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摘要： This study assessed 552 allogeneic hematopoietic cell transplantation (HCT) recipients with posttransplant cyclophosphamide (PTCy) to evaluate the incidence, characteristics, risk factors, and impact of early posttransplant cytokine release syndrome (CRS) on outcomes. The cohort included 36% matched sibling donors (MSD), 34% matched unrelated donors (MUD), 27% haploidentical donors, and 4% mismatched unrelated donors (MMUD). CRS was observed in 182 patients, with the highest incidence in haploidentical transplants (80%) compared to MMUD (32%), MUD (23%), and MSD (8%). Most CRS cases were mild, with 93% classified as grade 1 and 6% as grade 2, with only one severe case of grade 3. In haploidentical transplants, CRS was linked to a lower risk of severe chronic graft-versus-host disease (GVHD) and non-relapse mortality (NRM), leading to improved overall survival. In contrast, among HLA-matched recipients (MSD and MUD), there were no significant differences in outcomes between those with or without CRS. However, subgroup analysis revealed that CRS in patients with myeloid malignancies, including acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms, was associated with a reduced relapse rate, improving survival outcomes. In conclusion, while CRS is typically mild and short-lived, it significantly impacts survival, particularly in haploidentical transplants and HLA-matched patients with myeloid malignancies.

关键词： COPD   chronic obstructive pulmonary disease   DPI   dry powder inhaler   FeNO   fractional exhaled nitric oxide   ICS   inhaled corticosteroids   IL   interleukin   ILC2   type 2 innate lymphoid cells   LABA   long-acting β agonist(s)   LAMA   long-acting muscarinic antagonist(s)   LTRA   leukotriene receptor antagonist   M1, M2, M3   muscarinic receptor subtypes (1, 2, and 3)   OCS   oral corticosteroids   pMDI   pressurized metered-dose inhaler   SABA   short-acting β agonist(s)   Th1   type 1 T helper cells   Th2   type 2 T helper cells   Th17   type 17 T helper cells   TNF   tumor necrosis factor   TSLP   thymic stromal lymphopoietin  

摘要： Asthma is a disease of airway inflammation and bronchial hyperresponsiveness affecting over 300 million individuals worldwide. Although described as early as 460 BC, the recognition of asthma as a disease, and the development and implementation of therapies to control it, emerged in the early 1900s. Pharmacological Reviews 77 (2025) 100062 The subsequent century introduced the utilization of immunotherapy, inhaled medications, and antiinflammatory corticosteroids for disease control. Since the beginning of the 21st century, however, the emergence of novel asthma pharmacotherapies has accelerated greatly. Our understanding of various asthma phenotypes and their underlying mechanisms (endotypes) has crystallized, leading to an era of precision medicine. Management strategies increasingly use targeted biologic medications aimed at interrupting key components of the inflammatory cascade. Monoclonal antibodies targeting the IgE, thymic stromal lymphopoietin, or interleukin-4,-5, and-13 pathways have revolutionized the care we provide our patients, resulting in a reduction in exacerbations and oral corticosteroid (OCS) dose, while improving lung function and asthma-related quality of life. Although they are able to provide relief for many sufferers of severe disease, and even remission in some, these biologic therapies are still in their infancy. Because their roles become further established, new therapeutic targets and modalities offer significant promise of an even greater personalized medicine approach. This review addresses historical standard-of-care strategies for asthma treatment, current recommendations, and a glimpse into future novel therapies that are likely to help millions worldwide. Significance Statement: Asthma affects hundreds of millions of individuals worldwide. In the last few decades, asthma treatment paradigms have transformed from recommendations to use antiinflammatory and bronchodilatory inhalation-based therapies including corticosteroids and be

关键词： anti-HLA antibodies   HLA evolutionary divergence   liver transplantation   rejection  

摘要： HLA evolutionary divergence (HED), a continuous metric quantifying the differences between each amino acid of two homologous HLA alleles, reflects the importance of the immunopeptidome presented to T lymphocytes. It has been associated with rejection after liver transplantation. This retrospective cohort study aimed to analyse the potential effect of donor or recipient HED on liver transplant rejection in a new series of patients transplanted during childhood and followed in adulthood. The study included 120 children who had been transplanted between 1991 and 2010 and were followed by routine biopsies and histological evaluations with a median of 14.1 years post-LT. Liver biopsies were performed routinely 1, 5, 10 and 20 years after transplantation and in the event of liver dysfunction. HED was calculated using the physicochemical Grantham distance for donor and recipient Class I (HLA-A, -B, -C) and Class II (HLA-DRB1, -DQB1) alleles. The influence of HED on rejection was analysed using inverse probability weighting (IPW) and target trial emulation using the g method. Based on the IPW score, donor HED class I was correlated with the occurrence of late (> 90 days) rejection (HR, 1.19, 95% CI: 1.01-1.40) independently of HLA mismatches, donor age and initial induction. The emulated target trial confirmed that donor HED Class I has a causal effect on liver graft rejection and this relationship was observed long-term.

关键词： CICARE communication nursing   inflammatory factor levels   lung function   outpatient service   patients with acute bronchitis  

摘要： OBJECTIVE: The objective of the study was to investigate the impact of CICARE communication nursing on the improvement of serum interleukin-10 (IL-10), interleukin-6 (IL-6), interleukin-4 (IL-4), and interleukin-2 (IL-2) and lung function in outpatients with acute bronchitis (AB). METHODS: One hundred and twenty suffers with AB who are treated in the outpatient department during Revised to 2021 to March 2023 are chosen and grouped according to the time of admission and different nursing practices. The control group consists of 60 patients from March 2021 to March 2022 who receive routine outpatient care;the experimental group consists of 60 patients from April 2022 to March 2023, and CICARE communication nursing is implemented additionally. Before and after intervention, the cognitive level of self-care knowledge, the level of peripheral blood inflammatory factors, and the improvement of lung function are compared. RESULTS: Before intervention, there were no remarkable differences in self-care knowledge cognition scores, peripheral blood inflammatory factors, and lung function levels between them (P > 0.05). After intervention, the cognitive scores of treatment coordination, medication method, daily attention, diet, and activity in experimental groups are superior to control group (P < 0.05). The levels of IL-10, IL-6, IL-4, and IL-2 in test groups are inferior to control group (P < 0.05). Forced vital capacity, forced expiratory volume in 1 s, maximum air volume, and peak flow rate in test groups are superior to control group (P < 0.05). CONCLUSION: CICARE communication nursing can improve the cognition level of self-care knowledge of patients with AB, reduce the inflammatory response of the body, and promote the recovery of lung function.

关键词： HLA   HLA-DRB1*12:110   new allele   next-generation sequencing  

摘要： The HLA-DRB1*12:110 allele differs from the HLA-DRB1*12:01:01:05 allele by a single nucleotide at codon 179 in exon 3.

摘要： Excessive inflammation and cytokine release are hallmarks of severe COVID-19. Certain programmed cell death processes can drive inflammation, however, their role in the pathogenesis of severe COVID-19 is unclear. Pyroptosis is a pro-inflammatory form of regulated cell death initiated by inflammasomes and executed by the pore-forming protein gasdermin D (GSDMD). Using an established mouse adapted SARS-CoV-2 virus and a panel of gene-targeted mice we found that deletion of the inflammasome (NLRP1/3 and the adaptor ASC) and pore forming proteins involved in pyroptosis (GSDMA/C/D/E) only marginally reduced IL-1 beta levels and did not impact disease outcome or viral loads. Furthermore, we found that SARS-CoV-2 infection did not trigger GSDMD activation in mouse lungs. Finally, we did not observe any difference between WT animals and mice with compound deficiencies in the pro-inflammatory initiator caspases (C1/11/12-/-). This indicates that the classical canonical and non-canonical pro-inflammatory caspases known to process and activate pro-IL-1 beta, pro-IL-18 and GSDMD do not substantially contribute to SARS-CoV-2 pathogenesis. However, the loss of IL-1 beta, but not the absence of IL-18, ameliorated disease and enhanced survival in SARS-CoV-2 infected animals compared to wildtype mice. Collectively, these findings demonstrate that IL-1 beta is an important factor contributing to severe SARS-CoV-2 disease, but its release was largely independent of inflammasome and pyroptotic pathways.

关键词： Leiomyoma   Uterin fibroid   Polymorphism   ERS-1   IL-8   ICAM-1   TNFAIP2  

摘要： Objective: In this study, we aimed to investigate the difference between ICAM-1, IL-8, and ER-alpha gene polymorphisms and the effects of the formation of leiomyomas by measuring serum levels of IL-8 and ICAM-1 in uterine leiomyoma and control patients. Study Design. The roles of ERS-1, TNSFIP2, ICAM-1, and IL-8 gene polymorphisms in leiomyoma development were investigated using TaqMan SNP genotyping assay. In addition, serum IL-8 and ICAM-1 levels of leiomyoma and control group individuals were measured using the ELISA method. The sample included in the study consisted of 75 people diagnosed with uterine leiomyoma (leiomyoma group) and 75 healthy volunteers without ovarian pathology (control group) who came to Sivas Cumhuriyet University Medical Faculty Gynaecology and Obstetrics Clinic. Results: TNFAIP2 rs8126, ICAM-1 rs5498 and ESR-1 rs17847075 polymorphisms were not associated with leiomyoma disease. In addition, individuals carrying heterozygous genotypes of ESR-1 rs9322331 (p = 0.01, OR = 2.4), IL-8 rs4073 (p = 0.02, OR = 2.4) and IL-8 rs2227306 (p = 0.01, OR = 2.246) polymorphisms may be at risk for leiomyoma. Similarly, mutant alleles of ESR-1 rs9322331 (p = 0.005, OR = 2.172), IL-8 rs4073 (p = 0.01, OR = 2.204) and IL-8 rs2227306 (p = 0.004, OR = 2.2) polymorphisms were found to be risk alleles. Furthermore, it was observed that IL-8 serum levels increased more in the leiomyoma group (1.83 f 0.4 pg/mL) compared to the control group (1.02 f 0.2 pg/mL). Likewise, a significant decrease in ICAM-1 levels was found in the leiomyoma group (1595.5 f 80 ng/mL) compared to the control group (2939.3 f 104 ng/mL). Conclusion: In this context, it was concluded that polymorphisms of IL-8 and ESR-1 genes, which are thought to be risk factors in leiomyoma harvests, and factors affecting IL-8 and ICAM-1 expression should be further investigated.

关键词： HLA   HLA-DQA1*01:175   new allele   next-generation sequencing  

摘要： The HLA-DQA1*01:175 allele differs from the HLA-DQA1*01:02:01:03 allele by a single nucleotide at codon 49 in exon 2.

关键词： pertussis vaccine   Treg cell   T-RM cell   Th17 cell   IL-10  

摘要： Tissue-resident memory T (T-RM) cells play a key role in sustained protective immunity against Bordetella pertussis infection of the nasal mucosa. Current alum-adjuvanted acellular pertussis (aP) vaccines protect against severe pertussis disease but fail to prevent nasal infection with B. pertussis. Here we demonstrate that immunization of mice with an aP vaccine failed to generate respiratory T-RM cells, but did induce antigen-specific CD4(+) Treg cells that expressed Foxp3, CD49b, PD-1 and LAG-3, and CD8(+) Treg cells that expressed CD122, PD-1, and IL-10. B. pertussis-specific CD4(+) and CD8(+) T cell lines established from aP-immunized mice expressed the regulatory markers and suppressed activation of Th1 and Th17 cells. Blockade of IL-10 signaling during aP immunization or B. pertussis challenge promoted the induction of IL-17-secreting CD4(+) T-RM responses and enhanced bacterial clearance from the nose. Addition of the adjuvant LP-GMP, comprising TLR2 and STING agonists, to the aP vaccine and delivery by the nasal route promoted the induction of antigen-specific IL-17-producing CD4(+) T-RM cells and enhanced vaccine efficacy. Our findings demonstrate that aP vaccines suppress the induction of protective T-RM cells in part through the induction of CD4(+) and CD8(+) Treg cells, which can be overcome using a potent adjuvant and delivery of the vaccine intranasally.

关键词： Chikungunya   Cytokine   Chemokine   Chronic chikungunya arthritis  

摘要： Background: Cytokines and chemokines play a crucial role in orchestrating the immune response to chikungunya virus (CHIKV) infection, influencing disease course and outcome. Although significant efforts have been made to understand the cytokine signatures associated with CHIKV infection, the identification of specific cytokine biomarkers across different disease stages remains incomplete. Material and method: We have assessed CHIKV-specific cytokine, chemokine profiles of 17 analytes in 50 acute chikungunya patients, 31 chronic chikungunya arthritis patients, 30 recovered individuals, and 23 healthy controls. The cytokine and chemokines were measured in the supernatant of PBMCs stimulated in vitro with inactivated chikungunya virus. Results: It was observed that chronic chikungunya arthritis patients exhibited significantly higher levels of IL1(3, IL-6, and GM-CSF compared to all other groups. MCP-1 levels were elevated in patient groups compared to recovered and control individuals. IL-1(3 emerged as a potential biomarker for chronic chikungunya arthritis based on ROC analysis. A negative correlation between IFN-gamma levels and CHIKV load was observed in acute patients, suggesting its antiviral role. IL-12 levels were higher in recovered individuals compared to all other groups, while IFN-gamma levels were elevated in recovered individuals compared to acute patients. Conclusion: Our findings highlight IL-1(3 as a potential biomarker for chronic chikungunya arthritis and suggest that GM-CSF inhibition could serve as a therapeutic intervention for disease-associated chronic inflammation. The observed co-regulation of IL-12 and IFN-gamma in recovered individuals needs further investigation into their role in disease resolution. These insights provide a deeper understanding of the immunopathogenesis of CHIKV infection and may contribute in future diagnostic and therapeu tic strategies.