Clinical trials

The goal of this clinical trial is to learn whether aerobic exercise can improve sleep and nervous system regulation in adults with mild to moderate obstructive sleep apnea (OSA). The study will also examine whether exercise changes blood markers related to inflammation and brain health. The main questions this study aims to answer are: 1. Does four weeks of aerobic exercise change blood levels of irisin, brain-derived neurotrophic factor (BDNF), and markers related to inflammation? 2. Does aerobic exercise improve sleep apnea, heart rate variability, cognitive function, daytime sleepiness, sleep quality, and daily functioning? Researchers will compare an aerobic exercise group with a sleep education group to determine whether adding regular aerobic exercise provides additional benefits for people with mild to moderate OSA. Participants will be randomly assigned to one of two groups. Participants in the aerobic exercise group will: 1. Receive sleep education. 2. Complete four weeks of supervised treadmill exercise, three to five times per week. Each session will last about 45 to 60 minutes. Exercise intensity will be adjusted to each participant's heart rate and physical condition. Participants in the comparison group will: 1. Receive sleep education about OSA, common symptoms, treatment options, and healthy sleep habits. 2. Practice the recommended healthy sleep habits at home during the four-week study period. Participants in both groups will complete assessments before and after the four-week study period. These assessments will include an overnight sleep study, blood tests, heart rate measurements, cognitive tests, and questionnaires about daytime sleepiness, sleep quality, and daily functioning.

Reducing balance problems and anxiety severity are the top two research uncertainties for people with Parkinson's disease (PD). Besides having a mutually aggravating relationship between postural impairment and anxiety severity, dual tasking is a critical condition that would increase postural instability and anxiety level concurrently. High-intensity aerobic exercise could improve balance and reduce anxiety. However, the training benefits from high-intensity aerobic exercise are limited in people with PD due to disease-related symptoms. Blood flow restriction (BFR) has been applied to low-intensity exercise. By creating localized hypoxia and increasing metabolic stress, BFR could facilitate aerobic system and neural adaptations. However, for the PD population, only one study applied BFR to aerobic exercise with the research design of a single-case report, let alone investigating the effects of BFR aerobic exercise on postural control and anxiety level under a dual-task condition. With the measurements of behavioral performance, subjective anxiety questionnaire, skin conductance response, and electroencephalogram (EEG), the purpose of the 3-year research project is to investigate the effects of BFR aerobic exercise on dual-task postural performance, anxiety, and related brain activities in people with PD. In the first year, the investigators will investigate the immediate effect of one bout of BFR aerobic exercise on dual-task postural control and anxiety level. In the second and third years, the investigators will investigate the long-term training effects of BFR aerobic exercise on dual-task postural control, anxiety modulation, brain plasticity, and patient satisfaction. The present project is expected to have significant contributions to gaining a better insight into the neural correlates of balance and anxiety with BFR aerobic exercise, particularly under dual-task conditions, and provide an optimized rehabilitation strategy for people with PD in clinical practice.

Atrial fibrillation (AF) is a common heart rhythm disorder associated with stroke, heart failure, and increased mortality. Catheter ablation with pulmonary vein isolation (PVI) is an effective rhythm-control strategy, but 20-30% of patients experience AF recurrence within one year. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist with anti-inflammatory, antifibrotic, and metabolic effects, was associated with a lower incidence of AF in prior large trials, and preclinical studies suggest it promotes "browning" of adipose tissue and improves epicardial adipose tissue (EAT) characteristics. This single-center, randomized, investigator-blinded pilot trial will enroll 40 patients undergoing first-time catheter ablation for AF. After successful PVI, participants will be randomized 1:1 to receive finerenone or usual care for 12 months. The primary endpoint is AF recurrence (any atrial arrhythmia episode lasting 30 seconds or longer) after a 90-day blanking period, within 12 months post-ablation. Mechanistic endpoints include EAT remodeling assessed by cardiac computed tomography and echocardiography, and circulating uncoupling protein-1 (UCP1) levels as a biomarker of adipose tissue browning. The investigators hypothesize that finerenone will lower AF recurrence after ablation, partly through modulation of EAT function.

This study aimed to develop and validate an innovative proprioceptive assessment instrument for the upper extremities, the PropArm-PosiMoF (PropArm). This observational study was conducted in three stages. The first stage focused on the development and validation of PropArm, including test-retest reliability, concurrent validity, and convergent validity. The second stage established age norms and cut-off points in healthy adults. In the final stage, PropArm was applied to patients with proprioceptive impairments (stroke, shoulder impingement syndrome, and diabetes mellitus patients) to examine its diagnostic accuracy and clinical applicability.

This randomized clinical trial will enroll patients at National Cheng Kung University Hospital who have upper gastrointestinal ulcer bleeding, have undergone endoscopic hemostasis, and have a Rockall score of 6 or higher. A total of 108 patients will be enrolled and randomly assigned to two groups: Standard-treatment group: 54 patients, Experimental group: 54 patients. Both groups will receive standard endoscopic hemostasis and 72 hours of intravenous PPI therapy. Thereafter, patients in the standard-treatment group will receive double-dose PPI therapy, whereas patients in the experimental group will receive a P-CAB per day. All patients will be followed for 28 days to assess the occurrence of rebleeding.

Subjects are divided into two groups, (1) Control (Ctrl) and (2) Smart Exercise (SE) group. Participants in the Ctrl group are instructed to perform combined muscle strength and coordination exercises twice weekly, with each session lasting 30 minutes, following an exercise guide recommended by a physical therapist. Participants in the SE group perform combined muscle strength and coordination training using the Smart Exercise System twice weekly, with each session lasting 30 minutes, for 12 weeks. Physical fitness tests, coordination tests, and questionnaires are administered to participants in both groups before and after the 12-week exercise program.

Subjects are divided into two groups, (1) Control (Ctrl) and (2) Smart Exercise (SE) group. Participants in the Ctrl group are instructed to perform resistance band training twice weekly according to a paper-based exercise guide, whereas participants in the SE group are instructed to perform resistance band training twice weekly for 12 weeks using the Resistance Band Training System. The physical fitness tests and questionnaire of both groups are performed before and after the 12-week exercise program.

Subjects are divided into two groups, (1) Control (Ctrl) and (2) Smart Exercise (SE) group. Ctrl group are instructed to maintain their daily life. SE participants are instructed to do exercise with smart exercise system twice per week for 12 weeks. The physical fitness tests and questionnaire of both group are performed before and after the 12-week exercise program.

Patients with EV bleeding often suffered from hematemesis, Tarry stool, and blood loss. Standard treatment for bleeding esophageal varices includes hemodynamic stabilization, pharmacological control, and endoscopic intervention. For endoscopic intervention, endoscopic variceal ligation (EVL) is the first-line therapy with 95% initial hemostasis success rate. However, after variceal ligation, esophageal ulcers form 3 days later. These ulcers expose underlying vessels in friable esophageal mucosa, exacerbated by portal hypertension and coagulopathy in cirrhosis patients. Bleeding peaks around day 5-10 when bands detach. Among these patients, 7-9% of patients experience recurrent bleeding as a result. Recurrent bleeding from esophageal ulcers carries an extremely high mortality rate, particularly in patients with advanced stage cirrhosis. Therefore, how to promote esophageal ulcer healing and prevent ulcer rebleeding is an important clinical issue. Proton pump inhibitors (PPIs) are the primary drugs for preventing and treating gastric ulcers, but clinical evidence for their role in preventing post-ligation esophageal ulcers is insufficient. Sucralfate, a complex of aluminum hydroxide and sucrose octa sulfate, can bind to the wound base. This protective barrier can prevent the wound from further environmental injury. Sucralfate has been widely used for wounds and ulcer treatment, e.g., skin wounds, oral ulcers, and peptic ulcers. Our recent clinical trial also proved topical sucralfate can prevent postpolypectomy bleeding. Therefore, this study aimed to investigate whether the topical administration of sucralfate after standard endoscopic hemostasis can promote the esophageal ulcer healing and reduce the rebleeding event.

This clinical trial will enroll patients at National Cheng Kung University Hospital. All patients who are hospitalized for lower gastrointestinal bleeding and undergo colonoscopy will be invited to participate. This study uses random allocation, with one Intervention group and one Standard group. Both groups will receive standard endoscopic hemostasis. Afterward, patients in the Intervention group will receive local administration of 1.5 g of tranexamic acid and 3 g of sucralfate. Following the endoscopic procedure, patients will be directly observed for 5 minutes to confirm successful hemostasis. All patients will be followed for 28 days to assess the occurrence of post-procedural rebleeding.

Driving ability in older adults is essential for independent mobility and social participation, yet declines under high cognitive load or distraction often lead to visual attention failures such as "look-but-fail-to-see," increasing crash risk. Older adults and individuals with mild cognitive impairment (MCI) show impairments in visual attention, executive control, and visuomotor integration, which are not adequately captured by conventional assessments. Virtual reality (VR) integrated with eye-tracking and upper-limb motion analysis enables ecologically valid simulation of driving scenarios and precise quantification of visuomotor behavior. However, current studies are limited by single-scenario designs, unimodal AI models, and insufficient integration of action-related data. This study proposes a multi-phase framework: Year 1 develops an eye-movement-based AI model for MCI identification; Year 2 integrates multimodal data in VR driving tasks; and Year 3 establishes an explainable AI system with longitudinal validation. The study aims to advance cognitive assessment and develop a digital tool for early MCI detection and driving risk prediction.

In this study, the investigators hypothesized that Virtual Reality Mirror Therapy with Focused Object-Directed Attention (VRMTFOA) would yield superior therapeutic effects compared to conventional Virtual Reality Mirror Therapy (VRMT) in individuals with unilateral stroke. The aim of this study is to compare the immediate effects of a single session of VRMT, VRMTFOA, and VRMTFOA with auditory feedback on upper extremity function and brain activity in stroke patients.

Although antipsychotic is effective for schizophrenia, however, still certain proportion of patients were not responsive to treatment. Treatment resistant schizophrenia (TRS) is accompanied by function decline and heavy burden. In recent decades, the biological mechanism of schizophrenia extended from dopamine theory to the role of glutamate system. This shift could be an alternative pathway to developing the treatment of TRS. Sodium benzoate (SB) could be an option as a glutamatergic agent for the patients with TRS. However, most evidence of SB is for treating patients with schizophrenia and other mental disorders but the evidence for treating patients with TRS is scarce. To predict the treatment response of SB will be an urgent topic in the future. Little is known about the precise medicine for treating patients with TRS. The present project will extend our pilot randomized clinical trial on SB for TRS. A total of 90 patients with TRS will be enrolled from three centers and will be assigned to 8 weeks of treatment with SB or placebo (2:1). A comprehensive battery of potential markers will be employed, including 1H- magnetic resonance spectroscopy (MRS), brain functional connectivity, genotyping, immune biomarkers, cognitive function, and clinical characteristics. The efficacy of SB on TRS will be confirmed in this project. Predictors for treatment response will be identified. Artificial intelligence algorithms will be used for probing the feasibility of precision medicine.

Background Gastrointestinal bleeding is a common disease among the population in Taiwan, with gastrointestinal tumor bleeding accounting for 3-5% of cases. The pathophysiology of gastrointestinal tumor bleeding is unique, involving fragile surface mucosa, abnormal vascular proliferation, and malformation, making endoscopic hemostasis challenging. Conventional endoscopic hemostasis methods such as hemostatic injections, clips, or thermal coagulation have suboptimal success rates below 80%, with recurrence rates exceeding 50%. Recent clinical trials have demonstrated that hemostatic powder spraying effectively enhances hemostasis for gastrointestinal ulcers and reduces recurrence rates. Our previous research repurposed tranexamic acid in a powder form to enhance hemostasis for peptic ulcer and applied sucralfate powder to prevent postpolypectomy wound bleeding. Study aim Our research team combines previous experience by using tranexamic acid and sucralfate drug powders to spray onto bleeding gastrointestinal tumors to achieve hemostatic effects. Additionally, tumor-derived exosomes are associated with tumor angiogenesis and growth, so we hypothesize that gastrointestinal tumor bleeding may be linked to VEGF and miR-21 expression within gastrointestinal tumor exosomes. Study method This study is a clinical randomized controlled trial conducted at National Cheng Kung University Hospital. We will recruit 60 patients with gastrointestinal tumor bleeding undergoing endoscopic hemostasis. Patients in the experimental treatment group will receive additional topical administration of 1.5 g of tranexamic acid and 3 g of sucralfate drug powder. Immediate hemostasis and 30-day bleeding recurrence will be observed. Enrolled patients will also provide blood and tumor specimens for exosome analysis, evaluating the predictive effect of extracted tumor exosomes' VEGF and miR-21 on bleeding risk. This study will explore the association between specific tumor exosome expression levels and bleeding, serving as a basis for bleeding risk assessment and innovative therapies.

In the proposed study, the investigators assumed that Virtual Reality-Based Generative Bimanual Cooperative Task-Oriented Therapy (VRMCTOMT) will provide a better treatment effects than traditional virtual reality mirror therapy (VRMT) for the patients with unilateral stroke. The aim of the study is to examine the difference in the treatment effects among the combination of task-oriented training with either VRMCTOMT, or VRMT on the upper extremity function and brain activity of the stroke patients.

In this phase 2 study, the efficacy of total neoadjuvant therapy in Taiwanese patients with rectal cancer will be investigated. Patients with stage II or III middle/low rectal cancer will be prospective enrolled. The total neoadjuvant therapy with the short-course radiotherapy (5×5 Gy over a maximum of 8 days) followed by chemotherapy with mFOLFOX6 for 9 cycles will be administered. The primary endpoint is the complete response (CR) rate which will take into account the patients with clinical and pathological complete response.

Shoulder arthroscopic surgery is associated with moderate to severe postoperative pain, which may hinder early mobilization and functional recovery. Interscalene block (ISB) is commonly used to provide effective analgesia but is frequently associated with hemidiaphragmatic paralysis due to phrenic nerve involvement. Cervical erector spinae plane block (ESPB) has been proposed as an alternative regional technique that may provide analgesia while reducing respiratory-related adverse effects. This randomized controlled trial aims to compare the analgesic efficacy and safety of cervical ESPB versus continuous ISB in patients undergoing shoulder arthroscopic surgery.

The goal of this randomized controlled trial is to evaluate the effectiveness of the Safe Haven app in reducing mental health symptoms and enhancing mental health literacy in undergraduates at a national university in southern Taiwan. The main questions it aims to answer are: Does the Safe Haven app lead to significantly greater reductions in general psychological distress, depression, anxiety, and stress compared to standard campus care? Does the app result in greater improvements in mental health literacy among participants? Researchers will compare an experimental group (receiving the Safe Haven app in addition to standard campus care) to a waitlist control group (receiving standard campus care only) to see if the intervention provides superior improvements in mental health outcomes over time. Participants will: Complete online assessments at three time points: baseline (T0), post-intervention (3 months, T1), and follow-up (3 months post-intervention, T2). Experimental Group: Download the Safe Haven app to complete daily mood self-monitoring and weekly assessments, and receive psychoeducational content, personalized suggestions for 3 months. Control Group: Maintain access to standard campus care and receive access to the app after the final follow-up assessment.

Background： Colonoscopy can detect colon polyps and perform excision to the polyps to prevent colon cancer. However, delayed polypectomy bleeding is one of the complications to be noticed, which has an occurrence rate of about 1-2%, especially large polyps over 1cm with hot snare polypectomy. Colonoscopic clipping was applied for the treatment of bleeding. However, prophylactic clipping after polypectomy was not proved to reduce the rate of delayed polypectomy bleeding. Sucralfate is used for peptic ulcer treatment, which can become a protective layer on the wound to prevent environmental injury. Our preliminary data revealed the endoscopic sucralfate spray could reduce the delayed bleeding rate among general populations. Whether sucralfate can prevent polypectomy wounds from delayed bleeding in high-risk polyps is unknown. Aim： This study aimed to compare the efficacy in reducing delayed bleeding rate between sucralfate administration and prophylactic clipping on high-risk polypectomy wounds. Method： This is a randomized clinical trial. The study will recruit 160 patients. After randomization, 80 patients will be classified into the Sucralfate group and 80 into the Clipping group. The participants will receive an endoscopic survey as routine, and we will enroll all patients who take antiplatelets or anticoagulants with polyp size ≥ 1 cm after hot snare polyp excision. Exclusion criteria include patients with an allergy to sucralfate. If immediate polypectomy bleeding occurs, we will apply standard endoscopic therapy by either local injection of diluted epinephrine, heater probe coagulation, and/or hemoclipping. After then, we will spray 3g of sucralfate powder through colonoscopy precisely on the polypectomy wound in the Sucralfate group, and prophylactic clipping will be placed on the polypectomy wound in the Clipping group. All enrolled patients will be monitored for delayed bleeding for 28 days after the colonoscopy. Expected results and clinical importance: This study is expected to find that the use of sucralfate powder can more effectively reduce the bleeding risk in high-risk wounds compared to prophylactic clips. In addition to promoting the implementation of national health policies and reducing public exposure to the risk of complications, it can also help avoid medical expenses resulting from complications.

Endoscopic retrograde cholangiopancreatography (ERCP) is a technically demanding procedure combining endoscopy and fluoroscopy to diagnose and treat pancreaticobiliary disorders such as bile duct stones, strictures, and cholangitis. Despite its therapeutic value, ERCP carries a relatively high complication risk of about 10%, with severe complications occurring in roughly 24% of those affected and mortality rates between 0.2% and 0.7%. The most common and significant complication is post-ERCP pancreatitis (PEP), occurring in 2% to 10% of average patients and up to 40% or higher in high-risk groups. PEP ranges from mild, self-limiting inflammation to severe, life-threatening conditions including pancreatic necrosis and multi-organ failure. PEP arises from mechanical trauma, hydrostatic injury, chemical irritation, or infection during ERCP that activates inflammatory pathways within the pancreas. Key patient-related risk factors include young age, female sex, prior pancreatitis, and sphincter of Oddi dysfunction; procedural factors include difficult biliary cannulation, pancreatic duct manipulation, and precut sphincterotomy. Preventive strategies focus on minimizing mechanical injury and pharmacologic prophylaxis. Rectal NSAIDs (indomethacin, diclofenac) administered immediately before ERCP are well-supported for reducing PEP risk. Periprocedural aggressive intravenous hydration and prophylactic pancreatic duct stenting in high-risk cases also lower PEP incidence. Nitroglycerin, a smooth muscle relaxant acting via nitric oxide-mediated sphincter relaxation, has shown promise in PEP prevention, especially in patients contraindicated for NSAIDs. Clinical trials indicate that transdermal or sublingual nitroglycerin reduces PEP rates, and combined use with NSAIDs may enhance protection. However, current guidelines do not routinely recommend nitroglycerin due to limited consensus on its efficacy. Topical nitroglycerin, known to relax smooth muscles locally and used in anorectal conditions, might reduce sphincter of Oddi pressure without systemic side effects. This suggests potential benefit in lowering PEP incidence or severity when applied topically during ERCP, pending further investigation. This study aimed to investigate whether topical delivery of nitroglycerin can reduce the incidence rate of PEP or the severity of pancreatitis.

This study aims to improve treatment strategies for Obstructive Sleep Apnea (OSA), a disorder characterized by recurrent upper airway collapse during sleep, resulting in reduced oxygenation, sleep fragmentation, and excessive daytime sleepiness. The objectives are twofold: to evaluate whether an artificial intelligence (AI)-based model can accurately predict the most effective treatment for individual patients, and to assess whether a mobile health application can enhance adherence to oropharyngeal rehabilitation (OPR) and improve therapeutic outcomes. The study will be conducted in two phases. In Phase I, a retrospective analysis will be performed using a large dataset of polysomnography (PSG) records obtained from the Sleep Center at National Cheng Kung University Hospital. Machine learning algorithms will be applied to identify predictive features that differentiate responders from non-responders across Continuous Positive Airway Pressure (CPAP), surgical, and OPR interventions. These findings will inform the development of a predictive treatment recommendation model. In Phase II, a prospective clinical trial will validate the predictive accuracy and clinical utility of the model. Patients newly diagnosed with OSA will be assigned to CPAP, surgery, or OPR interventions according to the model's recommendations, in combination with physician judgment and patient preference. Each intervention will last 12 weeks, followed by repeat PSG and clinical assessments. Within the OPR arm, participants will be further randomized to monitor adherence via an exercise diary or a smartphone application equipped with a pressure sensor and facial motion recognition technology, enabling real-time feedback and remote monitoring. This trial is expected to determine whether AI can provide clinically reliable treatment recommendations and whether digital telerehabilitation can improve adherence and outcomes, thereby advancing precision medicine in OSA management.

This study aims to investigate the factors influencing adherence to pelvic floor muscle training (PFMT) devices among patients with pelvic floor dysfunction (PFD) through structured questionnaires, while simultaneously comparing the effectiveness of different feedback modalities, including non-invasive ultrasound imaging and invasive manometry with electromyography (EMG). By integrating subjective adherence data with objective performance outcomes, the project seeks to evaluate the potential of system-level integration for personalized therapeutic strategies, ultimately enhancing treatment efficacy, improving patient satisfaction, and promoting sustained engagement in PFMT.

The dosage of paclitaxel, an adjuvant chemotherapy agent for endometrial and ovarian cancer, is typically calculated based on the patient's body surface area (BSA). However, cancer patients with the same BSA may exhibit significant differences in body composition, which could influence the distribution pattern of paclitaxel in the body. These variations may lead to individual differences in drug tolerance and adverse effects. Such variability not only impacts the patient's treatment experience and quality of life but may also increase medical costs, including hospitalization, emergency department visits, and additional treatments required to manage chemotherapy-induced toxicities. Our preliminary study results indicate that skeletal muscle area (SMA) and skeletal muscle index (SMI), as assessed through computed tomography (CT) imaging, are significantly associated with the incidence of Grade 3 or higher leukopenia or neutropenia following the first two cycles of chemotherapy in patients with endometrial cancer. Furthermore, the predictive accuracy of these CT-derived muscle measurements surpasses the clinical judgment made by physicians based on conventional treatment guidelines. Patients who develop Grade 3 or higher leukopenia or neutropenia during the first two cycles are more likely to experience more frequent occurrences of Grade 3 or higher chemotherapy-related adverse effects in subsequent treatment cycles. However, no study has comprehensively investigated the relationship between body composition, chemotherapy dosing, and adverse effects. Therefore, this trial aims to examine the impact of body composition on chemotherapy dose adjustments and adverse effects. By utilizing body composition data extracted from abdominal CT imaging through this product, this study seeks to establish a risk stratification tool to assist physicians in treating patients with endometrial and ovarian cancer by providing a reference for chemotherapy dose reduction. It is expected that through a precision chemotherapy strategy, the incidence of chemotherapy-related adverse effects can be reduced, thereby lowering medical resource expenditures incurred from managing these adverse effects, such as emergency department visits, hospitalizations, additional diagnostic tests, and supportive medication costs. Furthermore, this approach aims to improve patients' health-related quality of life and achieve a dual benefit of medical economic efficiency and clinical effectiveness.

The goal of this clinical trial is to investigate the safety and efficacy of a new treatment approach for T4-stage esophageal cancer, which involves chemoradiotherapy after induction chemotherapy. The main questions it aims to answer are: * Does the new induction chemotherapy followed by chemoradiation reduce esophageal perforation rate? * Does the new induction chemotherapy followed by chemoradiation increase treatment response rate and patient survival? Researchers will analyze the above data to see if the new treatment approach works to treat T4 esophageal cancer. Participants will: * Receive induction chemotherapy for 4 to 8 cycles, followed by chemoradiation therapy if downstage to T3 * Visit the clinic once every week for checkups and tests * Keep a diary of their symptoms

Previous studies have found that graded motor imagery (GMI) training can provide continuous activation of the cerebral cortex compared to traditional rehabilitation therapy. One of the steps in this strategy, mirror therapy, has also been widely used in the clinical treatment of hemiplegic patients. Also, comparing with traditional rehabilitation treatments, mirror therapy can continuously provide cortical activation. Besides, several studies indicated that game-based interventions contribute to brain activation in the elderly due to their interest can improve users' motivation in the training program execution. In addition, force control training has positive effects on hand dexterity, and specific doses of motor control training not only improve motor function but also have positive effects on brain function. Currently, hand function training primarily focuses on range of motion, strength, and hand function, although there is comparatively less emphasis on enhancing both force control and brain function. Moreover, studies related to mirror therapy has primarily focused on the execution of functional movements, but has not explored whether hand strength control training can achieve the same training effects on the affected or non-dominant side through the concept of mirror therapy. Furthermore, the effects of combining a hand strength control system with a synchronous contralateral clip-on force feedback device on brain activation and hand function have not yet been studied. Therefore, this study aimed to investigate the effects of integration a finger force control training system with synchronous contralateral force feedback and mirror visual feedback device on brain activation and hand function, aiming to develop a clinically applicable hand rehabilitation system. Additionally, visual feedback from force control training in our study is through the hints displayed virtually on the game interface of the tablet, which were represented as the height of the targets, not as typical as actual movement-based mirror therapy or task-based mirror therapy. Therefore, the purpose of the study is to understand the differences among training effects of integrating Graded-Pressure Haptic Device-TiPR closed-loop system and MVF; MVF and force control training, as well as isolated force control training, and to explore the training effects on hand strength, hand function and brain activation.