Clinical and Experimental Medicine最新文献

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.

As a novel dietary assessment tool, the dietary index for gut microbiota (DI-GM) measured food intake patterns that influenced GM balance. The association of DI-GM with advanced cardiovascular-kidney-metabolic syndrome (CKM) remained unclear. We aimed to explore the relationship between DI-GM and the advanced CKM risk. Participants from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018 were included. The DI-GM was defined based on intake levels of 10 beneficial and 4 unfavorable foods. To assess the association of DI-GM with advanced CKM risk, we employed multivariate logistic regression, receiver operating characteristic (ROC) analysis, and weighted quantile sum (WQS) regression. About 13,226 eligible participants were enrolled. Multivariable logistic regression showed that each 1-point increment in the DI-GM and beneficial food scores were associated with a 6% (95% CI: 0.92-0.97) and 7% (95% CI: 0.90-0.97) reduction in advanced CKM risk, respectively. Unfavorable food scores showed no significant association with advanced CKM risk. ROC analysis indicated that compared with the baseline model, the addition of the DI-GM (AUC: 0.743 vs. 0.741; P = 0.013) and the beneficial food scores (AUC: 0.743 vs. 0.741; P = 0.005) significantly improved the discriminatory ability of the baseline model for advanced CKM. WQS regression further identified broccoli, soybeans, fermented dairy products, and dietary fiber as the key dietary components strongly associated with advanced CKM. The DI-GM can function as a promising tool for assessing advanced CKM risk. For the general population, especially individuals with metabolic risk factors, increasing the intake of broccoli, soybeans, fermented dairy products, and dietary fiber may help reduce advanced CKM risk.