TCM-DiffRAG: Personalized Syndrome Differentiation Reasoning Method for Traditional Chinese Medicine based on Knowledge Graph and Chain of Thought

Large language models have advanced medical reasoning, but clinically grounded reasoning in traditional Chinese medicine (TCM) remains challenging because prescription decisions require integrating domain knowledge, syndrome differentiation, treatment principles, herbal prescription composition, and dosage determination. We develop a TCM language model family comprising models with 4 billion, 8 billion, and 14 billion parameters. The artificial intelligence contribution is a staged clinical alignment framework integrating large scale continued pretraining on TCM and clinical records, complementary reasoning supervision, and prescription-centered reinforcement learning (RL). We further formulate herbal prescription generation as a structured RL problem with prescription-level feedback, enabling direct optimization of clinical decision outputs beyond knowledge reproduction and generic instruction following. The engineering application is TCM clinical decision support, particularly herbal prescription recommendation. We evaluate the models on a public benchmark containing 25,620 expert-verified items across 13 TCM knowledge and clinical reasoning tasks and on a private retrospective dataset of 4,348 spleen and stomach disease prescription cases. The 14 billion parameter reinforcement aligned model achieves a prescription generation F1 of 37.0 on the public benchmark, compared with 32.3 for DeepSeek-R1 with 671 billion total parameters, and a herb-level F1 of 52.8 on the clinical dataset with improved dosage agreement. Reinforcement post-training consistently improves prescription recommendation across all scales, while physician-source analysis shows that expert heterogeneity affects reward stability. These findings demonstrate a scalable pathway from domain grounding and reasoning supervision to clinically oriented prescription decision support.

Applying large language models to Traditional Chinese Medicine (TCM) prescription generation reveals three clinically critical gaps: models produce end-to-end mappings without auditable reasoning following the li-fa-fang-yao paradigm (SR Gap), treat each encounter in isolation without follow-up adjustment via sui zheng jia jian (LA Gap), and fail to enforce absolute contraindication rules such as Shi Ba Fan (SC Gap). We propose a progressive four-stage framework (SFT $\to$ PG-CoT $\to$ Dynamic $\to$ K-RL) that addresses each gap: PG-CoT constrains CoT distillation under the li-fa-fang-yao paradigm to produce auditable diagnostic chains, Dynamic SFT models patient trajectories with explicit transition reasoning, and K-RL encodes deterministic pharmacological rules as rule-based DPO preference signals. Across 12 fine-tuned models and 6 zero-shot baselines, our framework substantially improves prescription quality over zero-shot baselines---with a 7B model (Mistral-7B) surpassing zero-shot GPT-5 on all three TCM evaluation metrics.

Large language models (LLMs) can generate clinical narratives that are insufficiently grounded in patient-specific evidence. In traditional Chinese medicine (TCM), errors can propagate from etiology and pathogenesis through syndrome diagnosis and treatment principles to prescription generation. We developed TCMClinicalReason-Bench using 2,000 multicenter electronic health record cases to distinguish case-grounded responses from fluent but unsupported diagnostic and therapeutic conclusions. Five general-purpose and two TCM-specific LLMs were evaluated in zero-shot settings. An evidence-constrained rubric assessed seven diagnostic and therapeutic components and three cross-block relations, allowing case-supported alternatives. Qwen3.7-Plus with TCM retrieval served as the automated judge, alongside parallel blinded ratings by five senior TCM clinicians on a 600-case subset. Structural completeness was nearly saturated (99.3-100.0%), but normalized content scores ranged from 40.7% to 54.1%. The five general-purpose models averaged 50.0%, versus 41.3% for the two smaller TCM-specific models. Cross-block logic consistency ranged from 60.8% to 66.8% and correlated moderately with content across cases (Pearson's r = 0.515-0.656). Deficits were greatest in prescription generation, prescription analysis, and symptom-guided modification. In judge stress testing on 100 independent cases, perturbation detection rates across the three relations were 57%, 56%, and 31%, with contradictions detected more reliably than omissions. Separating component quality from cross-block consistency localizes failures missed by endpoint and completeness metrics and identifies where clinician oversight remains necessary.