Clinical trials

Sepsis is a major cause of morbidity and mortality in intensive care units. Sepsis-associated liver injury (SALI) and sepsis-associated acute kidney injury (S-AKI) are common complications associated with adverse clinical outcomes. Altered gut microbial diversity, microbial metabolites, intestinal barrier dysfunction, and systemic inflammation may contribute to hepato-renal injury during sepsis. However, prospective longitudinal evidence in patients with SALI and S-AKI remains limited. This prospective, multicenter, longitudinal observational cohort study will enroll adult patients with sepsis across eight intensive care units at six medical centers and healthy adult volunteers as a baseline reference cohort. For patients with sepsis, stool and blood samples will be collected on Day 0, Days 3-5, Days 7-10, and Days 14-20 after sepsis diagnosis. Healthy volunteers will provide a single baseline stool and blood sample at enrollment. Fecal microbial alpha diversity and community structure will be assessed by metagenomic sequencing and bioinformatic analysis. Plasma metabolites, including total short-chain fatty acids, indoxyl sulfate, and additional targeted plasma metabolites, will be measured by ultra-high-performance liquid chromatography-tandem mass spectrometry. Intestinal barrier and clinical biomarkers will also be assessed. The primary objectives are to evaluate the associations between longitudinal trajectories of fecal microbial alpha diversity, measured by the Shannon diversity index, and the occurrence of SALI and S-AKI within 7 days after sepsis diagnosis. Secondary objectives include evaluating the associations between longitudinal changes in fecal microbial beta diversity and the occurrence of SALI and S-AKI; assessing the associations between longitudinal trajectories of fecal microbial alpha diversity and organ recovery status at Days 14-20 among patients who develop SALI or S-AKI; describing selected plasma metabolite and intestinal biomarker concentrations at prespecified time points; and assessing 28-day all-cause mortality. Exploratory multi-omics analyses will evaluate microbial taxa, microbial functional genes, metabolites, and host biomarkers to identify candidate biomarkers and biological pathways associated with the development and clinical course of sepsis-associated hepato-renal injury.

The aim of this study is to evaluate the lesion detection performance and safety of 18F-S2P positron emission tomography (PET) in patients with large-artery atherosclerosis.

This is a prospective, multicenter, randomized controlled trial designed to evaluate the efficacy and safety of venetoclax-enhanced BUCY (Ven-BUCY) conditioning compared to the standard BUCY regimen in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Eligible participants aged 12 to 60 years will be randomized 1:1 to receive either Ven-BUCY or standard BUCY conditioning. The primary endpoint is relapse-free survival (RFS) at two years post-transplant. Secondary outcomes include overall survival, relapse rate, non-relapse mortality, measurable residual disease (MRD), and treatment-related adverse events. The study aims to improve post-transplant outcomes by deepening disease remission through the addition of venetoclax, a BCL-2 inhibitor known to target leukemia stem cells and enhance chemotherapy sensitivity.

This is a prospective, multicenter, randomized controlled trial designed to evaluate whether short-term blinatumomab intensification before allogeneic hematopoietic stem cell transplantation (allo-HSCT) can improve survival outcomes in adults with high-risk BCR::ABL1-negative B-cell acute lymphoblastic leukemia (B-ALL) who have achieved measurable residual disease (MRD) negativity. Blinatumomab, a CD19/CD3 bispecific T-cell engager, has shown promising efficacy in eradicating MRD and prolonging survival in B-ALL patients. In this study, eligible participants will be randomly assigned to receive either short-term blinatumomab consolidation prior to allo-HSCT or proceed directly to allo-HSCT. The primary endpoint is relapse-free survival (RFS). This study aims to optimize treatment strategies and improve long-term outcomes for patients with high-risk BCR::ABL1-negative B-ALL.

This prospective, randomized, open-label, multicenter trial aims to compare second-line treatment strategies for hepatic cGVHD after allo-HSCT. Ruxolitinib and belumosudil are both effective for cGVHD, but no head-to-head comparison specifically in hepatic cGVHD has been reported. Two cohorts are enrolled: Cohort 1 comprises patients with steroid-refractory hepatic cGVHD without prior ruxolitinib or belumosudil exposure, randomized to receive either agent. Cohort 2 includes patients who develop new-onset hepatic cGVHD after ≥4 weeks of therapy with ruxolitinib or belumosudil for other-organ cGVHD (stable for ≥2 weeks), or patients with non-response/progression on either agent for hepatic cGVHD; these patients will be switched to the opposite drug. Key questions include: • In steroid-refractory hepatic cGVHD, does 24-week hepatic overall response rate differ between belumosudil and ruxolitinib? • What is the hepatic response rate after drug switching in Cohort 2? • How do the two agents compare in safety and tolerability for hepatic cGVHD? • What are their impacts on corticosteroid tapering, failure-free survival, and long-term outcomes? Participants will: • Receive assigned treatment per cohort and randomization • Undergo regular efficacy/safety monitoring, including hepatic cGVHD scoring, liver function tests, and adverse event recording • Provide peripheral blood samples at baseline and multiple on-treatment time points for exploratory biomarker analysis • Complete 24-week primary efficacy assessment with follow-up until progression or discontinuation Primary endpoint is 24-week hepatic overall response rate (CR+PR, per 2014 NIH cGVHD criteria). Secondary endpoints include duration of response, failure-free survival, corticosteroid tapering rate, safety (AE/SAE incidence), liver function improvement, and patient-reported outcomes. This head-to-head comparison will provide high-level evidence for selecting second-line and beyond therapies for hepatic cGVHD.

The goal of this clinical trial is to observe whether different gastric protection strategies affect the incidence of acute graft-versus-host disease (aGVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Proton pump inhibitors (PPIs) are routinely used for gastric protection during transplantation, but their prolonged use may suppress gastric acid, alter gut microbiota, and potentially increase the risk of aGVHD. Teprenone, a gastric mucosal protective agent (GMPA), enhances mucosal defense mechanisms including promoting mucus secretion, increasing gastric mucosal blood flow, and facilitating epithelial cell repair, without affecting gastric acid secretion, and may therefore preserve microbial diversity and modify aGVHD risk. This study compares two strategies: continuous PPI use versus switching from PPIs to teprenone after transplantation. The main questions this study aims to answer are: * Does switching from PPIs to teprenone after transplantation reduce the cumulative incidence of aGVHD within +100 days post-transplantation compared with continuous PPI use? * What adverse events do participants experience with teprenone versus continuous PPI therapy? * Does teprenone therapy provide better preservation of gut microbial diversity and lower rates of gastrointestinal and infectious complications compared with continuous PPI use? In this prospective, randomized, parallel-controlled, single-center trial, approximately 198 patients undergoing allo-HSCT will be enrolled and assigned in a 1:1 ratio using a central randomization system. The experimental group (teprenone group) will receive standard-dose PPIs (esomeprazole, 40 mg/d, intravenous/oral) during conditioning and switch to teprenone (50 mg tid, orally) after transplantation through day +100. The control group (PPI group) will receive continuous standard-dose PPIs from conditioning through day +100. Probiotic use is prohibited from conditioning through day +100 in both groups. All other anti-infective, GVHD prophylaxis, and supportive care regimens are identical between the two groups. The primary endpoint of this study is the cumulative incidence of aGVHD within +100 days post-transplantation. Secondary endpoints include grade II-IV and grade III-IV aGVHD, lower gastrointestinal aGVHD, steroid-refractory aGVHD, gut and salivary microbiome dynamics (α-diversity, β-diversity, and specific taxa at pre-conditioning, day 0, day +14, and day +28), plasma biomarkers related to intestinal barrier integrity, systemic inflammation, and immune regulation , infectious and gastrointestinal complications (febrile neutropenia, diarrhea, C. difficile infection, bacteremia, EBV/CMV reactivation, upper GI bleeding, reflux), and 1-year survival outcomes (non-relapse mortality, overall survival, GVHD-free/relapse-free survival). During the study, participants will: * Receive the assigned gastric protection regimen (teprenone or PPI) according to randomization * Undergo regular assessments for safety and efficacy monitoring, including aGVHD surveillance and infection screening * Provide fecal and saliva samples at pre-conditioning, day 0, day +14, and day +28 post-transplantation for microbiome analysis * Provide peripheral blood samples at pre-conditioning, day 0, day +14, and day +28 post-transplantation for exploratory analysis * Be followed for up to 1 year post-transplantation

The goal of this clinical trial is to evaluate the efficacy and safety of Iptacopan as a second-line treatment for high-risk hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA). Iptacopan is a selective oral small-molecule complement factor B inhibitor. It acts by inhibiting factor B, blocking the formation of C3 convertase, reducing C3b deposition, thereby suppressing C5 convertase (C3bBbC3b) and ultimately decreasing the formation of the membrane attack complex (MAC), which is expected to mitigate endothelial damage in TA-TMA pathology. The main questions this study aims to answer are: * Does Iptacopan improve 6-month overall survival in high-risk TA-TMA patients? * What adverse events do participants experience while taking Iptacopan? * Does Iptacopan provide hematological response and organ function recovery in TA-TMA patients? In this prospective, multicenter, open-label, single-arm Phase II study, all participants will receive Iptacopan treatment. The primary endpoint of this study is the 6-month overall survival rate from TA-TMA diagnosis. Secondary endpoints include safety evaluation, hematological response, and organ function recovery. During the study, participants will: * Receive Iptacopan treatment according to protocol * Undergo regular assessments for safety and efficacy monitoring * Be followed for up to 24 months post-treatment initiation

This is a prospective, open-label, phase II, multicenter exploratory clinical study. Eligible female patients aged 18-75 years with stage II-III HER2-positive breast cancer will receive 4 cycles of SHR-A1811 (4.8 mg/kg, intravenous infusion every 3 weeks). After 4 cycles, tumor response will be assessed per RECIST 1.1 criteria. Patients with a ≥50% reduction in tumor burden will continue with another 4 cycles of SHR-A1811 followed by definitive surgery. Patients with \<50% reduction will receive 4 cycles of the THPy regimen (docetaxel + trastuzumab + pyrotinib) before surgery. Circulating tumor DNA (ctDNA) will be assessed for minimal residual disease (MRD) at baseline, after 4 cycles of treatment, and postoperatively. The primary endpoint is total pathological complete response (tpCR), assessed by an independent review committee (IRC). This study aims to evaluate the efficacy, safety, and feasibility of imaging- and MRD-guided neoadjuvant therapy in HER2-positive breast cancer.

This study evaluates whether chidamide maintenance therapy can effectively reduce the risk of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with high-risk T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma (T-ALL/LBL). Chidamide is an oral selective histone deacetylase inhibitor (HDACi) with dual anti-tumor and immunomodulatory effects. Participants will be randomized in a 1:1 ratio to receive either chidamide maintenance for up to 24 months or standard follow-up without maintenance. The primary endpoint is relapse-free survival (RFS). Key secondary endpoints include cumulative incidence of relapse (CIR), overall survival (OS), non-relapse mortality (NRM), incidence and severity of graft-versus-host disease (GVHD), safety profile, and patient-reported outcomes (PROs). This multicenter, open-label, randomized controlled trial aims to provide high-level evidence on the efficacy and safety of chidamide as a post-transplant maintenance strategy. Approximately 132 patients will be enrolled across 6 transplant centers in China.

The goal of this observational study is to valuate the sensitivity and specificity of different blood biomarkers for monitoring and assessing Aβ-PET-confirmed mitigation of amyloid pathology by lencanumab treatment in subjects treated with lencanumab.

The goal of this clinical trial is to evaluate the synergistic efficacy and safety of the Tongluo Huayu Formula combined with conventional Western medical treatment for RVO, thereby providing high-quality evidence to support its subsequent clinical promotion and application. The control group will receive conventional Western medical therapy, including laser photocoagulation and intravitreal Conbercept injection. Specifically, Conbercept will be injected intravitreally once a month for 3 consecutive months. If large areas of retinal non-perfusion or fundus neovascularization occur during the study period, laser photocoagulation will be administered based on the patient's condition. The experimental group will receive the Tongluo Huayu Formula in addition to the standard therapy provided to the control group. The Tongluo Huayu Formula will be administered for 1 month. Relevant examinations and assessments for participants in both groups will be conducted at baseline (before treatment), and at 1, 2, 3, and 6 months after treatment.

High-risk, complement-mediated, untreated transplant-associated thrombotic microangiopathy (hrTA-TMA) carries a very poor prognosis due to multiple organ dysfunction syndrome (MODS). The complement C5 inhibitor eculizumab has shown promising efficacy in children with hrTA-TMA, but has not been prospectively studied in adult allogeneic hematopoietic stem cell transplantation (HSCT) recipients. The investigators plan to conduct the first multicenter prospective study in adults to evaluate eculizumab as an early targeted intervention for hrTA-TMA. The investigators hypothesize that eculizumab will more than double the survival rate of hrTA-TMA in adult HSCT recipients compared with untreated hrTA-TMA patients from our previous study, who will serve as historical controls. Inclusion criteria are a confirmed diagnosis of TA-TMA with at least one of the following hrTA-TMA features: random urine protein-to-creatinine ratio (rUPCR) ≥2 mg/mg, multiple organ dysfunction syndrome (MODS), or elevated plasma IL-10 (≥2× upper limit of normal). The primary endpoint is survival at 6 months after diagnosis of hrTA-TMA. Secondary endpoints are the cumulative incidence of MODS at 6 months after diagnosis of hrTA-TMA, and 1-year post-transplant survival. The eculizumab regimen consists of an intensive loading dose, an induction dose, and a maintenance dose, with a total treatment duration of up to 24 weeks. This study aims to investigate the safety and efficacy of eculizumab in the treatment of high-risk TA-TMA.

National and international guidelines/consensus recommend G-CSF (granulocyte colony-stimulating factor) at 10 μg/kg/day as a single daily dose or divided into two daily doses for mobilization in healthy donors for allogeneic hematopoietic stem cell transplantation. However, there is no consensus or standard regarding single versus divided dosing, and high-quality evidence is lacking. Existing randomized controlled trials have small sample sizes and inconsistent conclusions, and none have focused on Asian population characteristics (e.g., body weight and drug metabolism differences). This study aims to provide level I evidence to optimize donor experience and define the optimal administration strategy. Inclusion criteria: Healthy allogeneic stem cell donors aged 18-60 years, meeting institutional standard donor screening criteria (HLA matching, normal blood counts, normal liver and kidney function, negative infection screening), and providing written informed consent. Primary endpoint: The rate of achieving a first apheresis yield of ≥ 4 × 10⁶ CD34⁺ cells/kg (donor body weight) after 5 days of G-CSF mobilization. Secondary endpoints: The rate of achieving ≥ 2 × 10⁶ CD34⁺ cells/kg with at most one apheresis; time to myeloid, platelet, and erythroid engraftment in recipients; the proportion and composition of immune cells (CD34⁺, CD3⁺, CD19⁺, CD56⁺, etc.) in the apheresis product; donor adverse events; donor-reported outcomes; and the difference in CD34⁺ stem cell yields between single-dose and divided-dose mobilization. Intervention: G-CSF will be administered at a total dose of 10 μg/kg/day, either as a single daily injection or divided into two equal daily injections. This study is designed to investigate whether single-dose or divided-dose G-CSF administration is superior for mobilizing healthy donors in allogeneic hematopoietic stem cell transplantation.

This is a prospective, multicenter, randomized controlled trial designed to evaluate whether the combination of ruxolitinib and etanercept provides superior efficacy compared with ruxolitinib monotherapy in patients with severe corticosteroid-refractory acute graft-versus-host disease (SR-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Acute graft-versus-host disease (aGVHD) is one of the most common and life-threatening complications following allo-HSCT. Although corticosteroids remain the standard first-line treatment, many patients do not respond adequately. For patients with severe steroid-refractory aGVHD, the prognosis is extremely poor, with high short-term mortality and very low long-term survival. Ruxolitinib, a JAK1/2 inhibitor, has been approved for the treatment of SR-aGVHD, but response rates remain suboptimal, particularly in patients with gastrointestinal involvement. Etanercept, a tumor necrosis factor-alpha (TNF-α) inhibitor, has shown activity in GVHD by targeting inflammatory pathways. Previous observational studies from our center suggested that combining ruxolitinib with etanercept may improve response rates, especially in gastrointestinal and hepatic GVHD, without significantly increasing relapse risk. In this trial, approximately 122 patients with grade III-IV SR-aGVHD will be randomized 1:1 to receive either ruxolitinib alone or ruxolitinib plus etanercept. The primary endpoint is the overall response rate (ORR) at day 28. Secondary endpoints include durable response, best overall response, failure-free survival, overall survival, cumulative incidence of relapse, non-relapse mortality, incidence of chronic GVHD, and safety outcomes. This study seeks to provide new clinical evidence for an optimized treatment strategy for patients with severe SR-aGVHD, aiming to improve outcomes in this high-risk population.

Healthy donors are commonly mobilized with granulocyte colony-stimulating factor (G-CSF) to collect peripheral blood stem cells for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the efficiency of mobilization varies among donors, and suboptimal mobilization may require additional collection procedures or rescue strategies. This prospective, multicenter, randomized trial evaluates whether the timing of daily G-CSF administration (morning vs evening) affects the level of circulating CD34+ cells prior to apheresis in healthy donors. Participants will be randomly assigned to receive subcutaneous G-CSF 10 μg/kg once daily for 5 consecutive days either at 08:00 (±15 minutes) or at 20:00 (±15 minutes). The primary endpoint is the peripheral blood CD34+ cell count measured approximately 12 hours after the last G-CSF dose and within 60 minutes before the start of the first apheresis session. Secondary endpoints include collection efficiency and CD34+ yield metrics, the proportion of donors achieving the target CD34+ dose on the first collection day, the need for a second collection day, and donor safety outcomes. The goal of the study is to identify a practical dosing schedule that may improve stem cell mobilization and streamline donor collection procedures.

This is a multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating the efficacy and safety of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for the early regression of albuminuria in adults with type 2 diabetes mellitus and chronic kidney disease (eGFR \>= 30 mL/min/1.73 m\^2 and UACR 30-2000 mg/g) who are already receiving a maximum tolerated dose of an ACE inhibitor or ARB. A total of 148 participants are randomized 1:1, stratified by baseline UACR (\<300 vs \>=300 mg/g), to oral finerenone (10 or 20 mg once daily, titrated by serum potassium and eGFR) or matching placebo, on top of standard background therapy, for 180 days, followed by a 30-day off-treatment follow-up. Albuminuria regression is defined as both an improvement in Kidney Disease: Improving Global Outcomes albuminuria category, from A3 to A2 or A1, or from A2 to A1, and a more than 30% reduction in urinary albumin-to-creatinine ratio from baseline. The outcome will be reported as the percentage of participants meeting this definition at Day 180.

This project is based on the biphasic instability model and social timing theory, utilizing IPSRT to help regulate social interactions and establish regular daily habits, alleviate emotional symptoms, and prevent. The included patients with bipolar II disorder who did not take medication for the first time or relapsed within the past month were randomly divided into a medication only group (Q group), a only IPSRT group (I group). Group Q received treatment with quetiapine alone (starting at 50mg/day, with an additional 50mg to 300mg/day per week, and the dosage can be flexibly adjusted); Group I received 12 weeks of interpersonal and social rhythm therapy (12 sessions, once a week, 40 minutes each time, with relatively fixed tasks and agendas for each meeting). Compare the changes in various clinical evaluation scales and skin potential before and after treatment, explore the safety and effectiveness of drug therapy and psychotherapy for patients with bipolar II disorder with rhythm disorders, and investigate the potential biological mechanism of IPSRT by collecting data on salivary cortisol and melatonin, peripheral circadian rhythm genes (PER1/PER2/PER3/BMAL1), and magnetic resonance.

The objective of this clinical trial is to evaluate the safety and tolerability of BY002 in healthy subjects. Investigators will compare BY002 to a placebo (a pharmacologically inactive substance) to assess the safety and tolerability of BY002 in healthy subjects. Participants will undergo: 1. Single/multiple subcutaneous (SC) administrations of BY002/placebo 2. A 7-day safety follow-up period following the last dose

HIV viral reservoirs represent the major barrier to curing AIDS, and effectively reducing viral reservoirs in people living with HIV through different strategies has become a research priority in the HIV field. Ipilimumab-tovorafenib monoclonal antibody injection (Aituo combination antibody, QL1706) contains two engineered monoclonal antibodies targeting PD-1 and CTLA-4. Chidamide is the first independently developed histone deacetylase inhibitor in China. This study aims to evaluate the safety and efficacy of Aituo combination antibody combined with chidamide in people living with HIV. This study adopts a modified "1+3+3" dose-escalation design. Initially, one participant will be enrolled at dose level 1 (DL1) for safety observation. If the treatment is well tolerated, the study will proceed to a standard 3+3 design, with sequential dose escalation to DL2 and DL3. Three dose levels are planned: DL1, the starting dose, consists of ipilimumab-tovorafenib monoclonal antibody injection at 0.3 mg/kg once every 4 weeks ± 1 day for a total of three doses, in combination with chidamide 10 mg orally twice weekly for 12 weeks. DL2 consists of ipilimumab-tovorafenib monoclonal antibody injection at 1 mg/kg once every 4 weeks ± 1 day for a total of three doses, in combination with chidamide 10 mg orally twice weekly for 12 weeks. DL3 consists of ipilimumab-tovorafenib monoclonal antibody injection at 2 mg/kg once every 4 weeks ± 1 day for a total of three doses, in combination with chidamide 10 mg orally twice weekly for 12 weeks. During dose escalation, progression to the next dose level or discontinuation of escalation will be determined according to the occurrence of dose-limiting toxicities (DLTs). The DLT observation window is 28 days after the first dose. Participants evaluable for DLT are those who complete the observation window or experience a DLT. After completion of dose escalation, the maximum tolerated dose (MTD) will be determined based on safety and tolerability. If the MTD is not reached, DL3 will be selected as the dose for subsequent study. After determination of the MTD or the subsequent study dose, an additional 11 participants will be enrolled at that dose level to further evaluate safety, tolerability, and preliminary efficacy. The maximum total sample size of the study will be 29 participants.

Background: Gastric cancer remains a significant health burden globally, particularly in China, where the majority of patients present with advanced disease at diagnosis. While immune checkpoint inhibitors (ICIs) targeting PD-1 have revolutionized treatment for various malignancies, their efficacy in proficient mismatch repair (pMMR) or microsatellite stable (MSS) gastric cancer-which constitutes over 85% of cases-remains limited. Recent Phase III trials (CheckMate 649, ATTRACTION-04, Orient-16) have demonstrated that combining PD-1 inhibitors with chemotherapy improves outcomes in advanced gastric cancer, leading to approved indications. However, the benefit in pMMR/MSS populations is modest, highlighting an urgent need for novel combination strategies to overcome immunotherapy resistance. Preclinical research published in Nature (Liu et al., 2020) revealed that inhibiting PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9)-a key regulator of cholesterol metabolism-can potentiate immune checkpoint therapy through a novel mechanism independent of its lipid-lowering function. PCSK9 inhibition was shown to increase tumor cell surface expression of MHC class I molecules by preventing their lysosomal degradation, thereby enhancing tumor antigen presentation and promoting cytotoxic T lymphocyte infiltration. This mechanistic insight suggests that combining a PCSK9 inhibitor with PD-1 blockade could synergistically improve antitumor immunity, particularly in immunologically "cold" tumors like pMMR/MSS gastric cancer. Tafolecimab is the first domestically developed fully humanized PCSK9 monoclonal antibody approved in China for hypercholesterolemia, with a favorable safety profile and extended half-life. Based on this strong preclinical rationale and the established efficacy of PD-1 plus chemotherapy in gastric cancer, this investigator-initiated trial aims to clinically translate the concept of PCSK9 inhibition as an immunomodulatory strategy. Study Population: This study will enroll 30 patients with the following key eligibility criteria: Inclusion: Adults aged 18-75 years with histologically confirmed pMMR/MSS gastric or gastroesophageal junction adenocarcinoma; initially unresectable or advanced disease (including metastatic); ECOG performance status 0-1; measurable disease per RECIST v1.1; adequate organ function. Exclusion: HER2-positive, EBER-positive, or CLDN18.2-positive tumors; prior systemic anticancer therapy for advanced disease; active autoimmune disease requiring immunosuppression; uncontrolled intercurrent illness; LDL-C \<30 mg/dL; history of PCSK9 inhibitor allergy; prior exposure to anti-PD-1/PD-L1 or PCSK9-targeted therapies. Study Objectives: This is a multicenter, prospective, single-arm exploratory trial with a safety run-in phase (first 6 patients monitored for dose-limiting toxicities). The treatment regimen consists of: Sintilimab (PD-1 inhibitor): 200 mg IV, day 1, every 3 weeks (Q3W) Tafolecimab (PCSK9 inhibitor): 300 mg subcutaneous injection, day 1, Q3W (dose reduction to 150 mg if DLTs occur) SOX chemotherapy: Oxaliplatin 130 mg/m² IV, day 1 + S-1 40 mg/m² orally twice daily, days 1-14, Q3W cycles Treatment continues until disease progression, unacceptable toxicity, or withdrawal of consent. Primary Endpoint: Objective Response Rate (ORR) assessed by RECIST v1.1 Secondary Endpoints: Progression-Free Survival (PFS) Disease Control Rate (DCR) Conversion surgery rate and R0 resection rate Pathological Complete Response (pCR) and Major Pathological Response (MPR) rates in resected patients Overall Survival (OS) Safety and tolerability (incidence of TRAEs, ≥Grade 3 AEs, irAEs per CTCAE v5.0) Exploratory Endpoints: Association between tumor biomarkers (including PD-L1 CPS, H. pylori infection status, and tumor PCSK9 expression) and treatment efficacy Multi-omics analyses using paired pre- and post-treatment tumor tissue, peripheral blood, and fecal samples Sample Size and Duration: A fixed sample size of 30 patients will be recruited over approximately 12 months, with survival follow-up extending to 36 months. This exploratory study is designed to generate preliminary efficacy and safety signals to inform future larger-scale investigations. The safety run-in design ensures close monitoring for potential additive toxicities, particularly given the novel combination of PCSK9 inhibition with immunotherapy and chemotherapy.

This study is a multicenter cross-sectional observational study, aiming to include approximately 200 patients aged 18-75 years who are using hydrocodone sustained-release tablets or oxycodone sustained-release tablets for pain management of moderate to severe cancer pain. Baseline information, tumor history, and comorbidities of the subjects will be collected through electronic patient-reported outcomes (ePRO), and the pain condition will be evaluated using BPI, acute pain assessment tools, etc. Sleep-related indicators will be collected using Huawei smart wearable devices and PSQI, ISI scales. Psychological emotional states will be assessed using NCCN psychological distress thermometer, HAMA, HAMD, etc. Blood samples will also be collected for relevant tests. The study sets up a screening baseline assessment period, a 1-week assessment period, and 1-month and 3-month follow-up periods after enrollment. The changes in relevant indicators will be tracked throughout the process, aiming to quantify the association between pain and insomnia, anxiety and depression, and to verify the potential mediating role of sleep disorders between pain and emotional disorders, providing a basis for optimizing the comprehensive symptom management of cancer pain patients.

The aim of this study was to explore the efficacy and safety of temporal interference stimulation to improve bipolar depression, as well as to explore the corresponding neuroimaging mechanisms using magnetic resonance and electroencephalogram to provide novel intervention protocols and objective indicators of efficacy prediction for depressive episodes in bipolar disorder.

This study intends to investigate the intervention efficacy of temporal interference stimulation (TI) on mood symptoms in depressed patients, as well as to explore the neuroimaging mechanisms of TI improvement in depressed patients using pre- and post-treatment magnetic resonance.

This study aims to stabilize the patients with bipolar disorder (BD) comorbid with obesity in the stable phase by using temporal interference stimulation (TIS ) intervention. It intends to investigate the changes in key metabolic molecules such as GLP-1 circadian rhythm, and further explore the molecular mechanism of their metabolic disorders.

The goal of this clinical trial is to learn if inulin and spirulina, used alone or in combination, can improve insomnia disorder in adults aged 18 to 60 years with chronic insomnia disorder. It will also learn about the safety of these interventions. The main questions it aims to answer are: Does inulin plus spirulina improve sleep quality, as measured by the reduction rate in Pittsburgh Sleep Quality Index (PSQI) score? Does the intervention improve sleep-related, mood, anxiety, and cognitive outcomes after 12 weeks? Researchers will compare an inulin group, a spirulina group, a combined inulin plus spirulina group, and a placebo group to see if the combined intervention provides greater benefit than either single intervention or placebo. Participants will: be randomly assigned to 1 of 4 groups: inulin, spirulina, inulin plus spirulina, or placebo; take the assigned study product once daily for 12 weeks; complete sleep, mood, anxiety, and cognitive assessments at baseline and week 12; undergo polysomnography and provide blood and stool samples at baseline and week 12; and be monitored for adverse events throughout the study.