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关键词： 肺结核   菌阴性   白细胞介素-27   结核感染T细胞斑点试验   诊断价值  

摘要： 目的：探讨血清白介素-27(IL-27)联合结核感染T细胞斑点试验（***）对菌阴性肺结核的诊断价值。方法：回顾性分析2023年4月～2024年7月我院收治的168例肺结核患者的临床资料。分为痰菌阳性肺结核组（n=84）和痰菌阴性肺结核组（n=84），另选取同期体检健康者84例为对照组（n=84）。收集患者临床资料，所有患者均进行***、血清IL-27及外周血红细胞沉降率（ESR）检测。比较三组***、血清IL-27及ESR的差异，绘制受试者特征（ROC）曲线评价***、血清IL-27单独及二者联合检测对痰菌阴性肺结核的诊断效能。结果：痰菌阳性肺结核组与痰菌阴性肺结核组***检出阳性率显著高于对照组（P<0.0125），痰菌阳性肺结核组与痰菌阴性肺结核组***检出阳性率比较差异无统计学意义（P>0.0125）。肺结核组血清IL-27及外周血ESR均高于对照组（P<0.05）；痰菌阳性肺结核组血清IL-27高于痰菌阴性肺结核组（P<0.05），痰菌阳性肺结核组与痰菌阴性肺结核组ESR无显著性差异（P>0.05）。以临床综合诊断为参考标准，***、血清IL-27单独及二者联合诊断肺结核的效能如下：***诊断的AUC为0.815，敏感度和特异度分别为84.52%(95%CI为78.2～89.6)和78.50%(95%CI为68.3～86.8)；血清IL-27诊断的AUC为0.848，敏感度和特异度分别为65.48%(95%CI为57.8～72.6)和94.05%(95%CI为86.7～98.0)；联合诊断的AUC为0.936，敏感度和特异度均为86.90%,95%CI分别为（80.8～91.6）和（77.8～93.3）。诊断痰菌阴性肺结核时，血清IL-27及***单独及联合检测诊断效能如下：***诊断的AUC为0.845，敏感度和特异度分别为82.14%(95%CI为72.3～89.6)和86.9%(95%CI为77.8～93.3)；血清IL-27诊断的AUC为0.867，敏感度和特异度分别为91.67%(95%CI为83.6～96.6)和64.29%(95%CI为53.1～74.4)；联合诊断的AUC为0.955，敏感度和特异度分别为90.48%(95%CI为82.1～95.8)和86.90%(95%CI为77.8～93.3)。结论：***及血清IL-27二者联合检测会进一步提高痰菌阴性肺结核患者的诊断效能。

关键词： Biologic therapy   Crohn’s disease   IL23   Inflammatory bowel disease   P19 inhibitors   Ulcerative colitis  

摘要： PURPOSE OF THE REVIEW:Review the efficacy and safety of IL2319 inhibitors in the management of IBD. RECENT FINDINGS:Risankizumab, mirikizumab, and guselkumab have been found to be efficacious and safe in the management of IBD. IL23p19 inhibitors have been found to be successful in the management of IBD. The new class of biologics adds to the growing armamentarium of medical options and could additionally prove beneficial as dual therapy.

关键词： A2A receptor   HLA-E   NK cells   Radiotherapy-resistant-TNBC   phospho-STAT1 (Y701)  

摘要： Triple-negative breast cancer (TNBC) patients have lower survival rates and higher recurrence risks than non-TNBC patients. Moreover, radiotherapy-resistant TNBC (RT-R-TNBC) exhibits enhanced chemotherapy resistance and invasiveness. Therefore, there is a critical need for innovative treatments for RT-R-TNBC and TNBC patients. Our previous study indicated that NK cells exhibit reduced cytotoxicity against RT-R-TNBCs due to HLA-E upregulation. Thus, this study aimed to identify the mechanism responsible for the upregulation of HLA-E and to suggest potential therapeutic targets for overcoming the RT-resistance of TNBC. We found that HLA-E expression was significantly higher in TNBC tumor tissues than in normal epithelial tissues and non-TNBC tissues, correlating with A2AR levels. In addition, MDA-MB-231 (TNBC) and RT-R-MDA-MB-231 (RT-R-TNBC) showed an A2AR-dependent HLA-E overexpression. NK cell-mediated cytotoxicity against MDA-MB-231 and RT-R-MDA-MB-231 was reduced and restored by A2AR or STAT1 knockdown. Interestingly, STAT1 phosphorylation (Y701) by adenosine (ADO) aligned with the HLA-E expression pattern by ADO, and fludarabine, a STAT1 inhibitor, effectively reduced phospho-STAT1 (Y701) levels, but not phospho-STAT1 (S727) levels. Fludarabine also inhibited ADO-induced HLA-E expression in MDA-MB-231 and RT-R-MDA-MB-231, including basal HLA-E expression in RT-R-MDA-MB-231. Additionally, fludarabine reduced tumor progression, lung metastasis, HLA-E expression, and phospho-STAT1 (Y701) in RT-R-MDA-MB-231-injected mice. Moreover, Monalizumab, an NKG2A monoclonal antibody, significantly reduced tumor progression and lung metastasis with increased population of cytotoxic NK cells (CD25+NK1.1+ and CD69+NK1.1+) in the inguinal lymph nodes of RT-R-MDA-MB-231-injected mice. This study suggests that the A2AR-phospho-STAT1 (Y701)-HLA-E axis may serve as an alternative target for overcoming RT-resistance in TNBC.

关键词： IL-6   Integrins   Mechanical stress   NF-κB signaling   Osteoarthritis   Temporomandibular joint  

摘要： OBJECTIVES:Temporomandibular joint osteoarthritis (TMJOA) is a multifactorial degenerative disorder involving biomechanical and inflammatory processes. Yet, how mechanical stress causes synovial inflammation and cartilage degradation is unclear. This study aimed to explore the relationship between mechanical stress and inflammatory responses in TMJOA. METHODS:Synovial fluid cytokine profiles from TMJOA patients and controls were analyzed using high-throughput antibody microarrays and validated by ELISA. Finite element analysis (FEA) was employed to map mechanical stress distributions in the mandibular condyle post-surgery. A unilateral anterior crossbite (UAC) rats model was established to mimic mechanical stress-induced OA, with subsequent evaluation of cartilage degeneration and synovial IL-6 expression. RNA sequencing was employed to identify mechanosensitive genes regulating IL-6/IL-8 induction, followed by in vitro validation of signalling pathway using primary synovial fibroblasts and chondrocytes. RESULTS:Synovial IL-6 and IL-8 levels were significantly elevated in TMJOA patients post-mandibular advancement surgery compared with those with temporomandibular joint disc displacement. ELISA confirmed these findings, demonstrating a strong positive correlation between IL-6 levels and both joint pain score and reduced maximum mouth opening. FEA revealed uneven mechanical stress redistribution in the condyle post-surgery, with IL-6 levels correlating with mandibular advancement distance. In a murine model of mechanical stress-induced OA, cartilage exhibited OA-like degenerative changes accompanied by elevated synovial IL-6 levels. Mechanistically, mechanical loading induced IL-6 via integrin αIIbβ3 activation, triggering non-canonical NF-κB signalling. CONCLUSION:Mechanical stress drives TMJOA synovial inflammation via integrin αIIbβ3/NF-κB-mediated IL-6 secretion, linking biomechanical perturbations to cartilage degradation. Targeting this pathway may offer novel

关键词： 细胞因子   粒细胞缺乏   降钙素原   感染   早期预测  

摘要： 目的 探讨细胞因子检测在粒细胞缺乏并发感染患者早期识别、早期预测的临床价值。方法 选取2022年1月-2023年12月在白银市第一人民医院血液科住院治疗的粒细胞缺乏并发感染的50例患者作为观察组，另选取同期住院年龄相当无感染的粒细胞缺乏住院患者32例作为对照组。收集统计并比较两组细胞因子（IL-2、IL-4、IL-6、IL-10、IL-17、TNF-α、IFN-γ）、感染指标（PCT、CRP）。结果 观察组IL-2、IL-4、IL-6、IL-10、IL-17、PCT、CRP高于对照组，差异有统计学意义（P＜0.05），TNF-α、IFN-γ低于对照组，但差异无统计学意义（P＞0.05）。观察组发热6h内IL-6、IL-10出现升高（P＜0.001），而PCT、CRP未见明显上升（P＞0.05）；发热6h后PCT、CRP升高（P＜0.01）。结论粒细胞缺乏并发感染患者可以通过细胞因子检测早期识别、预测感染的存在，及时进行药物干预治疗，提高患者感染控制的疗效。

关键词： Alzheimer's disease   Cognitive Impairment   MLKL   Necroptosis   Neuroinflammation   Oxidative Stress   Piperine   Scopolamine   TNF-α  

摘要： Alzheimer's disease (AD) is the leading cause of dementia, characterized by cognitive decline and neurodegeneration. Given the limitations of current treatments, research has turned to natural substances such as piperine, which is known for its neuroprotective properties. This study investigates the effects of piperine on cognitive function and genes associated with oxidative stress, inflammation, and necroptosis-related genes in a rat model of cognitive impairment. Fifty adult male Wistar rats were used, divided into five groups: an intact group, a control group (vehicle solution followed by scopolamine), and three experimental groups receiving piperine (5, 10, and 20 mg/kg) followed by scopolamine during the training period. Behavioral assessment was conducted using the Morris Water Maze (MWM) test. Hippocampal tissue was collected after euthanasia for gene expression analysis of Nrf2, HO‑1, TNF‑α, Fas, TRAIL, MLKL, and Caspase‑8. Spatial learning and memory improved significantly in piperine-treated groups, with no impact on swimming velocity, indicating cognitive enhancement without affecting motor functions in the scopolamine-induced cognitive impairment model. Piperine pretreatment prevented oxidative stress and inflammation, as evidenced by the restoration of Nrf2, HO-1, and Caspase-8 and the reduction of TNF-α, Fas, TRAIL, and MLKL expression levels. These findings suggest that piperine has antioxidative, anti‑inflammatory, and cognitive‑enhancing effects, with particular effects possibly on necroptosis, and could be a valuable addition to the current AD treatment paradigm, warranting further investigation in clinical trials.

关键词： Endometriosis   IL-6 receptor monoclonal antibody   Mice   Tocilizumab  

摘要： Endometriosis is a gynecological inflammatory disorder characterized by the presence of endometrial tissue outside of the uterus. It affects 10-15% of reproductive aged women, causing pelvic pain and infertility. Existing treatments for endometriosis, including invasive and non-invasive therapies, are plagued by treatment resistance and adverse effects. Dissecting molecular mechanisms or signaling pathways that are involved in the pathophysiology of endometriosis may reveal new molecular targets. IL-6 is classically considered an inflammatory cytokine that is highly expressed in endometriosis. Here, we studied the effect of an anti-IL-6R antibody that interferes with the IL-6 signaling pathway in endometriosis. Endometriosis was induced in c57BL/6 female mice that were subsequently treated with either a murine-specific anti-IL-6 receptor monoclonal antibody (15A7) or IgG2b as a control. We found that there was no change in endometriosis lesion number or volume. However, we observed that the lesion attachment to underlying peritoneum was significantly increased after treatment with the 15A7 antibody, indicating a possible effect on invasion. As expected, IL-6 mediated pathways of p38 MAPK and STAT3 in JAK/STAT signaling were decreased in the anti-IL-6R treatment group compared to isotype control group. There were no differences in N-Cadherin and ICAM between groups. IL-6 had a paradoxical role in endometriosis - preventing or limiting invasion and adhesion.

关键词： 结核感染T细胞斑点试验   细胞因子   活动性肺结核   非活动性肺结核   准确性  

摘要： 目的 探讨结核感染T细胞斑点试验(***)联合细胞因子鉴别活动性肺结核(ATB)的诊断效能及影响因素。方法 选择2019年1月—2023年10月于河北省胸科医院就诊的240例患者为研究对象,其中ATB组123例,非ATB组117例。采用曲线下面积(AUC)分析***联合细胞因子鉴别ATB的诊断效能,Kappa一致性检验分析一致性水平,多因素logistic回归分析影响***诊断准确性因素。结果 两组患者肺结核接触史、胸腔积液总蛋白、肺部细菌感染、结核菌素(PPD)试验阳性、结核分枝杆菌抗体(TB-Ab)检测阳性、胸腔积液***阳性、空洞直径、胸膜肥厚、胸膜粘连、结节性红斑和血供方面,差异均有统计学意义(P<0.05);与非ATB组相比,ATB组白细胞介素(IL)-6[(43.98±21.32)ng/L]、IL-8[(27.95±12.26)ng/L]和干扰素-γ(IFN-γ)[(40.75±19.11)ng/L]水平较高(P<0.05);受试者工作特征(ROC)曲线显示,细胞因子IFN-γ、IL-6、IL-8和***斑点数联合诊断ATB患者的AUC值高于各指标单独检测(P<0.05);肺部细菌感染为影响***诊断准确性的影响因素(P=0.018,OR=5.703,95%CI:1.358～23.953)。结论 ***联合IFN-γ、IL-6和IL-8对ATB的诊断效能良好,值得在临床推广实践。

摘要： I tumori neuroendocrini ipofisari (PitNET)/adenomi ipofisari costituiscono un insieme eterogeneo di neoplasie la cui classificazione diagnostica anatomo-patologica è stata oggetto di numerose revisioni nonostante le quali diversi aspetti rimangono oggetto di discussione. L’obiettivo principale della presente rassegna è di fornire un riepilogo dell’attuale sistema classificativo, delle relative limitazioni, dei possibili algoritmi diagnostici e del ruolo della diagnostica molecolare.