Fan Yi

BACKGROUND: Endothelial dysfunction is recognized as a crucial initiating factor for hypertension and associated cardiovascular/renal injury. Although MYDGF (myeloid-derived growth factor) is mainly derived from bone marrow cells, recent studies have also found the expression of MYDGF in different parenchymal cells. However, the expression pattern and the role of endothelial MYDGF in hypertension remain unclear. METHODS: Endothelial-specific knockout of MYDGF mice and recombinant MYDGF were used to examine the role of MYDGF in hypertension and associated cardiovascular/renal injury. RESULTS: Endothelial MYDGF was significantly downregulated in hypertensive mice. MYDGF deficiency in the endothelium aggravated endothelial dysfunction and cardiovascular/renal injury in hypertensive mice, which was attenuated by the overexpression of MYDGF or recombinant MYDGF. Functionally, MYDGF maintained endothelial homeostasis via pleiotropic protective effects, including anti-inflammation, antiapoptosis, inhibiting aberrant endothelial permeability and senescence, and inducing NO generation. Mechanistically, MYDGF promoted the activation of HMOX1 (heme oxygenase-1) transcription by mediating STAT3 (signal transducer and activator of transcription 3) phosphorylation, thereby reestablishing endothelial homeostasis. CONCLUSIONS: MYDGF governs endothelial homeostasis in hypertension through regulating HMOX1 expression. Targeting MYDGF may offer an innovative approach for treating hypertension and its cardiovascular complications.

Emerging evidence demonstrates the important role of ferroptosis, a novel regulated cell death, in the initiation and progression of acute kidney injury (AKI). However, the activation mechanism of ferroptosis in AKI has not been fully revealed. The pivotal function of interferon inducible protein 16 (IFI16) in DNA damage response (DDR) as DNA sensor and regulator of cell death pathways encouraged us to examine its role in ferroptosis of renal tubular epithelial cells (TECs) in AKI. Here we report that the levels of IFI16 and its mouse ortholog p204 were elevated in the kidney of patients with acute tubular necrosis (ATN) and in TECs of mice with renal ischemia/reperfusion (I/R)-induced AKI (I/R-AKI). Under I/R conditions, tubule-specific p204 deficiency in mice and IFI16 knockout in HK-2 cells significantly ameliorated TEC ferroptosis. Mechanistically, IFI16 binds to poly(ADP-ribose) polymerase 1 (PARP-1) and enhances protein Poly ADP-ribosylation (PARylation), which in turn potentiates the ataxia-telangiectasia mutated (ATM)-p53 signaling contributing to lipid peroxidation and ferrous ion accumulation in TECs. In addition, IFI16-amplified DDR was dependent on its HIN and PYRIN domains. Thus, our findings provide a better understanding of a critical pathogenic axis linking DNA damage to ferroptosis and suggest that targeting IFI16 may be an innovative therapeutic strategy for treating patients with AKI.

Objectives: Since its establishment in 1864, Cheeloo College of Medicine (CCM) has been committed to cultivating high-caliber health professionals. Responding to national strategies such as Healthy China 2030 and the New Medicine initiative, the college has pursued reforms to meet 21st-century demands. This study aims to examine the reform strategies and early outcomes, thereby providing evidences to support the generalization of such reform on a larger scale. Methods: This study employs a single-case study design, focusing on CCM’s medical education reforms. Key reform strategies, such as teaching paradigm innovation, disciplinary structure optimization, and physician-scientist cultivation, are analyzed through qualitative sources. Reform outcomes were assessed through students’ achievements as reflected in quantitative data from the 2022–2024 China Medical Student Survey, as well as institutional achievements demonstrated by changes in Academic Ranking of World Universities. Results: CCM has implemented strategic initiatives including “Medicine+X” interdisciplinary programs, digital and intelligent teaching technologies, promoting physician-scientist training, and cultivating global and humanistic competencies. Significant progress has been made in developing innovative talent models and adapting curricula to technological and societal changes. However, scaling CCM’s reform experience requires attention to gaps in resources and talents. Conclusions: The comprehensive reforms at CCM demonstrate an evidence-based, transformative approach to 21st-century medical education. By balancing traditional values with modernization, these innovations address evolving healthcare challenges and establish Cheeloo as a model for medical education reform. Measurable outcomes across ethics, academics, technology, and global competencies provide a replicable framework for cultivating future-ready health professionals.

Background: Critical thinking skills (CTS) are essential in medical education. Problem‐based learning (PBL) effectively develops CTS, with generative AI (e.g., ChatGPT) offering enhancement potential. Objectives: This study investigates how a tutor‐managed ChatGPT‐PBL model: (1) reconfigures tutor/peer roles and CTS compared to traditional PBL; (2) establishes predictive relationships between tutor/peer roles and CTS and (3) confirms optimal operational parameters for tutor‐managed ChatGPT to enhance CTS. Methods: A quasi‐experimental study assigned 170 medical students to either a ChatGPT‐PBL or a traditional PBL group. Data from a 31‐item survey assessing tutor and peer roles and CTS, along with learning logs and tutor observations for 36 participants, recorded AI engagement metrics (e.g., query frequency, multi‐source validation, comparative questioning). The intervention used a pre‐defined “3–2‐60 Rule” (≥3 queries/session, ≥2 authoritative sources/claim, >60% comparative framing), derived from existing literature, to guide ChatGPT engagement. Interrelationships were examined. Results: ChatGPT‐PBL improved CTS outcomes, enhancing tutor‐guided constructive/self‐directed/contextual/collaborative learning and peer‐driven information processing/communication/critical analysis. Regression identified collaborative learning and information processing as CTS predictors in both approaches, but ChatGPT shifted their influence: collaborative learning's role decreased while information processing's increased. High adherence to the “3–2‐60 Rule” correlated with CTS gains, with high‐engagement groups (>3 queries, ≥2 sources, comparative framing) outperforming peers. Conclusions: Tutor‐managed ChatGPT reconfigures tutor/peer roles in PBL to enhance CTS development. Structured peer‐ChatGPT‐tutor interactions (following the 3–2‐60 rule) contributed to enhancing CTS. Given ChatGPT's socioemotional limitations, future implementations should embed adversarial ChatGPT tasks and ethical transparency protocols.

The global surge in the population of people 60 years and older, including that in China, challenges healthcare systems with rising age‐related diseases. To address this demographic change, the Aging Biomarker Consortium (ABC) has launched the X-Age Project to develop a comprehensive aging evaluation system tailored to the Chinese population. Our goal is to identify robust biomarkers and construct composite aging clocks that capture biological age, defined as an individual’s physiological and molecular state, across diverse Chinese cohorts. This Perspective outlines the core objectives, methodological framework and key deliverables of the X-Age Project, including cohort recruitment, standardized sample collection, multimodal data acquisition and clock model development. By integrating interdisciplinary expertise, we aim to provide a practical and scalable platform for understanding aging complexity and heterogeneity, early detection of accelerated aging and evaluation of aging interventions.