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关键词： 早产儿   呼吸窘迫综合征   支气管肺发育不良   白细胞介素-18   25-羟基维生素D_(3)   C1q/肿瘤坏死因子相关蛋白4  

摘要： 目的探究呼吸窘迫综合征早产儿血清白细胞介素-18(IL-18)、25-羟基维生素D_(3)[25(OH)D_(3)]、C1q/肿瘤坏死因子相关蛋白4(CTRP4)对支气管肺发育不良(BPD)的预测价值。方法选取2022年1月至2024年2月濮阳市人民医院呼吸窘迫综合征早产儿265例,以出院时BPD发生情况为终点事件,根据呼吸窘迫综合征早产儿是否发生BPD分为发生组(n=65)与未发生组(n=200)。比较发生组与未发生组患儿的临床资料及血清IL-18、25(OH)D_(3)、CTRP4水平,采用受试者工作特征(ROC)曲线评价血清IL-18、25(OH)D_(3)、CTRP4对呼吸窘迫综合征早产儿BPD的预测价值。采用Logistic回归分析呼吸窘迫综合征早产儿BPD发生的影响因素,相加模型评价血清IL-18、25(OH)D_(3)、CTRP4对呼吸窘迫综合征早产儿BPD风险的交互作用。结果发生组患儿的胎龄、出生体质量分别为(29.72±0.56)周、(1348.25±407.36)g,明显低于未发生组的(30.47±0.52)周、(1594.32±395.61)g,呼吸机治疗时间为(3.24±0.75)d,明显长于未发生组的(1.96±0.52)d,差异均有统计学意义(P<0.05);发生组患儿的血清IL-18、25(OH)D_(3)、CTRP4水平分别为(4.87±1.50)ng/L、(8.94±2.56)ng/mL、(15.24±3.12)μg/L,明显高(低)于未发生组的(3.74±1.19)ng/L、(12.11±3.02)ng/mL、(12.87±2.49)μg/L,差异均有统计学意义(P<0.05);ROC曲线分析结果显示,血清IL-18、25(OH)D_(3)、CTRP4预测呼吸窘迫综合征早产儿BPD的最佳截断值分别为3.79 ng/L、9.40 ng/mL、13.42μg/L,三者联合预测的及曲线下面积(AUC)值最大,为0.915(95%CI:0.875~0.946);Logistic回归分析结果显示,调整胎龄、出生体质量、呼吸机治疗时间等其他混杂因素前后,血清IL-18、25(OH)D_(3)、CTRP4均为呼吸窘迫综合征早产儿发生BPD的独立影响因素(P<0.05);交互作用分析结果显示,调整胎龄、出生体质量、呼吸机治疗时间等其他混杂因素后,血清IL-18、25(OH)D_(3)、CTRP4同时暴露对呼吸窘迫综合征早产儿BPD发生存在协同作用,三者同时暴露时,其协同效应为三者单独存在产生效应之和的1.864倍。结论呼吸窘迫综合征早产儿血清IL-18、CTRP4水平升高、25(OH)D_(3)水平下降与BPD发生密切相关,三者存在交互作用,联合检测BPD效能较高。

关键词： 颅脑损伤   白介素1β   超氧化物歧化酶   还原型谷胱甘肽   预后  

摘要： 目的探讨白介素1β(IL-1β)、超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)与创伤性颅脑损伤(TBI)患者肠道屏障功能的关系及其对患者预后不良的预测价值。方法回顾性选取2022年8月—2024年8月南京鼓楼医院集团宿迁医院收治的114例TBI患者为研究对象,收集患者的临床资料,检测肠道屏障功能指标〔二胺氧化酶(DAO)、D-乳酸〕及IL-1β、SOD、GSH。随访6个月根据格拉斯哥预后评分(GOS)将患者分为预后良好组(79例)和预后不良组(35例)。采用Pearson相关分析探讨TBI患者IL-1β、SOD、GSH与DAO、D-乳酸的相关性;采用多因素Logistic回归分析探讨TBI患者预后的影响因素;采用ROC曲线探讨IL-1β、SOD、GSH及三者联合对TBI患者预后不良的预测价值。结果预后不良组与预后良好组严重程度、DAO、D-乳酸、IL-1β、SOD、GSH比较,差异有统计学意义(P<0.05)。Pearson相关分析结果显示,TBI患者IL-1β与DAO、D-乳酸呈正相关,SOD、GSH与DAO、D-乳酸呈负相关(P<0.05)。多因素Logistic回归分析结果显示,严重程度〔OR=4.311,95%CI(1.490~12.472)〕、DAO〔OR=1.281,95%CI(1.084~1.513)〕、D-乳酸〔OR=5.650,95%CI(1.637~19.499)〕、IL-1β〔OR=5.172,95%CI(2.046~13.070)〕、SOD〔OR=0.613,95%CI(0.479~0.783)〕、GSH〔OR=0.104,95%CI(0.032~0.338)〕是TBI患者预后的独立影响因素(P<0.05)。ROC曲线分析结果显示,IL-1β、SOD、GSH及三者联合预测TBI患者预后不良的AUC分别为0.771〔95%CI(0.674~0.869)〕、0.813〔95%CI(0.728~0.899)〕、0.794〔95%CI(0.699~0.889)〕、0.902〔95%CI(0.839~0.965)〕。结论TBI患者IL-1β、SOD、GSH与肠道屏障功能相关。IL-1β、SOD、GSH是TBI患者预后的独立影响因素,且三者联合对TBI患者预后不良有较好的预测价值。

关键词： 干扰素-γ   白细胞介素-2   艾滋病   结核病   人类免疫缺陷病毒   联合检测  

摘要： 目的探讨结核特异性细胞因子干扰素-γ(IFN-γ)和白细胞介素-2(IL-2)双因子联合检测在人类免疫缺陷病毒(HIV)感染者中结核病(TB)的诊断价值及漏诊的影响因素。方法选取2022年7月—2024年9月贺州市人民医院感染性疾病科收治的接受TB相关检查的HIV感染者,根据临床诊断标准分为HIV感染合并TB患者组(HIV/TB组)和排除TB的HIV感染者组(对照组),评估双因子联合检测的诊断效能。根据检测结果将HIV/TB组分为真阳性组和假阴性组,采用多因素logistic回归分析漏诊的独立影响因素。结果共纳入患者306例,平均年龄(55.69±14.02)岁,HIV/TB组105例,对照组201例。双因子联合检测在所有HIV感染者中TB检测灵敏度为72.4%(76/105),特异度为87.1%(175/201)。三个CD4^(+)T淋巴细胞计数梯度间,双因子联合检测的灵敏度比较,差异具有统计学意义(χ^(2)=9.488,P=0.009),而特异度差异无统计学意义(χ^(2)=5.846,P=0.054)。其中,CD4^(+)T细胞计数<100个/μL的患者双因子检测灵敏度(58.8%)低于≥200个/μL(88.9%)和100~199个/μL(81.5%)的患者,差异均有统计学意义(均P<0.05);且在CD4^(+)T淋巴细胞计数≥100个/μL的HIV/TB共感染患者中,双因子联合检测的综合灵敏度为85.2%(46/54),特异度为82.0%(91/111)。多因素分析显示,CD4^(+)T淋巴细胞计数是HIV/TB组患者双因子联合检测漏诊的独立影响因素(P<0.05),而年龄、性别、病原学结果、有无TB等因素对双因子联合检测结果的影响无统计学意义(均P>0.05)。结论结核特异性细胞因子IFN-γ和IL-2双因子联合检测在HIV感染者TB诊断中具有较高的诊断价值,尤其是在CD4^(+)T淋巴细胞计数≥100个/μL的HIV感染者中,可为临床HIV感染合并TB的诊断提供一定的辅助诊断价值。

关键词： 重症肺炎   心力衰竭   卵泡抑素样蛋白1   降钙素原   白细胞介素-6  

摘要： 目的 探讨血清卵泡抑素样蛋白1(FSTL1)、降钙素原(PCT)、白细胞介素-6(IL-6)水平与重症肺炎(SP)伴心力衰竭(HF)患者病情严重程度及预后的相关性。方法 选取2022年6月至2024年6月收治的98例SP伴HF患者作为研究对象。比较不同美国纽约心脏病协会(NYHA)心功能分级患者的血清FSTL1、PCT、IL-6水平;采用Spearman相关性分析评估血清FSTL1、PCT、IL-6水平与SP伴HF患者病情严重程度的相关性;采用单因素分析、多因素Logistic回归分析探讨SP伴HF患者预后不良的危险因素;通过受试者工作特征(ROC)曲线评估血清FSTL1、PCT、IL-6对预后不良的预测效能。结果 Ⅱ级、Ⅲ级、Ⅳ级患者的血清FSTL1、PCT、IL-6水平比较,差异具有统计学意义(P<0.05)。Spearman相关性分析结果显示,血清FSTL1、PCT、IL-6水平与SP伴HF患者病情严重程度呈正相关(P<0.05)。98例患者中预后不良45例,预后良好53例;两组的NYHA心功能分级、FSTL1、PCT、IL-6水平比较,差异具有统计学意义(P<0.05)。NYHA心功能分级、FSTL1、PCT、IL-6是SP伴HF患者预后不良的危险因素(P<0.05)。ROC曲线分析结果显示,血清FSTL1、PCT、IL-6联合检测对SP伴HF患者预后不良的预测效能高于单独检测(P<0.05)。结论 血清FSTL1、PCT、IL-6水平不仅与SP伴HF患者的病情严重程度呈正相关,同时与预后不良存在密切关联。

关键词： headaches   inflammatory skin disease   interferon-γ   seborrheic dermatitis   transcutaneous   vagus nerve   vagal nerve stimulation   IL   interleukin   tVNS   transcutaneous vagal nerve stimulation   SD   seborrheic dermatitis   SEDASI   SEborrheic Dermatitis Area and Severity Index   VNS   vagal nerve stimulation  

摘要： Introduction The vagus nerve is a critical bidirectional communication pathway between the central nervous system and multiple organs. This mixed nerve facilitates the transmission of both afferent sensory signals and efferent impulses, functionin...

关键词： 急性淋巴细胞白血病   ETP-ALL   KMT2A::TBC1D5  

摘要： 患者,男,41岁,因"反复发热、咳嗽、咳痰1个月"于2024年6月19日来我院就诊。患者既往健康。血常规:WBC 5.5×10^(9)/L、单核细胞比例20%、HGB 74g/L、PLT 140×10^(9)/L。骨髓涂片:有核细胞增生活跃,原、幼淋巴细胞比例为75%;POX染色病理细胞100%阴性;外周血涂片:淋巴细胞比例增多至55%,原、幼淋巴细胞比例为12%。骨髓免疫分型:异常细胞占有核细胞比例为19.71%,主要表达CD7、胞质CD3(cCD3)、CD34、CD38、CD2、CD99、CD45RA dim;部分表达CD117、CD79a、CD33、CD25、CXCR4;不表达CD123、TCR、TCR4、CD19、CD20、CD10、CD5、CD4、CD8、CD1a、CD13、CD71、cMPO、CD57、CD56、CD3、CD45RO、HA-DR、nTDT,免疫表型符合早期前体T细胞急性淋巴细胞白血病(ETP-ALL)。染色体核型:46,XY[20]。多重PCR筛查64种融合基因阴性。基因突变筛查(二代测序):Ⅰ类突变(具有强烈临床意义):NOTCH1,c.4721T>C,p.L1574P,突变丰度8.38%;NRAS,c.38G>A,p.G13D,突变丰度4.83%。FISH:KMT2A基因重排占19.5%。全转录组mRNA测序检测融合基因:KMT2A::TBC1D5。KMT2A::TBC1D5新融合基因经实时逆转录PCR及Sanger测序得以验证。Sanger测序显示KMT2A基因的第8号外显子(NM_001197104.2)和TBC1D5基因的第19号外显子(NM_014744.2)之间存在融合。综上,患者被明确诊断为ETP-ALL伴KMT2A::TBC1D5融合基因阳性。

关键词： IL-6 receptor   Curcumin   ADAM10   Shedding   Membrane domain  

摘要： Proteolytic cleavage and release of single-spanning transmembrane receptors, a process called shedding, is vital for normal physiological functions and pathological responses, including inflammation and cancer. Interleukin-6 receptor (IL-6R) is one of the principal single-spanning transmembrane receptors expressed in hepatocytes and subpopulations of leukocytes, including monocytes and macrophages. Soluble IL-6R (sIL-6R) is also present in human plasma. Herein, we report that membrane-modulating agents including curcumin, enhance IL-6R shedding in human monocytes via a mechanism involving a disintegrin and metalloprotease 10 (ADAM10). Furthermore, amphiphilic derivatives of turmeric curcuminoids increased sIL-6R levels in culture supernatants and altered the membrane domains formed on giant vesicles. These findings offer insights into the mechanism underlying the induction of ectodomain cleavage of IL-6R and ascertain the function of liberated sIL-6R. They can provide a novel strategy to develop therapeutic intervention using membrane-active compounds, such as curcuminoids, for diseases such as inflammation and cancer.

关键词： ASCs   MSCs derived from adipose tissue   BCA   Bicinchoninic acid assay   BMPs   Bone morphogenetic proteins   BMSCs   MSCs derived from bone marrow   CM   Conditioned medium   EVs   Extracellular vesicles   FDA   Food and Drug Administration   GO   Gene Ontology   GSEA   Gene Set Enrichment Analysis   IDO1   indoleamine 2,3-dioxygenase   IL6   interleukin-6   IL10   Interleukin-10   IFN-γ   Interferon-γ   MI   Myocardial infarction   MSCs   Mesenchymal stromal cells   NGS   miRNA Analysis by Next-Generation Sequencing   NPX   Normalized Protein eXpression   NTA   Nanoparticle Tracking Analysis   PL   Platelet lysate   Qpcr   Quantitative Real-Time PCR   TNF   Tumor necrosis factor   ZP   Z potential   Mesenchymal stromal cells   Secretome   Priming  

摘要： Mesenchymal stromal cells (MSCs) have emerged as a promising tool in regenerative medicine, with recent focus shifting towards their secretome as a cell-free therapeutic approach. This study investigates the impact of various priming strategies on the immunomodulatory, anti-inflammatory, and regenerative potential of adipose-derived MSCs (ASCs) secretomes. We evaluated the effects of hypoxia, pro-inflammatory cytokines, and spheroid culture conditions on ASC secretome composition and functionality. Gene expression analysis, nanoparticle tracking, protein quantification, and functional assays were performed to characterize the secretomes. RNA sequencing revealed significant differences in gene expression profiles across priming conditions, particularly in pathways related to osteogenesis, angiogenesis, inflammation, and neurotrophic factors. Notably, spheroid culture combined with hypoxia and inflammation resulted in a substantial increase in extracellular vesicle production and altered protein content. Functional assays demonstrated enhanced neutrophil inhibition by secretomes from hypoxia-primed ASCs. Our findings indicate that tailored priming strategies can significantly modulate the therapeutic properties of ASC secretomes, potentially enhancing their efficacy in various clinical applications. This study provides valuable insights for optimizing cell-free therapies in regenerative medicine and offers a basis for developing more targeted and effective treatments.

关键词： Systemic juvenile idiopathic arthritis   Still's disease   Immunotherapy   Interleukin-18   Interleukin-1β   Autoimmunity   Macrophage activation syndrome   MAS825  

摘要： Graphical abstract

摘要： The claim that a universal National health service (Nhs) is unsustainable is frequently accepted as fact, yet pharmaceutical care in Italy demonstrates otherwise. Italy ranks among European Union leaders in public drug access, contradicting the narrative of Nhs unsustainability. Achievements stem from national strategies in drug evaluation, reimbursement criteria, price negotiation and the presence of a competitive context. Private pharmaceutical spending remains substantial, mainly because of lack of price negotiation. Shifting drug costs to citizens and promoting private insurance would increase both private and public expenditures. The US example shows that higher private spending correlates with higher public spending. Reducing Nhs coverage would worsen existing challenges rather than solve them. © 2025, Il Pensiero Scientifico Editore s.r.l.. All rights reserved.