Iter-4360dd15-0011-transcript
第 11 轮执行轨迹
→ call search_memory({"limit":8,"query":"4360dd15 rapamycin 2024 systematic review 19 studies Table 1 included trials endpoint"}) → call list_recent({"n":6})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹
→ cal"}, {"title": "Iter-4360dd15-0007-transcript", "tags": "iteration transcript", "modified": "20260424174944000", "preview": "!! 第 7 轮执行轨迹 → call search_memory({\\\"limit\\\":10,\\\"query\\"}, {"title": "Iter-4360dd15-0009-transcript", "tags": "iteration transcript", "modified": "20260424175555000", "preview": "!! 第 9 轮执行轨迹 【tool:list_recent】
{"ok": true, "items": [{"title": "Iter-4360dd15-0010-reflection", "modified": "20260424175843000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424175843000", "tags": "pinned focus"}, {"title": "先用可访问综述骨架锁定缺口", "modified": "20260424175843000", "tags": "lesson evidence retrieval human-trials rapamycin"}, {"title": "Iter-4360dd15-0010-transcript", "modified": "20260424175830000", "tags": "iteration transcript"}, {"title": "2024 rapamycin systematic review: abstract-level constraints and what remains missing", "modified": "20260424175824000", "tags": "lesson fact 4360dd15 evidence retrieval"}, {"title": "Iter-4360dd15-0009-reflection", "modified": "20260424175603000", "tags": "iteration reflection"}]}
→ call search_memory({"limit":10,"query":"4360dd15 2024 rapamycin systematic review remaining 11 included trials names primary endpoint"})
→ call read_note({"title":"NEXT_FOCUS"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹
→ call search_memory({\"limit\":8,\"query\":\"4360dd15 rapamycin review 2024 trial endpoint remaining 11\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":20,\"tag\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0007-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424174944000\", \"preview\": \"!! 第 7 轮执行轨迹 → call search_memory({\"limit\":8,\"query\":\"4360dd15 rapamycin mTOR systematic review 2024 trial endpoint PMC table remaining included studies\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":20,\"tag\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0007-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424174944000\""}, {"title": "Iter-4360dd15-0007-transcript", "tags": "iteration transcript", "modified": "20260424174944000", "preview": "!! 第 7 轮执行轨迹 【tool:read_note】
{"ok": true, "title": "NEXT_FOCUS", "tags": "pinned focus", "text": "!! 下轮焦点（来自 mission 4360dd15 · Iter-0010）\n\n下一轮只做一件事：找到2024综述中剩余11项纳入试验的具体名称和各自主要终点。"}
→ call web_search({"limit":8,"query":"2024 systematic review rapamycin human trials 19 studies Table 1 endpoint mTOR review"})
→ call pubmed_search({"limit":8,"query":"rapamycin systematic review human trials 2024"})
→ call wiki_search({"lang":"en","limit":5,"query":"rapamycin human trial systematic review 2024"})
【tool:web_search】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://html.duckduckgo.com/html/?q=2024+systematic+review+rapamycin+human+trials+19+studies+Table+1+endpoint+mTOR+review'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
【tool:pubmed_search】
{"ok": true, "query": "rapamycin systematic review human trials 2024", "results": [{"pmid": "41579604", "title": "The efficacy of immunotherapies for pregnancy outcomes of patients with recurrent implantation failure as defined by ESHRE guidelines: A systematic review and network meta-analysis.", "source": "J Reprod Immunol", "pubdate": "2026 Feb", "authors": ["Li Y", "Lan P", "Tang J", "Wang W", "Chen H"], "url": "https://pubmed.ncbi.nlm.nih.gov/41579604/"}, {"pmid": "40840330", "title": "The impact of standard- versus reduced-dose tacrolimus exposure on clinical outcomes in adult kidney transplant recipients: A systematic review and meta-analysis.", "source": "Transplant Rev (Orlando)", "pubdate": "2025 Dec", "authors": ["Udomkarnjananun S", "Soliman M", "Min S", "An HPH", "Lee CY", "Lu Y", "van Gelder T"], "url": "https://pubmed.ncbi.nlm.nih.gov/40840330/"}, {"pmid": "40722827", "title": "Revolutionizing Allogeneic Graft Tolerance Through Chimeric Antigen Receptor-T Regulatory Cells.", "source": "Biomedicines", "pubdate": "2025 Jul 18", "authors": ["Chan AML", "Sakthiswary R", "Lokanathan Y"], "url": "https://pubmed.ncbi.nlm.nih.gov/40722827/"}, {"pmid": "40619100", "title": "Effectiveness and safety of sirolimus in the treatment of venous malformations: A meta-analysis of prospective studies.", "source": "J Vasc Surg Venous Lymphat Disord", "pubdate": "2025 Nov", "authors": ["Wang G", "Lu W", "Zhu Y", "Wang C", "Yang X"], "url": "https://pubmed.ncbi.nlm.nih.gov/40619100/"
【tool:wiki_search】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://en.wikipedia.org/w/api.php?action=query&list=search&srsearch=rapamycin+human+trial+systematic+review+2024&srlimit=5&format=json'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
→ call search_memory({"limit":12,"query":"4360dd15 2024 rapamycin systematic review abstract title PMC Table 1 19 studies"})
→ call list_by_tag({"limit":20,"tag":"4360dd15"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹
→ call search_memory({\"limit\":8,\"query\":\"4360dd15 rapamycin review 2024 trial endpoint remaining 11\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":20,\"tag\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0007-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424174944000\", \"preview\": \"!! 第 7 轮执行轨迹 → call search_memory({\"limit\":10,\"query\":\"4360dd15 rapamycin rapalog human trial Table 1 remaining endpoint PMC review trial name primary endpoint\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0006-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424174703000\", \"preview\": \"!! 第 6 轮执行轨迹 → call search_memory({\"limit\":10,\"query\":\"4360dd15 rapamycin rapalog human trial Table 1 remaining endpoint PMC review\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0007-transcript【tool:list_by_tag】
{"ok": true, "items": [{"title": "2024 rapamycin systematic review: abstract-level constraints and what remains missing", "modified": "20260424175824000"}, {"title": "Added included ADPKD rapalog trial CRAD001ADE12 and its body-weight endpoint", "modified": "20260424174657000"}, {"title": "Rapamycin human trials: completed studies table from PMC review", "modified": "20260424174352000"}, {"title": "Iter-4360dd15-0004-critique-rapamycin-evidence", "modified": "20260424174226000"}, {"title": "Rapamycin human trials: extracted endpoints and outcomes from the 2024 systematic review review pass 1", "modified": "20260424173529000"}, {"title": "Human longevity interventions evidence maturity matrix 2026-04-25", "modified": "20260424173237000"}]}
→ call read_note({"title":"2024 rapamycin systematic review: abstract-level constraints and what remains missing"})
→ call read_note({"title":"Rapamycin human trials: completed studies table from PMC review"})
→ call read_note({"title":"Rapamycin human trials: extracted endpoints and outcomes from the 2024 systematic review review pass 1"})
【tool:read_note】
{"ok": true, "title": "2024 rapamycin systematic review: abstract-level constraints and what remains missing", "tags": "lesson fact 4360dd15 [[evidence retrieval]]", "text": "!! What I could verify this round\nI could not yet recover the remaining 11 included-study names from the 2024 systematic review, but I did verify the paper’s abstract via PubMed XML and extracted a few important constraints.\n\n!! Verified bibliographic identity\n- PMID: 38310895\n- Title: ''Targeting ageing with rapamycin and its derivatives in humans: a systematic review.''\n- Journal: //Lancet Healthy Longev// 2024 Feb; 5(2):e152-e162\n- DOI: 10.1016/S2666-7568(23)00258-1\n\n!! Abstract-level findings worth retaining\nThe abstract states that:\n# 18,400 unique articles were screened\n# 19 studies were included\n# benefits were observed in the immune, cardiovascular, and integumentary systems\n# no significant effects were found in the endocrine, muscular, or neurological systems\n# respiratory, digestive, renal, and reproductive systems were not assessed\n# no serious adverse events attributed to rapamycin/derivatives were reported in healthy individuals\n# in individuals with ageing-related diseases, infections and lipid increases were reported\n\n!! Why this matters\nThis is stronger than a generic \"rapamycin is anti-aging\" claim, but still weaker than a study-level map. The review’s abstract already tells us the evidence is:\n- multi-system but fragmented\n- partly positive in healthy or ageing-
【tool:read_note】
{"ok": true, "title": "Rapamycin human trials: completed studies table from PMC review", "tags": "knowledge fact 4360dd15", "text": "!! PMC review Table 1: completed human rapamycin / rapalog trials\n\nI re-read the accessible PMC review [[Blazing a trail for the clinical use of rapamycin as a geroprotecTOR]] (GeroScience 2023; PMCID PMC10643772) and extracted its completed-trial table.\n\n!! What this source actually contains\nThe table lists ''8 completed human studies'' and gives each study’s primary endpoint.\n\n!! Extracted trial list\n| Study | Agent | Population | Primary endpoint |\n|---|---|---|---|\n| Krebs et al. 2007 | rapamycin | 11 men, 28 ± 1 y | Increase in peripheral insulin sensitivity during insulin clamp plus amino acid infusion |\n| Drummond et al. 2009 | rapamycin | 15 men, 29 ± 2 y | Difference in post-resistance-exercise mixed-muscle protein synthesis rates |\n| Gunderman 2014 | rapamycin | 16 men, 26 ± 1 y | Difference in post-blood-flow-restricted resistance-exercise mixed-muscle protein synthesis rates |\n| Mannick et al. 2014 | everolimus | 218 adults ≥65 y | Improvement in influenza vaccination response |\n| Mannick et al. 2018 | everolimus / BEZ235 | 264 adults ≥65 y | Improvement in influenza vaccination response |\n| Kraig et al. 2018 | rapamycin | 25 healthy adults 70–95 y | Immunological response |\n| Chung et al. 2019 | topical rapamycin | 36 adults with aging skin >40 y | Decreased p16-positive senescent cells in skin |\n| Mannick et al. 20
【tool:read_note】
{"ok": true, "title": "Rapamycin human trials: extracted endpoints and outcomes from the 2024 systematic review review pass 1", "tags": "knowledge fact experiment 4360dd15", "text": "!! Rapamycin human trial evidence from a 2024 systematic review\nThis round I narrowed the long-longevity question to a single mechanism: //rapamycin / mTOR//.\n\n!! Source\n[[Targeting ageing with rapamycin and its derivatives in humans: a systematic review]] (Lee, Hodzic Kuerec, Maier), //Lancet Healthy Longevity// 2024; 5(2):e152-e162. The VU repository page includes the abstract and full bibliographic metadata.\n\n!! Extracted human trial snapshot\nThe review reports: 18,400 unique records screened, 19 included studies. Benefits were seen mainly in immune, cardiovascular, and integumentary systems; no significant effects in endocrine, muscular, or neurological systems.\n\n| Study | Population | Agent | Dose / schedule | Design | Primary endpoint | Result |\n|---|---|---|---|---|---|---|\n| Krebs et al. 2007 | 11 men, 28 +/- 1 y | rapamycin | 6 mg single dose | randomized, double-blind, placebo-controlled, crossover | peripheral insulin sensitivity during insulin clamp + amino acid infusion | met |\n| Drummond et al. 2009 | 15 men, 29 +/- 2 y | rapamycin | 12 mg single dose 2 h before resistance exercise | acute exercise +/- rapamycin | post-exercise mixed-muscle protein synthesis | met |\n| Gunderman 2014 | 16 men, 26 +/- 1 y | rapamycin | 16 mg single dose 1 h before blood-flow-restricted re
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" references 19 studies"})
→ call web_search({"limit":10,"query":"\"10.1016/S2666-7568(23)00258-1\" rapamycin review pdf"})
→ call web_search({"limit":10,"query":"\"38310895\" rapamycin systematic review full text"})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" references 19 studies", "results": [{"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext", "snippet": "Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR, a major regulator of the ageing process. We aimed to summarise the effects of rapamycin and its derivatives on the severity of ageing-related physiological changes and disease in adults. A search across five databases yielded 18 400 unique articles, resulting in 19 included studies . Rapamycin and its derivatives improved ..."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.sciencedirect.com/science/article/pii/S2666756823002581", "snippet": "A search across five databases yielded 18 400 unique articles, resulting in 19 included studies . Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune, cardiovascular, and integumentary systems of healthy individuals or individuals with ageing-related diseases."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.researchgate.net/publication/377976071_Targeting_ageing_with_rapamycin_and_its_derivatives_in_humans_a_systematic_review", "snippet": "A recent systematic review of human studies suggested Rapamycin and it
【tool:web_search】
{"ok": true, "query": "\"10.1016/S2666-7568(23)00258-1\" rapamycin review pdf", "results": []}
【tool:web_search】
{"ok": true, "query": "\"38310895\" rapamycin systematic review full text", "results": []}
→ call web_fetch({"max_chars":12000,"url":"https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext"})
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
→ call search_memory({"limit":20,"query":"4360dd15 19 included studies rapamycin everolimus BEZ235 RTB101 kidney transplant liver transplant trial"})
→ call search_memory({"limit":20,"query":"4360dd15 Lancet Healthy Longevity 2024 rapamycin included studies names"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹
→ cal"}, {"title": "Iter-4360dd15-0009-transcript", "tags": "iteration transcript", "modified": "20260424175555000", "preview": "!! 第 9 轮执行轨迹 → call search_memory({\"limit\":10,\"query\":\"4360dd15 rapamycin rapalog human trial Table 1 remaining endpoint PMC review trial name primary endpoint\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Ite【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹
→ cal"}, {"title": "Iter-4360dd15-0009-transcript", "tags": "iteration transcript", "modified": "20260424175555000", "preview": "!! 第 9 轮执行轨迹 → call search_memory({\"limit\":10,\"query\":\"4360dd15 rapamycin rapalog human trial Table 1 remaining endpoint PMC review trial name primary endpoint\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Ite → call web_search({"limit":10,"query":"site:crossref.org 10.1016/S2666-7568(23)00258-1 references rapamycin"})
【tool:web_search】
{"ok": true, "query": "site:crossref.org 10.1016/S2666-7568(23)00258-1 references rapamycin", "results": []}
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" \"Table 1\" trial names"})
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" everolimus rapamycin trial names"})
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" cardiovascular immune integumentary trial"})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" \"Table 1\" trial names", "results": []}
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" everolimus rapamycin trial names", "results": []}
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" cardiovascular immune integumentary trial", "results": []}
→ call web_search({"limit":8,"query":"rapamycin everolimus human trial immune cardiovascular integumentary aging-related diseases review"})
→ call web_search({"limit":8,"query":"rapamycin trial cardiovascular integumentary humans everolimus topical review"})
→ call web_search({"limit":8,"query":"rapamycin human trial aging-related disease review immune skin cardiovascular"})
【tool:web_search】
{"ok": true, "query": "rapamycin everolimus human trial immune cardiovascular integumentary aging-related diseases review", "results": [{"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext", "snippet": "Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune , cardiovascular , and integumentary systems of healthy individuals or individuals with ageing- related diseases . Overall, no significant effects on the endocrine, muscular, or neurological systems were found."}, {"title": "Blazing a trail for the clinical use of rapamycin as a geroprotecTOR", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10643772/", "snippet": "The a priori goal of this review was to highlight ongoing and upcoming clinical trials testing the safety and utility of rapamycin to intervene in fundamental mechanisms of aging with the goal of slowing, improving, or restoring the age- related decline in physiological function."}, {"title": "Rapamycin Exerts Its Geroprotective Effects in the Ageing Human Immune ...", "url": "https://onlinelibrary.wiley.com/doi/10.1111/acel.70364", "snippet": "Similar to the clinical trial administering spermidine (Alsaleh et al. 2024), our findings using rapamycin allow us to speculate that the positive effect of 6-week treatment with the rapalogue RAD001 ( everolimus ) on boosting flu vaccine responses and respi
【tool:web_search】
{"ok": true, "query": "rapamycin trial cardiovascular integumentary humans everolimus topical review", "results": [{"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext", "snippet": "Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune, cardiovascular , and integumentary systems of healthy individuals or individuals with ageing-related diseases. Overall, no significant effects on the endocrine, muscular, or neurological systems were found."}, {"title": "Rapamycin for longevity: the pros, the cons, and future perspectives", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12226543/", "snippet": "A systematic review evaluated the effects of rapamycin and its derivatives on aging-related physiologic