中西医结合科研范式的升级：从“单靶点”验证到“态靶因果”验证

doi:10.12122/j.issn.1673-4254.2026.10.01

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (10): 2285-2295.doi: 10.12122/j.issn.1673-4254.2026.10.01

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中西医结合科研范式的升级：从“单靶点”验证到“态靶因果”验证

杜庆锋¹^,²(), 仝小林³()

^1.南方医科大学中医药学院，广东广州 510515
^2.南方医科大学中西医结合医院，广东广州 510315
^3.中国中医科学院广安门医院，北京 100053

收稿日期:2026-08-09 出版日期:2026-10-20 发布日期:2026-10-26
通讯作者: 仝小林 E-mail:dqf1689@smu.edu.cn;tongxiaolin@vip.163.com
作者简介:杜庆锋，博士，教授，E-mail: dqf1689@smu.edu.cn
杜庆锋：南方医科大学中医药学院院长、附属中西医结合医院院长。任国家教育部重点学科（中西医结合临床）带头人、国家一流专业（中西医临床）建设点负责人、全国中医药行业高等教育“十五五”规划教材《中医基础理论》主编、国家一流课程《伤寒论》主讲负责人。师承仝小林院士，探索构建实施中医经典“五进工程”，强化了中医经典与基础理论在中西医结合学科高质量发展中的核心地位。
仝小林：中国科学院院士，国家中西医结合医学中心专家委员会主任委员，中国中医科学院广安门医院代谢病研究所所长。长期致力于中医药传承与创新研究，首倡并系统推进“两个重构”研究，重构中西医结合诊疗体系和现代本草体系。以重大代谢性疾病为示范，建立了“核心病机-分类分期分证-糖络并治”为框架的现代糖尿病中医诊疗体系。
基金资助:
癌症、心脑血管、呼吸和代谢性疾病防治研究国家科技重大专项“中西医结合降低糖尿病肾脏疾病复合终点事件发生风险的循证评价研究”(2024ZD0523400);羊城中医药创新人才团队建设项目(2026YC003);广州市卫生健康科技重大项目“基于医防融合和慢病多病一体化融合管理理念的广州市慢性病管理创新模式研究”(2024A031007);胰岛素抵抗相关代谢性慢病中西医结合防治创新团队(2022KCXTD003)

Upgrading the scientific research paradigm of integrated traditional Chinese and Western medicine: from "single-target" validation to "state-target causality" validation

Qingfeng DU¹^,²(), Xiaolin TONG³()

^1.School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China
^2.Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou 510315, China
^3.Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China

Received:2026-08-09 Online:2026-10-20 Published:2026-10-26
Contact: Xiaolin TONG E-mail:dqf1689@smu.edu.cn;tongxiaolin@vip.163.com

摘要/Abstract

摘要：

中西医结合学科历经七十年发展，逐步形成了以“单靶点”验证为主导的科研范式。该范式在“线性因果、变量较少”的问题域中成效卓著，但面对“非线性、多因素交织”的复杂问题域，其解释力日益不足。本文梳理了这一范式的成就与局限，深入分析其与学科核心问题域之间的结构性错配，进而提出“态靶因果”验证的科研范式。该范式以“宏观状态与微观事件之间的跨层级因果耦合”为验证对象，通过“寻找耦合-证明耦合-运用耦合”三个递进层次，以及“定义宏观表型、捕捉微观变量、干预验证共变、反向验证因果”四步研究闭环来实现操作化。文章进一步用“态靶因果”范式对吴以岭团队基于脉络学说防治微血管共病、陈香美团队基于“风湿扰肾”理论治疗IgA肾病、张亭栋-王振义-陈竺团队基于“以毒攻毒”理论治疗急性早幼粒细胞白血病等3个案例进行回顾分析与解读，展示了新范式对前期重要研究的内在逻辑解释力。最后，提出了宏观表型标准化、候选靶点库建设、跨层级统计方法发展、实验性反向验证、多中心平台建设、AI技术辅助应用以及方法学推广等未来重点任务。本文认为，“态靶因果”范式标志着中西医结合研究从“借用他人范式”走向“自主建构范式”，为学科建立与自身问题域相匹配的科研方法论提供了系统框架。

关键词: 中西医结合, 科研范式, 态靶因果, 单靶点验证, 复杂性疾病, 跨层级因果耦合

Abstract:

Over the past 7 decades, the discipline of integrated traditional Chinese and Western medicine (ITCWM) has developed a research paradigm centered on "single-target" validation. This paradigm has been highly effective in problem domains involving linear causality with a limited number of variables, but its explanatory power is increasingly constrained in more complex domains with nonlinearity and multiple interacting factors. This review summarizes the major achievements and limitations of the prevailing paradigm, examines its structural mismatch with the core problem domain of ITCWM, and proposes a "state-target causality" validation paradigm. This new paradigm focuses on establishing cross-level causal coupling between macroscopic states and microscopic events. Methodologically, it comprises 3 progressive levels—identifying, demonstrating, and applying such coupling- and a four-step research cycle: defining macroscopic phenotypes, capturing microscopic variables, verifying covariation through intervention, and reverse-validating causality. Herein this framework is used to reinterpret 3 representative lines of research: WU Yiling and colleagues' prevention and treatment of microvascular comorbidities based on the vessel-collateral theory; CHEN Xiangmei and colleagues' treatment of IgA nephropathy based on the "wind-dampness disturbing the kidney" theory; and the principle of "using poison as medicine" proposed by the research team led by ZHANG Tingdong, WANG Zhenyi, and CHEN Zhu for treatment of acute promyelocytic leukemia. These case studies illustrate how the proposed paradigm clarifies the cross-level causal logic underlying major advances in ITCWM research. Future priorities include the standardization of macroscopic phenotypes, construction of candidate target libraries, development of cross-level statistical methods, experimental reverse validation, establishment of multicenter platforms, AI-assisted applications, and broader methodological dissemination. The "state-target causality" paradigm marks the transition of ITCWM research from relying on externally derived paradigms to developing its own discipline-specific paradigm for establishing a research methodology aligned with the discipline's own problem domains.

Key words: Integrated traditional Chinese and Western medicine, research paradigm, state-target causality, single-target validation, complex diseases, cross-level causal coupling

杜庆锋, 仝小林. 中西医结合科研范式的升级：从“单靶点”验证到“态靶因果”验证[J]. 南方医科大学学报, 2026, 46(10): 2285-2295.

Qingfeng DU, Xiaolin TONG. Upgrading the scientific research paradigm of integrated traditional Chinese and Western medicine: from "single-target" validation to "state-target causality" validation[J]. Journal of Southern Medical University, 2026, 46(10): 2285-2295.

图/表 4

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Dimension	Problem domains with linear causality and limited variables	Problem domains with nonlinearity and multiple interacting factors
Dominant paradigm	"Single target" validation paradigm	"State-target causality" validation paradigm
Causal structure	Clear, decomposable, and traceable causal chains	Entangled causal networks with nonlinear characteristics and emergent effects
Optimal epistemic strategy	Open the black-box and directly trace the causal chain	Grey-box approach: start from the macro level and gradually extend to the micro level
Causal inference methods	Reductionist analysis, controlled experiments, randomized controlled trials	Systems science, network analysis, multi-level causal inference
Validation logic	Verify the linear chain of "drug-target-effect"	Verify the cross-level causal coupling of " state-target-effect"
Evaluation endpoints	Changes in specific indicators or pathways	Symptom relief, functional recovery, quality of life improvement
Philosophical foundation	Reductionism	Systems theory

Dimension	Problem domains with linear causality and limited variables	Problem domains with nonlinearity and multiple interacting factors
Dominant paradigm	"Single target" validation paradigm	"State-target causality" validation paradigm
Causal structure	Clear, decomposable, and traceable causal chains	Entangled causal networks with nonlinear characteristics and emergent effects
Optimal epistemic strategy	Open the black-box and directly trace the causal chain	Grey-box approach: start from the macro level and gradually extend to the micro level
Causal inference methods	Reductionist analysis, controlled experiments, randomized controlled trials	Systems science, network analysis, multi-level causal inference
Validation logic	Verify the linear chain of "drug-target-effect"	Verify the cross-level causal coupling of " state-target-effect"
Evaluation endpoints	Changes in specific indicators or pathways	Symptom relief, functional recovery, quality of life improvement
Philosophical foundation	Reductionism	Systems theory

Four-step research loop	Wu Yiling team (microangiopathy)	Chen Xiangmei team (IgA nephropathy)	Arsenic trioxide therapy for acute promyelocytic leukemia (APL)
Define macroscopic phenotypes	Established diagnostic criteria for "Vessel-collateral and vascular system disease" based on syndrome differentiation; clarified the correspondence between the Yingwei theory and vascular endothelial function as well as neurohumoral regulation.	Established a "four-in-one" evaluation system integrating TCM syndromes, Western-medicine clinical features, pathology, and biomarkers; promoted the standardization and objectification of TCM syndrome in IgA nephropathy.	Took deficiency of healthy Qi and toxic pathogens as the core; defined major TCM syndrome classifications for APL (e.g., deficiency of Qi -blood, intense exuberant heat toxin, etc.) without objectively characterizing or standardizing the state.
Capture microscopic variables	Used mesenteric microcirculation and cardiac surface microvasculature techniques to reveal four categories of microscopic pathological features at the "Minute collaterals and microvessels" level.	Correlated TCM syndromes with immune-inflammatory factors, renal injury biomarkers, and renal histopathological changes.	Identified the molecular target of arsenic trioxide (ATO) as the PML-RARα fusion protein; elucidated the molecular mechanism by which ATO induces degradation of this protein.
Verify covariation through intervention	Administration of collateral-dredging drugs (Tongxinluo, Shensong Yangxin, and Qili Qiangxin) regulate both "Ying-Wei, Qi-blood" and the micro-pathological changes in "Minute collaterals and microvessels" in parallel.	Multi-center randomized controlled trials (RCT) confirmed that Huangkui Capsule reduced proteinuria and preserved renal function, while simultaneously improving immuno-inflammatory responses and renal microcirculation.	Verified that PML-RARα degradation after ATO treatment occurred synchronously with clinical remission in patients.
Reverse-validate causality	Systematic reverse validation has not yet been completed; percutaneous coronary intervention (PCI) and vasodilator interventions provided indirect supporting evidence for the restoration of Ying-Wei, Qi-blood regulation in the vessel collaterals.	Mechanistic studies have suggested regulatory effects on certain pathways; systematic target-blockade and rescue experiments remain insufficient.	ATO directly targets PML-RARα; altering the binding site reduces therapeutic efficacy.

Four-step research loop	Wu Yiling team (microangiopathy)	Chen Xiangmei team (IgA nephropathy)	Arsenic trioxide therapy for acute promyelocytic leukemia (APL)
Define macroscopic phenotypes	Established diagnostic criteria for "Vessel-collateral and vascular system disease" based on syndrome differentiation; clarified the correspondence between the Yingwei theory and vascular endothelial function as well as neurohumoral regulation.	Established a "four-in-one" evaluation system integrating TCM syndromes, Western-medicine clinical features, pathology, and biomarkers; promoted the standardization and objectification of TCM syndrome in IgA nephropathy.	Took deficiency of healthy Qi and toxic pathogens as the core; defined major TCM syndrome classifications for APL (e.g., deficiency of Qi -blood, intense exuberant heat toxin, etc.) without objectively characterizing or standardizing the state.
Capture microscopic variables	Used mesenteric microcirculation and cardiac surface microvasculature techniques to reveal four categories of microscopic pathological features at the "Minute collaterals and microvessels" level.	Correlated TCM syndromes with immune-inflammatory factors, renal injury biomarkers, and renal histopathological changes.	Identified the molecular target of arsenic trioxide (ATO) as the PML-RARα fusion protein; elucidated the molecular mechanism by which ATO induces degradation of this protein.
Verify covariation through intervention	Administration of collateral-dredging drugs (Tongxinluo, Shensong Yangxin, and Qili Qiangxin) regulate both "Ying-Wei, Qi-blood" and the micro-pathological changes in "Minute collaterals and microvessels" in parallel.	Multi-center randomized controlled trials (RCT) confirmed that Huangkui Capsule reduced proteinuria and preserved renal function, while simultaneously improving immuno-inflammatory responses and renal microcirculation.	Verified that PML-RARα degradation after ATO treatment occurred synchronously with clinical remission in patients.
Reverse-validate causality	Systematic reverse validation has not yet been completed; percutaneous coronary intervention (PCI) and vasodilator interventions provided indirect supporting evidence for the restoration of Ying-Wei, Qi-blood regulation in the vessel collaterals.	Mechanistic studies have suggested regulatory effects on certain pathways; systematic target-blockade and rescue experiments remain insufficient.	ATO directly targets PML-RARα; altering the binding site reduces therapeutic efficacy.

中西医结合科研范式的升级：从“单靶点”验证到“态靶因果”验证

Upgrading the scientific research paradigm of integrated traditional Chinese and Western medicine: from "single-target" validation to "state-target causality" validation

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