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关键词： Asthma   weighted gene co-expression network analysis (WGCNA)   ferroptosis  

摘要： Background: Asthma is a heterogeneous chronic inflammatory disease of the airway, and its development is the result of genetic factors, environmental factors, immune dysfunction, and other factors. This study aimed to identify biomarkers of asthma. Methods: A differential gene expression (DGE) analysis and a weighted gene co-expression network analysis (WGCNA) were conducted to identify the asthma-related genes in the GSE67472 dataset, and these genes were intersected with immune genes from the Immuport database to identify the asthma-associated immune genes. Least absolute shrinkage and selection operator (LASSO) regression was used to identify the key asthma-associated immune genes, and receiver operating characteristic (ROC) curves were used to assess the diagnostic potential of these genes. Subsequently, the mechanism of action of the inducible factor interleukin 13 (IL-13) in human bronchial epithelial (HBE) cells and its effect on markers of asthma were verified in vitro. Results: The DGE analysis and WGCNA identified 62 asthma-related genes, and eight asthma-associated immune genes were identified after the intersection of the asthma-related genes and the immune-related genes. Utilizing LASSO regression, five key immune genes linked to asthma were uncovered. These included S100 calcium binding protein A16 (S100A16), Lactotransferrin (LTF), BPI fold containing family A member 1 (BPIFA1), cystatin 4 (CST4), and growth-related protein (GRP). The area under the curve (AUC) values of S100A16 and CST4 were greater than 0.8. The single-cell analysis showed that S100A16 was highly expressed in asthmatic neutrophils. Finally, the results of the in vitro experiments showed that IL-13 not only induced lipid peroxidation to promote iron death in the HBE cells, but also promoted the expression of S100A16. Conclusions: This study identified a new biomarker, S100A16, for the diagnosis of asthma. S100A16 may serve as a new potential target for asthma treatment, and may be an

关键词： Adalimumab   Cytokine   Etanercept   Infliximab   Paradoxical  

摘要： The inhibition of tumor necrosis factor-α (TNF-α) signaling with inhibitors (TNFi) like infliximab, adalimumab, or etanercept has become a staple of dermatological and rheumatological therapy. Intriguingly, a sizeable minority of patients under TNFi therapy develop alopecia areata (AA), the most common inflammatory hair loss disease, at a higher prevalence than the general population. This appears paradoxical, since the pro-inflammatory Th1 cytokine TNF-α, inhibits hair follicle (HF) growth, but encourages one to reconsider the as yet under-investigated roles of TNF-α in human HF physiology. Because AA only affects HFs whose immune privilege (IP) has collapsed, the occurrence of AA under TNFi therapy raises the question if inhibiting TNF-a signaling could be detrimental to the maintenance of HF IP. Here, we probe this question by exploring lesser-known aspects of TNF-α biology, notably within the context of skin inflammation. We hypothesize that, under inflammatory conditions, TNF-α exerts underappreciated functions as a HF IP guardian, e.g., by stimulating perifollicular immunoinhibitory cells and suppressing IFN-α secretion. Thus, TNFi may weaken HF IP and facilitate the onset of AA. We delineate how this provocative hypothesis can be tested experimentally, and why it is both biologically and clinically important to do so.

关键词： occupational factors   aluminum dust   IL-1 beta   genetic polymorphism   cognitive function   interaction  

摘要： Background: Various occupational hazards in the electrolytic aluminum environment have been linked to cognitive decline. However, the interactive effects of these hazards and genetic factors on cognitive function remain unclear. Objective: This study aimed to identify the primary occupational hazards, examine their interaction with IL-1 beta gene polymorphisms in relation to cognitive function. Methods: A cross-sectional study was conducted in June 2024 at an electrolytic aluminum company in China, involving 478 male workers. Cognitive function was assessed using the Montreal Cognitive Assessment. Calculate the cumulative exposure dose of harmful factors such as aluminum dust. Additionally, IL-1 beta gene polymorphisms (rs1143627, rs1143643, rs16944, rs3917356) and serum protein levels were analyzed. The associations between environmental exposure, genetic factors, and cognitive function were examined using multivariate stepwise linear regression, restricted cubic splines, generalized linear models, and hierarchical analysis. Covariance analysis and independent sample t-tests were employed to assess the potential mediating effect of peripheral blood IL-1 beta levels. Results: Cumulative exposure to aluminum dust was significantly associated with cognitive decline (beta = -0.18, 95% CI: 0.27, -0.10), and the relationship was linear. Compared to the wild genotype, individuals carrying rs1143627 G/G, rs1143643 C/C, and rs16944 A/A exhibited significantly lower cognitive scores (P < 0.01), whereas rs3917356 C/T and T/T conferred a protective effect (P < 0.01). The model was adjusted for age, body mass index, and cumulative aluminum dust exposure. The genetic effect associated with IL-1 beta was more pronounced in individuals with high aluminum exposure (>2.37 mg/m(3) x year). IL-1 beta serum protein levels showed no significant association with cognitive function (P > 0.05). Conclusion: Cumulative exposure to aluminum dust is a key risk factor for cognitive decline. IL-

关键词： cancer   cardiac magnetic resonance   constrictive   echocardiography   imaging   nuclear medicine   pericardial effusion   positron emission tomography   shortness of breath   treatment   CMR   cardiac magnetic resonance imaging   CRP   c-reactive protein   CT   computed tomography   FDG   fluorodeoxyglucose   IL   interleukin   LGE   late gadolinium enhancement   NSAID   nonsteroidal anti-inflammatory drug   T-ALL   T-cell acute lymphoblastic leukemia   TTE   transthoracic echocardiography  

摘要： Background Recurrent pericarditis affects up to 30% of patients after an initial episode, with the majority of recurring episodes occurring within 18 months. Younger age, subacute presentations, and initial treatment with steroids rather than colchicine are risk factors. Incorporation of multimodality imaging is essential in the diagnosis and management of recurrent pericarditis, particularly in complex cases. Case Summary A 32-year-old man was diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) and recurrent acute pericarditis complicated by constriction. Management included multimodality imaging, colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), strategic dosing of steroids, and weaning based on chemotherapy and clinical response. Cardiac magnetic resonance (CMR) guided treatment adjustments, demonstrating constrictive physiology and status of inflammation. Discussion This case highlights the role of multimodality imaging in the diagnosis and management of recurrent pericarditis in the setting of acute leukemia, enabling detailed assessment of inflammation and guiding treatment. Emerging therapies, such as interleukin (IL)-1 blockers, offer promising options for refractory cases, although their role in malignancy requires further study.

关键词： natural killer cells   parainfluenza virus 5   oncolytic virus   type 1 interferon   immunotherapeutic  

摘要： Natural killer (NK) cell adoptive immunotherapy is a promising therapeutic approach in which NK cells perform targeted lysis of tumor cells. Oncolytic viruses are also effective cancer therapeutic agents due to their ability to selectively target and kill tumor cells. Combination therapies that integrate NK cells and oncolytic viruses have been shown to enhance tumor killing compared to individual treatment strategies alone. Using in vitro expanded human NK cells (PM21-NK cells), we tested the relative ability of tumor cells infected with WT parainfluenza virus 5 (PIV5), which is a poor inducer of type 1 interferon (IFN-I), versus PIV5 P/V gene mutant, which is a strong inducer of IFN-I synthesis, to modulate NK cell activities. Both WT and P/V mutant viruses were capable of infecting PM21-NK cells and caused extensive cytopathic effects. Co-culturing of PM21-NK cells with virus-infected tumor cells resulted in spread of WT PIV5 to na & iuml;ve NK cells, but NK cells were protected from spread of the P/V mutant virus by IFN-I induction. Direct treatment of PM21-NK cells with IFN-I or media from P/V-virus-infected tumor cells enhanced NK cell cytotoxicity, at least in part due to upregulation of the death ligand, TRAIL. IFN-I-treated PM21-NK cells also showed a decrease in IFN-gamma secretion, a cytokine we have previously shown to reduce PM21-NK cell tumor killing. Our results highlight multiple mechanisms by which an IFN-I-inducing oncolytic virus can enhance NK-cell-mediated killing of target virus-infected and uninfected tumor cells.

关键词： IMQ-induced psoriasis-like skin inflammation   methotrexate   microneedle   psoriasis   recurrence  

关键词： 胃早癌   内镜下黏膜下剥离   异时性癌   调节性T细胞/辅助性T细胞17细胞因子   幽门螺杆菌  

摘要： 目的 探讨调节性T细胞/辅助性T细胞17（Treg/Th17）细胞因子与幽门螺杆菌（Hp）对胃早癌术后发生异时性癌的影响及作用。方法 采用1:3个体匹配病例对照研究，选取2020年1月至2023年12月西安长安医院收治的45例胃早癌术后异时性癌患者作为试验组，另选取135例胃早癌术后未发生异时性癌患者作为对照组。比较两组一般资料、Treg/Th17细胞因子[转化生长因子β1（TGF-β1）、白介素（IL）-10、IL-17、IL-23]、Hp感染情况，采用Logistic回归方程和森林图分析胃早癌术后发生异时性癌的影响因素，分析Treg/Th17细胞因子与Hp感染的交互作用。结果 两组肿瘤浸润深度、肿瘤肉眼病理分型比较，差异有统计学意义（P＜0.05）；试验组Hp感染阳性率及血清TGF-β1、IL-10、IL-17、IL-23含量高于对照组（P＜0.05）；Hp感染阳性率、TGF-β1、IL-17、肿瘤浸润深度是胃早癌术后发生异时性癌的影响因素（P＜0.05）；血清TGF-β1、IL-17高表达与Hp感染对胃早癌术后发生异时性癌存在正相交互作用。结论 TGF-β1、IL-17、Hp感染阳性率是胃早癌术后发生异时性癌影响因素，且存在正相交互作用。

关键词： 苓泽合剂   痛风性关节炎   MMP-1   IL-1β  

摘要： 目的：建立痛风性关节炎（gouty arthritis，GA）大鼠模型，通过观察病理形态学改变及检测血清中IL-1β、软骨中MMP-1表达水平，研究苓泽合剂对急性痛风性关节炎大鼠模型关节软骨治疗与防护作用。方法：将70只大鼠随机分成空白组、模型组、依托考昔组、痛风定组、苓泽合剂低、中、高组各10只。除空白组外，采用尿酸钠关节腔注射联合氧嗪酸钾腹腔注射诱导大鼠GA模型。造模成功后，给药组大鼠按规定剂量口服给药，模型组和空白组给予相同体积的蒸馏水，每日1次连续给药3 d。造模成功后取大鼠血清，检测血中白细胞介素-1β（IL-1β）含量；取大鼠右踝关节软骨，观察病理形态学改变，并通过免疫细胞化学技术检测其软骨中基质金属蛋白酶-1（MMP-1）表达。结果：给药后，苓泽合剂低、中、高组关节软骨破坏情况较模型组明显减轻，模型组血清中IL-1β、软骨中MMP-1含量明显增高，苓泽合剂组、依托考昔组及痛风定组血清中IL-1β、软骨中MMP-1含量均有所降低，苓泽合剂中、高剂量组与依托考昔组对降低血清中IL-1β、软骨中MMP-1含量优于苓泽合剂低剂量组。苓泽合剂低剂量组大鼠血清中IL-1β浓度较模型组明显降低，具有统计学意义（P<0.01）。苓泽合剂中、高剂量组大鼠血清中IL-1β浓度较模型组明显降低，具有统计学意义。（P<0.01）结论：苓泽合剂可能通过抑制IL-1β的表达，下调MMP-1的表达，从而达到治疗与防护痛风性关节炎关节软骨破坏的作用。

关键词： anti-TNF   Crohn's disease   early treatment   hospitalization   immunomodulators   inflammatory bowel disease   outcomes   timing   ulcerative colitis   visits  

摘要： Background: Early advanced inflammatory bowel disease (IBD) therapy is emphasised to prevent disease progression and restore quality of life. Aims: To evaluate the potential advantages of early versus late anti-tumour necrosis factor (TNF) therapy in patients with IBD. Methods: This retrospective study included patients with newly diagnosed IBD (2004-2018) who received anti-TNF therapy and had at least 1 year of follow-up. Patients were categorised as early or late users based on a 2-year post-diagnosis cut-off for first anti-TNF exposure. Outcomes included IBD-related surgeries, hospitalizations, emergency department (ED) visits, and drug persistence. Subgroup analysis examined concurrent immunomodulator use, and sensitivity analyses were employed 6 months or 1 year post-diagnosis cut-offs. Results: Among 8105 patients with ulcerative colitis (UC) and 8465 with Crohn's disease (CD), distinct outcomes emerged. Early anti-TNF users with UC had significantly higher hospitalization (hazard ratio [HR] 1.34, 95% confidence interval [CI] 0.91-1.96) and ED visit rates (HR 1.30, 95% CI 1.16-1.46) compared with late users. In CD, early users showed a non-significant trend toward fewer event rates. Drug persistence was longer among late users for both UC and CD. In UC, combining immunomodulators with early anti-TNF increased hospitalization and ED visits but not in CD. Sensitivity analyses confirmed the primary findings. Conclusions: While early anti-TNF use was associated with differential outcomes in CD, the relationship between treatment timing and clinical course diverged in UC, challenging the assumption that early intervention is universally advantageous across IBD subtypes. These findings underscore the need for further research to identify patient subgroups that might benefit most from early intervention.

关键词： 网络药理学   分子对接   菟丝子-丹参   复发性流产   IL-6/STAT3信号通路  

摘要： 目的 通过网络药理学、分子对接和细胞实验验证，研究菟丝子-丹参治疗复发性流产（RSA）的作用机制。方法 利用TCMSP数据库和Uniport数据库筛选并整理菟丝子-丹参的活性成分与相应靶点。利用OMIM、GeneCards、Drugbank、DisGeNET、TTD数据库，收集RSA的潜在治疗靶点。通过构建蛋白质相互作用（PPI）网络图，并进行拓扑分析，筛选出菟丝子-丹参治疗RSA的潜在核心靶点。同时，利用DAVID数据库对筛选出的交集靶点进行富集分析。在此基础上，采用AutoDock软件进行分子对接验证，再将数据导入Pymol软件进行可视化构图。最后，通过CCK-8实验、Transwell 实验和Westernblot检测评估菟丝子-丹参含药血清对滋养细胞（HTR-8/SVneo细胞）的影响，并观察对IL-6/STAT3通路及相关蛋白表达的影响。结果 通过网络药理学分析，共获得69个菟丝子-丹参的活性成分，73个潜在治疗靶点，筛选得到IL6、IL-10、STAT3等17个核心靶点。73个共有靶点富集于614个GO条目和57条KEGG信号通路。分子对接结果提示IL-6、STAT3与苦参碱、隐丹参酮、丹参酮IIA等活性成分具有较好的结合力。细胞实验结果表明，相比与对照组，菟丝子-丹参含药血清作用24 h后，HTR-8/SVneo细胞的存活率与侵袭率显著上升（P<0.05），IL-6/STAT3信号通路以及通路相关蛋白IL-10和c-Myc的表达均显著升高（P<0.05），含药血清组的作用趋势与通路激动剂一致。结论 菟丝子-丹参药对可能通过激活IL-6/STAT3信号通路，上调通路下游因子IL-10和c-Myc的表达，改善滋养细胞的存活率和侵袭活性，从而防治RSA。