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摘要： Allogeneic hematopoietic stem cell transplantation (alloHSCT) from mismatched unrelated donors (MMUD) carries high risks of non-relapse mortality (NRM) and graft-versus-host disease (GVHD). Post-transplant cyclophosphamide (PTCY) has emerged as an alternative to antithymocyte globulin (ATG) for GVHD prophylaxis. This single-center retrospective study compared PTCY (n=41) to high-dose ATG and low-dose ATG in 155 MMUD alloHSCT recipients. PTCY was associated with better OS with one-year OS of 78.7% vs. 56.5% in PTCY and HD groups (p=0.007) and vs 64.8% in LD group (p=0.059), driven by a significant reduction in NRM (p=0.008), with a one-year NRM in the PTCY group at 7.7% vs 24.4% in the HD group (p=0.031) and 29.8% in the LD group (p=0.026). The relapse incidence was similar between the groups (17.5% vs. 25.7% and 16.2% for PTCY, HD and LD group, p=0.830), despite a better PFS in the PTCY group (p=0.034) with one-year PFS at 78.4% vs. 50.0% in HD group (p=0.002) and 54.0% in LD group (p=0.041). Day-100 grade II-IV and grade III-IV acute GVHD, as well as one-year chronic GVHD and moderate/severe chronic GVHD were not significantly different. However, one-year GVHD-related mortality was lower in the PTCY group (2.6% vs. 14.4% and 14.9%, p=0.018). Infection-related mortality was similar across groups, but CMV and EBV infections were less frequent with PTCY, potentially linked to differences in immune reconstitution. PTCY prophylaxis was associated with improved OS, PFS, and lower NRM compared to HD and LD ATG in MMUD alloHSCT.

关键词： Biologics   Crohn’s Disease   Inflammatory Bowel Disease   JAK Inhibitors   Pregnancy   Ulcerative Colitis   5-ASA   5-aminosalicylate   6-mmpn   6-methylmercaptopurine nucleosides   aIRR   adjusted incidence rate ratio   aHR   adjusted HR   AMH   anti-Müllerian hormone   anti-TNF   anti-tumor necrosis factor   APGAR   Appearance, Pulse, Grimace, Activity, and Respiration   aOR   adjusted odds ratio   ART   assisted reproductive technology   ASD   autism spectrum disorder   ASGE   American Society for Gastrointestinal Endoscopy   ASQ3   Ages and Stages Questionnaire 3   BCG   Bacille Calmette-Guérin   CAs   congenital abnormalities   CCP-KNOW   Crohn's and Colitis Pregnancy Knowledge Score   CD   Crohn’s disease   CI   confidence interval   CRP   C-reactive protein   CS   cesarean delivery   CT   computed tomography   DBP   dibutyl phthalate   DI   disagreement index   ECCO   European Crohn’s Colitis Organization   FA   food additive   FC   fecal calprotectin   GBS   group B Streptococcus   GRADE   Grading of Recommendations Assessment, Development, and Evaluation   GWG   gestational weight gain   HBV   hepatitis B virus   HR   hazard ratio   IBD   inflammatory bowel disease   IBD-U   IBD unclassified   IgG   immunoglobulin   IL   interleukin   IPAA   ileal pouch–anal anastomosis   IQR   interquartile range   IRR   incidence rate ratio   IUS   intestinal ultrasound   JAKi   Janus kinase inhibitor   LARC   long-acting reversible contraceptive   LBW   low birth weight   MELODY   Modulating Early Life Microbiome through Dietary Intervention in Pregnancy   MHRA   Medicines and Health Products Regulatory Agency   MoBa   Mother and Child Cohort Study   MoMMY-IBD   Mother-to-Infant Transfer of Bacteriome, Virome, Fungome, and Metabolome in Health   MTX   methotrexate   NICU   neonatal intensive care unit   NSAIDS   non-steroidal anti-inflammatory agents   PIANO   Pregnancy IBD Inflammatory Bowel Disease and Neonatal Outcomes   PICO   population, intervention, comparison, outcome   PY   person-year   OR   odds ratio   RA   rheumatoid arthritis   RAND   Research and Development   RID   relative infant dose   RR   relative risk   RVF   rectovaginal fistula   SGA   small for gestational age   S1P   sphingosine-1-phosphate   UC   ulcerative colitis   VD   vaginal delivery   V  

摘要： Background & Aims Pregnancy can be a complex and risk-filled event for women with inflammatory bowel disease (IBD). High-quality studies in this population are lacking, with limited data on medications approved to treat IBD during pregnancy. For patients, limited knowledge surrounding pregnancy impacts pregnancy rates, medication adherence, and outcomes. Limited provider knowledge leads to highly varied practices in care affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus. The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike. The Global Consensus Consortium is a group of 39 IBD and content experts and 7 patient advocates from 6 continents who convened to review and assess current data and come to an agreement on best practices based on these data. Methods The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process was used when sufficient published data were available and the RAND (Research and Development) process in those instances where expert opinion was needed to guide consistent practice. Recommendations were informed by the guiding principle that maternal health best supports infant health. Results The topics were divided into ten categories with 34 GRADE recommendations and 35 consensus statements. Conclusions Overall, the goal of the group was to provide data-driven and practical guidance to improve the care of women with IBD around the globe based on the best available research.

摘要： The emergence of SARS-CoV-2 Variants of Concern (VOC) is a major clinical threat; however, VOC remain susceptible to cytotoxic T lymphocyte (CTL) recognition. Therefore, it is crucial to identify potent CTL responses targeting conserved epitopes across VOCs. Here, we demonstrate that the nucleocapsid (N) protein induces efficient CTL responses in early pandemic COVID-19 convalescent donors. In the context of the HLA-A24-B52-C12 haplotype, prevalent in Japan, the KF9 peptide (N: KAYNVTQAF) is immunodominant and restricted by HLA-C*12:02. KF9-specific T cells are cytotoxic and suppress viral replication of both the ancestral and multiple VOC SARS-CoV-2. KF9-specific CD8 T cells maintain effector memory and terminally differentiated phenotypes for 12 months post-infection and proliferate rapidly upon recall. We also determine the structure of a TCR in the context of the HLA-C*12:02-KF9 complex, providing a prototype for the interaction of HLA-C with viral peptides. Surprisingly, despite the TCR's high affinity, the CDR3β loop almost lacks contact with the KF9 peptide. These findings highlight the importance of conserved epitopes and the role of HLA-C molecules in controlling SARS-CoV-2 VOC.

关键词： 免疫球蛋白   美罗培南   c反应蛋白指标  

摘要： 探究大剂量免疫球蛋白联合美罗培南在败血症新生患儿c反应蛋白相关指标改善中的作用。方法 选取本院于2024年1月-2024年11月收治的50例新生儿败血症患者为研究对象,按照治疗方式差异分为对照组(美罗培南)、实验组(大剂量免疫球蛋白联合美罗培南)进行干预,各25例,对比两组患者临床疗效、C反应蛋白指标、免疫活性分子等指标。结果 经数据对比得知,实验组患者各项数据显著优于对照组,P<0.05.结论 针对新生儿败血症的治疗,采取大剂量免疫球蛋白联合美罗培南进行用药,可有效改善患儿c反应指标,提高临床疗效,值得大力推广。

关键词： immune suppression   tumor microenvironment   tumor vessel   tumor‐associated macrophage   tumor‐endothelial cells  

摘要： Tumor-associated macrophages (TAMs) and tumor endothelial cells (TECs) are important components in tumor microenvironments. This study examined the interaction between TECs and TAMs in hepatocellular carcinoma (HCC). The aim of this study is to clarify the mechanism of immune suppression and cancer progression mediated by the M2 polarization of TAMs. TECs were isolated from subcutaneous HCC tumors using murine BNL-T cells, and normal endothelial cells (NECs) were isolated from murine liver. M0 macrophages were obtained from bone marrow after incubation with M-CSF. Conditioned medium from TECs (TEC CM) or NECs (NEC CM) was added to M0 macrophages, and the polarization to M2 macrophages was assessed. The percentage of iNOSCD206 cells was increased in the TEC CM group than in the NEC CM group. The subcutaneous tumor model with co-injection of BNL-T and TECs or NECs was applied, and the ratio of M2 macrophages (CD206iNOSCD45CD11bF4/80 cells) was elevated in the BNL-T + TEC group. IL-4 expression in TECs was upregulated compared to NECs, and the secretion of IL-4 was increased in the TEC CM compared to the NEC CM. After IL-4 down-regulation in TECs, the ratio of iNOSCD206 cells decreased. The double immunofluorescent staining of CD31 and CD163 was performed in human HCC tissue. The number of CD31 endothelial cells correlated positively with CD163 TAMs. The high CD163/CD31 group showed poor prognosis in overall and disease-free survival. TECs induce M2 macrophage polarization through IL-4 secretion, leading to immune suppression and cancer progression.

关键词： acute heart failure   autoimmune   cardiac magnetic resonance   inotropes   positron emission tomography   reduced ejection fraction   FDG-PET   fluorodeoxyglucose–positron emission tomography   GCM   giant cell myocarditis   IVIg   intravenous immunoglobulin   LVEF   left ventricular ejection fraction   MMF   mycophenolate mofetil   NT-proBNP   N-terminal pro–B-type natriuretic peptide   PIMS-TS   pediatric inflammatory multisystem syndrome   TNF   tumor necrosis factor   TTE   transthoracic echocardiography  

摘要： Background Pediatric inflammatory multisystem syndrome (PIMS-TS) is a rare entity observed in children with postinfectious hyperinflammatory syndrome. Cases have been reported, although rarely, after the mRNA SARS-CoV-2 (COVID-19) vaccine. Case Summary We present a case of a young man who developed PIMS-TS with fulminant myocarditis after a first dose of COVID-19 vaccination, with persistent evidence of inflammation despite multiple lines of therapy over the course of 2 years. He then experienced fulminant myocarditis that was resistant to anti-inflammatory therapies. Repeat endomyocardial biopsy was consistent with giant cell myocarditis. Discussion Cases of giant cell myocarditis after COVID-19 vaccination have been reported in the past, however to our knowledge, none have been reported 2 years after a single dose and with intercurrent diagnosis of PIMS-TS myocarditis. This raises the question of a possible pathophysiologic association between the 2 diseases and immune dysregulation. Take-Home Message This case illustrates the importance of repeating the investigation and questioning the diagnosis when the progression of the disease is not typical.

关键词： 连翘脂苷A   H9N2禽流感病毒   TLR3-NF-κB信号通路   细胞因子   肺微血管内皮细胞   抗病毒治疗   中药  

摘要： 本研究旨在探讨连翘脂苷A(forsythiaside A， FTA)对H9N2亚型禽流感病毒(H9N2 AIV)在肺微血管内皮细胞(pulmonary microvascular endothelial cells， PMVECs)中复制的抑制作用及其潜在机制。采用不同浓度的连翘脂苷A处理H9N2 AIV感染的PMVECs，使用MTT法检测细胞毒性，采用RT-qPCR分析病毒复制情况。通过Western blot检测TLR3、TRIF和NF-κB蛋白表达水平，采用ELISA检测炎性细胞因子(TNF-α、IL-6)及I型干扰素(IFN-α、IFN-β)的分泌情况。研究结果表明，连翘脂苷A能显著抑制H9N2 AIV的复制（P<0.05），其抑制作用呈剂量依赖性；下调TLR3、TRIF及NF-κB蛋白的过表达（P<0.05），降低促炎性细胞因子分泌（P<0.05），同时增强I型干扰素的生成（P<0.05）。连翘脂苷A通过调控TLR3-NF-κB信号通路及细胞因子表达，展现出针对H9N2 AIV的显著抗病毒活性，具有作为新型宿主靶向抗病毒药物的潜力。

关键词： Human umbilical cord mesenchymal stem cells   Inflammation   Inflammatory bowel disease   T helper cells  

摘要： BACKGROUND:Human umbilical cord mesenchymal stem cells (HUMSCs) are effective therapies for inflammatory bowel disease. However, the mechanisms remain unresolved. We found HUMSCs express CD126 (IL-6 receptor), which indicated CD126 sub-populations might show a distinct response to inflammation. In the present study, we explored whether CD126 is a critical molecule for HUMSCs in regulating inflammation. METHODS:We assessed the regulatory effects of CD126 high (CD126) on the T lymphocyte subpopulations and related cytokines in the dextran sulfate sodium (DSS)-induced colitis model. The effect of CD126 was evaluated by Hematoxylin and Eosin (H&E) staining, fluorescence-activated cell sorting (FACS), and enzyme-linked immunosorbent assay (ELISA) analyses. Statistical significance was typically determined using Student's t-test or one-way analysis of variance (ANOVA) with Tukey test. RESULTS:The disease symptoms were markedly ameliorated and the interleukin-6 (IL-6), interleukin-17 (IL-17), interferon-γ (IFN-γ), Tumor necrosis factor-α (TNF-α), and interleukin-4 (IL-4) levels were significantly reduced in DSS-treated mice administered with CD126 HUMSCs but not in DSS-treated mice administered with CD126 low (CD126) HUMSCs. Intriguingly, CD126 HUMSCs significantly increased the levels of transforming growth factor-β (TGF-β1) and interleukin-10 (IL-10) in DSS-treated mice, accompanied by an increase in regulatory T cells (Treg cells). In vitro experiments showed that CD126 HUMSCs secreted TGF-β1 in response to IL-6 stimulation, while CD126 HUMSCs were latent in the inflammatory environment. We considered that TGF-β1 secreted by CD126 HUMSCs regulated the balance of Treg cells and thus promoted the recovery of murine colitis. CONCLUSION:Our results revealed a mechanism wherein CD126 HUMSCs function as inflammatory sensors and secrete anti-inflammatory cytokines to rebalance the population of T cells. This study shed light on the potential therapeutic application of CD126 HU

关键词： αMHC   403   cardiac   cTnI-G203S   mitochondria   prevention   AID   α-interaction domain   HCM   hypertrophic cardiomyopathy   I   Ca-L   calcium current   IVS   interventricular septum   LTCC   L-type calcium channel   LVED   left ventricular end dimension   LVOT   left ventricular outflow tract   LVPW   left ventricular posterior wall   MHC   myosin heavy chain   TAT   transactivator of transcription   ψ   m   mitochondrial membrane potential  

摘要： Mitochondrial dysfunction is considered to drive the development of hypertrophic cardiomyopathy (HCM). In search of a preventative HCM therapy, we explored the efficacy of amino acid peptide variants that could alter the L-type Ca 2+ channel’s regulation of mitochondrial energetics. We confirmed that 3 of the 4 variant peptides bound with high affinity to the beta subunit. In vivo treatment of cTnI-G203S and αMHC 403/+ mice with the peptide variants prevented the development of HCM and improved contractile function. Here, we describe a novel therapy that uniquely targets the L-type Ca 2+ channel to modify mitochondrial function and prevent HCM.

关键词： 中草药   中药   细胞因子风暴   细胞因子释放综合征   治疗   机制  

摘要： 细胞因子释放综合征(cytokine release syndrome,CRS)是机体的一种高免疫反应状态,可由多种疾病诱导产生,如移植物抗宿主反应(GVHD)、自身免疫性疾病、癌症免疫疗法和感染等。西药治疗CRS已被广泛报道,但产生的药物毒性等相关副作用仍是目前无法克服的医学问题。作为我国传统医学体系的核心组成部分,中医药在调节机体免疫稳态及抑制炎症反应方面展现出独特的治疗优势,同时,中药不限于剂量依赖,提示其在CRS干预中具有更广泛的治疗窗与安全性优势。故该综述以CRS的产生机制和西药治疗手段为引,从中医药的单方和复方两方面阐述中草药抑制CRS发生的具体机制,为缓解及治疗CRS提供中医方案。