Introduction Understanding CD8 + tissue-resident memory T cells (TRM) spatial characteristics in hepatocellular carcinoma (HCC) is challenging, and clarifying the spatial feature changes following immunotherapy represents an urgent research gap. Methods This study employs a multi-omics approach to analyze the spatial distribution and intercellular interactions of TRM cells in HCC tissues using radiomics, single-cell sequencing, and multiplex immunofluorescence histochemistry (m-IHC). Results Our results show that the number of CD8 + TRM cells in HCC increases following immunotherapy. Furthermore, after dividing tumor tissues into the tumor core (TC), invasion margin (IM), and normal tissue (N), a increase in CD8 + TRM cells from the IM to the TC can be observed. Consistent with the results of single-cell sequencing analysis, this change in spatial characteristics may be associated with the interactions between CD8 + TRM cells and CD68 + cells. Discussion Immunotherapy can modify the spatial characteristics of CD8 + TRM cells via regulating their crosstalk with other immune cells, and the spatial distribution of CD8 + TRM cells in the HCC tumor microenvironment (TME) correlates with immune checkpoint blockade (ICB) therapeutic efficacy. Clarifying the mechanisms of action of immunotherapeutic drugs and developing a non-invasive radiomics model to predict CD8⁺ TRM cell dynamics will facilitate the clinical management of HCC.

Background The choice of an appropriate cannulation technique should be important to increase the possibility of better outcomes in terms of arteriovenous fistulas (AVF) survival and comfort of the patient undergoing hemodialysis. Methods It is a retrospective study and microarray analysis was conducted to identify differentially expressed genes (DEGs) between failing and control access samples. Sixty-four patients who underwent early cannulation (3–4 weeks after AVF creation) were enrolled and divided into two groups: a plastic cannula group (n = 33) and a metal needle group (n = 31). Comparisons were made between the groups regarding complement components, blood flow, access intimal hyperplasia, and inflammatory cell infiltration. Results (1) AVF failure occurred in 13 patients (20.3%) over a mean follow-up of 241 ± 105 days. (2) Complement B factor (CFB) levels showed significant changes within the first two weeks post-cannulation. (3) Fluctuations in CFB strongly correlated with changes in AVF blood flow during follow-up. (4) CFB variation independently predicted AVF failure, with a hazard ratio of 4.54 (95% CI, 1.21–16.99). (5) The plastic cannula group exhibited significantly lower CFB expression in both blood and outflow access, along with marked improvements in intimal hyperplasia and inflammatory cell infiltration. (6) Compared with the metal needle group, serum from the plastic cannula more significantly induced endothelial cell proliferation and nitric oxide production, with CFB playing a critical role. Conclusions The alternative complement pathway is significantly activated during initial AVF cannulation, with excessive CFB production contributing substantially to AVF failure. The use of plastic cannulas may improve long-term AVF patency by mitigating endothelial dysfunction and inhibiting inflammatory cell infiltration through suppression of CFB generation.

Objectives Immune checkpoint inhibitor (ICI)-associated myocarditis is a rare but potentially fatal immune-related adverse event that can rapidly progress to life-threatening arrhythmias and cardiogenic shock, often necessitating mechanical circulatory support. Extracorporeal membrane oxygenation (ECMO) has emerged as a critical life-saving intervention in such cases. However, the role of ECMO in treating ICI-associated myocarditis remains underexplored, with limited literature available. Methods We present a case of fulminant ICI-associated myocarditis with cardiogenic shock successfully managed with ECMO. Additionally, we review and summarize data from 13 ECMO-assisted patients with ICI-associated myocarditis to provide insights into the clinical characteristics, management strategies, and outcomes. Main results Among the 13 patients (with a mean age 59.08 years), monotherapy using nivolumab or pembrolizumab represented the predominant ICI treatment regimen. The median treatment cycle was 3.0 (IQR: 2.0 ~ 7.0), and the median duration from first administration to myocarditis onset was 77.0 (IQR: 20.5 ~ 250.0) days. The median duration of myocarditis symptoms was 19.0 (IQR: 15.5 ~ 42.5) days. Common presenting symptoms included fever and dyspnea, while most patients exhibited elevated myocardial enzymes and BNP levels, arrhythmias, and an average left ventricular ejection fraction (LVEF) of 38.31% at admission. Myocardial biopsy was the primary diagnostic method. In addition to immunosuppressive therapy, most patients also required intra-aortic balloon pump (IABP) support. The median duration of ECMO and IABP support was 9.0 (IQR: 6.5 ~ 15.5) days and 11.5 (IQR: 7.5 ~ 13.0) days, respectively. Ultimately, nine of the thirteen patients (69.23%) survived. Conclusions Our analysis demonstrates ECMO’s potential as a bridge-to-recovery strategy for severe ICI-associated myocarditis with cardiogenic shock. The observed survival rate of 69.23% supports its judicious use in conjunction with prompt immunosuppression. Prospective studies are warranted to optimize ECMO initiation criteria, duration, and combination strategies with other circulatory support modalities.

Vascular inflammation is closely associated with the onset and progression of diseases, playing a pivotal role in the development of numerous acute and chronic conditions. The pathophysiological processes underlying vascular inflammation are highly complex, involving intricate cellular and molecular interactions. Recent scientific research suggests that epigenetics plays a significant role in vascular inflammation, offering new perspectives for deciphering its molecular mechanisms. Therefore, we review the role of epigenetics in vascular inflammation, explore its underlying mechanisms, and provide new insights for future clinical treatments.

Background Septic shock is characterized by dysregulation of the host response to infection Q5 which results in life-threatening organ dysfunction that can be partly attributed to immune alterations and endothelial dysfunction (endotheliopathy). This lethal condition is dynamic, complex, and heterogeneous. Aim Thus, an exploratory broad phenotypic and functional analysis of circulating immune cells and mediators were carried out to better understand the role of the immune system in a subgroup of septic shock patients with endotheliopathy defined by increased levels of soluble thrombomodulin (sTM). In this regard, especially the immune status of monocyte subtypes (classical, intermediate, and nonclassical) was investigated for surface thrombomodulin (TM), MHC class II molecules (HLADR, -DQ, and -DP) and immunomodulatory surface receptors (TREM-1, CD137, VISTA, HVEM and BTLA). Result and conclusion Our comprehensive immunophenotypic analysis on a septic shock cohort with endotheliopathy identified distinct immune perturbation patterns that potentially can lead to novel treatment avenues in the management of this life-threatening condition.

Introduction Tuberculosis (TB) rema\ins a major global health challenge. Mycobacterium avium ( M. avium ), a non-tuberculosis mycobacterium, causes pulmonary infections and can evade host immune surveillance by persisting within macrophages. MicroRNAs (miRNAs) are key regulators of host immunity; however, their roles in mycobacterial pathogenesis are not fully understood. This study investigated the role of miR-17-5p in macrophage-mediated immune responses during M. avium infection, with a focus on MAP3K2-mediated MAPK signaling. Methods Differentially expressed miRNAs were identified through small RNA sequencing of exosomes from M. avium -infected THP-1 macrophages. Candidate miRNAs were validated by RT-qPCR in THP-1 derived exosomes and serum samples from TB patients. MAP3K2 was evaluated as a miR-17-5p target using bioinformatics prediction, dual-luciferase reporter assays, and expression analysis. Effects on immune responses and MAPK signaling were assessed using qPCR, ELISA, Western blotting, ROS measurement, and CFU assays. Results miR-17-5p expression was significantly elevated in M. avium –infected macrophages, as well as in serum and peripheral blood mononuclear cells (PBMCs) from TB patients. Increased miR-17-5p suppressed MAP3K2 expression and attenuated MAPK signaling, reducing phosphorylation of ERK, JNK, and p38. This resulted in decreased production of inflammatory mediators (TNF-α, IL-6, IL-1β), reduced iNOS and ROS levels, and impaired bacterial clearance. Discussion miR-17-5p promotes M. avium survival by targeting MAP3K2 and suppressing MAPK-dependent immune functions in macrophages. These findings highlight miR-17-5p as a potential diagnostic biomarker and therapeutic target in TB and related mycobacterial infections.

Macrophages are key innate immune cells responsible for initiating and coordinating immune responses. A major determinant of macrophage function is their tissue-context-dependent polarization state, regulated by the cytokines present in the tissue microenvironment. Yet, the capability of characterizing macrophage polarization states in clinical studies remains limited. Here, we used a defined set of cytokines to polarize human PBMC-derived macrophages and determine their transcriptional signatures and stimulus responsiveness. The resultant atlas of transcriptional signatures for human macrophage polarization states was applied to a dataset of intestinal biopsies from Crohn’s disease patients and healthy controls. Our analysis identified a dominant population of IFNγ-polarized macrophages in areas of active Crohn’s intestinal inflammation and a loss of wound healing IL-4-, IL-10- and IL-13-polarized macrophages. This study demonstrates that in vitro datasets of macrophages in defined conditions can be leveraged to interpret the functionality of cells transcriptional profiled in clinical studies.

Background Skin cutaneous melanoma (SKCM) is extremely malignant, leading to poor prognosis. Epigenetic dysregulation, particularly histone modifications, contributes to disease progression. However, effective histone-based prognostic biomarkers are still lacking in clinical practice. Methods Transcriptomic data from TCGA-SKCM and five GEO datasets were analyzed. Ten machine learning algorithms were integrated to build 101 prognostic models. The optimal model, based on seven histone-related genes, showed the highest C-index and was validated in both training and validation cohorts. WDR77 was identified as the hub gene by random forest analysis. The expression of WDR77 was profiled in SKCM. Survival analysis, pathway enrichment analyses, single-cell and spatial transcriptomics were performed to investigate the role of WDR77 in SKCM. The therapeutic relevance of WDR77 was also investigated. In vitro experiments were conducted to validate the function of WDR77. Results WDR77, a histone methylation factor working with PRMT5, was identified as a key candidate. WDR77 was significantly upregulated in SKCM and correlated with poor clinical outcomes. Pathway analysis showed that WDR77 was primarily associated with cell-cycle dysregulation. CDC20, a cell cycle factor, emerged as a key co-expressed gene. Patients with concurrent high expression of WDR77 and CDC20 had the worst survival outcomes. WDR77 was predominantly expressed in malignant cells across pan-cancer datasets and positively correlated with CDC20. Spatial transcriptomics confirmed their co-localization and co-upregulation in tumor regions. Functional experiments demonstrated that WDR77 promotes proliferation, migration, and cell cycle progression. Overexpression of WDR77 also increased CDC20 protein levels. Conclusion WDR77 serves as both a prognostic biomarker and functional regulator in melanoma, highlighting its potential as a therapeutic target.

Background Severe COVID-19 is frequently associated with acute respiratory distress syndrome (ARDS) and prolonged pulmonary sequelae. Persistent immune activation, including dysregulated B cell responses and increased proinflammatory chemokines, has been linked to the post-acute sequelae of SARS-CoV-2 infection. However, the mechanisms linking these factors remain poorly defined. Methods Sixty patients were studied four months after acute COVID-19, including 34 who developed ARDS, 26 who did not develop ARDS, and 12 healthy controls. Clinical, computed tomography scan (CT), and diffusion capacity of the lungs for carbon monoxide (DLCOc) assessments were performed. Anti-SARS-CoV-2 IgM/IgG levels were quantified, circulating B cell subsets were characterized, and circulating cytokines and chemokines were measured. CXCR3 expression on B cells was analyzed by spectral flow cytometry. In vitro assays were performed to evaluate the effects of CXCL9 and CXCL10 on B cell activation, plasma cell differentiation, IgG production, and CD40L expression on CD4 + T cells. Associations between immunological markers and pulmonary sequelae were assessed. Results IgG, but not IgM, levels were significantly higher in patients with ARDS than in patients without ARDS. Both COVID-19 groups showed a reduction in CD19 + CD20 + B cells and an increase in plasmablasts compared to controls. Serum levels of CXCL9 and CXCL10, but not other cytokines, positively correlated with IgG levels. In vitro , CXCL9 increased CD86 expression on B cells, while both chemokines promoted plasma cell differentiation (CD27 + CD38 + , CD138 + ) and increased total IgG secretion. CXCL9 also increased the expression of CXCR3 and CD40L on activated CD4 + T cells. Clinically, patients with combined CT abnormalities and reduced DLCO had the highest levels of IgG, CXCL9, and CXCL10. Conclusion Four months after COVID-19, patients with prior ARDS and persistent pulmonary sequelae exhibit sustained elevations of anti-SARS-CoV-2 IgG and chemokines CXCL9 and CXCL10. Both chemokines directly enhance B cell differentiation into IgG-secreting plasma cells in vitro , while CXCL9 also increases CD4 + T cell help, suggesting a mechanistic link between chronic inflammation, increased humoral responses, and long-term lung impairment. Targeting CXCL9/CXCL10–CXCR3 signaling could offer therapeutic potential to mitigate post-COVID pulmonary complications.

Background Inflammatory responses that accompany the progression of type 1 (T1D) and type 2 diabetes mellitus (T2D) are fundamentally distinct in their underlying nature. T1D is predominantly driven by autoimmune-mediated inflammation, whereas T2D is characterized by a chronic, low-grade metabolic inflammation. A growing body of evidence has highlighted the involvement of natural killer (NK) cells in pathophysiology of both forms of diabetes; nevertheless, the precise mechanisms and the roles played by specific NK cell subsets remain incompletely understood. Methods Multicolor flow cytometry was used to identify several NK and innate-like T cell subpopulations in peripheral blood of patients with adult-onset T1D (n=23) and T2D (n=14) in comparison to healthy volunteers (n=24). Subset identification was based on expression of functional antigens (CD16 and CD56), co-receptors (CD8 and CD38), inhibitory receptors (NKG2A and CD161), and transcription factor EOMES. Quantitative analysis using Spearman’s rank correlation coefficients was performed to identify possible association between immune and clinical parameters and to rank the clinical parameters with respect to the number of connections with immune cell populations. Results T1D was accompanied by a reduction in overall NK cells and their dominant cytolytic CD56 dim CD16 bright subpopulation. Also a 50% increase in frequency of CD8+ NK cells was observed together with a growth of CD8+CD38+, CD8+CD161+, CD8+NKG2A+, and CD8+EOMES+ NK subsets. T2D was associated with a more than twofold decrease in the frequency of MAIT cell subset within CD8+ T cell population. Correlation analysis of the obtained data set revealed quantitative relationships between immune status parameters and clinical indicators, highlighting the involvement of NK cell subsets and innate-like T cells in shaping the phenotype of the pathological process and their complex role in regulating the immunopathogenesis of T1D and T2D. Conclusion In this pilot study, we provide evidence that different subpopulations of NK cells and innate-like T cells are involved in the immunopathogenesis of T1D and T2D, through a decline in the control of immune reactivity in T1D, while sustaining chronic metainflammatory responses in T2D. A critical elevation of CD8+ NK cells was associated with T1D, while loss of circulating MAIT cells was a hallmark of T2D.