Clinical And Experimental Medicine[JOURNAL]
Sun
200 papers
Clonal dynamic changes during the progression of myelodysplastic neoplasms to secondary acute myeloid leukemia: a paired-sample comparison.
Ou CW, Kao HW, Lin TL … +4 more , Kuo MC, Wu JH, Chang H, Shih LY
Clin Exp Med · 2026 Jul · PMID 42402084 · Publisher ↗
Patients with myelodysplastic neoplasms (MDS) have a risk of secondary acute myeloid leukemia (sAML) transformation, but previous studies on the paired samples at both MDS and sAML were very rare. This study aimed to inv...
Patients with myelodysplastic neoplasms (MDS) have a risk of secondary acute myeloid leukemia (sAML) transformation, but previous studies on the paired samples at both MDS and sAML were very rare. This study aimed to investigate the genetic changes during the progression from MDS to sAML by comparing both phases of MDS at diagnosis and sAML in the same individuals. Seventy-nine paired matched samples of MDS at diagnosis and sAML phase were examined for 32 gene mutations commonly occurring in myeloid neoplasms, including epigenetic regulators, cohesin complex, spliceosome complex, signaling pathway, tumor suppressors, and transcription factors by next-generation sequencing. The acquisition of gene mutations involving signaling pathway and transcription factors was significantly more frequent during the progression to sAML compared to other groups of genes. Mutations involving epigenetic regulators, cohesin complex, and spliceosome complex were generally stable or expanded when disease progressed. Loss of gene mutations was rare, and all mutations showed no apparent decline in their variant allele frequencies except STAG2 mutation. RUNX1 mutations were characterized by acquisition or clonal expansion with no loss or decline during disease progression. TP53 mutations exhibit unique mutational complexity and evolutionary patterns. The dynamic distribution pattern of various gene mutations remained similar regardless of BM blast counts at MDS or the rate of disease progression. Our results demonstrated a distinct pattern of clonal changes in different groups of gene mutations during the progression from MDS to sAML.
Silibinin promotes hepatocyte proliferation through PINK1/Parkin-mediated mitophagy to alleviate acetaminophen-induced liver injury.
Xu F, Albadry M, Dirsch O … +1 more , Dahmen U
Clin Exp Med · 2026 Jul · PMID 42397441 · Publisher ↗
Acetaminophen (APAP) intoxication is a common cause of liver injury. Silibinin has demonstrated potent hepatoprotective properties. However, its underlying mechanisms in APAP-induced liver injury (AILI) remain unclear. A...
Acetaminophen (APAP) intoxication is a common cause of liver injury. Silibinin has demonstrated potent hepatoprotective properties. However, its underlying mechanisms in APAP-induced liver injury (AILI) remain unclear. Autophagy is a critical adaptive response in AILI, contributing to the clearance of damaged mitochondria and the attenuation of oxidative stress. Therefore, we focused primarily on investigating the role of autophagy in mediating the hepatoprotective effects of silibinin. The effects of silibinin were evaluated in both AML12 cells and a C57BL/6J mouse model of AILI. Both the in vitro and in vivo experiments comprised four groups: a control group, an AILI model group, a silibinin treatment group, and a silibinin plus autophagy inhibitor group using PINK1-siRNA in cell culture and 3-Methyladenine in the animal experiment. Following induction of the AILI model in mice with APAP at a dose of 300 mg/kg, the animals received the designated interventions for five consecutive days. Histopathological alterations were assessed using hematoxylin-eosin staining. Hepatocyte proliferation and apoptosis were evaluated using the CCK-8 assay and immunohistochemical staining for Ki-67 and cleaved caspase-3, respectively, as well as ELISA for Cyclin D1. Liver function was assessed by serum biochemical analysis of alanine aminotransferase, aspartate aminotransferase, total bilirubin, and albumin. Mitochondrial oxidative stress-related parameters, including superoxide dismutase and malondialdehyde, were measured using colorimetric assays. The expression of autophagy-related genes and proteins (PINK1, Parkin, AMPK, LC3 and p62) was analyzed by quantitative PCR, immunofluorescence, and Western blotting. Transmission electron microscopy was employed to examine mitochondrial ultrastructure and the formation of autolysosomes in mouse liver tissue. In AML12 cells, silibinin mitigated AILI by activating the PINK1/Parkin pathway, thereby promoting mitophagy and enhancing cell proliferation. Co-treatment with autophagy inhibitor PINK1-siRNA attenuated these protective effects of silibinin. In AILI mice, silibinin treatment markedly improved liver function, attenuated inflammatory responses, restored mitochondrial function, and enhanced hepatocyte proliferation. These improvements were associated with increased LC3-II expression and reduced p62 accumulation, indicating enhanced autophagic activity. Notably, the protective benefits of silibinin were significantly attenuated by the autophagy inhibitor 3-Methyladenine. Our findings suggest that silibinin protects against AILI by activating PINK1/Parkin-dependent mitophagy, which mitigates oxidative stress and inflammation while promoting hepatocyte regeneration.
Serum GRP78 as a potential biomarker for early liver injury and active fibrogenesis in alcohol-associated liver disease.
Liu Y, Shen Y, Yu Y … +9 more , Meng Y, Zheng Y, Jiang X, Huang W, Yu K, Chen Y, Wu X, Chen C, Liu Y
Clin Exp Med · 2026 Jul · PMID 42384239 · Publisher ↗
Alcohol-associated liver disease(ALD) is an important cause of liver-related lesions and death, mainly caused by long-term or excessive alcohol consumption.Reactive oxygen species (ROS) produced during alcohol metabolism...
Alcohol-associated liver disease(ALD) is an important cause of liver-related lesions and death, mainly caused by long-term or excessive alcohol consumption.Reactive oxygen species (ROS) produced during alcohol metabolism induce an oxidative stress response, which GRP78 playing an important regulatory role. This study aims to investigate the relationship between serum GRP78 levels and liver fibrosis/cirrhosis in ALD patients. A case control study was conducted, involving ALD patients (n = 122) and healthy participants (n = 28). Liver steatosis and fibrosis/cirrhosis was assessed by transient elastography (TE) and biochemical parameters were collected. Serum GRP78 was measured by sandwich ELISA based on two monoclonal anti-GRP78 antibodies and calibrated with a standard of recombinant GRP78. Serum GRP78 levels increased in alcohol-associated steatohepatitis and alcoholic hepatitis patients correlated with early fibrosis severity (F1 fibrosis stage), but were significantly downregulated in patients with cirrhosis (F4 fibrosis stage). Furthermore, serum GRP78 levels showed a weak negative correlation with liver stiffness measurements (LSM; r = - 0.2064, p = 0.0365) and demonstrated a notable association with the severely advanced fibrotic stage in ALD patients, while showing no significant correlation with the controlled attenuation parameter (CAP) associated with liver steatosis. This study suggests that serum GRP78 is a potential noninvasive biomarker for early liver injury and active fibrogenesis in ALD patients. When combined with LSM, it improves diagnostic accuracy for advanced fibrosis and cirrhosis.
Beyond polarization: a receptor-centered framework for macrophage function and therapy in skin diseases.
Zhu Y, Yao H, Xiang W
Clin Exp Med · 2026 Jul · PMID 42380346 · Publisher ↗
Macrophages are key regulators of cutaneous immunity, but the traditional M1/M2 polarization model cannot fully explain their functional diversity across skin diseases. In this narrative review, we use selected skin dise...
Macrophages are key regulators of cutaneous immunity, but the traditional M1/M2 polarization model cannot fully explain their functional diversity across skin diseases. In this narrative review, we use selected skin diseases to discuss a receptor-centered view of macrophage function and to illustrate a modular "receptor-pathway-effector" framework. This perspective places macrophage receptors at the upstream sensing level, where microbial products, tissue damage signals, cytokines, immune complexes, stromal cues, and tumor-derived signals are translated into inflammatory, reparative, fibrotic, or immunosuppressive programs. We summarize representative receptor modules, including pattern-recognition receptors, cytokine and chemokine receptors, Fc and complement receptors, scavenger and efferocytosis receptors, and inhibitory checkpoint receptors. Across psoriasis, atopic dermatitis, autoimmune blistering diseases, lupus, systemic sclerosis, sarcoidosis, leprosy, melanoma, cutaneous T-cell lymphoma, diabetic wounds, and radiation-induced skin injury, these modules help explain macrophage involvement in inflammation, remodeling, host defense, impaired repair, and tumor immune escape. We also discuss selected biomarker and therapeutic examples, while distinguishing clinically explored approaches from preclinical or emerging concepts. This receptor-centered perspective may complement existing views of macrophage heterogeneity and provide a clearer way to link receptor signals with disease-related macrophage functions.
UBA2: the gatekeeper of the sumoylation pathway and its multifaceted roles in human diseases and therapeutic prospects.
Liu Y, Deng Q, Qu Y … +5 more , Yi M, Wang T, Li X, Zhang R, Wu Y
Clin Exp Med · 2026 Jun · PMID 42373928 · Publisher ↗
Ubiquitin-like modifier-activating enzyme 2 (UBA2), the core catalytic subunit of the ubiquitin-activating enzyme (E1) for the small ubiquitin-like modifier (SUMO)ylation pathway, is the "gatekeeper" determining cellular...
Ubiquitin-like modifier-activating enzyme 2 (UBA2), the core catalytic subunit of the ubiquitin-activating enzyme (E1) for the small ubiquitin-like modifier (SUMO)ylation pathway, is the "gatekeeper" determining cellular SUMOylation levels. However, a systematic, cross-disease integration of its pathogenic mechanisms and translational value in human diseases is currently lacking. In this review, a disease taxonomy framework was used for the first time to systematically elucidate the multidimensional pathogenic mechanisms of UBA2 in tumors, developmental malformations, autoimmune diseases, and infectious diseases. Research indicates that functional dysregulation of UBA2 is a central node connecting diverse diseases: Driving malignant progression and therapy resistance in tumors, causing congenital malformations during development, acting as a pathogenic factor or autoantigen in autoimmunity, and being targeted by various pathogens for immune evasion. Based on its pivotal role, UBA2 has emerged as an important prognostic biomarker and therapeutic target, with related inhibitors demonstrating promise in preclinical studies. This article further elucidates the strategies and challenges in the clinical translation of precision therapies targeting UBA2, providing a theoretical foundation and translational roadmap.
Clonal Metamorphosis: Deconstructing MPN Evolution with Single-Cell and Spatial Multi-Omics.
Iqbal MS, Alahmari AK, Khan MF … +6 more , Farooqui S, Iqbal MZ, Khan SU, Khan N, Seshadri VD, Abdelgawwad El-Sehrawy AAM
Clin Exp Med · 2026 Jun · PMID 42371175 · Full text
Myeloproliferative neoplasms (MPNs) present a fundamental paradox: despite sharing a small set of canonical driver mutations in JAK2, CALR, or MPL, patients exhibit striking heterogeneity in disease latency, clinical pre...
Myeloproliferative neoplasms (MPNs) present a fundamental paradox: despite sharing a small set of canonical driver mutations in JAK2, CALR, or MPL, patients exhibit striking heterogeneity in disease latency, clinical presentation, and evolutionary trajectories to myelofibrosis or secondary acute myeloid leukemia. This review synthesizes recent advances in single-cell and spatial multi-omic technologies that are resolving this paradox by moving analysis from bulk averages to individual cells and their microenvironmental ecosystems. We examine how targeted single-cell DNA sequencing reconstructs clonal architectures and phylogenies, revealing that driver mutations arise within complex mosaics where mutation order, co-mutation context, and cellular ancestry determine phenotypic outcomes. Integrated single-cell transcriptomic and epigenomic profiling exposes within-clone heterogeneity, lineage biases, and functional states that explain variable penetrance and therapy responses. Spatial transcriptomics, especially when integrated with single-cell transcriptomics, histopathology, and multiplex proteomics, further demonstrates that malignant hematopoietic stem and progenitor cells actively remodel bone marrow niches, creating localized inflammatory and fibrotic microenvironments that select for aggressive subclones. Together, these approaches support a new ecological model of MPN pathogenesis in which early epigenetic hits create permissive stem cell reservoirs, clonal competition and cooperation shape disease progression, and non-cell-autonomous niche and immune signals drive malignant metamorphosis. We discuss how this framework refines prognostication, informs rational combination therapies targeting both malignant cells and their ecosystem, and enables real-time monitoring of clonal dynamics, ultimately charting a course from descriptive atlases to actionable clinical strategies.
Identifying coagulation-related biomarkers in steroid-induced osteonecrosis of the femoral head: implications for early diagnosis and treatment.
Xie C, Du J, Liu Z … +3 more , Lv Y, Ni H, Yu F
Clin Exp Med · 2026 Jun · PMID 42366267 · Publisher ↗
Steroid-induced osteonecrosis of the femoral head (SONFH) is closely associated with coagulation dysfunction, but its molecular mechanisms remain incompletely understood. This study aimed to identify coagulation-related...
Steroid-induced osteonecrosis of the femoral head (SONFH) is closely associated with coagulation dysfunction, but its molecular mechanisms remain incompletely understood. This study aimed to identify coagulation-related biomarkers for SONFH and evaluate their diagnostic relevance. The GSE123568 dataset from the Gene Expression Omnibus database (GEO) was analyzed, and differentially expressed genes (DEGs) were intersected with coagulation-related genes (CRGs) from the Molecular Signatures Database to identify coagulation-related differentially expressed genes (CRDEGs). Functional enrichment analysis was performed to explore the biological processes and pathways associated with these genes, while protein-protein interaction network analysis and three machine learning algorithms were applied to identify key genes. A nomogram model was constructed and evaluated using bootstrap internal validation. Gene set enrichment analysis, single-sample gene set enrichment analysis, competing endogenous RNA network, and Drug Signature Database analyses were performed to explore potential regulatory mechanisms. The expression levels of the key genes were preliminarily assessed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). In total, 49 CRDEGs were identified and were mainly enriched in immune response, blood coagulation, and complement and coagulation cascades. PECAM1, LGALS3, and ANXA5 were identified as key genes. The prediction model constructed based on these genes showed favorable diagnostic discrimination, with a bootstrap AUC of 0.939 (95% CI: 0.840-0.977). RT-qPCR showed decreased PECAM1 and LGALS3 expression and increased ANXA5 expression in SONFH patients. These findings suggest that PECAM1, LGALS3, and ANXA5 may serve as potential coagulation-related biomarkers for SONFH, providing a basis for further clinical validation and mechanistic investigation.
KIF7 promotes the proliferation of clear cell renal cell carcinoma by activating the WNT/β-catenin signaling pathway.
Wang Y, Wang XM, Huo D … +10 more , Wang SB, Liu QY, Pang J, Shen T, Cui D, Zhao WJ, Luo QF, Li N, Chen AQ, Cui J
Clin Exp Med · 2026 Jun · PMID 42366250 · Full text
Aberrant activation of SHH signaling contributes to the progression of multiple malignancies, with KIF7 functioning as a critical mediator that regulates signal transduction from SMO to GLI transcription factors. However...
Aberrant activation of SHH signaling contributes to the progression of multiple malignancies, with KIF7 functioning as a critical mediator that regulates signal transduction from SMO to GLI transcription factors. However, the specific role of KIF7 in ccRCC has not been fully elucidated. In this study, we investigated the expression pattern, prognostic significance, functional role, and potential mechanisms of KIF7 in ccRCC. Analysis of TCGA-KIRC data demonstrated that KIF7 expression was significantly elevated in tumor tissues compared with adjacent normal tissues. High KIF7 expression was strongly associated with advanced pathological stage and poor overall survival. IHC performed on commercial tissue microarrays further confirmed increased KIF7 protein levels in ccRCC samples. Functional experiments in the 786-O cell line revealed that KIF7 overexpression markedly enhanced cell proliferation. Mechanistically, KIF7 overexpression activated the Wnt/β-catenin signaling pathway and upregulated downstream cell cycle regulators, including c-Myc and c-Jun. KIF7 expression was positively correlated with infiltration of CD4 + T cells, macrophages, and neutrophils. Moreover, it showed significant positive associations with immune checkpoint molecules PDCD1 and CD160. GSCA/GDSC-based drug sensitivity prediction suggested that high KIF7 expression was associated with increased predicted sensitivity to docetaxel and bleomycin, whereas no significant association was observed for I-BET-762. In conclusion, KIF7 plays a tumor-promoting role in ccRCC by enhancing proliferation, activating Wnt/β-catenin signaling. Additionally, it was associated with shaping the immune microenvironment. These findings highlight KIF7 as a potential prognostic biomarker and therapeutic target in ccRCC.
Correction: 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 Jun · PMID 42366234 · Full text
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Harnessing the gut microbiome for improved immune checkpoint inhibition in colorectal cancer immunotherapy: a narrative Review.
Abebaw D, Adugna A, Tegegne BA … +9 more , Teffera ZH, Selabat B, Kindie Y, Tilahun M, Belew H, Baylie T, Mengistu G, Jemal M, Atnaf A
Clin Exp Med · 2026 Jun · PMID 42365572 · Publisher ↗
Colorectal cancer (CRC) remains among the most prevalent and deadliest malignancies worldwide, with limited survival outcomes, particularly in patients with metastatic disease. Despite advances in immunotherapy, immune c...
Colorectal cancer (CRC) remains among the most prevalent and deadliest malignancies worldwide, with limited survival outcomes, particularly in patients with metastatic disease. Despite advances in immunotherapy, immune checkpoint inhibitors (ICIs) have shown efficacy mainly in mismatch repair-deficient (dMMR) CRC, while responses in mismatch repair-proficient (pMMR) microsatellite-stable (MSS) cases remain limited. Emerging evidence highlights the gut microbiome as a critical factor influencing CRC development, progression, and therapeutic response. In particular, the gut microbiota has been shown to affect the efficacy of ICIs, with dysbiosis contributing to treatment resistance and specific microbial taxa enhancing antitumor immune responses. Preclinical and clinical studies have demonstrated that microbiome-based interventions, including probiotics, fecal microbiota transplantation (FMT), dietary modulation, and traditional medicines, can restore immune function by modulating immune cell populations and producing immunoregulatory metabolites. These effects may enhance responsiveness to ICIs and contribute to the suppression of tumor growth. However, we also address key limitations in this field, including inconsistent findings and safety concerns, such as infection risks, to guide future translational efforts. Overall, while microbiome-based interventions represent a promising adjunct to CRC immunotherapy, rigorous clinical trials and mechanistic validation are required before their routine clinical implementation.
Beyond the JAK2 mutation: The inflammasome, clonal stability, and the thrombotic niche in myeloproliferative neoplasms.
Abdelgawwad El-Sehrawy AAM, Al-Khreisat MJ, Kibriyeva M … +5 more , Dilbar I, Axmedova F, Mohammed JA, Mishra S, Tailor NK
Clin Exp Med · 2026 Jun · PMID 42365545 · Full text
Philadelphia-negative myeloproliferative neoplasms (MPNs) carry a disproportionate thrombotic burden that cannot be explained by conventional cardiovascular risk factors or blood count parameters alone. This review synth...
Philadelphia-negative myeloproliferative neoplasms (MPNs) carry a disproportionate thrombotic burden that cannot be explained by conventional cardiovascular risk factors or blood count parameters alone. This review synthesizes emerging evidence positioning MPN-associated thrombosis as a distinct pathobiologic entity, clonal thrombo-inflammation, driven by the convergence of somatic mutations and innate immune activation. We examine the continuum from clonal hematopoiesis of indeterminate potential (CHIP) to overt MPN, highlighting how Janus kinase 2 (JAK2)V617F and other driver mutations reprogram myeloid cells toward hyperinflammatory phenotypes. A recurring mechanistic theme is NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and interleukin-1 family signaling, which may create a feed-forward loop in which mutant clones amplify inflammatory circuits that, in turn, may enhance clonal fitness and contribute to thrombogenicity across multiple cellular compartments. We propose the 'thrombotic niche' as a conceptual, multi-compartment model encompassing mutant hematopoietic stem cells, hyperinflammatory myeloid effectors, hyperreactive platelets, platelet-leukocyte aggregates, and activated endothelium, but it remains a hypothesis-generating framework that lacks direct prospective clinical validation. Current cytoreductive strategies inadequately address this underlying biology, leaving substantial residual vascular risk. Emerging anti-inflammatory and anti-clonal strategies targeting interleukin-1 beta (IL-1β) (canakinumab), mutant-selective JAK2 inhibition, NLRP3 inflammasome blockade, and P-selectin-mediated adhesion are biologically plausible, but their ability to reduce thrombotic events in MPN remains unproven and should be viewed as hypothesis-generating rather than established clinical benefit. We conclude by outlining a translational research agenda integrating inflammation-aware risk stratification, niche-directed imaging, and spatial multi-omics to guide precision anti-inflammatory interventions in MPN.
Serum TIMP-1 shows a potential association with metastatic disease in patients with pancreatic cancer: a pilot analysis without a healthy control cohort.
Vecurkovska I, Roskovicova V, Gajdzik T … +4 more , Soltes M, Maslankova J, Kocanova I, Katuchova J
Clin Exp Med · 2026 Jun · PMID 42365195 · Publisher ↗
Pancreatic ductal adenocarcinoma (PDAC) is most often diagnosed at an advanced stage, when distant metastases are already present and curative treatment options are limited. In this clinical context, biomarkers capable o...
Pancreatic ductal adenocarcinoma (PDAC) is most often diagnosed at an advanced stage, when distant metastases are already present and curative treatment options are limited. In this clinical context, biomarkers capable of reflecting tumor aggressiveness and metastatic potential are of particular relevance. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been implicated in tumor invasion and metastatic dissemination; however, its clinical significance in pancreatic cancer remains incompletely defined. We analyzed TIMP-1 concentrations in serum and pancreatic tissue of 154 patients (108 malignant tumors, 46 benign lesions) using ELISA. Associations with clinical stage and the presence of distant metastases were assessed using non-parametric tests and ROC curve analysis. TIMP-1 levels were significantly higher in malignant compared with benign tumors, both in tissue (24.28 vs. 21.62 ng/mL; p = 0.0318) and serum (28.03 vs. 25.52 ng/mL; p = 0.0106). Serum TIMP-1 showed superior diagnostic accuracy (AUC = 0.796) compared to tissue TIMP-1 (AUC = 0.745). Patients with distant metastases exhibited significantly higher serum TIMP-1 levels than non-metastatic cases (28.33 vs. 26.53 ng/mL; p = 0.0046; AUC = 0.785). Serum TIMP-1 is associated with malignant and metastatic pancreatic disease and reflects a more aggressive tumor phenotype in patients with established pancreatic cancer. While the observed differences are modest and limit its applicability as a stand-alone diagnostic or screening biomarker, TIMP-1 may provide clinically relevant information regarding metastatic status and could contribute to prognostic stratification or multimarker approaches in pancreatic cancer.
The burden and unique patterns of extraintestinal manifestations in Chinese inflammatory bowel disease: a nationwide multicenter investigation.
Zhao L, Fan Z, He J … +11 more , Tian L, Shen J, Gao H, Chen Y, Zhao X, Yu YB, Fan Y, Shi H, Cao H, Tian L, Liang J
Clin Exp Med · 2026 Jun · PMID 42360371 · Publisher ↗
Extraintestinal manifestations (EIMs) are a significant disease burden in inflammatory bowel disease (IBD). However, large-scale epidemiological data from the Chinese population remain scarce. This nationwide, multicente...
Extraintestinal manifestations (EIMs) are a significant disease burden in inflammatory bowel disease (IBD). However, large-scale epidemiological data from the Chinese population remain scarce. This nationwide, multicenter, retrospective cross-sectional study included 2,252 adult IBD inpatients from 10 clinical centers. Data on demographics, clinical features, and EIMs were collected and analyzed using descriptive statistics and logistic regression. Of the 2252 patients, 384 (17.1%) reported at least one EIM. Among these, data on temporal sequence were available for 310 patients, of whom 70 (22.6%) developed their first EIM before the onset of intestinal symptoms. The overall prevalence of EIMs was significantly higher in Crohn's disease (CD) than in ulcerative colitis (UC) (20.5% vs. 15.4%, P = 0.003). Joint manifestations (10.0%) and aphthous ulcers (5.5%) were most common, with aphthous ulcers significantly more frequent in CD (11.2% vs. 2.8%, P < 0.001). The prevalence of classic EIMs such as arthritis/arthralgia (8.0%), uveitis (0.5%), and erythema nodosum (0.9%) fell within the low-to-mid range of global reports. Significant co-occurrence was observed among EIMs. For example, arthritis/arthralgia showed strong associations with uveitis (OR = 31.88) and erythema nodosum (OR = 13.34). Analysis of medication history revealed higher use of infliximab in patients with arthritis/arthralgia (47.0%) and pyoderma gangrenosum (71.4%), and frequent glucocorticoid use in those with venous thromboembolism (72.4%). In this inpatient-based cohort, the lower prevalence of classic EIMs in Chinese IBD patients may reflect clinical underdetection or genuine epidemiological differences. EIMs can precede intestinal symptoms and influence each other, underscoring the need for proactive, systematic assessment in clinical practice.
Global trends in the burden of inflammatory bowel disease from 1990 to 2021: socioeconomic and sex-specific disparities with exploratory mendelian randomization analyses.
Cheng Y, Wang Z, Peng Y … +7 more , Dang Y, Deng Y, Sha S, Liu X, Wang J, Shi H, Xie N
Clin Exp Med · 2026 Jun · PMID 42350868 · Publisher ↗
Inflammatory bowel disease (IBD) shows substantial variation in burden across regions and populations worldwide. However, patterns of IBD b3urden across levels of socio-demographic development remain incompletely charact...
Inflammatory bowel disease (IBD) shows substantial variation in burden across regions and populations worldwide. However, patterns of IBD b3urden across levels of socio-demographic development remain incompletely characterized, and complementary evidence on selected individual-level exposures is limited. Utilizing GBD 2021 data, we assessed age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and disability-adjusted life years rate (ASDR) from 1990 to 2021 across socio-demographic index (SDI) strata. Temporal trends were estimated using estimated annual percentage change and Joinpoint regression. Pearson analysis and frontier analyses assessed SDI correlations, while inequality was measured using the concentration index and slope index. Decomposition analysis was performed to identify the contributors of population growth, population aging, and epidemiological change. Two-sample Mendelian randomization (MR) analysis was conducted to examine potential associations between selected exposures and IBD. From 1990 to 2021, the global ASIR rose by 0.29 annually, while ASPR, ASMR and ASDR decreased by 0.13, 0.31 and 0.52. Burden patterns differed across SDI strata. High SDI regions had the highest age-standardized burden in 2021. The largest increases in ASIR and ASPR were observed in middle SDI regions, and declines in ASMR and ASPR began later in low SDI regions than in high SDI regions. ASDR was positively correlated with SDI in females but not in males, and cross-country inequality in ASDR was greater in females than in males. Decomposition analysis showed that population aging contributed more to changes in ASMR and ASDR in high SDI regions, while population growth was the dominant contributor in low SDI regions. Fifteen countries showed large effective differences between observed ASDR and frontier values at comparable SDI levels. In MR analyses, several nominal associations were observed, but none remained significant after false discovery rate (FDR) correction. The burden of IBD showed substantial heterogeneity across SDI levels and between sexes in GBD 2021, with a more pronounced inequality pattern in disability burden among women. The MR findings did not remain significant after FDR correction and should therefore be interpreted cautiously as exploratory signals. These findings underscore the importance of context-specific strategies to reduce inequalities in IBD burden across populations and between women and men.
Mapping the research landscape of myelodysplastic syndromes: a scientometric analysis (2014-2025).
Li J, Seetoh WS, Xu H … +5 more , Tao Y, Liu M, Cai S, Lu J, Lu C
Clin Exp Med · 2026 Jun · PMID 42350707 · Publisher ↗
This scientometric study critically evaluates the global evolution of myelodysplastic syndromes (MDS) research from 2014 to 2025, aiming to integrate fragmented knowledge and identify emerging trends. A scientometric ana...
This scientometric study critically evaluates the global evolution of myelodysplastic syndromes (MDS) research from 2014 to 2025, aiming to integrate fragmented knowledge and identify emerging trends. A scientometric analysis was conducted using data retrieved from the Web of Science Core Collection on August 2, 2025. The search was restricted to "article" and "review" in English containing "Myelodysplastic syndrome" or "Myelodysplastic syndromes" in the abstract, covering the period from January 1, 2014 onward. Scientometric tools (VOSviewer, CiteSpace, R-bibliometrix) were employed to analyze annual publication trends, country/institution/author contributions, collaboration networks, journal distribution, reference co-citation clusters, emerging research topics. Analysis of 6,822 publications revealed that global MDS research output peaked in 2021. The USA dominated with 2,838 publications, followed by China (1,169) and Germany (717), while top institutions (e.g., University of Texas MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center) and prolific authors (e.g., Garcia-Manero G, Kantarjian HM) were predominantly USA-based. Collaboration networks revealed a core-periphery structure with strong transatlantic ties and emerging Asian contributions. Thematic analysis identified research hotspots across multiple dimensions, including 5q deletion, trisomy 8, germline predisposition, TP53 mutation, clonal hematopoiesis, inflammation, venetoclax, luspatercept, targeted therapy, immunotherapy, pediatric population, VEXAS syndrome, IPSS-R, relapse, prognosis, overall survival, and artificial intelligence. MDS research is shifting toward precision medicine. Future advances are expected to rely on multi-ethnic cohort building, mechanism exploration, combined treatment regimen optimization and novel drug development. Strengthening multidisciplinary collaboration is anticipated to facilitate clinical translation and foster more precise, equitable and clinically practical management of MDS globally.
C-reactive protein-to-lymphocyte ratio and stroke: associations with prevalence and subsequent mortality in NHANES 1999-2010.
Miao Y, Chen J, Zheng Z … +5 more , Zhang Y, Liu R, Chu J, Li S, Liu Y
Clin Exp Med · 2026 Jun · PMID 42348049 · Publisher ↗
Early risk detection is critical for timely intervention to reduce stroke morbidity and recurrence rate. This study systematically investigated the association between the CRP-to-lymphocyte ratio (CLR) and stroke prevale...
Early risk detection is critical for timely intervention to reduce stroke morbidity and recurrence rate. This study systematically investigated the association between the CRP-to-lymphocyte ratio (CLR) and stroke prevalence, aiming to evaluate whether CLR may serve as a convenient and readily accessible inflammatory biomarker for stroke prediction. Data were analyzed from the 23,483 participants in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2010. Multivariable logistic regression models were employed to assess the relationship between CLR and prevalent stroke. Among 789 individuals with a history of stroke, Cox proportional hazards models were used to examine the association between CLR and all-cause as well as cause-specific mortality. Kaplan-Meier survival curves were constructed to compare survival outcomes across CLR strata defined by an optimal cutoff. Restricted cubic spline (RCS) analysis was applied to explore potential nonlinear relationships. The predictive value of CLR was compared with that of established inflammatory markers using receiver operating characteristic (ROC) curve analysis. After adjusting for potential confounders, elevated CLR is significantly and independently associated with higher odds of stroke prevalence in the fully adjusted model (OR = 1.005, 95% CI: 1.002-1.007, P < 0.001). Kaplan-Meier analysis demonstrates significantly higher mortality risks among stroke participants with CLR above the optimal threshold. RCS models showed no evidence of nonlinearity between the CLR and mortality risks. Furthermore, ROC analysis indicated that CLR exhibited superior predictive ability compared to the established inflammation markers, including the Systemic Immune-Inflammation Index (SII), Neutrophil-to-Lymphocyte Ratio (NLR), C-reactive protein (CRP), and lymphocyte counts (all P < 0.05). These findings suggest that CLR is an independent and significant predictor of both the stroke prevalence and all-cause mortality in stroke patients, highlighting its potential utility as a readily accessible inflammatory biomarker for stroke prevalence stratification. Given its ease of derivation from routine examination data, CLR holds promise for broad clinical applicability. Further prospective studies are warranted to elucidate the underlying mechanisms and to validate its predictive value in diverse populations.Trial registration: This study is a secondary analysis of publicly available NHANES data and does not constitute a clinical trial; therefore, trial registration is not applicable.
Decoding the immunometabolic landscape identifies SLC7A5 as a vulnerability in chemo-immunotherapy resistant TNBC.
Zhong S, Yu B, Zhou S … +5 more , Chen W, Liu F, Zhu H, Min F, Qian F
Clin Exp Med · 2026 Jun · PMID 42347972 · Publisher ↗
Metabolic reprogramming within the tumor microenvironment (TME) limits the efficacy of chemo-immunotherapy in triple-negative breast cancer (TNBC). Despite advances in high-resolution profiling, the specific intercellula...
Metabolic reprogramming within the tumor microenvironment (TME) limits the efficacy of chemo-immunotherapy in triple-negative breast cancer (TNBC). Despite advances in high-resolution profiling, the specific intercellular metabolic crosstalk driving immune evasion remains incompletely understood. Here, we present a comprehensive single-cell metabolic atlas of the TNBC ecosystem to decode spatial and cell-type-specific metabolic vulnerabilities. Our multidimensional analysis reveals a distinct paracrine metabolic communication axis: CXCL9 macrophages upregulate rate-limiting enzymes (IDO1/2) to become a potential source of local kynurenine, which is subsequently imported by cytotoxic T cells. Through in vitro co-culture and in vivo models, we demonstrate that this kynurenine uptake triggers impaired effector function and phenotypic exhaustion. Crucially, pharmacological blockade of SLC7A5 with the specific inhibitor JPH203 abrogates this metabolic toxicity, restores T cell effector function, and enhances the anti-tumor efficacy of combined cisplatin and anti-PD-1 therapy. Collectively, our findings delineate the Kynurenine-SLC7A5 metabolic axis as a critical driver of immunosuppression, providing a compelling rationale for integrating amino acid transport blockade to overcome resistance to chemo-immunotherapy.
Decoding the association between microorganisms and autoimmunity: a multifaceted review of evidence on specific pathogens that trigger autoimmune diseases.
Zhang H, Hu J, Sun J … +2 more , Sun L, Xu C
Clin Exp Med · 2026 Jun · PMID 42340492 · Publisher ↗
The occurrence and progression of autoimmune diseases (AIDs) result from the combined effects of genetic susceptibility, immune response defects, and environmental triggers. Among these, microorganisms, as key environmen...
The occurrence and progression of autoimmune diseases (AIDs) result from the combined effects of genetic susceptibility, immune response defects, and environmental triggers. Among these, microorganisms, as key environmental factors, have been widely hypothesized to play a role in initiating AIDs, but the exact causal relationship remains to be demonstrated. This review aims to deeply explore the core role of specific microbial infections in triggering AIDs by integrating evidence from three dimensions: epidemiological investigations, clinical studies, and animal model research. We focused on analyzing nine AIDs, including Guillain-Barré syndrome, systemic lupus erythematosus, and rheumatoid arthritis, and confirmed that specific pathogens such as Campylobacter jejuni, Epstein-Barr virus, and Porphyromonas gingivalis can induce corresponding autoimmune pathological damage in susceptible individuals through mechanisms including molecular mimicry and bystander activation. Nevertheless, the field still faces important gaps that caused the chain from mechanism association to clinical application to break.This review integrates existing evidence and demonstrates that microbial infections are one of the important triggers for AIDS. It provides a new theoretical basis and direction for mechanistic research, risk early warning, and targeted intervention of related diseases.
GRP78 in viral pneumonia: dual regulatory mechanisms and translational prospects.
Ruan H, Huang QR, Zou LJ … +1 more , Li SS
Clin Exp Med · 2026 Jun · PMID 42337188 · Publisher ↗
Glucose-regulated protein 78 (GRP78), a core molecular chaperone governing the endoplasmic reticulum (ER) stress response, exerts dual regulatory effects during the pathogenesis of viral pneumonia. Beyond serving as a cr...
Glucose-regulated protein 78 (GRP78), a core molecular chaperone governing the endoplasmic reticulum (ER) stress response, exerts dual regulatory effects during the pathogenesis of viral pneumonia. Beyond serving as a critical cofactor that promotes viral invasion and replication, GRP78 functions as an indispensable protective chaperone that preserves pulmonary cellular homeostasis and attenuates lung injury. This review characterizes two distinct subcellular localizations of GRP78 in viral pneumonia, namely ER-resident GRP78 and cell surface GRP78 (csGRP78), and systematically summarizes its dual regulatory mechanisms. Specifically, csGRP78 mediates viral adhesion and internalization, whereas ER-GRP78 promotes viral replication and aggravates pulmonary inflammation by modulating ER stress and the unfolded protein response. Meanwhile, GRP78 alleviates pulmonary tissue damage via suppressing lung cell apoptosis and restraining excessive ERS activation. Moreover, this review provides a comprehensive overview of advances in GRP78-targeted therapeutic strategies. The covered therapeutic modalities include small-molecule inhibitors, biological macromolecular drugs, indirect regulatory compounds, and natural products. This review also elaborates their specific molecular targets, core mechanisms, and preclinical findings. Additionally, the current research trends, existing limitations, and future perspectives of GRP78-related investigations are critically discussed. This review aims to clarify the central regulatory role of GRP78 in viral pneumonia, providing theoretical basis and innovative research directions for the precision targeted therapy of viral pneumonia.
Inflammatory blood count ratios discriminate disease activity and remain persistently elevated during glucocorticoid-free remission in ANCA-associated vasculitis.
Davanzo F, Iorio L, Pelloso M … +8 more , Davanzo V, Prevedello R, Padoan A, Baggio C, Oliviero F, Ramonda R, Montagnana M, Padoan R
Clin Exp Med · 2026 Jun · PMID 42332125 · Publisher ↗
Inflammatory ratios derived from routine complete blood counts, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), have been proposed as activi...
Inflammatory ratios derived from routine complete blood counts, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), have been proposed as activity markers in ANCA-associated vasculitis (AAV), but their interpretation is limited by heterogeneous sampling and treatment-related confounding. We conducted a single-center cross-sectional study including adult patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Patients were sampled during active disease (new-onset prior to induction or relapse prior to escalation) or during stringent glucocorticoid-free remission (BVASv3 = 0). Healthy controls (HCs) were included for secondary comparisons. Ratios were compared across groups and correlated with BVASv3 and c-reactive protein (CRP). Between-group differences (active vs. remission; remission vs. healthy controls) were additionally quantified using age- and sex-adjusted log-linear models (log-transformed outcomes), reported as ratios of geometric means. Discriminative performance for active disease versus remission was assessed using unadjusted ROC analyses and age- and sex-adjusted logistic regression models. Sensitivity analyses stratified remission by maintenance immunosuppression at sampling. The study included 99 AAV patients (28 active, 71 remission) and 258 HCs. NLR, PLR, and MLR were significantly higher in active disease than in remission (all p ≤ 0.004), and remained significantly higher after age/sex adjustment in log-linear models (geometric mean ratios [Active/Remission]: NLR 1.97, PLR 1.64, MLR 1.40). NLR and PLR correlated moderately with BVASv3 (ρ = 0.506 and 0.478, respectively; both p < 0.001) and CRP. Discriminative performance was strongest for NLR and PLR: in age- and sex-adjusted models, AUC increased from 0.664 (age/sex only) to 0.832 after adding NLR and 0.827 after adding PLR (whereas the AUC after adding MLR was 0.724). During glucocorticoid-free remission, ratios remained higher than in HCs (geometric mean ratios: NLR 1.55 [1.39-1.74], PLR 1.18 [1.08-1.29], MLR 1.40 [1.27-1.55]; all p < 0.001). Treatment stratification within remission showed lower lymphocyte counts and higher PLR in patients on maintenance immunosuppression, while NLR discrimination remained robust across strata. Routine blood count-derived inflammatory ratios, particularly NLR and PLR, discriminate active AAV from stringent glucocorticoid-free remission independent of age/sex, and remain persistently altered during remission. These inexpensive and widely available indices may complement clinical assessment, warranting prospective validation and evaluation of prognostic value.
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