Inclusion Criteria:  Biopsy pathologically diagnosed as primary high-grade osteosarcoma (including ordinary osteosarcoma, vasodilatory osteosarcoma, small cell osteosarcoma, high-grade surface osteosarcoma); Age no less than 12 years old and no older than 60 years old; New-onset patients who have not received chemotherapy, radiotherapy, surgery, Chinese medicine and other treatments. The primary site is the limbs and pelvis.  Exclusion Criteria:  Pathological diagnosis of surgical gross specimens except primary high-grade osteosarcoma; Failure to collect circulating exosomes as planned; Suffering from chronic diseases, which may lead to an increase in non-tumor-related circulating exosomes, such as autoimmune diseases , Chronic infections, etc.; The use of targeted drugs may lead to a decrease in tumor-related circulating exosomes; Withdrawal from the trial for any reason.