Find Clinical Trials

Inclusion Criteria： 1. Histologically or cytologically confirmed her-2 negative, HR-positive progressive breast cancer (prior chemotherapy (including adjuvant or neoadjuvant) with anthracycline and/or paclitaxel required); 2. No more than 3 lines of chemotherapy for recurrent or metastatic breast cancer; 3. Must have progression previously used endocrine therapy and CDK4/6 inhibitors for recurrent or metastatic disease ; 4. PET-CT（SUV）\>5; 5. Age ≥18 years; 6. ECOG PS 0-1; 7. life expectancy ≥ 3 months 8. Have at least one measurable lesion as a target lesion confirmed by CT or MRI according to RECIST version 1.1 criteria. If the target lesion is a lymph node require a short diameter greater than 1.5 ，and the target lesion is not amenable to surgical treatment; the target lesion has not received radiotherapy or has recurred in the radiotherapy field; 9. Appropriate hematopoiesis； 10. Appropriate liver function； 11. Appropriate renal function； 12. Normal coagulation; 13. Females of childbearing potential willing to use contraception during the trial: negative serum or urine pregnancy test within 7 days prior to dosing. Exclusion Criteria: 1. Received radiation therapy within 28 days prior to enrollment. Radiotherapy for the relief of metastatic bone pain prior to enrollment is permitted, provided that no more than 30% of the total marrow-containing bone is irradiated, with the exception of patients with good bone feel prior to treatment; 2. The presence of evidence of central nervous system metastases; 3. Current or recent (within 30 days prior to enrollment) use of another investigational drug or participation in another clinical study 4. Other malignancy within 5 years (except adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or controlled basal cell carcinoma of the skin) 5. Uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg despite optimal pharmacologic therapy) 6. Myocardial ischemia or myocardial infarction of class II or greater, poorly controlled arrhythmias (including qtc intervals ≥450 ms in men and ≥470 ms in women); 7. Grade III-IV cardiac insufficiency according to NYHA criteria, or cardiac ultrasound suggesting left ventricular ejection fraction (LVEF) \<50%; 8. Abnormal coagulation function (INR \> 1.5 or prothrombin time (PT) \> ULN + 4 seconds or APTT \> 1.5 ULN), with bleeding tendency or under thrombolytic or anticoagulant therapy; 9. Have had clinically significant bleeding symptoms or a definite bleeding tendency within the previous 3 months, such as gastrointestinal bleeding, bleeding gastric ulcer, fecal occult blood +++ or more at baseline, or have vasculitis 10. Have undergone major surgical procedures or have sustained a severe traumatic injury, fracture, or ulcer within the previous 4 weeks 11. Having factors that significantly affect the absorption of oral medication, such as inability to swallow, chronic diarrhea and intestinal obstruction, etc; 12. Urine routine suggestive of urinary protein ≥ ++, or confirmed 24-hour urine protein volume ≥ 1.0 g; 13. Plasmapheresis (including pleural fluid, ascites, and pericardial effusion) that is clinically symptomatic and requires surgical management; 14. Other conditions that, in the judgment of the investigator, may affect the conduct of the clinical study and the determination of the study results.

Inclusion Criteria: 1. Age ≥18 years; 2. Use of endovascular therapy (EVT) within 24 hours of symptom onset or last known well according to local guidelines; 3. Sustained high systolic blood pressure ≥150 mmHg (2 readings \<10 mins apart) within 3 hours after completion of EVT. Exclusion Criteria: 1.Any definite contraindications to BP lowering treatment.

Inclusion Criteria: * histopathological diagnosis of breast cancer * age 18 years or older * male or female * treated with breast conserving surgery or mastectomy with curative intent * multidisciplinary decision of adjuvant radiotherapy after surgery Exclusion Criteria: * distant metastases * decision of preoperative radiotherapy * decision of partial breast irradiation * positive resection margins ('ink on tumour') * indication for boost on lymph node(s) * history of thoracic or ipsilateral axillary radiotherapy (including radiotherapy of the contralateral breast or chest wall) * need for bilateral irradiation * breast reconstruction or expander * patients unlikely to comply with the protocol (e.g. inability or unwillingness to complete the questionnaires at different time points).

Aims 1-3: Stage 2 T1DM with TZIELD® and GLP-1Ra Inclusion Criteria: * Age: 12-50 years * BMI: 18-31 kg/m2 (adults) or 5-95th %ile (pediatric) * Stage 2 T1DM (i.e., ≥ 2 islet auto-antibodies and: * fasting glucose ≥ 100 mg/dL and \< 126 mg/dL OR * 2-hr OGTT /MMTT ≥ 140 mg/dL and \< 200 mg/dL OR * During an OGTT having a glucose of \> 199 mg/dL at 30, 60, or 90 minutes) Exclusion Criteria: * Comorbidities: * SBP \> 140 mmHg and DBP \> 100 mmHg * eGFR by MDRD equation of \< 60 mL/min/1.73m2 * AST or ALT \> 2.5 times ULN * Family history of medullary thyroid carcinoma * Diagnosis of pancreatitis or gastroparesis within the past 3 years * Medications: Any diabetes medication, any antioxidant vitamin supplement (\<2 weeks before a study), any systemic glucocorticoid, antipsychotic, atenolol, metoprolol, propranolol, niacin, any thiazide diuretic, any OCP with \> 35 mcg ethinyl estradiol, growth hormone, any immunosuppressant, antihypertensive, any antihyperlipidemic * Other: pregnancy, peri- or post-menopausal women, active smoker Aim 4: Early Stage 3 T1DM with GLP-1Ra Monotherapy Inclusion Criteria * Age: 12-50 years * BMI: 18-31 kg/m2 (adults) or 5-95th %ile (pediatric) * Early stage 3 T1DM with either * HbA1c 6.5% to 8.0% at diagnosis OR * HbA1c 5.7% to 6.4% with oral glucose test meeting ADA criteria for stage 3 T1DM within the past three months prior to or during screening visit * Time of stage 3 diagnosis: within eight weeks of first study visit Exclusion Criteria * DKA history: history of diabetic ketoacidosis requiring hospital admission * Comorbidities: * Family history of medullary thyroid carcinoma * Diagnosis of pancreatitis or gastroparesis within the past 3 years * Medications: Any diabetes medication, any antioxidant vitamin supplement (\<2 weeks before a study), any systemic glucocorticoid, antipsychotic, atenolol, metoprolol, propranolol, niacin, any thiazide diuretic, any OCP with \> 35 mcg ethinyl estradiol, growth hormone, any immunosuppressant, antihypertensive, any antihyperlipidemic * Other: pregnancy, peri- or post-menopausal women, active smoker

Inclusion Criteria: * survivor was diagnosed as colon, rectal, colorectal, or/and anal cancer * aged at least 20 years * have had completed cancer treatments within the five years prior to enrolling in the study. * agree and obtain written consent * could using the online media(ex: Zoom or Google meet..) to attend intervention course Exclusion Criteria: * diagnosed with stage IV cancer * had a recurrence of CRC cancer * had the other type cancer diagnosis * now are undering cancer treatment

Inclusion Criteria: 1. must respond yes to three questions related to their history with serious mental illness (see below); 2. a score of 8 or higher on the Center for Epidemiologic Studies Depression Scale - Revised -10 (CES-D-R-10) 3. have Internet access; 4. be willing to carry a cell phone with a GPS tracking application; 5. indicate that they would like to participate more in the community; 6. be able to communicate in English; 7. be over the age of 18; and 8. and be available on for the day and time (i.e., Monday, Tuesday, Wednesday, Thursday, or Friday) the intervention is scheduled for each cohort. Questions related to history with serious mental illness: 1. "Have you ever been told by a psychiatrist or other mental health professional that you have major depression, bipolar disorder, manic depression, schizophrenia or schizoaffective disorder?", 2. "Have you ever been hospitalized for this mental health or emotional problem?", and 3. "Has this mental health or emotional problem substantially interfered with or limited your ability to participate in any major life activities such as work, school, recreation, social activities, religious activities, family relationships, or caring for yourself?" Answering yes to these 3 questions would be indicative of a lifetime serious mental illness. Exclusion Criteria: 1. those who are unable to give informed consent 2. those who report having a legal guardian -

Inclusion Criteria: * group 2 pulmonary hypertension with precapillary component with PVR more than 4 by RHC * Patients should be on HF medical therapy 90 days before enrollment in the study. Exclusion Criteria: * Anticipated cardiac resynchronization therapy within 3 months of enrollment. * Hypersensitivity, allergy, or intolerable side effects of PDE-5 inhibitors. * Contraindication to PDE-5 inhibitors, including current nitrate therapy. * All groups of PH, other than group 2 PH (isolated post capillary pulmonary hypertension). * History of heart transplant, ventricular-assist device, or any other solid-organ transplant * Likely to have solid-organ transplant or any other major surgery during study enrollment/treatment period. * Female subject who is pregnant, breast-feeding, or unwilling to practice an acceptable method of birth control unless postmenopausal or sterile. * Unreliability as a study participant, based on the investigator's (or designee's) knowledge of the subject (e.g., alcohol or other substance abuse, inability or unwillingness to adhere to the protocol, documented noncompliance, or vulnerable population) * Current enrollment, or enrollment completed \<30 days previously, in another investigational drug or device clinical study. * Undergoing dialysis for end-stage renal disease. * End-stage liver disease comorbidities, limiting exercise tolerance. * Morbid obesity (body mass index \> 40). * Severe peripheral vascular disease with intermittent claudication. * Status after amputation of lower extremity(s) at any level. * Severe degenerative joint disease preventing normal walking. * Cerebrovascular accident with long-term sequelae affecting ability to walk.

Inclusion Criteria: * Written informed consent according to country specific law and ICH GCP E6(R2) regulations before registration and prior to any trial specific procedures. * Newly histologically diagnosed, previously untreated locally advanced non-metastatic TNBC as defined by the most recent American Society of Clinical Oncology (ASCO) / College of American Pathologist (CAP) guidelines . * The following stages according to staging per American Joint Committee on Cancer (AJCC) for breast cancer staging criteria version 8 are included: cT1c (1.5-2cm) N1-3 M0 or cT2-4c N0-3 M0. * Multifocal and multicentric primary tumors are allowed and the tumor with the most advanced T stage should be used to assess eligibility. If multifocal or multicentric disease TNBC needs to be confirmed for each focus. * Measurable disease in the breast with at least one lesion with a diameter ≥ 1.5cm that is evaluable per RECIST v1.1, visible in ultrasound and injectable. * Male or female subject Age ≥ 18 years. * ECOG performance status 0-1 * Adequate bone marrow function (administration of G-CSF, EPO and/or blood transfusion within 14 days before registration is not allowed): * neutrophil count ≥ 1.5 x 109/L * platelet count ≥ 100 x 109/L * hemoglobin ≥ 90 g/L * Adequate hepatic function: * total bilirubin ≤ 1.5 x ULN, or direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 x ULN * AST and ALT ≤ 2.5 x ULN, * Albumin 30 ≥ g/L * Lactate Dehydrogenase (LDH) \<2.5 ULN * Adequate renal function: estimated glomerular filtration rate (eGFR) ≥ 50 ml/min/1.73 m2 (according to CKD-EPI formula) * Adequate cardiac function: Left ventricular Ejection Fraction (LVEF) ≥ 50% as determined by echocardiography (ECHO) * Adequate coagulation function: * INR ≤ 1.5 x ULN unless the patient is receiving anticoagulant therapy * aPTT ≤ 1.5 x ULN unless the patient is receiving anticoagulant therapy * If the patient is receiving anticoagulant therapy, the treating physician must determine that the anticoagulation can be stopped at least 24 hours prior to injection. * Women of childbearing potential must use highly effective contraception, are not pregnant or lactating and agree not to become pregnant during trial treatment and until 7 months after the last dose of INT230-6 or 6 months after standard of care treatment. A negative pregnancy test before inclusion into the trial is required for all women of childbearing potential. (www.swissmedicinfo.ch). * Men agree not to donate sperm or to father a child by using effective contraception during trial treatment and until 6 months after the last dose of INT230-6 or standard of care treatment (www.swissmedicinfo.ch). Exclusion Criteria: * Inflammatory Breast Cancer cT4d * Unfavorable relation between tumor size and breast size as determined by judgement of the treating physician, surgeon and/or investigator, where tumor shrinkage during neoadjuvant immunochemotherapy is required for breast conserving surgery to be considered. * Unfavorable tumor location that can potentially result in an unfavorable cosmetic outcome (e.g. high upper inner quadrant) and/or close skin contact by judgment of the treating physician, surgeon and/or investigator. * The following histological subtypes of TNBC are excluded: Classic adenoid cystic carcinoma, secretory carcinoma, low-grade adenosquamous carcinoma, tall cell carcinoma with reversed polarity, high-grade metaplastic * History of invasive malignancy ≤3 years prior to signing informed consent (except treated basal cell or squamous cell skin cancer or in situ cervical cancer) * Prior chemotherapy, targeted therapy, radiation therapy or anti-PD-L1 agent for previous breast cancer or Ductal Carcinoma in Situ (DCIS) on the same side. * Concurrent bilateral breast cancer * Concomitant treatment with any other experimental drug for recent breast cancer diagnosis in another clinical trial. * Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA II or IV; unstable angina pectoris, history of myocardial infarction and acute coronary syndrome requiring stenting/bypass surgery within the last six months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia), significant QT-prolongation, uncontrolled hypertension. * Known history of human immunodeficiency virus (HIV) or active chronic hepatitis C or hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment. * Active autoimmune disease that required systemic treatment in past 2 years (e.g., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroid hormone replacement, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. * History of (non-infectious) pneumonitis that required steroids or current pneumonitis. * Known history of tuberculosis. * Known history of allogeneic organ or stem cell transplant. * Receipt of live attenuated vaccine (including yellow fever vaccine) within 30 days prior to registration. * Diagnosis of immunodeficiency, concomitant or prior use of immunosuppressive medication within 7 days before registration, with the exceptions of local (intranasal, topical and inhaled) corticosteroids, or systemic corticosteroids which must not exceed 10 mg/day of prednisone or a dose equivalent corticosteroid, and the premedication for chemotherapy. * Concomitant anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon), factor Xa inhibitors (e.g. rivaroxaban, apixaban), direct thrombin inhibitors (e.g. dabigatran) or platelet inhibitors/antiplatelet agents that cannot be stopped 24 hours before the administration of INT230-6. Aspirin (up to 300 mg/day) is allowed. * Any concomitant drugs contraindicated for use with the trial drug according to the Investigator Brochure (IB) and the immuno-chemotherapy treatment according to the approved product information. * Known hypersensitivity to trial drug or to any component of the trial drug or immuno-chemotherapy treatment. * Incapacitated adults and any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

Inclusion Criteria: 1. adults 18 to 65 years old; 2. fluent in Swedish; 3. corrected to normal vision and hearing; 4. (for cases), newly diagnosed with MDD or SED (i.e., received as new diagnosis at the visit to the physician) according to the diagnostic criteria from DSM-V (MDD) and the Swedish Board of Health and Welfare (SED) Exclusion Criteria: 1. already ongoing treatment for MDD/SED or previous diagnosis of MDD/SED within the last year; 2. history of serious mental illness (defined as mental illness that has required psychiatric in-patient care); 3. acute cerebrovascular event or severe head trauma in the last 6 months; 4. known cognitive impairment; 5. substance dependence, ongoing or past; 6. motor disability or impairment affecting interaction with the digital tests; 7. photosensitive epilepsy or -migraines. For the MRI subgroup, any contraindication to MRI is an exclusion criterion.

Inclusion Criteria: * 1\. Age 18 - 75 years; ECOG PS 0 or 1. 2. Pathologically documented breast cancer that: 1. Is unresectable or metastatic. 2. Has a history of low HER2 expression (IHC 1+\& IHC 2+/ISH- or 0\<IHC\<1+). 3. Is HR-positive or HR-negative. 4. Has progressed on, and would no longer benefit from, endocrine therapy. 5. Has been treated with ≥1 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting. 3\. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1（Previously treated lesions with radiotherapy or focal therapy and no progression cannot be included as target lesion for assessment）. 4\. Has protocol-defined adequate bone marrow, renal, hepatic and blood clotting functions. 5\. Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and after the last dose for at least 6 months. Exclusion Criteria: 1. Has previously been treated with anti-angiogenic targeted small molecule therapy. 2. Prior treatment with antibody drug conjugate with a topoisomerase I inhibitor exatecan derivative. 3. Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. 4. Has unresolved toxicities from previous anticancer therapy. 5. Has uncontrolled or significant cardiovascular disease. 6. Has any bleeding event, unhealed wounds, ulcerative or fractures. 7. Has arterial or venous thromboembolic events occurred within 6 months. 8. Has spinal cord compression or clinically active central nervous system metastases. 9. Has any other condition that per protocol or in the opinion of the investigator is inappropriate for the study.

Inclusion Criteria for Participants with Remitted Depression: 1. Age 18-27. 2. Meeting criteria for lifetime major depressive disorder. 3. Currently meeting criteria for full remission (absence of clinically significant symptoms) for at least eight weeks, and having a Hamilton Depression Rating Scale score of less than or equal to 7. Inclusion Criteria for Healthy Volunteer Participants: 1. Age 18-27. 2. No lifetime history of any psychiatric disorder. 3. No first-degree relatives with a mood disorder. Exclusion Criteria (same for all participants): 1. Change in psychotropic medication use within the last 30 days 2. Autism spectrum disorder 3. Current eating disorder 4. Intellectual disability 5. Substance use disorder within the past 6 months 6. Contraindications for magnetic resonance imaging or electrocardiogram assessment (e.g., presence of metal in body, claustrophobia, cardiac device, pregnancy).

Inclusion Criteria: * 1．Voluntarily agree to participate in the study and sign the informed consent; * 2．Age≥18 years old; * 3．Patients with unresectable locally advanced or metastatic breast cancer confirmed by histology; * 4．Confirmed to be HER2 positive (HER2-positive is defined as IHC 3+ or IHC 2+ with ISH positive); * 5．Previously received regimens containing trastuzumab and taxanes at the advanced stage of disease. * 6．The Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2; * 7．Patients with adequate organ functions; * 8．Life expectancy ≥ 3 months; * 9．Female and male patients of childbearing age must agree to take adequate contraceptive measures during the entire study period. Exclusion Criteria: * 1\. Patients who have previously received tubulin inhibitor-loaded HER2 ADC therapy * 2\. History of any other malignant tumors within three years * 3\. With uncontrollable serous effusion within 14 days before randomization, which required frequent drainage or medical intervention. * 4\. Known contraindication to the study drugs; * 5\. Has not recovered from adverse reactions caused by previous anti-tumor treatments to ≤ Grade 1 or baseline (refer to NCI CTCAE 5.0); * 6\. NCI-CTCAE 5.0 ≥Grade 2 peripheral nephropathy occurred during previous systemic anti-tumor treatment; * 7\. Received immunotherapy, macromolecular targeted therapy or other anti-tumor biological therapy within 4 weeks before randomization, or received endocrine therapy, cytotoxic drug chemotherapy and small molecular targeted drug therapy within 2 weeks before randomization, or received traditional Chinese medicine preparations with anti-tumor indications within 2 weeks before randomization . * 8\. Major organ surgery (excluding needle biopsy) within 28 days before randomization; * 9\. Untreated (including baseline findings) or unstable cerebral parenchymal metastasis, spinal cord metastasis or compression, and cancerous meningitis. * 10.The cumulative amount of previous exposure to anthracyclines has reached the dosage; * 11.History of LVEF \< 40%, symptomatic congestive heart failure (CHF), * 12.Serious or uncontrolled cardiovascular disease; * 13.History of (non-infectious) interstitial lung disease/pneumonitis requiring steroid hormone therapy; * 14.Patients who currently have ocular diseases that require medication or surgical intervention; or unwilling to stop wearing contact lenses during the study. * 15.Active infections requiring intravenous antibiotics, antivirals, or antifungals within 14 days before randomization; * 16.There are other circumstances that may interfere with the subject's participation in the study procedures or do not meet the subject's maximum benefit from participating in the study or affect the study results.

Inclusion Criteria Group 1. Women occurring physiological pregnancies that sign the consent to participate in the study and agree to spontaneously return to the maternal hospital 40 days after delivery. Group 2. Patients diagnosed for PE (hypertension arisen suddenly after the 20th week of pregnancy with associated proteinuria, greater than or equal to 300 mg/24 hours often corresponding to 30 mg/dL (1+) on a single sample). Group 3. Women affected by SLE, APS, or autoimmune thyroiditis attending the medically assisted procreation department or the Department of Rheumatology, Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia Exclusion criteria 1. Women aged under 18 years 2. Viral or bacterial blood transmitted infections. 3. Patients whose informed consent cannot be obtained.

Inclusion Criteria: * Children must: * Have a current DSM-5 diagnosis of MDD, Persistent DD, or DDNOS (based on K-SADS-PL) OR not meet criteria for any DSM-5 mental health diagnosis (based on K-SADS-PL) * Be ages 7-12 * Be living with a parent(s) or guardian willing to participate * Be able and willing to provide informed consent/assent Parent must: * Not be currently pregnant * Be able to read, understand consent forms, and provide consent on their child's behalf * Be the biological parent (or grandparent in parental role) of the participating child \& have lived with the child for more than 75% of the child's life. All participants must: * Not have a disturbance that would interfere with participation such as autism spectrum disorder, psychosis, current substance dependence, current use of psychotropic medication, OCD, or MRI contraindication such as metal inside the body or claustrophobia * Be proficient in English Exclusion Criteria: * Thought or other disturbance in the child that would interfere with the ability to participate in treatment or assessments (e.g., psychotic disorder, autism spectrum disorder, OCD, active substance abuse/dependence, intellectual disability, as assessed on KSADS-PL) * Severe conduct disorders in the child that threaten the home stability (e.g. juvenile justice or children's protective service involvement as assessed on KSADS-PL) due to the potential impact on retention * Youth or primary caregivers do not speak English * Either parent or child has contraindications for neuroimaging (e.g., claustrophobia, metal implants, braces, electronically, magnetically, or mechanically activated devices such as cochlear implants) * The child is on an antidepressant medication, as it may complicate neuroimaging interpretation.

Inclusion Criteria: * Adult patients aged ≥ 18 years of age * Elevated triage BP AND increased average BP in three subsequent repeated measurements that are spaced at least 30 minutes after triage (systolic BP ≥ 160 mm Hg or diastolic BP ≥ 100 mm Hg) * Own a smart phone * Willing to measure and tele-transmit home BP readings Exclusion Criteria: * Hypertensive emergencies with evidence of end-organ damage, stroke, or acute coronary syndrome * Pregnant women * Acute intoxication * Acute surgical or trauma patients * Psychiatrically unstable patients * Advanced cognitive impairment * Patient requiring admission to hospital * Inability to use or care for home BP monitor correctly * From nursing home * Unstable housing * Non-English speaking or no family members who can help translate

Inclusion Criteria: * With a histological diagnosis of stage II or III localised breast cancer, with an indication for first or neoadjuvant chemotherapy validated by the RCP: HER2+, Triple negative * Affiliated or beneficiary of a social security scheme or similar * Having signed an informed consent for participation in the study. Exclusion Criteria: * Patients considered to be at very high risk (BRCA 1 and 2 mutation, Li Fraumeni syndrome, Lynch syndrome, previous thoracic irradiation for lymphoma) and high genetic risk as determined by an oncogenetic consultation * Pregnancy, breastfeeding * Contraindication to the injection of iodinated contrast material: hypersensitivity to the active substance or to one of the excipients of the contrast material, renal insufficiency with glomerular filtration rate \< 35ml/min * Patients who do not master the French language * Patient who is an adult protected by law, under curatorship or guardianship * Patient who has participated in another research study with a current exclusion period

Inclusion Criteria: * Adults ≥18 years old. * Able to swallow capsules. * If of childbearing potential, agree to practice an effective means of birth control throughout the duration of the study. * Meet the DSM-5-TR criteria for a diagnosis of major depressive disorder and are currently experiencing a major depressive episode of at least a 60-day duration at the time of Screening. * Have at least moderate severity of depression symptoms at Screening and Trial Baseline. Exclusion Criteria: * Participants who are pregnant, who intend to become pregnant during the trial, or who are currently nursing. * Have any of the following cardiovascular conditions: coronary artery disease, congenital long QT syndrome, cardiac hypertrophy, cardiac ischemia, congestive heart failure, clinically-relevant valvular heart disease, pulmonary hypertension, myocardial infarction, a clinically significant ECG abnormality, or tachycardia. * Have elevated blood pressure. * Have neurological conditions such as stroke, including transient ischemic attack, epilepsy, neurodegenerative disease (e.g., dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, etc.), or brain tumor. * Have severe hepatic or renal impairment. * Have uncontrolled diabetes mellitus or unstable existing thyroid disorder. * Are hepatitis or HIV positive. * Have a positive urine drug test for illicit, non-prescribed, or prohibited substances. * Meet DSM-5-TR criteria for schizophrenia spectrum or other psychotic disorders, including major depressive disorder with psychotic features ,bipolar disorder (types 1 or 2), antisocial personality disorder, borderline personality disorder or moderate or severe alcohol or drug use disorder * Meet DSM-5-TR criteria for active post-traumatic stress disorder within 6 months prior to Screening. * Have a first-degree relative with schizophrenia spectrum or other psychotic disorders, or bipolar I disorder.

Inclusion Criteria: * Male or female, aged between 30-65 years old. * Patients with resist hypertension (office systolic blood pressure ≥140 mmHg, and/or office diastolic blood pressure ≥90 mmHg, and/or 24-h average systolic blood pressure ≥130 mmHg) with rational lifestyle change and triple antihypertensive drugs (irbesartanhydrochlorothiazide 162.5 mg/d, amlodipine 5 mg/d) for at least 4 weeks. * Informed consent signed and agreed to participate in this trial. Exclusion Criteria: * Secondary hypertension * Adrenergic insufficiency. * adrenocortical insufficiency * Renal failure eGFR\<60 mL/min/1.73 m2 * Heart failure with NYHA grade Ⅱ-Ⅳ grade or unstable angina, severe cardiovascular and cerebrovascular stenosis, myocardial infarction, intracranial aneurysm, stroke and other acute cardiovascular events. * Acute infections, tumors and severe arrhythmias, psychiatric disorders, drugs or alcohol addicts. * Liver dysfunction or the following history of liver disease: AST or ALT 3 times higher than the upper limit, liver cirrhosis, history of hepatic encephalopathy, esophageal variceal history or portal shunt history. * Fertile woman without contraceptives. * Coagulation dysfunction. * Pregnant women or lactating women. * Participated in other clinical trials or admitted with other research drugs within 3 months prior to the trial. * Any surgical or medical condition which can significantly alter the absorption, distribution, metabolism, or excretion of any study drug. * Allergy or any contraindications for the study drugs, contrast agents and alcohol. History of depression, schizophrenia or vascular dementia. -Refused to sign informed consent

Inclusion Criteria: * Ability to understand and the willingness to sign a written informed consent document * Individuals with no health concerns that might affect the outcome of the study * Age 18-75 years of age * Ability to tolerate a simulated MRI brain scanning session * In the opinion of the investigator, capable and willing to grant written informed consent and cooperate with study procedures and requirements * High-affinity TSPO-binding genotype. Mixed (high/low) binding-affinity genotype may be included at PIs discretion * For participants with severe asthma: * Physician diagnosis of asthma for at least six months prior to screening (can be determined at the discretion of an asthma/allergy physician member of the study team) * Severe asthmatics must meet the ATS definition of severe asthma and/or be currently receiving a GINA Step 4 or 5 therapy or daily treatment of 320mcg budesonide. Therapy may include ongoing use of currently approved biologic immunomodulators Exclusion Criteria: * Current smoker (defined as more than 0.5 pack per week for the past 6 months and any smoking within two weeks of study procedures) or has a smoking history exceeding 5 pack years within the last 10 years * Currently receiving allergen immunotherapy unless on stable dose. * Use of psychotropic medication that might affect function of neurocircuitry implicated in our hypotheses (at the discretion of the PI/Co-I) * Inability to hold medications detailed in the medication hold schedule * Needle phobia or claustrophobia * Major health problems such any of the following in the last 6 months: stroke/TIA, myocardial Infarction, stent placement, or acute coronary syndrome are definitively exclusionary. Decisions regarding other major health problems, such as autoimmune disease, history of carotid stenosis, heart disease, uncontrolled hypertension, lung diseases other than asthma, history of significant arrhythmias, etc. will be based upon the judgement of the PI/Co-I. * Use of biologic medication that might affect signaling pathways under investigation (at the discretion of the PI/Co-I) * Pre-existing chronic infectious disease * Scheduled use of non-selective beta-blockers prior to each study visit. * Use of an investigational drug within 30 days of entering the study. This criterion will be reviewed on a case by case basis by the PI/Co-I to determine appropriate washout period. Appropriate wash out period may be greater than 30 days depending on the half-life of the investigational drug. Participants may be eligible for study participation after completing the washout period designated by the PI or Co-I (physician only). * Any MRI incompatibility as determined by most current MRI screening form * History of a diagnosed bipolar disorder, schizophrenia, or schizoaffective disorder * History of serious head trauma or seizure disorder (can be included at the discretion of the PI or Co-I) * Unable, in the judgement of the investigator, to comply with directions and/or tolerate the procedures required for participation in this study * Pregnant or breast-feeding or has a planned pregnancy during the course of the study * Any other medical condition or disease that would impact participant safety or data integrity in the opinion of the PI/CO-I

Inclusion Criteria: * Diagnosed T2DM * Outpatient status * Able to lay flat for imaging Exclusion Criteria: * A previous history of stroke * Current in-take of thiamine * Known thiamine allergy * Seizure disorder * Head trauma * Myocardial infarction * Current pregnancy (if female) * Diagnosed neuropsychiatric disorders (clinical depression, schizophrenia, manic-depression) * Diagnosed dementia * Sleep disordered breathing * Airway or chest deformities that would interfere with breathing * Chronic obstructive pulmonary disease * Cystic fibrosis * Presence of brain mass lesions * Any history of drug abuse (e.g., cocaine, tobacco, or cannabis) * Renal failure (requiring dialysis) * All T2DM adults with metallic and electronic implants (phrenic or cardiac pacemakers; although some pacemakers and cardioverter defibrillators are safe at a low magnetic field, they are not safe at 3.0-Tesla scanner) * Non-removable insulin pump/glucose sensor * Braces * Body weight more than 300 pounds (weight and height will be used to calculate BMI to determine if the patient will fit in the scanner and stay within parameters of size restrictions of MRI scanner table) * Any other contraindications to MRI, such as claustrophobia, or metallic-based tattoos, as per MRI safety website suggestions, will also be excluded.