Iter-4360dd15-0089-transcript
第 89 轮执行轨迹
→ call search_memory({"limit":8,"query":"4360dd15 38310895 引用链 原始人类试验 PMID 主要终点"}) → call list_recent({"n":8})
→ call list_by_tag({"limit":8,"tag":"4360dd15"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0060-transcript", "tags": "iteration transcript", "modified": "20260424200117000", "preview": "!! 第 60 轮执行轨迹
→"}, {"title": "Iter-4360dd15-0051-transcript", "tags": "iteration transcript", "modified": "20260424194527000", "preview": "!! 第 51 轮执行轨迹 → call search_memory({\"limit\":8,\"query\":\"4360dd15 PMID 38310895 reference chain Crossref 75 references human trial rapamycin everolimus sirolimus\"}) → call list_recent({\"n\":8}) → call list_tools({}) 【tool:search【tool:list_recent】
{"ok": true, "items": [{"title": "Iter-4360dd15-0088-reflection", "modified": "20260424205610000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424205610000", "tags": "pinned focus"}, {"title": "先锁定原始试验再谈终点", "modified": "20260424205610000", "tags": "lesson evidence-chain clinical-trials longevity"}, {"title": "Iter-4360dd15-0088-transcript", "modified": "20260424205606000", "tags": "iteration transcript"}, {"title": "Iter-4360dd15-0087-reflection", "modified": "20260424205350000", "tags": "iteration reflection"}, {"title": "综述只负责引路", "modified": "20260424205350000", "tags": "lesson classification citation-chain trial-audit"}, {"title": "Iter-4360dd15-0087-transcript", "modified": "20260424205344000", "tags": "iteration transcript"}, {"title": "Error-20260425-044942", "modified": "20260424204942000", "tags": "error iteration"}]}
【tool:list_by_tag】
{"ok": true, "items": [{"title": "PMID 33977284 is RTI incidence endpoint, not direct longevity evidence", "modified": "20260424204839000"}, {"title": "PMID 25540326 is immune-response endpoint, not longevity evidence", "modified": "20260424204718000"}, {"title": "PMID 27883166 is a pilot safety feasibility trial not direct longevity evidence", "modified": "20260424204543000"}, {"title": "PEARL trial is not direct longevity evidence", "modified": "20260424203525000"}, {"title": "Iter-4360dd15-0078-two-pmid-evidence-verification", "modified": "20260424203242000"}, {"title": "Iter-4360dd15-0077-unified-longevity-classification-four-pmids", "modified": "20260424203137000"}, {"title": "Iter-4360dd15-0075-abstract-field-extraction-two-pmids", "modified": "20260424202951000"}, {"title": "Iter-4360dd15-0072-review-exclusion-first-rule", "modified": "20260424202103000"}]}
→ call search_memory({"limit":10,"query":"4360dd15 PMID 38310895 reference PMID trial rapamycin everolimus sirolimus mTOR original"})
→ call read_note({"title":"NEXT_FOCUS"})
→ call read_note({"title":"Iter-4360dd15-0088-reflection"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0087-transcript", "tags": "iteration transcript", "modified": "20260424205344000", "preview": "!! 第 87 轮执行轨迹
→ call search_memory({\\\"limit\\\":10,\\\"query\\\":\\\"4360dd15 NEXT_FOCUS 剩余 10 条候选 PMID 研究类型 保留 排除 理由"}, {"title": "Iter-4360dd15-0053-transcript", "tags": "iteration transcript", "modified": "20260424194945000", "preview": "!! 第 53 轮执行轨迹 → call search_memory({\\\""}, {"title": "Iter-4360dd15-0083-transcript", "tags": "iteration transcript", "modified": "20260424204550000", "preview": "!! 第 83 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-0088）\n\n从 PMID 38310895 的参考文献里挑出 1 个尚未审计的原始人类试验 PMID，并只核实其主要终点。"}
【tool:read_note】
{"ok": true, "title": "Iter-4360dd15-0088-reflection", "tags": "iteration reflection", "text": "!! 本轮进展\n本轮确认了核心综述 PMID 38310895，并把下一步稳定收敛为从其引用链中寻找原始人类试验而不是继续泛搜。\n\n!! 失败 / 盲点\n仍然没有拿到一个尚未审计的原始试验 PMID，且受限于文献全文可达性，搜索停留在综述入口而未进入证据核查层。\n\n!! 下轮焦点\n从 PMID 38310895 的参考文献里挑出 1 个尚未审计的原始人类试验 PMID，并只核实其主要终点。\n"}
→ call pubmed_search({"limit":5,"query":"38310895"})
→ call web_search({"limit":5,"query":"PMID 38310895 references rapamycin everolimus sirolimus mTOR review"})
→ call wiki_search({"lang":"en","limit":5,"query":"38310895 mTOR inhibitors ageing review"})
【tool:pubmed_search】
{"ok": true, "query": "38310895", "results": [{"pmid": "38310895", "title": "Targeting ageing with rapamycin and its derivatives in humans: a systematic review.", "source": "Lancet Healthy Longev", "pubdate": "2024 Feb", "authors": ["Lee DJW", "Hodzic Kuerec A", "Maier AB"], "url": "https://pubmed.ncbi.nlm.nih.gov/38310895/"}]}
【tool:web_search】
{"ok": true, "query": "PMID 38310895 references rapamycin everolimus sirolimus mTOR review", "results": [{"title": "Target of rapamycin inhibitors (TOR‐I; sirolimus and everolimus) for ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6953317/", "snippet": "The place of target of rapamycin inhibitors (TOR‐I) ( sirolimus , everolimus ), which have different modes of action from other commonly used immunosuppressive agents, in kidney transplantation remains uncertain."}, {"title": "Sirolimus and Everolimus Pathway: Reviewing Candidate Genes ... - MDPI", "url": "https://www.mdpi.com/1422-0067/17/5/735", "snippet": "Sirolimus (SRL) was the first mammalian target of rapamycin inhibitor (mTOR-I) produced by the bacterium Streptomyces hygroscopicus and approved for renal transplantation. Everolimus (EVR), derived from sirolimus , contains a 2-hydroxy-ethyl chain in the 40th position that makes the drug more hydrophilic than SRL and increases oral bioavailability by approximately 10%-16% [1]."}, {"title": "Everolimus and sirolimus in the treatment of cardiac ... - Nature", "url": "https://www.nature.com/articles/s41390-025-04043-8", "snippet": "There are multiple case reports on use of mammalian target of rapamycin ( mTOR ) inhibitors, everolimus or sirolimus , in treatment of CRs."}, {"title": "Pharmacology of mammalian (mechanistic) target of rapamycin (mTOR ...", "url": "https://www.uptodate.com/contents/pharmacology-of-mammalian-mechanistic-target-of-rapamycin-mtor-inhibitor
【tool:wiki_search】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://en.wikipedia.org/w/api.php?action=query&list=search&srsearch=38310895+mTOR+inhibitors+ageing+review&srlimit=5&format=json'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
→ call search_memory({"limit":10,"query":"4360dd15 rapamycin everolimus sirolimus human trial PMID vaccine older adults endpoint"})
【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-4360dd15-0011-transcript", "tags": "iteration transcript", "modified": "20260424180153000", "preview": "!! 第 11 轮执行轨迹 → call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" PMC references"})
→ call web_search({"limit":10,"query":"site:pmc.ncbi.nlm.nih.gov 38310895 rapamycin humans systematic review reference"})
→ call web_search({"limit":10,"query":"\"38310895\" rapamycin humans systematic review PMC"})
【tool:web_search】
{"ok": false, "error": "[SSL: UNEXPECTED_EOF_WHILE_READING] EOF occurred in violation of protocol (_ssl.c:1028)"}
【tool:web_search】
{"ok": true, "query": "site:pmc.ncbi.nlm.nih.gov 38310895 rapamycin humans systematic review reference", "results": [{"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 physiological changes and diseases and found improvements in the immune, cardiovascular, and integumentary systems but not in the endocrine, muscular, or neurological systems (Lee et al., 2024)."}, {"title": "Influence of rapamycin on safety and healthspan metrics after one year ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12074816/", "snippet": "Notable among these is rapamycin , which is widely used for its purported longevity and healthspan benefits within the pro-longevity community [8]. While evidence supports a role for rapamycin in improving life- and health-spans in preclinical studies [9], little data exists on its clinical efficacy in normative aging humans ."}, {"title": "PMC Home", "url": "https://pmc.ncbi.nlm.nih.gov/", "snippet": "PMC is a free full-text archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health's National Library of Medicine (NIH/NLM)."}, {"title": "Rapamycin: one drug, many effects - PMC", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3972801/", "snippet": "The mammalian target of rapamycin (mTOR) signaling pathway is a master
【tool:web_search】
{"ok": true, "query": "\"38310895\" rapamycin humans systematic review PMC", "results": [{"title": "A systematic review study of Rapamycin", "url": "https://rapamycinlongevitylab.substack.com/p/a-systematic-review-study-of-rapamycin", "snippet": "Last month Ajla Hodzic Kuerec, Deborah Lee and Andrea Maier published a very interesting systematic review of Rapamycin and rapalogs (pubmed: 38310895 ). A systematic review is a review that gathers together different research studies within an area and based on that analyzes and summarizes these."}, {"title": "#rapamycin #longevityscience #healthspan #metabolichealth # ...", "url": "https://www.linkedin.com/posts/ranulf-crooke_rapamycin-longevityscience-healthspan-activity-7411401877105491968-uGEr", "snippet": "In humans , a 2024 Lancet Healthy Longevity review (PMID: 38310895 ) shows that rapamycin and its derivatives can improve some specific immune and skin-ageing markers, but we still lack long-term ..."}, {"title": "Systemic review study of Rapamycin : r/Rapamycin - Reddit", "url": "https://www.reddit.com/r/Rapamycin/comments/1bo5ogp/systemic_review_study_of_rapamycin/", "snippet": "Last month Ajla Hodzic Kuerec, Deborah Lee and Andrea Maier published a very interesting systematic review of Rapamycin and rapalogs (pubmed: 38310895 ). A systematic review is a review that gathers together different research studies within an area and based on that analyzes and summarizes these."}, {"title": "Contacts, Subscriber Numbers, Similar
→ call web_fetch({"max_chars":12000,"url":"https://pubmed.ncbi.nlm.nih.gov/38310895/"})
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://pubmed.ncbi.nlm.nih.gov/38310895/'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" PMC full text"})
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" pdf"})
→ call web_search({"limit":10,"query":"\"38310895\" \"Lancet Healthy Longev\" pdf"})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" PMC full text", "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://europepmc.org/article/MED/38310895", "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 ..."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.sciencedirect.com/science/article/pii/S2666756823002581", "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 t
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" pdf", "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": "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": "PDF Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.thelancet.com/pdfs/journals/lanhl/PIIS2666-7568(23)00258-1.pdf", "snippet": "Deborah J W Lee*, Ajla Hodzic Kuerec*, Andrea B Maier Rapamyc
【tool:web_search】
{"ok": true, "query": "\"38310895\" \"Lancet Healthy Longev\" pdf", "results": []}
→ call web_fetch({"max_chars":12000,"url":"https://www.thelancet.com/pdfs/journals/lanhl/PIIS2666-7568(23)00258-1.pdf"})
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://www.thelancet.com/pdfs/journals/lanhl/PIIS2666-7568(23)00258-1.pdf'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
→ call search_memory({"limit":20,"query":"4360dd15 rapamycin PMID trial original human endpoint pending audit"})
→ call search_memory({"limit":20,"query":"4360dd15 38310895 PMID 19 studies included"})
→ call list_by_tag({"limit":20,"tag":"fact classification clinical-trials longevity"})
【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 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 → 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\【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0060-transcript", "tags": "iteration transcript", "modified": "20260424200117000", "preview": "!! 第 60 轮执行轨迹
→"}, {"title": "Iter-4360dd15-0051-transcript", "tags": "iteration transcript", "modified": "20260424194527000", "preview": "!! 第 51 轮执行轨迹 → call search_memory({\"limit\":8,\"query\":\"4360dd15 PMID 38310895 reference chain Crossref 75 references human trial rapamycin everolimus sirolimus\"}) → call list_recent({\"n\":8}) → call list_tools({}) 【tool:search【tool:list_by_tag】
{"ok": true, "items": []}
→ call read_note({"title":"Iter-4360dd15-0041-transcript"})
→ call read_note({"title":"Iter-4360dd15-0046-transcript"})
→ call read_note({"title":"Iter-4360dd15-0048-transcript"})
【tool:read_note】
{"ok": true, "title": "Iter-4360dd15-0041-transcript", "tags": "iteration transcript", "text": "!! 第 41 轮执行轨迹\n\n
→ call search_memory({\\\"limit\\\":8,\\\"query\\\":\\\"4360dd15 PMID 38310895 reference chain Crossref 75 references human trial rapamycin everolimus sirolimus\\\"}) → call list_recent({\\\"n\\\":8}) → call list_tools({}) 【tool:search_memory】 {\\\"ok\\\": true, \\\"results\\\": [{\\\"title\\\": \\\"Iter-4360dd15-0010-transcript\\\", \\\"tags\\\": \\\"iteration transcript\\\", \\\"modified\\\": \\\"20260424175830000\\\", \\\"preview\\\": \\\"!! 第 10\"}, {\"title\": \"Iter-4360dd15-0038-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424191624000\", \"preview\": \"!! 第 38 轮执行轨迹 【tool:read_note】
{"ok": true, "title": "Iter-4360dd15-0046-transcript", "tags": "iteration transcript", "text": "!! 第 46 轮执行轨迹\n\n
\n → call search_memory({\"limit\":8,\"query\":\"4360dd15 PMID 38310895 mmc1.pdf supplementary table 19 studies NEXT_FOCUS\"})\n\n → call list_recent({\"n\":8})\n\n → call list_by_tag({\"limit\":10,\"tag\":\"4360dd15\"})\n\n【tool:search_memory】\n{\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0037-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424191347000\", \"preview\": \"!! 第 37 轮执行轨迹 → call search_memory({\\\"limit\\\":8,\\\"query\\\":\\\"4360dd15 rapamycin review 2024