2026年 · 第139卷第15期

Circular RNAs (circRNAs) are distinguished from other noncoding RNAs by their unique loop structure, without 5′ polar ends and 3′ polyadenylated tails. They are stable and abundant in a wide range of eukaryotic taxa and exert functions via interactions with microRNAs (miRNAs), proteins, and DNA, including tumor-suppressive or oncogenic functions. Emerging evidence suggests that circRNAs show specific expression patterns in tumor tissues or circulation and changes in expression with respect to tumor stage; therefore, they possess strong potential as diagnostic, prognostic, and predictive biomarkers. Nevertheless, translating theoretical achievements in circRNA research to clinical practice is challenging. Herein, this review focuses on the important functions of circRNAs, including their roles in cancer, highlighting their utility for early cancer detection, prognosis, and treatment, in addition to a summary of vital detection methods for circulating circRNAs.

Immune signaling has emerged as a central regulator of cardiac biology, extending far beyond its traditionally recognized roles in pathology. From embryogenesis to adulthood, immune cells orchestrate key processes, including coronary vasculature formation, cardiomyocyte maturation, mitochondrial homeostasis, and extracellular matrix (ECM) remodeling. In the setting of myocardial injury, immune responses unfold in tightly choreographed phases, initially clearing necrotic debris and later facilitating scar formation and, in certain contexts, promoting tissue regeneration. Recent advances in single-cell and spatial transcriptomics have revealed the remarkable heterogeneity and plasticity of immune cell populations in the heart, highlighting their metabolic and phenotypic adaptability across developmental and disease contexts. Alongside these biological insights, therapeutic interest has grown in targeting specific immune pathways to modulate inflammation, enhance repair, and restore cardiac function. This review integrates discoveries from developmental immunology, cardiac injury models, and regenerative medicine to illustrate how the immune system underpins cardiac resilience and plasticity. By synthesizing molecular, cellular, and systems-level data, we present a cohesive view of cardioimmune interactions that opens new avenues for precision therapies aimed at heart repair and regeneration.

Recent studies have challenged the once prevalent notion that the human lungs are sterile, instead unveiling a dynamic microbial environment that interacts intricately with both the host and external factors. This review describes the distinct microbial compositions between healthy individuals and those with respiratory diseases, as well as discussing the variations in microbial composition across different disease states. We explore the crucial role of the lung microbiome in maintaining respiratory health and describe its implications in various respiratory diseases. We discuss how these microbial differences correlate with the severity and progression of respiratory diseases, including chronic obstructive pulmonary disease, cystic fibrosis, lung cancer, asthma, coronavirus disease 2019, and tuberculosis. Furthermore, we analyze the pathogenic mechanisms of the lung microbiome, as well as the associations between changes in the lung microbiome and systemic effects, including the emerging concepts of the gut-lung axis and brain-lung axis, which highlight the interconnected influence of the microbiota on lung health. This review aims to provide a comprehensive understanding of the profound impact of microbial dynamics on respiratory health and disease, suggesting new avenues for targeted diagnostic and therapeutic strategies.

Background: Women with a history of gestational diabetes mellitus (GDM) are at increased risk of developing type 2 diabetes later in life. This study evaluated whether lifestyle intervention can reduce the risk of type 2 diabetes in women with previous GDM. Methods: This was a two-arm randomized controlled study conducted at the Tianjin Women and Children’s Health Center. Women in six urban districts of Tianjin with previous GDM were randomly assigned in a 1: 1 ratio to either a 4-year lifestyle intervention group or a standard care control group between August 1, 2009 and July 31, 2011. Random allocation sequences were generated in patients but not in study coordinators. Each participant in the intervention group received individualized counseling aimed at reducing body weight in overweight women, increasing physical activity, and maintaining appropriate intakes of fat and carbohydrates especially fiber. Major components included six face-to-face meetings with a dietitian in the first year and two additional sessions in each subsequent year. The primary outcome was the development of type 2 diabetes, assessed using an oral glucose-tolerance test (OGTT). Participants were followed until the date of the diagnosis of diabetes, the last date of an OGTT, or death, whichever occurred first, up to December 2020. For participants who missed any OGTTs, self-reported physician-diagnosed diabetes data were collected. Results: A total of 1180 women with a recent history of GDM were randomized to either an intensive lifestyle intervention (n = 586) or usual care (n = 594) 1-5 years postpartum (mean: 2.26 years). The mean follow-up was 4.5 years. During the trial, women in the intervention group, compared with the control group, lost more weight, increased physical activity and consumed more fiber. The incidence of diabetes after four years or more of follow-up was 9.0 and 15.3 cases per 1000 person-years in the lifestyle intervention and control groups, respectively. The lifestyle intervention reduced the incidence of diabetes by 46% (95% confidence interval: 10-67%) using the OGTT to diagnose diabetes, and by 40% (95% confidence interval: 11-59%) using either the OGTT or self-reported physician-diagnosed diabetes. Conclusions: Healthy lifestyle management significantly reduced the incidence of diabetes among young women with previous GDM.

Background: Chronic kidney disease (CKD) is a global public health concern that causes a remarkable disease burden. Although the prevalence of CKD in China has been investigated by previous national surveys, the incidence, disability-adjusted life years (DALYs), and death of CKD and their temporal trends over the past decades have not been well studied. Methods: Incidence, DALYs, and death of CKD, as well as risk-attributable DALYs and death in China from 1990 to 2023, were checked from the Global Burden of Diseases, Injuries, and Risk Factors Study 2023. The temporal trend of each indicator was estimated by join point analysis. Results: In 2023, in China, there were 156.15 (95% uncertainty interval: 146.77-167.88) million patients with CKD. The incidence, DALYs, and death rates of CKD were 240.59 (222.83-266.12), 355.86 (303.29-407.63), and 10.73 (8.96-12.70) per 100,000 population, respectively. Females had a higher incidence but lower DALYs and death rates than males. The elderly population had a much higher disease burden than middle-aged and young people. Incidence rates markedly increased, DALY rates slightly decreased, while death rates mildly increased from 1990 to 2023 with the respective average annual percent change of 1.67%, -0.17%, and 0.40%. However, the metrics all tended to decline after age standardization. Metabolic risk factors accounted for higher risk-attributable DALYs and deaths than other risk factors. High fasting plasma glucose ranked first in 2023 for risk-attributable DALYs and death, while high body mass index was the only risk factor maintaining a nondeclining contribution when comparing 2010 to 2023. Conclusions: CKD bears high levels of incidence, DALYs, and death in China, with an increasing trend for incidence observed from 1990 to 2023. The aging of the population and metabolic diseases are the main drivers of the CKD burden. Priority should be given to curb the CKD epidemic.

Background: Sorafenib resistance is the bottleneck in the clinical treatment of advanced hepatocellular carcinoma (HCC). Cigarette compounds accelerate HCC progression and chemotherapy resistance by forming a chemical microenvironment. Here, we aimed to further reveal the mechanisms by which the microenvironment formed by cigarette exposure contributes to sorafenib resistance. Methods: A cohort of 119 patients enrolled from the First Affiliated Hospital of Huzhou University (between Mar 2019 to Jan 2024) and the Second Affiliated Hospital of Nanjing Medical University (between Jan 2018 to Jan 2024) with advanced HCC who had recurrent disease and were receiving sorafenib treatment was analyzed. The public data of the expression of genes and survival of HCC patients were all obtained from The Cancer Genome Atlas (TCGA) database, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID). The phospho/angiogenesis antibody arrays were used to identify the key phosphorylated proteins/cytokines that have been differentially modified. HCC cell lines and xenografted nude mice were used as experimental models. Quantitative real-time polymerase chain reaction (qPCR), Western blotting, immunofluorescence and immunohistochemistry (IHC) were used to elucidate the role of key factors in regulating sorafenib resistance. Flow cytometry, TdT-mediated dUTP nick end labeling, caspase activity, enzyme-linked immunosorbent assay, and capillary tube formation assay were employed to investigate related biological functions. Results: Chronic cigarette smoking exposure continuously activated 14-3-3η via an epigenetic accumulation of DNA demethylation. This "switch-like" factor, 14-3-3η, upregulated its key downstream pathway, B-Raf/extracellular regulated protein kinases (ERK). 14-3-3η and its regulated B-Raf/ERK protein jointly blocked the caspase cascade, enhancing the pro-survival ability of HCC cells. 14-3-3η/B-Raf/ERK activated nuclear factor kappa-B (NF-κB), which in turn transcriptionally upregulated multidrug resistance protein 1 (MDR1) and adenosine triphosphate (ATP) binding cassette transporter G2 (ABCG2), accelerating drug efflux. NF-κB also transcriptionally regulated vascular endothelial growth factor (VEGF) and granulocyte colony stimulating factor (G-CSF), inducing the neo-vascularization. These critical processes together resisted the HCC to sorafenib. Furthermore, these effects were blocked and sorafenib resistance was reversed when 14-3-3η was targeted with its novel chemical inhibitor, arsenic trioxide. Conclusions: A cigarette compound-formed tumor microenvironment conferred sorafenib resistance to HCC by locking the adaptor protein 14-3-3η in a constitutively active state. This outcome provided a mechanistic rationale and a translational strategy to re-sensitize HCC patients exposed to cigarette to targeted therapy.

Background: Identifying high-risk populations for colorectal cancer (CRC) is critical for precise screening. This study aimed to develop a novel risk prediction model using blood DNA methylation biomarkers to identify individuals at high risk for colorectal neoplasms. Methods: The biomarker discovery phase involved 106 samples (56 advanced adenomas and 50 healthy controls) collected from the TARGET-C screening cohort between May 2018 and May 2021, which were analyzed using the Illumina Infinium MethylationEPIC v2.0 BeadChip, and 72 samples (22 CRC, 20 advanced adenomas, and 30 healthy controls) collected from clinical cohorts between July 2023 and July 2024, which were analyzed using reduced representation bisulfite sequencing (RRBS). Differentially methylated positions (DMPs) and regions (DMRs) were identified and independently validated in 147 samples (48 CRC, 50 advanced adenomas, and 49 healthy controls) collected from an independent clinical cohort between June 2022 and May 2024 using targeted bisulfite sequencing (TBS). A multi-marker prediction model was constructed using logistic regression, and its diagnostic performance was evaluated through receiver operating characteristic (ROC) curve analysis. Results: In the discovery set, 48 DMPs and 74 DMRs were identified, exhibiting significant differences between CRC/advanced adenomas and healthy controls. Of these, three DMPs and 11 DMRs were successfully validated in the independent set using TBS. Through machine learning approaches, five stable methylation markers were identified and incorporated into a multi-marker prediction model. This model demonstrated excellent diagnostic performance for detecting colorectal neoplasms, with an area under the curve (AUC) of 0.85 (95% confidence interval [CI]: 0.74-0.94), outperforming the traditional lifestyle score (AUC = 0.55, 95% CI: 0.46-0.68). Combining methylation markers with lifestyle scores further improved diagnostic accuracy, achieving an AUC of 0.89. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the significant markers indicated their involvement in tumorigenesis through pathways regulating developmental processes, transcriptional activation, and cancer-related signaling. Conclusions: Blood leukocyte DNA methylation markers show significant potential for identifying high-risk populations for CRC. The identified markers could contribute to the development of novel, effective tools for CRC screening, facilitating precision screening strategies.

Background: The efficacy of conversion therapy for gastric cancer with peritoneal metastasis (P1) and/or positive peritoneal lavage cytology (CY1) treated with immunotherapy remains unclear. This study aimed to clarify clinical outcomes in this setting. Methods: In this retrospective, single-institution cohort study, 144 patients with P1 and/or CY1 confirmed by staging laparoscopy at initial diagnosis received first-line immunotherapy with chemotherapy and/or trastuzumab between November 2019 and March 2024. Patients were divided into a conversion therapy group and a palliative therapy group. Results: Of 144 patients, 75 showed a clinical response and underwent second-look laparoscopy. Negative peritoneal metastasis and cytology were confirmed in 36 patients, all of whom underwent conversion surgery. Compared with the palliative group, the conversion group had significantly longer median progression-free survival (22.9 vs. 5.8 months; P <0.001) and overall survival (33.4 vs. 12.3 months; P <0.001). Among those who had surgery, 27 patients (75.0%, 27/36) achieved R0 resection (complete resection with no residual tumor). Patients with peritoneal cancer index ≤2 had a significantly longer median overall survival than those with peritoneal cancer index >2 (not reached vs. 28.5 months; P <0.006). No serious treatment-related adverse events led to treatment discontinuation or death. Conclusions: Conversion surgery following immunochemotherapy provided a significant survival benefit for gastric cancer patients with P1 and/or CY1. When immunochemotherapy is effective, active staging laparoscopy should be performed to assess surgical feasibility.