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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   HLA   Human leukocyte antigen   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 IRF1, GBP1, and TAP1. 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

关键词： salivary biomarkers   gingival inflammation   periodontal disease  

摘要： Background: Periodontal disease is a chronic inflammatory condition affecting the supporting tissues of the teeth. Early diagnosis is crucial for preventing severe complications. This study investigates and compares the utility of two salivary biomarkers, interleukin-1 beta (IL-1 beta) and matrix metalloproteinase-8 (MMP-8), in the early detection and staging of periodontal disease. Methods: This study included 189 patients, all of whom were evaluated both clinically and biologically. Each participant provided unstimulated saliva samples, which were analyzed using ELISA methods to quantify IL-1 beta and MMP-8 levels. Clinical periodontal data, including probing depth (3.9 +/- 0.6 mm), clinical attachment loss (3.4 +/- 0.6 mm), and Plaque Index (2.35 +/- 0.55), were collected for all subjects. Biomarker concentrations were then correlated with these clinical parameters and with disease severity, classified according to the 2018 EFP/AAP criteria. Results: IL-1 beta levels (210 +/- 95 pg/mL) were strongly associated with early gingival inflammation, while MMP-8 levels (185 +/- 140 ng/mL) correlated with periodontal tissue destruction (p < 0.01). MMP-8 showed a higher sensitivity for diagnosing advanced stages (p = 0.002), whereas IL-1 beta was more effective in detecting early inflammatory changes (p = 0.01). Logistic regression identified MMP-8 as a significant predictor of advanced disease (coefficient 0.85, p < 0.001) and IL-1 beta as an indicator of early inflammation (coefficient 0.25, p = 0.02). Conclusions: Both biomarkers are valuable tools for the diagnosis and staging of periodontal disease. MMP-8 is relevant for identifying advanced cases, while IL-1 beta supports early detection. Their combined use may enhance diagnostic accuracy and guide personalized periodontal care.

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： intervertebral disc   degeneration   back pain   link N   interleukin-1 beta   inflammation  

摘要： Intervertebral disc (IVD) disease is typically characterized by the degradation of IVD tissue, secretion of inflammatory and painful factors, and hyperinnervation of the disc. The pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) has been regarded as a principal factor in orchestrating disc degeneration. Link N (LN) is a peptide derived from the link protein that has been shown to promote extracellular disc regeneration even in an inflammatory milieu;however, no mechanism(s) has been described for their behaviour to date. Building on prior studies on LN, we hypothesize that LN directly inhibits IL-1 beta. IVD degeneration was experimentally induced in New Zealand white rabbits, followed by the injection of either sLN or saline as the vehicle control. To determine the expression of markers of pain, histology was performed. Cultured human Nucleus Pulposus disc cells (hNP) were used to determine the effects of LN on IL-1 beta-induced changes in gene expression, including the effects on IL-1 beta, TNF alpha, and IL6 signalling. Isolated murine dorsal root ganglia (DRG) neurons were used to assess the effect of LN on IL-1 beta-induced neuronal hyperactivity. LN significantly reduced IL-1 beta-induced NF-kappa B activation in a dose-dependent manner in disc cells and was further able to modulate IL-1 beta-induced gene expression, inflammatory mediators, and neurotrophic factors. Peptide docking simulations revealed that LN could interact with IL-1 beta. A direct interaction of LN and IL-1 beta was revealed through co-immunoprecipitation experiments. Although IL-1 beta was able to hypersensitize DRG neurons following a seven-day exposure, as demonstrated by Ca2+ imaging, this effect was significantly blunted when co-treated with LN. LN demonstrates a novel mechanism of action by directly inhibiting IL-1 beta, in addition to mitigating IL-1 beta-induced hypersensitivity in DRG neurons. These data suggest a potential role for LN in reducing discogenic pain.

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.

关键词： Zika virus   Placenta   Trophoblast   First trimester pregnancy   Interferon   Interferon lambda   Interferon stimulated genes  

摘要： BackgroundZika virus (ZIKV) is a positive-strand RNA virus of the Flaviviridae family. Maternal ZIKV infection during pregnancy can spread to the placenta and fetus causing severe neurological defects and infants born with microcephaly. Here, we investigated ZIKV infection and the cellular innate antiviral immune response in first trimester human placental explant cultures and isolated primary villus cytotrophoblasts (CTBs).MethodsPlacentas were obtained with informed consent from women undergoing elective pregnancy termination and either cultured as placental explants or used to isolate primary CTBs. Explants and CTBs were both infected with ZIKV (PRVABC59), and samples evaluated for infection by qRT-PCR, viral plaque and ELISA assays, and immunohistochemical or immunocytochemical *** demonstrate robust infection and production of ZIKV in placental explant and CTB cultures. Both displayed delayed upregulation of interferons (IFN), most notably IFN beta and IFN lambda 2/3, and a panel of interferon stimulated genes (ISG) (IFI6, IFIT1, IFIT2, IFITM1, ISG15, MX1, RSAD). Stimulation of explants and CTBs with the dsRNA mimic poly(I: C), caused immediate IFN and ISG upregulation, demonstrating the first trimester placenta is innate immune competent. This suggests that either ZIKV blocks the early innate response, or the placental response is inherently *** these data show that first trimester placenta is susceptible to ZIKV infection which induces a delayed type III IFN antiviral response. This delay likely creates an environment favourable to ZIKV replication and dissemination across the early gestation placenta to fetal tissue, causing pathologies associated with congenital ZIKV syndrome.