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Volume 32, Number 10—October 2026
Historical Review
Variolation Techniques, Medical Explanations, and Dissemination in Late Imperial China
Figure 2

Figure 2. Logical progression underlying intranasal variolation in study of variolation techniques, medical explanations, and dissemination in late Imperial China. Schematic outlines the cognitive evolution of smallpox in traditional Chinese medicine that gave rise to variolation, spanning from the introduction of smallpox (25–55 CE) to recognition of its transmissibility, formulation of fetal toxin etiology, and eventual formalization of intranasal variolation. Developmental trajectory underpins the indigenous originality of variolation in China. Screenshots of ancient medical texts from China are shown at the top, sequentially sourced from references (21), (22), (23), and (7). Direct excerpts from original ancient medical text are outlined in red, serving as the primary source supporting the summary descriptions at the bottom. Schematic is only an analytical simplification and does not imply a unidirectional or deterministic progression.
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1These first authors contributed equally to this article.