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关键词： IL-6   biocompatibility   curcumin   foam macrophages   poly(CL-co-TOSUO)  

摘要： Atherosclerotic plaque instability, driven by macrophage-derived foam cells and exacerbated by interleukin-6 (IL-6), necessitates localized anti-inflammatory strategies. To address this, we developed curcumin-loaded poly(ε-caprolactone-co-4-ethylenediol ketal-ε-caprolactone) (PCT) membranes via electrospinning, characterizing their sustained drug release, biodegradability, and morphology through SEM. Comprehensive in vitro assessments included endothelial/macrophage viability assays, hemolysis testing, foam cell modeling using Ox-LDL (80 μg/mL for 48 h, optimized for IL-6 upregulation), and inflammatory cytokine quantification (IL-6/TNF-α/IFN-γ) via RT-qPCR. Subcutaneous implantation in rats enabled histological evaluation via HE staining and IL-6 immunohistochemistry. Our results demonstrated that curcumin-PCT membranes exhibited sustained drug release and biodegradability while maintaining exceptional hemocompatibility and endothelial safety. The membrane extracts significantly inhibited macrophage activity and downregulated pro-inflammatory cytokines, with IL-6 suppression being the most pronounced. In vivo analyses corroborated these findings, showing reduced leukocyte infiltration and attenuated IL-6 expression compared to poly(ε-caprolactone) controls. Collectively, this study establishes curcumin-loaded PCT as a biocompatible platform with targeted efficacy against macrophage-driven vascular inflammation.

关键词： Lipid Nanoparticles   Lung-Targeted   IL-12 mRNA   Docetaxel Prodrug  

摘要： Despite the remarkable success of mRNA vaccines, extrahepatic tissue-specific delivery of therapeutic mRNAs remains challenging. Here, we report a lung-tropic lipid nanoparticles (LNPs) platform that is rationally engineered for simultaneously co-delivering interleukin-12 (IL-12) mRNA and docetaxel prodrug to address the lung metastatic issue. By optimizing a panel of synthetic cationic lipids, we identified N112 as the optimal cationic lipid, with N112-DOTAP LNP formulation demonstrating moderately enhanced transfection efficiency in lung tissue compared to the benchmark MC3-DOTAP LNP. Moreover, N112-DOTAP LNP has a uniform particle size and high encapsulation efficiency for both therapeutic payloads. In a B16F10 lung metastasis model, the combination therapy demonstrated superior antitumor efficacy, reducing tumor nodules compared to the saline treatment, while maintaining the safety profile with no significant body weight loss or organ toxicity. This study provides a robust therapeutic strategy for mRNA-based combination cancer therapy.

关键词： 淋巴瘤   糖尿病，2型   维布妥昔单抗   胰岛素抵抗   细胞因子  

摘要： 维布妥昔单抗（BV）是一种CD30定向抗体-药物偶联物，被用于治疗复发或难治性经典型霍奇金淋巴瘤和系统性间变性大细胞淋巴瘤。据文献报道，BV存在较多药物不良反应，其中内分泌系统相关的药物不良反应占3.28%，但国内关于BV治疗导致血糖失控的报道较少。该文报道了1例合并2型糖尿病的混合细胞型经典霍奇金淋巴瘤患者经BV治疗后出现胰岛素抵抗及血糖失控的病例，旨在为血液科医师和内分泌科医师诊治该类患者提供一定的启发与借鉴。患者为72岁男性，因“口干10年余，血糖失控2 d”入院，入院前8 d接受第1次BV+AVD（多柔比星、长春地辛、达卡巴嗪）抗淋巴瘤治疗，当时空腹血糖8~9 mmol/L，2 d前发现随机静脉葡萄糖27.8 mmol/L，指尖血酮0.6 mmol/L，入院后胰岛素联合口服药物降糖，胰岛素用量达1.53 U·kg -1·d -1（总量88.6 U，其中静脉输注60.0 U、皮下注射28.6 U），8 d后胰岛素迅速减量，出院时患者胰岛素减为25 U/d（德谷胰岛素16 U，1次/晚+门冬胰岛素3 U，3次/d），2周后胰岛素减量为德谷胰岛素10 U，1次/晚。在治疗期间监测到患者血清中细胞因子白细胞介素（IL）-5、IL-6、IL-8和肿瘤坏死因子-α的动态变化，提示细胞因子的变化可能与BV治疗后胰岛素抵抗有关。

关键词： 7-azaindole-3-acrylamide   IL-1β   Inflammasome   Inflammatory bowel disease   Inhibitors  

摘要： Currently, a significant proportion of patients with inflammatory bowel disease (IBD) fail to respond to conventional drug therapies such as immunosuppressants and biologic agents. IL-1 signaling blockade is a promising therapeutic strategy for these unresponsive IBD patients. In this study, we identified a novel anti-NLRP3/ IL-1β inhibitor, the 7-azaindole analogue Y19, which exhibits an IC value of 1.26 μM. Mechanistic investigations revealed that it suppresses NLRP3 inflammasome assembly and activation by disrupting critical protein-protein interactions, including NEK7-NLRP3, NLRP3-NLRP3, NLRP3-ASC, and ASC-ASC. Additionally, it also inhibits the AIM2 and NLRC4 inflammasome pathways. In a murine model of colitis, Y19, as a pan-inflammasome inhibitor, demonstrates anti-inflammatory efficacy comparable to that of tofacitinib, a Janus kinase inhibitor commonly prescribed for IBD patients refractory to conventional therapies. This finding highlights the potential of inflammasomes/ IL-1β inhibitors as a promising strategy for the treatment of IBD.

关键词： 药物性胰腺炎   地塞米松   儿童   急性淋巴细胞白血病  

摘要： 急性淋巴细胞白血病（ALL）儿童是药物性胰腺炎（DIP）的高危人群，但糖皮质激素诱发的胰腺炎罕见。本文报道1例9岁男性ALL患儿，在再诱导化疗第1周期间发生地塞米松相关性急性胰腺炎（AP），予停用地塞米松和支持治疗，后期化疗调整为泼尼松，未再发生胰腺炎。提示在ALL治疗中，对使用糖皮质激素患儿，应监测胰腺炎相关指标，需警惕AP的可能。

关键词： HLA ligands   KIR   anti-EGFR   cetuximab   metastatic colorectal cancer   natural killer cells  

摘要： Colorectal cancer (CRC) remains a major cause of cancer-related mortality. Cetuximab improves survival by combining EGFR inhibition with immune activation. This study evaluated the influence of killer cell immunoglobulin-like receptor (KIR)-mediated immune responses on cetuximab efficacy in 124 metastatic CRC patients: 55 with wild-type (WT) KRAS and 69 with KRAS mutations. Peripheral blood was genotyped for 19 KIR genes and relevant HLA alleles, focusing on key KIR-HLA interactions (2DL1-C2, 3DL1-Bw4, 3DS1-Bw4). KRAS-WT patients showed better outcomes, receiving more treatment cycles (median: 17 vs. 4) and showing slower disease progression (60% vs. 92.8% at 12 months). WT patients had higher frequencies of inhibitory KIRs and the Bw4 allele, with KIR3DS1-Bw4 heterozygosity linked to longer survival ( = 0.013). In KRAS-mutant patients, heterozygous KIR genotypes (AB) and mixed A/B semi-haplotypes were associated with improved survival ( = 0.002). Multivariate analysis confirmed KIR3DS1-Bw4 as a favorable factor in WT patients and AB genotypes as beneficial in KRAS-mutants. In conclusion, KIR-HLA interactions significantly impact cetuximab efficacy in metastatic CRC, with distinct immunogenetic profiles in WT and KRAS-mutant patients. These results highlight the potential of KIR-HLA profiling to guide personalized treatment strategies.

关键词： 肺腺癌胸腔积液   体液细胞形态学检查   联合检测   胸腔积液癌胚抗原   血清癌胚抗原  

摘要： 探讨体液细胞形态学检查联合癌胚抗原对老年肺腺癌相关胸腔积液的诊断价值。方法 收集2023年月6月至2024年10月老年患者标本,分为肺腺癌胸腔积液组143例和良性胸腔积液组150例,分别进行体液细胞形态学检查、胸腔积液CEA及血清CEA测定,计算胸腔积液/血清CEA比值,分析定量指标最适诊断临界值,并对诊断效能进行评价。结果 肺腺癌胸腔积液组中,体液细胞形态学检查、胸腔积液CEA、血清CEA及胸腔积液/血清CEA比值检测水平及阳性率均高于良性胸腔积液组(P<0.01),最适诊断值分别为5.4μg/L、5.88μg/L、2.41时;敏感度和特异度分别为88.11%、88%;72.03%、68%及86.01%、86%。联合检测中,四项指标并联检测敏感度(97.2%)高于任一单项指标检测(P<0.01)。四项指标串联检测特异度(97.33%)均高于任一单项指标检测(P<0.01)。结论 体液细胞形态学检查联合胸腔积液CEA、血清CEA以及二者比值,并联检测可提高敏感度,串联检测可提升特异度,在辅助诊断肺腺癌相关胸腔积液中具备良好的诊断价值和临床适用性。

摘要： Allogeneic hematopoietic cell transplantation (alloHCT) from 8/10 HLA-matched unrelated donor is performed in a minority of patients. There is little data on its outcomes and consequently, guidelines on optimal transplantation procedures are lacking. The Transplant complications working party of the EBMT performed a registry study comparing approaches to graft-versus-host disease (GVHD) prophylaxis in recipients of alloHCT from 8/10 HLA-mismatched unrelated donors (8/10 MMUD). The analysis included 450 adult patients with hematological malignancies receiving a first alloHCT between 2015 and 2021, GVHD prophylaxis strategies included ATG in 318 and PTCy in 132 patients. AlloHCT from 8/10 MMUD resulted in 21.1% non-relapse mortality, 28.5% cumulative incidence of relapse, 55.7% overall survival (OS), 50.4% progression-free-survival and 39.8% GVHD-relapse-free survival (GRFS). PTCy decreased the risk of grade II-IV (HR 0.63, 95%CI 0.40-0.99) and III-IV acute GVHD (HR 0.31, 95%CI 0.13-0.74), improved OS (HR 0.63, 95%CI 0.41-0.95) and GRFS (HR 0.65, 95%CI 0.47-0.91). No other differences between the groups were documented. Transplantation from female donors to male recipients increased the incidence of extensive chronic GVHD (HR 2.39, 95%CI 1.10-5.19) and decreased PFS (HR 1.49, 95%CI 1.01-2.20). AlloHCT from 8/10 HLA-matched unrelated donor is feasible and the use of PTCy in GVHD prophylaxis improves outcomes.

关键词： type I IFN   signaling   age   children   COVID-19   SARS-CoV-2   STAT1   STAT3   monocytes   T cells   B cells   antibodies   immune response  

摘要： Advanced age is the most important risk factor for severe disease or death from COVID-19, but a thorough mechanistic understanding of the molecular and cellular underpinnings is lacking. Multi-omics analysis of 164 samples from SARS-CoV-2-infected persons aged 1 to 84 years reveals a rewiring of type I interferon (IFN) signaling with a gradual shift from signal transducer and activator of transcription 1 (STAT1) to STAT3 activation in monocytes, CD4 + T cells, and B cells with increasing age. Diversion of IFN signaling is associated with increased expression of inflammatory markers, enhanced release of inflammatory cytokines, and delayed contraction of infection-induced CD4 + T cells. A shift from IFN-responsive germinal center B (GCB) cells toward CD69 high GCB and atypical B cells during aging correlates with immunoglobulin (Ig)A production in children, whereas complement-fixing IgG predominates in adults. Our data provide a mechanistic basis for inflammation-prone responses to infections and associated pathology during aging.