Iter-4360dd15-0092-transcript
第 92 轮执行轨迹
→ call search_memory({"limit":10,"query":"4360dd15 38310895 PMID 原始人类试验 主要终点"}) → call list_recent({"n":8})
→ call list_by_tag({"limit":20,"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-4360dd15-0090-transcript", "tags": "iteration transcript", "modified": "20260424210019000", "preview": "!! 第 90 轮执行轨迹 → call search_memory({\\\"limit"}, {"title": "Iter-4360dd15-0051-transcript", "tags": "iteration transcript", "modified": "20260424194527000", "preview": "!! 第 51 轮执行轨迹 【tool:list_recent】
{"ok": true, "items": [{"title": "Iter-4360dd15-0091-reflection", "modified": "20260424210210000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424210210000", "tags": "pinned focus"}, {"title": "先锁定唯一引用再看终点", "modified": "20260424210210000", "tags": "lesson evidence-chain clinical-trials endpoint-classification"}, {"title": "Iter-4360dd15-0091-transcript", "modified": "20260424210157000", "tags": "iteration transcript"}, {"title": "PMID 22115710 is phase I ocular safety study, not longevity evidence", "modified": "20260424210145000", "tags": "4360dd15 fact clinical-trials knowledge"}, {"title": "Iter-4360dd15-0090-reflection", "modified": "20260424210023000", "tags": "iteration reflection"}, {"title": "先从综述引用链落到原始试验", "modified": "20260424210023000", "tags": "lesson evidence-chain clinical-trials citation-chain"}, {"title": "Iter-4360dd15-0090-transcript", "modified": "20260424210019000", "tags": "iteration transcript"}]}
【tool:list_by_tag】
{"ok": true, "items": [{"title": "PMID 22115710 is phase I ocular safety study, not longevity evidence", "modified": "20260424210145000"}, {"title": "PMID 29408453 is feasibility/safety pilot, not direct longevity evidence", "modified": "20260424210012000"}, {"title": "PMID 31761958 is skin-senescence endpoint, not longevity evidence", "modified": "20260424205759000"}, {"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"}, {"title": "Iter-4360dd15-0071-minimal-audit-rules", "modified": "20260424201843000"}, {"title": "Iter-4360dd15-0069-standardized-audit-table-two-trials", "modified": "20260424201621000"}, {"title": "Iter-4360dd15-0068-abstract-endpoint-extraction", "modified": "2026042420140
→ call read_note({"title":"NEXT_FOCUS"})
→ call read_note({"title":"PMID 22115710 is phase I ocular safety study, not longevity evidence"})
→ call list_tools({})
【tool:read_note】
{"ok": true, "title": "NEXT_FOCUS", "tags": "pinned focus", "text": "!! 下轮焦点（来自 mission 4360dd15 · Iter-0091）\n\n从 38310895 的参考文献中找出 1 个尚未审计的原始人类试验 PMID，并只核实它的主要终点。"}
【tool:read_note】
{"ok": true, "title": "PMID 22115710 is phase I ocular safety study, not longevity evidence", "tags": "4360dd15 fact clinical-trials knowledge", "text": "!! PMID 22115710 的主要终点核实\n\n''试验身份''\n- PMID: 22115710\n- 题名: A randomized, dose-escalation study of subconjunctival and intravitreal injections of sirolimus in patients with diabetic macular edema.\n- 设计: randomized, open-label, dose-escalating phase I study\n\n''主要终点''\n- 目标是评估单次结膜下（SCJ）或玻璃体内（IVT）sirolimus 注射的 安全性与耐受性\n- 这意味着它的主要终点是 安全/耐受，不是死亡、生存、健康寿命或失能自由生存\n\n''证据判定''\n- 该研究属于眼科局部给药的早期安全性剂量递增试验\n- 不能作为长生不老/寿命延长的人类证据\n\n''可复现检索''\n- PubMed 检索词: 22115710\n- web_search 结果摘要显示: “To evaluate the safety and tolerability ... Design: Randomized, open-label, dose-escalating phase I study.”\n- PubMed URL: https://pubmed.ncbi.nlm.nih.gov/22115710/\n"}
【tool:list_tools】
{"ok": true, "tools": [{"name": "search_memory", "description": "在 TiddlyWiki 长期记忆中按关键字搜索（支持中文空格分隔），返回标题、标签、预览。每轮迭代开始前应先调用以回忆。", "custom": false}, {"name": "read_note", "description": "读取某一条 tiddler 的完整正文。", "custom": false}, {"name": "write_note", "description": "向 TiddlyWiki 写入（或覆盖）一条 tiddler。这是 Sisyphus 的长期记忆入口——每轮至少写一条。建议标签：knowledge, experiment, reflection, plan, idea, fact, question, lesson。TiddlyWiki 标记：!! 小标题，''粗体''，斜体，其它tiddler。", "custom": false}, {"name": "list_recent", "description": "列出最近修改过的 tiddler。", "custom": false}, {"name": "list_by_tag", "description": "按标签列出相关 tiddler。", "custom": false}, {"name": "run_python", "description": "在 workspace/ 下以子进程执行一段 Python 代码，返回 stdout/stderr。用于计算、模拟、验证假设、抓取公开数据（禁止任何破坏性操作）。", "custom": false}, {"name": "read_file", "description": "读取 workspace/ 下的某个文件。", "custom": false}, {"name": "write_file", "description": "向 workspace/ 下写入文件（默认覆盖，append=true 时追加）。", "custom": false}, {"name": "list_files", "description": "列出 workspace/ 下的文件。", "custom": false}, {"name": "web_fetch", "description": "抓取任意公开 URL（GET），返回剥离 HTML 后的纯文本。适合读论文摘要、文档、博客、百科。", "custom": false}, {"name": "web_search", "description": "用 DuckDuckGo 搜索互联网，返回 title/url/snippet 列表。找入口、找链接、调研时用。", "custom": false}, {"name": "wiki_search", "description": "维基百科搜索：返回若干条目的摘要和 URL。lang 默认 en，可传 zh 等。", "custom": false}, {"name": "arxiv_search", "description": "arXiv 论文检索：标题/作者/摘要/链接。理论、数学、物理、CS、bio 类前沿论文的主入口。", "custom": false}, {"name": "pubmed_search", "descriptio
→ call pubmed_search({"limit":10,"query":"38310895"})
→ call web_search({"limit":10,"query":"PMID 38310895 references rapamycin human trial PMID"})
【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 human trial PMID", "results": [{"title": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/", "snippet": "PubMed® comprises more than 40 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full text content from PubMed Central and publisher web sites."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://europepmc.org/article/MED/38310895", "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."}, {"title": "Rapamycin's Effects on Human Aging Explored in New Study", "url": "https://www.newsweek.com/anti-aging-rapamycin-off-label-study-2110873", "snippet": "A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: Immunological, physical performance, and cognitive effects."}, {"title": "Blazing a trail for the clinical use of rapamycin as a geroprotecTOR", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10643772/", "snippet": "It is important to note that this is not an endorsement for or against the use of mTOR inhibitors, but rather a compendium of upcoming clinical trials leveraging the last two decades of pre-clinical data to help advance our understanding of the i
→ call web_fetch({"max_chars":12000,"url":"https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext"})
→ call web_fetch({"max_chars":12000,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10643772/"})
→ call web_fetch({"max_chars":12000,"url":"https://europepmc.org/article/MED/38310895"})
【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"}
【tool:web_fetch】
{"ok": true, "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10643772/", "status": 200, "content_type": "text/html; charset=utf-8", "text": "Blazing a trail for the clinical use of rapamycin as a geroprotecTOR - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice GeroScience . 2023 Oct 6;45(5):2769–2783. doi: 10.1007/s11357-023-00935-x Search in PMC Search in PubMed View in NLM Catalog Add to search Blazing a trail for the clinical use of rapamycin as a geroprotecTOR Adam R Konopka Adam R Konopka 1 Division of Geriatrics, Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705 USA 2 William S. Middlet
【tool:web_fetch】
{"ok": true, "url": "https://europepmc.org/article/MED/38310895", "status": 200, "content_type": "text/html;charset=UTF-8", "text": "Europe PMC Europe PMC 1 Sign in | Create an account https://orcid.org https://plus.europepmc.org Europe PMC Menu About About Europe PMC Preprints in Europe PMC Funders Become a funder Governance Roadmap Outreach Tools Tools overview Article status monitor Grant finder External links service RSS feeds About SciLite annotations Annotations submission service Developers Developer resources Articles RESTful API Grants RESTful API API case studies SOAP web service Annotations API OAI service Bulk downloads Developers Forum Support User guide Search syntax guide Contact us Contact us Helpdesk Feedback Twitter Blog Tech blog Developer Forum Europe PMC plus NOTICE: The ORCID Claiming tool has been temporarily disabled, because of technical issues. Please check back in later.", "truncated": false}
→ call pubmed_search({"limit":10,"query":"rapamycin amino acid infusion peripheral insulin sensitivity healthy young men placebo crossover"})
→ call pubmed_search({"limit":10,"query":"rapamycin resistance exercise mixed-muscle protein synthesis randomized placebo men"})
→ call pubmed_search({"limit":10,"query":"rapamycin blood flow restricted resistance exercise mixed muscle protein synthesis"})
→ call pubmed_search({"limit":10,"query":"rapamycin healthy young men insulin clamp amino acid infusion PMID"})
【tool:pubmed_search】
{"ok": true, "query": "rapamycin amino acid infusion peripheral insulin sensitivity healthy young men placebo crossover", "results": []}
【tool:pubmed_search】
{"ok": true, "query": "rapamycin resistance exercise mixed-muscle protein synthesis randomized placebo men", "results": []}
【tool:pubmed_search】
{"ok": true, "query": "rapamycin blood flow restricted resistance exercise mixed muscle protein synthesis", "results": [{"pmid": "24691032", "title": "Activation of mTORC1 signaling and protein synthesis in human muscle following blood flow restriction exercise is inhibited by rapamycin.", "source": "Am J Physiol Endocrinol Metab", "pubdate": "2014 May 15", "authors": ["Gundermann DM", "Walker DK", "Reidy PT", "Borack MS", "Dickinson JM", "Volpi E", "Rasmussen BB"], "url": "https://pubmed.ncbi.nlm.nih.gov/24691032/"}, {"pmid": "22362401", "title": "Reactive hyperemia is not responsible for stimulating muscle protein synthesis following blood flow restriction exercise.", "source": "J Appl Physiol (1985)", "pubdate": "2012 May", "authors": ["Gundermann DM", "Fry CS", "Dickinson JM", "Walker DK", "Timmerman KL", "Drummond MJ", "Volpi E", "Rasmussen BB"], "url": "https://pubmed.ncbi.nlm.nih.gov/22362401/"}, {"pmid": "21606874", "title": "Exercise, amino acids, and aging in the control of human muscle protein synthesis.", "source": "Med Sci Sports Exerc", "pubdate": "2011 Dec", "authors": ["Walker DK", "Dickinson JM", "Timmerman KL", "Drummond MJ", "Reidy PT", "Fry CS", "Gundermann DM", "Rasmussen BB"], "url": "https://pubmed.ncbi.nlm.nih.gov/21606874/"}]}
【tool:pubmed_search】
{"ok": true, "query": "rapamycin healthy young men insulin clamp amino acid infusion PMID", "results": []}
→ call search_memory({"limit":10,"query":"4360dd15 24691032"})
→ call search_memory({"limit":10,"query":"4360dd15 21606874"})
→ call search_memory({"limit":10,"query":"4360dd15 22362401"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0060-transcript", "tags": "iteration transcript", "modified": "20260424200117000", "preview": "!! 第 60 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 extension follow-up secondary analysis\"}) → call list_recent({\"n\":10}) → call list_tools({}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0059-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424195947000\", \"preview\": \"!! 第 59 轮执行轨迹 → call search_memory({\"limit\":8,\"query\":\"4360dd15 38310895 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 → 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:sear【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-4360dd15-0090-transcript", "tags": "iteration transcript", "modified": "20260424210019000", "preview": "!! 第 90 轮执行轨迹 → call search_memory({\\\"limit"}, {"title": "Iter-4360dd15-0037-transcript", "tags": "iteration transcript", "modified": "20260424191347000", "preview": "!! 第 37 轮执行轨迹 【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0060-transcript", "tags": "iteration transcript", "modified": "20260424200117000", "preview": "!! 第 60 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 extension follow-up secondary analysis\"}) → call list_recent({\"n\":10}) → call list_tools({}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0059-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424195947000\", \"preview\": \"!! 第 59 轮执行轨迹 → call search_memory({\"limit\":8,\"query\":\"4360dd15 38310895 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 → 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:sear → call pubmed_search({"limit": 5, "query": "24691032"})
【tool:pubmed_search】
{"ok": true, "query": "24691032", "results": [{"pmid": "24691032", "title": "Activation of mTORC1 signaling and protein synthesis in human muscle following blood flow restriction exercise is inhibited by rapamycin.", "source": "Am J Physiol Endocrinol Metab", "pubdate": "2014 May 15", "authors": ["Gundermann DM", "Walker DK", "Reidy PT", "Borack MS", "Dickinson JM", "Volpi E", "Rasmussen BB"], "url": "https://pubmed.ncbi.nlm.nih.gov/24691032/"}]}
→ call web_fetch({"max_chars":9000,"url":"https://pubmed.ncbi.nlm.nih.gov/24691032/"})
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://pubmed.ncbi.nlm.nih.gov/24691032/'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
→ call web_search({"limit":10,"query":"24691032 abstract primary endpoint rapamycin blood flow restriction exercise inhibited by rapamycin"})
【tool:web_search】
{"ok": true, "query": "24691032 abstract primary endpoint rapamycin blood flow restriction exercise inhibited by rapamycin", "results": [{"title": "Activation of mTORC1 signaling and protein synthesis in human muscle ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4116405/", "snippet": "We conclude that activation of mTORC1 signaling and protein synthesis in human muscle following BFR exercise is inhibited in the presence of rapamycin . Keywords: blood flow restriction exercise , mammalian target of rapamycin , mammalian target of rapamycin complex 1, rapamycin , fractional synthetic rate"}, {"title": "Activation of mTORC1 signaling and protein synthesis in human muscle ...", "url": "https://europepmc.org/article/MED/24691032", "snippet": "Activation of mTORC1 signaling and protein synthesis in human muscle following blood flow restriction exercise is inhibited by rapamycin ."}, {"title": "Activation of mTORC1 signaling and protein synthesis in human muscle ...", "url": "https://database.clin-star.org/display/pmid-24691032", "snippet": "Humans Male Mechanistic Target of Rapamycin Complex 1 Multiprotein Complexes Muscle Contraction Muscle, Skeletal Protein Biosynthesis Regional Blood Flow Signal Transduction Sirolimus TOR Serine-Threonine Kinases Young Adult blood flow restriction exercise fractional synthetic rate mammalian target of rapamycin mammalian target of rapamycin ..."}, {"title": "Activation of mTORC1 signaling and protein synthesis in human muscle ...", "url
→ call web_fetch({"max_chars":12000,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4116405/"})
【tool:web_fetch】
{"ok": true, "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4116405/", "status": 200, "content_type": "text/html; charset=utf-8", "text": "Activation of mTORC1 signaling and protein synthesis in human muscle following blood flow restriction exercise is inhibited by rapamycin - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Am J Physiol Endocrinol Metab . 2014 Apr 1;306(10):E1198–E1204. doi: 10.1152/ajpendo.00600.2013 Search in PMC Search in PubMed View in NLM Catalog Add to search Activation of mTORC1 signaling and protein synthesis in human muscle following blood flow restriction exercise is inhibited by rapamyci
→ call write_note({"tags":["4360dd15","fact","knowledge","clinical-trials","endpoint-classification"],"text":"!! PMID 24691032 的主要终点核实\n\n''试验身份''\n- PMID: 24691032\n- 题名: Activation of mTORC1 signaling and protein synthesis in human muscle following blood flow restriction exercise is inhibited by rapamycin.\n- 设计: 16 名健康年轻男性，随机分配至 rapamycin 组与对照组；两组都完成 BFR（blood flow restriction）exercise。\n\n''主要终点''\n- 论文摘要明确写道：研)
【tool:write_note】
{"ok": true, "path": "C:\\Users\\yh599\\Documents\\GitHub\\LLM-yh\\Sisyphus\\wiki\\tiddlers\\PMID_24691032_is_muscle-protein-synthesis_endpoint_not_longevity_evidence.tid", "title": "PMID 24691032 is muscle-protein-synthesis endpoint, not longevity evidence"}
【assistant】
本轮完成了一个最窄、可核实的子任务：从综述 PMID 38310895 的引用链里选出一个原始人类试验 PMID **246