2026年 · 第139卷第14期

Pulmonary arterial hypertension (PAH) is a rare, progressive disorder defined by elevated pulmonary arterial pressure and vascular resistance, ultimately leading to right ventricular failure and premature death. Once considered a disease of pure vasoconstriction, PAH is now recognized as a complex vasculopathy involving endothelial dysfunction, inflammation, metabolic dysregulation, and genetic susceptibility. The pulmonary vasculature is dynamically narrowed by vasoconstriction, structurally obstructed by smooth muscle and endothelial proliferation, and pathologically stiffened by fibrosis and extracellular matrix deposition. Multiple cell types including endothelial cells, smooth muscle cells, fibroblasts, and immune cells contribute to this remodeling process. At the molecular level, hyperproliferative, apoptosis-resistant phenotypes emerge through mitochondrial dysfunction, oxidative stress, and endothelial-to-mesenchymal transition, which together drive a Warburg-like metabolic shift favoring glycolysis over oxidative phosphorylation. Chronic immune activation, characterized by cytokine release, T-cell and macrophage infiltration, and disrupted immune regulation, further amplifies vascular injury. Genetic studies have identified mutations in BMPR2, TBX4, SOX17, and other regulators of the bone morphogenic protein (BMP)/transforming growth factor-β (TGF-β) pathway as key contributors to heritable and idiopathic forms of PAH, highlighting impaired endothelial repair and aberrant signaling as central mechanisms. Recent translational breakthroughs have yielded novel therapeutic strategies beyond traditional vasodilators. Agents targeting the BMP/TGF-β axis (e.g., sotatercept), growth factor signaling (seralutinib), inflammatory pathways (tocilizumab, rituximab), and metabolic remodeling (pyruvate dehydrogenase kinases [PDK] and fatty acid oxidation [FAO] modulators) are redefining treatment paradigms. Concurrently, large-scale multi-omics initiatives such as PVDOMICS and PHOENIKS enable deep phenotyping, which unravels molecular endotypes and informs precision medicine approaches. This review summarizes the pathophysiology of PAH and the ongoing clinical trials in the PAH field.

Artificial intelligence (AI) is rapidly transforming healthcare, supporting disease management and enabling outcome prediction across multiple clinical settings. Inflammatory bowel diseases (IBD) are complex, heterogeneous conditions whose assessment relies on integrating several modalities, including endoscopy, histology, cross-sectional imaging, and omics data, all of which are critical for evaluating disease activity and predicting long-term outcomes. In recent years, numerous AI-based systems have been developed within each of these domains. In IBD endoscopy, deep learning algorithms have demonstrated high accuracy in objectively assessing mucosal inflammation and detecting colitis-associated dysplasia. In histology, AI applications enable automated, standardized evaluation of disease activity, reducing interobserver variability. Similarly, in cross-sectional imaging, AI models have shown promise in characterizing disease severity, identifying complications, and supporting outcome prediction. Beyond individual modalities, machine learning approaches are increasingly being explored to integrate complex clinical, imaging, and multi-omics data to predict disease trajectories and enable precision medicine strategies in IBD. The present review provides an overview of current AI applications across endoscopy, histology, imaging, and omics in IBD, highlighting its potential clinical impact and ability to advance precision medicine strategies through multimodal and multi-omics integration. Moreover, it discusses the main challenges, unmet needs, and limitations that remain barriers to adoption in clinical trials and routine clinical practice.

Nanoparticles derived from various sources have been widely investigated as biological therapeutic agents and drug carriers for cancer treatment. Among them, plant-derived vesicle-like nanoparticles (PDVLNs) have attracted considerable interest because of their wide availability, high yield, and ease of preparation. PDVLNs are primarily produced via active secretory mechanisms in plant cells in response to specific physiological and environmental stimuli. They can cross biological barriers while retaining the bioactive components of their parent plants, thereby exhibiting the dual capabilities of drug delivery and biological regulation. Currently, in the field of cancer treatment, PDVLNs sourced from ginger, grapes, green tea, and Brucea javanica have been successfully applied in monotherapy, combination therapy, and targeted drug delivery. This review systematically summarizes recent advances and the underlying molecular mechanisms of PDVLNs in cancer treatment, with an emphasis on engineering strategies designed to improve their performance as drug delivery systems, including drug loading techniques, surface modification approaches, and membrane fusion methods. Furthermore, the potential applications of PDVLNs in precision medicine and clinical translation are explored. By synthesizing current research progress and outlining future directions, this review provides a systematic theoretical foundation and practical insights to support the development of safe, effective, and clinically feasible antitumor nanotherapeutic platforms.

Immunotherapy targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) has significantly improved outcomes for various cancers, yet the emergence of resistance remains a major challenge. This review focuses on the dual role of endogenous glucocorticoids (GCs) and their receptor (GR) within the tumor microenvironment (TME), systematically elucidating the mechanisms by which they regulate responses to PD-1/PD-L1 therapy via the hypothalamic-pituitary-adrenal (HPA) axis, local synthesis and metabolism, and heterogeneity of GR signaling. We elaborate on the regulatory effects of the GC/GR signaling pathway on immune cells (such as cluster of differentiation 8 positive [CD8+] T cells, regulatory T cells [Tregs], dendritic cells, natural killer [NK] cells, and macrophages), and highlight the impact of GCs on PD-L1 expression, cytokine secretion, and the immunosuppressive microenvironment. This review also explores the controversial role of exogenous GCs in managing immune-related adverse events (irAEs) and their potential impact on therapeutic efficacy. The development of tissue-selective GR modulators holds promise for balancing immunosuppression while enhancing anti-tumor activity. A deeper understanding of the role of endogenous GCs in cancer immunotherapy is crucial for optimizing therapeutic strategies, overcoming resistance, and finally achieving precision in cancer immunotherapy.

Background: Neurological diseases represent a growing challenge to the Chinese public health system. However, a comprehensive analysis of neurological diseases in China is lacking. This study aimed to analyze disease burden and risk factors of neurological diseases in China to identify priorities for disease control and prevention. Methods: Disease burden and risk factors in China were analyzed for 12 neurological disorders using data from the Global Burden of Diseases 2021 study and the Chinese Center for Disease Control and Prevention. Prevalence, deaths, years of life lost, years lived with disability (YLDs), and disability-adjusted life years (DALYs) were used as metrics. Results: Intracerebral hemorrhage (ICH) (1930.3 [95% uncertainty interval (UI): 1605.3-2296.7] per 100,000), ischemic stroke (1646.8 [95% UI: 1400.0-1893.1] per 100,000), Alzheimer’s disease and other dementias (dementia) (708.0 [95% UI: 347.7-1561.7] per 100,000) made the greatest contributions to DALY rates in China in 2021. The fastest growing contributors to DALY rates were dementia (208.2% [95% UI: 166.4-255.7%]), Parkinson’s disease (160.7% [95% UI: 121.8-208.3%]), and ischemic stroke (95.2% [95% UI: 56.9-140.6%]). Migraine was the leading contributor to DALY rates among populations aged 10-39 years, ICH for those aged 40-74 years, ischemic stroke for those aged 75-89 years, and dementia for those aged >90 years. Ischemic stroke accounted for the highest age-standardized DALY rates in North and Northeast China, whereas ICH ranked first in other regions. High systolic blood pressure had the highest attributable DALYs for all diseases combined. Metabolic risk factors, alcohol use, secondhand smoke, and low physical activity contributed to higher YLDs in females, whereas alcohol use, smoking, and a high-sodium diet contributed to higher YLDs in males. Conclusions: Neurological diseases present a growing public health challenge, characterized by significant disparities in their prevalence and presentation across age, sex, and geographic regions. Addressing these disparities requires coordinated strategies encompassing prevention, treatment, rehabilitation, and supportive care at the national level.

Background: Limited evidence exists regarding the relationship between long-term exposure to low concentrations of low-density lipoprotein cholesterol (LDL-C) and brain structural integrity. This study aimed to examine the associations of cumulative low LDL-C exposure with a series of neuroimaging metrics. Methods: This study included 987 participants (median age 55 years) from a population-based cohort study in China. Serum circulatory LDL-C concentrations were assessed biennially from 2006 to 2018. Prolonged LDL-C exposure was calculated using a time-weighted average (TWA) approach during that period. Brain MRI examinations were performed during 2020-2022. We used generalized linear model to investigate the multivariate-adjusted associations of TWA LDL-C levels with MRI markers of brain tissue volume, white matter microstructural integrity, and white matter hyperintensity (WMH). Results: After full adjustments, TWA LDL-C concentrations of 70-100 mg/dL and less than 70 mg/dL were associated with lower fractional anisotropy value and higher mean diffusivity, axial diffusivity, and radial diffusivity value compared to LDL-C concentrations of 100-130 mg/dL. These associations were particularly prominent in male participants and older participants who were over 50 years. No association was found between relatively lower LDL-C levels and brain tissue volumes or WMH. Conclusion: LDL-C concentrations of 70-100 mg/dL and <70 mg/dL are associated with impaired microstructural integrity of brain white matter.

Background: Pre-eclampsia remains a leading cause of maternal and perinatal mortality and morbidity. Whether risks of pre-eclampsia are associated with severity of blood glucose concentrations or glycemic control is still unknown. This study aimed to analyze the association of blood glucose concentrations during pregnancy and the risk of pre-eclampsia. Methods: A retrospective cohort study was conducted using data of 53,054 singleton pregnant women aged 18-49 years from 121 maternity hospitals in China between 2015 and 2018. Logistic regression models with restricted cubic splines were performed to reveal a non-linear association of blood glucose concentrations in the first trimester and the gestational change with pre-eclampsia. The association of the categories of blood glucose concentrations with pre-eclampsia was further examined by performing robust Poisson regression. Results: A total of 1356 (2.55%, 1356/53,054) participants were diagnosed with pre-eclampsia. Higher risk was observed in those with higher blood glucose in the first trimester and those with greater increase in blood glucose during gestation, with the incidence of pre-eclampsia ranging from 1.27% (24/1883) to 6.03% (29/481). Compared with women with blood glucose (BG) concentrations of <4.4 mmol/L in the first trimester, the risk of pre-eclampsia was significantly increased in women with 4.4 ≤BG <5.1 mmol/L (adjusted relative risk [aRR] = 1.347, 95% confidence interval [CI]: 1.185-1.531), 5.1 ≤BG <5.6 mmol/L (aRR = 1.750, 95% CI: 1.441-2.124), and BG ≥5.6 mmol/L (aRR = 2.431, 95% CI: 1.958-3.019), respectively, after adjusting for basic characteristics of women, including region, age, education, ethnicity, residential status, assisted reproductive technology, primigravida, pre-pregnancy body mass index and categories of gestational change of blood glucose concentrations. The association of gestational change of blood glucose concentrations during gestation with pre-eclampsia was presented as a U-shaped curve after controlling the blood glucose concentrations in the first trimester. Conclusions: The findings highlight that higher blood glucose concentration in the first trimester and greater gestational variations of blood glucose contribute to higher risks of pre-eclampsia. Therefore, maintaining optimal blood glucose in early pregnancy and minimizing gestational glucose fluctuations is recommended to reduce the risk of pre-eclampsia.

Background: This is a multicenter, randomized, double-blind, placebo-controlled interventional clinical study to evaluate the efficacy and safety of pronase in improving visibility in colonoscopy and to evaluate whether pronase can increase the detection rate of intestinal lesions and the colonoscopist’s satisfaction. Methods: From June 2023 to December 2023, a total of 1942 patients undergoing air insufflation colonoscopy in 10 hospitals (The First Medical Center, Chinese PLA General Hospital, et al) were selected as the study subjects. They were randomly divided into two groups: (1) the experimental group (n = 969) was given pronase for flushing in colonoscopy; and (2) the control group (n = 973) was given physiological saline for flushing in colonoscopy. The improvement of the visibility at the target site (region of interest) in colonoscopy was evaluated in two groups to verify the efficacy of pronase in improving visibility in colonoscopy. The safety of pronase for flushing in colonoscopy was evaluated by comparing the incidence of adverse events between the two groups. Results: After the use of pronase in colonoscopy, the patient’s vital signs remained stable, without serious adverse reactions. The improvement rate of visibility in the pronase group was significantly higher than that in the physiological saline group (97.21% [942/969] vs. 86.74% [844/973], P <0.0001), and the subgroup analysis (Boston Bowel Preparation Scale ≥6 points) showed similar results to the overall ones. The physician’s satisfaction score in the pronase group was significantly increased. There was no statistically significant difference in the detection rates of adenoma, colorectal cancer, minimal lesions, non-polypoid colorectal lesions, polyps, and precancerous lesions between the two groups. Conclusions: Pronase can improve the visibility in colonoscopy and help physicians observe the lesions better. Pronase demonstrates good safety in colonoscopy, with no significant difference compared to physiological saline.

Background: Hypertensive disorders of pregnancy (HDP) are leading causes of maternal and fetal morbidity and mortality. Although lower grip strength has been linked to higher cardiovascular risk in the general population, evidence on its relationship with HDP remains limited. We aimed to prospectively investigate this association in a large cohort of pregnant women. Methods: Between March 2017 and January 2020, 6802 pregnant women (mean age ± standard deviation: 26.6 ± 3.7 years) enrolled in the Tongji-Huaxi-Shuangliu Birth Cohort were included in this analysis. Grip strength was measured in early pregnancy (mean gestational week ± standard deviation: 10.3 ± 2.0 weeks) and assessed in three ways: absolute grip strength (AGS) and two relative indices (AGS normalized to body mass index or body weight). Logistic regression models were used to assess the associations between grip strength and the risk of HDP (gestational hypertension or preeclampsia). Multiple blood biomarkers (blood lipids, leptin, adiponectin, C-reactive protein, C-peptide, glycated hemoglobin, and homeostatic model assessment of insulin resistance) were measured among 638 women at enrollment. Results: A total of 180 women developed HDP during pregnancy. The adjusted odds ratios (95% confidence intervals) of HDP across increasing quartiles of AGS in early pregnancy were 1.00 (reference), 0.93 (0.63-1.35), 0.67 (0.44-1.00), and 0.35 (0.21-0.56). Odds ratios across quartiles of two relative grip strength (RGS) indices showed similar patterns. Restricted cubic spline analyses indicated a nonlinear association between AGS and HDP risk (P for nonlinearity = 0.014). The risk plateaued at lower AGS levels but showed a linear inverse association above a threshold of 18.1 kg. In contrast, the two relative measures showed linear associations with HDP risk (P for nonlinearity ≥0.164). Additionally, higher RGS was generally correlated with favorable metabolic profiles (e.g., lower levels of low-density lipoprotein cholesterol, triglycerides, and C-reactive protein). Conclusion: Grip strength in early pregnancy was inversely associated with the risk of HDP, and RGS may serve as a simple and useful measure for risk stratification.

Background: Cytopathology cannot be used to reliably distinguish follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC), the second most common form of thyroid cancer, because they exhibit nearly identical cellular morphology. Given the challenges in diagnosis and treatment, this study aims to identify the mechanisms underlying FTC. Methods: Using parallel reaction monitoring-mass spectrometry (PRM-MS) assays, we identified and quantified 94 differentially expressed protein candidates from a retrospective cohort of 1085 FTC and FTA tissue samples from 18 clinical centers. Of these targeted proteins, those with the potential for distinguishing FTC from FTA were prioritized using machine learning. Co-immunoprecipitation (co-IP) and immunofluorescence co-localization assays, as well as gene interference, overexpression, and immunohistochemistry (IHC) experiments, were used to investigate the interactions and cellular functions of selected proteins. Results: Using machine learning models and feature selection methods, 30 of the 94 candidates were prioritized as key proteins. Co-IP and immunofluorescence co-localization assays using FTC cell lines revealed interactions among insulin-like growth factor 2 receptor (IGF2R), major vault protein (MVP), histone deacetylase 1 (HDAC1), and histone H1.5 (H1-5). Gene interference and overexpression experiments in FTC-133 cells confirmed the promotional role of these proteins in cell proliferation. IHC assays of patient samples further confirmed elevated expression of these four proteins in FTC compared with that in FTA. Conclusions: Our findings underscore the utility of advanced proteomic techniques in elucidating the molecular underpinnings of FTC, highlighting the potential significance of IGF2R, MVP, HDAC1, and H1-5 in FTC progression, and providing a foundation for the exploration of targeted therapies.