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关键词： en bloc heart-liver transplantation   adult congenital heart disease   heart transplantation   liver transplantation   BMI   body mass index   CPB   cardiopulmonary bypass   CHLT   combined heart-liver transplantation   CPRA   calculated panel reactive antibody   d-TGA   dextro-transposition of the great arteries   ECMO   extracorporeal membranous oxygenation   FALD   Fontan-associated liver disease   HLA   human leukocyte antigen   IVIG   intravenous immunoglobulin   L-TGA   levo-transposition of the great arteries   LVAD   left ventricular assist device   MELD   model for end-stage liver disease   MCS   mechanical circulatory support   VA-ECMO   venoarterial extracorporeal membrane oxygenation   VV-ECMO   venovenous extracorporeal membrane oxygenation  

摘要： Background: Combined heart-liver transplantation (CHLT) is a definitive therapy reserved for patients with concomitant heart failure and advanced liver disease. A limited number of centers perform CHLT, and even fewer use the en bloc implantation technique. Here we review clinical outcomes and immunoprotective effects following CHLT and describe our institution's more than two decades of experience in performing the en bloc technique. Methods: All patients who underwent CHLT at our institution between January 2003 and July 2023 were identified. Recipient and donor characteristics, operative details, and clinical outcomes were assessed. Kaplan-Meier analysis was performed to evaluate survival following CHLT. Results: A total of 20 patients underwent CHLT using the en bloc technique at our institution between January 2003 and July 2023. At a median follow-up of 3.8 years for patients who survived the perioperative period (n 1/4 18), estimated survival was 94% at 1 year and 75% at 5 years. There was 100% freedom from acute moderate rejection, acute severe rejection, and chronic rejection in all patients. No patients required retransplantation due to rejection. Conclusions: CHLT is a definitive therapy reserved for patients with multiorgan dysfunction. At our institution, the en bloc technique is the preferred operative approach, as it minimizes cardiac insult, requires fewer anastomoses, minimizes cold ischemia time, and allows for rapid correction of coagulopathy. Overall survival for this cohort is excellent. Episodes of acute rejection were rare, providing further support for the idea that the liver may serve an immunoprotective role in multiorgan transplantation. (J Thorac Cardiovasc Surg 2025;169:1254-62)

摘要： Therapy with pegylated interferon alpha (pegIFN alpha) can induce a deep molecular response in a subset of patients with myeloproliferative neoplasms (MPN). Here we investigated the role of Socs2, a negative regulator of cytokine signaling, in modulating the response to pegIFN alpha in a JAK2-V617F mouse model of MPN. Deleting Socs2 in JAK2-V617F mice resulted in increased sensitivity to cytokines, without causing significant alterations in the MPN phenotype. When subjected to pegIFN alpha, the loss of Socs2 enhanced the depletion of JAK2-mutant hematopoietic stem cells (HSCs), evidenced by reduced chimerism in peripheral blood and bone marrow compared to vehicle controls. Additionally, pegIFN alpha-treated Socs2-deficient JAK2-mutant HSCs exhibited functional impairments in secondary transplantations, reflecting long-term detrimental decline of their stemness. These findings demonstrate that loss of Socs2 enhances the effectiveness of pegIFN alpha in depleting the JAK2-mutant HSC clone. In line with the genetic ablation of Socs2, the SOCS2 inhibitor MN714 combined with IFN alpha exhibited better efficacy than IFN alpha alone in reducing the output of CD34+ cells from PV patients in vitro. Targeting SOCS2 could therefore improve therapeutic responsiveness in MPN patients receiving interferon therapy.

关键词： IL-17B   IL17RB   Colorectal cancer   Bioinformatics  

摘要： Background: The aim of the research is to investigate correlation of immune infiltration between IL-17B and IL17RB in colorectal cancer (CRC), then provide an experimental basis for clinical diagnostic marker screening of CRC. Methods: Gene expression levels were assessed via TIMER and GEPIA databases, protein expression through the Human Protein Atlas (HPA), clinicopathological correlations and prognosis via UALCAN and KM-Plotter, respectively. Mutation analysis was conducted using cBioPortal, immune cell infiltration via TIMER, and hub genes were identified through protein-protein interaction (PPI) networks. Biological functions and pathways were elucidated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, the expression of IL-17B, IL-17RB, and associated inflammatory cells in CRC were analyzed using immunohistochemical staining and special staining technique. Results: Bioinformatics analysis showed that IL-17B gene and protein expression levels decreased, while IL-17RB expression increased in CRC. IL-17B expression was affected by gender, body weight, histology, lymph node status, and tumour grade. Overexpression of IL-17B was negatively correlated with progression-free survival in CRC. IL-17B is involved in phosphatidylinositol 3-kinase/AKT signaling, vascular development, and other processes. IL-17B is associated with mitochondrial gene expression, regulation of mRNA metabolism, amino acid metabolism and other processes, as well as phosphatidylinositol-binding and liganding. Inositol 3-kinase/AKT signalling and vascular development. IL-17B was negatively correlated with mitochondrial gene expression, regulation of mRNA metabolism, amino acid metabolism and other processes as well as with molecular functions such as phosphatidylinositol binding and ligase activity. IL-17RB expression was correlated with the clinicopathological features described above and decreased with tumour progression. High levels of IL-17RB were a

关键词： genomic sequence   HLA-B   new allele   Saudi Arabia  

摘要： The novel HLA-B*49:01:01:23 allele differs from HLA-B*49:01:01:01 allele by single nucleotide polymorphism in the 3 ' UTR.

关键词： cloning   genomic sequence   HLA-A*24:85   long-range PCR   Sanger sequencing  

摘要： The full-length sequence of HLA-A*24:85 covers the 5 '-untranslated region (UTR), all introns and exons and the 3 ' UTR.

关键词： Hidradenitis suppurativa   Biologic   Small molecule inhibitor   TNF   IL-17   IL-12/23   IL-1   JAK   Biosimilar  

摘要： center dot Anti-inflammatory biologic and small molecule therapies are essential to successful management of Hurley stage 2 and 3 hidradenitis suppurativa. center dot Food and Drug Administration-approved options adalimumab and secukinumab reduce disease activity by 50% or more in roughly half of patients;off-label, various TNF, IL-17, IL-12/23, IL-1, and Janus kinase inhibitors-appear beneficial in clinical studies. center dot An iterative approach to medication dosing and frequency, coadministration, and use of surgical modalities may be necessary to obtain a sustained disease response.

关键词： IL-5   IL-5R   mast cells   mast cell progenitors