碳基生物生存指南

如果回到千年以前，这日子估计不好过，没人懂病毒，没人懂细胞，所有的医学科学都围绕着几乎无法被推翻的传统和宗教。但，在这所有的混乱和落后中，护肤，却好像一直没变。 从流程来说：清洁，保湿，去角质，甚至功能性的护理；从成分上来说：酒石刷酸，大麦爽肤，还有蜂蜜藏红花... 好像这么多年下来，也都是从自然中取样。 护肤这件事儿反馈及时、迭代快，经验医学就格外好用，以至于把理论研究抛在了千年以后的现在。但，在我们理解病毒，理解细胞之后，好多事儿也变了。从机制原理，我们更能知道什么物质好，它如何起效，以及是否能改进和编辑这些天然成分，来更好地为我们所用。 护肤史，也是医学史，也是科学史。 本期节目，由 碳基生物生存指南 的梦妮 和 美业Ken大瓜 的Ken共创，一起聊聊这千年以来护肤的过去，现在，和未来。 特别感谢娇兰对本期节目的支持 ✨ 御廷兰花系列20周年，万代兰御龄精华以再生科技结合兰花本身的非凡生命力，打造全方位抗老护肤体验。面霜质地舒适，成分天然，能显著改善12种衰老指标。以皮肤为蓝本，开启下一个抗衰时代 🌸 【时间轴】 01:41 在不了解细胞的千年以前，我们就护肤了？ 08:11 透明质酸…是从牛眼睛里来的！ 12:38 透明质酸在眼睛里干嘛？ 18:12 大分子皮肤真的可以吸收吗？ 23:02 娇兰万代兰御龄精华✨ 27:00 肉毒杆菌是真的毒，极为可怕的毒 32:25 一个生化武器，如何怎么走向皮肤？ 35:48 肉毒杆菌 vs 肉毒肽生物机制对比 38:57 肉毒肽如何进入皮肤？ 41:22 胶原蛋白到底是什么？ 47:02 我们如何吸收胶原蛋白，它有什么作用？ 52:51 皮肤，新科技的试验台 57:56 5-10 年后，护肤科学的未来期待 本期音乐：Pixabay（免版权音乐库）vicatestudio-beautiful-christmas-short-3-512320，finley-chill-sunset-chill-nature-529994

如果顶尖医学专家告诉你，针对你的癌症，所有已验证的疗法都已用尽，你会怎么做？如果给你无限的资源，你会从哪里入手，为自己博一线生机？ 这个问题，曾经摆在 Sid Sijbrandij 面前。他很普通，不是博士不是医生更不是学者，在生物医学面前，他只拥有基本的常识；但他，也不普通，乘着网络信息技术的爆发，他是一位白手起家的亿万富翁，拥有几乎无限的资源和财富。 在大部分情况下，这两者组合在一起都不会有什么好结果：过度自信，用做互联网的方式解构生物，被学界诟病嘲讽。但，他却成功召集了自身癌症领域的顶尖医生，免疫学家，病理学家，生物信息分析师，让大家都愿意一起试一试，在标准治疗以外，是不是还有路可走，该怎么走。 结果，还真被他走通了。癌症复发至今已有一年多，他身体内，没有疾病证据。 细看这个故事，他这一路很不容易，靠极强的学习能力拉齐了与专家沟通的知识差距，在无人领域试着在旧系统里找新出路。但更重要的是，他做对了很多事，从深度全方位不计目的地检测，到以个体为导向的单人临床实验。而不能更巧的是，就在这期播客上线的7个小时前，莫德纳宣布自己完成了个性化新抗原疗法的黑色素瘤三期临床，结果喜人。这位亿万富翁两年前的经历，此刻，似乎正在更多人身上被验证。 看到新闻的时候我想到一句话：“未来常常是缓慢地，然后突然地到来。”也许，我们现在就处在一切即将被改写、这样一个激动的，慌乱的，又最让人屏息以待的时刻。 【时间轴】 03:41 Sid 患病前的人生，美国梦的成功范本 06:50 Sid 所患的骨肉瘤，为什么这么难治，现在能怎么治？ 12:32 癌症复发，标准治疗已无药可医 20:09 Sid 的选择：不放弃，但也不盲目 24:28 最大化检测 - 单细胞测序，是什么？ 34:27 靶向 PET，靶向治疗的试验场 38:25 类器官构建，用体外分身试新药 39:41 一切的转折点 47:06 取样，怎么会这么难 - 你的组织，不是你的组织 54:25 如何让医生，信任你？ 64:47 单人临床实验，怎么过伦理监管？ 69:27 单人临床实验的中国体系 72:19 vs 美国体系，中美对比，哪个好？ 80:42 为了活，毫无保留的全方位投入，你愿意吗？ 87:08 个性化医疗的未来长什么样？ 91:51 现在该做些什么，让我们离未来更近一些？ 📃 本期播客提到的文献素材传送门： * 莫德纳个性户新抗原疗法原理及新闻稿： https://www.modernatx.com/media-center/all-media/blogs/individual.neoantigen-therapies ， https://news.modernatx.com/merck-and-moderna-announce-phase-3-interpath-001-trial-of-intismeran-plus-keytruda-met-endpoints-of-rfs-and-dmfs-in-melanoma * Sid 所有治疗及检测数据： https://osteosarc.com/#news * Sid 新闻报道（诊疗全记录）： https://centuryofbio.com/p/sid * Sid 个人网站： https://sytse.com/cancer/ * Future of Cancer Care Today（未来癌症治疗）免费咨询及资料分享： https://sijbrandijfoundation.org/fcct#resources * 美国学者呼吁FDA对新药研发的审批监管应更灵活： https://journals.sagepub.com/doi/full/10.1089/genedge.7.1.070 * Even one（哪怕只有一位）在投企业名录： https://evenone.ventures * 拓展资料：Sid Sijbrandij 的故事在叙述中有极大简述，包括在标准治疗阶段，Sid 就尝试过单人用药，以及 Sid 有广泛地使用 mRNA 疫苗技术，Sid 的完整诊疗过程可参见上述文献。另外，本期叙述还参考了 Sid 在多个播客接受的访谈，包括与 OpenAI （https://academy.openai.com/public/blogs/sid-sijbrandij-chatgpt-cancer-research） ，Outperform Cancer with MB Gilliam， Changelog，Infinita City。感兴趣的话，我最推荐 Sid 在 OpenAI 的演讲～ * 03:02 处的混剪内容均取自 Claude AI for Science 发布会： https://www.anthropic.com/events/the-briefing-ai-for-science-virtual-event 本期音乐：Pixabay（免版权音乐库）alanajordan-sprinkles-and-twinkles-263938，mickeyscat-moment-of-peace-mickeyscat-554494 封面设计特别感谢：wow lab 小红书账号：梦妮爱读文献 （ID：4196506308）

我们好像总是很累。身体提不上劲，心理也没有动力，感觉活着本身，就已经很累了。 这样低精力也总是跟没有目标、没有动力、倦怠、畏难绑在一起，好像谁都不想被贴上这个标签。但高精力就一定好吗？他们似乎从来感觉不到累，但会不会当真的垮下来的时候，才发现其实一直在透支。 所以，精力到底是什么，为什么日常生活就让人如此疲惫？精力真的是天生的吗？低精力的人，真的可以获得世俗意义上的成功吗？如果想要提升精力，除了人人都知道的睡好吃好运动好，还有其他解法吗？ 本期节目就想在这个话题上，对疲惫和精力，做一次更底层的拆解。希望能帮你在信息繁杂的方法论之外，真正了解精力，了解疲惫。从原理和数据入手，我们也终于可以回答：那些看起来精力充沛的“高精力人群”和似乎总容易疲惫的“低精力人群”，到底有没有优劣之分。 【时间轴】 05:03 计算每日卡路里消耗时，你会忽视什么 09:37 为啥我喝水都胖、哪怕吃了很多也懒得动 - 也许是因为你对能量的敏感性不够 17:20 心理疲惫从何而来 - 人与人间的动机响应敏感性差异 19:30 衡量疲惫时的主观感受和客观指标，到底哪个更可靠？ 22:42 该如何正确看待智能设备的数据焦虑 23:49 关于疲惫的客观指标：运动表现，静息心率，心率变异性 28:20 主观疲惫的不同分类测量 31:36 恢复和休息本身，就是进步的一部分 38:28 做自己感兴趣的事情还能拿到钱，怎么反而越做越没劲 44:34 钱，怎么会没用呢..？ 48:11 你的动力来源 - 基本心理需求：胜任感，归属感，自主性 49:35 为什么有些事儿你超有动力做，几乎让人上瘾？ 54:32 胜任感，归属感，自主性如何帮我们在生活中找回动力 58:07 我们该谈钱，但不能只谈钱 59:58 高精力 vs 低精力，到底谁好谁坏呢？ 62:07 低精力人群，也可以获得世俗意义上的成功；而高精力人群，也有需要注意的风险点 本期节目特别感谢 Eight Sleep 赞助播出。 Eight Sleep 智能温控床套搭配 AI 睡眠系统，为你动态调温，优化睡眠质量，帮助你在理解疲惫之外，能更好地从疲惫中恢复过来。🎁 碳基生物生存指南的听众可领取1000元的专属优惠券～ 听友们在天猫/京东/Eight Sleep小程序商城，联系客服，报出【碳基生物生存指南】暗号，就可以领取～ 天猫优惠券点击这里领取 👈 京东优惠券点击这里领取 👈 📃 本期播客提到的文献素材传送门： 第一部分 身体和心理的精力输出，比你想得要复杂得多 NEAT 在每日能量消耗的占比： https://journals.physiology.org/doi/full/10.1152/ajpendo.00562.2003 ：“EAT is therefore the most variable component of energy expenditure, both within and between subjects, ranging from ∼15% of total daily energy expenditure in very sedentary individuals to 50% or more of total daily energy expenditure in highly active individuals” 活动不足人群比例： https://pmc.ncbi.nlm.nih.gov/articles/PMC10351178/ ：“From 2010 to 2018, the age-adjusted prevalence of insufficient PA in China increased from 17.9% (95% confidence interval 16.3% to 19.5%) in 2010 to 22.3% (20.9% to 23.8%) in 2018 (P for trend < 0.001).”， https://www.ncbi.nlm.nih.gov/books/NBK279077/ ：“For the majority of subjects in industrialized countries, exercise is believed to be negligible. 不同人每天1000大卡的能量摄入实验： https://pubmed.ncbi.nlm.nih.gov/9880251/ NEAT 激活者与 NEAT 保存者： https://www.mayoclinicproceedings.org/article/S0025-6196(15)00123-8/fulltext：“NEAT activators are those animals with a copious and robust NEAT signal, and NEAT conservers have a blunted response to NEAT signals and expend lower levels of energy, resulting in obesity.” NEAT 遗传水平，测量的是体力活动水平，不是直接测量NEAT敏感度。但这两者方向上是一致的： https://journals.physiology.org/doi/full/10.1152/ajpendo.00562.2003 ：“On the basis of twin and family studies, the heritability for physical activity level is estimated to be between 29 and 62%.” 影响 NEAT 敏感性的非基因因素： https://www.mayoclinicproceedings.org/article/S0025-6196(15)00123-8/fulltext ：“The genetic regulation of NEAT is possibly influenced by multiple neuromediators located in the hypothalamus, including orexin, neuromedin U, ghrelin, and the agouti gene–related protein. This, plus the conditioning of the environment to different levels of physical activity and the behavioral factors that we learned from our main educators, will determine an individual to be a NEAT activator or a NEAT conserver, predisposing us to spend more time either sitting or moving. ” 所有人格特质的可遗传性元分析： https://pubmed.ncbi.nlm.nih.gov/25961374/ 生理 vs 心理，疲劳 vs 精力互相独立却也互相影响： https://www.tandfonline.com/doi/full/10.1080/21641846.2019.1573790 ：”Trait physical and mental fatigue were moderately correlated (r = .59, p < .001; table in online appendix). A similar association was found for physical and mental energy (r = .50, p < .001). Mental energy and fatigue were also associated (r =−.30, p < .001), as was physical energy and fatigue (r =−.32, p < .001). Interestingly, physical energy was not associated with mental fatigue (r =−.07, p = .67), but there was a small but signicant correlation between physical fatigue and mental energy (r =−.23, p < .001).“ 睡眠客观数据与主观感受并不匹配： https://pubmed.ncbi.nlm.nih.gov/27889439/ ：“Thirty-eight sleep, demographic and clinical correlates of sleep quality were considered. Together, these multivariable models explained only 11-17% of the variance in predicting subjective sleep quality.“ , “Overall, the commonly obtained measures of polysomnographically-defined sleep contributed little to subjective ratings of prior-night sleep quality.” 以及反例： https://academic.oup.com/sleep/article-abstract/26/2/117/2709164 ：“ Sleepiness ratings suggest that subjects were largely unaware of these increasing cognitive deficits, which may explain why the impact of chronic sleep restriction on waking cognitive functions is often assumed to be benign.” 主观疲惫水平会影响运动表现，但不是通过客观指标： https://journals.physiology.org/doi/full/10.1152/japplphysiol.91324.2008 ：“This negative effect was not mediated by cardiorespiratory and musculoenergetic factors as physiological responses to intense exercise remained largely unaffected.” 第二部分 疲惫，能被准确测量和预判吗 职业运动员客观测量指标： https://www.thieme-connect.com/products/ejournals/html/10.1055/a-2433-3930 HRV 高还是低好？该如何关注？（7 天均值测量） https://pmc.ncbi.nlm.nih.gov/articles/PMC11204851/：“A high HRV relative to baseline represents a healthy, flexible autonomic system and improved adaptability and recovery in response to a changing environment or stressor, such as travel or exercise.”，“valuating rolling 7-day averages of an individual’s HRV compared to daily values may provide a more meaningful context on HRV changes and overtraining compared to daily measurements or population norms.” 长期训练导致静息心率降低的具体机制： https://pubmed.ncbi.nlm.nih.gov/24825544/ ：“Endurance athletes exhibit sinus bradycardia, that is a slow resting heart rate, associated with a higher incidence of sinus node (pacemaker) disease and electronic pacemaker implantation.” 运动表现的客观变化是过度训练： https://pmc.ncbi.nlm.nih.gov/articles/PMC9460078/ ：“Functional overreaching is defined as a short-term decrease in performance (usually up to 2 weeks) followed by a supercompensation effect (adaptive improvement in performance). In cases where the performance decrement is of a slightly longer duration (usually up to 3-4 weeks) and not followed by supercompensation, the term nonfunctional overreaching is used. Finally, if reduced performance capacity lasts for more than 3 to 4 weeks and is followed by neither supercompensation nor improved athletic performance, the athlete is likely experiencing an overtraining syndrome (OTS).” 运动员倦怠程度评估： https://pubmed.ncbi.nlm.nih.gov/28682196/ ， 在线问卷： https://psytests.org/sport/abqen.html 通用的倦怠程度评估问卷： https://onlinelibrary.wiley.com/doi/pdf/10.1002/job.4030020205 ， 在线问卷： https://www.mindgarden.com/117-maslach-burnout-inventory-mbi 第三部分 自我决定理论 奖励，会削弱自主性： https://selfdeterminationtheory.org/SDT/documents/1983_RyanMimsKoestner.pdf：“Rewards in general appear to have a controlling significance to some extent and thus in general run the risk of undermining intrinsic motivation.“ 移除奖励后动力减弱（MRI 研究）： https://www.pnas.org/doi/full/10.1073/pnas.1013305107 ：“The strong incentive value of monetary reward pushed down the intrinsic value of task success. As a result, when the monetary reward was no longer promised, the intrinsic task value was underestimated, resulting in decreased motivation relative to the control group.” 关于奖励削弱动力的系统性综述： https://psycnet.apa.org/doiLanding?doi=10.1037%2F0033-2909.125.6.627 ：“As predicted, engagement-contingent, completion-contingent, and performance-contingent rewards significantly undermined free-choice intrinsic motivation (d = –0.40, –0.36, and –0.28, respectively), as did all rewards, all tangible rewards, and all expected rewards.” 自我决定论 - 胜任感，链接感，自主性决定动力： https://selfdeterminationtheory.org/SDT/documents/2000_RyanDeci_SDT.pdf 胜任感，链接感，自主性能预测玩家是否持续玩游戏： https://selfdeterminationtheory.org/SDT/documents/2006_RyanRigbyPrzybylski_MandE.pdf ：“Results show that SDT’s theorized needs for autonomy, competence, and relatedness independently predict enjoyment and future game play.“ 需求密度假说 - 最容易沉迷于电子游戏的孩子，是在日常生活中得不到胜任感，链接感，自主性满足的孩子： https://www.sciencedirect.com/science/article/abs/pii/S074756321830092X ：“As expected, we found strong support for the need-density hypothesis in terms of need satisfaction.” 生活幸福感直接影响线粒体效能： https://pubmed.ncbi.nlm.nih.gov/38889126/ ：“By combining longitudinal antemortem assessments of psychosocial factors with postmortem brain (dorsolateral prefrontal cortex) proteomics in older adults, we find that higher well-being is linked to greater abundance of the mitochondrial OxPhos machinery, whereas higher negative mood is linked to lower OxPhos protein content. Combined, positive and negative psychosocial factors explained 18 to 25% of the variance in the abundance of OxPhos complex I, the primary biochemical entry point that energizes brain mitochondria.” 第四部分 低精力人 vs 高精力人？ 同一个人一天内疲劳感的变化大于人与人之间的区别： https://pmc.ncbi.nlm.nih.gov/articles/PMC9124457/ ：“The majority of the variance for relaxation, satisfaction, insecurity, anxiousness, irritation, feeling down, fatigue, dizziness, intention, and self-efficacy is explained by the within subjects and within days variance (42.9% to 65.8%).” 外向型 vs 内向型领导优劣势对比： https://psycnet.apa.org/record/2011-15936-006 ：“Extraversion predicts leadership emergence and effectiveness, but do groups perform more effectively under extraverted leadership? Drawing on dominance complementarity theory, we propose that although extraverted leadership enhances group performance when employees are passive, this effect reverses when employees are proactive, because extraverted leaders are less receptive to proactivity.” 尽责性最能预测职业成功： https://www.sciencedirect.com/science/article/pii/S2352250X25000673 ：“Conscientiousness is the strongest predictor across performance outcomes.” https://www.sciencedirect.com/science/article/abs/pii/S0092656619300753 ：“A general conclusion from this literature is that conscientiousness is the strongest predictor of job performance among FFM traits for most jobs.” 拓展资料 * 现在越来越多的研究指出，疲劳和精力的驱动来源并不一致，背后的生理机制也不尽相同。研究者Loy等人（2013、2018）发现，主观精力感与多巴胺水平相关，而主观疲惫感则与血清素升高、组胺下降和炎症细胞因子升高相关，是两条独立的神经化学通路。在身体层面，客观疲惫的核心机制是肌肉代谢产物的积累（糖原耗竭、乳酸、无机磷酸盐），而客观身体精力的生物学基础更接近线粒体的ATP产能效率。这意味着：不管是身体还是心理层面，你都可以在很累的同时，仍然很有精力，两者不是一根轴上的两端，而是可以独立变化的两个维度。这一点在Boolani & Manierre（2019）的研究数据里得到了验证。本期播客没有详细探讨这个区分，如果你感兴趣，可以参考以下研究： Loy, Bryan D., Patrick J. O'Connor, and Rodney K. Dishman. "The effect of a single bout of exercise on energy and fatigue states: a systematic review and meta-analysis." Fatigue: Biomedicine, Health & Behavior1.4 (2013): 223-242. https://www.tandfonline.com/doi/full/10.1080/21641846.2013.843266 Loy, Bryan D., Michelle H. Cameron, and Patrick J. O'Connor. "Perceived fatigue and energy are independent unipolar states: Supporting evidence." Medical Hypotheses 113 (2018): 46-51. https://pmc.ncbi.nlm.nih.gov/articles/PMC5846196/ Boolani, Ali, and Matt Manierre. "An exploratory multivariate study examining correlates of trait mental and physical fatigue and energy." Fatigue: Biomedicine, Health & Behavior 7.1 (2019): 29-40. https://www.tandfonline.com/doi/full/10.1080/21641846.2019.1573790 饮食方案会影响活力水平，与低血糖负荷饮食相比，高血糖负荷饮食与更高的抑郁症状、总体情绪紊乱和疲劳感相关，尤其是在超重/肥胖但其他方面健康的成年人中： https://pmc.ncbi.nlm.nih.gov/articles/PMC5154680/ ：“In conclusion, a high-glycemic load diet was associated with higher depression symptoms, total mood disturbance, and fatigue compared to a low-glycemic load diet especially in overweight/obese, but otherwise healthy, adults.” 大脑耗能变化 - 虽然大脑仅占体重的2%，但它却消耗了人体20%的静息代谢。但同时，目标导向认知活动的代谢成本仅比静息神经活动和体内平衡的持续成本高出5%（每日能量总代谢变化量的1%。也就是说，你苦思冥想和躺着放松，脑部消耗的卡路里变化极小，但你却能感觉到真实的疲惫。因此，心理疲惫与卡路里消耗是相关，但独立的。”： https://www.sciencedirect.com/science/article/abs/pii/S136466132400319X ：“Although it accounts for only 2% of body weight, the human brain accounts for 20% of its resting metabolism, more than tenfold the amount expected based on its weight.”, “The metabolic costs of goal-directed cognition are only 5% greater than the ongoing costs of resting neural activity and homeostasis.” 周末效应 - 用自我决定理论来解释为什么周末的人类，都会更开心： https://selfdeterminationtheory.org/SDT/documents/2010_RyanBernsteinBrown_Weekends_JSCP.pdf ：“Results supported these hypotheses, showing that for both male and female workers, weekend and nonwork activities were associated with several indicators of well-being, and these relations were partially or fully mediated by basic psychological need satisfaction.“ 本期音乐：Epidemic Sound，Pixabay（免版权音乐库）Tired by Mindme，Sunset Chill Nature by Finley chill 封面设计特别感谢：wow lab 小红书账号：梦妮爱读文献 （ID：4196506308）

“那个”，大姨妈，生理期，例假。月经，她有过很多名字，但，却好像一直没有被好好地正视过。 如果不是做这期播客，我不会知道原来职业女性运动员，月经紊乱和闭经比例能达到60%，而且，这不是正常训练的结果，也不应被视为努力冲刺的勋章。我也不会知道，原来经期的子宫，在完成着人类世界里唯一的大规模无疤痕修复，而曾被污名化的经血，现在也是再生医学的研究热点之一。我更不会知道，整个代谢研究领域，至今都还没有高质量的研究，能回答这个很简单的问题：对于有月经的女性来说，断食，到底意味着什么？ 长久以来，现代医学研究都系统性地忽视了女性、避开了月经。因为月经，她太复杂又太难标准化。但这也意味着，月经，是足够敏感的，她是一个信号，所能反应的远不止是生殖，还有你身体的整体健康状态。 今天，我们就一起来看看这第五项生命体征 - 月经。她到底是什么，又能如何指导我们的生活。 🩸注：正常月经周期 24-38天，以28天为例：1-5天 经期；1-13天 卵泡期（包括经期，本期节目里为简化经期和卵泡期分开叙述）；14-28天 黄体期。 【时间轴】 01:05 Enhanced Games 嗑睾酮的女运动员们，还好吗？ 04:13 想当职业运动员，就逃不开闭经？ 07:41 月经，不止生育，还是女性的生命体征 13:24 从细胞层面看经期，子宫到底在发生什么？ 18:15 成人后唯一的无疤痕修复：子宫内膜 23:56 月经的炎症反应，从局部到全身 35:35 卵泡期 vs 黄体期：能量需求和代谢差异 43:41 免疫骨骼心血管，结论待定 45:13 不同月经周期，两种压力反应模式 48:58 卵泡期更适合高强度运动？ 54:10 断食，适合女性吗 55:46 代谢研究里月经周期的盲点 63:38 经前综合征，如何应对？ 68:14 更敏感，是雌性的生存优势 69:10 女性是活得更久，但也病得更久 70:02 女性在现代医学研究中，长期被系统性忽视 76:34 希望下一代女性，能看到的世界 感谢 专研高品质舒适感的她研社对本节目的支持。她研社，舒适刚刚好。【她研社均衡力】卫生巾，弱酸面层和人体健康肌肤pH值相近，有效抑制有害菌，干爽不漏不敏痒。复制下方淘口令 上天猫/淘宝获取节目专属优惠券 获取更多产品信息~ 97💲kzBCgl6lYsl🔐 https://s.tb.cn/h.RwcqfRu MF937 小宇宙专属她研社79元任选3组2 📃 本期播客提到的文献素材传送门： 第一部分：运动员月经稀发/闭经 运动员月经稀发/闭经比例： https://pubmed.ncbi.nlm.nih.gov/30644600/ ：“Forty-four percent of premenopausal females had oligomenorrhea/amenorrhea.” 舞蹈员和长跑运动员闭经比例： https://www.ccjm.org/content/85/4/313 ：“In small studies, the prevalence of secondary amenorrhea was as high as 69% in dancers and 65% in long-distance runners.” 职业运动员闭经常态化： https://pmc.ncbi.nlm.nih.gov/articles/PMC8609260/ ：“According to the participants, the five main reasons for not reporting the amenorrhea were: (1) normalizing of the subject, (2) the absence of menstruation is not perceived as a problem by the athletes themselves, (3) experienced shame and taboo, (4) prioritisation of sports performance, and (5) denial.” IOC 声明能量摄入与消耗失衡会导致包括闭经在内的生殖失调： https://stillmed.olympics.com/media/Documents/Athletes/Medical-Scientific/Consensus-Statements/REDs/BJSM-IOC-consensus-statement-on-Relative-Energy-Deficiency-in-Sport-REDs.pdf ：“A syndrome of impaired physiological and/or psychological functioning experienced by female and male athletes that is caused by exposure to problematic (prolonged and/or severe) low energy availability. The detrimental outcomes include, but are not limited to, decreases in energy metabolism, reproductive function, musculoskeletal health…” 月经应作为重要生命体征： https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2015/12/menstruation-in-girls-and-adolescents-using-the-menstrual-cycle-as-a-vital-sign，https://pubmed.ncbi.nlm.nih.gov/39906529/ ：“The menstrual cycle is a vital sign from menarche through menopause, an underutilized but powerful tool for understanding gynecological and general health.” 月经不规律与疾病的关联性： https://academic.oup.com/jcem/article-abstract/87/5/2013/2846638?redirectedFrom=fulltext ：“Compared with women reporting a history of very regular menstrual cycles, women reporting usually irregular or very irregular cycles had an increased risk for nonfatal or fatal CHD [age-adjusted relative risks (RR), 1.25 and 1.67, respectively; 95% confidence intervals (CI), 1.07–1.47 and 1.35–2.06, respectively].”， https://pmc.ncbi.nlm.nih.gov/articles/PMC12671990/ （超多疾病，不一一详细列出了） 古代神话和传说里对月经的态度： https://www.sciencedirect.com/science/article/abs/pii/S1521693416301250（有正面和负面） 第二部分 经期 经期子宫内免疫细胞的逐步参与： https://journals.physiology.org/doi/full/10.1152/physrev.00031.2019 ：Section VIII 及 Figure 5 记录了细胞凋亡先于内膜脱落发生的时序："endometrial apoptosis was extensive before the onset of breakdown, shedding, and bleeding"；Section VIII 下半段、Section IX 及 Figure 6 描述了中性粒细胞的大规模招募及其通过MMPs推动组织分解的机制："Neutrophils contain high levels of MMPs, and endometrial neutrophils may activate MMPs in situ, thereby contributing to endometrial breakdown"；巨噬细胞吞噬凋亡细胞后发生表型转变并释放IL-10、TGF-β等抗炎因子（即胞葬触发的促炎→抗炎转换）见于Section VIII，巨噬细胞的来源与定位动态见于Section IX；无疤痕修复的机制分布在 Introduction、Section X 和Section XI-C中 。 经期巨噬细胞功能转化： https://pmc.ncbi.nlm.nih.gov/articles/PMC10691302/ ：“After the acute endometrial shedding, exudated inflammatory cells can upregulate cytokine levels, mainly in elevated levels of TNF-α and IL-1. Following this, M1 macrophages accumulate in the wound, releasing TNF-α, IL-1, and IL-6. Cytokines involved in wound healing activate the NF-κB signaling pathway.” 在经期的免疫细胞修复功能： **https://www.frontiersin.org/journals/reproductive-health/articles/10.3389/frph.2021.779979/full ："analysis of this fluid is likely to be of value not only for treating endometrial bleeding problems but also in providing potential new therapies for poorly repairing wounds" 经血内物质可以帮助组织修复： https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.201800086R ：“Functionally, they promote repair of endometrial and keratinocyte wounds by promoting migration.”， “MF (4%) brought about complete repair/100% healing of the wounded HaCaT keratinocyte cell line monolayer within 24 h of addition, compared with only 40% repair in the presence of 4% PB plasma” 经血内干细胞可帮助疾病治疗： https://pmc.ncbi.nlm.nih.gov/articles/PMC7656201/ ：“Human menstrual blood-derived mesenchymal stem cells (MenSCs) have shown great potential in regenerative medicine.”，相关临床实验： https://clinicaltrials.gov/study/NCT01483248#study-plan ， https://clinicaltrials.gov/study/NCT07131150 经期外周血炎症水平增高： https://mednexus.org/doi/10.4103/2096-2924.232878 ：“The expression of inflammatory indexes, such as platelets (PLT), lymphocytes (Lym), the percentage of Lym (Lym%), neutrophils (Neu), the percantage of Neu (Neu%), neutrophil-to-lymphocyte ratio (NLR), interleukin-6 (IL-6), and cancer antigen 125 (CA125), reached the highest level during the menstrual period.”, ”The expression levels of IL-8, IL-1β, and IL-6 during the menstrual period and luteal phase were significantly higher than those in follicular phase.” 痛经患者外周血炎症水平更高： https://pmc.ncbi.nlm.nih.gov/articles/PMC3563666/ ：“Functional annotation revealed an excessive inflammatory response and insufficient TGF-β superfamily member signals with anti-inflammatory consequences, which may directly contribute to menstrual pain.” omega3 和健康饮食能缓解痛经： https://onlinelibrary.wiley.com/doi/full/10.1111/1747-0080.12835 ：“Findings suggest that daily supplementation of 300–1800 mg omega-3 long chain polyunsaturated fatty acids over 2–3 months are generally well tolerated and reduces pain and analgesic use in women with dysmenorrhoea.”， https://link.springer.com/article/10.1007/s00228-021-03263-1 ：“the highest effectiveness of treatment was seen at low doses of n-3 PUFAs, and with increasing daily intake, the effectiveness of treatment with n-3 PUFAs decreased.“ https://karger.com/goi/article-abstract/84/3/209/153726/Nutrition-as-a-Potential-Factor-of-Primary?redirectedFrom=fulltext ：“The increased consumption of fruits and vegetables as the sources of vitamins and minerals, as well as fish and milk and dairy products have positive associations with less menstrual pain.”， https://pmc.ncbi.nlm.nih.gov/articles/PMC5963185/ ：“subjects in the second and third tertiles of “snacks” pattern had a 4.23 (95% CI = 1.32–13.58, P = 0.01) and 3.41 (95% CI = 1.10–10.50, P = 0.03) times, respectively, higher chance to experience moderate to severe dysmenorrhea in comparison with subjects in the first tertile.” 运动特别是力量训练可以缓解痛经： https://pmc.ncbi.nlm.nih.gov/articles/PMC11896821/ ：“The majority of the studies on strength training interventions concentrated on the uterine region, emphasizing core training and isometric training. These uterine-specific exercise interventions facilitate the delivery of essential oxygen and nutrients to the uterine muscles and tissues, enhance blood circulation, and support repair processes. These also lower congestion and inflammation while optimizing the uterine microenvironment. This may provide a higher advantage than other therapies.” 热敷缓解痛经： https://pmc.ncbi.nlm.nih.gov/articles/PMC12876241/ ：“applied heat increases pelvic blood flow, which may help to dissipate and reduce the concentration of prostaglandins, thereby relieving ischemia and muscle cramps” 全球贫血和缺铁数据： https://ourworldindata.org/billions-people-suffer-anemia-cheap-ways-reduce 第三部分 卵泡期 卵泡期能量需求较少： https://pmc.ncbi.nlm.nih.gov/articles/PMC7357764/ ：“Overall, there was a small but significant effect favoring increased RMR in the luteal phase (ES = 0.33; 95% CI = 0.17, 0.49, p < 0.001).” https://academic.oup.com/nutritionreviews/article/81/7/869/6823870 ：“ Overall, energy intake appears to be lower in the follicular phase compared with the luteal phase, with a particular decrease in the days leading up to and including ovulation.” 卵泡期血糖调节能力更强： https://pmc.ncbi.nlm.nih.gov/articles/PMC10513929/ ：“Our study therefore highlights that brain insulin action improves peripheral insulin sensitivity also in women but only during the follicular phase.” 多囊患者胰岛素抵抗概率增高，妊娠风险，心血管疾病概率也增高： https://pmc.ncbi.nlm.nih.gov/articles/PMC9832677/ ：”IR and compensatory hyperinsulinaemia (HI) are present in 65–95% of women with PCOS, including the vast majority of overweight and obese women and more than half of women of normal weight.“， “Women with PCOS and IR have a significantly increased risk of adverse pregnancy outcomes and chronic diseases, such as type 2 diabetes mellitus (T2DM), cardiovascular disease, and metabolic syndrome, which seriously affect the physical and mental health of women of childbearing age, increasing their social burden” 柳叶刀建议更名多囊卵巢综合征为多内分泌代谢性卵巢综合征： https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)00717-8/fulltext 卵泡期免疫功能变化，骨代谢变化，心血管功能变化证据不强： https://pubmed.ncbi.nlm.nih.gov/37309068/， https://link.springer.com/article/10.1007/s00223-026-01482-1， https://journals.physiology.org/doi/full/10.1152/ajpheart.00341.2020 卵泡期皮质醇基础量更高，对急性刺激反应相对更温和 https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00311/full ： “In line with our hypothesis, our meta-analysis found that women in the follicular phase had higher cortisol levels than women in the luteal phase, with an overall Hedges' g of 0.13 (p < 0.01) for the random effects model.”， https://www.sciencedirect.com/science/article/abs/pii/S0149763423001811 ：“Three studies provided sufficient data for the meta-analysis and showed a significant, small-sized effect, indicating higher cortisol reactivity in the luteal than in the follicular cycle phase.” 卵泡期更倾向消耗碳水化合物，黄体期更常用脂肪和蛋白质： https://academic.oup.com/nutritionreviews/article/81/7/869/6823870 ：“Rates of carbohydrate and fat oxidation vary across the cycle, with greater glycogen storage at rest, and a stronger preference for fat utilization during exercise, in the luteal phase compared with the follicular phase.”， https://journals.physiology.org/doi/abs/10.1152/ajpendo.1994.267.3.E422 ：“This study shows small changes in protein metabolism during the menstrual cycle in women, with an increase in oxidative leucine metabolism during the luteal phase…fluctuations in protein metabolism and thyroid hormones throughout the menstrual cycle are causally related.” 特里尔社会压力测试流程： https://pmc.ncbi.nlm.nih.gov/articles/PMC3227197/ 高强度训练在卵泡期效果更好： https://pmc.ncbi.nlm.nih.gov/articles/PMC12538072/#abs0025 ：“High-frequency SIT during the follicular phase preserved mitochondrial function and enhanced tissue remodeling, while luteal phase-based training suppressed mitochondrial pathways and reduced cardiorespiratory fitness.” 120人的根据月经不同周期调整训练的 IMPACT 研究： https://pmc.ncbi.nlm.nih.gov/articles/PMC10823667/ 第四部分 黄体期 黄体期能量摄入及饮食推荐： https://www.mdpi.com/2072-6643/16/12/1911 ：“Researchers at the Mayo Clinic emphasize the importance of not only the composition of the diet but also eating smaller and more frequent meals to alleviate PMS symptoms such as bloating and feelings of fullness. Similarly, the ACOG stressed the importance of meal frequency, suggesting the consumption of six small meals instead of three larger meals. This dietary pattern may help to maintain stable blood glucose levels and potentially reduce PMS symptoms.” https://pmc.ncbi.nlm.nih.gov/articles/PMC8566643/ ：“Consuming a high carbohydrate snack 3–4 h before exercise can mitigate these effects during the luteal phase”， “Carbohydrate loading in the mid-luteal phase, however, has shown no change or small (13%) increase in muscle glycogen with a potential for improved performance”, “Because of increased progesterone levels in the luteal phase, the protein requirement may be higher due to higher rates of protein catabolism” https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1079417/full ：“It has been suggested that caloric intake, as well as preferential carbohydrate selection, during the premenstrual period is more significant in women with PMS, who are considered to be more sensitive to cyclical hormonal or neurotransmitter fluctuations.” 肥胖女性和肥胖成人断食好处对比： https://pmc.ncbi.nlm.nih.gov/articles/PMC12479299/ ， https://pmc.ncbi.nlm.nih.gov/articles/PMC12309044/ 断食研究者女性更难坚持： https://pmc.ncbi.nlm.nih.gov/articles/PMC6816332/ ：“It remains to be established why we experienced a gender difference (82% of dropouts were female).” 断食的优势与月经周期波动幅度相当： HOMA-IR（胰岛素抵抗指数）**断食改善：**−0.31（Miao et al., PMC8970877）至 −0.60（Lu et al., PMC12363089）**月经周期波动：**卵泡中期1.35 → 黄体早期1.59，差值+0.24（Yeung et al., BioCycle Study, PMC2999972） LDL胆固醇 断食改善：−5.44 mg/dL（Wang et al., PMC12309044）**月经周期波动：**综合多项研究范围为4–10%（Mumford et al., PMID 14764796）总胆固醇 断食改善：−6.31 mg/dL（Wang et al., PMC12309044）**月经周期波动：**综合多项研究的范围为4–10%（Mumford et al., PMID 14764796）还有炎症 CRP（C反应蛋白，炎症标志物）**断食改善：**−0.024 mg/dL，即−0.24 mg/L（Wang X et al., PMID 32947129）**月经周期波动：**卵泡早期（月经期第2–5天）1.8 mg/L vs 黄体期0.7 mg/L，差值1.1 mg/L，p<0.001（Gursoy et al., PMC4701164） 断食时间推荐在卵泡期： https://pmc.ncbi.nlm.nih.gov/articles/PMC13210042/ ：“These cyclical changes provide a physiological basis for the observation that women may tolerate longer fasting windows more easily during the early-to-mid-follicular phase, whereas the luteal phase may be associated with greater difficulty adhering to restrictive eating schedules.” 针对 PMS 和 PMDD 疗法简介： https://pmc.ncbi.nlm.nih.gov/articles/PMC9790166/#s0003 ， https://pubmed.ncbi.nlm.nih.gov/18852497/ ：“cognit