课程文献中心 更多>>

关键词： PCSK9   HMGB1   TLR4   Monocyte subtypes   Statin   Coronary artery disease  

摘要： Despite statin use in coronary artery disease (CAD), significant risk remains, potentially due to increased proprotein convertase subtilisin/kexin-type 9 (PCSK9) production, which raises LDL-C levels and induces inflammation. The exact relationship between PCSK9, inflammatory markers like TNF alpha, TLR4, CRP, and HMGB1, and monocyte subsets is poorly understood. This study aimed to explore these relationships in non-statin and statin-taking CAD patients. This case-control study included 91 controls and 91 stable CAD patients, divided into no-statin (NS, n = 25), low-dose statin (LDS, n = 25), and high-dose statin (HDS, n = 41) groups. Serum levels of LDL-C, CRP, PCSK9, TLR4, HMGB1, and TNF alpha were measured. Monocyte subsets were classified using flow cytometry into classical monocytes (CM), intermediate monocytes (IM), and non-classical monocytes (NCM). CAD patients showed elevated PCSK9, LDL-C, and inflammatory markers compared to controls. Statin groups (LDS, HDS) had lower LDL-C and inflammatory markers but higher PCSK9 than the NS group, with the HDS group showing the lowest LDL-C and inflammatory markers but the highest PCSK9. In the NS group, PCSK9 positively correlated with inflammatory markers (HMGB1, TNF alpha, TLR4, CRP) and monocyte subsets (IM%, NCM%). In the total statin group (LDS + HDS), PCSK9 negatively correlated with HMGB1, TLR4, and NCM%, for each, respectively, and positively with CM%. Multivariable linear regression showed significant associations between PCSK9 and HMGB1, NCM%, and IM% in the NS group, and HMGB1, NCM%, and TLR4 in the total statin group. In conclusion, we recommend combining PCSK9 inhibitors with statins in high-risk CAD patients. This may enhance statin efficacy, reduce LDL-C, and inhibit the TLR4/NF-& kcy;B inflammatory pathway, decreasing atherosclerotic inflammation.

关键词： HLA   HLA-B*35:629N   NGS  

摘要： The HLA-B*35:629N allele differs from HLA-B*35:01:01:02 by one nucleotide substitution in codon 74 in exon 2.

关键词： chronic hepatitis B   HBsAg loss   immunological factors   Peg IFN-alpha   relapse  

摘要： Background:Emerging evidence indicates that the treatment duration of pegylated interferon-alpha and HBsAb may predict relapse in chronic hepatitis B (CHB) patients who achieved clinical cure. However, the host immunological mechanisms contributing to clinical relapse remain poorly characterized. Objectives:This study aimed to identify the immunological factors associated with relapse in chronic hepatitis B (CHB) patients who achieved clinical cure based on pegylated interferon-alpha treatment. Methods:CHB patients who achieved HBsAg loss after discontinuing pegylated interferon-alpha therapy were enrolled and followed up for at least 96 weeks. HBcrAg and immunological markers, including the proportion of follicular helper T (Tfh) cells were assessed by flow cytometry. Peripheral blood cytokine levels were measured using a Luminex assay. The primary outcome was the correlation between immunological markers with relapse at the end of treatment (EOT) and end of follow-up (EOF). Results:A total of 456 CHB patients were included. During the 96-week follow-up period, 37 patients (8.11%) experienced a relapse. Propensity score matching was performed at a 1:2 ratio, resulting in the inclusion of 37 relapsed (R) and 74 non-relapsed (NR) patients. The NR group exhibited higher proportions of Tfh cells than the R group in both EOT and EOF (EOT: 12.52% vs. 8.78%, p=0.008;EOF: 11.38% vs. 8.29%, p=0.008). A significantly greater proportion of CCR7loPD-1hi Tfh cells was observed in the NR group at the EOT (9.4% vs. 4.5%, p=0.009). The frequency of CCR7loPD-1hi Tfh cells was significantly and positively correlated with anti-HB levels in EOT (p=0.015, r=0.392). Serum levels (median, pg/mL) of CTLA-4 (EOT: 14.87 vs. 7.84;EOF: 14.87 vs. 7.97), PD-1 (EOT: 321.44 vs. 203.96;EOF: 288.45 vs. 166.04), and TIM-3 (EOT:4487 vs. 21254;EOF:2973 vs. 1768) were significantly higher in the R group than in the NR group at both EOT and EOF (p<0.05). At EOT, the HBcrAg level was significantly greate

关键词： residency   artificial intelligence   ChatGPT   machine learning   postgraduate medical education   apprentissage machine   & eacute   ducation m & eacute   dicale postdoctorale   intelligence artificielle   r & eacute   sidence  

摘要： Introduction: Personal statements can be decisive in Canadian residency applications. With the rise in AI technology, ethical concerns regarding authenticity and originality become more pressing. This study explores the capability of ChatGPT in producing personal statements for plastic surgery residency that match the quality of statements written by successful applicants. Methods: ChatGPT was utilized to generate a cohort of personal statements for CaRMS (Canadian Residency Matching Service) to compare with previously successful Plastic Surgery applications. Each AI-generated and human-written statement was randomized and anonymized prior to assessment. Two retired members of the plastic surgery residency selection committee from the University of British Columbia, evaluated these on a 0 to 10 scale and provided a binary response judging whether each statement was AI or human written. Statistical analysis included Welch 2-sample t tests and Cohen's Kappa for agreement. Results: Twenty-two personal statements (11 AI-generated by ChatGPT and 11 human-written) were evaluated. The overall mean scores were 7.48 (SD 0.932) and 7.68 (SD 0.716), respectively, with no significant difference between AI and human groups (P = .4129). The average accuracy in distinguishing between human and AI letters was 65.9%. The Cohen's Kappa value was 0.374. Conclusions: ChatGPT can generate personal statements for plastic surgery residency applications with quality indistinguishable from human-written counterparts, as evidenced by the lack of significant scoring difference and moderate accuracy in discrimination by experienced surgeons. These findings highlight the evolving role of AI and the need for updated evaluative criteria or guidelines in the residency application process. Introduction: Les lettres personnelles peuvent & ecirc;tre d & eacute;cisives lors des candidatures canadiennes & agrave;la r & eacute;sidence. & Eacute;tant donn & eacute;l'int & eacute;r & ecirc;t pour la techn

关键词： cytokines   decidual natural killer cells   HLA-G/KIR2DL4   HTR-8/SVneo cells   miR-152  

摘要： Trophoblast cells are specialized placental epithelial cells essential for pregnancy maintenance. miR-152 is implicated in trophoblast cell regulation and pregnancy failure. This study explores the role of miR-152 in decidual natural killer (dNK) cell viability and trophoblast cell invasion. HTR-8/SVneo cells were transfected with miR-152-mimics/inhibitor or their respective controls, followed by co-culture with dNK cells. RT-qPCR assessed transfection efficiency, while cytokine secretion (IL-8, IP-10, VEGF), cell viability, apoptosis, and invasion were evaluated via ELISA, CCK-8, flow cytometry, Western blot, and Transwell assays. The interaction between miR-152 and HLA-G was examined via dual-luciferase reporter assay, and HLA-G/sHLA-G levels were measured. Co-cultures of dNK cells and miR-152/HLA-G-overexpressing HTR-8/SVneo cells were established, and anti-KIR2DL4/IgG1 was used to block HLA-G/KIR2DL4 binding. Co-immunoprecipitation confirmed protein interactions. miR-152 overexpression suppressed dNK cell cytokine secretion, reduced HTR-8/SVneo cell viability and invasion, and promoted apoptosis. miR-152 inhibition had the opposite effect. miR-152 directly targeted HLA-G, and HLA-G overexpression rescued dNK function and trophoblast invasion. Blocking the HLA-G/KIR2DL4 binding counteracted the effects of miR-152. miR-152 inhibits dNK cell function and trophoblast invasion by targeting HLA-G, reducing HLA-G/KIR2DL4 interaction. These findings highlight a potential regulatory mechanism in pregnancy maintenance.

关键词： Alloreactivity   Genetic risk   Acute graft-versus-host disease   Whole-genome sequencing   Machine-learning model  

摘要： Human leukocyte antigen (HLA) disparity between donors and recipients is a key determinant triggering intense alloreactivity, leading to a lethal complication, namely, acute graft-versus-host disease (aGVHD), after allogeneic transplantation. Moreover, aGVHD remains a cause of mortality after HLA-matched allogeneic transplantation. Protocols for HLA-haploidentical hematopoietic cell transplantation (haploHCT) have been established successfully and widely applied, further highlighting the urgency of performing panoramic screening of non-HLA variations correlated with aGVHD. On the basis of our time-consecutive large haploHCT cohort (with a homogenous discovery set and an extended confirmatory set), we first delineated the genetic landscape of 1366 samples to quantitatively model aGVHD risk by assessing the contributions of HLA and non-HLA genes together with clinical factors. In addition to identifying multiple loss-of-function (LoF) risk variations in non-HLA coding genes, our data-driven study revealed that non-HLA genetic variations, independent of HLA disparity, contributed the most to the occurrence of aGVHD. This unexpected major effect was verified in an independent cohort that received HLA-identical sibling HCT. Subsequent functional experiments further revealed the roles of a representative non-HLA LoF gene and LoF gene pair in regulating the alloreactivity of primary human T cells. Our findings highlight the importance of non-HLA genetic risk in the new era of transplantation and propose a new direction to explore the immunogenetic mechanism of alloreactivity and to optimize donor selection strategies for allogeneic transplantation.

关键词： MyD88   IRF11   IFN   Negative regulation   Anguilla japonica  

摘要： MyD88 is an intracellular adaptor protein that mediates signals from many TLRs and IL-1/IL-18 receptors to downstream kinases, by recruiting transcription factors, such as IFN regulatory factor (IRF) family members, to evoke the activation of a series of target genes. Recent studies imply a role of MyD88 in the regulation of type IFN signaling through MyD88-IRF interaction in teleosts. In this study, we explore the mechanistic role of MyD88 on IFN production mediated by IRF11, a fish-specific positive regulator in this pathway. Overexpression of MyD88 suppressed IRF11-induced activation of the IFN promoter. Conversely, MyD88 knockdown in zebrafish liver cells further increased IRF11-induced expression of IFN and IFN-stimulated genes (ISGs). Co-immunoprecipitation experiments identified the Toll/IL-1 receptor (TIR) domain of MyD88 and the region between amino acids 114 and 155 of IRF11 as critical for their interaction. Confocal microscopy and subcellular fractionation revealed that MyD88 co-localizes with IRF11 in the nucleus upon co-expression. These results suggest MyD88 negatively regulates IRF11-mediated IFN production through protein-protein interaction and nuclear co-localization. Thus our present study places MyD88 as negative regulator participating in IRF11-mediated IFN production and provides a novel mechanism for regulating the fish antiviral response.

摘要： Background and ObjectivesAssociation of human leukocyte antigen (HLA) with anti-aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD) has been reported. However, this association in the Korean population has not been previously investigated. We aimed to evaluate whether specific HLA subtypes were associated with Korean patients with AQP4-IgG NMOSD and whether the HLA genotype is associated with specific clinical *** compared the HLA subtypes of 122 patients with AQP4-IgG NMOSD with those of 485 (HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1) and 173 (HLA-DPB1) healthy controls. In addition, we compared the clinical features of patients with and without specific HLA *** most significant risk allele for AQP4-IgG NMOSD was HLA-DRB1*03:01 (24 patients [19.67%], odds ratio [OR]: 3.997, pc value = 0.0001). Susceptibility of AQP4-IgG NMOSD was significantly associated with the HLA-DRB1*03:01-DQB1*02:01 (23 patients [18.85%], OR: 3.792, pc value = 0.0002) and DRB1*12:02-DQB1*03:01 (23 patients [18.85%], OR: 3.402, pc value = 0.0009) haplotypes. Patients with the DRB1*12:02-DQB1*03:01 haplotype showed more frequent spinal involvement, a higher Expanded Disability Status Scale score at disease-onset nadir, and a shorter time to second attack than patients without this *** a Korean cohort of patients withAQP4-IgG NMOSD, the HLA-DRB1*12:02-DQB1*03:01 haplotype was associated with disease severity at onset. HLA-DRB1*03:01, broadly reported as a significant susceptibility allele across diverse ethnic groups, showed a significant risk association in Korean patients with AQP4-IgG NMOSD.

关键词： HIV   Food allergy   Th2   Asthma   Atopic dermatitis  

摘要： Background. - Human Immunodeficiency Virus infection is known to cause significant immunological changes, including a shift towards a Th2-dominant immune response, which is typically associated with allergic conditions. However, the relationship between HIV infection and the incidence of food allergies remains unclear. Objective. - This study aims to investigate the incidence of food allergies in HIV-infected patients compared to a non-HIV population. Methods. - This retrospective cohort study utilized observational data including individuals diagnosed with HIV between 2004 and 2023. A control group matched for age and sex (1:60) was created from non-HIV individuals. Data on allergic conditions were extracted using ICD9 codes, and statistical analyses were conducted using Cox proportional hazards models to assess the effect of HIV on food allergy incidence over a 10-year follow-up period. Results. - The study included 1616 HIV-positive patients and 95,773 controls. While higher rates ofasthma and atopic dermatitis were observed in the HIV group, no cases of food allergy were detected among HIV patients, compared to 185 cases in the non-HIV cohort. The adjusted hazard ratios indicated that factors such as asthma, atopic dermatitis, vitamin D insufficiency, and kidney transplantation were associated with increased food allergy risk in the non-HIV population. Conclusion. - Despite the Th2-dominant immune environment associated with HIV infection, no increased risk of food allergy was observed in HIV-positive individuals over a 10-year period. This suggests that the immunological alterations caused by HIV may not predispose patients to food allergies as they do to other allergic conditions. (c) 2025 Les Auteurs. Publie par Elsevier Masson SAS au nom de Societe franc,aise d'allergologie. Cet article est publie en Open Access sous licence CC BY (http://***/licenses/by/4.0/).

关键词： HLA-A*26:254   mestizo   next-generation sequencing (NGS) typing  

摘要： The novel HLA-A*26:254 allele (HLA-A*26:01P) was identified from a healthy mestizo from Ecuador.