Clinical trials

Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Severe sepsis is the most common cause of death among critically ill patients in non-coronary intensive care units (ICU). Sustained excessive inflammation and immune dysfunction have been confirmed to play a key role in organ damage and early death of sepsis patients. Therefore, it is important to reduce excessive inflammatory response mediated by immune cells and pro-inflammatory cytokines in the acute phase of sepsis. Single-cell RNA sequencing performed on both septic patients and mice suggest that changes in Tcm (CD3+ CD8+ CD44+ CD127+ CD62L+) and Tem (CD3+ CD8+ CD44+ CD127+ CD62L -) in the acute phase of sepsis may play an important role in sepsis. In addition, animal researches showed that Tcm and Tem decreased decreased continuously at 24, 48 and 72h after cecal ligation and perforation (CLP) in mice, and the adoptive transfer of Tcm , sorting from spleen of mice 24h after CLP , but not Tem improved 7-day survival rate of sepsis mice. This observational study is aimed to investigate the quantity and proliferation of Tcm and Tem in the acute phase of sepsis and their correlation with severity level and mortality of septic patients in ICU.

Some adults in the intensive care unit (ICU) cannot receive enough nutrition through a feeding tube because of persistent digestive problems, even after standard measures to improve feeding. This condition is called refractory enteral feeding intolerance. The community of microorganisms living in the gut, known as the gut microbiota, and the substances produced by these microorganisms and the body may be associated with feeding tolerance and recovery. This prospective observational study will enroll approximately 180 adults with refractory enteral feeding intolerance at a single hospital. It aims to describe changes in their gut microbiota and metabolic profiles over time and identify combinations of microbial markers associated with improved feeding tolerance and adequate nutritional intake. Stool samples or rectal swabs will be collected at enrollment, on days 3-5 and day 7, and, when feasible, near the end of the ICU stay. The samples will be used to examine the types of microorganisms present. Selected samples will also be analyzed for metabolic substances. Clinical information about nutrition, digestive symptoms, medications, illness severity, and treatments will be collected. Participants will be followed for up to 90 days to assess survival and unplanned hospital readmissions. The study will examine whether microbial and metabolic patterns provide additional information about feeding improvement by day 7 beyond routine clinical assessments. Where suitable public datasets are available, findings will also be evaluated in other patient groups. Participants will continue to receive usual medical care. The study does not assign treatments or change feeding decisions. Its findings may help guide future research on feeding intolerance, but participants are not expected to receive a direct medical benefit from taking part.

Sepsis is a life-threatening condition in which the body's response to an infection damages its own organs. This study aims to understand how the bacteria living in the gut change during sepsis and whether patterns of gut bacteria and chemicals found in stool can help identify patients at greater risk of death or poor recovery. This observational study plans to enroll approximately 180 adults with sepsis receiving care in the intensive care unit (ICU) at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. All participants will receive usual medical care. The study will not assign experimental treatments or change treatment decisions. Researchers will collect stool samples or, when stool is unavailable and sampling is safe, rectal swabs. Samples will be collected within the first 48 hours of the study, on days 3-5, on day 7, and near ICU discharge when feasible. Researchers will examine the types and amounts of gut bacteria. Samples from a selected group of participants will also be tested for chemicals related to metabolism. Information about illness severity, medicines, nutrition, and organ support will be collected from medical records. Participants will be followed for 90 days, using medical records and telephone follow-up. The main clinical outcome is death from any cause within 28 days. Other outcomes include death and unplanned hospital readmission within 90 days. Researchers will assess whether gut bacterial patterns add useful information to routine clinical assessments and compare findings with available data from other sepsis studies.

This study will test whether electrical stimulation applied to the outer ear can improve tolerance of tube feeding in critically ill adults in the intensive care unit (ICU). Some ICU patients develop digestive problems, such as vomiting, diarrhea, or a buildup of feeding liquid in the stomach. These problems can prevent them from receiving enough nutrition through a feeding tube. This is called enteral feeding intolerance. The treatment being studied is called transcutaneous auricular vagus nerve stimulation (taVNS). It delivers small electrical pulses through electrodes placed on the skin of the outer ear, usually the left ear. It does not require surgery. The treatment targets a branch of the vagus nerve, which helps regulate digestion. Researchers want to find out whether adding this treatment to usual ICU care improves feeding tolerance and whether it causes side effects. The study will enroll 60 adults aged 18 years or older with enteral feeding intolerance at one hospital. Participants will be assigned by chance to one of two groups, with an equal chance of joining either group: * Usual ICU care alone. * Usual ICU care plus ear stimulation for 60 minutes once daily for five days. Stimulation will stop earlier if a participant leaves the ICU or the study team determines that it should be stopped for safety reasons. The main measure will be the proportion of participants whose feeding intolerance improves between 24 and 120 hours after enrollment. Improvement means receiving the study's target amount of calories through tube feeding for at least 48 consecutive hours without stopping feeding because of intolerance. Researchers will also collect blood samples and rectal swabs to study intestinal function, gut bacteria, and substances produced by the body and gut bacteria. They will record the use of pain medicines and sedatives, changes in illness severity, and possible side effects, including skin irritation, a slow heartbeat, or low blood pressure. Study assessments and sample collection in the ICU will continue for up to seven days after enrollment, ending earlier if the participant leaves the ICU. Follow-up at 28 and 90 days will assess survival and, at 90 days, new infections and hospital readmissions.

Cone Beam CT (CBCT) is an imaging modality used in interventional digital subtraction angiography (DSA). It produces three-dimensional images via cone-beam X-ray scanning and computer reconstruction. Clinically, CBCT guides puncture for pulmonary and hepatic lesions and evaluates post-intervention outcomes in liver cancer and cerebrovascular diseases. However, CBCT-guided interventions carry high patient radiation exposure; dose reduction often degrades image quality and impairs procedural results. Studies report that each 100 mGy radiation increment elevates cancer risk by 1.96-fold. Artificial intelligence enables low-dose CBCT. Our prior DeepPriorCBCT model embedded anatomical priors using neural discrete representation learning, reducing thoracic CBCT dose to one-sixth of routine protocols while preserving image quality. We further developed DeepPriorCBCT-V2 using 55 000 pre-reconstruction CBCT datasets covering brain, thorax and abdomen. This multi-organ model maintains image quality at one-sixth standard radiation dose. Nevertheless, its real-world clinical performance remains unvalidated. We therefore designed this prospective multicenter randomized controlled trial to evaluate the clinical applicability of DeepPriorCBCT-V2.

This study aims to evaluate a new pre-surgery (neoadjuvant) treatment for patients with stage II-III non-small cell lung cancer (NSCLC). Currently, standard pre-surgery treatment involves immunotherapy combined with chemotherapy. While effective, many patients still have residual tumor cells after this standard treatment. Radiation therapy can not only kill tumor cells but also help the immune system recognize and fight cancer. The type of radiation used in this study is called "Quad Shot" (QS) radiotherapy. It is a short, high-dose, cyclical treatment designed to boost the effects of immunotherapy with less toxicity than standard daily radiation. Patients in this study will receive 3 cycles of QS radiotherapy combined with Tislelizumab (an immunotherapy drug) and standard platinum-based chemotherapy before surgery. The main goal of this study is to see if this combined approach can make the tumor completely disappear under a microscope (called pathological complete response, or pCR). Researchers will also monitor the safety of the treatment, side effects, and how well patients tolerate the treatment before undergoing surgery. Approximately 12 patients will be enrolled in this study.

The goal of this clinical trial is to compare how esketamine and propofol affect blood pressure in critically ill adults who need a breathing tube in an intensive care unit (ICU). Placing a breathing tube into the windpipe is called tracheal intubation. Medicines are given to make patients unconscious and relax their muscles so the tube can be placed quickly. This procedure is called rapid sequence intubation. Blood pressure can fall during this process. The main question is whether esketamine leads to a higher minimum blood pressure than propofol during the first 10 minutes after the study medicine is given. Researchers will measure mean arterial pressure, which is the average pressure in the arteries during one heartbeat. The study will also compare the need for medicines to support blood pressure, complications around tube placement, survival, time on a breathing machine, and length of ICU stay. The study will enroll 130 adults aged 18 years or older at one hospital in China. Participants will be assigned by chance, like flipping a coin, to receive either esketamine or propofol through a vein before tube placement. Each participant will have an equal chance of receiving either medicine. The treating team will know which medicine is given. Both groups will receive a muscle relaxant and follow the same standard procedures for tube placement and blood pressure support. The care team will closely monitor blood pressure, heart rate, and blood oxygen levels before and after tube placement. Researchers will record side effects, including high blood pressure, a fast heart rate, and confusion after the procedure. Participants will continue to receive usual ICU care and will be followed until hospital discharge or death, for up to 60 days.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, representing one of the leading causes of death in intensive care units (ICUs) worldwide. Gut microbiota disruption is increasingly recognized as a key driver of persistent inflammation and multiple organ dysfunction in septic patients. Fecal microbiota transplantation (FMT) has emerged as a promising approach to restore gut microbial homeostasis. This study hypothesizes that FMT acts not through long-term engraftment of donor microbes, but via a "functional pulse" - a potent, transient biological intervention that delivers high-dose microbial metabolites (e.g., short-chain fatty acids), competitively inhibits pathogens, and rapidly modulates intestinal immune cell functions. This is a single-center, open-label, randomized controlled trial conducted in the ICU of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. A total of 60 adult patients diagnosed with sepsis according to Sepsis-3 criteria within 24 hours of ICU admission will be randomized in a 1:1 ratio to receive either ICU standard care alone (control group) or ICU standard care plus FMT administered via a nasojejunal tube for three consecutive days (intervention group). The primary endpoint is all-cause mortality at 90 days. Secondary endpoints include ICU mortality, in-hospital mortality, 28-day mortality, changes in gut microbiota composition and metabolites, serum citrulline levels as a marker of intestinal barrier function, Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, vasopressor requirements, C-reactive protein and procalcitonin levels, fluid balance, incidence of ICU delirium and feeding intolerance, and 90-day hospital readmission rate. Safety outcomes include gastrointestinal symptoms and transient fever.

Sepsis remains a leading cause of critical illness worldwide, yet the underlying mechanisms driving its profound and persistent immune dysfunction are incompletely understood. The bone marrow, as the birthplace of all immune cells, plays a central role in orchestrating systemic immune responses. Emerging evidence from animal models suggests that sepsis triggers emergency myeloid-biased hematopoiesis in the bone marrow, characterized by expansion of myeloid progenitors and myeloid-derived suppressor cells (MDSCs) at the expense of lymphoid and erythroid lineages. This bone marrow remodeling precedes peripheral immune alterations and may represent the initiating event of sepsis-induced immunosuppression. However, direct clinical evidence in humans is scarce. This prospective, single-center cohort study aims to systematically characterize bone marrow hematopoietic remodeling in patients with septic shock, compared to critically ill non-septic patients and healthy volunteers, and to determine whether the degree of myeloid lineage bias correlates with disease severity, immunosuppression, and adverse clinical outcomes. This study will enroll three cohorts. Bone marrow aspirates and peripheral blood samples will be collected at 48-72 hours post-enrollment for flow cytometric immunophenotyping of hematopoietic stem/progenitor cells, MDSC subsets, and PD-L1 expression, as well as cytokine profiling and exploratory single-cell transcriptomics. Rectal swabs will be collected synchronously for 16S rRNA sequencing and untargeted metabolomics to investigate the association between gut microbiota, microbial metabolites, and bone marrow myeloid skewing, testing the gut-bone marrow-immune axis hypothesis. Clinical severity (SOFA/APACHE II), secondary infections, and 90-day mortality will be assessed to evaluate prognostic value. By integrating bone marrow hematopoiesis, gut microbiome, and clinical outcomes, this study seeks to provide novel mechanistic insights into sepsis-induced immunoparalysis and identify potential biomarkers or therapeutic targets for immune restoration.

Efficacy and safety of retlirafusp alfa combined with bevacizumab and chemotherapy with or without short-course radiotherapy in conversion therapy for advanced colorectal cancer liver metastases: an exploratory study.

This investigator-initiated, single-center study consists of a retrospective artificial intelligence model-development stage and a prospective physician reader-study stage. Deidentified chest CT examinations acquired during routine clinical care between January 1, 2021, and December 31, 2024, will be used to develop, validate, and lock artificial intelligence models for lung cancer-related imaging tasks. In the prospective stage, approximately 12 to 15 physicians with experience in chest CT interpretation will complete two reading sessions in randomized order: unaided interpretation and AI-assisted interpretation. The sessions will be separated by a washout period of at least 4 weeks. The primary objective is to compare diagnostic performance between AI-assisted and unaided interpretation. Secondary objectives include reading time, diagnostic confidence, inter-reader agreement, and errors related to incorrect AI suggestions. All readings will be performed in an offline research environment. AI outputs will not be used for patient care, and the study will not add imaging examinations, treatment, or follow-up for patients.

This prospective observational cohort study investigates the subset-specific metabolic adaptation and functional remodeling of cytotoxic γδT cells in critically ill patients with and without sepsis. Emerging evidence indicates that γδT cells, as a bridge between innate and adaptive immunity, play a critical role in early anti-infection defense during sepsis. However, the functional status and underlying regulatory mechanisms of cytotoxic γδT cells in septic patients remain incompletely understood. Our preliminary single-cell transcriptomic analysis revealed that cytotoxic γδT cells from septic patients exhibit significant alterations in cytotoxicity-associated molecules (GZMB, PRF1, GNLY) and mitochondrial oxidative phosphorylation (OXPHOS) pathway genes, particularly COX6C, which correlates with cytotoxic effector molecule expression. This study aims to systematically characterize the proportion, cytotoxicity, and mitochondrial metabolic function of circulating cytotoxic γδT cells across three cohorts: healthy controls, critically ill non-septic patients, and critically ill septic patients. By integrating flow cytometry, mitochondrial function assays, and functional validation experiments, we seek to elucidate the role of COX6C-mediated mitochondrial metabolic abnormalities in cytotoxic γδT cell dysfunction, providing theoretical basis for understanding immune dysregulation in sepsis and identifying novel therapeutic targets.

Critically ill patients admitted to the intensive care unit (ICU) frequently present with gastrointestinal dysfunction and are at elevated risk of malnutrition. Gastrointestinal dysfunction is correlated with adverse clinical outcomes, including prolonged mechanical ventilation duration, extended ICU length of stay, and increased 90-day mortality. In critically ill ICU patients, severe gut microbiota dysbiosis and intestinal barrier impairment may occur due to the burden of primary critical illnesses, as well as the administration of proton pump inhibitors and antibiotics. This cascade contributes to a high prevalence of gastrointestinal dysfunction, alongside profound gut-derived systemic inflammatory responses and organ damage. Given the pivotal role of gut microbiota in maintaining intestinal homeostasis, fecal microbiota transplantation (FMT) holds promise as a novel therapeutic strategy for enteral feeding intolerance secondary to gastrointestinal dysfunction in critically ill ICU patients. This study intends to deliver FMT via a nasojejunal tube to critically ill patients with gastrointestinal dysfunction admitted to the ICU. Its objectives are to evaluate the intervention's effects on gastrointestinal function recovery and the alleviation of enteral feeding intolerance, while also assessing its impacts on intestinal barrier function, gut microbiota composition and metabolic profiles, serum metabolite signatures, immune-inflammatory responses (including lymphocyte subsets, cytokines, C-reactive protein, and procalcitonin), ICU delirium, ICU sleep quality, and clinical outcomes (encompassing ICU mortality, in-hospital mortality, 28-day all-cause mortality, 90-day all-cause mortality, 90-day readmission rate, and 90-day incidence of secondary infections).

The purpose of this study is to learn how well a combination of iparomlimab and tuvonralimab (QL1706), lenvatinib, radiotherapy, and hepatic arterial infusion chemotherapy (HAIC) works and how safe it is for people with hepatocellular carcinoma (HCC) that has grown into the portal vein, forming a portal vein tumor thrombus (PVTT). Participants will receive iparomlimab and tuvonralimab together with lenvatinib, radiotherapy directed at the portal vein tumor thrombus, and HAIC, which delivers chemotherapy directly through the hepatic artery. Researchers will evaluate how long the cancer remains controlled without getting worse, how much the tumors shrink, how long participants survive, and whether the treatment makes surgery possible for some participants. Treatment-related side effects will also be assessed. The study will also explore whether features in tumor tissue and blood are associated with treatment response and may help identify patients who are more likely to benefit from this treatment strategy.

This phase III trial aims to evaluate the efficacy and safety of induction chemotherapy combined with serplulimab (induction/maintenance therapy) with omission of concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).

This study is a prospective, single-arm, multicenter phase II clinical trial. The study plans to enroll 40 patients with HR+/HER2- advanced breast cancer to explore the efficacy and safety of patients receiving olmesartan, dalpiciclib and aromatase inhibitor treatment.

Coronary heart disease (CAD) is caused by myocardial ischemia, hypoxia or necrosis due to coronary artery stenosis, spasm or obstruction. Although standard drug therapy can greatly improve the prognosis of patients with CAD after percutaneous coronary interventions (PCI), these patients are still at high risk of major adverse cardiovascular events (MACE). At present, the concept of residual inflammation risk (RIR) has aroused widespread concern. RIR is an important independent risk in patients with CAD. Foreign studies indicate that hsCRP ≥ 2mg / L is the definition standard of RIR in CAD. In China, there is no defined value of RIR for patients undergoing PCI, and the incidence of RIR has not been investigated clearly. At the same time, the impact of dynamic changes of hsCRP on MACE in PCI population needs to be further explored. Therefore, in this study, we plan to recruit patients undergoing PCI, and observe the impact of RIR by serial hsCRP measurements on the prognosis of these patients followed up for 5 years.

This study will compare three anesthesia medicines used to put people into a deep sleep during surgery: ciprofol, propofol, and sevoflurane. All three are commonly used for general anesthesia, but they work in different ways. Ciprofol and propofol are given through a vein. Sevoflurane is breathed in as a gas. After brain tumor surgery, some older adults may develop sudden confusion and memory problems called delirium. Researchers want to learn which of these three medicines is best at preventing delirium and protecting brain function in older adults undergoing brain tumor surgery. About 381 participants aged 65 to 90 will take part. Participants will be randomly assigned to one of three groups. One group will receive ciprofol. Another group will receive propofol. The third group will receive sevoflurane. All participants will receive standard care during and after brain tumor removal. The main goal is to compare how many participants develop delirium within 7 days after surgery. Researchers will also look at how long delirium lasts, how severe it is, thinking and memory skills at 7, 30, 90, and 180 days after surgery, quality of recovery, blood pressure and heart rate during surgery, and treatment safety. Blood tests will be used to measure markers of body stress, inflammation, and nerve cell injury before surgery, 3 hours after surgery, and 1 day after surgery. Researchers will also test thinking and memory with simple questions twice a day for 7 days after surgery. Later follow-up will be done by phone at 30, 90, and 180 days after surgery. This study is designed to explore which anesthesia medicine is safest and best at protecting the brain after surgery in older adults with brain tumors. The results may help doctors choose the best anesthesia for this group of patients in the future.

This is a single-center, prospective, randomized, three-period crossover physiological study in adult patients with moderate-to-severe acute respiratory distress syndrome (ARDS, PaO₂/FiO₂ ≤150 mmHg). Each enrolled subject will receive all three APRV ventilation conditions in random sequence: low-level spontaneous breathing (spontaneous minute-ventilation proportion 10%-30%), high-level spontaneous breathing (31%-50%), and fully suppressed spontaneous breathing as control. A 30-minute wash-out period is set between each condition to restore unified physiological baseline. Primary outcome is ventilation-perfusion mismatch percentage (mismatch%) measured by Electrical Impedance Tomography (EIT). Secondary outcomes include EIT-derived pulmonary parameters, respiratory mechanics, hemodynamics, diaphragmatic function and safety profiles. Only short-term, reversible ventilator and sedation adjustments will be performed; routine clinical management remains unchanged throughout the trial.

The goal of this prospective observational study is to evaluate how well a previously developed prediction model can estimate outcomes in adults with gastric cancer. The model combines information from computed tomography (CT) images obtained before treatment with routine clinical information. The main questions are how well the model predicts how long participants live after treatment begins and whether their cancer progresses. Participants will receive their usual medical care. Researchers will collect pretreatment CT images, basic clinical and tumor information, laboratory and tumor marker results, treatment information, and follow-up outcomes obtained during routine care. These data will be entered into the predefined prediction model, and the model's predictions will be compared with what actually happens during follow-up. The study will not change the participants' usual treatment. Model predictions will be used for research purposes only and will not be used to make treatment decisions.

The goal of this clinical trial is to determine whether a semaglutide dose-tapering regimen is non-inferior to a treatment-dose maintenance regimen for weight-loss maintenance in adults with overweight or obesity who have achieved stable weight loss. This trial will also evaluate the safety of the dose-tapering regimen. The primary research questions are: Is the semaglutide dose-tapering regimen non-inferior to the treatment-dose maintenance regimen for weight-loss maintenance at 24 weeks? Can the dose-tapering regimen alleviate adverse events and offer a more personalized, sustainable pathway for medication discontinuation? Researchers will compare the semaglutide dose-tapering regimen against a treatment-dose maintenance regimen to assess whether the tapering strategy preserves weight loss and improves cardiometabolic markers. Participants will: Be randomly assigned to receive either the semaglutide dose-tapering regimen or the treatment-dose maintenance regimen for 24 weeks. Complete a 24-week follow-up period after medication discontinuation (48 weeks total study duration). Attend scheduled clinic visits for physical examinations and laboratory testing to assess weight, BMI, waist circumference, cardiometabolic markers (including blood glucose, blood pressure, and lipids), and to monitor adverse events.

A Multicenter, Single-Arm, Prospective Phase II Clinical Study of Trastuzumab Rezetecan Combined with Radiotherapy in Patients with HER2-Mutated Oligoprogressive Advanced Non-Small Cell Lung Cancer

This is a single-arm, open-label, dose-escalation study designed to enroll approximately 5-30 patients with TDT or SCD. The objectives are to evaluate the safety and tolerability in patients following intravenous administration of YOLT-204 and to preliminarily assess its effect on fetal hemoglobin levels in plasma. In this study, the maximum screening period of the main study is 60 days, the treatment day is Day 0 (D0), and the safety follow-up period is up to Week 52 after administration.

Neoadjuvant therapy has been widely applied to locally advanced rectal cancer. However, about 50% of patients receiving this therapy do not respond well as evidenced by the fact that their T or N stages are not effectively decreased judged by postoperative pathological examination. The purpose of this trail is to identify the biomarkers (from within patients' tumor mass before neoadjuvant therapy) to predict resistance to neoadjuvant therapy. These biomarkers can help stratify neoadjuvant-resistant patients towards surgery while avoiding unnecessary chemoradio-based neoadjuvant therapy.

The goal of this clinical trial is to learn if sorbitol works to enhance the therapeutic effect of neoadjuvant chemotherapy combined with Tirellizumab (PD-1 inhibitor) in patients with locally advanced gastric cancer. It will also learn about the safety of sorbitol. The main questions it aims to answer are: Does sorbitol enhance the therapeutic effect of immunotherapy and increase the major response rate in patients with locally advanced gastric cancer? Does sorbitol with neoadjuvant chemotherapy combined with Tirellizumab (PD-1 inhibitor) can improve the prognosis of patients with locally advanced gastric cancer? Researchers will compare sorbitol to a standard-of-care treatment (aPD-1 + SOX chemotherapy) to see if sorbitol works to enhance the therapeutic effect (Add-on Effect) of neoadjuvant chemotherapy combined with Tirellizumab (PD-1 inhibitor) in patients with locally advanced gastric cancer. Participants will: Take sorbitol every day for 3 months in 3 treatment cycles Visit the clinic once every 4 weeks for checkups and tests Keep a diary of their symptoms and the number of times they use a rescue inhaler Participants will follow up as planned until PD occurs, informed consent is withdrawn, or follow-up is lost (whichever occurs first). After the end of treatment and safety follow-up, all subjects will be followed up for survival (OS data collected every 3 months ±14 days).