Xin Yang Shi

Researchers are evaluating the safety, tolerability, and effectiveness of a combination of drugs including RC118, Toripalimab, and RC148 in patients with Claudin 18.2-positive, locally advanced unresectable or metastatic malignant solid tumors, especially focusing on gastric and gastro-esophageal junction cancers. This open, multi-center study includes Phase I to establish safe dosage levels and Phase II to assess treatment outcomes. The trial is sponsored by RemeGen Co., Ltd. and aims to improve options for patients who have failed standard therapies. Participants receive RC118 administered every two weeks at one of two dose levels, combined with a fixed dose of Toripalimab every three weeks. Based on initial dose escalation results in Phase I, an extension cohort will evaluate combinations of RC118 plus Toripalimab or RC148. The study involves careful dose adjustment to find the maximum tolerated dose and recommended Phase II dose. During the study, participants will undergo regular assessments including measurement of adverse events, tumor response, and survival outcomes over up to 15 months. Tumor tissue samples will be collected to confirm Claudin 18.2 expression and monitor biomarkers. Safety monitoring includes tracking dose-limiting toxicities early in treatment and overall tolerability. Participants must meet specific health criteria and will be followed closely throughout the trial duration, with study visits scheduled to assess treatment effects and side effects.

People with end stage kidney disease ESKD who require dialysis face a much higher risk of cardiovascular disease compared to the general population, with cardiac issues causing 58% of deaths in this group. However, while aspirin is known to reduce cardiovascular problems in the general population, there is limited evidence about its effects in dialysis patients. The ASPIrin to Reduce Event in Dialysis ASPIRED trial aims to study whether taking low-dose aspirin can safely improve cardiovascular outcomes in people with ESKD receiving dialysis. This study is a multi-center, double-blind, randomized controlled trial that will compare daily low-dose aspirin 100 mg to a placebo pill in patients undergoing dialysis. The trial uses an existing dialysis registry platform to screen, recruit, and collect data during routine clinical care, minimizing participant burden and study costs. Randomization is managed through a secure web-based system, and follow-up visits occur every six months as part of regular clinic visits. The trial is expected to last approximately five years and includes oversight by an independent safety and monitoring board. Participants will be involved in regular six-monthly clinic visits where their health will be monitored as part of their usual dialysis care. Researchers will track the occurrence of major cardiovascular events, including heart attacks, strokes, vascular complications, and deaths, throughout the study period. Data will be collected from routine clinical procedures and the dialysis registry to evaluate outcomes. Safety and efficacy will be closely monitored, and the study will follow participants for up to five years to assess the long-term effects of aspirin use in this population.

Researchers are evaluating the long-term effectiveness and safety of drug-coated balloon DCB strategies, including DCB alone or combined with drug-eluting stents DES, compared to DES-only treatment in patients with chronic total occlusion CTO of coronary arteries after successful reopening. This multicenter randomized controlled trial aims to fill the gap in direct comparative data between DCB and DES treatments for CTO, with the goal of optimizing treatment strategies, reducing stent use, lowering complication risks, and improving patient outcomes. Participants will be randomly assigned to either the DCB group, which involves balloon angioplasty with drug coating and possible provisional DES implantation if needed hybrid strategy, or the DES-only group receiving standard drug-eluting stent placement. Both groups receive standard medical therapy including at least 12 months of dual antiplatelet therapy DAPT. The study includes a 9-month primary endpoint assessment and a 36-month follow-up period to monitor long-term outcomes. During the study, patients will undergo angiographic evaluation for late lumen loss at 9 months, assessed by an independent laboratory using quantitative coronary angiography. Clinical events such as target lesion failure, cardiac death, myocardial infarction, and repeat revascularization will be monitored up to 36 months. Patient-reported outcomes like angina status and quality of life, as well as intravascular imaging and safety parameters, will also be collected. Overall participation spans over three years with regular follow-up visits to assess treatment effects and safety.

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.

Obesity greatly increases the risk of heart failure, and current treatments like caloric restriction, exercise, medications, or surgery may not be suitable for obese patients with heart failure. This research aims to study whether a combined approach using a diet management app and an intelligent weight scale can help obese patients with heart failure and reduced ejection fraction lose weight and improve their heart condition. The trial compares the effectiveness of a fully functional app and scale versus a limited-function version to assess their impact on heart failure outcomes and overall quality of life. Participants are randomly assigned to two groups one using a fully featured diet management app and intelligent weight scale with various monitoring tools and health metrics, and the other using a limited version of both. The full app tracks food intake, exercise, weight, and provides dietary analysis and recommendations, while the full scale measures body composition and vital signs. The limited versions offer fewer features. Participants use the app at every meal and weigh themselves daily for 12 months. During the study, participants will visit the clinic at 12 months for checkups. Researchers will evaluate outcomes such as a composite of death and heart failure hospitalizations over one year, changes in quality of life related to heart failure, and weight change. The trial includes monitoring of heart failure frailty and quality of life assessments at baseline, 3 months, and 1 year, with ongoing safety and condition tracking throughout the study period.

Researchers are conducting a multicenter, prospective observational study to evaluate the effectiveness and safety of Proline Plus Empagliflozin Tablets in treating type 2 diabetes mellitus in real-world clinical settings. This post-marketing study does not interfere with routine care and allows the drug to be used alone or alongside other treatments based on patient needs. The study aims to better understand how this medication performs across different patient subgroups and conditions. Participants prescribed Proline Plus Empagliflozin Tablets will follow a treatment plan with doses starting at one tablet once daily with meals. For those needing stronger blood sugar control and tolerating the initial dose, the medication may be increased to two tablets once daily. The study includes a screening period up to 14 days before treatment, followed by three treatment follow-up visits at approximately 12, 24, and 48 weeks to monitor outcomes. During the study, researchers will collect data from routine examinations, medication use, and any side effects or adverse events. Patients will complete quality of life assessments EQ-5D, while those aged 50 or older with at least elementary education will also undergo cognitive testing MoCA. The primary outcome is achieving blood sugar control with HbA1c below 7.0% at 24 weeks. Additional analyses will explore effects in subgroups based on age, HbA1c levels, body mass index, other medications, and related health conditions like kidney, heart, eye diseases, and cognitive impairment.

Researchers are conducting a multicenter, prospective observational study across 200 hospitals in China to examine current treatment patterns for chronic hepatitis B CHB. The study aims to compare patient outcomes under different treatment regimens to provide evidence-based data that can improve CHB treatment strategies and follow-up care, ultimately advancing efforts toward a functional cure for chronic hepatitis B. Participants include those receiving or planned to receive treatments such as entecavir ETV, tenofovir disoproxil fumarate TDF, tenofovir alafenamide fumarate TAF, tenofovir amibufenamide TMF, or peginterferon alpha-2b injection. The study observes real-world clinical practice without assigning treatments, capturing data on these therapies over an extended period. During the study, researchers will monitor outcomes including the percentage of patients developing HBsAg-associated hepatocellular carcinoma HCC, incidence of HCC, rates of HBsAg seroclearance and seroconversion, changes in HBsAg levels, HBV DNA levels, liver fibrosis improvement, and liver-related complications. Data collection spans from week 4 up to week 240, with continuous follow-up to assess treatment effects and patient status over time.

Researchers are studying the safety and effectiveness of starting direct oral anticoagulants DOACs early versus delaying their start in adults who have had an acute ischemic stroke related to atrial fibrillation and received emergency endovascular therapy EVT. This trial is a multicenter, randomized controlled study designed to compare different timings for beginning DOAC treatment after stroke. Participants are randomly assigned to one of two groups. One group will begin taking any DOAC within 96 hours 4 days of stroke onset, while the other group will start DOAC treatment between 5 and 14 days after stroke onset. The study compares these two approaches to see which timing is safer and more effective. During the study, participants will be monitored for outcomes including recurrent ischemic stroke, symptomatic brain bleeding, and death over 90 days. Researchers will also assess other events like venous clots, heart attacks, and overall quality of life. Follow-up visits and assessments will track these health outcomes and safety measures throughout the study period, which lasts up to one year for some outcomes.

Researchers are evaluating the safety and effectiveness of starting direct oral anticoagulants DOACs early versus delayed in patients who have an acute ischemic stroke related to atrial fibrillation and develop bleeding in the brain after emergency endovascular treatment. This multicenter, open-label, randomized controlled trial focuses on the best timing to begin DOAC therapy to help manage these patients and reduce risks of complications such as recurrent stroke or bleeding. Participants will be randomly assigned to one of two groups an early anticoagulation group starting DOACs within 4 weeks of stroke onset, and a delayed anticoagulation group starting DOACs between 4 and 8 weeks after stroke onset. The study compares these two approaches to determine which timing is safer and more effective for this condition. The treatments involve any direct oral anticoagulant drug, and the trial is conducted at multiple centers with an open-label design. During the study, participants will be closely monitored for outcomes including recurrent ischemic stroke, symptomatic brain bleeding, and death over 90 days. Other assessments include measuring quality of life, hospital stay length, vascular events, and functional recovery using the modified Rankin scale. Researchers will collect data through imaging, clinical evaluations, and questionnaires. Follow-up is planned for 90 days after starting treatment to assess safety and overall health outcomes.