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摘要： INTRODUCTION:This paper aimed to unravel the value of interleukin-6 (IL-6), D-dimer (D-D), and white blood cell (WBC) tests in the diagnosis of severe pneumonia. METHODS:Sixty cases of pneumonia patients were selected as the observation group, which were divided into the non-severe group (35 cases) and the severe group (25 cases) following the severity of the disease; and 50 health check-up participants in the same time period were chosen as the control group. The general information of the control and the observation groups were compared; IL-6, D-D, and WBC levels were observed in the non-severe and the severe groups. Logistic multivariate regression analysis was implemented to analyze the independent factors predicting severe pneumonia, and the ROC curve was adopted to observe the diagnostic value of IL-6, D-D, and WBC for severe pneumonia. RESULTS:There was no difference in general information between the observation and the control groups, and between the severe and the non-severe groups (P > 0.05); IL-6, D-D, and WBC levels in the severe group were markedly higher relative to the non-severe group; the multivariate logistic regression analysis showed that IL-6 (P < 0.05, 95% CI: 1.076-1.443) and D-D (P < 0.05, 95% CI: 1.367-66.079) were independent factors predicting severe pneumonia; the ROC curve analysis revealed that the AUCs of IL-6, D-D, and WBC were 0.957, 0.874, and 0.639, respectively; the combined AUC of the three was 0.978, demonstrating that the predictive value of the combined test was higher than that of the single test. CONCLUSION:IL-6, D-D, and WBC are significantly elevated in severe pneumonia and have predictive value in severe pneumonia.

关键词： 胃癌   Th17细胞   IL-17   MMP2   Gastric Cancer   Th17 Cells   IL-17   MMP2  

摘要： 目的：探讨Th17细胞、血清白细胞介素-17 (IL-17)、基质金属蛋白酶(MMP2)在评估胃癌(GC)淋巴结转移中的临床应用价值。方法：选取2023年1月~2024年10月入住于天津市武清中医院的36例胃癌患者(GC组)及38例胃良性病变患者(对照组)，采用流式细胞术检测各组外周血Th17细胞水平，采用酶联免疫吸附法(ELISA)测定血清中IL-17和MMP2水平，评估这三个检测指标在GC淋巴结转移中的应用价值及三者联合检测的诊断效能。结果：与对照组对比，GC组患者外周血Th17细胞水平明显增高，血清IL-17和MMP2水平也明显较高，差异均有统计学意义(均p < 0.05)；GC组中，淋巴结转移者Th细胞水平、血清IL-17和MMP-2水平与未转移者对比，明显较高，差异均有统计学意义(均p < 0.05)；Th17、IL-17和MMP2三项联合检测准确度、特异度、灵敏度分别为95.82%、94.21%和97.69%，与单项检测对比，均明显较高，差异均有统计学意义(均p < 0.05)。结论：Th17细胞、IL-17和MMP2与评估GC淋巴结转移有一定关联，三者联合检测有助于GC的鉴别诊断。

关键词： tendinopathy   interleukin-6   tendon   assembloid   scleraxis   fibroblast   Human   Mouse  

摘要： Tendinopathies are debilitating diseases currently increasing in prevalence and associated costs. There is a need to deepen our understanding of the underlying cell signaling pathways to unlock effective treatments. In this work, we screen cell signaling pathways in human tendinopathies and find positively enriched IL-6/JAK/STAT signaling alongside signatures of cell populations typically activated by IL-6 in other tissues. In human tendinopathic tendons, we also confirm the strong presence and co-localization of IL-6, IL-6R, and CD90, an established marker of reparative fibroblasts. To dissect the underlying causalities, we combine IL-6 knock-out mice with an explant-based assembloid model of tendon damage to successfully connect IL-6 signaling to reparative fibroblast activation and recruitment. Vice versa, we show that these reparative fibroblasts promote the development of tendinopathy hallmarks in the damaged explant upon IL-6 activation. We conclude that IL-6 activates tendon fibroblast populations which then initiate and deteriorate tendinopathy hallmarks.

关键词： Acute anterior uveitis   Ethiopia   HLA-B27 allele  

摘要： Purpose: We compared the distribution of the HLA-B27 allele among Ethiopian patients with acute anterior uveitis (AAU) and controls without that disease. Methods: The clinical features of patients were collected from their medical records. HLA-B27 genotyping was performed for 64 patients, with AAU using the real-time polymerase chain reaction (RT-PCR), and the results were compared to those from a panel of 192 healthy, unrelated volunteer control participants (refraction patients and volunteers) free of signs of anterior uveitis. Other outcomes were assessed comparing HLA-B27 positive vs. negative patients. Results: The histocompatibility antigen HLA-B27 was identified in 6 out of 64 (9.4%) AAU patients, compared with 1.0% in controls (Odds Ratio = 9.8, 95% CI (1.93, 50.01)). Sub-group analysis of the cases revealed that patients with HLA-B27 positivity had a higher incidence of ocular hypertension (Odds Ratio = 5.93, 95% CI (1.29, 27.2)). Conclusion: The antigen HLA-B27 was represented similar to 10-fold more frequently in the patient group than in the control group. HLA-B27 allele distribution in both cases and controls is lower than in reports from Caucasian and Asian populations, but similar to South Africa.

关键词： BCR   DADA2   TCR   TNF   autoimmunity   immune architecture   immune repertoire   machine learning  

摘要： BACKGROUND:Adenosine deaminase 2 deficiency (DADA2) is a genetic disorder caused by biallelic hypomorphic or loss-of-function mutations in the ADA2 gene that encodes a protein deaminase regulating extracellular adenosine metabolism. Clinical features encompass inflammatory vasculopathy, early-onset strokes, and a complex presentation involving both immunodeficiency and autoinflammation/autoimmunity. OBJECTIVE:To determine a DADA2-specific adaptive immune architecture. METHODS:We profiled immunoglobulin levels and peripheral B and T cell phenotypes in 47 previously reported and 5 unreported DADA2 patients. Levels of 21 cytokines/chemokines were quantified in patients with or without anti-TNF treatment. To characterize the DADA2 immune architecture, we performed T and B cell receptor (TCR/BCR) immunosequencing. We trained a binary LightGBM classifier to distinguish DADA2 T and B cell immune repertoires from heathy individuals. RESULTS:We detected hypogammaglobulinemia in 65% of DADA2 patients (34/52) and cytopenias in 48% (25/52). Flow cytometric profiling revealed contraction of B and T cell memory compartments. In addition, we observed elevated levels of TNF, IL-8, several interferons, APRIL, BAFF and sCD40L. High serum levels of TNF, BAFF and sCD40L persisted under anti-TNF therapy. Next-generation immunosequencing of peripheral lymphocytes showed restricted TCR repertoires and B cells, which were particularly skewed towards IGHV4-34 rearrangements. Our machine learning algorithm separated DADA2 with high accuracy from healthy individuals based on immunogenetic parameters regarding B cell clone fraction, CDR3 length, and selected Kidera factors. CONCLUSIONS:Our findings underscore ADA2's significant influence on the adaptive immune system, which results in a highly specific immunogenetic signature in DADA2 patients.

摘要： Parasitic helminths induce the production of interleukin-4 (IL-4), which causes the expansion of virtual memory CD8+ T cells (TVM cells), a cell subset that contributes to the control of coinfection with intracellular pathogens. However, the mechanisms regulating IL-4-dependent TVM cell activation and expansion remain ill defined. Here, we used single-cell RNA sequencing of CD8+ T cells to identify pathways that control IL-4-dependent TVM cell responses. Gene signature analysis of CD8+ T cells identified a cell cluster marked by CD22, a canonical regulator of B cell activation, as a selective surface marker of IL-4-induced TVM cells. CD22+ TVM cells were enriched for interferon-gamma and granzyme A and retained a diverse TCR repertoire while enriched in self-reactive CDR3 sequences. CD22 intrinsically regulated the IL-4-induced CD8+ T cell effector program, resulting in reduced responsiveness of CD22+ TVM cells and regulatory functions to infection and inflammation. Thus, helminth-induced IL-4 drives the expansion and activation of TVM cells that is counterinhibited by CD22.

关键词： Chronic apical periodontitis   Hepcidin   Liver   IL-6/STAT3 signaling   Iron metabolism   Porphyromonas gingivalis  

摘要： Background and Aims: Chronic apical periodontitis (CAP), an inflammatory disease of the oral cavity caused by bacterial infections with Porphyromonas gingivalis (P. gingivalis) as a key pathogen, has been associated with systemic effects, potentially influencing distant organs including liver. The liver plays a key role in iron metabolism and immunity by hepcidin. This study aims to investigate the impact of P. gingivalis-induced CAP on liver and systemic iron metabolism, focusing on the role of the IL-6/STAT3 signaling pathway in hepatic hepcidin synthesis. Methods: A murine model of CAP was established by pulp chamber infection with P. gingivalis. Serum levels of IL6, ferritin, and hepcidin were measured via ELISA. High-throughput sequencing was used to analyze hepatic gene expression, and immunohistochemistry with fluorescent staining was performed to validate protein expression in liver tissues. Results: CAP led to significant changes in serum iron, ferritin, and IL-6. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed enrichment in pathways like JAK/STAT signaling and acute-phase responses, and gene set enrichment analysis (GSEA) also indicated activation of IL-6/ JAK/STAT3 signaling pathway. Iimmunofluorescence confirmed increased IL-6, p-STAT3, and hepcidin expression. These levels were alleviated by stattic treatment, mitigating CAP-induced inflammatory and ironregulatory effects. Conclusion: P. gingivalis-induced CAP triggered systemic inflammation and disrupts iron metabolism via the IL-6/ STAT3 signaling pathway, potentially affecting liver function. Targeting this pathway may offer therapeutic strategies for managing iron dysregulation in chronic inflammatory diseases like CAP.

关键词： 系统性红斑狼疮   中医诊断   淋巴细胞亚群   细胞因子   CD8+T细胞   白介素-10   肿瘤坏死  

摘要： 目的 “红蝴蝶疮”“阴阳毒”和“痹病”是系统性红斑狼疮（Systemic lupus erythematosus,SLE）的不同中医诊断，目前尚不清楚这3种类型的中医诊断在生物学上是否存在差异。本研究旨在从淋巴细胞亚群和细胞因子角度比较SLE患者的不同中医诊断。方法 回顾性收集2021年6月1日至2023年12月1日经我院确诊SLE的患者，通过单因素方差分析或非参数检验比较不同组之间T细胞亚群、NK细胞、B淋巴细胞及其Th1类、Th2类、Th17类细胞因子差异，以及红细胞沉降率（ESR）、C-反应蛋白（CRP）、免疫球蛋白、补体等实验室检测指标的差异，以受试者操作特征曲线（Receiver operating characteristic curve,ROC curve）分析这些指标对不同类型的SLE鉴别诊断价值。结果 收集2021年6月1日至2023年12月1日经我院确诊SLE的首次住院患者291例，纳入符合本研究纳排标准的病例104例，其中红蝴蝶疮31例、阴阳毒30例、痹病43例。三组SLE不同中医诊断患者组间CD8+T细胞绝对数量和百分比、白介素-10(IL-10)含量、肿瘤坏死因子α(TNF-α)含量相比有所差异，并且红蝴蝶疮组CD8+T细胞绝对数量显著高于阴阳毒组（P=0.039）与痹病组（P=0.008），红蝴蝶疮组CD8+T细胞百分比显著高于阴阳毒组（P=0.014）与痹病组（P=0.004），红蝴蝶疮组IL-10及TNF-α水平显著低于痹病组（P=0.015,P=0.036），且ROC曲线分析显示，CD8+T细胞绝对数量和百分比能有效区别红蝴蝶疮与阴阳毒（AUC=0.65,AUC=0.61,P<0.05）,CD8+T细胞绝对数量和百分比、IL-10,TNF-α能有效区别红蝴蝶疮与痹病（AUC=0.68,AUC=0.66,P<0.01;AUC=0.67,AUC=0.64,P<0.05）。结论免疫淋巴细胞亚型，细胞因子，特别是CD8+T细胞绝对数量和百分比、IL-10及TNF-α可能在鉴定SLE不同中医诊断中具有重要作用。

关键词： ACSM3   cell proliferation   IFN-gamma/JAK/STAT3 signaling pathway   ovarian cancer  

摘要： This study aimed to investigate the role of Acyl-CoA medium-chain synthetase 3 (ACSM3) in ovarian cancer (OC) progression. ACSM3 expression in OC tissues and cells is detected by real-time quantitative polymerase chain reaction, immunohistochemistry, or western blot. The influences of ACSM3 on OC progression are assessed in vitro and in vivo experiments. Gene set enrichment analysis is performed to find significantly enriched pathways related to ACSM3. In this study, ACSM3 expression in OC tissues and cells is downregulated. ACSM3 inhibited tumor growth in vivo. Knockdown of ACSM3 promoted cell proliferation, migration, and invasion, inhibited cell apoptosis, and activated JAK/STAT3 signaling pathway in SKOV3 cells, while overexpression of ACSM3 in A2780 cells led to the opposite results. Moreover, treatment with interferon-gamma (IFN-gamma) in A2780 cells reversed the effects of ACSM3 on cell proliferation, migration, invasion, and apoptosis, but IFN-gamma further enhanced the effects of ACSM3 knockdown on SKOV3 cell proliferation, migration, invasion, and apoptosis. In conclusion, ACSM3 inhibited OC cell proliferation, migration, and invasion, and promoted cell apoptosis by suppressing the IFN-gamma/JAK/STAT3 signaling pathway, which might provide a promising therapeutic target for OC treatment.