Clinical And Experimental Medicine[JOURNAL]
Sun
200 papers
LncRNA SNHG25 promotes proliferation, migration, and invasion of acute myeloid leukemia by competitively binding to miR-205-5p.
Zeng J, Huang L, Sun Q … +2 more , Liang M, Guo F
Clin Exp Med · 2026 Mar · PMID 41865170 · Full text
As a hematological malignancy, acute myeloid leukemia (AML) demonstrates considerable heterogeneity. The pathogenesis and progression are associated with aberrant long non-coding RNA (lncRNA) expression. Research indicat...
As a hematological malignancy, acute myeloid leukemia (AML) demonstrates considerable heterogeneity. The pathogenesis and progression are associated with aberrant long non-coding RNA (lncRNA) expression. Research indicates that lncRNA SNHG25 exerts a pro-cancerous role in various tumors, but its function in AML remains unclear. The aim was to investigate whether SNHG25 regulates AML cells function by competitive binding to miR-205-5p, thereby promoting disease progression. RT-qPCR was utilized to detect SNHG25 and miR-205-5p expression. ROC analysis was applied to evaluate diagnostic capability of SNHG25 for AML. CCK8 and Transwell assays were employed to assess proliferation, migration, and invasion of AML cells. Dual-luciferase reporter system was applied to examine interaction between SNHG25 and miR-205-5p. SNHG25 was upregulated in AML patient serum and AML cell lines. SNHG25 demonstrated a remarkable ability to distinguish AML patients from healthy controls. Overexpression of SNHG25 enhanced AML cell proliferation and accelerated migration and invasion, while silencing SNHG25 showed the opposite trend. Additionally, SNHG25 directly targets miR-205-5p, and co-suppression of SNHG25 and miR-205-5p counteracted functional consequences of silencing SNHG25 on AML cells. SNHG25 promoted malignant phenotypes of AML by adsorbing miR-205-5p, which provides a potential new target for therapy of AML.
Effects and molecular mechanism of inhibiting p53 signaling pathway by NSUN4 on the resistance to BCL-2 inhibitor for diffuse large B-cell lymphoma.
Shi Y, Wen H, Cao T … +7 more , Zhao Y, Xu Y, Sun J, Zheng X, Jin J, Tong H, Xie W
Clin Exp Med · 2026 Mar · PMID 41865121 · Full text
A significant proportion of patients with recurrent and refractory diffuse large B-cell lymphoma (DLBCL) exhibit high levels of BCL-2 expression. However, some of these patients are resistant to BCL-2 inhibitors, and the...
A significant proportion of patients with recurrent and refractory diffuse large B-cell lymphoma (DLBCL) exhibit high levels of BCL-2 expression. However, some of these patients are resistant to BCL-2 inhibitors, and the underlying mechanisms remain unclear. In venetoclax-resistant DLBCL cell line, a Cell Counting Kit-8 (CCK8) assay was used to determine the half-maximal inhibitory concentration (IC50) value. Flow cytometric was performed to determine mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and cell apoptosis rates, respectively. The construction of NSUN4 knockdown/overexpression cell line using CRISPR-Cas9 technology. KEGG pathway enrichment analysis indicated that NSUN4 modulates venetoclax resistance. Furthermore, we used Western blotting to explore the mechanism underlying venetoclax-resistant. Finally, the antileukemic activity was further evaluated in an in vivo xenograft model. We identified that NSUN4, an m5C methyltransferase, is highly expressed not only in the venetoclax-resistant cell line but also in the lymph nodes of recurrent and refractory DLBCL patients primarily by inhibiting the p53 signaling pathway, although the precise mechanism warrants further investigation, and is correlated with poor prognosis. Moreover, we discovered that Apatinib could reduce NSUN4 expression and effectively reverse venetoclax resistance. These findings suggest that NSUN4 is a critical target for overcoming venetoclax resistance in DLBCL patients. Our study reveals the role of NSUN4 and the p53 signaling pathway in venetoclax resistance at the molecular, cellular, and animal levels. Understanding how m5C methylation mediates venetoclax resistance and regulates the p53 pathway will provide a theoretical foundation for overcoming venetoclax resistance in patients with recurrent and refractory DLBCL.
Differential DNAm-GDF15 and mitochondrial profile in lean MAFLD.
Alarabi M, Pan Z, George J … +1 more , Eslam M
Clin Exp Med · 2026 Mar · PMID 41863691 · Full text
Metabolic dysfunction associated fatty liver disease in people of healthy weight (so-called “lean” MAFLD) shows a comparably favorable clinical profile yet paradoxically has an increased risk of mortality. The underlying...
Metabolic dysfunction associated fatty liver disease in people of healthy weight (so-called “lean” MAFLD) shows a comparably favorable clinical profile yet paradoxically has an increased risk of mortality. The underlying mechanisms for this phenomenon, especially their mitochondrial profiles, cellular stress responses and levels of Growth Differentiation Factor 15 (GDF15), a stress-responsive cytokine involved in mitochondrial function and metabolic regulation, and associated with adverse health outcomes, remains unclear. We examined the prognostic value of DNA methylation-predicted GDF15 (DNAm-GDF15) in relation to all-cause and cause-specific mortality, utilizing data from the National Health and Nutrition Examination Survey (NHANES). We assessed the mitochondrial profile and stress response in lean and non-lean MAFLD using murine dietary models and human liver biopsies. Lean MAFLD patients had higher DNAm-GDF15 levels (951.6 ± 151.7 vs. 918.9 ± 143.8; P = 0.01). Elevated DNAm-GDF15 was associated with increased all-cause (Q4 vs. Q1: HR 8.33; 95% CI, 6.84–10.15; P < 0.001) and cause-specific mortality risk. Lean MAFLD has a distinct mitochondrial profile characterised by increased size, impaired function, altered mitochondrial dynamics, augmented endoplasmic reticulum stress responses and reactive oxygen species (ROS) generation. Differences in DNAm-GDF15 levels and mitochondrial profile explain at least partially the paradox of increased mortality risk among individuals with lean MAFLD compared to their non-lean counterparts. It also offers new avenues for therapy to mitigate the risk.
Multi-omics profiling identifies ectopic olfactory receptors as putative drivers of tumor progression and prognostic indicators in clear cell renal cell carcinoma.
Yeo DJ, Cho HJ
Clin Exp Med · 2026 Mar · PMID 41863682 · Full text
Olfactory receptors (ORs) are a subclass of G-protein-coupled receptors (GPCRs) that are primarily expressed in olfactory sensory neurons. Furthermore, ORs have recently been identified in the tumor microenvironment (TME...
Olfactory receptors (ORs) are a subclass of G-protein-coupled receptors (GPCRs) that are primarily expressed in olfactory sensory neurons. Furthermore, ORs have recently been identified in the tumor microenvironment (TME) of various cancers, suggesting potential involvement for ORs in tumor progression. However, the roles of ORs in clear cell renal cell carcinoma (ccRCC), the most prevalent and aggressive subtype of kidney cancer, characterized by limited therapeutic response and a 5-year survival rate of only 10% in advanced stages, have yet to be elucidated. In this study, an integrative multi-omics analysis combining bulk transcriptomic profiles from The Cancer Genome Atlas (TCGA) and single-cell RNA- and ATAC-sequencing datasets from ccRCC patients to characterize the context- and cell-type-specific functions of ORs within the TME. Notably, ORs exhibited distinct, cell-type-specific expression profiles within ccRCC TME. OR51E1 was predominantly expressed in pericytes and correlated with vascular remodeling and angiogenic activity, whereas OR2T10 was enriched in malignant epithelial cells and associated with invasive and metastatic potential, with each OR being associated with resistance to therapeutic agents. In addition, OR-based prognostic modeling and tumor clustering both identified unfavorable prognostic signatures associated with poor patient outcomes and TME-related immunosuppression. These findings highlight ectopic OR networks as clinically relevant molecular features of ccRCC progression and position ORs as potential actionable biomarkers and potential therapeutic targets, offering new avenues for precision oncology in ccRCC.
Unveiling the prognostic and therapeutic landscape of the zinc transporter protein SLC39A family in colorectal cancer through multi-omics and machine learning approaches.
Chen H, Chen C, Chen J … +9 more , Zheng H, Zhu X, Yu Q, Zhou J, Zong J, Lu T, Sun J, Shao Y, Zheng M
Clin Exp Med · 2026 Mar · PMID 41863577 · Full text
Colorectal cancer (CRC) remains a significant global health challenge due to its high prevalence and mortality rates. Zinc transporter proteins of the SLC39A family are crucial mediators of metal ion transport and have b...
Colorectal cancer (CRC) remains a significant global health challenge due to its high prevalence and mortality rates. Zinc transporter proteins of the SLC39A family are crucial mediators of metal ion transport and have been implicated in numerous diseases, including cancer. However, the specific molecular mechanisms underpinning their impact on CRC progression remain poorly understood. By analyzing thousands of CRC patient samples from large-scale public databases, we constructed a SLC39A family-related signature (SFRS) for prognostic prediction through the integration of 101 combinations of 10 machine learning algorithms. This model was utilized to explore tumor biology, immune microenvironment composition, mutation patterns, and responses to immunotherapy in CRC patients. To reinforce these findings, immunohistochemistry (IHC) analyses were conducted on our in-house cohort (RJ-TMA-Cohort) to examine expression levels of two key molecules, SLC39A8 and SLC39A14, and their associations with CRC progression. The SFRS model demonstrated excellent predictive performance, effectively stratifying CRC patients based on tumor characteristics, immune microenvironment, mutation features, and immunotherapy responses. Moreover, IHC and bioinformatic analyses revealed that SLC39A8 and SLC39A14 expression levels are closely associated with CRC progression, emphasizing their potential roles in tumor microenvironment regulation and their value as biomarkers and therapeutic targets. This study is the first to comprehensively investigate the functions of the SLC39A family in CRC, offering novel insights into their roles in tumor development, prognosis, and potential relevance to immunotherapy response. The SFRS model represents a powerful tool for clinical applications, while SLC39A8 and SLC39A14 present promising avenues for future research and therapeutic strategies.
Investigation of the expression and potential mechanistic role of BYSL in acute myeloid leukemia.
Gao J, Wang F, Chen Y … +3 more , Wu P, Jia Y, Song X
Clin Exp Med · 2026 Mar · PMID 41854887 · Full text
BYSL, located on chromosome 6p21.1, is implicated in tumor progression, but its role in acute myeloid leukemia (AML) remains unclear. BYSL expression was analyzed using public databases and AML clinical samples. A progno...
BYSL, located on chromosome 6p21.1, is implicated in tumor progression, but its role in acute myeloid leukemia (AML) remains unclear. BYSL expression was analyzed using public databases and AML clinical samples. A prognostic model incorporating BYSL was constructed and validated. Functional assays were performed by knocking down BYSL in AML cell lines to evaluate proliferation, apoptosis, and cell cycle regulation. To investigate the underlying mechanism, Gene set enrichment analysis (GSEA), Western blotting and chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) assays were performed. BYSL was significantly overexpressed in AML, with high expression correlating with severe anemia and poor overall survival. A risk model incorporating BYSL along with clinical factors (age, cytogenetic risk, transplantation, gene mutations) demonstrated strong predictive accuracy (c-index = 0.754). Functional assays showed that BYSL knockdown significantly inhibited cell proliferation, reduced colony-forming ability, and induced cell cycle arrest at the G0/G1 phase. Mechanistically, BYSL suppression notably decreased PI3K and AKT phosphorylation, implicating this signaling pathway. Additionally, ChIP-qPCR experiments confirmed that BYSL is transcriptionally regulated by c-MYC through direct promoter binding. Our findings support a role for BYSL in AML pathogenesis, potentially through modulation of the PI3K/AKT signaling pathway. Transcriptionally regulated by c-MYC, BYSL may serve as a prognostic biomarker and warrants further investigation as a potential therapeutic target.
Superior outcomes with the FABT regimen in haploidentical transplantation for aplastic anemia in patients under 40 years old: a single-center retrospective study.
Tan Z, Zhu N, Zhao Y … +7 more , Hu H, Yu Q, Zhang Y, Hu T, Wu D, Ye B, Liu W
Clin Exp Med · 2026 Mar · PMID 41851549 · Full text
To compare the efficacy and safety of the FABT regimen versus the conventional FCA regimen in patients under 40 years old with aplastic anemia (AA) underwent haploidentical hematopoietic stem cell transplantation (haplo-...
To compare the efficacy and safety of the FABT regimen versus the conventional FCA regimen in patients under 40 years old with aplastic anemia (AA) underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT). This single-center retrospective study included 75 AA patients under 40 years old who underwent haplo-HSCT between January 2021 and January 2025. Patients were categorized into the Fludarabine-ATG-Busulfan-Thiotepa (FABT) group (n = 25) and the Fludarabine-Cyclophosphamide-ATG (FCA) group (n = 50) based on their conditioning regimen. The FABT regimen featured reduced-dose busulfan, fludarabine, cyclophosphamide, thiotepa, and low-dose anti-thymocyte globulin (ATG), followed by post-transplant cyclophosphamide (PTCy), calcineurin inhibitors, and mycophenolate mofetil for Graft-versus-host disease (GVHD) prophylaxis. Primary endpoints were GVHD-free/relapse-free survival (GRFS) and overall survival (OS). Secondary endpoints included engraftment rates, incidence of acute and chronic GVHD, viral reactivation and treatment response. The 3-year GRFS was significantly higher in the FABT group compared to the FCA group (96% vs. 76%, P = 0.032). The 3-year OS was 96% for FABT and 88% for FCA (P = 0.263). The FABT group demonstrated a significantly higher 1-year complete response (CR) rate (96% vs. 78%, P = 0.021) and a lower 3-year CMV reactivation rate (12% vs. 30%, P = 0.019). No significant differences were observed in engraftment rate, EBV reactivation, or cumulative incidence of acute or chronic GVHD between the two groups. The FABT conditioning regimen demonstrates superior outcomes compared to the FCA regimen in young AA patients underwent haplo-HSCT, characterized by significantly improved GRFS and CR rates, and reduced CMV reactivation, without compromising engraftment or increasing GVHD. This regimen represents a promising therapeutic strategy for this patient population.
TCF7L2/DEPDC1 axis contributes to tumor progression by promoting cell proliferation, aerobic glycolysis, and immunosuppression in pancreatic cancer.
Tasiheng Y, Kenjiabieke J, Tasiheng N … +2 more , Adilijiang K, Cheng H
Clin Exp Med · 2026 Mar · PMID 41851532 · Full text
The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) still remains poor and the exact molecular mechanisms still unclear. Dysregulation of DEP domain containing 1 (DEPDC1) has been implicated in the pat...
The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) still remains poor and the exact molecular mechanisms still unclear. Dysregulation of DEP domain containing 1 (DEPDC1) has been implicated in the pathogenesis of a variety of cancers. However, the role of DEPDC1 in PDAC is poorly understood. Here in this study, we identified that DEPDC1 was high-expressed in PDAC tissues compared with the adjacent normal pancreatic tissues, and its expression level was correlated with poor prognosis of PDAC. We also found that TCF7L2 up-regulated DEPDC1 expression by binding to its promoter sequence specifically. Further bioinfromatic and functional analysis demonstrated that the TCF7L2/DEPDC1 axis can promote tumor cell proliferation and invasion by upregulating glycolysis. Glycolysis reprogramming influences the activation and function of immune cells, ultimately leading to immune escape and cancer progression. In consistent with this, our results showed that the TCF7L2/DEPDC1 axis could form an immunosuppressive tumor microenvironment via promoting tumor glycolysis. Our findings revealed the critical role of TCF7L2/DEPDC1 axis in the carcinogenesis and development of PDAC, which provided a promising therapeutic strategy to improve the prognosis of PDAC patients.
Association of small intestinal bacterial overgrowth with portal hypertension in HCV-related cirrhosis: a cross-sectional study.
Salman T, El-Azab G, Khalil F … +2 more , Elkazaz R, Helal A
Clin Exp Med · 2026 Mar · PMID 41838205 · Full text
Small intestinal bacterial overgrowth (SIBO) is a frequent and clinically significant complication in patients with liver cirrhosis. However, its association with portal hypertension (PH) in HCV-related cirrhosis remains...
Small intestinal bacterial overgrowth (SIBO) is a frequent and clinically significant complication in patients with liver cirrhosis. However, its association with portal hypertension (PH) in HCV-related cirrhosis remains underexplored. To determine the prevalence, predictors, and clinical associations of SIBO in patients with HCV-related cirrhosis, with particular emphasis on its relationship to portal hypertension. In this cross-sectional study, we evaluated 90 patients with HCV-related cirrhosis and 30 control subjects without liver disease. SIBO was diagnosed using quantitative duodenal aspirate cultures. Clinical, laboratory, and endoscopic data were collected. Multivariate logistic regression was performed to identify independent predictors of SIBO. SIBO was detected in 63% of cirrhotic patients with portal hypertension, 41.7% of those without portal hypertension, and 6.7% of controls (p < 0.001). Detectable HCV RNA was significantly associated with higher SIBO prevalence and increased bacterial colony counts (p < 0.001). The most frequently isolated organisms were Enterococcus faecalis and Streptococci. Multivariate analysis identified age (OR = 1.09, p = 0.002), FIB-4 (OR = 1.61, p = 0.001), MELD score (OR = 1.15, p = 0.005), and portal hypertension (OR = 2.89, p = 0.048) as independent predictors of SIBO. SIBO is highly prevalent in HCV-related cirrhosis, especially in patients with portal hypertension and ongoing HCV replication. Age, FIB-4, MELD, and portal hypertension are independent predictors of SIBO. Screening for and managing SIBO may be particularly important in patients with advanced liver disease, especially those with portal hypertension.
Single-cell spatial transcriptomics reveals clonal smooth muscle cell heterogeneity and programs associated with atherosclerotic plaque calcification.
Kong D, Duan X, Zhang T … +16 more , Li Q, Xie Y, Li K, Chen J, Feng Y, Liu X, Deng Z, Shu K, Zhao Q, Zhang X, Wang Y, Liu Y, Lai Z, Wang Y, Shao J, Liu B
Clin Exp Med · 2026 Mar · PMID 41832370 · Full text
Osteochondrogenic transdifferentiation of vascular smooth muscle cells (SMCs) is a key driver of atherosclerotic calcification. Although SMC phenotypic plasticity has been well described, how clonally related SMCs intera...
Osteochondrogenic transdifferentiation of vascular smooth muscle cells (SMCs) is a key driver of atherosclerotic calcification. Although SMC phenotypic plasticity has been well described, how clonally related SMCs interact with spatially defined microenvironments to drive calcification remains incompletely understood. We integrated single-cell RNA sequencing, mitochondrial mutation-based lineage tracing, and high-resolution spatial transcriptomics to construct a spatially resolved transcriptomic atlas of human carotid atherosclerotic plaques across AHA stages III-V. Plaque SMCs originated from multiple distinct clones, each capable of differentiating into diverse phenotypes. Pseudotime analysis revealed that fibroblast-like SMCs (FLSMCs), which arose from clones with higher mitochondrial mutation burdens, could transition into multiple SMC subtypes, including osteogenic-like SMCs (OLSMCs). In AHA stage IV-V plaques, OLSMCs were markedly enriched compared with stage III, particularly within peri-calcification zones located 0.16–0.32 mm from calcified regions. Within these niches, OLSMCs and foam macrophages (MPs) showed pronounced spatial enrichment (80–160 µm) and significant co-localization. Mechanistically, SPP1/FN1 signaling from foam MPs activated CD44/integrin pathways in OLSMCs, promoting calcification. These findings indicate that mitochondrial mutation-linked clonal expansion drives osteogenic differentiation within peri-calcification niches. Our data also suggest that the SPP1/FN1-CD44/integrin axis mediates inflammation-driven crosstalk between foam MPs and OLSMCs, providing a foundation for future studies of plaque calcification.
Association between weekend catch-up sleep and Metabolic dysfunction-associated steatotic liver disease in US adults.
Chen J, Wang W, He J … +1 more , Fang X
Clin Exp Med · 2026 Mar · PMID 41831129 · Full text
The present study aims to investigate the relationship between weekend catch-up sleep (WCS) and Metabolic dysfunction-associated steatotic liver disease (MASLD) in US adults aged 20 years and above. Data were obtained fr...
The present study aims to investigate the relationship between weekend catch-up sleep (WCS) and Metabolic dysfunction-associated steatotic liver disease (MASLD) in US adults aged 20 years and above. Data were obtained from the National Health and Nutrition Examination Survey (2017–2020), a total of 4803 eligible participants were included in this study. Weighted logistic regression modeling, stratified subgroup analysis, and restricted cubic splines (RCS) were employed to examine the association between WCS and MASLD. In weighted logistic regression analyses, a significant positive association was observed between WCS and MASLD risk. When modeled as a continuous variable, each 1-hour increase in WCS was associated with a 9% higher odds of MASLD (OR = 1.09, 95% CI: 1.02–1.16, P = 0.02). Similarly, binary analysis (WCS > 1 h vs. ≤1 h) showed a robust and significant association, with a 38% increase in MASLD odds in the fully adjusted model (OR = 1.38, 95% CI: 1.14–1.67, P = 0.006). The subgroup analyses revealed statistically significant positive associations were specifically observed among older adults (≥ 60 years), individuals with hypertension, and current smokers(P < 0.05), while no statistically significant interactions (all P for interaction > 0.05). A linear dose-response relationship between WCS and MASLD risk was observed in the RCS analysis(P for non-linearity = 0.222; P for overall = 0.003). Prolonged WCS was significantly associated with an elevated risk of metabolic MASLD.
PD-L2 deficiency in Alveolar macrophages drives fibrosis, apoptosis, and ferroptosis via M1 polarization in connective tissue disease-associated interstitial lung disease.
Lu J, Feng X, Chang X … +3 more , Cheng W, Pan P, Wu J
Clin Exp Med · 2026 Mar · PMID 41824094 · Full text
Macrophages play a pivotal role in modulating immune responses in connective tissue disease-associated interstitial lung disease (CTD-ILD). The role of programmed death ligand-2 (PD-L2), an immune checkpoint molecule exp...
Macrophages play a pivotal role in modulating immune responses in connective tissue disease-associated interstitial lung disease (CTD-ILD). The role of programmed death ligand-2 (PD-L2), an immune checkpoint molecule expressed on macrophages, in macrophage polarization in CTD-ILD remains poorly understood. Serum PD-L2 levels were measured in CTD-ILD patients, CTD-nonILD patients, and healthy controls. Alveolar macrophages (AMs) were transfected with PD-L2-targeting shRNA or control constructs, and their effects on macrophage phenotype and fibroblast fate were evaluated. M1/M2 polarization was assessed by RT-PCR, Western blotting, and flow cytometry. Human embryonic lung fibroblasts (HELFs) were co-cultured or treated with macrophage-conditioned media, and assays for cell viability, apoptosis, fibrosis, and ferroptosis were performed. A bleomycin (BLM)-induced CTD-ILD mouse model was used to evaluate the effects of PD-L2 knockout on lung fibrosis and ferroptosis markers. Serum PD-L2 levels were significantly lower in CTD-ILD patients compared with CTD-nonILD patients and healthy controls, and negatively correlated with the extent of lung fibrosis. In vitro, PD-L2 knockdown in AMs promoted M1 polarization, suppressed M2 related markers, and induced fibroblast apoptosis, fibrosis, and ferroptosis. Conditioned media from PD-L2-deficient macrophages produced similar effects. In vivo, PD-L2 knockout mice exhibited decreased numbers of CD206 macrophages and regulated ferroptosis markers (ACSL4 upregulation, GPX4 and FTH1 downregulation) in lung tissues following BLM treatment. This study identifies PD-L2 as an important regulator of macrophage polarization and fibroblast responses in CTD-ILD. Our findings suggest that serum PD-L2 levels may reflect disease severity, and that restoring PD-L2 function could represent a potential therapeutic direction warranting further investigation in preclinical models.
Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Ameliorates Testicular injury to improve spermatogenic disorder through PRDX1/TRAF6/TGFβ signaling pathway.
Tian Y, Quan L, Li Q … +4 more , Zhou X, Peng F, Gong Y, Huang G
Clin Exp Med · 2026 Mar · PMID 41801482 · Full text
Infertility is a significant global health challenge, with male factors contributing to approximately 50% of cases. Here, this experiment investigated the effects of Umbilical Cord Mesenchymal Stem Cells (UCMSCs)-Derived...
Infertility is a significant global health challenge, with male factors contributing to approximately 50% of cases. Here, this experiment investigated the effects of Umbilical Cord Mesenchymal Stem Cells (UCMSCs)-Derived Exosomes Ameliorates Testicular injury and its molecular mechanisms. In a mouse model of testicular injury, treatment with UCMSC-Exos improved spermatogenic dysfunction. We found that these exosomes carried and released PRDX1 mRNA. PRDX1 expression was downregulated in the injured testis, primarily within testicular epithelial cells. Knockdown of PRDX1 (sh-PRDX1) exacerbated spermatogenic disorder, whereas PRDX1 overexpression attenuated oxidative stress in vitro. PRDX1 reduced oxidative stress and inflammation in mice model of Testicular injury. PRDX1 reduced Epithelial fibrosis in Testicular injury model. PRDX1 reduced mitochondrial induced ferroptosis in Testicular injury model. The inhibition of PRDX1 promoted mitochondrial induced ferroptosis in Testicular injury model. PRDX1 suppressed TRAF6/TGFβ Signaling Pathway in mice model of Testicular injury. PRDX1 protein interlinked TRAF6 protein to promote TRAF6 ubiquitination in vitro model of Testicular injury. TRAF6 inhibitor reduced the effects of si-PRDX1 on ferroptosis and Epithelial fibrosis in Testicular injury model through the inhibition of oxidative stress and inflammation. Our findings demonstrate that UCMSC-derived exosomes ameliorate testicular injury and improve spermatogenic disorder. The mechanism involves the exosomal delivery of PRDX1, which subsequently interacts with TRAF6 to promote its ubiquitination, thereby inhibiting the TRAF6/TGFβ signaling pathway. This inhibition attenuates oxidative stress, inflammation, mitochondrial dysfunction-induced ferroptosis, and epithelial fibrosis, ultimately promoting testicular repair.
Real-world single-center analysis of efficacy and safety in newly diagnosed marginal zone lymphoma.
Zhou X, Ruan J, Shi Y … +1 more , Shan N
Clin Exp Med · 2026 Mar · PMID 41795758 · Full text
This study aimed to analyze newly diagnosed marginal zone lymphoma (MZL) patients treated in the Department of Hematology at our center. A retrospective analysis was conducted to evaluate the efficacy and safety profiles...
This study aimed to analyze newly diagnosed marginal zone lymphoma (MZL) patients treated in the Department of Hematology at our center. A retrospective analysis was conducted to evaluate the efficacy and safety profiles of various treatment regimens for MZL. Data were retrospectively collected from 177 newly diagnosed MZL patients hospitalized in the Department of Hematology at Shandong Provincial Hospital Affiliated to Shandong First Medical University between October 2006 and October 2024. Compared to chemotherapy alone, treatment combining CD20 monoclonal antibody with chemotherapy significantly improved the complete response (CR) rate in patients with MZL. Additionally, the incidence of progression of disease within 24 months (POD24) was significantly lower in patients receiving CD20 monoclonal antibody ± chemotherapy than in those treated with chemotherapy alone (11.7% vs. 35.7%, P = 0.018). Comparative analysis of rituximab combined with various chemotherapy regimens revealed no statistically significant differences in either short-term or long-term efficacy (P > 0.05). When comparing short-term outcomes at initial diagnosis, numerically higher CR rates (86.7% vs. 56.3%) and overall response rates (ORR) (100% vs. 90.6%) were observed with the obinutuzumab (G) regimen ± chemotherapy compared to the rituximab (R) regimen ± chemotherapy; however, these differences were not statistically significant (P = 0.144 and P = 0.541, respectively). Compared with chemotherapy alone, CD20 monoclonal antibody-containing regimens significantly improved CR rates and effectively prolonged progression-free survival (PFS) and overall survival (OS) in MZL patients. No statistically significant differences were found among various chemotherapy regimens combined with rituximab, irrespective of whether short-term or long-term outcomes were assessed. Similarly, no significant differences were observed between obinutuzumab (G) ± chemotherapy and rituximab (R) ± chemotherapy in terms of PFS, CR rate, or ORR. However, grade 3–4 adverse events occurred more frequently in patients treated with the G ± chemotherapy regime.
Single-cell profiling reveals MIF-mediated immune evasion and CD8 + T cell exhaustion in relapsed multiple myeloma.
Ma J, Gao S, Liu S … +5 more , Chen L, Lin L, Zhang Z, Zhao Z, Li Q
Clin Exp Med · 2026 Mar · PMID 41795737 · Full text
Multiple myeloma (MM) is a heterogeneous hematologic cancer marked by clonal plasma cell expansion in the bone marrow. Although treatments have improved, relapse remains common due to clonal evolution, tumor microenviron...
Multiple myeloma (MM) is a heterogeneous hematologic cancer marked by clonal plasma cell expansion in the bone marrow. Although treatments have improved, relapse remains common due to clonal evolution, tumor microenvironment changes, ultimately leading to drug resistance. This study utilized single-cell RNA sequencing data analysis to explore immune microenvironment dynamics during MM progression and relapse, aiming to uncover key pathways and cellular interactions correlated with disease relapse. ScRNA-seq data from 20 MM patients (10 primary, 2 remission, 8 relapsed) from the GEO dataset GSE223060 were analyzed. After quality control and batch correction, cells were clustered and annotated. Differential gene expression and functional enrichment analyses were conducted to explore cellular functions. Pseudotime analysis was used to trace plasma cell differentiation, and cell-cell communication was analyzed. Immunohistochemistry and flow cytometry were used for validation.60,234 high-quality single cells were classified into 12 distinct populations. Relapsed MM showed increased T cell infiltration and decreased plasma cells. Relapsed samples had more regulatory T cells (Tregs) and impaired CD8 + T cells. MIF was identified as a key regulator in plasma cell evolution, linked to B cell receptor and interferon-alpha signaling. Enhanced MIF pathway activity was noted between plasma cells and CD8 + T cells in relapsed MM. Increased MIF expression was confirmed in relapsed tissues. Our findings reveal profound immune microenvironment remodeling in relapsed MM, characterized by MIF-mediated signaling, NF-κB suppression, and CD8⁺ T cell dysfunction. These results provide new insights into the mechanisms of MM relapse and highlight potential therapeutic targets for preventing disease relapse.
MFAP4 promotes cell prognosis of non-small cell lung cancer through the inhibition of ferroptosis by FAK.
Li X, Xu C, Min Y … +2 more , Zhu Y, Zhai Z
Clin Exp Med · 2026 Mar · PMID 41795725 · Full text
Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, accounting for 80% of lung cancer types, with a high metastasis rate and mortality. Here, this experiment investigated the effects of MFAP4 in...
Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, accounting for 80% of lung cancer types, with a high metastasis rate and mortality. Here, this experiment investigated the effects of MFAP4 in NSCLC and its molecular mechanisms of ferroptosis in NSCLC. Patients with NSCLC and normal volunteer were obtained from our hospital. The mRNA and protein expression levels of MFAP4 were upregulated in a mouse model of NSCLC. MFAP4 expression levels in cancer cells of NSCLC model through Single Cell Analysis. Sh-MFAP4 reduced cancer growth, and increased Mitochondrial oxidation-induced ferroptosis in mice model of cancer. MFAP4 promoted cell growth, and reduced Mitochondrial oxidation of NSCLC. Si-MFAP4 increased Mitochondrial oxidation of NSCLC. MFAP4 induced FAK expression of NSCLC through the inhibition of FAK Ubiquitination. The m6A/METTL3 modifies MFAP4 expression stability in model of NSCLC by YTHDF1. In conclusion, MFAP4 induced FAK expression to reduce Mitochondrial oxidation-induced ferroptosis of NSCLC model through the inhibition of FAK Ubiquitination. Targeting MFAP4 is thus a potentially effective therapeutic strategy for patients with NSCLC or other cancer.
The role of macrophages and cytokines in the occurrence and development of MDS.
Li P, Li S, Guan D … +5 more , Xu W, Bian J, Deng J, Wang H, Ren F
Clin Exp Med · 2026 Mar · PMID 41795719 · Full text
Myelodysplastic syndrome (MDS) is a clonal hematopoietic system disease characterized by decreased blood cells, hematopoietic failure, and a higher risk of conversion to acute myeloid leukemia (AML). There are a large nu...
Myelodysplastic syndrome (MDS) is a clonal hematopoietic system disease characterized by decreased blood cells, hematopoietic failure, and a higher risk of conversion to acute myeloid leukemia (AML). There are a large number of inflammatory cytokines present in the tumor microenvironment, which play different roles in different stages of tumor development. The pathogenesis of MDS is complex, persistent inflammatory signaling and cytokine dysregulation play critical roles in disease initiation, progression, and leukemic transformation.This article provides a review of the relationship between interaction between immune cells—particularly macrophages—and inflammatory cytokines in the tumor microenvironment and the occurrence and development of MDS.
Impact of albumin infusion on 30-day mortality in ICU patients with acute-on-chronic liver failure: a retrospective cohort using MIMIC-IV database.
Lu S, Weng X, Cao J … +1 more , Zhang J
Clin Exp Med · 2026 Mar · PMID 41794960 · Full text
Human serum albumin (HSA) possesses oncotic, antioxidant, and immunomodulatory properties. Although recent studies suggest that albumin may promote resolution of acute-on-chronic liver failure (ACLF) and reduce the incid...
Human serum albumin (HSA) possesses oncotic, antioxidant, and immunomodulatory properties. Although recent studies suggest that albumin may promote resolution of acute-on-chronic liver failure (ACLF) and reduce the incidence of infection, its impact on overall prognosis with daily administration remains unestablished. Patients meeting the Asian Pacific Association for the Study of the Liver (APASL) criteria for ACLF were extracted from the Medical Information Mart for Intensive Care (MIMIC-IV 2.2) database. The primary outcome was 30-day mortality. To balance baseline characteristics between the albumin and non-albumin groups, we applied stabilized inverse probability of treatment weighting (SIPTW). The association between daily albumin infusion and 30-day mortality was subsequently assessed using Cox regression analyses. A total of 505 patients were enrolled in the study, of whom 325 received albumin therapy within the first 24 h of ICU admission. After applying SIPTW, the cohort comprised 169 patients in the non-albumin group and 319 in the albumin group. Overall, albumin administration was not significantly associated with 30-day mortality in patients with ACLF. However, subgroup analyses revealed that albumin infusion conferred the most substantial survival benefit in specific patient populations. These included individuals with spontaneous bacterial peritonitis, a Model for End-Stage Liver Disease score of ≥ 30.1, a mean arterial pressure below 73 mmHg, a daily albumin dosage of ≤ 1.0 g/kg, or those receiving a combination of 5% and 25% albumin concentrations. Conversely, a dosage exceeding 1.0 g/kg/day was associated with inferior 30-day survival. Albumin administration is associated with reduced mortality in specific subpopulations of patients with ACLF. Key clinical parameters-including serum albumin concentration, SBP, MELD score, and MAP-were identified as significant modifiers of treatment efficacy and should be incorporated into clinical decision-making when initiating albumin therapy.
Real‑life diagnostic and therapeutic approach to CLL/SLL in tuscany: the 2025 consensus.
D'Amato M, Rapolla CM, Benedetti E … +15 more , Bocchia M, Capochiani E, Carlomagno G, Ciofini S, Giachetti R, Maestrini G, Moretti S, Nasso D, Papini G, Pirrotta MT, Simonetti F, Santini S, Vannucchi A, Galimberti S, Sanna A
Clin Exp Med · 2026 Mar · PMID 41793543 · Full text
Management of chronic lymphocytic leukemia/ small lymphocytic lymphoma. (CLL/SLL) has undergone a significant paradigm shift, with chemo immunotherapy being virtually abandoned in favor of targeted agents. A panel of CLL...
Management of chronic lymphocytic leukemia/ small lymphocytic lymphoma. (CLL/SLL) has undergone a significant paradigm shift, with chemo immunotherapy being virtually abandoned in favor of targeted agents. A panel of CLL/SLL experts from Tuscany proposes an updated real-life diagnostic and therapeutic approach that integrates genomic and somatic prognostic factors into routine risk stratification and treatment decisions. While the safety and efficacy of new agents are well-established in both clinical trials and real-world series, the rapid introduction of second-generation BTK inhibitors and BCL-2 antagonists necessitates a uniform and shared approach for daily clinical practice. This updated consensus reinforces the essential role of FISH for 17p deletion and TP53 mutational status before every treatment line, while IGHV mutation status should be performed for initial risk assessment. Reflecting current evidence, the proposal emphasizes a comprehensive pretreatment workup, with a particular focus on cardio-oncological screening and monitoring according to recent ESC guidelines to mitigate risks associated with BTKIs. The consensus reaffirms abdominal and superficial lymph node ultrasound as the gold standard radiological investigation for both diagnosis and response evaluation in CLL, offering a practical and radiation-free tool for longitudinal monitoring. Treatment selection is tailored based on age, genetic risk, and comorbidities, prioritizing zanubrutinib, acalabrutinib, and venetoclax-based regimens to prevent unnecessary toxicities. Furthermore, the consensus addresses the management of high-risk scenarios, including Richter transformation and the emerging role of pirtobrutinib and BTK degraders. By combining the latest clinical evidence with extensive daily experience, this updated Tuscany consensus provides a practical framework for optimized, personalized management of CLL/SLL patients in the modern therapeutic era.
CAR-T therapy for autoimmune rheumatic diseases: navigating clinical frontiers between breakthroughs and uncertainties.
Cheng J, Zhang X, Fan Y … +1 more , Zhang Z
Clin Exp Med · 2026 Mar · PMID 41793501 · Full text
Chimeric antigen receptor (CAR) T-cell therapy, a transformative breakthrough originally pioneered in oncology, is being successfully repurposed for the treatment of refractory autoimmune rheumatic diseases (ARDs). By en...
Chimeric antigen receptor (CAR) T-cell therapy, a transformative breakthrough originally pioneered in oncology, is being successfully repurposed for the treatment of refractory autoimmune rheumatic diseases (ARDs). By enabling profound depletion of pathogenic B cells—a central driver in conditions such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myopathies (IIM)—CAR-T offers a promising therapeutic strategy for patients who have failed conventional therapies. Preliminary clinical evidence from early-phase trials indicates encouraging short-term efficacy across these ARDs. In SLE, treatment with CD19-directed CAR-T has been associated with high rates of lupus low disease activity state and a drug-free remission in a majority of patients. In SSc, CAR-T effectively suppresses inflammatory activity, although established fibrosis often requires continued adjunctive therapy. Promising clinical responses have also been observed in refractory IIM. The short-term safety profile appears favorable, with cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome being predominantly low-grade and manageable. Nevertheless, significant challenges remain. Key knowledge gaps include the long-term durability of responses, the patterns and functional competence of B-cell reconstitution, potential risks of secondary malignancies, and the substantial economic burden of current autologous platforms. Future translation efforts should focus on optimizing patient selection, developing next-generation CAR constructs (including allogeneic “off-the-shelf” products), exploring rational combination strategies, and establishing standardized outcome measures through larger prospective studies with extended follow-up. If validated in rigorous clinical development, CAR-T cell therapy may offer a novel and potent treatment option for carefully selected patients with severe, refractory autoimmune rheumatic diseases.
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