方法 以2023年1月1日至12月31日期间于本院接受诊治的58例输卵管异位妊娠合并腹腔内出血患者为研究样本。采用随机数字表法将研究对象均等分为试验组(实施腹腔镜手术)与对照组(实施传统开腹手术),通过比较两组临床指标差异以评估不同术式的治疗效果。结果 试验组的术后恢复及住院时间均短于对照组(P<0.05),而两组不良反应率无显著差异(P>0.05)。试验组术后炎症因子水平降低更明显(P<0.05)。结论 腹腔镜手术治疗输卵管妊娠腹腔内出血具有显著疗效,能够有效降低炎症细胞因子水平并对患者的恢复具有积极影响,是一种安全、有效的治疗手段。

关键词： rheumatoid arthritis   CD1c+dendritic cells   intermediate monocytes   myeloid cells   low-density granulocytes   antigen-presenting cell  

摘要： Introduction: Rheumatoid arthritis (RA) is a systemic autoimmune disease that leads to inflammation of synovial joints and other organs. Many RA patients "share" a common peptide sequence within the HLA-DR (MHC II) molecule expressed on antigen-presenting cells (APC), suggesting that HLA-DR+ cells are important in RA inflammation. We use HLA-DR positivity to comprehensively immunophenotype APC by spectral cytometry. Methods: We measured mean fluorescence intensities (MFI) of HLA-DR and molecules associated with dendritic cells (CD141, CD1c, CD163, CD11c, CD123, and CD303), monocytes (CD14 and CD16), granulocytic markers (CD15 and CCR3), co-stimulatory molecules (CD86 and CD275), and chemokine receptors (CCR2, CCR3, and CCR7) from RA patients and healthy donors by spectral flow cytometry. Results: DC2 (CD1c+) showed higher CD86, CD275 (ICOS-L), CD56, and CCR7 in RA (all p < 0.05). CD56 was also increased in (CD163+) DC3 (p = 0.0453). CD15 was increased throughout RA dendritic cell subsets and classical and intermediate monocytes (all p < 0.01). Except for B cells, HLA-DR was not different in RA. A distinct HLA-DR+CD15+CD16+ population appeared in RA (p = 0.0004), which contributed a mean of 1.3% (+/- SD 2.85%) to the overall HLA-DR+ APC compartment. This HLA-DR+CD15+CD16+ subset was positive for CD83, CD275, and, like plasmacytoid pDC, CD303+. However, in contrast to pDC, it formed distinct t-SNE clusters and differed from reference pDC (CD123+CD303+) by much less CD123 (p < 0.01). The HLA-DR+CD15+CD16+ phenotype correlated with clinical markers of systemic inflammation (p < 0.01). Discussion: In conclusion, dendritic cell and monocyte alterations in RA include an increased co-stimulatory phenotype of CD1c+ DC2 and CD163+ DC3 with increased CD56 and CD15 in dendritic cells and monocytes. Moreover, the blood of RA patients contains HLA-DR+ cells with shared dendritic cell and granulocytic features. These phenotypic characterizations of RA patients implicate CD1c+ DC2

关键词： Prdm1   IFN-gamma   antisense oligonucleotides   intestinal epithelium   neonates   LncRNAs   Swi/Snf   Pias1   innate defense   Cryptosporidium  

摘要： Intestinal epithelial cells (IECs) serve as the front line of host defense in the intestine, with IFN signaling playing a critical role in regulating epithelial cell-intrinsic defense against intracellular pathogens. However, IFN-gamma-mediated antimicrobial defense is usually reduced in the gastrointestinal tract in infants, and the underlying mechanisms remain unclear. We previously observed that the lncRNA XR_001779380 promotes IFN-gamma-stimulated gene transcription in murine IECs. Interestingly, its interaction with Prdm1, a DNA-binding protein expressed in the neonatal but not adult intestinal epithelium, attenuates IFN-gamma-stimulated gene transcription, thereby contributing to suppression of IFN-gamma-mediated, epithelial cell-intrinsic defense in the neonatal intestine. In this study, we further investigated the role of Prdm1 in suppressing IFN-gamma response in murine neonatal IECs. Additionally, we explored the development of specific antisense oligonucleotides to interfere with XR_001779380-Prdm1 interaction to promote IFN-gamma response in IECs. Our data show that Prdm1 suppresses IFN-gamma-mediated gene transcription, and its induction inhibits IFN-gamma-stimulated cell-intrinsic defense against Cryptosporidium, an apicomplexan parasite and a leading cause of infectious diarrhea and diarrheal-related death in young children worldwide. Furthermore, antisense oligonucleotides designed to block Prdm1-XR_001779380 interaction can promote the IFN-gamma response in murine neonatal IECs, leading to enhanced cell-intrinsic anti-Cryptosporidium *** with adults, the innate antimicrobial defense of intestinal epithelium in neonates and infants is typically reduced, leading to increased susceptibility to infection;however, the underlying mechanisms remain incompletely understood. Cryptosporidium is a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. Prdm1 is a DNA-binding protein that is expressed in ne

关键词： PB-ECFC   Diabetes Mellitus   TNF-alpha Pathway   MiRNAs   Vascular Regeneration  

摘要： Background Endothelial colony-forming cells (ECFCs) are progenitors of endothelial cells and have shown angiogenic effects in pre-clinical studies in ischaemic tissues. ECFCs may represent a potential therapy for patients who require vascular repair, including those with diabetes mellitus (DM). However, some, but not all, studies have reported a decrease in the number and impaired function of peripheral blood-derived ECFCs (PB-ECFCs) from patients with diabetes. This study aimed to compare the gene expression profiles and pathways between control and diabetic PB-ECFCs in order to understand mechanisms of diabetes-induced dysfunction. Methods Bulk RNA sequencing (RNA-Seq) was performed to compare the gene expression patterns of PB-ECFCs from control and diabetes groups. Subsequently, gene enrichment analysis (GSEA) was used to identify enriched pathways in PB-ECFCs from the diabetes group. To mimic the inflammatory environment of DM, PB-ECFCs were treated with TNF-alpha. Changes in gene and microRNA (miRNA) expression following TNF-alpha exposure were analysed via qRT-PCR. The proliferation, cell adhesion and tube formation ability of PB-ECFCs were assessed using Prestoblue, THP-1 cell adhesion, and in vitro Matrigel assays, respectively. Results We identified 66 differentially expressed genes (28 upregulated and 38 downregulated) between control and diabetic PB-ECFCs. GSEA showed that the TNF-alpha pathway was markedly enriched in PB-ECFCs from the diabetes group. We then exposed ECFCs to TNF-alpha and demonstrated activation of inflammatory pathways, which resulted in inhibition of proliferation and potential impairment of tube formation (reducing the number of nodes and total length) in control PB-ECFCs, and enhanced cell adhesion to THP-1. Additionally, we found that three miRNAs (miR-146a-5p, miR-199a-3p, and miR-199a-5p) were upregulated in control PB-ECFCs upon exposure to TNF-alpha. Conclusion In summary, this study suggested that the TNF-alpha pathway may pl

关键词： Breast neoplasms   Inflammation   Interleukin-8   Interleukin-6   Survival   Mortality  

摘要： ObjectiveOur earlier work reported the association of inflammatory biomarker with a reduced breast cancer chemotherapy relative dose intensity (RDI) resulting in an unfavourable survival outcome. This current study aimed to assess the prognostic role of inflammatory biomarkers in patients with breast cancer, particularly Interleukin-8 (IL-8). ResultsThis study included 168 breast cancer patients. The median follow-up was 24.3 (range 3-77) months. Kaplan-Meier and log-rank test showed that the 3-year overall survival (OS) in patients with high IL-8 plasma level (> 6.88pg/mL) were significantly lower than those with low level (<= 6.88pg/mL) (59.6% vs. 76.4%, P = 0.049). Multivariate Cox regression analysis adjusted with stage and HER2 showed high IL-8 as prognostic factor for poor OS (HR 1.70, 95%CI [1.01-2.84], P = 0.044). Multivariate comparisons for disease-free survival (DFS) and progression-free survival (PFS) revealed none of the investigated inflammatory biomarkers having prognostic significance. More patients with older age and stage IV disease had a high IL-8 level than their counterparts (54 vs. 51 years, P = 0.020 and 61% vs. 39%, P = 0.012). High IL-8 level may serve as potential prognostic biomarker in the clinical setting in order to deliver more personalized care and strategy toward better outcomes.

关键词： sinus node microenvironment   sinus node dysfunction   M2-type macrophages   cardiac fibroblasts   IL-34   iPSC-CMs   action potential   AP   beating per minute   BPM   diastolic depolarization/diastolic depolarization rate   DD/DDR   heart rate   HR   induced pluripotent stem cell-derived cardiomyocytes   iPSC-CMs   M0/1/2-type macrophages   M0/1/2s   right atria   RA   sinus node/sinus node dysfunction   SN/SND  

摘要： Background The human sinus node (SN) contains cardiac fibroblasts and resident macrophages, with microRNAs (miRNAs) and interleukins as regulators of SN function. However, the mechanisms how they influence heart rate (HR) remain unclear. Objectives This study aims to investigate the SN microenvironment, encompassing miRNAs, interleukins, macrophages and fibroblasts and modulating iPSC-CMs hence beating rate. Methods Multi-omics analysis was conducted to compare human SN vs. right atria (RA). Human iPSC-derived cardiomyocytes (iPSC-CMs) were co-cultured with M2-type macrophages (M2s) and fibroblasts. Mechanistic studies involved the application of IL-34 and the silencing or overexpression of CSF1R and STAT3. mRNA-miRNA interactions were predicted using Ingenuity Pathway Analysis (IPA). miR-363-5p was applied to three cell lines and a co-culture system and, along with IL-34, was tested in human serum samples. Results M2s and fibroblasts markers were identified. Co-culturing iPSC-CMs with M2s induced a more nodal-like phenotype. Elevated IL-34 in the co-culture medium suggested that M2s may secrete IL-34, driving these nodal like feature. IL-34 promoted a nodal-like phenotype in iPSC-CMs by upregulating HCN4 expression probably through CSF1R/STAT3 signaling. Three key miRNAs were identified, with miR-363-5p inhibiting the differentiation of macrophages into the M2 phenotype. The nodal-like shift of iPSC-CMs in the co-culture system was reversed by miR-363-5p. While miR-363-5p (together with miR-486-3p) was highly expressed, IL-34 was reduced in aged individuals with SND. Conclusion M2 macrophages contribute to the SN microenvironment by secreting IL-34 and thus enhance SN function via upregulating HCN4. Elevated miR-363-5p, seen in age-related SND, may reverse these effects.

关键词： feline trivalent vaccines   immunity   adjuvant   IL-23   IL-15   metabolic modulators   Mn  

摘要： The feline calicivirus, herpesvirus, and panleukopenia viruses are major infections that cause serious diseases in cats;however, current trivalent vaccines have limitations in immune efficacy and their duration of protection. This study assesses the immune-enhancing effects of novel adjuvants (feline IL-15, IL-23, and metabolic modulators) on vaccine responses. Forty mice were randomly assigned to four groups: Group A (composite adjuvants), Group B (metabolic regulatory molecules and Mn adjuvant), Group C1 (Mn adjuvant), and Group C2 (a blank commercial vaccine). The results showed that Group A had significantly higher neutralizing antibody titers against calicivirus post-booster immunization, while both Groups A and B exhibited enhanced antibody responses against the herpesvirus and panleukopenia viruses. Notably, Group A displayed increased proportions of memory T cells, follicular B cells, and activated B cells. These findings suggest that the combination of feline IL-15, IL-23, and metabolic modulators are safe and effective immunoadjuvants for trivalent feline vaccines to promote immune cell differentiation and antibody production, thus representing a promising strategy to optimize vaccine efficacy.

关键词： Janus kinase inhibitors   Vaccination   T cell response   SARS-CoV-2 vaccination   JAK- inhibitors   TH1-response   TNF- inhibitors  

摘要： BackgroundJanus kinase inhibitors (JAKi) represent a well-established therapeutic option for the treatment of autoimmune diseases. However, there is a paucity of evidence regarding their impact on de novo immune responses to vaccinations. T cells may confer long-lasting immunity and cross-recognise evolving epitopes of new viral variants, as evidenced by the SARS-CoV-2 vaccination. Consequently, we investigated the de novo T-cell response to SARS-CoV-2 vaccination in patients with rheumatic diseases undergoing treatment with JAK ***-sectional study, conducted in an outpatient department. Patients with rheumatic disease who had received two vaccinations against SARS-CoV-2 while under therapy with JAKi (n = 22) or tumour necrosis factor-blocking biologicals (TNFi) (control group n = 16) were recruited. To evaluate the vaccine-induced T cell response, the patients' PBMCs were stimulated with SARS-CoV-2 spike protein peptides. The percentage of CD4+ T cells responding specifically to this stimulation by producing IFN gamma was then measured using intracellular cytokine staining and flow cytometry. In addition antibody response to vaccination was *** specific T cell response was detected in 11 out of 22 (50.0%) of patients in the JAKi cohort, compared to 13 out of 16 (81.3%) of the TNFi cohort (p = 0.088). Patients on JAKi had a lower percentage of CD4+ T cells responding to stimulation with SARS-CoV-2 spike peptides than patients on TNFi (p = 0.021). The proportion of patients with an antibody response and absolute anti-spike IgG levels did not significantly differ between the *** on JAKi exhibited a compromised de novo T cell response to SARS-CoV-2 vaccination compared to TNFi patients. There is a need for further research on the effect of JAKi on T cell responses to vaccination.

关键词： Mesenchymal stromal cells (MSCs)   Cytokine licensing   Extracellular vesicles (EVs)   Immunomodulation   Regulatory T cells (Treg)   t-distributed stochastic neighbor embedding (t-SNE) analysis   Transforming growth factor beta 1 (TGF-beta 1)   Tumor necrosis factor alpha (TNF-alpha)  

摘要： Background Mesenchymal stromal cells (MSCs) possess strong immunomodulatory properties, making them attractive candidates for regenerative medicine and immune-related therapies. Pre-activation, or licensing, of MSCs with cytokines such as interferon-gamma (IFN-gamma) and transforming growth factor-beta 1 (TGF-beta 1) has been shown to enhance their immunosuppressive efficacy. Recent attention has turned to extracellular vesicles (EVs) released by licensed MSCs as a cell-free therapeutic alternative. Methods Small EVs were isolated from MSCs licensed with a combination of IFN-gamma and TGF-beta 1. These EVs were characterized according to standardized criteria. Their immunomodulatory effects were assessed in vitro using two human immune models: a THP-1-derived macrophage polarization system and a peripheral blood mononuclear cell (PBMC) co-culture assay. Pro/anti-inflammatory molecules secretion, T cell proliferation, and regulatory T cell induction were quantified. Dimensionality reduction using t-distributed stochastic neighbor embedding (t-SNE) was applied to multiparametric flow cytometry data for immune profiling. In addition, publicly available transcriptomic datasets (GSE122091 and GSE46019) were analyzed to identify differentially expressed genes (DEGs) in IFN-gamma- and TGF-beta 1-licensed MSCs, providing insight into potential molecular drivers of EV-mediated immunoregulation. Results Licensed EVs significantly inhibited pro-inflammatory THP-1 macrophage activation and promoted an anti-inflammatory phenotype, with reduced secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), increased IL-10 production, and decreased nitric oxide (NO) levels.. Compared to EVs from non-licensed MSCs, licensed EVs induced a greater proportion of regulatory T cells and exhibited enhanced suppression of allogeneic T cell proliferation. t-SNE analysis revealed a distinct immunoregulatory signature induced by licensed EVs, characterized by the em