Clinical and Experimental Medicine最新文献

The introduction of vonoprazan has markedly enhanced the effectiveness of the first-line Helicobacter pylori (H. pylori) eradication regimens. This study aimed to compare the effectiveness of vonoprazan-amoxicillin based dual therapy with that of quadruple therapy as second-line treatments, while also investigating potential clinical predictors of therapeutic success. From January 2023 to June 2025, we retrospectively analyzed clinical data from H. pylori-infected patients who received second-line treatment with either: vonoprazan-amoxicillin dual therapy (VA) or VA based quadruple therapy (VAMB; vonoprazan, amoxicillin, minocycline, and colloidal bismuth pectin). The eradication status was evaluated by ^13/14C-urease breath test four weeks after treatment completion. Adverse events and medication compliance were systematically documented during follow-up. The study included 241 patients, with 107 receiving VA dual therapy and 134 undergoing VAMB quadruple therapy. Eradication rates were comparable between groups: 90.7% (VA) versus 92.5% (VAMB) by modified intention-to-treat (mITT) analysis, and 91.4% versus 93.7% by per-protocol (PP) analysis (all p > 0.05). Notably, the VA regimen demonstrated significantly fewer adverse events (8.4% vs 17.9%, p = 0.033). Both treatment arms maintained excellent medication adherence. Compared to the vonoprazan-amoxicillin-minocycline-bismuth (VAMB) quadruple regimen, vonoprazan-amoxicillin (VA) dual therapy achieved comparable eradication efficacy with a more favorable safety profile in second-line H. pylori treatment, representing a simplified yet effective rescue therapy option.

Multiple myeloma (MM) is a complex hematologic malignancy characterized by the abnormal proliferation of plasma cells in the bone marrow. Despite advances in therapy, resistance remains a significant obstacle to curing the disease. Long non-coding RNAs (lncRNAs), a broad family of regulatory RNA molecules, have recently been recognized as important players in MM biology, influencing disease progression and treatment response. This review explores current insights into the diverse roles of lncRNAs in MM, focusing on their involvement in key molecular processes, including miRNA sponging, epigenetic regulation, apoptosis, and interactions with signaling pathways such as PI3K/Akt and STAT3. Additionally, the review evaluates emerging treatment strategies targeting lncRNAs, including RNA-based therapeutics, CRISPR/Cas9 technology, and exosome-mediated delivery systems, assessing their potential to overcome drug resistance and improve clinical outcomes. By integrating molecular research with clinical implications, this review emphasizes the promise of lncRNAs as biomarkers and therapeutic targets in MM and offers a framework for future research and development.

Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced clear cell renal cell carcinoma (ccRCC), but the biomarkers predicting benefits from ICI-based therapies over conventional VEGFR/mTOR inhibitors remain incompletely elucidated. In this study, we analyzed clinical, mutational, and/or transcriptomic data of multiple cohorts, including five clinical trials (JAVELIN Renal 101 [n = 885], IMmotion151 [n = 715], and CheckMate-009/010/025 [n = 1006]), two prognostic cohorts (TCGA-KIRC, n = 537; ICGC, n = 475). Pharmacogenomic analysis was conducted using the cancer cell line encyclopedia (CCLE) database. Our results revealed that only NF1/2 mutations exhibited a consistent relationship with benefits from ICI-based therapies over VEGFR/mTOR inhibitors among all the common mutations in the JAVELIN Renal 101, IMmotion151, and CheckMate-009/010/025 trials (pooled estimate of interaction effect, P = 0.028). In the multivariable models, ICI benefits were higher in the NF1/2-mutant group compared with the NF1/2-wildtype group (avelumab plus axitinib vs. sunitinib: HR_mut = 0.35/HR_wildtype = 0.64; atezolizumab plus bevacizumab vs. sunitinib: HR_mut = 0.55/HR_wildtype = 0.82; nivolumab vs. everolimus: HR_mut = 0.17/HR_wildtype = 0.73). NF1/2 mutations were associated with greater expression of the genes related to FGFR rather than VEGFR or PI3K-AKT-mTOR in advanced ccRCCs and higher sensitivity to FGFR inhibitors instead of VEGFR/PI3K-AKT-mTOR inhibitors in ccRCC cell lines. Compared with the NF1/2-wildtype advanced ccRCCs, those with mutated NF1/2 had an inferior prognosis (HR = 2.53). This tendency was not changed by everolimus (HR = 2.66), but was abrogated slightly by sunitinib (HR = 1.59) and considerably by ICI-based therapies, including nivolumab monotherapy (HR = 1.12), atezolizumab plus bevacizumab (HR = 1.10), and avelumab plus axitinib (HR = 0.69). Overall, our findings suggest that NF1/2 mutations can serve as predictive biomarkers for favorable benefits from ICI-based treatments over VEGFR/mTOR inhibitors in advanced ccRCCs.

Hepatocellular carcinoma (HCC) is a cancer with poor prognosis and high mortality, necessitating the development of various biomarkers to meet clinical treatment needs. Anoikis, a form of programmed cell death, has been shown to be closely related to processes such as cancer proliferation and invasion. However, the role of differentially expressed anoikis-related genes (DEANRGs) in HCC and its control samples remains unclear. Therefore, this study utilized various bioinformatics analysis methods to identify 12 prognostic DEANRGs and constructed a prognostic model for HCC using these genes. This paper thoroughly explores the impact of high- and low-risk groups on participating signaling pathways and the immune infiltration landscape. Subsequently, two reliable HCC subtypes were identified based on the expression levels of DEANRGs. Incorporating scRNA-seq data, cell scores for different cell types were obtained based on the expression levels of DEANRGs using the AUCell algorithm. Finally, several communication pathways between the top-scoring hepatocyte populations and other cell groups were identified. Furthermore, the expression levels of key genes were validated in HCC cell lines (HepG2 and LO2) using qRT-PCR and Western blot. The prognostic DEANRGs obtained in this study can provide references for the treatment and prognostic evaluation of HCC.

Clear cell renal cell carcinoma (ccRCC) remains a major clinical challenge, with high rates of recurrence and limited long-term survival despite surgical resection and VEGF-targeted therapy. Immune checkpoint inhibitors (ICIs)-targeting PD-1, PD-L1, and CTLA-4-have revolutionized first-line systemic treatment, particularly in combination with VEGF tyrosine kinase inhibitors or as dual ICI regimens. However, primary and acquired resistance, immune-related adverse events (irAEs), and heterogeneous treatment responses limit the durability of benefit in many patients. This review aims to address a central question: how can immunotherapy for ccRCC evolve from incremental survival extension to durable, potentially curative control? We highlight emerging strategies-including next-generation checkpoint inhibitors (LAG-3, TIM-3, TIGIT), bispecific T cell engagers, cytokine-based agents, CAR-T and TCR-T therapies, and cancer vaccines-designed to enhance and sustain anti-tumor immunity. In parallel, we examine the role of multi-omic and spatial biomarkers, such as PBRM1 mutations, interferon-γ signatures, single-cell spatial atlases, and gut microbiome profiles, in refining patient selection and predicting therapeutic outcomes. This review uniquely integrates mechanistic insights with translational advances, providing a forward-looking synthesis of precision immunotherapy in ccRCC. We also emphasize rational combination strategies, biomarker-guided personalization, and irAE management as key priorities to overcome resistance and improve long-term outcomes.

Clear cell renal carcinoma (ccRCC) is a prevalent kidney cancer with limited effective biomarkers for prognosis and treatment guidance. Despite advancements, a significant portion of ccRCC cases progress to advanced stages, necessitating novel diagnostic tools. Here, we investigated the expression of MUC1 and its soluble form, CA15-3, in ccRCC, evaluating their potential as biomarkers for angiogenesis and response to sunitinib therapy. Molecular analyses showed that MUC1 expression was associated with angiogenesis, epithelial-mesenchymal transition, hypoxia/metabolism regulation, and complement system activation. In particular MUC1 overexpression correlated with increased microvascular density in vitro and in vivo models. Elevated CA15-3 levels were associated with tumor burden and predict clinical response to sunitinib in metastatic ccRCC. Metabolomic analysis showed that sunitinib-responding tumors were characterized by specific metabolic changes involving glucose and lipid metabolism, in association with impaired oxidative phosphorylation. MUC1 expressing ccRCC is a high angiogenic tumor that presents characteristics of increased aggressiveness, and a specific metabolic profile. Serum CA15-3 is a marker of poor survival and predicts response of sunitinib in patients with metastatic disease.

Hereditary angioedema (HAE), a rare genetic disorder, is classified into 3 types: Type 1 (low C1 esterase inhibitor [C1-INH]), Type 2 (dysfunctional C1-INH), and HAE-nl-C1INH (normal C1-INH levels). This study aimed to compare characteristics among individuals with HAE Type 1/2 and HAE-nl-C1INH. A cross-sectional online survey was conducted (June 2020-September 2021) among adults with HAE to capture various patient-specific data and health care utilization. Statistical analyses included Fisher exact test, t test, and odds ratios (OR) with 95% confidence intervals (CI). Eighty-nine participants were included (HAE Type 1/2, n = 44; HAE-nl-C1INH, n = 45). No significant differences in demographics, treatment characteristics, and HAE triggers were observed between groups. Participants with HAE-nl-C1INH were less likely to be diagnosed before 18 years of age (4% vs. 32%; OR, 0.10; 95% CI, 0.02-0.50) and had higher odds of experiencing frequent HAE attacks (47% vs. 14%; OR, 5.5; 95% CI, 2.0-15.7) than those with HAE Type 1/2. Participants with HAE-nl-C1INH also had increased odds of orofacial-laryngeal swelling (31% vs. 16%; OR, 2.3; 95% CI, 1.1-4.7), more frequent doctor visits (> 1 visit/month: 31% vs. 11%; OR, 3.5; 95% CI, 1.1-10.8), and more concomitant conditions (93% vs. 77%; OR, 3.8; 95% CI, 1.6-9.2). The total health-related quality of life score was significantly worse in participants with HAE-nl-C1INH (53.6 vs. 38.2; p = 0.0001). Participants with HAE-nl-C1INH experience a significantly greater disease burden than those with HAE Type 1/2, emphasizing the need for improved diagnosis, targeted treatment strategies, and a deeper understanding of the prevalence and pathophysiology of HAE-nl-C1INH.

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.