Clinical and Experimental Medicine最新文献

Sarcopenia and arthritis, characterized by age-related progressive loss of skeletal muscle mass and function, profoundly impact the well-being of older adults. Our study endeavors to explore the unclear genetic structure between them. Using advanced statistical genetic approaches and genome-wide association study (GWAS) summary statistics, we explored the shared genetic basis among multiple manifestations of sarcopenia and four distinct arthritic conditions: osteoarthritis, rheumatoid arthritis, psoriatic arthritis, and gouty arthritis. We employed global and local genetic methods to gain potential shared biological mechanisms and determine binary local genetic correlations. Cross-phenotype association GWAS studies have revealed many genetic variations associated with complex traits. Transcriptome-wide association studies were conducted using weights from various human tissues to identify risk loci. We functionally annotated genomic multi-markers and fine-mapping colocalization by conducting the whole-genome unified testing of molecular characteristics. Significant correlations between sarcopenia and arthritis were detected through comprehensive and local genetic correlation analyses. At the genomic level, we identified 19 unique bivariate regions, including chr3q27.3, chr5q35.3, and chr12q13.2-q13.3, involving multiple human genes such as KBM7, GM12878, and IMR90. Gene enrichment analyses revealed that the selected loci primarily signaled through elementary pathways, including central nervous system neuron axonogenesis, glutamatergic synapse, and beta-catenin binding. Specifically, GDF5 and DNAJC27 were prioritized as the most probable candidate genes via transcriptomics. Our study has identified pleiotropic genomic regions linking sarcopenia and arthritis, providing novel insights into their genetic mechanisms.

Background: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder whose prevalence increases with age and may progress to multiple myeloma. The tumor microenvironment plays a crucial role in MGUS pathogenesis and progression. Systemic immune-inflammatory markers can reflect tumor microenvironment(TME) dynamics, but their association with MGUS odds remains understudied.

Methods: This cross-sectional study analyzed data from 12,080 adults aged ≥ 50 years (including 350 MGUS cases) in the National Health and Nutrition Examination Survey (NHANES III and 1999-2004 cycles). Multivariable logistic regression assessed associations between systemic immune-inflammatory markers [lymphocyte-to-monocyte ratio(LMR), Platelet-to-lymphocyte ratio(PLR), Hemoglobin, albumin, lymphocyte, platelet score(HALP), and their individual components] and MGUS. Generalized additive models identified nonlinear relationships and threshold effects across stratified groups.

Results: Higher LMR quartiles were positively associated with MGUS prevalence (Q4 vs. Q1: OR = 1.454, 95% CI 1.048-2.016), while elevated monocyte counts (OR = 0.624, 95% CI 0.456-0.853) and albumin levels (OR = 0.446, 95% CI 0.317-0.627) correlated with reduced MGUS odds. Nonlinear analysis revealed a U-shaped association between PLR and MGUS. There are race-specific nonlinear correlations involving LMR, PLR, and lymphocyte counts with MGUS.

Conclusions: Systemic immune-inflammatory markers are significantly associated with MGUS odds in older adults, highlighting their potential for early detection and longitudinal monitoring.

Multi-disciplinary treatment (MDT) has become a routine practice in clinical cancer diagnosis and treatment, playing an indispensable role in clinical decision-making. By integrating expertise from multiple disciplines, MDT provides patients with individualized diagnosis and treatment strategies. However, there is not yet a specialized clinical data visualization tool for MDT. This paper develops a novel clinical data analysis visualization tool for MDT, which analyzes in-depth and displays patient data comprehensively. Specifically, this tool designs a latent Dirichlet allocation (LDA)-based visualization model for clinical unstructured data, and Z-Score-3σ transformation and hierarchical strategies for clinical structural data. Moreover, we propose to predict personalized anti-tumor drug efficacy based on topic keywords. The results showed that, compared with users who did not use the tool, the time cost in MDT decision-making for users who used the tool was reduced by 26.17%. Furthermore, the proposed drug efficacy prediction method achieved an accuracy rate of 71.08% on a dataset of 958 patients with non-small cell cancer treated with anti-tumor drugs. The proposed tool is potentially helpful for doctors in MDT tasks by vividly visualizing the large-scale complex clinical data and improving the MDT efficiency.

The treatment of corticosteroid-resistant or dependent primary immune thrombocytopenia (ITP) remains a clinical challenge. This study aims to evaluate the efficacy and safety of eltrombopag (Elt) in combination with cyclosporine A (CsA) in adults with primary ITP who are corticosteroid-resistant or dependent. This prospective phase II trial enrolled 28 patients from December 2020 to December 2023. All patients fulfilled the diagnostic criteria for ITP and were refractory to prior glucocorticoid (GC) therapy, defined as meeting at least one of the following criteria: (1) GC-resistant (failure to respond to both standard-dose prednisone and high-dose dexamethasone regimens); (2) GC-dependent (relapse during tapering or after discontinuation of GCs). The patients were administered combination therapy consisting of Elt with an initial dose of 50 mg taken nightly, and CsA at a dosage of 3-5 mg/kg/day targeting a trough concentration of 150-250 µg/L, with dose adjustments made in accordance with platelet counts. Efficacy was evaluated at the 8-week mark, with a response defined as a platelet count of ≥ 30 × 10⁹/L and a two-fold increase from baseline, in the absence of bleeding that required clinical intervention. Patients who achieved a response continued with maintenance therapy with the same regimen. Among the 25 evaluable patients, 92.0% (23/25) achieved a response (platelet count ≥ 30 × 10⁹/L), with 72.0% (18/25) attaining a complete response (platelet count ≥ 100 × 10⁹/L). The median time to response was 14 days, the median bleeding score decreased from 2.0 to 1.0, and 78.3% (18/23) maintained remission. Adverse events were systematically evaluated using the Common Terminology Criteria for Adverse Events version 5.0. The most frequently observed adverse events included gingival hyperplasia (60.7%, predominantly Grade 1), hirsutism (35.7%, all Grade 1), and infections (10.7%, including two fatal cases). The combination of Elt and CsA shows rapid and durable efficacy in adults with corticosteroid-resistant or dependent ITP, but necessitates careful monitoring for CsA-related toxicities and infections, contributing to clinical treatment of adult refractory ITP patients. This trial was registered in the Chinese Clinical Trial Registry under the number ChiCTR2000040991.

The present study aims to investigate the relationship between blood selenium and NAFLD. Data were obtained from the National Health and Nutrition Examination Survey (2017-2020), a total of 3940 eligible participants were included in this study. Multivariable logistic regression, subgroup analyses, and smooth curve fitting assessed the blood selenium-NAFLD relationship. A piecewise linear regression model identified potential thresholds. Model robustness was evaluated using multiple imputation. Among 3,940 participants, NAFLD prevalence was 45% (n = 1,173). Compared to the lowest blood selenium quartile (Q1: 103.10-169.49 µg/L), the adjusted odds ratios for NAFLD were 1.44 (95% CI: 1.16-1.78; P < 0.01) in Q3 (184.56-201.29 µg/L) and 1.26 (95% CI: 1.02-1.57; P = 0.035) in Q4 (201.30-562.23 µg/L) after full covariate adjustment (Q2 was non-significant). Each 1-standard deviation increase in log-transformed blood selenium corresponded to an adjusted odds ratios of 1.16 (95% CI: 1.08-1.26) for NAFLD. Gender significantly modified this association (P for interaction < 0.05). Adjusted smooth curve fitting demonstrated a significant non-linear positive dose-response relationship (P for non-linearity = 0.026). Elevated blood selenium concentration is significantly associated with an increased risk of NAFLD in US adults, exhibiting a non-linear dose-response pattern. This finding requires confirmation in future prospective cohort studies. Such association, if confirmed, will be of considerable public health relevance given the epidemic of NAFLD.

Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play vital, context-specific roles in cancer, functioning as either tumor suppressors or oncogenic factors. Preliminary evidence suggests that a primary mechanism of ncRNA influence is through the interferon (IFN) signaling pathway, with a focus on how they may regulate IFN-induced immune surveillance and immunotherapy outcomes. Types I, II, and III IFNs regulate antitumor immunity, antigen presentation, and immune checkpoint activity, but can also support tumor growth in certain scenarios. Evidence indicates ncRNAs modulate IFN signaling by targeting IFN receptors, JAK-STAT components, interferon-stimulated genes (ISGs), and IRFs. Some ncRNAs suggest potential to enhance antitumor immune responses and improve responses to IFN-based therapies, while others may dampen immune activity, contribute to therapy resistance, or promote metastasis. This review centers on how ncRNAs act as tumor suppressors or promoters through modulating IFN signaling to influence immunotherapy efficacy, demonstrating their versatile roles in shaping immune surveillance across various cancers. Although encouraging, experimental findings face challenges like functional complexity, delivery barriers, and off-target effects that must be addressed before clinical application. By integrating mechanistic and translational perspectives, this review highlights potential new opportunities to target ncRNA-IFN interactions for personalized medicine and advanced immunotherapies.

MZB1 is an endoplasmic reticulum (ER)-resident chaperone that facilitates immunoglobulin assembly and secretion, particularly polymeric IgM and dimeric IgA. Accumulating evidence links MZB1 to the regulation of intracellular Ca²⁺ signaling, integrin activation, and ER stress responses, which could influence innate-like B-cell functions and the maintenance of immune homeostasis. Aberrant expression of MZB1 has been implicated in the development of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), as well as in tumor progression, including hepatocellular carcinoma and multiple myeloma. In certain cancer, MZB1 expression is associated alterations in the tumor microenvironment that may be permissive for tumor progression. Conversely, its ability to enhance antibody responses suggests potential applications in immunotherapy. This review integrates current insights into MZB1 biology, summarizes its role in disease pathogenesis, and discusses future directions for therapeutic targeting.

Background: Endoscopic submucosal dissection is the standard treatment for superficial esophageal squamous cell carcinoma. However, esophageal preservation following this procedure increases the risk of metachronous multiple cancers. Lugol-voiding lesion grade and alcohol-related genetic polymorphisms have been identified as risk factors, but the role of nonspecific mediastinal lymphadenopathy remains unclear.

Methods: We retrospectively analyzed the data of 154 patients who underwent curative endoscopic submucosal dissection for esophageal squamous cell carcinoma at Hamamatsu University Hospital between 2015 and 2024. Pretreatment computed tomography was used to evaluate the Lugol-voiding lesion grade and nonspecific mediastinal lymphadenopathy. Associations with pathological findings and the development of metachronous multiple esophageal squamous cell carcinoma were assessed using Kaplan-Meier and Cox regression analyses.

Results: Nonspecific mediastinal lymphadenopathy was identified in 68 patients (59.6%). Pathological analysis including 154 patients revealed that nonspecific mediastinal lymphadenopathy was significantly associated with lymphovascular invasion (P = 0.026) but not with invasion depth or curative resection. During follow-up and metachronous analysis including 114 patients, 21 patients developed metachronous multiple esophageal squamous cell carcinoma. Both Lugol-voiding lesion grade and nonspecific mediastinal lymphadenopathy were independent predictors of recurrence. Subgroup analysis restricted to Lugol-voiding lesion grade B/C cases confirmed that nonspecific mediastinal lymphadenopathy remained predictive of recurrence-free survival (P = 0.007).

Conclusions: Nonspecific mediastinal lymphadenopathy independently predicts the development of metachronous esophageal squamous cell carcinoma after endoscopic submucosal dissection. Evaluation of nonspecific mediastinal lymphadenopathy in combination with Lugol-voiding lesion grade may improve risk stratification and optimize surveillance strategies.