The construction of a training system for visiting physicians in the department of rare diseases in China is an important measure to improve the overall diagnosis and treatment capacity for rare diseases and address the critical challenge of insufficient knowledge and skills among clinicians in practice. This article systematically describes the visiting physician training system established by the Department of Rare Diseases at Peking Union Medical College Hospital. It summarizes the training objectives and positioning, design logic, and learning modules of the system, aiming to provide a reference for the construction of the specialized talent team for rare diseases in China.

Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent clinical syndrome with limited effective therapies, representing a major unmet need in cardiovascular medicine. A comorbidity-driven systemic proinflammatory state, together with coronary microvascular endothelial inflammation, has emerged as a central paradigm in HFpEF pathogenesis. Accumulating evidence over the past decade has highlighted the extensive crosstalk between inflammation, metabolic dysregulation, and aging-related processes. In this review, we summarize key advances defining the roles of systemic and microvascular inflammation, metabolic abnormalities, and cellular senescence, and integrate these findings into an interconnected inflammation-metabolism-aging axis in HFpEF. We further discuss the current clinical and emerging preclinical therapeutic strategies targeting these pathways. By linking mechanistic insights with translational perspectives, this review provides a conceptual framework to guide precise therapeutic development for this complex and heterogeneous syndrome.

Background Long‐term efficacy and safety of mavacamten in Chinese patients with obstructive hypertrophic cardiomyopathy are unknown. Methods Patients who completed the 30‐week, double‐blind, placebo‐controlled treatment period in EXPLORER‐CN (A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM), with no active safety concerns, were eligible to enter the long‐term extension period to receive 48‐week mavacamten treatment. Patients previously on mavacamten continued mavacamten (dose at week 30; mavacamten–mavacamten group); patients previously on placebo received mavacamten (starting dose, 2.5 mg once daily; placebo–mavacamten group). Key efficacy end points included change from baseline in echocardiographic measures, New York Heart Association functional class, 23‐item Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, and cardiac biomarkers through week 78. Analyses were descriptive; no between‐group hypothesis testing was performed. Results Seventy‐nine patients (mean age, 51.6 years; 27.8% women) entered the long‐term extension period (mavacamten–mavacamten, n=54; placebo–mavacamten, n=25). In the mavacamten–mavacamten group, numerical improvements in Valsalva and resting left ventricular outflow tract peak gradients were maintained through week 78 (mean change from baseline, −73.0 mm Hg [95% CI, −86.4 to −59.5]; and −56.3 mm Hg [95% CI, −67.1 to −45.5], respectively). Numerical improvements were also observed for other echocardiographic parameters, New York Heart Association class, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, and cardiac biomarkers through week 78. In the placebo–mavacamten group, numerical improvements with mavacamten in these parameters were noted from week 30 to week 78. Long‐term mavacamten treatment appeared well tolerated; left ventricular ejection fraction <50% was rare. Conclusions In this exploratory long‐term extension study, 78‐week mavacamten treatment appeared well‐tolerated and was associated with numerical improvements from baseline in echocardiographic parameters, New York Heart Association class, patient‐reported health status, and cardiac biomarkers in Chinese patients with obstructive hypertrophic cardiomyopathy. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05174416.

BACKGROUND:Abnormal inflammatory responses and viral infections play a critical role in the pathogenesis of critical illnesses. Critically ill patients frequently develop multiple organ dysfunction syndrome (MODS), a key determinant of clinical outcomes and a marker of poor prognosis. Interferon-γ (IFNγ), an important inflammatory regulatory cytokine, may serve as a more accurate indicator of viral infection severity and holds potential as a predictor of MODS and prognosis in critically ill patients. PURPOSE:To evaluate the association between IFNγ levels and clinical outcomes in critically ill patients. METHODS:This prospective study, conducted from January 1 to May 31, 2023, at Peking Union Medical College Hospital, used data from electronic medical records to collect baseline characteristics, ICU parameters, laboratory tests, and clinical outcomes. MODS was diagnosed on the basis of Sequential Organ Failure Assessment (SOFA) scores. Generalized Additive Models were employed to explore linear and nonlinear associations, while survival analyses were performed using the Kaplan-Meier method. RESULTS:A total of 208 patients were analyzed. IFNγ levels demonstrated a significant positive linear correlation with MODS in both sepsis (odds ratio [OR] 1.041, 95% confidence interval [CI]: 0.962-1.126) and non-sepsis (OR 1.025, 95% CI: 0.907-1.157) subgroups (intergroup P < 0.001). The relationship between IFNγ levels and 28-day mortality followed a U-shaped curve, with a threshold of 5.3 ng/mL. In the sepsis subgroup, patients with low IFNγ levels exhibited poorer prognoses compared with those with high IFNγ levels (P = 0.021). No significant difference in prognosis was observed between procalcitonin (PCT) subgroups (P = 0.087). Among patients with elevated IFNγ levels, a positive correlation between PCT and 28-day mortality was identified (OR 1.098, 95% CI: 0.815-1.481). CONCLUSION:IFNγ is strongly associated with MODS and prognosis in critically ill patients, highlighting its potential as a biomarker for predicting MODS occurrence and patient outcomes. These findings underscore the clinical value of IFNγ in critical care, providing a foundation for further research in this area.

Background:Balance impairment following stroke is a leading cause of disability and falls. Hemoglobin (Hb) affects systemic and cerebral oxygen delivery and may influence neuromuscular function and post-stroke balance, but evidence from large multicenter clinical samples is limited. We investigated the association between hemoglobin concentration and balance performance in a Chinese multicenter cross-sectional study of stroke patients. Methods:We studied 2,006 neuroimaging-confirmed stroke patients from 26 hospitals. Balance impairment was defined as BBS ≤ 40. Admission Hb (g/dL) was analyzed per 1 g/dL and by tertiles (<12.6 g/dL, 12.6-14.0 g/dL, ≥14.0 g/dL). Multivariable logistic regression with sequential adjustment, restricted cubic splines, and prespecified subgroup and sensitivity analyses evaluated associations. Results:Balance impairment occurred in 70.5% (1,414/2,006). Each 1 g/dL higher Hb was associated with lower odds of impairment in unadjusted (OR 0.83, 95% CI 0.78-0.87; p < 0.001) and fully adjusted models (OR 0.89, 95% CI 0.83-0.96; p = 0.002). This association remained robust after comprehensive adjustment for demographic, lifestyle, comorbidity, stroke characteristics, and lesion location factors. Compared with the lowest tertile, adjusted ORs were 0.72 (95% CI 0.53-0.99; p = 0.042) for the middle tertile and 0.62 (95% CI 0.45-0.85; p = 0.003) for the highest tertile. Spline analyses suggested a broadly linear inverse association; results were consistent across subgroups and sensitivity checks. Conclusion:Higher admission hemoglobin was independently associated with better balance after stroke. Prospective studies should test whether Hb optimization improves rehabilitation outcomes.

In accordance with the Pharmaceutical Administration Law of the People's Republic of China revised in 2019 and the Implementing Regulations of the Pharmaceutical Administration Law of the People's Republic of China effective in 2026, Peking Union Medical College Hospital led the development of The Chinese Management Consensus on Compassionate Use of Investigational New Drugs in Medical Institutions(2026). This consensus was formulated by convening a multidisciplinary panel of experts, including health policy specialists, clinicians, pharmacists, methodologists, ethicists, and industry representatives, following the consensus development process recommended by the World Health Organization handbook and the Chinese Medical Association. As the first management consensus in China specifically addressing compassionate use of investigational drugs, this document provides 19 recommendations across eight key domains: eligibility criteria for compassionate use, scope of application, target patient populations, responsibilities of relevant stakeholders, key points for application and review, patient informed consent, risk prevention and control, and cost-bearing arrangements. This consensus aims to standardize the clinical practice of compassionate use of investigational drugs within medical institutions, enhance awareness of this issue among healthcare institutions in China, address the clinical needs of critically ill patients requiring urgent treatment, and provide recommendations and references for the establishment of standardized compassionate use management procedures.

Low QRS voltage relative to left ventricle (LV) thickness is one of the red flag characteristics in the diagnosis of cardiac amyloidosis, and it can be measured by specific indexes. Few studies have clearly defined the diagnostic threshold of voltage indexes for light chain amyloidosis cardiomyopathy (AL-CA) patients and other patients with LV hypertrophy. This case–control study analyzed electrocardiograms and echocardiograms of patients with AL-CA, hypertrophic cardiomyopathy (HCM), and hypertension left ventricular hypertrophy (HTN-LVH) seen at a single university center from 2008 to 2022. Low QRS voltage and three different precordial voltage indexes were evaluated. Diagnostic thresholds for rule-in and rule-out were calculated for AL-CA against each control group. A single voltage–mass ratio based on cross-sectional area (CSA) exhibited most accurate diagnostic accuracy, and the value of ≤1.72 aids the rule-in of AL-CA against other causes of left ventricular hypertrophy, providing a positive predictive value (PPV) of 86% versus HCM and 75% versus HTN-LVH.

The gut microbiota has emerged as a metabolically active endocrine-like organ with a crucial role in coronary artery disease (CAD), yet its contribution to adverse clinical outcomes remains incompletely understood. In this prospective cohort of 319 participants, we integrated metagenomic and metabolomic profiling with longitudinal follow-up over a median of 1.85 years. Fecal microbiota transplantation from patients with CAD transmitted susceptibility to atherosclerosis in antibiotic-treated ApoE -/- mice, accompanied by microbiota-induced vascular inflammation mediated through LPS-TLR4 signaling. Gut microbiota-derived aromatic amino acid metabolism was associated with thrombotic risk and major adverse cardiac events (MACE). Machine learning identified gut microbial features that improved prospective prediction of MACE. Together, these findings implicate the gut microbiome in CAD progression and support the development of microbiome-based strategies for cardiovascular risk prediction and prevention.

Prior studies have identified atypical expression of protein tyrosine phosphatase receptor type E (PTPRE) in animal models of salt-sensitive hypertension (SSH). This study investigates PTPRE's role in SSH and clarifies its mechanism of action. Through gene knockdown and overexpression of PTPRE in DOCA-salt hypertensive mice, we assessed the vasomotor function of aortic rings. PTPRE-induced phenotypic changes in vascular smooth muscle cells (VSMCs) were identified using phenotypic markers and related functional parameters. The phosphorylation levels of the MAPK signaling pathway subfamilies were assessed using Western blot analysis. Upregulation of PTPRE was observed in the VSMCs of DOCA-salt-induced SSH mice. This upregulation was associated with impaired vasoconstriction and vasodilation of arteries, as well as increased blood pressure (BP) (all p  < 0.01). Altering PTPRE expression via knockdown and overexpression markedly affected the expression of synthetic (OPN) and contractile (α-SMA and SM22α) phenotype markers in the aortic media and VSMCs of SSH mice (all p  < 0.01). Moreover, PTPRE expression influenced the phosphorylation activation within the MAPK signaling pathway. Specifically, regulation of PTPRE expression in SSH modulated the phosphorylation of the JNK and p38 MAPK subfamilies, along with the upstream phosphorylation of MKK3 and MKK6 (all p  < 0.05). Our findings indicate that PTPRE significantly contributes to vascular vasomotor dysfunction and the phenotypic transformation of VSMCs in SSH. This involvement in SSH development seems to occur mainly via modulation of the JNK and p38 MAPK pathways.

Background Cardiovascular diseases are often associated with altered protein subcellular localization. As a major cause of inherited cardiomyopathy, LMNA deficiency could trigger nuclear envelope rupture and broadly impair the localization of nuclear and cytoplasmic proteins. Systemic approaches to identify, dissect and manipulate the localization of endogenous proteins are important for mechanistic and therapeutic investigation. Method Proximity proteomics of the nuclear lamina was performed specifically in cardiomyocytes in Lmna-deficient murine models. AAV-mediated Cas9-based gene silencing and subcellular gene upregulation were conducted via the nuclear localization signal (NLS) and nuclear export signal (NES). Cas9-based somatic mutagenesis was supplemented with the single-strand DNA templates of AAV to achieve robust homology-directed repair (HDR) and targeted NLS knock-in, which translocated cytoplasmic proteins into nuclei. Result In vivo proximity proteomics detected increased epoxide hydrolase 2 (EPHX2) in cardiomyocyte nuclei in mice carrying germline or cardiac-specific Lmna truncating variants. This phenotype was associated with ruptured nuclear envelope. Cas9-mediated Ephx2 knockout in cardiomyocytes ameliorated cardiac dysfunction in Lmna-deficient mice. Strikingly, overexpression of NLS-EPHX2, but not NES-EPHX2, also mitigated cardiac dysfunction. The cardiac protective EPHX2 substrates, epoxyeicosatrienoic acids (EETs), did not alter upon NLS-EPHX2 overexpression. By contrast, the Lmna-related DNA damage marker γ-H2AX was reduced. The EPHX-D333A mutant lacking hydrolase activity recapitulated the effects of wildtype EPHX2 in nuclei. AAV-Cas9-based HDR achieved efficient NLS knock-in and EPHX2 nuclear translocation in more than 60% cardiomyocytes, which improved cardiac function. Conclusion Lmna deficiency leads to the nuclear translocation of EPHX2, which ameliorated cardiac dysfunction in a hydrolase-independent manner. AAV-HDR-mediated somatic gene editing provides an efficient approach to manipulate the subcellular localization of endogenous proteins in cardiomyocytes in vivo. ### Competing Interest Statement The authors have declared no competing interest. National Natural Science Foundation of China, 82570307 State Key Laboratory of Complex Severe and Rare Diseases, 2025-O-PY-002 Beijing Natural Science Foundation, F252059

Emotional disorders (EDs) are prevalent in heart failure (HF) and predict poor outcomes, yet their interplay with oral health and systemic inflammation remains unclear. This integrated cross-sectional analysis of NHANES data and a prospective oral microbiome cohort revealed that EDs were significantly associated with poorer cardiovascular health (Life’s Essential 8 score), an effect partially mediated by tooth loss and self-rated oral health. Furthermore, HF patients with EDs exhibited distinct oral dysbiosis, marked by depletion of beneficial bacteria (e.g., Cardiobacterium) and enrichment of pro-inflammatory taxa (e.g., Megasphaera), which correlated with systemic inflammation. Our findings posit that EDs may impact cardiovascular health by disrupting the oral microbiome and promoting inflammation, highlighting a potential psychoneuroimmunological pathway in HF progression.

Rare diseases, despite their low individual incidence, collectively impact around 300 million people worldwide due to the vast number of diseases. The involvement of multiple organs and systems, and the shortage of specialized doctors with relevant experience, make diagnosing and treating rare diseases more challenging than common diseases. Recently, agents powered by large language models (LLMs) have demonstrated notable applications across various domains. In the medical field, some agent methods have outperformed direct prompts in question-answering tasks from medical examinations. However, current agent frameworks are not well-adapted to real-world clinical scenarios, especially those involving the complex demands of rare diseases. To bridge this gap, we introduce RareAgents, the first LLM-driven multi-disciplinary team decision-support tool designed specifically for the complex clinical context of rare diseases. RareAgents integrates advanced Multidisciplinary Team (MDT) coordination, memory mechanisms, and medical tools utilization, leveraging Llama-3.1-8B/70B as the base model. Experimental results show that RareAgents outperforms state-of-the-art domain-specific models, GPT-4o, and current agent frameworks in diagnosis and treatment for rare diseases. Furthermore, we contribute a novel rare disease dataset, MIMIC-IV-Ext-Rare, to facilitate further research in this field.

Rare diseases pose a substantial clinical and public health burden, with timely and accurate diagnoses remaining a formidable challenge in many countries and settings. Large language models (LLMs) have the potential to enhance the screening and diagnosis of rare diseases. However, existing evaluations of such capacities of LLMs are insufficient due to the low sample sizes, poor coverage of different rare diseases, and weak real-world clinical relevance. To address these issues, we developed an automated data collection pipeline, RareArena, to curate a comprehensive rare disease dataset from PubMed Central case reports. Two tasks were considered: rare disease screening (RDS), which involved rare disease recognition before confirmatory diagnostic tests; and rare disease confirmation (RDC), which required diagnosis with complete information. The constructed RDS task comprised 49 760 cases of 4597 rare diseases, whereas the RDC task comprised 22 901 cases of 3522 rare diseases. Human evaluations by two physicians across three dimensions-leakage, fidelity, and complexity-validated the high quality of our dataset. We systematically benchmarked ten state-of-the-art LLMs of varying sizes (GPT-4o, Llama3·1-70B, Llama3·1-8B, Qwen2·5-72B, Qwen2·5-7B, Gemma2-9B, Phi3-7B, Llama3-70B-UltraMedical, Llama3-8B-UltraMedical, and MedLlama-7B) and found that GPT-4o achieved the best performance in both the tasks (RDS: 33·1% top-1 recall, 56·9% top-5 recall; RDC: 64·2% top-1 recall, 85·9% top-5 recall). Additionally, GPT-4o performed better on genetically inherited diseases than on non-genetically inherited diseases in both the tasks, with its highest performance observed in systemic or rheumatologic diseases (RDS: 48·5% top-1 recall, 76·5% top-5 recall; RDC: 76·0% top-1 recall, 93·5% top-5 recall). To our knowledge, our dataset represents the largest rare disease diagnostic benchmark to date, featuring broad and deep disease coverage and reflecting clinically relevant scenarios. RareArena highlights the potential of LLMs in rare disease screening and diagnosis, providing a foundation for improved care for individuals with rare diseases around the world.

Cardiac amyloidosis (CA) is an under-recognized cause of left-ventricular hypertrophy (LVH) that is often misclassified as hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD). We aimed to develop and externally validate an AI model using electrocardiograms (ECG) and echocardiography to distinguish CA from other LVH aetiologies. A retrospective, multicenter study was conducted, with a derivation cohort collected from PUMCH (290 CA patients, 215 HCM patients, and 160 HHD patients) and an external validation cohort recruited from 10 other hospitals across China (126 CA patients, 240 HCM patients, and 190 HHD patients). Twenty-eight clinical, ECG, and echocardiographic predictors were included, and we selected the top 7 important features by recursive feature elimination strategy. The Super Learner model combines predictions from 11 machine learning models, and model performance was evaluated via macro-AUC, accuracy, precision, F1 score, and etc. We developed a simplified scoring system to diagnose CA, and classifying patients into three groups based on CA probability to minimize misdiagnosis risk. Ranking by feature importance, the top seven features were included and used for model construction, including Sokolow–Lyon index, interventricular septal thickness, systolic blood pressure, left-ventricular posterior wall thickness, tricuspid annular plane systolic excursion, average E/e′, and left-ventricular ejection fraction. The Super Learner model, combining Extra Trees, Histogram-based Gradient Boosting, LightGBM, and Multi-Layer Perceptron, achieved the highest AUC of 0.97 (95

Fine particulate matter (PM2.5) is increasingly recognized as a significant environmental risk factor for neurodegenerative disorders, including Alzheimer’s disease (AD) and mild cognitive impairment (MCI). With China’s rapidly aging population, the potential cognitive benefits of improving air quality merit timely evaluation. This study applied the BenMAP-CE tool, incorporating concentration–response parameters from meta-analyses, national monitoring data, demographic statistics, and cost-of-illness estimates, to quantify the health and economic benefits of PM2.5 reductions in China between 2015 and 2023. We assessed changes in national and provincial burdens under observed conditions and counterfactual PM2.5 scenarios. The results indicate that, compared with 2015 levels, reductions in PM2.5 concentrations by 2023 were associated with an estimated 0.79 million potentially avoidable new AD cases (40.3 per 10,000) and 3.4 million new MCI cases (173.6 per 10,000) among individuals aged ≥65 years, with associated economic savings of about 17 billion USD for AD and 19 billion USD for MCI. Projections suggest that lowering 2023 PM2.5 levels to 15 μg/m3 could prevent an additional 0.65 million AD cases (33.2 per 10,000) and 2.8 million MCI cases (143.0 per 10,000), yielding further savings of 14 billion USD and 16 billion USD, respectively. Using the WHO 2021 guideline level (5 μg/m³) as a counterfactual scenario indicated further gains beyond the 15 μg/m³ target. These estimates are subject to methodological uncertainty stemming from the observational concentration–response evidence and key assumptions on incidence, exposure, and costs. These findings underscore the substantial health and economic gains achievable through continued PM2.5 mitigation, highlighting the need to integrate cognitive health protection into air pollution control strategies in China.

Improvement of symptoms, physical function, and quality of life is one treatment goal for patients with obstructive hypertrophic cardiomyopathy (HCM). Mavacamten improved left-ventricular outflow tract gradients in Chinese patients with obstructive HCM in the EXPLORER-CN trial. We report here a detailed analysis of patient-reported health status per the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ-23) in Chinese patients after 78 weeks of mavacamten. Patients who completed the double-blind, placebo-controlled (DBPC) period of EXPLORER-CN with no active safety concerns could enter a long-term extension (LTE) period to receive mavacamten for 48 weeks at either the 30-week dose (mavacamten-mavacamten group) or a once-daily starting dose of 2.5 mg (subsequently adjusted via pharmacodynamics-based dose titration: placebo-mavacamten group). Health status endpoints included KCCQ-23 clinical summary score (CSS), overall symptom score (OSS), total symptom score (TSS), physical limitations score, and quality-of-life scores through week 78. Week 78 endpoint analyses were descriptive. In the DBPC period, 54 patients received mavacamten and 27 received placebo; of these, 54 and 25, respectively, entered the LTE period. KCCQ-23 CSS, OSS, and TSS improved with mavacamten and worsened with placebo during the DBPC period (mean change baseline to week 30: 5.7, 6.4, and 8.1, respectively [mavacamten-mavacamten group] and – 5.4, – 4.3, and – 4.8, respectively [placebo-mavacamten group]). CSS, OSS, and TSS continued to improve in the mavacamten-mavacamten group during the LTE period (mean change baseline to week 78: 7.1, 8.2, and 10.0, respectively). Scores improved in the placebo-mavacamten group after switching to mavacamten (mean change week 30 to week 78: 7.3, 9.5, and 5.7, respectively). Similar improvements in KCCQ-23 physical limitations and quality-of-life scores with mavacamten were observed throughout both study periods. Long-term mavacamten treatment for up to 78 weeks led to sustained improvements in patient-reported health status, supporting long-term treatment with mavacamten for Chinese patients with symptomatic obstructive HCM. ClinicalTrials.gov identifier NCT05174416.

Short-chain acyl-CoA dehydrogenase (SCAD) is a critical enzyme in mitochondrial fatty acid β-oxidation, catalyzing the initial dehydrogenation of short-chain acyl-CoAs. Mutations in the ACADS gene cause SCAD deficiency (SCADD), a disorder with remarkably heterogeneous clinical presentation. However, the molecular mechanisms underlying substrate specificity and the pathogenicity of most ACADS variants remain poorly understood. Here, we present high-resolution cryo-EM structures of human SCAD in complex with its physiological substrate butyryl-CoA (C4) and the longer substrate hexanoyl-CoA (C6). The butyryl-CoA-bound structure at 2.1 Å resolution details a pre-catalytic geometry ideal for hydride transfer, with Glu392 positioned as the catalytic base. We systematically characterized nineteen disease-associated mutations, which we classify into three functional categories: those disrupting FAD binding, those impairing substrate binding, and those compromising protein folding and stability. In addition, using the W177R mutant as a representative model, we demonstrate that folding-defective mutations provoke protein aggregation, leading to proteotoxicity, oxidative stress, and apoptosis, revealing a pathogenic mechanism beyond mere catalytic loss. In brief, our integrated findings elucidate the structural determinants of substrate specificity and catalytic mechanism in SCAD, and provide mechanistic insights into the functional impairments caused by mutations linked to SCADD.

The long-term prognosis of left ventricular noncompaction (LVNC) compared to dilated cardiomyopathy (DCM) remains inconclusive, as prior studies have frequently failed to adequately adjust for heart failure severity. We conducted a single-center, retrospective, comparative study enrolling 96 patients with dilated LVNC (dLVNC) and 437 patients with DCM diagnosed at Peking Union Medical College Hospital between January 2010 and December 2022. dLVNC was defined as meeting the Jenni criteria, with left ventricular ejection fraction (LVEF) ≤45% and increased left ventricular end-diastolic diameter (LVEDD). A 1:1 propensity score matching (PSM) was performed, with matching variables including sex, age, history of heart failure (HF) hospitalization, arrhythmia, LVEF, and LVEDD, resulting in 96 matched pairs. The primary endpoint was major adverse cardiovascular events (MACEs), comprising cardiovascular death or heart transplantation, HF hospitalization or cardiac resynchronization therapy implantation, severe arrhythmias, and systemic embolism. After a median follow-up of 5.46 (2.14–8.62) years in the dLVNC group and 5.26 (2.47–8.50) years in the DCM group, the Kaplan–Meier survival curves between the groups were highly overlapping and revealed no significant differences in MACEs (log-rank p = 0.88), all-cause mortality (log-rank p = 0.84), and individual components of MACEs. After adjusting for heart failure severity, dLVNC and DCM exhibit no substantial difference in long-term prognosis, and the morphological feature of excessive trabeculation itself does not independently increase the risk of adverse events.

In the face of the new scientific and technological revolution and the transformation of medical paradigms, the field of rare disease medicine, as a cross-disciplinary emerging discipline integrating basic research, clinical practice, drug development, and policy support, is experiencing unprecedented development opportunities. This paper systematically sorts out the disciplinary connotation, construction paths and practical challenges of the Department of Rare Diseases, and puts forward countermeasures and suggestions for promoting the high-quality development of this emerging discipline in China.