Clinical And Experimental Medicine[JOURNAL]
Sun
200 papers
Multiple Myeloma in Children and Young Adults: A Systematic Literature Review.
Poultsaki G, Vassilakopoulos TP, Terpos E … +1 more , Papadakis V
Clin Exp Med · 2026 May · PMID 42168658 · Publisher ↗
Multiple myeloma (MM) is extremely rare in pediatric and young adult populations, and its clinical characteristics, therapeutic strategies, and outcomes remain poorly defined. This systematic review consolidates all publ...
Multiple myeloma (MM) is extremely rare in pediatric and young adult populations, and its clinical characteristics, therapeutic strategies, and outcomes remain poorly defined. This systematic review consolidates all published cases of MM in patients aged ≤ 25 years, aiming to define epidemiology, presentation, treatment, and theraupeutic outcomes. A systematic literature search was conducted in PubMed up to December 31, 2024, to identify case reports and series of MM in patients ≤ 25 years. Articles lacking patient-specific data, definitive diagnostic criteria, or full English text were excluded. Data on demographics, clinical features, cytogenetics, treatment regimens, and outcomes were extracted. Forty-two patients were included from 33 publications, with a median age of 17 years (range 8-25). Male predominance was noted (M: F = 1.47:1). Common presenting features included bone pain (42.9%) and neurological symptoms (21.4%). IgG myeloma was most frequent, followed by IgA, light-chain only and IgD subtypes. Plasmacytomas were observed in 61.9%, including 30.8% with extramedullary and 57.7% with paramedullary involvement. Cytogenetic abnormalities were detected in 75% of evaluable patients. First-line therapy varied by era, with regimens including conventional chemotherapy, novel agents, and hematopoietic stem cell transplantation (HSCT). Among the 16 patients with evaluable treatment response, the overall response rate to first-line therapy was 75%. Hematopoietic stem cell transplantation (HSCT) was performed in 10 patients and was associated with deeper treatment responses. Contemporary therapeutic regimens were generally well tolerated, and no therapy-related mortality was reported. MM in patients aged ≤ 25 years is a rare clinical entity that may present with distinctive features, including a high frequency of plasmacytomas and extramedullary disease. Modern treatment strategies incorporating novel agents and HSCT appear feasible and effective in this population. Further collaborative studies are required to better define the biological characteristics and optimal management of MM in very young patients.
Prediction of mRECIST tumor response at firstfollow-up after DEB-TACE using a combined radiomics-clinical model and explainability methods.
Yang J, Hu Y, He X … +7 more , Zhao Q, Wang J, Wang F, Shi Z, Liu H, Lü W, Cui L
Clin Exp Med · 2026 May · PMID 42162354 · Full text
To investigate the value of preoperative enhanced computed tomography (CT) radiomics combined with clinical features in predicting the tumor response according to mRECIST of initial drug-eluting bead transarterial chemoe...
To investigate the value of preoperative enhanced computed tomography (CT) radiomics combined with clinical features in predicting the tumor response according to mRECIST of initial drug-eluting bead transarterial chemoembolization (DEB-TACE) in hepatocellular carcinoma (HCC) patients by utilizing the Shapley additive explanations (SHAP) algorithm for model interpretation. A retrospective analysis was conducted on 110 patients. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors. Radiomic features were extracted from arterial phase computed tomography images and reduced using the least absolute shrinkage and selection operator. These features were combined with clinical indicators to construct predictive models, including logistic regression, naive Bayes, support vector machine, random forest, and XGBoost. The model performance was evaluated using the area under the curve, calibration curve, and decision curve. The combined model showed optimal predictive performance, with area under the curve values of 0.838 and 0.802 for the training and test sets, respectively, statistically outperforming the single models (DeLong test, P < 0.05).Furthermore, SHAP analysis revealed key predictors and their directional effects. Preoperative enhanced computed tomography radiomics combined with clinical indicators can effectively predict the initial tumor response to DEB-TACE. SHAP visualization analysis enhances interpretability and identifies key predictors, offering support for precise treatment and individualized decision-making.
Tacrolimus has better performance in B cell reconstitution after allo-HSCT compared to cyclosporine A: a real-world study.
Zhou H, Zhou G, Xiang W … +9 more , Ren G, Dou X, Chen J, Tang X, Zhang H, Wang X, Luo X, Liu L, Wang L
Clin Exp Med · 2026 May · PMID 42162342 · Publisher ↗
B-cell reconstitution is closely associated with prognosis, infection risk, and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the impact of different calc...
B-cell reconstitution is closely associated with prognosis, infection risk, and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the impact of different calcineurin inhibitors (CNIs) on B-cell recovery remains unclear. We retrospectively analyzed 312 allo-HSCT recipients receiving cyclosporine (CsA, n = 211) or tacrolimus (FK506, n = 101). B-cell proportions in bone marrow and peripheral lymphocyte subsets were compared, and propensity score matching was applied to balance confounders. Multivariate analysis demonstrated that FK506 was independently associated with superior B-cell reconstitution at 3 months (OR 2.93, 95% CI 1.49-5.76, p = 0.010) and 4 months post-transplant (OR 3.53, 95% CI 1.11-11.15, p = 0.024). Higher B-cell proportions at 3-5 months were associated with a significantly lower risk of viral infection. Mediation analysis further revealed that improved B-cell reconstitution at day + 90 partially mediated the protective effect of FK506 against viral infection. These findings suggest that FK506 promotes improved B-cell recovery and may reduce viral infection risk after allo-HSCT.
Single-cell atlas reveals the key role of pro-inflammatory IREB2⁺ microglia subsets in the microenvironment of Alzheimer's disease.
Rong W, Xu J, Li B … +2 more , Li Y, Xu Y
Clin Exp Med · 2026 May · PMID 42159858 · Full text
Chronic neuroinflammation driven by activated microglia is a critical hallmark of Alzheimer's disease (AD) progression. Metabolic dysregulation, particularly iron metabolism, has been implicated in neurodegeneration, yet...
Chronic neuroinflammation driven by activated microglia is a critical hallmark of Alzheimer's disease (AD) progression. Metabolic dysregulation, particularly iron metabolism, has been implicated in neurodegeneration, yet the role of iron-responsive element-binding protein 2 (IREB2) in AD-associated neuroinflammation remains poorly understood. We performed integrative analysis of single-cell RNA sequencing (scRNA-seq) data from AD brain tissues, using non-negative matrix factorization (NMF) and intercellular communication algorithms to map cellular landscapes. We identified microglial subpopulations and their inflammatory signaling. To experimentally validate the functional role of IREB2 in inflammatory responses, we conducted siRNA-mediated knockdown in the human neuroblastoma cell line SH-SY5Y, which serves as a neuronal model for assessing IREB2's effect on cytokine expression. Single-cell analysis revealed a distinct microglial subpopulation (IREB2⁺ MC C1) that is significantly expanded in AD. This subpopulation exhibits a hyper-inflammatory state, with enrichment of Toll-like receptor and IL-17 signaling pathways, and functions as a primary source of outgoing inflammatory signals (CCL3, CCL4). Furthermore, IREB2 knockdown in SH-SY5Y cells significantly suppressed the expression of key pro-inflammatory cytokines (IL6, IL-1β, and TNF-α), confirming that IREB2 positively regulates inflammation in neurons as well. IREB2 drives both microglial activation and neuronal inflammatory responses in AD, potentially via the NF-κB pathway. The IREB2⁺ microglial subpopulation represents a specific pathogenic entity that orchestrates the inflammatory microenvironment. Targeting IREB2 may therefore offer a dual-pronged therapeutic strategy to mitigate neuroinflammation and slow AD progression.
Bortezomib synergizes with homoharringtonine in FLT3-ITD-relapsed/refractory acute myeloid leukemia by inducing FLT3-ITD protein degradation.
Wei M, Wang F, Huang D … +5 more , Kang Z, Yang Y, Zhang C, Lou J, Yan J
Clin Exp Med · 2026 May · PMID 42159798 · Publisher ↗
Mutations in Fms-like tyrosine kinase 3 (FLT3) are strongly associated with relapse and resistance in acute myeloid leukemia (AML) patients, and the treatment of relapsed or refractory AML (R/R AML) remains a major clini...
Mutations in Fms-like tyrosine kinase 3 (FLT3) are strongly associated with relapse and resistance in acute myeloid leukemia (AML) patients, and the treatment of relapsed or refractory AML (R/R AML) remains a major clinical challenge. We previously conducted a prospective clinical trial on R/R AML with chemotherapy regimen BHA (bortezomib, homoharringtonine and cytarabine), which demonstrated promising efficacy in patients with FLT3-mutated R/R AML. However, the therapeutic mechanism remains unclear. In this study, we aim to elucidate the therapeutic mechanism of BHA regimen on the basis of its efficacy for FLT3-mutated R/R AML. We retrospectively analyzed twenty-nine patients with R/R AML, after one course of therapy, patients harboring FLT3 mutations had a significantly higher complete remission/complete remission with incomplete hematologic recovery rate than those without FLT3 mutations (46.67% vs. 7.14%, respectively; P = 0.035). To further explore the underlying mechanisms, we conducted combination index analysis, inhibition of proliferation and apoptosis assays. Compared with 293 T-FLT3 cells, 293 T-FLT3-ITD cells were more sensitive to bortezomib, with significantly lower IC50 values. Bortezomib in combination with homoharringtonine had a synergistic effect on FLT3-ITD cells. Moreover, compared with monotherapy, the combination of bortezomib (4 nM) and homoharringtonine (1 nM) markedly increased total cell death in FLT3-ITD cell lines (MV4-11 and Molm-13). Mechanistically, bortezomib promoted the degradation of FLT3-ITD protein, and the degradation of FLT3-ITD protein was further enhanced by homoharringtonine. Notably, this degradation effect was partially reversed by chloroquine. These findings demonstrate that bortezomib and homoharringtonine have synergistic effects and lead to degradation of FLT3-ITD oncoprotein, potentially contributing to a higher complete remission rate in FLT3-ITD R/R AML.
PFAS is associated with perineural invasion in triple-negative breast cancer with a potential role for Cathepsin D dysregulation: a multi-omics and experimental study.
Chen S, Su R, Yin Z … +3 more , Chen H, Liu Y, Li A
Clin Exp Med · 2026 May · PMID 42159784 · Publisher ↗
Per- and polyfluoroalkyl substances (PFAS) are persistent pollutants linked to breast cancer (BC), but their role in perineural invasion (PNI) of triple-negative breast cancer (TNBC) is unclear. Cathepsin D (CTSD), a lys...
Per- and polyfluoroalkyl substances (PFAS) are persistent pollutants linked to breast cancer (BC), but their role in perineural invasion (PNI) of triple-negative breast cancer (TNBC) is unclear. Cathepsin D (CTSD), a lysosomal protease, is hypothesized to mediate PFAS-induced PNI, though systematic evidence is lacking. We integrated multi-omics data from TCGA-BRCA, METABRIC, and single-cell RNA-seq datasets. Analyses included differential gene expression, Mendelian randomization, consensus clustering, and machine learning for prognostic modeling. Single-cell analyses were performed using Seurat, Monocle2, and CellChat. GraphBan screened natural CTSD-binding compounds, with binding affinity evaluated by molecular docking and dynamics simulations. Experimental validation included immunohistochemistry, immunofluorescence, Transwell, and Western blot assays. We identified 5 PFAS-associated PNI-related genes (PPGs), with CTSD central to TNBC PNI. PPG-based molecular subtyping revealed a high-risk subgroup exhibiting enhanced epithelial-mesenchymal transition (EMT) activity, proliferation capacity, and significantly poorer overall survival. The PPG-based prognostic model effectively stratified patient outcomes and immunotherapy response. Mendelian randomization confirmed a causal link between genetically predicted CTSD levels and BC risk. Single-cell analysis showed CTSD specifically enriched in myeloid cells; CTSD⁺ myeloid cells displayed immunosuppressive signatures and therapy resistance. CTSD⁺ epithelial cells interacted with cancer-associated fibroblasts via FGF signaling and showed altered metabolism. GraphBan predicted and experiments confirmed Aurantio-obtusin as a high-affinity CTSD inhibitor. Molecular simulations demonstrated stable binding of both PFAS and Aurantio-obtusin to CTSD. Histologically, elevated CTSD expression co-localized with CD68⁺ macrophages in PNI-positive TNBC tissues, while Aurantio-obtusin suppressed CTSD expression and inhibited TNBC cell proliferation and migration. This study suggests that PFAS exposure is associated with PNI and malignant progression in TNBC, potentially involving dysregulation of CTSD. The robust PPG-based prognostic signature and the natural inhibitor Aurantio-obtusin offer novel biomarkers and a potential therapeutic strategy for mitigating PFAS-related cancer risks.
Multi-omics data integration using time-to event endpoint and supervised Cox penalized regression: a comprehensive review.
Dubray-Vautrin A, Le Tourneau C, Mullaert J
Clin Exp Med · 2026 May · PMID 42159777 · Publisher ↗
The integration of multi-omics data, encompassing genomics, transcriptomics, epigenomics, and proteomics, has revolutionized medical research by enabling a more comprehensive understanding of complex diseases like cancer...
The integration of multi-omics data, encompassing genomics, transcriptomics, epigenomics, and proteomics, has revolutionized medical research by enabling a more comprehensive understanding of complex diseases like cancer. Multi-omics prognostic models facilitate improved patient stratification through personalized prognostication. However, the high dimensionality, heterogeneity, and correlations between omics layers pose significant challenges for predictive modelling building, particularly in time-to-event analyses. This review synthesizes current methodologies for variable selection and regularization in high-dimensional settings, focusing on their application to survival outcomes. We explore global penalty approaches, such as LASSO, Ridge, and Elastic Net, which apply uniform penalties to control model complexity and improve generalizability. Parallel regression methods, which independently analyse different omics layers before integrating results, offering robustness but potentially missing critical correlation. Group regularization techniques, including Group LASSO and OSCAR regression, address multicollinearity by clustering correlated predictors, enhancing interpretability in high-dimensional datasets. Hierarchical regression models, such as Priority LASSO and IPF-LASSO, leverage prior knowledge of omics relationships to improve integration and interpretability but may overlook platform interactions. Kernel-based methods like KEN-COX are also examined for their ability to handle nonlinear relationships and reduce dimensionality. Each method presents unique trade-offs between interpretability, computational efficiency, and predictive performance. This review highlights the need for tailored approaches that balance these factors, emphasizing the importance of model transparency and clinical applicability. Future research should focus on refining these techniques to better capture the complex interplay of omics data in disease progression and survival outcomes.
A microfluidic lung cancer-vascular tumor-on-a-chip model for precise evaluation of anti-invasion therapeutics.
Lu J, Huang Y, Ma S … +10 more , Hu S, Xuzhan L, Huang Y, Wu B, Hu Z, Zhao C, Huang J, Tan B, Liu X, Guo Z
Clin Exp Med · 2026 May · PMID 42159639 · Publisher ↗
Lung cancer remains the single leading cause of cancer-related incidence and mortality worldwide, with approximately 90% of all cancer-related deaths due to tumor invasion and metastasis. However, traditional in vitro an...
Lung cancer remains the single leading cause of cancer-related incidence and mortality worldwide, with approximately 90% of all cancer-related deaths due to tumor invasion and metastasis. However, traditional in vitro and animal models are not able to accurately replicate the biologically complex tumor microenvironment; therefore, they limit the exact evaluation of anti-invasion therapies. In the present study, we designed, fabricated and characterized a lung cancer-vascular tumor-on-a-chip utilizing microfluidic technology following previous studies to replicate tumor growth, invasion and interactions with the extracellular matrix (ECM). We discovered that tumor cell invasion into the ECM is profoundly related to cytoskeletal remodeling. We evaluated the drug-screening potential of this model by evaluating five clinically used anti-invasion agents: paclitaxel; cisplatin; irinotecan; oxaliplatin; and gemcitabine. We discovered that gemcitabine inhibited tumor growth, invasion of tumor cells, cytoskeletal remodeling and the ability to invade the ECM, while oxaliplatin principally inhibited invasion. In addition, we also found the model to be very effective for screening for active compounds derived from traditional Chinese medicine, as demonstrated by the natural compound rocaglamide (ROC-A) which inhibited the invasion of tumor cells in a dose-dependent manner at 50 nM. Taken together, our lung cancer-vascular tumor-on-a-chip provides a sound model for studying tumor invasion and demonstrates potential as a platform for precise evaluation.
Dual-positive gastric cancer co-expressing AFP and CEA: an aggressive subtype defined by unique clinical and biological profiles.
Jiang J, Liu H, Liu Y … +2 more , Cao L, Gong W
Clin Exp Med · 2026 May · PMID 42154089 · Publisher ↗
While alpha-fetoprotein-producing gastric cancer (AFPGC) is a highly aggressive variant, a distinct subpopulation exhibits concurrent elevation of both AFP and carcinoembryonic antigen (CEA). In this review, patients wit...
While alpha-fetoprotein-producing gastric cancer (AFPGC) is a highly aggressive variant, a distinct subpopulation exhibits concurrent elevation of both AFP and carcinoembryonic antigen (CEA). In this review, patients with gastric cancer presenting with concurrent elevation of serum AFP (> 7 ng/mL) and CEA (> 5 ng/mL) are classified as dual-positive gastric cancer (DPGC). Compared to AFPGC and common gastric cancer, this phenotype exhibits profoundly more aggressive clinicopathological characteristics. Nearly all cases present at advanced clinical stage III-IV (98.25%) and exhibit extensive lymph node involvement (98.25%), alongside a remarkably high incidence of hepatic metastasis affecting 82.86% of the patients. Beyond its aggressiveness, DPGC frequently presents with severe systemic manifestations, including prominent immune-inflammation, malnutrition and cancer-associated thrombosis. While patients exhibit a median overall survival of merely 6 months under standard chemotherapy, they paradoxically achieve an extended survival of 18 months with combined immunochemotherapy, even though immune infiltration profiling reveals a highly immunosuppressive baseline microenvironment. Since the initial description of concurrent CEA and AFP elevation in gastric cancer in 1977, standardized diagnostic criteria for this extreme phenotype have remained undefined. To address this diagnostic gap, concurrent AFP and CEA evaluation is imperative for prognostic stratification and timely immunotherapeutic interventions. The clinical cohort data were derived from our previously published retrospective study enrolling 127 patients in total, including 57 dual-positive (DPGC) and 70 AFP single-positive (SPGC) individuals. Bioinformatic analyses were based on the TCGA stomach adenocarcinoma cohort. Normal samples and tumor samples without clinical data were excluded, leaving 370 gastric adenocarcinoma cases for analysis. AFP and CEACAM5 were used as transcriptomic surrogates for AFP and CEA, respectively. An AFP-CEA based risk score was calculated using Cox regression coefficients and corresponding gene expression values. Patients were divided into high- and low-risk groups according to the median score. All statistical analyses were performed using R software (version 4.5.1). Kaplan-Meier curves were used to estimate survival outcomes, and group differences were compared using the log-rank test. Cox proportional hazards regression was used for univariate and multivariate survival analyses. Immune infiltration analysis and gene expression comparisons were performed according to the risk groups. Between-group comparisons were performed using the Wilcoxon rank-sum test. All statistical tests were two-sided, and P < 0.05 was considered statistically significant.
DNA methylation biomarkers associated with early gastric cardia carcinogenesis.
Liao X, Zhang Z, Xu G … +5 more , Zheng D, Lei Z, Chen S, Zhao S, Lin R
Clin Exp Med · 2026 May · PMID 42143664 · Publisher ↗
Gastric cardia cancer (GCC) is an aggressive malignancy with poor prognosis, underscoring the need for better characterization of molecular alterations during early gastric cardia carcinogenesis. This study aimed to iden...
Gastric cardia cancer (GCC) is an aggressive malignancy with poor prognosis, underscoring the need for better characterization of molecular alterations during early gastric cardia carcinogenesis. This study aimed to identify and validate tissue-based DNA methylation markers associated with early precancerous and neoplastic lesions of the gastric cardia. We integrated genome-wide DNA methylation data (850 K array) from 69 gastric cardia samples, including normal mucosa (n = 22), intestinal metaplasia (IM, n = 32), intraepithelial neoplasia (IEN, n = 7), and GCC (n = 8). Differential methylation analysis revealed stage-specific methylation patterns. Machine learning algorithms, including Least Absolute Shrinkage and Selection Operator (LASSO) regression and Random Forest, were used to refine candidate diagnostic biomarkers, followed by immunohistochemical validation of candidate gene expression in an independent cohort (n = 212). GCC progression showed increasing epigenetic dysregulation, with hyper-differentially methylated probes (DMPs) predominating in precancerous lesions (79.3-86.3%) and hypo-DMPs in GCC (87.7%). Hyper-DMPs were enriched in promoter-associated cytosine-phosphate-guanosine (CpG) islands (P < 0.001). Two DMPs, EDNRB_cg04390523 and SALL1_cg09016242, were consistently identified by both algorithms and showed good diagnostic accuracy (AUC = 0.947, 95% CI: 0.897-0.997) for distinguishing precancerous gastric cardia lesions and GCC from normal tissue in the integrated dataset. Consistent with methylation findings, EDNRB protein expression progressively decreased from normal to IM/IEN tissues (P < 0.001). This study identifies EDNRB and SALL1 promoter hypermethylation as promising tissue-based candidate biomarkers associated with early neoplastic transformation and provides a basis for further longitudinal and translational studies in gastric cardia precancerous lesions and cancer.
Predictors of pathologic complete response in triple‑negative breast cancer treated with neoadjuvant chemotherapy: a systematic review and meta-analysis.
Li X, Peng K, Li Q
Clin Exp Med · 2026 May · PMID 42143190 · Publisher ↗
Preoperative neoadjuvant chemotherapy (NAC) is a commonly employed treatment strategy for triple-negative breast cancer (TNBC). Various clinical factors may influence the likelihood of achieving a pathological complete r...
Preoperative neoadjuvant chemotherapy (NAC) is a commonly employed treatment strategy for triple-negative breast cancer (TNBC). Various clinical factors may influence the likelihood of achieving a pathological complete response (pCR) following NAC. This study conducted a meta-analysis to identify factors associated with pCR to inform clinical decision-making. EMBASE, PubMed, WOS, Scopus databases were selected as the information sources to identify studies published before July 1, 2025. Predefined inclusion and exclusion criteria were applied, and the quality of included studies was assessed. Commonly reported factors were subjected to meta-analysis. Thirteen studies published between 2011 and 2025 were included, with eight published before 2020 and five thereafter. Seven potential influencing factors were analyzed, including individual characteristics, pathological features, and serum biomarkers. The pooled results indicated that clinical tumor stage (OR (odds ratio) = 0.35, 95% CI: 0.21-0.59, p = 0.032), Ki-67 expression (OR = 2.91, 95% CI: 1.64-5.16, p < 0.001), BRCA1/2 mutation status (OR = 1.95, 95% CI: 1.04-3.66, p = 0.037), and neutrophil-to-lymphocyte ratio (NLR) (OR = 5.61, 95% CI: 2.05-15.34, p < 0.001) were significantly associated with pCR. In contrast, age at diagnosis, histological grade, and nodal status were not statistically significant predictors. The likelihood of achieving pCR in TNBC patients undergoing NAC is significantly associated with clinical stage, Ki-67 expression, BRCA1/2 mutation status, and NLR. These factors should be evaluated prior to chemotherapy to help tailor treatment strategies and optimize therapeutic outcomes.
Integrative bioinformatics and experimental validation identify IL1A as a novel therapeutic target for diabetic wound healing.
Zhang G, An T, Dai S … +2 more , Huang J, Chen P
Clin Exp Med · 2026 May · PMID 42142275 · Publisher ↗
Diabetic foot ulcers (DFUs) represent a severe complication of diabetes mellitus, characterized by impaired wound healing and persistent inflammation. Despite advances in understanding the molecular mechanisms underlying...
Diabetic foot ulcers (DFUs) represent a severe complication of diabetes mellitus, characterized by impaired wound healing and persistent inflammation. Despite advances in understanding the molecular mechanisms underlying DFU pathogenesis, effective therapeutic targets remain limited. This study aimed to identify novel biomarkers and therapeutic targets for diabetic wound healing through integrative bioinformatics analysis and experimental validation. We performed comprehensive transcriptomic analysis of DFU samples (n = 6) compared to normal skin controls (n = 6) from the GEO database (GSE80178). Differential expression analysis, functional enrichment, gene set enrichment analysis (GSEA), and protein-protein interaction network analysis were conducted to identify hub genes. Key findings were validated through in vitro experiments using keratinocyte cell lines cultured under normal glucose (NG), low glucose (LG), and high glucose (HG) conditions, with functional assays including colony formation and scratch wound healing assays. We identified 8,269 differentially expressed genes (DEGs), including 1,852 upregulated and 6,417 downregulated genes in DFU samples. Functional enrichment analysis revealed significant alterations in skin development, keratinocyte differentiation, inflammatory responses, and IL-17 signaling pathways. Hub gene analysis identified interleukin-1 alpha (IL1A) as a central hub gene and a key inflammatory mediator (log2FC = 5.18, adjusted p < 0.001), participating in seven distinct biological pathways. Experimental validation demonstrated that high glucose conditions impaired keratinocyte colony formation and wound closure capacity, accompanied by dysregulated inflammatory responses, consistent with the bioinformatics predictions. Through integrative computational and experimental approaches, we identified IL1A as a critical therapeutic target in diabetic wound healing. Our findings provide mechanistic insights into DFU pathogenesis and establish IL1A as a promising biomarker for developing targeted interventions to improve diabetic wound healing outcomes.
Development and validation of an explainable machine learning model using routine laboratory biomarkers for identifying prevalent MASLD: Evidence from two observational studies.
Wu J, Wei W, Yip TC … +10 more , Deng X, Chen B, Lyu Y, Yu P, Feng T, Xie F, Zhang G, Zhuang K, Li A, Kang W
Clin Exp Med · 2026 May · PMID 42141301 · Publisher ↗
Although many predictive models for metabolic dysfunction-associated steatotic liver disease (MASLD) have been developed, their performance remains suboptimal. We aimed to develop an interpretable machine learning (ML)-b...
Although many predictive models for metabolic dysfunction-associated steatotic liver disease (MASLD) have been developed, their performance remains suboptimal. We aimed to develop an interpretable machine learning (ML)-based plasma biomarker model for identifying prevalent MASLD. Data from the National Health and Nutrition Examination Survey (NHANES 2017-2020) were randomly divided into a training cohort (N = 2760) and an internal cohort (N = 1184). Eleven ML algorithms were employed to construct classification models. Model interpretability was visualized via the SHapley Additive exPlanations (SHAP) method. External validation of these models was further conducted using data from the Korea NHANES (KNHANES) 2019-2021. The association between the selected features and prevalent MASLD was evaluated using restricted cubic spline regression analysis. Feature selection was performed using LASSO regression and the Boruta algorithm. Key predictors included diabetes mellitus (DM), waist circumference (WC), age, hypertension, and atherogenic index of plasma (AIP). All evaluated ML algorithms demonstrated robust predictive capabilities, with areas under the curve (AUC) exceeding 0.70. Among these, the Extra Trees (ET) performed the best, achieving an AUC of 0.879 (95% CI 0.856-0.897) in the internal testing group and maintaining good performance in the external KNHANES cohort with an AUC of 0.822 (95% CI 0.815-0.829). The DeLong test revealed significant differences in AUC between ET and other algorithms. These findings suggest that age, WC, DM, hypertension, and AIP are informative features associated with prevalent MASLD. The ET model showed strong discriminative performance and may serve as a practical tool for MASLD screening.
Integrating Network Pharmacology and Experimental Validation to Elucidate the Role of Huaier in Attenuating Liver Fibrosis via the AKT Signalling Pathway.
Ding J, Ren J, Chen F … +14 more , Lu Y, Ma Y, Zhang T, Shao Z, Tian H, Wang S, Gao Z, Song Y, Zeng J, Wu J, Feng Z, Zhou C, Wang Z, Qian W
Clin Exp Med · 2026 May · PMID 42141267 · Publisher ↗
Liver fibrosis, a critical pathological precursor of cirrhosis and hepatocellular carcinoma, represents a significant unmet global health challenge because of the lack of effective targeted therapies that can reverse est...
Liver fibrosis, a critical pathological precursor of cirrhosis and hepatocellular carcinoma, represents a significant unmet global health challenge because of the lack of effective targeted therapies that can reverse established fibrotic scarring. An integrated strategy was employed. Network pharmacology was used to identify potential targets, followed by molecular docking and dynamics simulations. In vivo validation utilized two established murine models: carbon tetrachloride (CCl4) and bile duct ligation (BDL)-induced fibrosis. In vitro studies employed human LX-2 hepatic stellate cells to assess the antifibrotic effects on myofibroblasts. Huaier administration significantly attenuated liver fibrosis, improved liver function and reduced collagen deposition in both animal models. Histopathological analysis confirmed diminished inflammatory infiltration and fibrotic scarring. In vitro, Huaier suppressed LX-2 cell proliferation and migration. Bioinformatics and simulation analyses suggested AKT1 as a central target, with high-affinity binding with the bioactive steroidal components of Huaier. Mechanistically, Huaier specifically inhibited the phosphorylation and activation of the AKT signalling pathway in hepatic myofibroblasts. This study provides the first compelling evidence that Huaier granules alleviate liver fibrosis by targeting the AKT pathway to inhibit myofibroblast activation. These findings illuminate its mechanistic basis and suggest that Huaier is a promising, multitarget therapeutic candidate for combating fibrotic liver disease.
Pre-transplant JAK-inhibition improves post-transplant outcome in myelofibrosis.
Zielińska P, Wieczorkiewicz-Kabut A, Spałek A … +6 more , Kopińska A, Koclęga A, Woźniczka K, Boral K, Butrym A, Helbig G
Clin Exp Med · 2026 May · PMID 42133107 · Publisher ↗
Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the only curative approach in myelofibrosis (MF). Janus-Associated Kinase inhibitors (JAKi) have changed the treatment paradigm of MF patients, becomi...
Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the only curative approach in myelofibrosis (MF). Janus-Associated Kinase inhibitors (JAKi) have changed the treatment paradigm of MF patients, becoming a therapeutic mainstay in those with splenomegaly and/or constitutional symptoms. The impact of JAKi prior to allogeneic transplant is still under investigation. The aim of the current study was to analyze the outcome and prognostic factors, especially JAKi impact on transplantation outcome in MF patients. The study comprised 96 patients (64 - MF, 21 - post-polycythemia vera (PV), 11 - post-essential thrombocythemia (ET) at a median age of 54 years at transplant (44 females, 52 males) who underwent alloHSCT in years 2008-2025. Forty-seven patients (49%) had previously received JAKi with a median treatment duration of 11 months. Median follow-up after alloHSCT was 11 months. A 2-year probability of overall survival (OS) was 78.5% for JAKi exposed patients and 48.2% for JAKi naïve ones (p = 0.005), event free survival (EFS) was 70.0% and 46.2%, respectively (p = 0.02). A 2-year relapse incidence (RI) was 13.7% and 22.6% (p = 0.298) and non-relapse mortality (NRM) was 18.9% and 40.3% (p = 0.033) in JAKi and no-JAKi exposed group, respectively. Prior JAKi use was the only factor favorably impacting post-transplant overall survival both in uni- and multivariable analysis (p = 0.02 and p = 0.03, respectively). Low ECOG score and low HCT-CI positively affected survival. Transfusion dependency prior to alloHSCT was identified as an unfavorable factor. It was demonstrated that pre-transplant JAK inhibition significantly improved post-transplant overall survival. Patient's performance status and comorbidities are variables significantly affecting survival. Transfusion burden not only adversely impacts quality of life but was also found as an adverse factor in terms of EFS, NRM and RI.
Ultra-Low BCR::ABL1 positivity by digital PCR does not improve post-transplant risk stratification beyond real-time PCR in Ph+ acute lymphoblastic leukemia post-transplant.
Luo Y, Chen WM, Zhao XS … +12 more , Chang YJ, Zhao T, Wu Y, Cheng YF, Mo XD, Sun YQ, Wang Y, Xu LP, Zhang XH, Huang XJ, Qin YZ, Lv M
Clin Exp Med · 2026 May · PMID 42126687 · Publisher ↗
BACKGROUND: Post-transplant relapse remains a major clinical challenge in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Real-time quantitative PCR (RQ-PCR) for BCR::ABL1 is the current standar...
BACKGROUND: Post-transplant relapse remains a major clinical challenge in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Real-time quantitative PCR (RQ-PCR) for BCR::ABL1 is the current standard for measurable residual disease (MRD) monitoring, whereas digital PCR (dPCR) offers substantially higher analytical sensitivity. Whether this increased sensitivity translates into additional prognostic value after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. METHODS: In this prospective study (NCT06211166), 270 patients with Ph + ALL were longitudinally monitored after allo-HSCT. MRD was assessed in parallel using dPCR, RQ-PCR, and MFC. Based on the first post-transplant MRD detection pattern, patients were categorized into four groups: double-negative (n = 80), dPCR-single-positive (n = 158), RQ-PCR-single-positive (n = 3), and double-positive (n = 29). RESULTS: The dPCR-single-positive pattern was the most prevalent MRD status, accounting for 58.5% of patients. dPCR positivity independently predicted subsequent MFC-MRD conversion (HR 9.56, P = 0.029), with a median lead time of 77 days. In addition, dPCR detected BCR::ABL1 positivity earlier than RQ-PCR, preceding subsequent hematologic relapse by a median of 64.5 and 91.5 days, respectively. However, the cumulative incidence of hematologic relapse (CIR), the primary endpoint of this study, did not differ significantly among the four MRD-defined groups (P = 0.60). Consistently, isolated dPCR positivity was not associated with inferior 2-year leukemia-free survival (LFS; P = 0.30) or overall survival (OS; P = 0.60). CONCLUSIONS: Although dPCR detects molecular disease earlier and anticipates MFC-MRD by 2 months after allo-HSCT in Ph + ALL, isolated ultra-low-level BCR::ABL1 positivity does not impact relapse risk, LFS, or OS. Routine MRD monitoring with RQ-PCR plus MFC remains sufficient for prognostic stratification, while dPCR primarily provides an ultra-early signal to guide timely intervention rather than improving survival prediction.
Optimized interpretation of p53 immunohistochemistry for prediction of TP53 mutations and patient survival in DLBCL.
Ruan J, Wang Y, Jia C … +6 more , Zhou D, Zhang Y, Zhao D, Chen X, Wei C, Zhang W
Clin Exp Med · 2026 May · PMID 42126463 · Publisher ↗
The prognostic value of p53 immunohistochemical (IHC) staining in diffuse large B cell lymphoma (DLBCL) remains controversial. We retrospectively included 149 patients who were diagnosed with and treated for DLBCL at Pek...
The prognostic value of p53 immunohistochemical (IHC) staining in diffuse large B cell lymphoma (DLBCL) remains controversial. We retrospectively included 149 patients who were diagnosed with and treated for DLBCL at Peking Union Medical College Hospital (PUMCH). TP53 IHC staining and TP53 sequencing was performed from paraffin-embedded biopsy tissues. Clinical information including basic characteristics and outcome was collected for data analysis. An internal validation cohort of 58 patients with DLBCL was also retrospectively recruited in PUMCH. In the 149 DLBCL cohort, TP53 mutations were detected in 40 patients, with 29 harboring damaging mutations. TP53 mutation showed no significant correlation with either PFS (p = 0.065) or OS (p = 0.140), whereas damaging TP53 mutations were significantly correlated with poor PFS (p = 0.008) and OS (p = 0.030). A novel P53 IHC reading pattern was identified. Using the percentage of cells with strong p53 intensity (p53str) as IHC readout, we discovered a significant correlation of high p53str staining (p53strhigh) with TP53 damaging mutation (p = 0.001). Importantly, p53strhigh was significantly correlated with poorer PFS (p < 0.001) and OS (p = 0.001). The estimated 5-year PFS and 5-year OS rates were 58.8% and 74.3% for p53strlow, and 17.9% (p = 0.001) and 30.1% (p < 0.001) for p53strhigh. Incorporating p53str into the IPI score significantly improved risk stratification of DLBCL. An internal validation cohort of 58 DLBCL patients confirmed the prognostic value of p53str. These results indicate p53str as a promising readout for p53 IHC staining and support its role as a surrogate marker for TP53 mutations and patient survival in DLBCL.
Natural phenolic compounds as modulators of radiation response in hepatocellular carcinoma.
Imani A, Rassouli FB
Clin Exp Med · 2026 May · PMID 42118408 · Publisher ↗
Radiotherapy remains a cornerstone in the treatment of hepatocellular carcinoma (HCC), yet its clinical efficacy is constrained by the intrinsic radioresistance of liver tumors and the dose-limiting toxicity to surroundi...
Radiotherapy remains a cornerstone in the treatment of hepatocellular carcinoma (HCC), yet its clinical efficacy is constrained by the intrinsic radioresistance of liver tumors and the dose-limiting toxicity to surrounding healthy tissue. Natural phenolic compounds (NPCs), including flavonoids (apigenin, genistein, quercetin, fisetin, wogonin, isoliquiritigenin, corylin and epigallocatechin gallate) and other classes (ellagic acid, ferulic acid, chlorogenic acid, pterostilbene, resveratrol, magnolol, curcumin, liensinine, emodin, verbascoside and caffeic acid phenethyl ester), have emerged as promising agents to expand this therapeutic window. Evidence suggests that many NPCs enhance radiosensitivity in HCC cells through convergent mechanisms such as disrupting redox homeostasis to impair Nrf2-mediated antioxidant defenses, inhibiting DNA repair pathways, and reversing hypoxia-driven metabolic reprogramming. Nevertheless, radiosensitizing effects of NPCs is context-dependent, for instance, resveratrol (under hypoxic condition) and chlorogenic acid have demonstrated radioprotective properties, potentially counteracting therapeutic goals. Additionally, methodological limitations-including the use of misidentified cell lines-raise concerns about the reliability of the reported safety and selectivity outcomes for NPCs. Translational success will hinge on overcoming challenges such as poor bioavailability, which may be addressed through tumor-microenvironment-responsive nanotechnology, and exploring synergistic strategies that combine NPCs with radiotherapy and immunotherapy. While NPCs hold considerable promise as radiosensitizers for HCC, future progress requires rigorous validation in authentic adult HCC models to ensure clinical relevance and efficacy.
A prospective, open, single-arm clinical trial of fludarabine- cyclophosphamide-porcine anti-lymphocyte globulin conditioning combined with matched sibling donor hematopoietic stem cell transplantation in the treatment of severe aplastic anemia.
Zhao X, Xu Z, Sun Y … +10 more , Yao Y, Li F, Liu M, Wang L, Zhang Y, Yuan G, Xia L, Liu A, Zhou X, Wang H
Clin Exp Med · 2026 May · PMID 42118371 · Publisher ↗
Hematopoietic stem cell transplantation (HSCT) remains an effective treatment for severe aplastic anemia (SAA), but the optimal conditioning regimen has yet to be established. This study aimed to evaluate the safety and...
Hematopoietic stem cell transplantation (HSCT) remains an effective treatment for severe aplastic anemia (SAA), but the optimal conditioning regimen has yet to be established. This study aimed to evaluate the safety and efficacy of a conditioning regimen consisting of fludarabine (Flu), cyclophosphamide (Cy), and porcine anti-lymphocyte globulin (p-ATG). This prospective single-arm clinical trial enrolled 48 SAA patients who underwent HLA-matched sibling transplantation. The conditioning regimen consisted of p-ATG (120 mg/kg), Cy (120 mg/kg), and Flu (120 mg/m²). All patients achieved neutrophil engraftment (median time of 12 days), with 98% attaining platelet recovery (median time of 13 days). Complete donor chimerism was achieved in 95.8% of patients by day + 30. Cardiac toxicity was observed in three patients. No grade 4 regimen-related toxicity was observed. The cumulative incidences of grade acute GVHD and chronic GVHD were 21.0% (95% CI: 8.5% to 31.8%) and 15.8% (95% CI: 4.2% to 25.9%), respectively. The 1-year overall survival rate was 97.9% (95% CI: 94% to 100%). In this single-arm study, these results indicate that the conditioning regimen of p-ATG combined with Flu and Cy is associated with stable engraftment, an acceptable safety profile, and a manageable incidence of GVHD.
Association of the RDW-to-albumin ratio with MAFLD and hepatic fibrosis in the U.S. population: a national cross-sectional study.
He X, Zeng Q, Liu W … +4 more , Liu Y, Ning M, Zeng X, Luo J
Clin Exp Med · 2026 May · PMID 42113268 · Publisher ↗
Systemic inflammation plays a key role in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD). The red blood cell distribution width (RDW) and serum albumin levels are well-recognized biomark...
Systemic inflammation plays a key role in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD). The red blood cell distribution width (RDW) and serum albumin levels are well-recognized biomarkers reflecting inflammatory and nutritional status. This study systematically investigates the association between the RDW-to-albumin ratio (RAR) and MAFLD, while further analyzing the dose-response relationship between RAR and the severity of hepatic steatosis (assessed by Controlled Attenuation Parameter, CAP) and fibrosis (assessed by Liver Stiffness Measurement, LSM). This cross-sectional analysis was based on data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020. MAFLD was diagnosed in accordance with the 2020 global consensus, combining evidence of hepatic steatosis (via (CAP ≥ 248 dB/m detected by Vibration-Controlled Transient Elastography [VCTE] or ultrasound) and metabolic dysfunction. Multivariate weighted logistic regression models were used to analyze the association between RAR and MAFLD. Restricted Cubic Spline (RCS) analysis was employed to evaluate the dose-response relationships between RAR and CAP, as well as(LSM). Among the 4,453 participants, 2,482 were diagnosed with MAFLD. After full adjustment for confounding factors, each 1-unit increase in RAR was associated with a 69% higher prevalence of MAFLD (OR = 1.69, 95% CI: 1.24-2.31). When RAR was categorized into tertiles, compared with the lowest tertile (RAR < 3.10), the highest tertile (RAR > 3.40) was associated with a 66% increased prevalence of MAFLD (OR = 1.66, 95% CI: 1.09-2.53). RCS analysis revealed a significant linear dose-response relationship between RAR and MAFLD prevalence (P-overall < 0.001, P-nonlinear = 0.09), and significant nonlinear dose-response relationships between RAR and CAP (P-overall < 0.01, P-nonlinear = 0.004) as well as LSM (P-overall < 0.01, P-nonlinear = 0.05). CAP and LSM values increased significantly with elevated RAR. RAR is significantly positively associated with MAFLD prevalence in a linear manner among the U.S. population, and is closely correlated with the severity of hepatic steatosis and fibrosis.
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