Ziyun Li

JOURNAL/mgres/04.03/01612956-202701000-00006/figure1/v/2026-11-03T121139Z/r/image-tiff Hydrogen, an emerging medical gas, has demonstrated diverse biological effects, including anti-oxidant, anti-inflammatory, and anti-apoptotic activities, offering significant therapeutic potential in cardiovascular diseases. This study aimed to explore the applications of hydrogen therapy in cardiovascular diseases and to illustrate both the current research status and future trends. 162 publications (129 original articles and 33 reviews) on hydrogen therapy in cardiovascular diseases were retrieved from the Web of Science Core Collection database up to April 9, 2025. The information was analyzed using Excel 2019, OriginPro 2024, VOSviewer 1.6.20 and CiteSpace 6.2. The number of publications on hydrogen therapy for cardiovascular diseases has shown a significant increase, with China, Japan, and the United States of America being the leading contributors. Keio University published the largest number of articles, and Sano Motoaki, the most prolific author ( n = 14), is also from Keio University. Keyword clustering analysis shows that current research hotspots include “ischemia-reperfusion injury,” “cardiac arrest,” “oxidative stress,” “inflammation,” and “apoptosis,” while emerging directions may focus on the “NLRP3 inflammasome,” “pyroptosis,” and “micro/nanomaterials.” The underlying mechanisms of hydrogen therapy and its delivery approaches remain key research hotspots of hydrogen therapy for cardiovascular diseases; however, further high-quality clinical studies are needed to strengthen the evidence base and support its wider clinical application.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for metastatic colorectal cancer (mCRC) exhibiting DNA mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). However, the comparative efficacy and safety of monotherapy versus dual immunotherapy remain inadequately quantified. This meta-analysis aims to evaluate the benefits and risks of these strategies by quantitatively synthesizing data from randomized controlled trials (RCTs) to inform clinical decision-making. We systematically searched major databases (PubMed, Web of Science, Cochrane, Embase) from inception to September 2025 for relevant RCTs. Outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and adverse events. Statistical analyses were performed using RevMan 5.3 and Stata 18.0. Six RCTs (1,460 patients) were included. Pooled analysis showed that PD-1/PD-L1 monotherapy significantly improved ORR compared with chemotherapy (OR = 1.52, 95% CI: 1.02–2.27, P = 0.04), based on two RCTs (n = 429), and demonstrated a significantly lower incidence of grade ≥ 3 adverse events (OR = 0.14, 95% CI: 0.08–0.23, P < 0.00001; 2 studies). Dual immunotherapy with nivolumab plus ipilimumab significantly improved ORR versus monotherapy (OR = 1.77, 95% CI: 1.25–2.49, P = 0.001), based on one RCT (n = 582), with a significantly increased toxicity risk (OR = 1.73, 95% CI: 1.22–2.44, P = 0.002). For PFS, KEYNOTE-177 (HR = 0.59, 95% CI: 0.45–0.79) and CheckMate 8HW (HR = 0.62, 95% CI: 0.48–0.81) showed significant benefits, while SAMCO-PRODIGE 54 and CheckMate 9 × 8 did not demonstrate statistically significant PFS improvement. OS hazard ratios across four studies ranged from 0.74 to 1.03, with all 95% confidence intervals crossing 1.0, indicating no statistically significant survival benefit in any individual study. DOR was consistently longer with immunotherapy, with median not reached for pembrolizumab versus 10.6 months for chemotherapy in KEYNOTE-177. Effect estimates for PFS, OS, and DOR generally favored immunotherapy; however, confidence intervals were wide and statistical significance was not consistently observed across trials. PD-1/PD-L1 monotherapy demonstrated a favorable safety profile and a statistically significant improvement in ORR compared with chemotherapy (OR = 1.52, 95% CI: 1.02–2.27, P = 0.04). Dual immunotherapy significantly improved ORR compared with monotherapy (OR = 1.77, 95% CI: 1.25–2.49, P = 0.001), but this benefit was accompanied by significantly increased toxicity (OR = 1.73, 95% CI: 1.22–2.44, P = 0.002) and did not consistently translate into statistically significant PFS or OS benefits across trials. These findings highlight the need for personalized risk-benefit assessment. Future research should focus on biomarker-driven patient selection and strategies to overcome resistance. The online version contains supplementary material available at 10.1186/s12885-026-16033-y.

Cold tumors, defined by insufficient immune cell infiltration and a highly immunosuppressive tumor microenvironment (TME), exhibit limited responsiveness to conventional immunotherapies. This review systematically summarizes the mechanisms of immune evasion and the therapeutic strategies for cold tumors as revealed by multi-omics technologies. By integrating genomic, transcriptomic, proteomic, metabolomic, and spatial multi-omics data, the review elucidates key immune evasion mechanisms, including activation of the WNT/β-catenin pathway, transforming growth factor-β (TGF-β)–mediated immunosuppression, metabolic reprogramming (e.g., lactate accumulation), and aberrant expression of immune checkpoint molecules. Furthermore, this review proposes multi-dimensional therapeutic strategies, such as targeting immunosuppressive pathways (e.g., programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors combined with TGF-β blockade), reshaping the TME through chemokine-based therapies, oncolytic viruses, and vascular normalization, and metabolic interventions (e.g., inhibition of lactate dehydrogenase A (LDHA) or glutaminase (GLS)). In addition, personalized neoantigen vaccines and engineered cell therapies (e.g., T cell receptor-engineered T (TCR-T) and natural killer (NK) cells) show promising potential. Emerging evidence also highlights the role of epigenetic regulation (e.g., histone deacetylase (HDAC) inhibitors) and N6-Methyladenosine (m6A) RNA modifications in reversing immune evasion. Despite the promising insights offered by multi-omics integration in guiding precision immunotherapy, challenges remain in clinical translation, including data heterogeneity, target-specific toxicity, and limitations in preclinical models. Future efforts should focus on coupling dynamic multi-omics technologies with intelligent therapeutic design to convert cold tumors into immunologically active (“hot”) microenvironments, ultimately facilitating breakthroughs in personalized immunotherapy.

The endoplasmic reticulum (ER) is a key organelle in eukaryotic cells, responsible for a wide range of vital functions, including the modification, folding, and trafficking of proteins, as well as the biosynthesis of lipids and the maintenance of intracellular calcium homeostasis. A variety of factors can disrupt the function of the ER, leading to the aggregation of unfolded and misfolded proteins within its confines and the induction of ER stress. A conserved cascade of signaling events known as the unfolded protein response (UPR) has evolved to relieve the burden within the ER and restore ER homeostasis. However, these processes can culminate in cell death while ER stress is sustained over an extended period and at elevated levels. This review summarizes the potential role of ER stress and the UPR in determining cell fate and function in various diseases, including cardiovascular diseases, neurodegenerative diseases, metabolic diseases, autoimmune diseases, fibrotic diseases, viral infections, and cancer. It also puts forward that the manipulation of this intricate signaling pathway may represent a novel target for drug discovery and innovative therapeutic strategies in the context of human diseases.

Background: Aortic dissection (AD) is one of the crucial and common cardiovascular diseases, and pyroptosis is a novel cell delivery mechanism that is probably involved in the pathogenesis of various cardiovascular diseases. However, no study has investigated the role of pyroptosis in AD. Methods: We obtained two AD datasets, GSE153434 and GSE190635, from the Gene Expression Omnibus database. The differential expression of AD-related genes was determined by differential analysis, and their enrichment analysis was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Additionally, a protein–protein interaction network was established. Next, potential biomarkers were screened by Lasso regression analysis, and a neural network model was constructed. Finally, the potential biomarkers were validated by constructing a mouse model of AD. Results: A total of 1033 differentially expressed related genes were distinguished and these genes were mainly associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase signaling pathways. The Lasso regression results showed five potential biomarkers, namely platelet endothelial cell adhesion molecule-1 (PECAM1), caspase 4 (CASP4), mixed lineage kinase domain-like pseudokinase (MLKL), APAF1-interacting protein (APIP), and histone deacetylase 6 (HDAC6) and successfully constructed a neural network model to predict AD occurrence. The results showed that CASP4 and MLKL were highly expressed, whereas PECAM1 and HDAC6 were lowly expressed in AD samples, and no statistically significant difference was observed in APIP expression in AD samples. Conclusion: Pyroptosis plays a crucial role in AD occurrence and development. Moreover, the five potential biomarkers identified in the present study can act as targets for the early diagnosis of AD in patients.

In nature, the hierarchical structure of biological tissues endows them with outstanding mechanics and elaborated functions. However, it remains a great challenge to construct biomimetic hydrogels with well‐defined nanostructures and good mechanical properties. Herein, polymerization‐induced self‐assembly (PISA) is for the first time exploited as a general strategy for nanostructured hydrogels and organogels with tailored nanodomains and outstanding mechanical properties. As a proof‐of‐concept, PISA of BAB triblock copolymer is used to fabricate hydrogels with precisely regulated spherical nanodomains. These nanostructured hydrogels are strong, tough, stretchable, and recoverable, with mechanical properties correlating to their nanostructure. The outstanding mechanical properties are ascribed to the unique network architecture, where the entanglements of the hydrophilic chains act as slip links that transmit the tension to the micellar crosslinkers, while the micellar crosslinkers dissipate the energy via reversible deformation and irreversible detachment of the constituting polymers. The general feasibility of the PISA strategy toward nanostructured gels is confirmed by the successful fabrication of nanostructured hydrogels, alcogels, poly(ethylene glycol) gels, and ionogels with various PISA formulations. This work has provided a general platform for the design and fabrication of biomimetic hydrogels and organogels with tailorable nanostructures and mechanics and will inspire the design of functional nanostructured gels.

Gastric cancer (GC) is a potential dominant disease in tumor immunotherapy checkpoint inhibitors, and adoptive cell therapy have brought great hope to GC patients. However, only some patients with GC can benefit from immunotherapy, and some patients develop drug resistance. More and more studies have shown that long non-coding RNAs (lncRNAs) may be important in GC immunotherapy’s prognosis and drug resistance. Here, we summarize the differential expression of lncRNAs in GC and their impact on the curative effect of GC immunotherapy, discuss potential mechanisms of activity in GC immunotherapy resistance regulated by lncRNAs. This paper reviews the differential expression of lncRNA in GC and its effect on immunotherapy efficacy in GC. In terms of genomic stability, inhibitory immune checkpoint molecular expression, the cross-talk between lncRNA and immune-related characteristics of GC was summarized, including tumor mutation burden (TMB), microsatellite instability (MSI), and Programmed death 1 (PD-1). At the same time, this paper reviewed the mechanism of tumor-induced antigen presentation and upregulation of immunosuppressive factors, as well as the association between Fas system and lncRNA, immune microenvironment (TIME) and lncRNA, and summarized the functional role of lncRNA in tumor immune evasion and immunotherapy resistance.

Oxidative stress is crucial to the biology of tumors. Oxidative stress’ potential predictive significance in colorectal cancer (CRC) has not been studied; nevertheless here, we developed a forecasting model based on oxidative stress to forecast the result of CRC survival and enhance clinical judgment. The training set was chosen from the transcriptomes of 177 CRC patients in GSE17536. For validation, 65 samples of colon cancer from GSE29621 were utilized. For the purpose of choosing prognostic genes, the expression of oxidative stress‐related genes (OXEGs) was found. Prognostic risk models were built using multivariate Cox regression analysis, univariate Cox regression analysis, and LASSO regression analysis. The outcomes of the western blot and transcriptome sequencing tests were finally confirmed. ATF4, CARS2, CRP, GPX1, IL1B, MAPK8, MRPL44, MTFMT, NOS1, OSGIN2, SOD2, AARS2, and FOXO3 were among the 14 OXEGs used to build prognostic characteristics. Patients with CRC were categorized into low‐risk and high‐risk groups according on their median risk scores. Cox regression analysis using single and multiple variables revealed that OXEG‐related signals were independent risk factors for CRC. Additionally, the validation outcomes from western blotting and transcriptome sequencing demonstrated that OXEGs were differently expressed. Using 14 OXEGs, our work creates a predictive signature that may be applied to the creation of new prognostic models and the identification of possible medication candidates for the treatment of CRC.