Andrea West还记得，她在2021年第一次听说，有一种新药可能会终结折磨她数十年的偏头痛。那时她在广播里听到科学家讨论CGRP受体拮抗剂 （gepant）的前景。这种药当时首次显现出预防偏头痛发作的潜力。West于是开始密切关注这些药物的新闻。去年她听说阿托吉泮（atogepant）在英国获 批，立刻去找了医生。 West患有偏头痛70年了。自从用了这种药，她再也没有发作过。"这药太神奇了。它彻底改变了我的生活。"她说。 插图：Aleksandra Czudżak 长期以来，人们对偏头痛的印象都是难以缓解的痛苦。在古埃及，医生会把泥做的鳄鱼绑在患者头上，并祈祷奇迹发生。直到17世纪，外科医生会在患者 头骨上钻孔，有人说这样能把偏头痛"释放出来"。20世纪有了更有效的治疗药物，但它们对全球10亿患者中很大一部分人依然不起作用。 如今，这个领域涌现出一批新的进展，这来自多个方向的突破。过去几十年的医学进步——包括gepant和相关疗法的获批——已经将偏头痛变成了"可治 疗和可管理的疾病"，加州大学欧文分校的神经药理学家Diana Krause说。 同时，研究正逐步加深我们对这种疾病的理解，并指明未来的努力 ...

Core Viewpoint - Colorectal cancer (CRC) is the third most common cancer globally, with nearly 2 million new cases annually, and the second leading cause of cancer-related deaths, claiming nearly 1 million lives each year. The study published by Wuhan University researchers identifies a significant single nucleotide mutation (rs10871066) associated with increased risk of precancerous lesions and colorectal cancer, revealing underlying oncogenic mechanisms [2][5]. Group 1 - The research utilized multi-omics data from 533 colorectal tissue samples, ranging from normal tissues to early adenomas and cancers, to establish a dynamic epigenetic map [5]. - A total of 7,492 differential cis-regulatory elements (CREs) were identified, linked to 5,490 target genes [5]. - High-throughput CRISPR interference (CRISPRi) screening revealed 265 functional CREs associated with colorectal cancer cell proliferation [5]. Group 2 - A polygenic risk score (PRS) model based on functional CRE mutations effectively predicted colorectal cancer and precancerous lesions in 476,770 individuals [5]. - The functional mutation rs10871066 is significantly correlated with increased risk of precancerous lesions and colorectal cancer [5]. - Mechanistically, rs10871066 mediates the conversion from silencers to enhancers through FOXP1 and TCF7L2, leading to the upregulation of KLF5 and activation of oncogenic pathways, while also upregulating PIBF1 to inhibit natural killer (NK) cell cytotoxicity [5].

Core Insights - There is a growing interest among Silicon Valley parents in using genetic testing services to screen embryos for traits such as intelligence, with costs reaching up to $50,000 [1][4] - Startups like Genomic Prediction and Nucleus Genomics are at the forefront of providing embryo genetic testing services, with Nucleus charging around $6,000 and Herasight up to $50,000 for their services [4][5] - The fertility tech sector has seen significant investment, with approximately $400 million raised annually from 2021 to 2023, attracting high-profile investors from the tech industry [5] Industry Trends - The demand for embryo genetic testing services is particularly high in the San Francisco Bay Area, driven by a demographic of ultra-high-net-worth individuals and rationalists obsessed with intelligence [1][4] - Companies like Herasight and Nucleus Genomics are expanding their offerings, with Herasight claiming to predict the likelihood of 17 different diseases and intelligence scores for embryos [4][5] Ethical and Legal Considerations - The practice of embryo genetic testing raises significant ethical and legal questions, including the reliability of the scoring methods and the transparency of the algorithms used [6][7] - While embryo screening for traits like intelligence is legal in the U.S., it faces strict prohibitions in countries like Germany, the UK, and Italy [7][8] - Concerns have been raised about the normalization of concepts like "superior" and "inferior" genes, potentially reinforcing societal inequalities based on biological factors [8]