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关键词： 人文关怀   预见性护理   急性非淋巴细胞白血病   癌因性疲乏   并发症  

摘要： 探讨开展人文关怀结合预见性护理在白血病化疗中的收获。方法 研究对象为126例急性非淋巴细胞白血病化疗患者,以2024年1月为最早资料收集时间点,以2024年12月为最终资料收集时间点,纳入者分组方式为随机数字表法,每组例数均为63,将接受常规护理者纳为对照组,将接受人文关怀结合预见性护理者纳为研究组,最后评价干预效果。结果 (1)在疾病心理适应方面,干预后两组患者均明显改善,且数据显示明显研究组更佳(P<0.05);(2)在化疗依从性方面,研究组明显更高(P<0.05);(3)评比研究组与对照组患者癌因性疲乏,干预后明显前者缓解更加突出(P<0.05);(4)评比研究组与对照组患者并发症发生率,明显前者更低(P<0.05);(5)评比研究组与对照组生活质量,干预后明显牵正改善更佳(P<0.05)。结论 对急性非淋巴细胞白血病化疗患者联合开展人文关怀与预见性护理有助于提高患者疾病心理适应能力及化疗依从性,缓解癌因性疲乏,减少并发症,对改善患者生活质量具有促进作用。

关键词： HLA-B*58:01   Allopurinol   Drug hypersensitivity   Severe cutaneous adverse reaction  

摘要： Evidence on the prevalence of HLA-B*58:01 genotyping and its association with allopurinol-induced severe cutaneous adverse reactions (SCARs) is lacking, especially in low-resource settings. We addressed these gaps by conducting comprehensive and race/ethnic origin-specific evaluations. We conducted a systematic search from inception to 31 December 2022 using databases (PubMed, Embase, and medRxiv), Google (for Vietnamese articles), and manual searching. We included original studies that investigated the association between HLA-B*58:01 genotyping and allopurinol-induced SCARs. We excluded studies on: (1) animals; (2) pharmacokinetics/pharmacodynamics; (3) genetic markers or genetic testing methods; (4) single group; and (5) cost-effectiveness of screening. Risk of bias was assessed using Newcastle-Ottawa Scale. We used random-effects model to report the summary estimates and 95% confidence interval (95% CI) in the meta-analysis. We included 13,719 patients from 24 case-control studies. The prevalences of HLA-B*58:01 genotyping (overall 5.8%; 95% CI 2.9% to 11.5%; I = 98%) varied by races (Asian [7.7%; 95% CI 3.4% to 16.8%; I = 98%] and White in Eastern/Western Europe [2.3%; 95% CI 1.2% to 4.3%; I = 86%]) and ethnic origins (East and Central Asia [5.5%; 95% CI 1.5% to 17.8%; I = 98%] and South and Southeast Asia [12.9%; 95% CI 9.5% to 17.3%; I = 79%]). HLA-B*58:01 genotyping was associated with substantially increasing risk of allopurinol-induced SCARs (odds ratio 117.6; 95% CI 70.3 to 196.8; I = 45%) regardless of the subgroups. We found a higher prevalence of HLA-B*58:01 genotyping in some Asian populations compared with the Whites. There is evidence to confirm a strong association between this allele and allopurinol-induced SCARs.

关键词： anti-HLA donor–specific antibody   antibody-mediated rejection   intragraft anti-HLA donor–specific antibody   lung transplantation  

摘要： Background The diagnosis of pulmonary antibody mediated rejection (AMR) remains challenging with lack of specific defining features. This study evaluated the diagnostic and prognostic significance of intragraft anti-HLA donor-specific antibodies (gDSA) in pulmonary AMR. Methods This multicenter prospective study enrolled adult lung transplant recipients (LTR) with serum anti-HLA DSA (sDSA) >1000 Luminex mean fluorescence intensity. Transbronchial biopsies (TBBx) were obtained for both standard histologic analysis and cryopreservation to detect anti-HLA class I and II gDSA, using Luminex single-antigen beads assay. Clinical follow-up was conducted over 24 months. An expert pathologist reviewed all TBBx using a predefined checklist. A blinded adjudication panel categorized clinical diagnoses as possible, probable or definite AMR and non-AMR conditions. The primary objective was to assess gDSA sensitivity and specificity for AMR diagnosis. Additionally, we compared graft outcomes between gDSA+ vs gDSA- patients. Results 77 LTR from 5 centers were included from August 2019 to July 2022. Twenty-nine patients were classified as probable or definite clinical/subclinical AMR. Among the cohort, 13 had positive gDSA. gDSA sensitivity, specificity and positive predictive value for AMR diagnosis were 34.4%, 93.7%, and 76.9%, respectively. gDSA diagnostic performance for AMR was better than sDSA > 12500 MFI (sensitivity 37.9%, specificity 85.4%, positive predictive value 61.1%). Event-free survival analysis (10% FEV1 decline or graft-loss) showed no significant differences by gDSA positivity. Limited biopsy sampling and spatial heterogeneity may have biased sensitivity and prognostic performances of the technique. Conclusion gDSA might offer a specific complementary support for the clinical diagnosis of AMR following lung transplantation.

关键词： 呼吸道合胞病毒   病毒样颗粒   疫苗   单克隆抗体  

摘要： 病毒样颗粒（Virus-like particles,VLP）是由一种或多种结构蛋白组成的与病毒结构相似的颗粒，具有良好的免疫原性，可以刺激机体产生高效的免疫应答。同时，由于VLP缺乏复制能力且安全性良好，其在疫苗研究中的发展广受关注。呼吸道合胞病毒（Respiratory syncytial virus,RSV）是一种引起婴幼儿、老年人和免疫缺陷人群急性呼吸道感染的主要病原体之一，在全世界范围内造成了巨大的疾病负担。疫苗是预防传染病最有效的手段之一。已上市的三款RSV疫苗在免疫保护效果与适用人群覆盖上仍有提升空间，亟需优化完善。本文对RSV已上市疫苗、单克隆抗体及RSV病毒样颗粒疫苗研究进展进行介绍和总结，为我国开发VLP形式的RSV疫苗研究提供参考和借鉴。

关键词： Hematopoietic stem cell transplantation   T cell progenitor   T lymphocyte   Lymphopoiesis   Immune reconstitution   Thymus   DLL4   ATO   artificial thymic organoids   CAR   chimeric antigen receptor   CB   cord blood   cTECs   cortical TECs   DLL1/4   delta-like ligand 1/4   EC   ethics committee   GMP   good manufacturing practice   GvHD   graft-versus-host disease   HCT   hematopoietic cell transplant   HLA   human leukocyte antigen   HSCT   hematopoietic stem cell transplantation   HSPCs   hematopoietic stem/progenitor cells   HTLP   human T-lymphoid progenitor   ICIs   immune checkpoint inhibitors   iPSCs   induced pluripotent stem cells   LTA   lymphotoxin alpha   MAIT   mucosal-associated invariant T   mPB   mobilized peripheral blood   mRNA   messenger ribonucleic acid   mTEC   medullary TEC   NSG   Nod SCID gamma   PTCy   post-transplantation cyclophosphamide   RANKL   receptor activator of nuclear factor kappa-B ligand   RNA   ribonucleic acid   TCEs   T-cell engagers -TCR   T cell receptor   TEC   thymic epithelial cell   TECs   thymic epithelial cells   TNFα   tumor necrosis factor alpha   Treg: regulatory T   TSPs   thymus-seeding progenitors   VCAM1   vascular cell adhesion molecule 1   Vα   variable alpha chain   Vδ   variable delta chain   αβ   alpha beta   γδ   gamma delta  

摘要： Reconstitution of the T cell compartment is essential in the treatment of several immune disorders. Similarly, individuals with hematological malignancies undergoing allogeneic hematopoietic stem cell transplantation experience prolonged T cell deficiencies, which increase the risk of infections and relapses. Various strategies for addressing T cell deficiencies are based on adoptive T cell therapies. However, challenges related to specificity, safety, scalability, and manufacturing have yet to be overcome. Human T lymphoid progenitor (HTLP)-based immunotherapy might be a valuable, complementary approach for increasing the effectiveness of current treatments for T cell deficiencies. We developed a feeder-free culture system that leverages a human DLL4-Fc fusion protein (Notch ligand) to generate HTLP from CD34+ hematopoietic stem and progenitor cells within 7 days. The cell product, called ProTcell, is mainly constituted of cells expressing CD7, chemokine receptor proteins (e.g. CCR9) and adhesion molecules (e.g. L-selectin). After injection in NSG mice, ProTcell can differentiate and be educated in the thymus to generate simple positive T-cells. Here, we summarize the current state of preclinical and clinical research using this approach, highlighting its potential advantages and current limitations for immune reconstitution therapies.

关键词： 基于患者反馈的强化护理   变态反应疾病   舌下含服特异性免疫治疗护理   负面情绪指数  

摘要： 对比研究探讨,基于患者反馈的强化护理在变态反应疾病患者舌下含服特异性免疫治疗护理工作中的实践价值。方法 观察组(基于患者反馈的强化护理)、对照组(给予常规护理)使用抛硬币法各自分得30例变态反应疾病患者,就2组负面情绪指数、疾病不确定感、自护能力及生活质量等数据展开对比。结果 干预后焦虑、抑郁、沮丧指数评分,疾病不确定感量表各维度得分比,观察组均较之对照组低,而自护能力各维度与生活质量各项目评分比,观察组则更高(P<0.05)。结论 变态反应疾病患者舌下含服特异性免疫治疗护理中实施基于患者反馈的强化护理干预,可以淡化患者负面情绪,减轻疾病不确定感,提升其自护能力及生活质量。

关键词： IFN-β   Pcdh7   Pydc3   osteoclast differentiation  

摘要： Protocadherin-7 (Pcdh7) is a member of the protocadherin family, a subgroup of the cadherin superfamily. We previously demonstrated that Pcdh7 functions as a signaling receptor in osteoclast differentiation. In this study, we investigated the potential gene regulatory role of Pcdh7 in this process and identified Pyrin domain-containing protein 3 (Pydc3) as a key mediator of Pcdh7-mediated regulation of osteoclast differentiation. Differential gene expression analysis comparing wild-type (Pcdh7) and Pcdh7-deficient (Pcdh7) cells revealed a significant upregulation of in Pcdh7 cells. RNAi-mediated knockdown of rescued the impaired osteoclast differentiation in Pcdh7 cells, whereas overexpression of suppressed osteoclast differentiation in Pcdh7 cells, suggesting that Pydc3 negatively regulates osteoclast differentiation. Additionally, Pcdh7 cells showed elevated expression of interferon response genes and increased production of interferon-β (IFN-β). Neutralization of IFN-β signaling using anti-IFN-β and/or anti-interferon alpha and beta receptor 1 (IFNAR1) antibodies significantly restored osteoclast differentiation in Pcdh7 cells. Collectively, these findings uncover a novel role for Pcdh7 in osteoclast differentiation through regulation of expression and IFN-β production.

关键词： ET-1   IFN-γ   ROCK inhibitor   Vitiligo   bFGF   co-culture   dendrites   iPS   keratinocyte   melanocyte  

摘要： Vitiligo is a chronic autoimmune dermatosis defined by selective melanocyte depletion and patchy depigmentation. IFN-γ-driven recruitment of autoreactive CD8 T cells and induction of melanocyte apoptosis are central to its pathogenesis. Current therapies-including UVB phototherapy, tacrolimus, vitamin D3 analogs, and surgical methods-show limited and inconsistent efficacy. Emerging treatments like JAK inhibitors and WNT activators offer potential but require further validation. Translational progress is hindered by a lack of scalable human models. Here, we describe a tunable in vitro vitiligo platform in which human iPSC-derived melanocytes (iMc) are co-cultured with keratinocytes on Matrigel and exposed to precise graded IFN-γ concentrations. Our data revealed dose-dependent decreases in iMc survival and dendritic structure, faithfully mirroring derived melanocyte pathology. Leveraging this platform, we first evaluated the short-term efficacy of the ROCK inhibitor Y27632 under early-stage patient IFN-γ concentrations representative of patient lesional thresholds. At three days, Y27632 significantly upregulated adhesion molecules E-cadherin and DDR1, and two central factors-ET1 and bFGF. Importantly, ROCK inhibition reversed dendritic retraction and improved overall viability of iMc-keratinocytes. These findings position ROCK blockade as a promising adjunctive strategy and establish a pre-clinical platform for evaluating combination therapies for durable pigment restoration.