Nature Medicine：胡志斌/沈洪兵/王铖合作揭示父亲孕前因素影响孩子新生突变及早期发育
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TL;DR — A Nature Medicine study (Nanjing Medical University; Hu Zhibin / Shen Hongbing / Wang Cheng; published 2026-08-07) performed ~30× whole-genome sequencing on 7,851 parent-offspring trios (24,030 individuals) from the China National Birth Cohort, building the largest population-scale de novo mutation (DNM) map and showing that paternal preconception factors shape offspring DNMs and, through them, early developmental health.
- Parental age acts differently by parent of origin: paternal germline DNMs (gDNMs) accumulate linearly with age, whereas maternal gDNMs accelerate after ~29–32 years and shift in mutational spectrum.
- Advanced paternal age is not a direct cause of adverse outcomes: its gDNM burden acts indirectly through early developmental phenotypes such as gestational age and birth weight.
- ART decomposed step by step: ICSI was associated with increased paternal gDNMs (mediating preterm birth and low birth weight risk), while GnRH-antagonist ovarian stimulation was associated with increased maternal gDNMs.
- Early post-zygotic mosaic mutations (EPZMs) extended the analysis: embryo culture/transfer procedures correlated with higher EPZM burden, and specific EPZM types with neurodevelopmental delay risk at age 1.
- Scale and implication: ~20× the team's 2021 Cell Research pilot, supporting a shift from mother-focused to joint parental preconception risk management.
Note: only one source describes this work; the second supplied summary covers an unrelated Nature Medicine paper (a King's College London psilocybin feasibility trial for treatment-resistant depression) and was excluded as off-topic.
Sources (2)
Nature Medicine：胡志斌/沈洪兵/王铖合作揭示父亲孕前因素影响孩子新生突变及早期发育
TL;DR - A Nature Medicine study (Nanjing Medical University, published 2026-08-07) used ~30× whole-genome sequencing of 7,851 parent-offspring trios (24,030 individuals) from the China National Birth Cohort to build the largest population-scale de novo mutation (DNM) map, showing paternal preconception factors shape offspring DNMs and, through them, early developmental health.
- Parental age effects differ by origin: paternal germline DNMs accumulate linearly with age, while maternal gDNMs accelerate after ~29–32 years with an altered mutational spectrum.
- Advanced paternal age did not directly cause adverse outcomes; its gDNM burden acted indirectly via early developmental phenotypes such as gestational age and birth weight.
- Decomposing ART steps: ICSI was associated with increased paternal gDNMs (mediating preterm birth and low birth weight risk), while GnRH-antagonist ovarian stimulation was associated with increased maternal gDNMs.
- Extended detection to early post-zygotic mosaic mutations (EPZMs): embryo culture/transfer procedures correlated with higher EPZM burden, and specific EPZM types with neurodevelopmental delay risk at age 1.
- Scale is ~20× the team's 2021 Cell Research pilot, supporting a shift from mother-focused to joint parental preconception risk management.
Nature Medicine：裸盖菇素治疗难治性重度抑郁症
TL;DR - A King's College London randomized, double-blind, placebo-controlled feasibility trial published in Nature Medicine (Aug 6, 2026) tested single-dose 25 mg psilocybin-assisted therapy for treatment-resistant major depressive disorder within the UK NHS. It matters because it moves psychedelic therapy out of specialist research settings into a public healthcare system, where access to existing TRD options (ketamine, ECT, rTMS) is limited.
- 60 participants meeting DSM-5 MDD criteria with non-response to ≥2 antidepressants (or 1 antidepressant plus ≥1 psychotherapy) were randomized 1:1, balanced by age, sex, and prior psilocybin exposure; 59 completed MADRS at all follow-up timepoints over 6 weeks.
- Intervention was a single 25 mg psilocybin dose (vs placebo) wrapped in preparation, in-session support, and post-dose integration therapy; primary outcomes were feasibility metrics — recruitment, retention, and estimation of MADRS variability — not efficacy.
- Adjusted between-group MADRS difference at week 3 was −10.41 favoring psilocybin, with the effect sustained at week 6.
- Non-serious adverse events totaled 123 (placebo) vs 164 (psilocybin); authors conclude the results support proceeding to a larger confirmatory trial.
Note: this is a feasibility-stage trial, so the efficacy signal is preliminary and not powered for definitive conclusions.