Clinical And Experimental Medicine[JOURNAL]
Sun
200 papers
Benchmarking LLM decision support in inflammatory aneurysms: DeepSeek-R1, DeepSeek-V3 and ChatGPT-4o.
Hao J, Zhang C
Clin Exp Med · 2026 Apr · PMID 41931161 · Full text
Decision support for inflammatory aneurysms demands guideline-concordant specificity. We compared three large-language-model systems-DeepSeek-R1, ChatGPT-4o and DeepSeek-V3-on accuracy and time efficiency for core diagno...
Decision support for inflammatory aneurysms demands guideline-concordant specificity. We compared three large-language-model systems-DeepSeek-R1, ChatGPT-4o and DeepSeek-V3-on accuracy and time efficiency for core diagnostic, interventional and surveillance decisions. In a prospective, rater-blinded evaluation, each model completed a 50-item instrument aligned to contemporary aortic guidance in five independent clean-context sessions (15 answer sets). Five consultant vascular specialists scored all outputs using a prespecified 0/1/2 rubric. The primary outcome was total accuracy (0-100); secondary outcomes were completion time and domain subscores. Inter-rater reliability was summarised with Fleiss' κ and ICC(2,k). Mean total scores were 89.8 ± 1.8 (DeepSeek-R1), 88.4 ± 1.8 (ChatGPT-4o) and 77.8 ± 1.5 (DeepSeek-V3). One-way ANOVA showed a significant model effect (F(2,12) = 75.34, p = 1.61 × 10⁻⁷); Tukey contrasts indicated near-parity between R1 and 4o (Δ 1.44, p = 0.397) with both exceeding V3 (R1-V3 Δ 12.00, p = 2.80 × 10⁻⁷; 4o-V3 Δ 10.56, p = 1.13 × 10⁻⁶). Completion time separated strongly (R1 58.5 ± 0.95 s; 4o 33.4 ± 0.46 s; V3 19.8 ± 0.89 s; F(2,12) = 3053, p = 5.69 × 10⁻¹⁷), and accuracy rose with time (Pearson r = 0.802, 95% CI 0.49-0.93, p = 3.24 × 10⁻⁴; Theil-Sen 0.285 points·s⁻¹). Differences concentrated in guideline-derived items (R1 36.44 ± 1.49; 4o 36.32 ± 1.45; V3 29.16 ± 0.86). Inter-rater agreement was substantial at item level (κ = 0.662) and excellent for totals (ICC[2,k] = 0.973); intra-model variability was ≈ 2%. In rule-dense, safety-critical decisions for inflammatory aneurysms, slower, reasoning-oriented decoding yields the highest accuracy, while a low-latency multimodal system achieves near-parity at markedly shorter times; a throughput-optimised model trades speed for omission-prone answers. Model selection should align with task criticality, with human verification retained.
Opposing prognostic roles of tumor-associated and circulating MMP8 in colorectal cancer.
Loukasmäki I, Tuomisto A, Sirniö P … +15 more , Kastinen M, Karjalainen H, Äijälä VK, Tapiainen VV, Tervahartiala T, Sorsa T, Pohjanen VM, Mattila TT, Lindgren O, Rintala J, Meriläinen S, Saarnio J, Rautio T, Mäkinen MJ, Väyrynen JP
Clin Exp Med · 2026 Apr · PMID 41931149 · Full text
Local and systemic inflammation play key roles in colorectal cancer (CRC). Matrix metalloproteinase 8 (MMP8), an enzyme involved in extracellular matrix remodeling, has been linked to both inflammatory processes and canc...
Local and systemic inflammation play key roles in colorectal cancer (CRC). Matrix metalloproteinase 8 (MMP8), an enzyme involved in extracellular matrix remodeling, has been linked to both inflammatory processes and cancer progression. This study investigates MMP8 serum concentration and MMP8 expression within the tumor microenvironment, and their relationship with tumor characteristics, inflammation, and survival. The study included 776 stage I-IV CRC patients. MMP8+ cell densities within tumors were analyzed using immunohistochemistry combined with digital image analysis, while preoperative serum MMP8 levels were analyzed using an immunofluorometric assay. Survival analyses were performed using the Kaplan-Meier method and Cox regression models. Correlations with systemic inflammatory markers and immune cell densities were assessed using linear regression models. We found that MMP8 was predominantly expressed by CEACAM8+ granulocytes. High MMP8+ cell density within tumors was associated with favorable prognostic factors, including low disease stage, absent lymphovascular invasion, and mismatch repair (MMR) deficiency, but also with improved cancer-specific survival independent of these factors. The multivariable HR for low (vs. high) MMP8+ cell density was 1.76 (95%CI 1.18–2.60). MMP8+ cell density positively correlated with T-cell densities, but not with serum MMP8 levels or conventional systemic inflammation markers. In contrast, high serum MMP8 levels were associated with systemic inflammation and worse survival, but did not remain an independent prognostic factor in multivariable models. In conclusion, serum MMP8 levels do not correlate with MMP8 expression in the tumor microenvironment, suggesting distinct roles for circulating and tumor-associated MMP8 in CRC progression. High MMP8+ cell densities within tumors are associated with better prognosis and local immune activity, while elevated serum MMP8 levels indicate systemic inflammation and advanced disease.
Gut microbiome remodeling across hepatocellular carcinoma progression and transarterial chemoembolization is associated with therapeutic response and prognosis.
Liu B, Wan SH, Zhang YT … +4 more , Lin JH, Ke XC, Lin WH, Zhan MX
Clin Exp Med · 2026 Apr · PMID 41931121 · Full text
Clinical outcomes after transarterial chemoembolization (TACE) for intermediate–to–advanced hepatocellular carcinoma (HCC) are highly variable, and reliable predictive biomarkers are lacking. Although gut microbiota dysb...
Clinical outcomes after transarterial chemoembolization (TACE) for intermediate–to–advanced hepatocellular carcinoma (HCC) are highly variable, and reliable predictive biomarkers are lacking. Although gut microbiota dysbiosis has been implicated in HCC pathogenesis and immunotherapy response, its role in TACE outcomes remains unclear. This study aimed to delineate gut microbiome remodeling across HCC progression and TACE treatment and to evaluate its association with clinical outcomes. Fecal samples were collected from healthy controls (n = 10), newly diagnosed untreated HCC patients (n = 30), post-TACE HCC patients (n = 29), and a longitudinal cohort of TACE-treated patients (n = 56). Gut microbiota profiles were analyzed using 16S rDNA sequencing. Differential taxa, microbial diversity, functional pathways, and survival associations were assessed using bioinformatics and Kaplan–Meier analyses. Gut microbiome composition differed markedly across healthy controls, untreated HCC, and post-TACE patients. Bacteroides abundance progressively decreased, whereas Prevotella_9 increased across disease progression and treatment. Among TACE-treated patients, progressive disease was characterized by higher Prevotella_9 and lower Bacteroides and Ruminococcus abundance, accompanied by significantly reduced microbial diversity. Kaplan–Meier analysis showed that low Prevotella_9 (P = 0.001) and high Bacteroides (P = 0.001) and Faecalibacterium (P = 0.04) were associated with prolonged progression-free survival, while higher Phascolarctobacterium and Veillonella abundance correlated with shorter overall survival. Functional prediction revealed alterations in pathways related to lipid metabolism, carbohydrate metabolism, and immune regulation. Gut microbiome remodeling is closely associated with HCC progression and TACE outcomes. Specific microbial taxa, particularly Bacteroides and Prevotella_9, were associated with therapeutic response and prognosis; however, these findings are exploratory and warrant We hypothesized that specific microbial taxa and metabolic pathways could serve as predictive biomarkers of TACE efficacy and clinical outcomes.
Prognostic value of the neutrophil-to-lymphocyte ratio in POEMS syndrome.
Zhang T, Chen Q, Shen X … +4 more , Jin Y, Shen N, Chen L, Xu J
Clin Exp Med · 2026 Apr · PMID 41925928 · Full text
POEMS syndrome is a rare paraneoplastic disorder driven by clonal plasma cell proliferation and systemic inflammation, but existing prognostic models inadequately incorporate inflammation-related parameters. The neutroph...
POEMS syndrome is a rare paraneoplastic disorder driven by clonal plasma cell proliferation and systemic inflammation, but existing prognostic models inadequately incorporate inflammation-related parameters. The neutrophil-to-lymphocyte ratio (NLR)-a simple, accessible marker of systemic inflammation and immune status-lacks systematic prognostic validation in POEMS syndrome. This single-center retrospective study enrolled 61 patients. The cohort was stratified into two eras (2010-2017 and 2018-2025) to assess temporal consistency. Receiver operating characteristic analysis was used to derive an exploratory NLR cut-off for overall survival. Kaplan-Meier curves and Cox proportional hazards regression were used to assess associations between NLR and progression-free survival (PFS), overall survival (OS), and independent prognostic significance. The effect modification by Li's prognostic risk strata was explored using interaction and stratified analyses. Correlations were tested by Spearman's coefficient between NLR and C-reactive protein (CRP), and AUCs were compared by DeLong's test. ROC analysis showed moderate discrimination of baseline NLR for OS (AUC 0.736, 95% CI 0.613-0.860; P = 0.006), and the exploratory cut-off was 2.773. Patients with NLR > 2.773 had significantly shorter PFS (median 62 months vs not reached; P < 0.001) and OS (median 76 months vs not reached; P < 0.001) than those with NLR ≤ 2.773. Multivariable Cox regression confirmed NLR > 2.773 as an independent prognostic factor for inferior PFS (HR 3.547, 95% CI 1.086-11.586; P = 0.036). In Li's high-risk subgroup, high NLR further separated survival curves, although the formal interaction for PFS was not significant (P for interaction = 0.270), and OS interaction modeling was limited by few death events. CRP showed prognostic relevance, NLR correlated moderately with CRP (Spearman's ρ = 0.49, P < 0.001). A combined NLR + CRP model did not significantly improve OS discrimination over either marker alone (DeLong tests, all P > 0.05). Collectively, elevated baseline NLR is associated with inferior PFS and OS in POEMS syndrome and may reflect an inflammation-related risk phenotype. As a simple and widely available index, NLR may complement existing prognostic frameworks by incorporating an inflammation-immune dimension. External validation in independent multi-center cohorts is warranted.
Research progress on the mechanisms of EB virus reshaping the immune microenvironment in nasopharyngeal carcinoma.
Yudie L, Weihua X, Xinping C
Clin Exp Med · 2026 Apr · PMID 41925921 · Full text
Nasopharyngeal carcinoma (NPC) is the most common EBV (Epstein-Barr virus) related epithelial malignant tumor. Over 90% of patients diagnosed with undifferentiated nasopharyngeal carcinoma are infected with EB virus. EBV...
Nasopharyngeal carcinoma (NPC) is the most common EBV (Epstein-Barr virus) related epithelial malignant tumor. Over 90% of patients diagnosed with undifferentiated nasopharyngeal carcinoma are infected with EB virus. EBV infection of nasopharyngeal carcinoma leads to the remodeling of the immune microenvironment. There are now numerous research mechanisms regarding the remodeling of the immune microenvironment by EBV. This article systematically integrates single-cell transcriptomics, spatial metabolomics, and clinical research evidence, and from four dimensions: effector cell exhaustion, inhibitory cell expansion, metabolic reprogramming, and spatial organization of tertiary lymphoid structures, it analyzes the multi-level mechanisms by which EBV remodels the immune microenvironment. The core findings indicate that EBV constructs a multi-target and multi-level coordinated regulatory network through its encoded proteins (LMP1, LMP2A, EBNA1, and BRRF2) and non-coding RNAs (miR-BARTs and circRNAs). This regulatory mechanism dynamically evolves at different stages of the disease, with synergistic effects during the latent and lytic phases, forming an immunosuppressive microenvironment. However, the limitations in mechanism understanding have led to difficulties in clinical translation and drug use. The objective response rate of PD-1 inhibitors is only 20–30%. Single-target blockade is difficult to improve treatment efficacy. Therefore, based on previous research data, we propose that in the future, we need to shift from single-target blockade to the overall ecosystem regulation of the immune microenvironment, combined with targeted inhibition of immune checkpoints, chemokine axes, metabolic nodes, and viral own products, and based on EBV DNA load and TLS status for precise stratification. This is expected to break through the current treatment limitations and promote EBV-positive nasopharyngeal carcinoma from empirical treatment to mechanism-driven precise immunotherapy intervention.
TIM-3 in AML: pathogenic roles and therapeutic targetability.
Zhong L, Soleimani Samarkhazan H
Clin Exp Med · 2026 Apr · PMID 41925920 · Full text
Acute Myeloid Leukemia (AML) remains a therapeutic challenge due to immune evasion and relapse. T-cell immunoglobulin and mucin domain-containing-3 (TIM-3) is an immune checkpoint receptor aberrantly expressed on immune...
Acute Myeloid Leukemia (AML) remains a therapeutic challenge due to immune evasion and relapse. T-cell immunoglobulin and mucin domain-containing-3 (TIM-3) is an immune checkpoint receptor aberrantly expressed on immune cells and leukemic stem cells (LSCs) in AML. Biologically, TIM-3 predominantly mediates deleterious effects, promoting T-cell/NK dysfunction and supporting LSC self-renewal, but this pathogenic expression also makes TIM-3 a therapeutically actionable target. This narrative review synthesizes current preclinical and clinical evidence on the role of TIM-3 in AML. We examined its structure, signaling pathways, and dual functions in promoting immune suppression and LSC self-renewal. A comprehensive analysis of ongoing therapeutic strategies, including monoclonal antibodies and cellular therapies, was conducted. Relevant literature was identified through searches of PubMed, Scopus, and Web of Science databases, with a focus on recently published studies. TIM-3 contributes to immune dysregulation by inducing T-cell exhaustion, impairing NK cell cytotoxicity, and enhancing immunosuppressive myeloid cells. Concurrently, its expression on LSCs drives leukemogenesis through autocrine signaling loops involving Galectin-9 and the β-catenin pathway. Preclinical studies show that TIM-3 blockade reduces leukemic stem-cell frequency and impairs LSC reconstitution in xenograft models, and can reinvigorate anti-leukemic immunity in experimental systems; however, these findings are preclinical and have not yet translated into consistent, randomized clinical benefit in human trials, underscoring the need for biomarker-guided and combination approaches in clinical development (Kikushige et al. Cell Stem Cell 17(3):341–352, 2015; Kikushige et al. Cell Stem Cell7(6):708–717, 2010; Zeidan et al. Lancet Haematol11(1):e38–e50, 2024). Clinically, the anti-TIM-3 antibody sabatolimab showed a tolerable safety profile and preliminary signals of activity when combined with hypomethylating agents; however, randomized phase II data did not demonstrate statistically significant improvements in the primary endpoints (complete response rate and progression-free survival), and the development program has since been re-evaluated in light of these results. TIM-3 also shows promise as a diagnostic and prognostic biomarker. TIM-3 plays an important and multifaceted role in AML pathogenesis, with evidence supporting both immune-regulatory functions and roles in leukemic stem cell biology; however, definitive proof that TIM-3 is essential for LSC maintenance across all AML subtypes requires additional genetic and functional validation. Targeting TIM-3 remains a biologically compelling strategy to address immune suppression and LSC biology in AML, but definitive clinical benefit has not been established in randomized studies to date; further investigation, especially in biomarker-enriched, low-tumor-burden settings and rational combinations, is required to define its clinical role.
Multi-omics identification of a programmed cell death-related signature and potential target P4HB for bladder cancer based on a 101-combination machine learning and experimental validation.
Cao Y, Li C, Hua Y … +4 more , Wu T, Shen Q, Lin Z, Huang Y
Clin Exp Med · 2026 Apr · PMID 41925913 · Full text
Bladder cancer (BLCA) poses a significant clinical challenge due to its high mortality rates and the inadequacy of current prognostic biomarkers. Programmed cell death (PCD) is crucial in BLCA initiation, progression, an...
Bladder cancer (BLCA) poses a significant clinical challenge due to its high mortality rates and the inadequacy of current prognostic biomarkers. Programmed cell death (PCD) is crucial in BLCA initiation, progression, and treatment, yet the interplay and specific roles of different PCD pathways in BLCA prognosis remain elusive. This study aimed to develop and validate predictive models by integrating 14 PCD patterns using comprehensive analyses of bulk RNA and single-cell RNA transcriptomic data from TCGA-BLCA and six GEO datasets. Through weighted gene co-expression network (WGCNA) analyses, 24 hub PCD-related genes (PCDGs) were identified in BLCA. Subsequently, we implemented a computational framework that integrated 10 machine learning algorithms along with 101 of their combined permutations. This framework was used to develop a programmed cell death-related signature (PCDRS). The final PCDRS consisted of 12 prognostic genes: P4HB, CHEK2, PTPN2, ATP13A2, CCT6A, TFRC, RRP12, TRAF7, POLR1B, B4GALT3, SIVA1, and TP73.The PCDRS was validated in training and external validation sets, with multivariate analysis confirming its independent prognostic value in BLCA. The PCDRS-integrated nomogram was also developed as a quantitative clinical tool. Furthermore, differences in reactive oxygen species (ROS) levels were observed in the tumor microenvironment between high- and low-risk groups based on PCDRS risk scores. Additionally, the elevated expression and tumorigenic role of P4HB in BLCA were validated through in vitro assays. In summary, P4HB may serve as a candidate gene with potential relevance to BLCA prognosis that could enhance personalized treatment strategies for patients with BLCA.
Neutrophil extracellular Trap-related genes in NAFLD: Biomarkers and therapeutic targets.
Rao H, Chen J, Chen Y … +1 more , Jiang J
Clin Exp Med · 2026 Apr · PMID 41925905 · Full text
The etiology of non-alcoholic fatty liver disease (NAFLD) is complex. This study seeks to clarify the importance of neutrophil extracellular traps (NETs) -related genes in NAFLD. Integrated NAFLD datasets were obtained f...
The etiology of non-alcoholic fatty liver disease (NAFLD) is complex. This study seeks to clarify the importance of neutrophil extracellular traps (NETs) -related genes in NAFLD. Integrated NAFLD datasets were obtained from GEO. NETs-related differentially expressed genes (NETsRDEGs) were identified and analyzed for functional enrichment. A diagnostic model was developed using logistic regression and Least Absolute Shrinkage and Selection Operator regression (LASSO) methods, followed by validation through receiver operating characteristic curve analysis. Immune cells infiltration assessments, regulatory network analyses, and protein domain predictions were conducted to illuminate the molecular mechanisms underlying NAFLD. We identified 22 NETsRDEGs and constructed an 8-gene diagnostic model (TLR7, LDLR, CCL2, S100A8, PADI4, F3, CD274, NFIL3) that effectively distinguished NAFLD from controls (area under the curve [AUC] = 0.920). Enrichment analyses revealed significant involvement of PI3K-AKT signaling and negative regulation of NOTCH4 signaling. Immune infiltration analysis demonstrated altered abundances of activated CD8 + T cells and Type 2 T helper in NAFLD. Several compounds, including resveratrol and curcumin, were identified as potential therapeutics. Our findings underscore the significance of NETs in NAFLD pathogenesis, involving inflammatory pathways and immune dysregulation. The identified NETsRDEGs and diagnostic model offer promising biomarkers and therapeutic avenues for NAFLD.
Exploratory study of PD-1 inhibitors with or without ruxolitinib for the treatment of adult EBV-associated hemophagocytic lymphohistiocytosis: a real-world data-based preliminary investigation.
Chen Z, Li W, Liu C … +7 more , Chen J, Tan X, Li W, Zhou C, Li F, Lei P, Zhou M
Clin Exp Med · 2026 Apr · PMID 41925894 · Full text
To preliminarily analyze the clinical efficacy and safety of PD-1 inhibitors as monotherapy or in combination with ruxolitinib (RUX) for adult Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) ba...
To preliminarily analyze the clinical efficacy and safety of PD-1 inhibitors as monotherapy or in combination with ruxolitinib (RUX) for adult Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) based on real-world retrospective data. A retrospective case series analysis was performed on clinical data of 4 adult EBV-HLH patients treated with sintilimab (a PD-1 inhibitor) alone or combined with RUX at the Department of Hematology, Hunan Provincial People’s Hospital, from April 1, 2020 to February 1, 2024. Clinical efficacy, survival outcomes, dynamic changes of laboratory indicators and adverse reactions were observed. Among the 4 patients, 2 achieved complete remission (CR), 1 experienced treatment interruption due to non-adherence and was lost to follow-up, and 1 died of multi-organ failure induced by COVID-19, with a 1-year overall survival (OS) rate of 75.00%. All patients received sintilimab with a median treatment course of 9.5 cycles and a median infusion dose of 1900 mg; 3 patients were combined with RUX. After one cycle of treatment, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and interleukin-10 (IL-10) decreased significantly, while white blood cell (WBC), hemoglobin (HGB) and platelet (PLT) levels increased significantly (all P < 0.05). Ferritin (Ferr) returned to the normal range and fibrinogen (Fbg) showed an upward trend. The number of peripheral blood T, B and natural killer (NK) cells increased in 3 patients who completed lymphocyte subset detection. No drug-related severe adverse reactions of grade 3 or above were observed in all patients. PD-1 inhibitors alone or combined with RUX show preliminary favorable efficacy and high tolerability in the treatment of adult EBV-HLH, which can effectively improve blood cell levels, control inflammatory responses and increase clinical remission rates. However, large-sample prospective studies are required to verify the long-term efficacy due to the small sample size of this study.
Development and validation of an interpretable machine learning model for predicting portal vein system thrombosis following splenectomy in Wilson's disease.
Shen Y, Zheng Z, Min HC … +5 more , Peng H, Huang L, Zhang WZ, Feng H, Yu QS
Clin Exp Med · 2026 Apr · PMID 41925807 · Full text
Post-splenectomy portal vein system thrombosis (PVST) is a serious complication that adversely affects patient prognosis. The aim of this study was to develop and validate a machine learning-based model for early risk pr...
Post-splenectomy portal vein system thrombosis (PVST) is a serious complication that adversely affects patient prognosis. The aim of this study was to develop and validate a machine learning-based model for early risk prediction of PVST after splenectomy. A total of 594 patients who underwent splenectomy were included in this study. The data were randomly divided into a training set (n = 417) and a validation set (n = 177) in a 7:3 ratio. Clinical characteristics associated with PVST risk were screened using LASSO regression and univariate analysis. Seven machine learning algorithms were applied for model training, and the models’ performance on the validation set was evaluated using the area under the curve (AUC), sensitivity, specificity, and F1 score. SHAP interpretability analyses and web-based deployment were used to derive clinical insights. In the training set, the key variables identified included splenomegaly grade, splenic thickness, portal vein flow velocity (PVV), portal vein diameter (PVD), portal vein flow (PVF), splenic vein diameter (SVD), postoperative platelet count (POD PLT), and postoperative D-dimer level (POD D-dimer). The XGBoost model outperformed the logistic regression (LR) and random forest (RF) models, achieving an AUC of 0.971 (95% CI: 0.950–0.987), accuracy of 92.8%, sensitivity of 91.2%, and specificity of 94.6%. In the validation set, the XGBoost model exhibited stable performance, with an AUC of 0.970, accuracy of 91.5%, precision of 89.9%, sensitivity of 88.6%, and specificity of 93.5%. the SHapley Additive exPlanations (SHAP) summary analysis indicated that PVV, PVF, and POD D-dimer were the top three predictors of PVST risk (SHAP Value = 0.076, 0.074 and 0.064). SHAP dependency plots and force plots provided explanations of the model’s predictions at the feature and individual levels, respectively. The XGBoost model demonstrated excellent discrimination and calibration for predicting PVST risk after splenectomy. It can serve as an early warning tool to identify high-risk patients, enabling timely interventions and improved clinical outcomes.
Identification of plasma exosome circRNA as potential novel biomarkers for DLBCL and circrna-miRNA-mRNA network analysis.
Cao Y, Guo L, Ge J … +5 more , Qiu Y, Wang F, Li F, Gu W, Lin Y
Clin Exp Med · 2026 Apr · PMID 41925757 · Full text
Diffuse large B-cell lymphoma (DLBCL), the most common aggressive non-Hodgkin lymphoma, urgently requires novel biomarkers for clinical diagnosis and therapeutic monitoring. Plasma exosomes from three DLBCL patients and...
Diffuse large B-cell lymphoma (DLBCL), the most common aggressive non-Hodgkin lymphoma, urgently requires novel biomarkers for clinical diagnosis and therapeutic monitoring. Plasma exosomes from three DLBCL patients and three healthy controls were isolated via ultracentrifugation, and differentially expressed circular RNAs (circRNAs) were screened using Arraystar V2 microarrays (fold change [FC] ≥ 1.2, P ≤ 0.05). Candidate circRNAs were validated by quantitative real-time PCR (qRT-PCR) in 55 DLBCL patients and 25 controls. Microarray analysis identified 269 dysregulated circRNAs (152 upregulated, 117 downregulated; FC ≥ 1.2, P ≤ 0.05). RT-qPCR confirmed significantly elevated expression of hsa_circ_400230, hsa_circ_001393, and hsa_circ_404447 in DLBCL (P < 0.05), with areas under the ROC curve (AUCs) of 0.7622, 0.7244, and 0.6618, respectively. High hsa_circ_001393 expression correlated with advanced age (> 60 years), stage III/IV, high International Prognostic Index (IPI 3–5), elevated β2-microglobulin (> 2 mg/L), and non-complete remission (Non-CR) status (P < 0.05). Combined detection with lactate dehydrogenase (LDH) improved predictive efficacy (AUC = 0.817, P = 0.002). Post-chemotherapy complete remission (CR) patients exhibited significant reduction in hsa_circ_001393 (P = 0.0174). Competing endogenous RNA (ceRNA) network analysis identified MLLT3 as a hub gene, with overexpression associated with shorter survival (hazard ratio [HR] = 2.31, P = 0.0042). These findings demonstrate that Plasma exosomal hsa_circ_400230/001393/404,447 are novel diagnostic biomarkers. hsa_circ_001393 predicts therapeutic resistance and dynamically reflects chemotherapy response, potentially via the hsa-miR-1290/MLLT3 axis. This study advances liquid biopsy strategies for DLBCL management.
CD59 silencing enhances doxorubicin sensitivity in DLBCL cells and is associated with poor prognosis in patients treated with CHOP regimen.
Linzhu, Xianmusiya M, Wen S … +3 more , Wu M, Li S, Liang X
Clin Exp Med · 2026 Apr · PMID 41920217 · Full text
Diffuse large B-cell lymphoma (DLBCL) remains challenging due to high relapse and refractory rates after R-CHOP therapy. The role of complement regulatory protein CD59 in DLBCL progression and drug resistance is poorly u...
Diffuse large B-cell lymphoma (DLBCL) remains challenging due to high relapse and refractory rates after R-CHOP therapy. The role of complement regulatory protein CD59 in DLBCL progression and drug resistance is poorly understood. This study aimed to investigate the effects of knocking-down complement-regulatory protein, CD59, on disease progression, and chemo-resistance in DLBCL cells, as well as to establish the clinicopathological relevance and prognostic significance of CD59 in DLBCL. Lentiviral-mediated knockdown of CD59 was established in SU-DHL-4 and U2932 DLBCL cell lines. Cell viability, cell cycle distribution, and apoptosis were assessed using CCK-8 and flow cytometry. Immunohistochemistry for CD59 was performed on tumor biopsies from 103 treatment-naive DLBCL patients. Survival analyses were conducted using Kaplan-Meier and Cox regression models. Stable silencing of CD59 significantly reduced cell viability, induced G₀/G₁ arrest, and promoted apoptosis in both cell lines. The combination with doxorubicin resulted in enhanced growth inhibition and apoptosis compared to monotherapy. In clinical samples, CD59 positivity (n = 43, 41.75%) was correlated with a higher IPI score (p < 0.05), elevated LDH (p < 0.05), and a poorer response to therapy (CHOP, p < 0.05). In CHOP-treated patients, CD59 + predicted shorter PFS (rate, 9.1% vs. 61.4%, p < 0.05) and OS (45.5% vs. 86.9%, p < 0.05), while no significant difference was observed in the R-CHOP subgroup. Multivariate analysis confirmed that CD59 overexpression was an independent predictor of poor PFS and OS (HR = 4.254, p < 0.05). CD59 knockdown suppresses DLBCL cell growth and enhances doxorubicin sensitivity in vitro. Clinically, the prognostic value of CD59 is highly treatment-regimen dependent: high CD59 expression is an independent predictor of poor prognosis specifically in CHOP-treated DLBCL patients, but not in those receiving the standard R-CHOP regimen. These findings highlight CD59 as a potential modulator of chemotherapy response rather than a broadly applicable biomarker.
Development and validation of a risk prediction model and management strategy for red blood cell irregular antibodies a retrospective cohort study of 521 patients.
Wang L, Yang J, Guo Z … +3 more , Qiu D, Fu Y, Xu Y
Clin Exp Med · 2026 Apr · PMID 41920210 · Full text
This study aimed to systematically identify independent risk factors for difficult cross-matching and to construct a predictive model for early clinical risk warning and stratified management. A derivation cohort of 521...
This study aimed to systematically identify independent risk factors for difficult cross-matching and to construct a predictive model for early clinical risk warning and stratified management. A derivation cohort of 521 patients with positive red blood cell irregular antibody screening results was retrospectively enrolled. Based on the screening results, patients were categorized into a 1-2 positive wells group (n = 428) and a 3 positive wells group (n = 93). Univariate and multivariate logistic regression analyses were performed to identify independent predictors of difficult cross-matching. A simplified clinical risk scoring system was developed based on the regression coefficients, and the predictive performance of the model was evaluated. Multivariate analysis identified six independent influencing factors: 3 positive wells (OR = 2.34, 95% CI: 1.18-4.65), diagnosis of multiple myeloma (OR = 5.05, 95% CI: 2.54-10.05), hospitalization in the hematology department (OR = 2.25, 95% CI: 1.27-3.98), age ≥ 60 years (OR = 1.97, 95% CI: 1.12-3.48), pregnancy-related diseases (protective factor; OR = 0.24, 95% CI: 0.08-0.73), and difficult blood typing (OR = 4.57, 95% CI: 2.30-9.08). The risk scoring model incorporating these factors demonstrated good predictive performance, with an area under the curve (AUC) of 0.819 (95% CI: 0.766-0.872), a sensitivity of 74.4%, and a specificity of 76.5%. Patients were stratified into three risk tiers (low, medium, and high) based on their scores, with corresponding differentiated clinical management pathways and resource allocation plans established. This study successfully identified and quantified key clinical and laboratory predictors for difficult cross-matching. The established risk scoring model demonstrates good predictive accuracy, providing a reliable tool for precise pre-transfusion risk assessment. The stratified management system based on this model facilitates a shift from reactive to proactive intervention in transfusion workflows, offering significant clinical translational value for optimizing blood bank resource allocation and ensuring transfusion safety for high-risk patients.
S100A8-associated inflammatory microenvironment is related to its cell-of-origin and potentiates BRAF inhibitor resistance in papillary craniopharyngioma.
Zhao C, Lin Y, Chen H … +10 more , Liu H, Hu W, Wang X, Chen J, Luo N, Qi X, Han S, Li X, Wang X, Lin Z
Clin Exp Med · 2026 Apr · PMID 41920205 · Full text
Papillary craniopharyngioma (PCP) is a BRAF mutant inflammation-related tumor that exhibits resistance to targeted therapies. This study aimed to discover mechanisms critical for PCP therapy resistance and identify new t...
Papillary craniopharyngioma (PCP) is a BRAF mutant inflammation-related tumor that exhibits resistance to targeted therapies. This study aimed to discover mechanisms critical for PCP therapy resistance and identify new therapy target for PCP cells resistant to BRAF V600E inhibition. The microenvironment of PCP was examined using various molecular techniques, including whole-exon sequencing, transcriptome analysis, methylation profiling, and spatial data analysis. Molecular biomarkers, immunohistochemistry (IHC), and multiplex immunofluorescence (mIF) were utilized to explore the relationship between the highly inflammatory microenvironment and tumor origin-related tissue properties (TORTP). Our findings revealed that drug-resistant PCP exhibited high expression of S100A8, a biomarker associated with immune cell activation and inflammation. Crucially, this S100A8-high inflammatory signature was not exclusive to BRAF-mutant PCP. Compared to pituitary tissue, PCP displayed elevated levels of inflammatory markers, particularly S100A8. Spatial analysis within PCPs demonstrated a higher proportion of CK+/S100A8+ cells in the basal layer and S100A8+ cells in the stroma compared to RCC (Rathke’s cleft cyst). The highly S100A8-associated inflammatory microenvironment in PCP was closely linked to leukemia inhibitory factor (LIF). These factors potentiate resistance to BRAF inhibition in papillary craniopharyngioma. The distinct inflammatory microenvironment characterized by high expression of S100A8 is intrinsically linked to TORTP. Combination treatments targeting both the mutated aspects and TORTP-related factors hold significant potential to improve treatment outcomes.
Correction: Subclinical cardiac dysfunction in idiopathic inflammatory myopathies: the role of global longitudinal strain.
Romano S, Sartorio A, Pont CD … +7 more , Segatta F, Piazzola M, Vicardi M, Cominacini M, Aldegheri F, Bixio R, Viapiana O
Clin Exp Med · 2026 Mar · PMID 41910835 · Full text
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CXCL12-mediated T cell infiltration drives breast cancer metastasis.
Liu X, Chen C, Liu L … +4 more , Tang J, Zhang H, Jin G, Chen Y
Clin Exp Med · 2026 Mar · PMID 41902967 · Full text
Breast cancer (BC) is a malignant tumor with the highest incidence rate in women. This work explored the function of CXCL12 in tumor metastasis. CXCL12 protein expression levels were assessed by IHC in breast cancer tiss...
Breast cancer (BC) is a malignant tumor with the highest incidence rate in women. This work explored the function of CXCL12 in tumor metastasis. CXCL12 protein expression levels were assessed by IHC in breast cancer tissues. Protein–protein interaction analysis (STRING) indicated that CXCL12 interacts with CXCL10 protein molecules. Correlation analysis in GEPIA2 showed that CXCL12 was negatively correlated with CXCL10. The effects of CXCL12 on invasion and migration were detected by scratch and transwell experiments in breast cancer cells. CD4 + T and CD8 + T cells in the inflammatory microenvironment of breast cancer patients were evaluated with the NGDC database and verified by IF. CXCL12 knockdown efficiency was 55.4% (P < 0.05). the migration inhibition percentage is 7.7% in CXCL12 knockdown group (P < 0.05). CXCL12 knockdown enhanced the expression and secretion of CXCL10 in BC. CXCL10 is responsible for the recruitment of CD4 + and CD8 + T lymphocytes into tumors and enhances antitumor effects. The IF data showed that the patients in the CXCL10 + CD4+/CD8 + T-cell group and the CXCL12-CD4+/CD8 + T-cell group had better prognoses. CXCL12 promoted BC migration and invasion. On the other hand, CXCL12 inhibited the expression and secretion of CXCL10, further inhibiting T lymphocyte infiltration and promoting breast cancer metastasis in the TME.
The predictive value of lymph node status pre-operation by ultrasound and MRI in early and newly diagnosed breast cancer.
Taher HJ, Baharishargh R, Sharifian F … +5 more , Rad FN, Mirhosseini S, Sharifpour S, Yarahmadi D, Alizadeh Z
Clin Exp Med · 2026 Mar · PMID 41902891 · Full text
BACKGROUND: Accurate pre-operative assessment of axillary lymph node status is key for planning surgeries in early and newly diagnosed breast cancer. Ultrasound (US) and magnetic resonance imaging (MRI) are widely used,...
BACKGROUND: Accurate pre-operative assessment of axillary lymph node status is key for planning surgeries in early and newly diagnosed breast cancer. Ultrasound (US) and magnetic resonance imaging (MRI) are widely used, but their performance is inconsistent across studies. This meta-analysis evaluates and compares the predictive performance of MRI and US for pre-operative lymph node metastasis in early and newly diagnosed breast cancer. METHODS: We searched PubMed/MEDLINE, Embase, Scopus, and Web of Science (inception-31 December 2025) for studies on diagnostic performance in preoperative axillary staging using ultrasound and/or MRI. Two independent reviewers extracted or reconstructed true positive, true negative, false positive, false negative, and applied QUADAS-2. Sensitivity and specificity were pooled with random-effects GLMM, with direct comparisons and prevalence-based predictive values. RESULTS: Twenty-nine studies (n = 8,544) were included. Pooled sensitivity/specificity were 61.1%/92.0% for MRI and 59.8%/90.3% for ultrasound, yielding LR + 7.64 vs. 6.19 and DOR 18.1 vs. 13.9. HSROC AUCs were 0.863 (MRI) and 0.843 (ultrasound). In paired cohorts (k = 12), sensitivity did not differ, and MRI showed a non-significant specificity advantage. CONCLUSION: MRI and ultrasound showed comparable, moderate sensitivity and high specificity for preoperative axillary metastasis. MRI tended toward higher specificity and positive predictive value, whereas sensitivity did not differ in paired studies. Imaging can guide triage, but histopathology remains necessary for definitive staging.
TMEM132A is associated with metabolic reprogramming, macrophage-oriented immune remodeling, and breast cancer progression.
Chen Y, Lin R, Pan J … +8 more , Lau LY, Hua Y, Chen Q, Aldridge RJ, Whitmore EA, Guo W, Hong Z, Li B
Clin Exp Med · 2026 Mar · PMID 41874757 · Full text
Breast cancer progression reflects malignant cell programs coupled with immune remodeling. Biomarkers that connect tumor intrinsic states with microenvironmental interactions remain needed. We evaluated TMEM132A as a can...
Breast cancer progression reflects malignant cell programs coupled with immune remodeling. Biomarkers that connect tumor intrinsic states with microenvironmental interactions remain needed. We evaluated TMEM132A as a candidate marker in breast cancer. Bulk cohorts from The Cancer Genome Atlas, Genotype Tissue Expression, and Gene Expression Omnibus were analyzed to quantify TMEM132A expression, diagnostic discrimination, and associations with clinicopathologic features and survival. Single cell RNA sequencing and spatial transcriptomics localized TMEM132A across cell populations and tissue regions. Cell communication inference with correlation based validation and differential expression based enrichment, including GSEA and GSVA, were performed to characterize TMEM132A related biology. TMEM132A was consistently upregulated in tumors and separated tumor from normal tissue across datasets. High TMEM132A expression was associated with poorer outcomes and more advanced clinical categories. Single cell and spatial analyses localized TMEM132A mainly to malignant epithelial populations and tumor enriched regions, with reproducible links to macrophage related features. Cell communication analyses suggested that TMEM132A-positive malignant cells engage macrophage-associated signaling via the ANXA1–FPR3 and IL34–CSF1R axes; this inference was supported by correlation-based validation and is consistent with macrophage-oriented immune remodeling during breast cancer progression. TMEM132A-high tumors were enriched for cell cycle and DNA replication programs and showed higher activity in glycolysis, pentose phosphate pathway, oxidative phosphorylation, and pyrimidine metabolism. TMEM132A marks a malignant-associated state linked to adverse prognosis, proliferative and metabolic activation, and macrophage-oriented immune interactions, supporting its value for risk stratification and future mechanistic studies in breast cancer.
The global clinical landscape of human-derived extracellular vesicles: an analysis based on ClinicalTrials.gov (2010-2025).
Wei W, Wu X, Wang L … +4 more , Yu Y, Yang L, Zhang C, Wang D
Clin Exp Med · 2026 Mar · PMID 41874702 · Full text
Extracellular vesicles (EVs), with their ability to precisely regulate the cellular microenvironment, have fundamentally transformed the way we explore and treat diseases in many respects. Characterizing past and ongoing...
Extracellular vesicles (EVs), with their ability to precisely regulate the cellular microenvironment, have fundamentally transformed the way we explore and treat diseases in many respects. Characterizing past and ongoing clinical trials involving EVs as circulating biomarkers or therapeutic interventions for various diseases will yield valuable insights for academic research, disease surveillance, and biopharmaceutical development. Based on the ClinicalTrials.gov database, we retrospectively analyzed 355 clinical trials initiated by the end of 2025. This study provides a detailed description of these trials and discusses key considerations regarding current research priorities and future trends in this field.
MEG3 in glioma stem cells promotes glioblastoma angiogenesis through FUBP3-mediated VGF expression.
Li Y, Li Y, Tang J … +4 more , Kong X, Sun S, Wang W, Wu H
Clin Exp Med · 2026 Mar · PMID 41866561 · Full text
Glioblastoma (GBM) is the most prevalent primary malignant tumor of the adult central nervous system, characterized by pronounced vascularity that facilitates tumor proliferation, invasion, and progression. Although anti...
Glioblastoma (GBM) is the most prevalent primary malignant tumor of the adult central nervous system, characterized by pronounced vascularity that facilitates tumor proliferation, invasion, and progression. Although anti-angiogenic therapy has emerged as a potential treatment strategy for GBM, currently available anti-angiogenic agents, such as bevacizumab targeting VEGF, have demonstrated limited efficacy in improving patient survival. This underscores the urgent need for novel therapeutic targets and strategies. In this study, we identified that the expression of maternally expressed gene 3 (MEG3), a tumor-suppressive long non-coding RNA (lncRNA), is negatively correlated with patient prognosis. Spatial transcriptomics sequencing and RT-qPCR analyses revealed that MEG3 is highly expressed in glioma stem cells (GSCs). In vitro tube formation assays further demonstrated that MEG3 in GSCs promotes angiogenesis in human brain microvascular endothelial cells (HBMECs). Transcriptome sequencing identified VGF nerve growth factor inducible (VGF), a secreted pro-angiogenic protein, as a downstream target, and showed that MEG3 regulates the pro-angiogenic activity of GSCs by modulating VGF expression. RNA pull-down assays revealed that MEG3 binds to far upstream element-binding protein 1 (FUBP3), which also regulates VGF expression. In vivo, knockdown of MEG3 significantly extended survival in orthotopic xenograft models of GSCs. Immunohistochemical analysis of mouse tumor tissues showed a corresponding reduction in VGF levels and microvessel density following MEG3 knockdown. In conclusion, this study demonstrates that MEG3 in GSCs promotes GBM angiogenesis through a FUBP3-dependent induction of VGF expression, highlighting MEG3 as a potential therapeutic target for anti-angiogenic intervention in GBM.
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