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Inclusion Criteria: * Age \>= 18 years * Women with a diagnosis of breast cancer who are being treated with curative intent, with the one exception being women who are receiving CDK4/6 inhibitors (these patients being allowed to have more advanced disease) * Provide informed consent * Ability to complete questionnaire(s) by themselves or with assistance * Filling into one of the 5 groups (understanding that groups will close once they complete their accrual goals of 30 patients) * Willingness to complete questionnaires every 3 months * Ability to complete the first questionnaire within 2 weeks of therapy initiation (for the four arms that are receiving adjuvant hormonal therapy) * For patients starting tamoxifen or an aromatase inhibitor: within 2 weeks of starting tamoxifen or aromatase inhibitor * For patients starting a CDK 4/6 inhibitor: within 2 weeks of starting the CDK 4/6 inhibitor (patients may have started an aromatase inhibitor at any time prior to initiation of CDK 4/6 inhibitor). Exclusion Criteria: * Verbal baseline alopecia \>= 2 on an 11 point scale (from none = 0 to severe = 10). The question to use for this item is: Please rate your hair thinning or loss on a scale from 0 to 10, with 0 being no hair loss and 10 being complete hair loss * Planned receipt of chemotherapy or another cancer-directed therapy concurrently (e.g., everolimus, etc.; note that a CDK4/6 inhibitor is allowed within cohort 3) * Prior use of endocrine therapy for breast cancer * Receipt of chemotherapy over the previous 6 months

Inclusion Criteria: * All patients receiving OAT at participating sites Exclusion Criteria: * Not willing to participate * Unable to sign informed consent

Inclusion Criteria: * New cardio-oncology consultation for breast cancer patients, or * New cardio-oncology consultation for Hodgkin's or non-Hodgkin's lymphoma patients, or * New cardio-oncology consultation for acute or chronic leukemia patients, or * New cardio-oncology consultation for multiple myeloma or AL amyloidosis, or * New cardio-oncology consultations for immune check-point inhibitors cardiac evaluation. * All patients have to be 18 years old or older Exclusion Criteria: * Cardio-oncology patients who have previously had cardio-oncology evaluation and follow up by the investigators. * Minors less than 18 years old. * Inability or unwillingness to consent to participate

Inclusion Criteria: * Diagnosed with type II diabetes for at least 3 months * Between the age of 18-64 * BMI ≥ 25 * Monitors blood glucose regularly (at least once per day) * Owns or has access to a bathroom weight scale * Owns a smartphone and willing to download mobile app Exclusion Criteria: * Does not check blood glucose at least once per day * On medications that promote weight gain such as antipsychotic, antidepressant, and steroid hormone medications. Medications for diabetes such as insulin, thiazolidinediones or sulfonylureas are oka

Inclusion Criteria: * U.S. Men and women meeting the age of majority, defined as follows: Age 19 or older in Nebraska and Alabama; Age 21 or older in Mississippi; Age 18 or older in all other states * Prior diagnosis of type 2 diabetes mellitus Exclusion Criteria: * Use of recreational drugs in the past 6 months * Pregnancy or intention to become pregnant during the study period, as verified by self-report * Unstable medical or psychiatric illness * Lack of English fluency * Inability to maintain current medication regimen * Inability or unwillingness to participate in all components of the study

Inclusion Criteria: * 18-85 years * HIV-1 viral load \<200 copies/mL on antiretroviral therapy (ART) at screening visit * Center for Epidemiological Studies - Depression (CES-D) score ≥ 20 Exclusion Criteria: * Contraindication to magnetic resonance imaging (MRI) or poor-quality baseline MRI preventing image analyses as determined by radiologist assessment * Recent severe infections including opportunistic infections, active bacterial, mycobacterial, fungal, or certain viral infections * Vulnerable populations (e.g., pregnant/nursing, severe cognitive or intellectual impairment, incarcerated) * Use of cobicistat or ritonavir * High risk for suicide (active suicidal ideation (SI) with plan/intent as assessed by using the Columbia Suicide Severity Rating (C-SSRS) or \> 2 attempts in lifetime or any in the past 6 months) or expresses homicidal ideation necessitating clinical intervention or representing an imminent concern * Any severe (life-threatening or unstable) medical condition as determined by clinician assessment * Blood pressure, with the lowest reading taken after three repeat readings during screening visit, ≥ 160 mmHg systolic OR ≥ 95 mmHg diastolic or other life-threatening vital signs as determined by clinician assessment * Clinically significant abnormalities in physical examination or ECG that would interfere with study participation * Decompensated cirrhosis, active liver inflammation (alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≥ 5 times the upper limit of normal) or unsuppressed viral hepatitis B or C infection * Severe renal disease (estimated glomerular filtration rate ≤ 30 mL/min/1.73m2) * Seizure disorder requiring antiepileptic treatment * History of allergic reaction or side effects with prior pregnenolone use * Currently using testosterone enanthate, testosterone cypionate, or estrogen containing preparations that significantly increase systemic estrogen levels, including but not limited to oral and transdermal forms of estrogen. All other forms of exogenous sex steroid hormones will be evaluated at the discretion of the PI and/or clinical delegates. * Currently using systemic immunosuppressive agents, including corticosteroids, chemotherapy, or specific immunomodulating agents, such as monoclonal antibodies and TNF-inhibitors * Excessive alcohol or other substances use that would interfere with classification of major depression disorder, study procedures and/or follow-up * Current diagnosis of bipolar disorder * Diagnosis of a psychotic disorder (current or lifetime) * Diagnosis of schizophrenia (current or lifetime) * \<70% adherence to study drug prior to randomization * Inability to swallow pills/capsules * Not able to complete neuropsychological testing in English * Concurrent participation in another interventional trial, except for lifestyle and device studies (For vaccination studies, individuals in the observation period are not exclusionary. Other interventions will be evaluated at the discretion of the PI and/or clinical delegates.)

Inclusion Criteria: 1. Adults 18 years or older 2. English fluency in order to complete study procedures 3. Normal vision or corrected to normal vision 4. QIDS score ≥ 5 and ≤ 15 to include individuals with elevated, but not severe symptoms of depression 5. No presence of psychotic symptoms that interfere with functioning 6. No current hazardous alcohol or drug use 7. No previous experience with mindfulness-based treatment (i.e., enrollment in MBSR or MBCT previously) 8. No current symptoms of mania indicative of a manic episode 9. No current cognitive impairment 10. No history of a formally diagnosed learning disability in reading, intellectual disability or other developmental disorder 11. No history of a neurologic illness affecting cognition 12. If on psychiatric medications, no change in medications for at least 4 weeks 13. If in psychotherapy, no change in therapy status for at least 4 weeks Exclusion Criteria: Exclusion criteria include: (a) presence of psychotic symptoms that interfere with one's ability to function as determined by the SCID-5 Psychotic Screening Module; (b) current hazardous alcohol or drug use as indicated by a score of \>10 for men and women on the AUDIT and the DUDIT for cannabis use, and \>6 for men and women on the DUDIT for all other drugs (everything but cannabis), (c) change in psychiatric drug prescription within 4 weeks; (d) started psychotherapy or other psychiatric treatment within the past 4 weeks; (e) current suicide ideation or behavior which requires urgent intervention due to safety concerns; (f) Previous enrollment in MBCT or MBSR; (g) symptoms of mild cognitive impairment as indicated by a score of \<26 on the MoCA; (h) formally diagnosed learning disability, intellectual disability, or other developmental disorder; (i) history of neurologic illness affecting cognition; (j) current symptoms indicative of a manic episode per the SCID-5 Mood Disorders Module.

Key Inclusion Criteria: 1. History of AERD, defined as meeting the diagnostic triad with: 1. History of physician-diagnosed asthma and 2. History of physician-diagnosed nasal polyposis and 3. History of pathognomonic reactions to aspirin or other nonselective COX inhibitors. 2. Visible nasal polyps bilaterally on otoscope physical exam at the time of screening. 3. Evidence of sense of smell impairment, with a University of Pennsylvania Smell Identification Test (UPSIT) score of \<34. 4. Stable asthma (no glucocorticoid burst for at least 4 weeks prior to Visit 1, and no hospitalizations or ER visits for asthma for at least the prior 3 months). 5. Consistent (daily) use of an intranasal steroid for at least 4 weeks prior to Screening. 6. No current smoking (not more than one instance of smoking in the last 3 months). 7. For females: Practicing FDA-approved methods of birth control for the duration of the study. Female participants of childbearing potential must have a negative pregnancy test upon study entry. Key Exclusion Criteria: 1. Use of investigational drugs within 12 weeks of Screening. 2. Use of any biologic agent within 4 months prior to Screening. 3. Use of systemic (enteral or injected) glucocorticoids within 4 weeks prior to Screening. 4. History of any sinonasal surgery within 4 months prior to Screening 5. Current use of zileuton 6. Current use of high-dose aspirin therapy (no more than 325 mg aspirin per day will be allowed) 7. Pregnant, nursing, or planning to become pregnant Note: Other inclusion and exclusion criteria apply.

Main inclusion criteria 1. Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast untreated and recently diagnosed 2. ER-positive and/or PgR-positive and HER2-negative tumor 3. Ki67% ≥ 20% locally assessed and/or high genomic risk (defined by gene signature): 4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 5. Breast cancer eligible for primary surgery. 6. Availability of pre-treatment tumor tissue sample of FFPE tumor block from primary tumor for biomarker analysis. 7. Participants must be deemed eligible for neoadjuvant chemotherapy 8. Participants must be deemed eligible for surgery. 9. Adequate hematologic and end-organ function, defined by the following laboratory results 10. Baseline LVEF ≥ 50% measured by echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan Main exclusion criteria 1. Metastatic (Stage IV) breast cancer. 2. Bilateral invasive breast cancer. 3. Any treatment, local or systemic, including prior chemotherapy, ET, targeted therapy, and/or radiation therapy for the currently diagnosed BC prior to enrollment. 4. Patients in whom a primary tumor excisional biopsy was performed. 5. Prior treatment with a HER3 antibody, topoisomerase I inhibitor, with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g., DS-8201) and with a govitecan derivative (e.g., IMMU-132). 6. Patient has active cardiac disease or a history of cardiac dysfunction. 7. Medical history of clinically significant lung diseases (e.g., interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or who are suspected to have these diseases by imaging at screening period. 8. Patients with a history of any malignancy are ineligible except specific cases 9. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary or metabolic disease; wound healing disorders; ulcers; bone fractures, psychiatric illness/social situations, geographical factors, substance abuse) or other factors which in the Investigator's opinion makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol 10. Concurrent, serious, uncontrolled infections or current known infection with HIV or active hepatitis B and/or hepatitis C. 11. History of significant co-morbidities that, in the judgment of the investigator, may interfere with the conduction of the study, the evaluation of response, or with ICF. 12. Known hypersensitivity to either the drug substance components (including an antibody, a drug-linker, or a topoisomerase I inhibitor) or inactive ingredients in the drug product or history of severe hypersensitivity reactions to other monoclonal antibodies. 13. History of exposure to cumulative anthracycline doses greater than follows: a. Adriamycin \> 100 mg/m2; Epirubicin \> 180 mg/m2; Mitoxantrone \> 40 mg/m2; Idarubicin \> 22.5 mg/m2. If another anthracycline or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of 100 mg/m2 of adriamycin. 14. Any history of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during screening. 15. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e. pulmonary emboli within three months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e. rheumatoid arthritis, Sjögren's syndrome, sarcoidosis etc.), or prior pneumonectomy. 16. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, grade ≤1 or baseline. Subjects with chronic grade 2 toxicities may be eligible per the discretion of the Investigator. 17. Non-eligible for taxanes therapy. Previous sensory neuropathy \> grade 1, according to NCI-CTCAE criteria, due to any reason. 18. Is receiving chronic systemic corticosteroids dosed at \>10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Subjects who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study. 19. Evidence of any leptomeningeal disease. 20. Has clinically significant corneal disease. 21. Female subject who is pregnant or breastfeeding or intends to become pregnant during the study. 22. Subjects who are currently receiving chloroquine or hydroxychloroquine. A washout period of \> 14 days is required prior to randomization or Cycle 1 Day 1

Inclusion Criteria: 1. are outpatients; 2. are voluntary and competent to consent to treatment; 3. have a Diagnostic and Statistical Manual for Mental Disorders, 5th edition major depressive episode based on the Mini International Neuropsychiatric Interview (MINI) 4. are 18yo to 65yo; 5. have a score of ≥18 on the Hamilton Rating Scale for Depression (HRSD-17) item at screening 6. have not had a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of ≥ 3 in the current episode or have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF 1 or 2); 7. are agreeable to keeping their current medication constant during the study 8. are able to adhere to the study and treatment schedules 9. meet TMS and MRI safety criteria Exclusion Criteria: 1. have a concomitant unstable medical illness 2. are pregnant or intend to become pregnant during the study 3. have a current MINI diagnosis of bipolar disorder, psychotic disorder, obsessive compulsive disorder, concurrent substance use disorder (aside from nicotine) or post-traumatic stress disorder (current or within the last year) 4. have failed a course of electroconvulsive therapy within the current depressive episode due to the lower likelihood of response to rTMS; 5. have any significant neurological disorder (e.g., space occupying brain lesion, history of stroke, cerebral aneurysm, seizure disorder, Parkinson's disease, Huntington's chorea, multiple sclerosis) or confirmed diagnosis of dementia or cognitive impairment 6. present with a medical condition, medication, or laboratory abnormality that could cause a major depressive episode in the opinion of the investigator 7. have an intracranial implant or any other metal object that cannot be safely removed, precluding safety of TMS or MRI exposure within or near the head, excluding the mouth 8. require benzodiazepine equivalent to lorazepam 2 mg/day or higher or any anticonvulsant due to the potential of these medications to limit the efficacy of rTMS \[45\] 9. have inadequate English fluency to complete clinical assessments. 10. are participating in a new course psychotherapy initiated within the last 3 months or finishing prior to the end of scheduled treatments; 11. have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

Eligible participants are women aged ≥18 years, with a history of GDM diagnosed according to the 2013 WHO criteria (at 24-32 weeks gestation or \<24 weeks for early GDM). Participants must have prediabetes diagnosed between 6 weeks and 12 months postpartum according to ADA criteria (FPG 5.6-6.9 mmol/L, 2-hour OGTT glucose 7.8-11.0 mmol/L and/or HbA1c 39-46 mmol/mol \[5.7-6.4%\]). Additional inclusion criteria include cessation of breastfeeding, no intention to become pregnant within the next year, use of effective contraception and no use of medication affecting glucose metabolism. Written ICF is obtained prior to any study-related procedures. Exclusion criteria include established diabetes, presence of autoantibodies suggestive of type 1 diabetes, normal glucose tolerance, history of pancreatitis, previous bariatric surgery or planned surgery within two years, unable to understand and speak Dutch, French or English and current pregnant or planning to become pregnant within one year after participating in the study.

Inclusion Criteria: * Patients: Biopsy and/or radiograph proven diagnosis of hepatocellular carcinoma, cholangiocarcinoma, gallbladder carcinoma or breast, ovarian, or colorectal cancer with liver metastases with a life expectancy of at least one year; age \>21 years; no evidence of thought disorder, delusions, or active suicidal ideation is observed or reported. * Caregivers: A spouse or cohabitating intimate partner of an advanced cancer patient being evaluated the UPMC's Liver Cancer Center and age \>21 years Exclusion Criteria: * Patients: Age \< 21 years, Lack of fluency in English, Evidence of thought disorder, delusions, hallucinations, or suicidal ideation. * Caregivers: Age \< 21 years, Lack of fluency in English, Evidence of thought disorder, delusions, hallucinations, or suicidal ideation.

Inclusion Criteria: * lymph node + breast cancer requiring dissection Exclusion Criteria: * previous lymphedema * BMI \>35

Inclusion Criteria: 1. Men and women of all ages are welcome. 2. Pathological diagnosis of malignant tumor in our hospital. 3. Received at least one hospitalization at this hospital. 4. The expected survival time is greater than 1 year. Exclusion Criteria: 1.There was no pathological report of malignancy.

Inclusion Criteria: 1. Males and females 4- ≥40 years of age with a clinical diagnosis of T1D 2. T1D clinical diagnosis with insulin start date no more than 100 days prior to the time of randomization 3. Random non-fasting C-peptide level of \>0.2 pmol/mL (equivalent to \>0.6ng/ml) at screening. 4. Positive for any one of the following diabetes-related autoantibodies (IAA, GAA, IA-2, or ZnT8) 5. Treatment naïve of any immunomodulatory agent 6. Normal hearing at screening, defined as acceptable results of pure-tone audiometry (\<20 decibel \[dB\] baseline thresholds for all frequencies tested Exclusion Criteria: 1. Presence of severe, active disease that interferes with dietary intake or requires the use of chronic medication, with the exception of well-controlled hypothyroidism and mild asthma not requiring oral steroids. Presence of any psychiatric disorder that will affect ability to participate in study. 2. Diabetes other than T1D 3. Chronic illness known to affect glucose metabolism (e.g. Cushing syndrome, polycystic ovarian disorder, cystic fibrosis) or taking medications that affect glucose metabolism (e.g. steroids, metformin) 4. Inability to swallow pills 5. Psychiatric impairment or current use of anti-psychotic medication 6. Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results. 7. Neutropenia (\< 1,500 neutrophils/μL) 8. Leukopenia (\< 3,000 leukocytes /μL) 9. Lymphopenia ( \< 800 lymphocytes/μL) 10. Thrombocytopenia (\<100,000 platelets/μL) 11. Clinically significant anemia or Hemoglobin as defined below: In Adults: Hgb \<12.0g/dL in females and \<13.0g/dL in males In Children: 12- \<18: \<11.4 g/dL in females and \<12.4 g/dL in males In Children: 4- \<12: Hgb \<11.2 g/dL 12. Impaired renal function (assessed by history and BUN/Creatinine, DFMO is renally excreted) 13. Allergy to milk or soy (components of Boost® drink used for mixed meal tolerance testing) 14. Female participants of child-bearing age with reproductive potential, must not be pregnant and agree to use 2 effective forms of birth control or be abstinent during the study period (see below). Male participants (including men who have had vasectomies) whose partners are pregnant or may be pregnant should use condoms while on study drug, until 2 weeks after discontinuation of drug, while the partner is pregnant. 15. Active seizure disorder, defined as requiring chronic medication at the time of study or having had a seizure within the past 12 months at the time of screening 16. Enrollment into another intervention trial. 17. Use of an automated insulin delivery system, including hybrid closed loop or fully closed loop insulin pumps) that do not allow for manual suspension or temporary modification of insulin delivery for bolus dosing.

Inclusion Criteria: * Children and Adults, aged 15 - 80 * Diagnosed with idiopathic or heritable, pulmonary arterial hypertension (PAH), defined according to standard criteria * Unaffected Mutation Carriers: Healthy participants with a known BMPR2 gene mutation and normal pulmonary pressure and RV function on echo * Healthy Controls: Healthy individuals without cardiopulmonary disease. * WHO functional class I-III * Stable PAH-specific medication regimen for three months prior to enrollment. Subjects with only a single diuretic adjustment in the prior three months will be included. Adjustments in IV prostacyclin for side effect management are allowed. Exclusion Criteria: * Prohibited from normal activity due to wheelchair bound status, bed bound status, reliance on a cane/walker, activity-limiting angina, activity-limiting osteoarthritis, or other condition that limits activity. * Pregnancy * Diagnosis of PAH etiology other than idiopathic, heritable * Functional class IV heart failure * Requirement of \> 2 diuretic adjustment in the prior three months.

Inclusion Criteria village level: * Village size of 40 to 100 households * Village consent obtained from village chief * Possibility to identify or recruit a CC-VHW from the village population meeting the following requirements which are largely in line with the criteria of the Lesotho VHW Program Policy: o Criteria of the Lesotho Village Health Program Policy: * Having primary residence in the village (according to village chief) * Having a proven record of trustworthiness in the resident village * Having proven ability to maintain confidentiality on public matters * Being aged between 20 and 50 years * Being able to provide written reports and being able to do basic mathematical calculations * Having at least educational level equivalent to high school leaving certificate (Junior Certificate) o Additional ComBaCaL criteria: * Having the ability and willingness to work with a tablet-based eHealth tool * Having good social and communication skills * Having the ability and willingness to interact with health professionals and the village population * Being able to speak, understand and write in English- * Having successfully completed the ComBaCaL CC-VHW training including final assessment Inclusion criteria individual level: * Having primary residence in the village (self-reported at time of enrolment) * Being able and willing to consent to participation or in case of individuals aged below 18

Inclusion Criteria: 1. Female aged ≥18 years; 2. HR+/HER2- invasive breast cancer confirmed by histology (specific definition: ER \>10% positive tumor cells by immunohistochemistry is defined as ER positive, PR \>10% positive tumor cells is defined as PR positive, ER and/or PR positive is defined as HR positive; HER2 0-1+ or HER2 + but negative by FISH without amplification was defined as HER2 negative); 3. Locally advanced breast cancer (unable to undergo radical local treatment) or recurrent metastatic breast cancer; 4. HR+/HER2- advanced breast cancer patients who had previously received CDK4/6 inhibitor therapy; 5. At least one measurable lesion according to RECIST 1.1 (conventional CT scan ≥20 mm, spiral CT scan ≥10 mm, measurable lesion has not received radiotherapy); 6. The functions of the main organs are basically normal and meet the following conditions: I. Blood routine examination criteria shall meet: HB ≥90 g/L (no blood transfusion within 14 days); The ANC acuity 1.5 x 109 / L; PLT acuity 75 x 109 / L; Ii. Biochemical tests should meet the following criteria: TBIL ≤1.5×ULN (upper limit of normal value); ALT and AST ≤3×ULN; If liver metastases were present, ALT and AST≤ 5×ULN; Serum Cr ≤1×ULN, endogenous creatinine clearance \> 50 ml/min (Cockcroft-Gault formula); 7. They have not received radiotherapy, molecular targeted therapy, or surgery within 3 weeks before the start of the study, and have recovered from the acute toxicity of previous treatment (if surgery was performed, the wound has healed completely); No peripheral neuropathy or grade I peripheral neurotoxicity; 8. ECOG score ≤2, and life expectancy ≥3 months; 9. Fertile female subjects were required to use a medically approved contraceptive method during the study treatment period and for at least 3 months after the last use of the study drug; 10. Subjects volunteered to join the study, signed informed consent, had good compliance, and cooperated with follow-up. Exclusion Criteria: 1. Radiotherapy (except for palliative causes), chemotherapy, and immunotherapy were used in the first 3 weeks of treatment, except bisphosphonate (which can be used for bone metastasis); 2. Uncontrolled central nervous system metastases (indicating symptomatic or symptomatic treatment with glucocorticoids or mannitol); 3. A history of clinically important or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction, or ventricular arrhythmia within the last 6 months; 4. Persistent grade 1 or higher adverse reactions caused by previous treatments. The exception to this is hair loss or something the researchers don't think should be ruled out. Such cases should be clearly documented in the investigator's notes; 5. Underwent major surgery (except minor outpatient procedures, such as placement of vascular access) within 3 weeks of the first course of trial treatment; 6. Pregnant or lactating patients; Malignancy (except basal cell carcinoma of the skin, which has been cured, and carcinoma in situ of the cervix) in the past 5 years.

Inclusion Criteria: * Subject with depression or anxiety symptom diagnosed by ICD-10. * Depression 7≤HAMD-17≤29，anxiety 7≤HAMA-14≤29. * Subject has a clear mind and the ability to read, to talk and to communicate. * Subject agrees to participate in this study and sign to the informed consent. Exclusion Criteria: * Subject with bipolar disorder, psychotic disorder, organic mental disorder and cognitive disorder. * Subject with alcohol abuse, substance dependence and suicidal behavior in past-year. * Subject has severe somatic disease. * Subject is pregnant or lactating women.

Inclusion Criteria: * Diagnosis of major depressive episode (MDE), in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5), in the context of unipolar major depressive disorder or bipolar affective disorder. * 18 years or older in age. * Treatment resistant depression at Stage II of the Thase and Rush classification.56 * Baseline Montgomery Åsberg Depression Rating Scale score of ≥ 20 (moderate-to-severe depression severity).57,58 * No increase or initiation of new antidepressant therapy in the four weeks prior to screening. * Demonstrated capacity to give informed consent. Exclusion Criteria: * Inability to provide informed consent. * Medically unstable patients at the discretion of the investigator. * Concomitant neurological disorder or a history of a seizure disorder. * Participants who are pregnant. * Current substance use meeting DSM-5 criteria for substance use disorder. * Per DSM-5, had ever met diagnostic criteria for schizophrenia, schizoaffective disorder, schizophreniform disorder or delusional disorder as assessed by the Mini-International Neuropsychiatric Interview (MINI) at the time of screening. * Diagnosis of any other mental disorder that is the participant's primary diagnosis or main mental health syndrome of concern at the time of screening, which may significantly affect psychiatric status and assessed as likely to impact trial participation, in the clinical judgement of the investigator.