Luliang

This research aims to develop and evaluate a stepwise screening approach for early detection of Alzheimers disease AD in community populations aged 50 and above. The study addresses the growing global burden of AD, which accounts for 60-80% of dementia cases worldwide, with a focus on scalable, accessible methods suitable for low- and middle-income settings. The study integrates digital cognitive assessments and blood-based biomarkers to improve early diagnosis during the prolonged preclinical phase of the disease. The screening process involves two main steps. The first step uses digital tools including the SCD-9 questionnaire to capture subjective cognitive complaints, a digital cognitive test PCAT assessing memory and symbol matching, and a predictive model for future dementia risk. The second step confirms AD pathology through blood-based biomarkers, comparing multiple candidates such as p-tau217, p-tau181, and A240 measured via assay platforms like Simoa and CLEIA. Amyloid PET scans serve as the gold standard for AD pathology confirmation. Participants will be community residents aged 50 years or older, without prior cognitive impairment or anti-dementia drug use, and able to communicate in Chinese. Researchers will collect and analyze data on screening sensitivity and specificity, program completion, time to completion, community feasibility, compliance, and cost-effectiveness. The study spans multiple centers nationwide and involves clinical dementia rating assessments and biomarker testing, with the goal of creating a model applicable to primary healthcare systems in developing countries.

Researchers are evaluating a standardized full-course extracorporeal membrane oxygenation ECMO management pathway for adults with moderate-to-severe acute respiratory distress syndrome ARDS in China. The study aims to address challenges in ECMO care, such as inconsistent clinical practices, low weaning success, and high complication rates. It focuses on creating a reproducible and evidence-based management strategy to improve the quality and outcomes of ECMO treatment nationwide. The study includes developing a multidisciplinary consensus-based ECMO management pathway covering all stages from assessment and initiation to maintenance, complication prevention, weaning, rehabilitation, and follow-up. Patients treated before pathway implementation receive usual care based on local protocols, while those treated after follow the standardized pathway with individualized adjustments allowed. The study uses a real-world, before-and-after design conducted across multiple centers. Participants undergo ECMO treatment as part of their care, with data recorded on key parameters and deviations from the pathway through an intelligent platform. Regular multidisciplinary reviews analyze outcomes, process barriers, and adverse events to enable continuous pathway improvement. The primary outcome measured is 90-day all-cause mortality after ECMO initiation. Secondary outcomes include mortality at 28 days, liberation from mechanical ventilation, ICU and hospital mortality and length of stay, respiratory support needs, and ECMO-related complications. The study runs from screening through treatment and follow-up with continuous data feedback until February 2030.

Acute respiratory distress syndrome (ARDS) poses a major threat to public health and consumes substantial healthcare resources. Based on the National Hospital Quality Monitoring System (HQMS), our group found that more than 2.5 million patients with ARDS are admitted to intensive care units (ICUs) annually in China, resulting in total hospitalization costs of approximately RMB 29.32 billion. The in-hospital mortality rate is about 39%, which is substantially higher than the international average (12-37%). Extracorporeal membrane oxygenation (ECMO) represents the most important rescue therapy for patients with moderate-to-severe ARDS; however, mortality among ARDS patients receiving ECMO support remains as high as 60%. Therefore, reducing mortality in moderate-to-severe ARDS is essential for achieving the goals of the Healthy China 2030 Initiative. Inflammatory and immune dysregulation occurs in 38.7-70% of patients with ARDS, frequently leading to multiple organ dysfunction. Despite ECMO support, mortality among patients with severe ARDS remains extremely high. Three major challenges contribute to poor outcomes. First, immune dysregulation under ECMO support significantly increases the incidence and mortality of severe complications, while targeted therapeutic strategies based on underlying mechanisms are lacking. Second, the marked heterogeneity of ARDS complicates the identification of optimal timing and modalities of ECMO support. Third, the effects of different invasive mechanical ventilation strategies on lung injury and repair remain poorly understood, and mechanism-guided precision ventilation approaches are still unavailable. Building upon the largest ARDS and ECMO clinical-biological database in China established by our group, this project aims to develop a Chinese precision management strategy for ECMO-supported patients with moderate-to-severe ARDS. 1. Comprehensive characterization of immune spatiotemporal dynamics in moderate-to-severe ARDS is essential for identifying therapeutic targets Current biomarkers reflecting disease progression in ARDS are largely limited to static clinical parameters and single-dimensional measurements, making biomarker-guided precision therapy difficult. Previous studies have identified biomarkers such as soluble receptor for advanced glycation end-products (sRAGE), angiopoietin-2 (Ang-2), and surfactant protein D (SPD) as prognostic indicators, yet these markers provide limited mechanistic insights and have not translated into individualized therapeutic strategies. Our group has established the largest ARDS and ECMO biospecimen cohort in China and has preliminarily characterized the spatiotemporal immune landscape of moderate-to-severe ARDS. We identified VCAM1 and tRF-5004b as potential immune-related targets closely associated with disease progression, providing a solid foundation for the proposed study. 2. Elucidating inflammatory and immune mechanisms underlying severe ECMO-related complications is critical for targeted intervention Among ARDS patients receiving ECMO support, the incidence rates of acute kidney injury (AKI), bleeding/thrombosis, and infection are approximately 45.7%, 40.2%, and 44.7%, respectively. Systemic inflammatory and immune dysregulation is considered a major contributor to these complications, although the underlying mechanisms remain unclear. In addition to the excessive inflammatory response characteristic of ARDS, restoration of oxygen delivery after ECMO initiation may trigger bursts of reactive oxygen species, calcium overload, and endothelial injury, thereby exacerbating inflammation and causing multiple organ dysfunction. Clarifying these mechanisms is essential for developing individualized interventions against severe ECMO-related complications. 3. Establishing multidimensional ARDS subphenotypes provides the basis for precision awake ECMO therapy ARDS is highly heterogeneous with respect to etiology, clinical manifestations, pathophysiology, and molecular characteristics, resulting in variable responses to ECMO support. Conventional classification based on oxygenation or isolated physiological parameters fails to capture the complex biological and immunological evolution of the disease. Our group previously identified hyperinflammatory and hypoinflammatory ARDS phenotypes using multidimensional clinical and biological data, but differences in ECMO responsiveness between these phenotypes have not been systematically investigated. Therefore, comprehensive characterization of ARDS biological heterogeneity and development of an integrated subphenotyping model incorporating clinical, physiological, imaging, and immune molecular features are required to identify patients most likely to benefit from awake ECMO. 4. Deciphering mechanisms of lung injury and repair is crucial for individualized mechanical ventilation strategies Inappropriate mechanical ventilation can exacerbate ventilator-induced lung injury and impair lung repair. Understanding the cellular and molecular mechanisms underlying lung injury and regeneration and clarifying the relationship between ventilatory parameters and tissue stress responses are fundamental to achieving personalized lung-protective ventilation. This project will integrate multimodal imaging, respiratory mechanics, and multi-omics data to characterize the dynamic processes governing lung injury and repair in ARDS, thereby establishing precision mechanical ventilation strategies to enhance lung protection and promote tissue recovery. Perspectives and Expected Impact Focusing on the major challenges in the management of moderate-to-severe ARDS, this project will elucidate the mechanisms responsible for severe complications during ECMO support, establish a multidimensional phenotyping framework to identify patients most likely to benefit from awake ECMO, and decode the mechanisms of lung injury and repair to develop individualized ventilation strategies. Ultimately, this work will provide a comprehensive precision management framework for ECMO-supported ARDS patients, improve the standard of care for moderate-to-severe ARDS in China, and reduce disease-related mortality.

Researchers are evaluating normobaric hyperoxia NBO as a treatment for patients who have experienced an acute ischemic stroke and are transferred for endovascular thrombectomy EVT. The study aims to assess the effectiveness and safety of NBO in improving functional outcomes at 3 months after stroke. Stroke is a leading cause of death and disability, and although reperfusion treatments like thrombectomy improve blood flow, less than half of patients achieve favorable recovery. NBO is thought to protect the brain by rescuing hypoxic tissue and reducing damage processes, with advantages such as low cost and easy use. Participants will be randomly assigned to receive either NBO, which involves inhaling 100% oxygen alongside the best medical care, or best medical care alone. The study compares these two groups to see if NBO provides additional benefits. The treatment is given during the acute phase before or during transfer for EVT. The study includes a single-blind design and follows patients for outcomes over time. During the study, participants will have their disability level measured using the modified Rankin Scale at 90 days and one year after randomization. Other assessments include neurological function scores, imaging scans, infarct volume changes, and quality of life questionnaires at various time points. Safety and recovery progress are closely monitored throughout, with follow-up visits to track long-term effects. The total participation duration includes initial treatment and follow-up through one year.