Clinical And Experimental Medicine[JOURNAL]
Sun
200 papers
HSP90AA1 inhibits the Jun/Fos pathway to rescue hepatocytes from cuproptosis during ischemia-reperfusion injury.
Xu S, Liu Y, Han Y … +3 more , Ling M, Nie J, Pan L
Clin Exp Med · 2026 May · PMID 42113073 · Publisher ↗
Hepatic ischemia-reperfusion injury (HIRI), a frequent complication in procedures like hepatic lobectomy and organ transplantation, remains a significant clinical challenge despite advances in protective strategies. Cupr...
Hepatic ischemia-reperfusion injury (HIRI), a frequent complication in procedures like hepatic lobectomy and organ transplantation, remains a significant clinical challenge despite advances in protective strategies. Cuproptosis, a copper-dependent form of cell death, has recently been linked to various inflammatory diseases, including HIRI. In this study, bioinformatic analyses were employed to identify differentially expressed core genes, and animal and cellular models of HIRI were established using C57BL/6 mice and AML12 cells to investigate the roles of HSP90AA1 and c-Jun/c-Fos-mediated cuproptosis in HIRI. Techniques including RT-qPCR, Western blotting, immunohistochemistry, immunofluorescence, and electron microscopy were used to assess cuproptosis, inflammation, and mitochondrial damage. Bioinformatic results indicated that HSP90AA1 and the Jun/Fos pathway are likely key targets in HIRI. Notably, increased cuproptosis and elevated HSP90AA1 expression in hepatocytes were observed both in vivo and in vitro following HIRI. Furthermore, HSP90AA1 overexpression significantly attenuated I/R-induced liver injury and cuproptosis by suppressing the Jun/Fos pathway. These findings reveal, for the first time, that HSP90AA1 can mitigate cuproptosis induced by HIRI via regulation of the Jun/Fos pathway, suggesting a potential novel therapeutic approach for HIRI.
FDX1 as a predictive biomarker and therapeutic target for lymph node metastasis in gastric cancer.
Zhang T, Liu J, Duan P … +8 more , Li Z, Huang Z, Zhao Z, Cheng Y, Liang Z, Chen J, Cai M, Ma J
Clin Exp Med · 2026 May · PMID 42107026 · Full text
The prognostic values of cuproptosis-related genes (CRGs) in gastric cancer with lymph node metastasis (GCLM), especially in the tumor immune microenvironment (TIME), remain unclear. We analyzed the expression, mutation,...
The prognostic values of cuproptosis-related genes (CRGs) in gastric cancer with lymph node metastasis (GCLM), especially in the tumor immune microenvironment (TIME), remain unclear. We analyzed the expression, mutation, immunity, drug sensitivity, and prognostic value of CRGs in GCLM using TCGA and GEO cohorts. Consensus clustering was performed to identify CRG subtypes, with differences characterized by multi-omics analysis. A CRG-based prognostic risk score and immune score were constructed for individualized assessment, and the role of CRGs was validated through in vitro and in vivo experiments. Consensus clustering revealed that CRGs were significantly enriched in biological processes related to mitosis and energy metabolism, as well as in immune-related and cancer-associated pathways. Four distinct CRG subtypes were identified, showing marked differences in expression profiles, prognosis, genetic alterations, TIME, and chemotherapeutic drug sensitivity. We developed an exploratory CRG-based prognostic risk score for preliminary individualized assessment, and the functional relevance of CRGs in GCLM was further validated through in vitro experiments. Among these, FDX1, LIAS, DLAT, MTF1, and GLS were identified as key determinants of overall survival in patients with GCLM, with FDX1 emerging as a potential independent prognostic factor. Notably, upregulation of FDX1 significantly suppressed lymph node metastasis of gastric cancer cells in a mouse popliteal lymph node metastasis model. Our data uncovers FDX1 might be a potential favorable prognostic factors in GCLM patients. These findings may improve our understanding of CRGs in GCLM and provide new in-sights for assessing prognosis and developing more effective treatment strategies.
Circ-ABCA1 promotes breast cancer stem cell-mediated malignant progression by modulating miR-33a-5p/EIF4A3 axis.
Wang B, Guo X, Sui Y
Clin Exp Med · 2026 May · PMID 42105164 · Full text
To explore new circRNA and underlying mechanisms through which they regulate breast cancer progression. In this study, high-throughput sequencing were used to reveal the different expression of circRNA among breast cance...
To explore new circRNA and underlying mechanisms through which they regulate breast cancer progression. In this study, high-throughput sequencing were used to reveal the different expression of circRNA among breast cancer tissues and para-carcinoma tissue. Fluorescence in situ hybridization (FISH) were used to analysis the expression and subcellular localization of circ-ABCA1 in both breast cancer tissues and cells line. The regulatory mechanism and targets were then investigated utilizing bioinformatics analyses, luciferase reporter assay, transwell migration, CCK8, and EdU analysis. The in vivo experiments was used to elucidate the roles of circ-ABCA1 in breast cancer tumor metastasis and growth. The result show that circ-ABCA1 expression was increased in both breast cancer tissues and cells line. Downregulation circ-ABCA1 inhibit cells proliferation and tumor growth. Luciferase report analysis confirmed both miR-33a-5p and EIF4A3 were the downstream target of circ-ABCA1. Overexpression of EIF4A3 or inhibit miR-33a-5p restored breast cancer cells proliferaion, migration and breast cancer cells stemness ability after silence circ-ABCA1. Overexpression of EIF4A3 restored breast cancer proliferaion, migration and breast cancer cells stemness ability after expression miR-33a-5p. Taken together, our study confirmed that circ-ABCA1 promotes breast cancer stem cell-mediated malignant progression by modulating miR-33a-5p/EIF4A3 axis.
Advances in Cell Therapy for Chronic Graft-versus-Host Disease: Prophylactic and Therapeutic Perspectives.
Taghinejad Z, Moradi N, Talebi A … +3 more , Jafari L, Soleimanzadeh H, Hamidieh AA
Clin Exp Med · 2026 May · PMID 42084784 · Publisher ↗
Chronic graft-versus-host disease (cGvHD) can affect about 70% of people who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). This condition is characterized by a complex immune dysregulation that...
Chronic graft-versus-host disease (cGvHD) can affect about 70% of people who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). This condition is characterized by a complex immune dysregulation that leads to persistent inflammation and fibrosis. These complications can lead to long-term health issues that significantly affect the quality of life after HSCT. Conventional therapies such as corticosteroids and broad immunosuppressants are partially effective and have significant toxicity. They also fail to reverse established fibrotic damage. Advances in targeted pharmacological agents, including Bruton's tyrosine kinase inhibitors and JAK inhibitors, show improved outcomes for steroid-refractory cGvHD. However, their high costs and variable responses highlight the unmet need for more effective approaches. Cell-based therapies have emerged as promising strategies to modulate pathogenic immune responses and prevent or even treat cGvHD. Mesenchymal stromal cells (MSCs), regulatory T cells (Tregs), natural killer (NK) cells, and chimeric antigen receptor (CAR) T cells are being investigated for their immunoregulatory potential in preclinical and clinical trials, and they are considered a safer, more effective, and targeted approach to managing cGvHD. MSC-derived cytokines and exosomes can suppress Th17 cells and promote the generation of IL-10-expressing Tregs. This dual action helps reduce inflammation and tissue fibrosis associated with the cGvHD. Tregs and NK cells also help rebalance immune responses and suppress alloreactivity through different mechanisms. This review highlights underlying mechanisms, clinical efficacy, and challenges in translating these therapies into routine clinical practice. Additionally, it suggests that future trials should incorporate patient stratification based on cGvHD phases and phase-relevant biomarkers for managing disease progression more precisely.
Dynamic changes in gut microbiota and discovery of prognostic biomarkers in locally advanced pancreatic cancer during chemoradiotherapy.
Wang H, Wang F, Guo Q … +6 more , Zou B, Li P, Xu X, He J, Jiang S, Yue J
Clin Exp Med · 2026 May · PMID 42071032 · Full text
Pancreatic cancer has an exceptionally poor prognosis, with the majority of cases diagnosed at an advanced stage. Concurrent chemoradiotherapy (CCRT) remains the standard of care for locally advanced pancreatic cancer (L...
Pancreatic cancer has an exceptionally poor prognosis, with the majority of cases diagnosed at an advanced stage. Concurrent chemoradiotherapy (CCRT) remains the standard of care for locally advanced pancreatic cancer (LAPC); however, its therapeutic efficacy is limited. Emerging evidence suggests that the gut microbiota is an important modulator of cancer progression and treatment response. Nevertheless, the dynamic changes in the gut microbial ecosystem in LAPC patients undergoing CCRT remain poorly understood. This study aimed to characterize longitudinal alterations in the gut microbiota during CCRT, identify candidate microbiome-based prognostic markers, and explore their potential associations with host responses. This longitudinal study included 16 patients with LAPC. Fecal and peripheral blood samples were collected at three predefined time points: before CCRT initiation, during CCRT, and after CCRT completion. Gut microbiota composition and community structure were analyzed using 16 S rRNA sequencing targeting the V3–V4 region. Bioinformatic analyses were performed to assess taxonomic distribution, alpha and beta diversity, and microbial co-occurrence patterns. The prognostic relevance of microbial features was further evaluated using machine learning models integrating clinical parameters to predict overall survival. CCRT was associated with dynamic changes in specific microbial taxa across multiple taxonomic levels, with marked inter-individual heterogeneity in microbiota responses. In addition, microbial co-occurrence network complexity was reduced during treatment. Certain microbial taxa during CCRT showed associations with tumor-related serum biomarkers. Using integrated machine learning models, we identified candidate microbiota-based prognostic markers. In particular, Bifidobacterium and Bacteroides were associated with survival prediction, achieving areas under the receiver operating characteristic curve (AUC) of 0.833 and 0.722, respectively. CCRT is associated with longitudinal alterations in the gut microbiome of patients with LAPC, involving both compositional and structural changes. These findings suggest that microbiome dynamics may have potential value as exploratory prognostic indicators. However, given the limited sample size and observational design, further validation in larger cohorts and mechanistic studies are required before clinical application.
Signal Transduction and Transcription Activator 1 in Pan-Cancer: Prognostic and Immunological Value.
Wang Y, Zhang Y, Wang F … +4 more , Tang L, Xiao X, Zhao H, Sheng Q
Clin Exp Med · 2026 Apr · PMID 42053628 · Publisher ↗
STAT1, a key mediator of cellular responses to interferons and cytokines, has not been comprehensively analyzed in pan-cancer studies regarding its role in tumor biology. This study investigated STAT1 expression, its pro...
STAT1, a key mediator of cellular responses to interferons and cytokines, has not been comprehensively analyzed in pan-cancer studies regarding its role in tumor biology. This study investigated STAT1 expression, its prognostic value, and its correlation with immune status in various types of cancer. We analyzed STAT1 expression, methylation, genomic alterations, survival, immune cell infiltration, and functional pathways using the TCGA, GTEx, GEO, TIMER, CCLE, and The Human Protein Atlas (HPA) databases. STAT1 expression was significantly higher in tumor tissues than in normal tissues and correlated with poorer overall survival. It was associated with the infiltration of B cells, CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells. Enrichment analysis linked STAT1 to cancer-related pathways, cytokine-receptor interactions, and toll-like receptor signaling. Elevated STAT1 expression is associated with poor prognosis and immune infiltration, suggesting its potential as a biomarker and therapeutic target for cancer.
Innovations in biomarker stratification for precision oncology.
Naeemaee R, Harris K, Cross N … +2 more , Griffin J, Quayle LA
Clin Exp Med · 2026 Apr · PMID 42047885 · Full text
Biomarker stratification underpins precision oncology, yet survival analysis often relies on arbitrary thresholds that undermine reproducibility and clinical relevance, particularly for continuous biomarkers. This review...
Biomarker stratification underpins precision oncology, yet survival analysis often relies on arbitrary thresholds that undermine reproducibility and clinical relevance, particularly for continuous biomarkers. This review focuses on methodological approaches for stratifying continuous biomarkers within survival analysis frameworks, examining conventional strategies alongside data-driven and machine learning methods in the context of threshold selection and clinical interpretability. We evaluate the extent to which these approaches address key challenges including heterogeneity, confounding, and overfitting, and critically appraise their strengths and limitations for clinically actionable risk stratification. By synthesising current evidence, we highlight opportunities for more robust and reproducible prognostic modelling and outline future directions to improve the reliability of biomarker-driven decision-making in oncology.
Comorbidities in lipedema: toward a systemic perspective - a narrative review.
Fiengo E, Sbarbati A
Clin Exp Med · 2026 Apr · PMID 42047836 · Full text
Lipedema has historically been classified within obesity- and lymphedema-related frameworks, despite its distinct clinical features and frequent occurrence in individuals with normal or low body mass index. This narrativ...
Lipedema has historically been classified within obesity- and lymphedema-related frameworks, despite its distinct clinical features and frequent occurrence in individuals with normal or low body mass index. This narrative review examines whether the distribution of associated conditions reported in clinical cohorts is more consistent with a localized adipose-centered model or may suggest broader systemic involvement. Recent clinical and epidemiological studies have reported a clustering of manifestations affecting multiple biological domains in patients with lipedema, including connective tissue laxity and hypermobility, chronic venous disease, thyroid dysfunction and autoimmunity, endocrine–gynecological alterations, vitamin D deficiency, gastrointestinal disturbances, chronic widespread pain, and neuropsychological burden. Histopathological and microvascular investigations have also described alterations in extracellular matrix organization, stromal components, and endothelial structures within affected tissues. However, much of the available evidence derives from observational, cross-sectional, or survey-based studies, and potential confounding factors such as referral bias, obesity, and healthcare-seeking behavior should be considered when interpreting these associations. Taken together, these observations raise the possibility that lipedema may involve biological processes extending beyond adipose tissue alone. While current evidence does not yet establish a unified mechanism, the recurrent co-occurrence of connective, vascular, endocrine, and systemic features across multiple cohorts may be compatible with a broader vulnerability affecting connective tissue integrity and stromal microenvironment regulation. A multisystem perspective may therefore provide a useful conceptual framework for interpreting the clinical heterogeneity of lipedema and for guiding future mechanistic and longitudinal studies.
Reducing false positives in breast cancer screening with computer-aided detection.
Wan T, Sang X, Wu Z … +3 more , Li L, Liu N, Yi H
Clin Exp Med · 2026 Apr · PMID 42045696 · Full text
The development of an advanced computer-aided detection (CAD) system for breast cancer detection is essential to improving diagnostic accuracy and reducing unnecessary interventions. This study introduces a multi-dimensi...
The development of an advanced computer-aided detection (CAD) system for breast cancer detection is essential to improving diagnostic accuracy and reducing unnecessary interventions. This study introduces a multi-dimensional CAD system that combines Mask R-CNN, dual-view mammography (CC/MLO), and nipple localization techniques to enhance the detection of breast tumors while minimizing false positive rates (FPR). A retrospective study involving 226 mammograms from 113 patients with 234 pathologically confirmed tumors was performed. Image preprocessing included DICOM-to-PNG conversion, orientation correction, and background removal, followed by Mask R-CNN processing. The system incorporated dual-view spatial consistency checks to align views from CC and MLO projections, nipple localization using Sauvola thresholding and Laplacian filtering, and optimization of the tumor-to-nipple distance for improved accuracy. Evaluation metrics (precision, recall, F1-score, FPR, FNR) were analyzed, and statistical significance was assessed using chi-square tests. The results showed a significant 87.3% reduction in FPR (8.26% vs. 38.46%, p < 0.001) and an increase in precision (91.74% vs. 61.54%). The recall slightly decreased, but the F1-score showed a balanced improvement. These findings demonstrate the potential of this advanced CAD system to support high-specificity breast cancer screening and improve clinical decision-making.
A genomic and transcriptomic integration study of CCL19-driven macrophage-immune crosstalk in chronic hepatitis B.
Pan T, Yang L, Liu J
Clin Exp Med · 2026 Apr · PMID 42033468 · Full text
Chronic hepatitis B (CHB) progression features stage-dependent immune dysfunction, transitioning from high viremia in immune-tolerant phases to persistent liver injury during immune activity. While inflammatory mediators...
Chronic hepatitis B (CHB) progression features stage-dependent immune dysfunction, transitioning from high viremia in immune-tolerant phases to persistent liver injury during immune activity. While inflammatory mediators facilitate hepatitis B virus (HBV) persistence and hepatocyte damage, their causal orchestration remains undefined. This multi-omics investigation systematically identifies inflammation-related therapeutic targets through causal inference analysis of CHB pathogenesis. We conducted two-sample Mendelian randomization (TSMR) analysis to investigate causal associations with circulatory inflammatory mediators. Subsequent integrative multi-omics investigations incorporated single-cell transcriptomic profiling (GSE186343 and GSE182159) and bulk tissue sequencing data (GSE65359 and GSE83148). Single-cell data processing involved Seurat pipelines with Harmony batch correction. Transcriptomic alterations were systematically characterized using limma-based differential analysis coupled with CIBERSORT-mediated immune composition deconvolution. Molecular networks were established through pySCENIC transcriptional regulation modeling, cellular differentiation patterns were resolved via Monocle2 trajectory inference, and ligand-receptor dynamics were examined using CellChat/NicheNet frameworks. Therapeutic compound identification was achieved through computational screening of CMAP pharmacogenomic signatures. This investigation applied TSMR to pinpoint CCL19 as a principal mediator among 91 circulatory inflammatory proteins exhibiting causal positivity in CHB pathogenesis. Mechanistic multi-omics integration delineated its immunomodulatory pathways. Genomic epidemiology demonstrated that heightened circulating CCL19 concentrations substantially elevate hepatitis B viral susceptibility. Single-cell resolution profiling revealed CCL19 spatial enrichment specifically within antigen-presenting macrophage clusters (M4 phenotype) in CHB hepatic microenvironments. Functional coordination was observed with pro-inflammatory cytotoxic macrophage populations (M3 phenotype) through IFNG and HLA signaling crosstalk, simultaneously potentiating antiviral defense mechanisms and inflammatory tissue damage. Subsequently, we postulated a transcriptional regulatory cascade involving RB1, MEF2A, and SEMA4A that may control CCL19 expression. The investigation demonstrated a dysregulation in the balance of macrophage and T cell subsets among CHB patients, while pinpointing CCL19 as a critical macrophage-derived biomarker. This chemokine’s upregulated expression may exhibit significant correlations with amplified chemotactic signaling and engagement of the antigen processing/presentation cascade.
The SUMO specific peptidase SENP3 promotes papillary thyroid cancer progression by deSUMOylation of SETDB1 and regulating GLI2 transcription.
Wang Z, Yang Z, Chen Y … +4 more , Zhao X, Gao D, Wang N, Williams A
Clin Exp Med · 2026 Apr · PMID 42026393 · Full text
SUMO-specific protease 3 (SENP3) was reported to be dysregulated in osteosarcoma and ovarian cancer. However, the role of SENP3 in carcinogenesis of papillary thyroid cancer (PTC) has not been defined. Herein, we found t...
SUMO-specific protease 3 (SENP3) was reported to be dysregulated in osteosarcoma and ovarian cancer. However, the role of SENP3 in carcinogenesis of papillary thyroid cancer (PTC) has not been defined. Herein, we found that the expression of SENP3 protein was upregulated in PTC tissues and cell lines. Then, a PTC cell line, K-1 cells were transfected with SENP3 overexpression plasmid (pcDNA-SENP3) or small interfering RNA targeting SENP3 (SENP3 siRNA). We found that SENP3 overexpression facilitated cell proliferation and invasion, induced cell cycle arrest at G0/G1 phase and inhibited apoptosis in PTC cells, whereas SENP3 knockdown showed the opposite results. We further found that SET domain bifurcated 1 (SETDB1) can be regulated by SENP3-dependent deSUMOylation. Furthermore, SUMOylation of SETDB1 promoted SETDB1 to form a complex with MBD1-containing chromatin-associated factor 1 (MCAF1), and in turn to occupy the promoter locus of GLI family zinc finger 2 (GLI2) gene to suppress GLI2 expression through trimethylation of histone H3 Lys9 (H3K9me3). Then rescue experiments showed that GLI2 overexpression reversed the effects of SENP3 silencing on K-1 cell functions. The PI3K/AKT pathway inhibitor XL147 suppressed the effects of SENP3 overexpression on K-1 cell behaviors. Additionally, SENP3 knockdown significantly inhibited the xenograft tumor growth of PTC in vivo. This study revealed that SENP3 promoted PTC progression in vitro and in vivo by deSUMOylating SETDB1, thereby relieving SETDB1-mediated repression of GLI2 H3K9 trimethylation, which may provide a potential therapeutic target for PTC.
Simvastatin in liver diseases: therapeutic value and research advances.
Zhang H, Xu L, Cui Y … +2 more , Gou W, Li J
Clin Exp Med · 2026 Apr · PMID 42002701 · Full text
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Hepatogenous diabetes in the era of precision medicine: diagnosis, management, and future directions.
El-Azab G, Rady MA, Assem M … +1 more , Nagdy H
Clin Exp Med · 2026 Apr · PMID 42001361 · Full text
Hepatogenous diabetes (HD) is a distinct clinical entity that arises as a direct consequence of chronic liver disease, particularly cirrhosis. The complex interplay between hepatic dysfunction and glucose metabolism give...
Hepatogenous diabetes (HD) is a distinct clinical entity that arises as a direct consequence of chronic liver disease, particularly cirrhosis. The complex interplay between hepatic dysfunction and glucose metabolism gives rise to unique pathophysiological mechanisms, including severe hepatic insulin resistance, pancreatic β-cell dysfunction, chronic inflammation, oxidative stress, and alterations in gut microbiota. HD is frequently underdiagnosed due to the limitations of traditional diagnostic criteria, as patients often exhibit normal fasting glucose and HbA1c levels despite significant postprandial hyperglycemia. The oral glucose tolerance test is more sensitive for detecting HD in this population. HD differs from type 2 diabetes mellitus in its temporal relationship with liver disease, absence of classic metabolic risk factors, greater glycemic variability, and a lower prevalence of microvascular complications. The prevalence of HD increases with the severity of liver dysfunction and varies according to the underlying etiology, with the highest rates observed in metabolic-associated fatty liver disease and hemochromatosis. HD is associated with accelerated liver fibrosis, increased risk of hepatocellular carcinoma, higher rates of hepatic decompensation, and increased mortality. Management strategies require careful consideration of the altered pharmacokinetics and increased risk of hypoglycemia in advanced liver disease. Individualized management strategies, including risk stratification and targeted therapies, hold promise for improving outcomes. This review synthesizes current knowledge on the epidemiology, pathophysiology, clinical implications, diagnosis, and management of HD, and highlights areas for future research to enhance recognition and treatment of this important but often overlooked complication of chronic liver disease.
Leukemia during pregnancy and survivorship: gestational age-stratified multidisciplinary management framework.
Zhang N, Jiang Y, Li X … +5 more , Fu W, Gao Z, He H, Zhang X, Gao B
Clin Exp Med · 2026 Apr · PMID 42001344 · Publisher ↗
To synthesize contemporary evidence on the epidemiology, management, and maternal–fetal outcomes of leukemia during pregnancy and survivorship, and to propose a gestational age–stratified multidisciplinary care pathway....
To synthesize contemporary evidence on the epidemiology, management, and maternal–fetal outcomes of leukemia during pregnancy and survivorship, and to propose a gestational age–stratified multidisciplinary care pathway. We performed a structured narrative review informed by a systematic search of PubMed, Embase, and Scopus (1 January 2000–30 November 2025), supplemented by citation snowballing. Evidence was prioritized toward multicenter cohorts/registries and international consensus guidance; case reports were used selectively to inform rare, high-stakes decision points. No quantitative meta-analysis was undertaken. Clinical decision-making is chiefly driven by gestational age and the immediacy of disease control. In acute leukemia, timely induction is often required to preserve maternal prognosis. First-trimester diagnoses pose the greatest teratogenic risk; when standard induction cannot be deferred, termination is commonly recommended, whereas pregnancy continuation typically involves intensive counseling and postponement of induction until organogenesis is complete. In the second and third trimesters, anthracycline/cytarabine-based regimens are frequently feasible with obstetric timing adaptations; chemotherapy should be avoided within approximately 3 weeks of delivery, which is ideally planned during hematologic recovery. Acute promyelocytic leukemia requires urgent coagulopathy management; all-trans retinoic acid is a cornerstone after the first trimester, while arsenic trioxide is generally deferred when feasible. For chronic myeloid leukemia, sustained deep molecular response enabling treatment-free remission is preferred preconception; during pregnancy, interferon-α and/or leukapheresis are typical bridging strategies, with cautious consideration of imatinib after organogenesis if response is lost, whereas dasatinib and later-generation TKIs should be avoided. Among survivors, pregnancy is often achievable but warrants preconception risk assessment and high-risk surveillance for cardiomyopathy, venous thromboembolism, and placental dysfunction/fetal growth restriction. A gestational age–stratified, MDT-led pathway aligning leukemia therapy with obstetric timing may preserve maternal curative intent while reducing fetal and neonatal risks. Progress will depend on global registries and long-term offspring follow-up, particularly after in utero TKI exposure.
Identification of key programmed cell death genes-necroptosis-related genes in systemic lupus erythematosus.
Wang L, Li Y, Liu X … +8 more , Song S, Han Y, Mo L, Li H, Wang X, Pan Y, Sun J, Wang J
Clin Exp Med · 2026 Apr · PMID 42001335 · Full text
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with challenging early diagnosis. Aberrant programmed cell death (PCD) is critical in SLE pathogenesis. This study aimed to identify key PCD genes...
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with challenging early diagnosis. Aberrant programmed cell death (PCD) is critical in SLE pathogenesis. This study aimed to identify key PCD genes for SLE diagnosis and disease activity assessment. Integrated bioinformatics analysis was conducted on three whole-blood transcriptomic datasets (GSE65391, GSE110174, GSE154851) from GEO. Machine learning algorithms (LASSO, SVM-RFE) identified hub genes across 18 PCD types. ssGSEA and logistic regression determined the predominant PCD pathway. Immune infiltration and correlation analyses evaluated clinical relevance. Necroptosis was identified as the most discriminative PCD pathway (AUC = 0.950, 95% CI: 0.921–0.979). Seven necroptosis-related genes (STAT1, STAT2, ZBP1, CASP1, TNFSF10, RIPK3, IL1B) were validated as key diagnostic biomarkers. A multivariate logistic regression model demonstrated robust performance across training and external validation cohorts, confirmed by internal validation (20 SLE patients and 16 healthy controls). The seven genes correlated significantly with dysregulated immune cells and were positively associated with SLEDAI, dsDNA levels, and neutrophil percentages. Necroptosis is a critical PCD pathway in SLE. The seven necroptosis-related genes represent promising diagnostic biomarkers and therapeutic targets.
Exploring the applicability, combined strategies, and challenges of ablation in hematology based on its characteristics and immunomodulatory mechanisms.
Wu M, Fu J, Sun R … +4 more , Yu M, Xia M, Yang Y, Cui X
Clin Exp Med · 2026 Apr · PMID 41973089 · Full text
Malignant hematological diseases, such as lymphoma, leukemia, and multiple myeloma, are frequently accompanied by clinical challenges including local progressive lesions, relapsed/refractory conditions, and poor toleranc...
Malignant hematological diseases, such as lymphoma, leukemia, and multiple myeloma, are frequently accompanied by clinical challenges including local progressive lesions, relapsed/refractory conditions, and poor tolerance to standard treatments in special populations. Systemic therapies represented by chemotherapy and targeted therapy have inherent limitations in addressing local tumor burden, relieving organ compression, and being suitable for frail patients. As a minimally invasive local treatment technology, ablation has been widely used in solid tumor therapy due to its advantages of precise targeting, controllable tissue damage, and potential immune activation. However, its application in hematological diseases remains scattered and lacks systematic integration. This review focuses on three mainstream ablation technologies—radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation (CA)—systematically elaborating their core mechanisms, technical advancements, and clinical applications in hematological diseases. We analyze the clinical value of ablation in reducing tumor burden, relieving symptoms, adapting to special populations, intervening in myeloma bone disease, and treating aspergilloma. Additionally, we clarify the indications and contraindications of ablation in hematological diseases. We also discuss in depth the current challenges, including insufficient evidence, technical application boundaries, and limited immunomodulatory effects. Finally, we explore the future development directions of ablation technology in this field from the aspects of clinical evidence construction, treatment strategy optimization—such as combinations with immunotherapy and nanomedicine—and technical popularization and standardization. This review aims to provide a comprehensive theoretical basis and practical reference for the clinical application and in-depth research of ablation technology in hematological diseases.
A gene interaction network-based molecular taxonomy of dilated cardiomyopathy highlighting immune and inflammatory heterogeneity.
Zheng Y, Wan F, Ma S … +6 more , Chen H, Wang L, Deng Y, Zhang G, Song L, Zhang M
Clin Exp Med · 2026 Apr · PMID 41945162 · Publisher ↗
Dilated cardiomyopathy (DCM) is a highly heterogeneous disease, complicating mechanistic understanding and limiting effective patient stratification. To capture this complexity, a gene interaction network-based taxonomy...
Dilated cardiomyopathy (DCM) is a highly heterogeneous disease, complicating mechanistic understanding and limiting effective patient stratification. To capture this complexity, a gene interaction network-based taxonomy was developed. A total of 245 DCM samples and 174 controls from four cohorts were included. Gene–gene interactions were quantified for each sample to build interaction networks based on transcriptomic data and Reactome database, and representative interactions were used for consensus clustering to identify subtypes. Subtype stability was assessed with Uniform Manifold Approximation and Projection (UMAP), silhouette, and nearest-template prediction. Weighted gene co-expression network analysis (WGCNA), enrichment analysis, and immune-infiltration profiling were applied to characterize subtype heterogeneity. An immunoadsorption-treated cohort was used to predict therapeutic responsiveness. Finally, subtype-specific differentially expressed genes (DEGs) were validated by qPCR in an Angiotensin II–stimulated cardiomyocyte model. Three reproducible DCM subtypes were consistently identified, with EPS1 comprising 43.2–52.5% of patients, EPS2 40.0–44.2%, and EPS3 7.5–13.5%. These subtypes exhibited distinct molecular characteristics, reflecting heterogeneous biological states. Edge-perturbation subtype 1 (EPS1) showed mitochondrial/TCA-cycle and proteostasis dysregulation and corresponded to responders to immunoadsorption with IgG substitution (IA/IgG). EPS2 was characterized by enrichment of humoral immune and platelet activation pathways, accompanied by broad immune cell infiltration. EPS3 displayed abnormalities in respiratory chain and endocytosis, together with cytotoxic and T follicular helper (Tfh) cell–associated signals. qPCR analysis in Angiotensin II–treated cardiomyocytes validated the subtype-specific genes, further supporting subtype stability. This gene interaction network–based taxonomy identifies distinct DCM subtypes with differential therapeutic responsiveness, particularly highlighting that EPS1 patients may benefit from IA/IgG therapy. The classification reveals immune and inflammatory heterogeneity that can guide personalized treatment strategies and improve patient stratification in DCM management.
Bidirectional interplay between gut and liver in inflammatory bowel disease and hepatobiliary conditions.
Abdulla A, Sheikhnoor AM, Ferrao K … +2 more , Stiles LI, Mehta KJ
Clin Exp Med · 2026 Apr · PMID 41944905 · Full text
Inflammatory bowel disease (IBD) can affect extraintestinal organs, including the liver. The bidirectional relationship between the gut and liver underpins the interplay between IBD and liver pathologies; both are predic...
Inflammatory bowel disease (IBD) can affect extraintestinal organs, including the liver. The bidirectional relationship between the gut and liver underpins the interplay between IBD and liver pathologies; both are predicted to rise. This review discusses the anatomical-physiological context of the gut-liver axis, the influence of IBD on the liver and vice versa, and hepatobiliary conditions co-existing with IBD, namely, MASLD, ARLD, PSC and gallstones. About 70% of the liver’s blood supply comes from the gut via the portal vein, which carries both nutrients and gut-derived microbial products, as regulated by the intestinal barrier. IBD is associated with gut dysbiosis and compromised intestinal barrier integrity (both exacerbated by alcohol consumption, an IBD risk factor), allowing microbial translocation to the liver, which triggers hepatic inflammation/injury. This exacerbates pre-existing liver disease or increases its risk; for example, IBD increases MASLD risk. However, translocated lipopolysaccharides may alleviate cholestatic liver injury, enabling IBD to ameliorate PSC. In turn, PSC can promote a favourable gut microbiota profile to alleviate IBD. The liver maintains gut homeostasis/microbiota through bile acid secretion. Disrupted bile acid secretion in gallstones increases IBD risk, while disrupted bile acid reabsorption in IBD increases gallstone risk. Disrupted bile acid metabolism and an abnormal gut microbiota in MASLD may exacerbate the IBD course. For co-existing IBD-hepatobiliary pathology, management strategies are unestablished, and adverse effects of IBD therapeutics on hepatobiliary pathologies are observed (and vice versa). This review facilitates a structured understanding of the pathophysiological connections and may inform/improve the current management of coexisting IBD-hepatobiliary conditions.
The neutrophil-percentage-to-albumin ratio (NPAR) shows a nonlinear correlation with all-cause mortality in patients with anemia.
Peng A, Li J, Huang J … +3 more , Yang Y, Jiang Y, Huang D
Clin Exp Med · 2026 Apr · PMID 41940982 · Publisher ↗
The neutrophil percentage-to-albumin ratio (NPAR) is an emerging indicator of inflammation that has been associated with the prognosis of various diseases, including hypertension, diabetes, and cardiovascular disease. NP...
The neutrophil percentage-to-albumin ratio (NPAR) is an emerging indicator of inflammation that has been associated with the prognosis of various diseases, including hypertension, diabetes, and cardiovascular disease. NPAR is calculated by multiplying the neutrophil percentage by 100 and dividing it by the albumin value. This study aimed to evaluate the predictive value of NPAR for all-cause mortality in anemic patients. We employed Kaplan–Meier analysis, multiple regression models, restricted cubic splines (RCS), and threshold effect analysis to explore these associations. This study included 3,258 anemic individuals. The relationship between NPAR and all-cause mortality was evaluated using Kaplan–Meier analysis and multiple regression models. RCS curves were employed to assess potential nonlinear relationships, while threshold effect analysis was used to identify breakpoints in the association between NPAR and mortality risk. Subgroup analyses were conducted to examine variations in this relationship across different population strata. The study population included 3,258 anemic patients, with a mean follow-up period of 94.3 months. During follow-up, 904 participants (27.75%) died. Kaplan–Meier analysis revealed that individuals in the highest NPAR quartile (Q4) exhibited significantly higher cumulative mortality compared with those in the lowest quartile (Q1) (p < 0.001). Multiple regression analysis showed that, in model 3, each unit increase in NPAR among individuals in the highest quartile was associated with a 51.8% increased risk of all-cause mortality. RCS and threshold effect analyses revealed a nonlinear relationship between NPAR and mortality, with a breakpoint at NPAR = 15.119. Below this threshold, no statistical association was observed, while above the threshold, NPAR was positively associated with increased mortality risk. Subgroup analysis revealed a significant positive correlation between anemia in individuals under 60 years of age, with diabetes mellitus and a body mass index ≥ 30 kg/m², and all-cause mortality. Our findings indicate that elevated NPAR is independently associated with increased all-cause mortality in anemic individuals. The nonlinear relationship and identified breakpoint suggest that NPAR may serve as a valuable prognostic biomarker for mortality risk in this population. Further research should focus on the clinical utility of NPAR in guiding therapeutic interventions for anemia.
A DLBCL Prognostic model superior to the IPI score: Mechanistic study and clinical validation based on RFC2- and RFC4-mediated DNA damage repair.
Wang S, Liu Y, Zang H … +9 more , Guo L, Du W, Song J, Wang F, Lu L, Li Q, Shi Y, Chen T, Gu W
Clin Exp Med · 2026 Apr · PMID 41934523 · Full text
Approximately 30% to 40% of patients with Diffuse Large B-cell Lymphoma (DLBCL) experience treatment failure, whereas the current International Prognostic Index (IPI) fails to adequately reflect the intrinsic biological...
Approximately 30% to 40% of patients with Diffuse Large B-cell Lymphoma (DLBCL) experience treatment failure, whereas the current International Prognostic Index (IPI) fails to adequately reflect the intrinsic biological features. This study aimed to investigate the prognostic value of Replication Factor C genes (RFCs) in DLBCL and construct a prognostic risk model. Three DLBCL datasets were downloaded from the Gene Expression Omnibus (GEO) database (GSE181063, GSE10846, GSE31312). Multivariate Cox proportional hazards regression analysis identified high expression of RFC2 and RFC4 as independent adverse prognostic factors (RFC2: HR = 1.46, P = 0.037; RFC4: HR = 1.36, P = 0.034), which were significantly associated with age ≥ 60 years, elevated lactate dehydrogenase (LDH) levels, and poor Eastern Cooperative Oncology Group (ECOG) performance status. Mechanistically, the RFC2 high-expression group exhibited a significant increase in tumor mutational burden (TMB). Protein-protein interaction (PPI) analysis revealed that RFC2 and RFC4 interact with CHTF18, PCNA, and other proteins to maintain genomic stability. Gene set enrichment analysis (GSEA) indicated that RFC2 and RFC4 high-expression groups were enriched in the DNA replication and DNA damage repair (DDR) pathways. Competing endogenous RNA (ceRNA) network analysis predicted miR-34a-5p as an upstream regulator; PARD6G-AS1, TERC, and LINC00662 upregulating RFC2 and RFC4 by sponging miR-34a-5p. The RFC-based prognostic model significantly stratified high- and low-risk patients, with superior predictive performance compared to the IPI score. Validation in our clinical cohort confirmed that the high-risk group had significantly shorter overall survival (OS) (P = 0.003). This study provides a novel tool for individualized prognostic assessment in DLBCL and suggests RFC2 and RFC4 as potential therapeutic targets.
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