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关键词： Antithymocyte globulin   Comparison   GVHD   Matched unrelated donor   Outcomes   Peripheral blood   Post-transplantation cyclophosphamide  

摘要： In 2015, dual T cell depletion with antithymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) combined with cyclosporine A (CsA) replaced our prior institutional graft-versus-host disease (GVHD) prophylaxis regimen of 4.5 mg/kg ATG, CsA, and mycophenolate mofetil (MMF) (ATG-based) in 10/10 HLA-matched unrelated donor (MUD) peripheral blood allogeneic hematopoietic stem cell transplantation (allo-HCT). The initial ATG dose of 4.5 mg/kg [ATG(4.5)/PTCy] was reduced to 2 mg/kg [ATG(2)/PTCy] in 2018. This study compares the results obtained from 444 adults undergoing MUD allo-HCT at our institution who received ATG(4.5)/PTCy (n = 127) or ATG(2)/PTCy (n = 223) with those who received ATG-based prophylaxis without PTCy (n = 84). The rates of grade II-IV and grade III-IV acute GVHD (aGVHD) at day +100 and moderate/severe chronic GVHD (cGVHD) at 1 year were 35.7%, 21.6%, and 14.7%, respectively, in patients receiving ATG-based prophylaxis without PTCy; 16.5%, 4.9%, and 4.3% in patients receiving ATG(4.5)/PTCy; and 23.3% (P = .004), 8.0% (P < .001), and 14.1% (P =.006) in patients receiving ATG(2)/PTCy. One-year overall survival (OS), nonrelapse mortality (NRM), and GVHD-free relapse-free survival (GRFS) were 69.8%, 25.3%, and 52.0%, respectively, for patients receiving ATG-based prophylaxis without PTCy; 82.7%, 17.3%, and 59.8% for patients receiving ATG(4.5)/PTCy; and 78.3% (P = .446), 14.7% (P = 101), and 56.2% (P = .448) for patients receiving ATG(2)/PTCy. On univariate analyses, the use of ATG(2)/PTCy was associated with a lower risk of NRM (hazard ratio, .54; P = .023) compared with the use of ATG-based prophylaxis without PTCy. ATG(2)/PTCy prophylaxis effectively prevents GVHD and is associated with comparable relapse risk, OS, and GRFS as seen with ATG(4.5)/PTCy and ATG-based prophylaxis without PTCy. © 2024 The American Society for Transplantation and Cellular Therapy

关键词： 精神分裂症   白介素-1β   白介素-16   阴性症状  

摘要： 目的 探究首发精神分裂症患者、复发精神分裂症患者和健康人群血清炎症因子的差异性以及精神分裂症患者血清炎症因子与阴性症状的相关性，为临床干预提供参考依据。方法 该研究共纳入就诊的首发精神分裂症患者86例(首发组)、复发精神分裂症患者80例(复发组)和健康对照人群82例(对照组),分析三组间血清炎症因子的差异性及患者组(首发组、复发组)血清炎症因子与阴性症状的相关性。结果 三组间血清白细胞介素(IL)-1β水平、IL-16比较差异有统计学意义(P<0.05)。两组间比较首发组血清IL-1β明显高于复发组和对照组(P<0.05),首发组和复发组血清IL-16明显高于对照组(P<0.05)。首发组血清IL-1β与阳性和阴性症状量表(PANSS)中一般精神病理量表因子分呈负相关(P<0.05),复发组血清IL-16与PANSS量表的阴性症状量表因子分呈正相关(P<0.05)。IL-16水平可能是影响首发组和复发组发病的独立危险因素(P<0.05)。结论 精神分裂症患者与健康人群血清IL-1β、IL-16水平存在差异。复发精神分裂症患者血清IL-16水平与阴性症状存在相关性。IL-16水平可能是影响精神分裂症发病的独立危险因素。

关键词： 广泛期小细胞肺癌   免疫治疗   免疫检查点抑制剂   临床进展  

摘要： 小细胞肺癌(SCLC)约占肺癌病例的15%,其生长迅速、恶性程度高、易远处转移，是临床最难治的疾病之一。经过几十年的研究，广泛期小细胞肺癌(ES-SCLC)患者的预后仍然很差。近年来，免疫检查点抑制剂(ICIs)的出现改变了ES-SCLC的治疗格局。目前，指南推荐ICIs联合含铂双药化疗用于ES-SCLC的一线治疗。但ICIs治疗ES-SCLC的体系尚未成熟，有关ICIs联合治疗方案的探索仍在进行。本文总结了ICIs在ES-SCLC中的治疗现状及进展，为探索ES-SCLC的最佳免疫治疗模式提供了思路。

关键词： dexamethasone   glioblastoma   IkBα   Interleukin-33   MAPK.   NF-κB  

摘要： BACKGROUND: Interleukin (IL)-33 is highly expressed in glioblastoma (GBM) and promotes tumor progression. Targeting IL-33 may be an effective strategy for the treatment of GBM. Dexamethasone (DEX) is a controversial drug routinely used clinically in GBM therapy. Whether DEX has an effect on IL-33 is unknown. This study aimed to investigate the effect of DEX on IL-33 and the molecular mechanisms involved. METHODS: U87MG cells were induced by tumor necrosis factor (TNF)-α to express IL-33 and then treated with DEX. The mRNA levels of IL-33, NF-κB p65, ERK1/2, and p38 were determined by real-time quantitative PCR. The expression of IL-33, IkBα (a specific inhibitor of NF-κB) and MKP-1 (a negative regulator of MAPK), as well as the phosphorylation of NF-κB, ERK1/2 and p38 MAPK, were detected by Western blotting. The secretion of IL-33 was measured by ELISA. The proliferation, migration and invasion of U87MG cells were detected by CCK8 and transwell assays, respectively. RESULTS: DEX significantly reduced TNF-α-induced production of IL-33 in U87MG cells, which was dependent on inhibiting the activation of the NF-κB, ERK1/2 and p38 MAPK signaling pathways, and was accompanied by the increased expression of IkBα but not MKP-1. Furthermore, the proliferation, migration and invasion of U87MG cells exacerbated by IL-33 were suppressed by DEX. CONCLUSION: DEX inhibited the production and tumor-promoting function of IL-33. Whether DEX can benefit GBM patients remains controversial. Our results suggest that GBM patients with high IL-33 expression may benefit from DEX treatment and deserve further investigation. Copyright© Bentham Science Publishers; For any queries, please email at epub@***.

关键词： IL1A   NRF2   Nutrition starvation   OSCC   Oxidative stress  

摘要： Understanding the intrinsic mechanisms underpinning cancer metabolism and therapeutic resistance is of central importance for effective nutrition-starvation therapies. Here, we report that Interleukin 1A (IL1A) mRNA and IL-1α protein facilitate glutathione (GSH) synthesis to counteract oxidative stress and resistance against nutrition-starvation therapy in oral squamous cell carcinoma (OSCC). The expression of IL1A mRNA was elevated in the case of OSCC associated with unfavorable clinical outcomes. Both IL1A mRNA and IL-1α protein expression were increased under glucose-deprivation in vitro and in vivo. The transcription of IL1A mRNA was regulated in an NRF2-dependent manner in OSCC cell lines under glucose-deprivation. Moreover, the IL-1α conferred resistance to oxidative stress via GSH synthesis in OSCC cell lines. The intratumoral administration of siRNAs against IL1A mRNA markedly reversed GSH production and sensitized OSCC cells to Anlotinib in HN6 xenograft models. Overall, the current study demonstrates novel evidence that the autocrine IL-1α favors endogenous anti-oxidative process and confers therapeutic resistance to nutrition-starvation in OSCCs. © 2024

摘要： Interferon gamma (IFNγ) is a critical cytokine known for its diverse roles in immune regulation, inflammation, and tumor surveillance. However, while IFNγ levels were elevated in sera of most newly diagnosed acute myeloid leukemia (AML) patients, its complex interplay in AML remains insufficiently understood. We aim to characterize these complex interactions through comprehensive bulk and single-cell approaches in bone marrow of newly diagnosed AML patients. We identify monocytic AML as having a unique microenvironment characterized by IFNγ producing T and NK cells, high IFNγ signaling, and immunosuppressive features. IFNγ signaling score strongly correlates with venetoclax resistance in primary AML patient cells. Additionally, IFNγ treatment of primary AML patient cells increased venetoclax resistance. Lastly, a parsimonious 47-gene IFNγ score demonstrates robust prognostic value. In summary, our findings suggest that inhibiting IFNγ is a potential treatment strategy to overcoming venetoclax resistance and immune evasion in AML patients. © The Author(s) 2024.

关键词： biomarker   Chronic rhinosinusitis   CRSsNP   CRSwNP   endotype   nasal polyps   patient-reported outcome measures  

摘要： Background: Type 2 (T2) inflammation plays a pathogenic role in chronic rhinosinusitis (CRS). The effects of endoscopic sinus surgery (ESS) on T2 inflammation are unknown. Objective: The aim of this study was to compare T2 inflammatory biomarkers from middle meatal (MM) mucus for distinguishing patients with CRS from CRS-free patients, identifying major phenotypes (CRS without nasal polyps [CRSsNP] and CRS with nasal polyps [CRSwNP]), assessing endotypic change, and establishing cross-sectional and longitudinal outcomes in patients undergoing ESS. Methods: MM mucus samples were collected from patients with CRSsNP and patients with CRSwNP before and 6 to 12 months after ESS and compared with samples from CRS-free control patients. T2 biomarkers were evaluated both continuously and using threshold-based definitions of T2 endotype to identify relationships with patient-reported (based on the 22-Item Sinonasal Outcomes Test and Chronic Rhinosinusitis Patient-Reported Outcomes Measure) and clinician-reported (radiographic and endoscopic) severity. Linear mixed models were developed to analyze clinical variables associated with T2 biomarker levels. Results: A total of 154 patients with CRS (89 with CRSsNP and 65 with CRSwNP) were enrolled, with a mean interval of 9 months between ESS and follow-up. An analysis of pre-ESS MM mucus samples revealed elevated levels of T2 mediators in patients with CRSwNP versus in patients with CRSsNP and CRS-free controls. Temporally stable correlations between levels of IL-13 and IL-5, levels of periostin and complement 5a, and levels of eosinophil cationic protein (ECP) and eotaxin-3 were observed. On this basis and on the basis of pathologic significance, levels of IL-13, periostin and ECP were further analyzed. After ESS, levels of IL-13 and periostin decreased significantly, whereas ECP levels remained unchanged. Across pre- and post-ESS evaluation, the T2 endotype was associated with radiographic severity but did not predict outcomes. CRSwNP status and African American race were as

摘要： OBJECTIVES: To evaluate the genetic polymorphisms in IL-2 and IL-2RA genes in schizophrenia (SCZ) patients by comparing them with healthy controls. METHODS: A sample of 127 patients with SCZ and 100 healthy volunteers were included in the case-control study. These individuals were consecutively selected from the Malazgirt State Hospital Psychiatry Outpatient Clinic in Mus, Turkey, over the three months from October 2020 to December 2020. The Structured Clinical Interview for DSM-5 Disorders, Clinician Version (SCID-5-CV) was used to confirm the diagnosis according to the DSM-5 criteria. In addition, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine gene polymorphisms from DNA material. RESULTS: Our findings indicated significant differences in the IL-2 genotype and allele frequencies between SCZ patients and the healthy control group. Specifically, the frequency of the homozygous GG genotype was notably higher in SCZ patients compared to the control group. Conversely, when comparing the IL-2RA genotype and allele frequencies of SCZ patients with the control group, no statistically significant differences were observed between the 2 groups. When compared to individuals with other genotypes, interaction analysis indicated that carriers of the GG/AG (IL-2/IL-2RA) genotype demonstrated a significantly increased risk of SCZ. CONCLUSION: In light of the analyses, our study indicates that while the IL-2 genotype polymorphism may be considered a risk factor for developing SCZ, the IL-2RA variant was not associated with SCZ among Turkish patients. Copyright: © Neurosciences.

关键词： 年龄相关性黄斑变性   地图状萎缩   补体   治疗进展  

摘要： 年龄相关性黄斑变性(age-related macular degeneration, AMD)所致地图状萎缩(geographic atrophy, GA)目前仍缺乏有效的治疗方法。越来越多的证据表明，AMD所致GA的发生和发展与补体级联失调密切相关。作为先天性免疫系统的一部分，补体系统在维持人体内环境稳态中起到了重要作用，补体过度激活将打破这一平衡，促进年龄相关性黄斑变性的进展。基于此，针对补体激活途径的潜在靶点包括C1q、C3、C5、CFB、CFD、CFH、CFI和膜攻击复合物，依据药物形式又可分为生物大分子药物、化学小分子药物及基因治疗药物。目前已有多种治疗AMD所致GA的药物进入临床试验，本文总结了GA的补体疗法的临床试验进展，以评估其安全性和有效性。

关键词： HLA-C*01:255   novel allele   sequencing-based typing  

摘要： HLA-C*01:255 differs from HLA-C*01:02:01:01 by one nucleotide in exon 2. © 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.