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关键词： 剖宫产瘢痕妊娠   细胞因子   酶联免疫吸附试验  

摘要： 探讨Th1、Th2细胞因子在剖宫瘢痕妊娠(cesarean scar pregnancy,CSP)患者血清中的表达及相互关系。方法 选取2023年1月-2024年1月就诊于我院诊断为CSP的患者30例(CSP组)及同期剖宫产后正常妊娠并行人工流产的患者30例(对照组)作为研究对象,采用流式细胞术检测两组患者血清中 Th1、Th2 细胞比例及比值,酶联免疫吸附法检测血清Th1型细胞因子IFN-γ、IL-2,Th2型细胞因子IL-4、IL-10的水平并进一步分析相关性。结果 CSP组Th1比例高于对照组,Th2比例低于对照组,Th1/Th2比值高于对照组,差异均有统计学意义(P<0.05);CSP组血清IFN-γ、IL-2水平均高于对照组,IL-4、IL-10水平低于对照组,差异均有统计学意义(P<0.05);CSP组INF-γ 与IL-4、INF-γ 与IL-10、IL-2 与IL-10均有相关性,呈负相关(P<0.05)。结论 INF-γ、IL-4细胞因子水平升高,IL-4、IL-10细胞因子水平降低,Th1/Th2细胞比例升高可能是导致CSP发生的机制之一。

关键词： Asthma, airway remodeling   Interlukin-4 (IL-4)   Interlukin-13 (IL-13)   Anti-IL-4   Anti-IL-13  

摘要： Asthma is a chronic respiratory disorder affecting individuals across all age groups. It is characterized by airway inflammation and remodeling and leads to progressive airflow restriction. While corticosteroids remain a mainstay therapy, their efficacy is limited in severe asthma due to genetic and epigenetic alterations, as well as elevated pro-inflammatory cytokines interleukin-4 (IL-4), interleukin-13 (IL-13), and interleukin-5 (IL-5), which drive structural airway changes including subepithelial fibrosis, smooth muscle hypertrophy, and goblet cell hyperplasia. This underscores the critical need for biologically targeted therapies. This review systematically examines the roles of IL-4 and IL-13, key drivers of type-2 inflammation, in airway remodeling and their potential as therapeutic targets. IL-4 orchestrates eosinophil recruitment, immunoglobulin class switching, and Th2 differentiation, whereas IL-13 directly modulates structural cells, including fibroblasts and epithelial cells, to promote mucus hypersecretion and extracellular matrix (ECM) deposition. Despite shared signaling pathways, IL-13 emerges as the dominant cytokine in remodeling processes including mucus hypersecretion, fibrosis and smooth muscle hypertrophy. While IL-4 primarily amplifies inflammatory cascades by driving IgE switching, promoting Th2 cell polarization that sustain cytokine release, and inducing chemokines to recruit eosinophils. In steroid-resistant severe asthma, biologics targeting IL-4/IL-13 show promise in reducing exacerbations and eosinophilic inflammation. However, their capacity to reverse established remodeling remains inconsistent, as clinical trials prioritize inflammatory biomarkers over long-term structural outcomes. This synthesis highlights critical gaps in understanding the durability of IL-4/IL-13 inhibition on airway structure and advocates for therapies combining biologics with remodeling-specific strategies. Through the integration of mechanistic insights and

关键词： 急性白血病   淋巴细胞亚群   免疫功能   治疗干预   临床意义  

摘要： 研究旨在分析急性白血病患者淋巴细胞亚群的变化及其临床价值。对象为66例急性白血病患者,分为两组:对照组(33例)和观察组(33例),确保两组基线资料均衡。对照组实施标准治疗,而观察组在标准治疗基础上增加特定干预措施。研究比较了两组的外周血T淋巴细胞亚群(CD3+、CD4+、CD8+)水平变化及并发症发生情况。结果 观察组在干预后,其CD3+、CD4+和CD8+的水平较干预前有显著提升,与对照组相比,差异具有统计学显著性(P<0.05)。此外,观察组的并发症发生率相较于对照组显著降低(P<0.05)。在护理满意度方面,观察组的表现也优于对照组,差异同样具有统计学显著性(P<0.05)。针对急性白血病患者实施的淋巴细胞亚群相关干预,不仅能够有效优化患者的淋巴细胞亚群指标,还能减少并发症的发生,并提升患者的护理满意度,展现出重要的临床应用价值。

关键词： 益生菌联合特异性免疫疗法   小儿尘螨过敏性哮喘   临床疗效  

摘要： 深入探寻益生菌联合特异性免疫疗法针对小儿尘螨过敏性哮喘的临床治疗效果,致力于为该疾病的治疗提供更为有效的干预举措,推动儿科医学在这一病症治疗领域迈向新的高度。方法 将 200 名符合标准的儿童患者,依据随机原则,科学地划分成实验组与对照组。其中,实验组在常规治疗的根基上,接受益生菌与特异性免疫疗法的协同干预;对照组仅开展常规治疗。如此分组旨在遵循循证医学原则,保障两组在各方面因素上具有均衡性与可比性。结果 从多个层面的指标分析可知,实验组的成效可谓斐然,明显优于对照组。在临床症状方面,随着治疗工作的持续推进,实验组的哮喘发作频率、严重程度、夜间症状以及生活质量评分均不断朝着良好方向发展,至第 6 个月时,与对照组的差异达到了极为显著的程度(P<0.01)。在肺功能评估方面,实验组的 FEV1 和 PEF 值始终保持着领先态势(P<0.01)。从免疫学角度来看,实验组的过敏原特异性 IgE 水平显著降低,Th1 细胞比例显著攀升、Th2 细胞比例显著下降、Treg 细胞比例显著增多(P<0.01)。就临床治疗反应而言,实验组的急性发作次数和药物使用频率明显减少,症状缓解率显著提高(P<0.01)。在副作用方面,实验组的总副作用发生率相对较低(12% vs.22%,P=0.022)。结论 益生菌联合特异性免疫疗法能够切实有效地改善小儿尘螨过敏性哮喘患者的临床症状与肺功能,精准地调节免疫反应,显著减少药物使用频率,具备良好的安全性,在儿科临床治疗中展现出广阔的应用前景。

关键词： Head and Neck Cancer   Human leukocyte antigen - HLA   Immune modulatory   Major histocompatibility complex - MHC  

摘要： BACKGROUND:Adenoid cystic carcinoma (ACC) is a rare, but lethal cancer with low response rates to systemic therapies, such as cytotoxic chemotherapy and immune-checkpoint inhibitors (ICIs). Despite extensive clinical trials, no effective treatments for patients with recurrent or metastatic ACC are available, and ACC mortality rates remain poor. METHODS:We employed automated multiplex immunofluorescence (mIF), single-cell RNA sequencing (scRNA-seq) Gene Expression analysis, RNA in-situ hybridization, and spatial transcriptomics analysis to characterize the immune landscape of ACC tumors, ACC metastasis, and normal tissues from regions where ACCs arise. Based on results from these studies, we treated freshly resected ACCs with interferon-γ or a stimulator of the interferon genes (STING) agonist in vitro. Additionally, we included one patient with ACC in a phase 1 clinical study of a novel STING agonist (dazostinag) plus pembrolizumab. RESULTS:The mIF analysis revealed that ACC tumors are immunologically "cold", with few tumor-infiltrating T-lymphocytes and low programmed death-ligand 1 (PD-L1) expression. The most striking finding was a very low beta-2-microglobulin (B2M) expression in nearly all ACCs, with only focal expression found in some ACC metastases. mIF and RNA sequencing analyses of normal salivary gland and breast tissues revealed a p63+, NFIB+, basal duct cell population, with similarly low B2M/human leukocyte antigen (HLA) class I expression. Spatial transcriptomics analysis of the focally B2M-positive ACC metastases uncovered the genetic pathway driving upregulation of B2M, an interferon-γ program mediating the reintroduction of HLA-I/B2M; the significantly upregulated genes included and . On short-term treatment of primary ACC tissues in vitro with interferon-γ or a STING agonist, we observed strongly upregulated HLA class I/B2M expression. Moreover, treatment of a patient with recurrent, metastatic breast ACC with a STING agonist and pembrolizumab led

摘要： BackgroundTumor-associated macrophages (TAMs) in the tumor microenvironment (TME) primarily polarize into the M2-phenotype. Our previous study showed that the small GTPase Rab37 mediates IL-6 trafficking in macrophages for M2 polarization. Here, we uncover an unconventional role of Rab37, independent of vesicle trafficking, in promoting M2 polarization of *** gene profiles in wild-type and Rab37 knockout (KO) bone marrow-derived macrophages (BMDMs) were analyzed using cDNA microarray. The mechanism of Rab37 in regulating the interferon (IFN) pathway was confirmed through in vitro/vivo assays and clinical *** I IFN signaling was highly enriched in BMDMs from Rab37 KO mice. Moreover, Rab37 induction and decreased type I IFN genes were observed in macrophages treated with lung cancer-conditioned medium and epigenetic drugs, indicating an epigenetic regulation of Rab37 in TAMs. Mechanistically, GDP-bound Rab37 interacted with the nuclear localization sequence of STAT1 to sequest it in the cytosol from its transcription activities, thus leading to the downregulation of IFN genes. Clinically, CD163+/Rab37+/STAT1cytosol in TAMs expression signature correlated with advanced tumor stages and poor survival of lung cancer *** findings highlight the cytosolic interaction of Rab37-STAT1 in M2 TAM polarization, with CD163+/Rab37+/STAT1cytosol TAMs as a lung cancer prognosis biomarker.

关键词： RA   TNF-alpha   PPI networking   Virtual screening   DFT and MD simulations  

摘要： In humans, rheumatoid arthritis (RA) is a deadly autoimmune disease that affects bone health. Although the specific etiology of RA is unknown, scientific evidence suggests that smoking, genetic abnormalities, and environmental factors may all contribute to the disease's progression. We employed protein-protein interaction (PPI) networking analysis to identify a possible therapeutic target for RA. The lead-like molecule for the selected target was then found via virtual screening in the Indian medicinal plants phytochemistry and therapeutics database. Molecular dynamics has confirmed the stability of drug target-lead-like molecule complexes. The networking analysis identifies TNF-alpha as a potential therapeutic target for RA. TNF-alpha expression was verified using in vitro studies. Cassamedine was identified as a possible lead molecule among 17,967 chemicals in the Indian Medicinal Plants Phytochemistry and Therapeutics database using virtual screening experiments. The molecular docking results of the lead compound interaction with TNF-alpha were clarified by the quantum mechanism (QM) technique, namely, density functional theory (DFT). The stability of the lead-like compound with TNF-alpha was confirmed using 200 ns of molecular dynamics simulations. Energy calculations using molecular mechanics Poisson-Boltzmann surface area (MMPBSA) confirm the free energy between TNF-alpha and lead-like molecules.

关键词： Platelet transfusion refractoriness   HLA-I antibodies   Compatible blood transfusion   Immune microsphere liquichip  

摘要： To investigate the differences in HLA-I antibody distribution and corresponding platelet transfusion effectiveness among patients with a history of platelet transfusion refractoriness(PTR) in the Han population of Zhejiang, China, to ensure the rational utilization of platelet resources.A retrospective analysis was conducted on 77 patients with a history of PTR admitted to the Hematology Department of Zhejiang Provincial Hospital of Traditional Chinese Medicine from May 2018 to December 2022. Testing was conducted for HLA-I antibodies in platelets were tested using an immune microsphere liquid chip. The distribution of antibodies and their intensities were analyzed along with the distribution characteristics of antibodies by disease type, sex, age, and blood type. Furthermore, the relationships between HLA-I antibody intensity distribution and transfusion frequency, as well as transfusion outcomes, were *** average positive rates of HLA-A, -B, and -C antibodies were 0.393, 0.527, and 0.242. The number of weakly positive and total positive HLA-I antibodies in the ITP group was significantly lower than in the other disease categories (P < 0.05).Positive HLA-I antibody count was not related to the patient's sex, blood type, or age. In contrast, positive HLA-I antibody count was significantly higher for platelet transfusions > 10 than for platelet transfusions <= 10. As anticipated, the effectiveness of HLA standard antigen-matched platelet transfusions was significantly superior to random platelet transfusions (P < 0.001).The distribution of HLA-I antibodies in PTR patients among the Han Chinese population in Zhejiang, China is relatively extensive. An increase in the frequency of platelet transfusions leads to higher frequency and stronger intensity of HLA-I antibody production, resulting in poorer transfusion outcomes. HLA standard antigen-matched platelet transfusions can effectively address the occurrence of PTR.

关键词： Gastric cancer   Prognostic nutrition index   LAG3   MHC class II  

摘要： BackgroundThe prognostic nutrition index (PNI) has recently been highlighted as a predictor of immune checkpoint (IC) inhibitor efficacy in gastric cancer (GC). Although LAG3, an IC molecule, has gained considerable attention, its association with PNI remains *** and methodsWe retrospectively analyzed clinical data from 796 GC patients who underwent radical gastrectomy to identify which previously reported nutritional index had the greatest impact on prognosis. Single-cell RNA sequencing was performed on 38 GC tissues, and multiplex immunofluorescence staining was conducted on 59 GC tissues to evaluate the relationship between nutritional indices and IC molecule expression in cytotoxic CD8-positive T *** low preoperative PNI was identified as the strongest predictor of poor prognosis among the nutritional indices in GC patients. The expression of not only PDCD1 (encoding PD1) but also LAG3 in cytotoxic CD8-positive T cells was significantly higher in GC with low PNI compared to those with high PNI. Among cytotoxic CD8-positive T cells, the proportion of LAG3-positive cells was greater than that of PDCD1-positive cells, particularly in GC with low PNI, and most LAG3-positive cells did not co-express PDCD1. Additionally, the expression of MHC class II, a ligand for LAG3, was higher in GC cells with high levels of epithelial-mesenchymal transition-related molecules in GC with low PNI compared to those with high *** can reflect LAG3 expression in cytotoxic CD8-positive T cells and MHC class II expression in GC cells.