Artificial intelligence technology plays a crucial role in recommending prescriptions for traditional Chinese medicine (TCM). Previous studies have made significant progress by focusing on the symptom-herb relationship in prescriptions. However, several limitations hinder model performance: (i) Insufficient attention to patient-personalized information such as age, BMI, and medical history, which hampers accurate identification of syndrome and reduces efficacy. (ii) The typical long-tailed distribution of herb data introduces training biases and affects generalization ability. (iii) The oversight of the 'monarch, minister, assistant and envoy' compatibility among herbs increases the risk of toxicity or side effects, opposing the 'treatment based on syndrome differentiation' principle in clinical TCM. Therefore, we propose a novel hierarchical structure-enhanced personalized recommendation model for TCM formulas based on knowledge graph diffusion guidance, namely TCM-HEDPR. Specifically, we pre-train symptom representations using patient-personalized prompt sequences and apply prompt-oriented contrastive learning for data augmentation. Furthermore, we employ a KG-guided homogeneous graph diffusion method integrated with a self-attention mechanism to globally capture the non-linear symptom-herb relationship. Lastly, we design a heterogeneous graph hierarchical network to integrate herbal dispensing relationships with implicit syndromes, guiding the prescription generation process at a fine-grained level and mitigating the long-tailed herb data distribution problem. Extensive experiments on two public datasets and one clinical dataset demonstrate the effectiveness of TCM-HEDPR. In addition, we incorporate insights from modern medicine and network pharmacology to evaluate the recommended prescriptions comprehensively. It can provide a new paradigm for the recommendation of modern TCM.

Traditional Chinese Medicine (TCM) formulas play a significant role in treating epidemics and complex diseases. Existing models for TCM utilize traditional algorithms or deep learning techniques to analyze formula relationships, yet lack comprehensive results, such as complete formula compositions and detailed explanations. Although recent efforts have used TCM instruction datasets to fine-tune Large Language Models (LLMs) for explainable formula generation, existing datasets lack sufficient details, such as the roles of the formula's sovereign, minister, assistant, courier; efficacy; contraindications; tongue and pulse diagnosis-limiting the depth of model outputs. To address these challenges, we propose ZhiFangDanTai, a framework combining Graph-based Retrieval-Augmented Generation (GraphRAG) with LLM fine-tuning. ZhiFangDanTai uses GraphRAG to retrieve and synthesize structured TCM knowledge into concise summaries, while also constructing an enhanced instruction dataset to improve LLMs' ability to integrate retrieved information. Furthermore, we provide novel theoretical proofs demonstrating that integrating GraphRAG with fine-tuning techniques can reduce generalization error and hallucination rates in the TCM formula task. Experimental results on both collected and clinical datasets demonstrate that ZhiFangDanTai achieves significant improvements over state-of-the-art models. Our model is open-sourced at https://huggingface.co/tczzx6/ZhiFangDanTai1.0.

Traditional Chinese Medicine diagnosis and treatment principles, established through centuries of trial-and-error clinical practice, directly maps patient-specific symptom patterns to personalised herbal therapies. These empirical holistic mapping principles offer valuable strategies to address remaining challenges of reductionism methodologies in modern biomedicine. However, the lack of a quantitative framework and molecular-level evidence has limited their interpretability and reliability. Here, we present an AI framework trained on ancient and classical TCM formula records to quantify the symptom pattern-herbal therapy mappings. Interestingly, we find that empirical TCM diagnosis and treatment are consistent with the encoding-decoding processes in the AI model. This enables us to construct an interpretable TCM embedding space (TCM-ES) using the model's quantitative representation of TCM principles. Validated through broad and extensive TCM patient data, the TCM-ES offers universal quantification of the TCM practice and therapeutic efficacy. We further map biomedical entities into the TCM-ES through correspondence alignment. We find that the principal directions of the TCM-ES are significantly associated with key biological functions (such as metabolism, immune, and homeostasis), and that the disease and herb embedding proximity aligns with their genetic relationships in the human protein interactome, which demonstrate the biological significance of TCM principles. Moreover, the TCM-ES uncovers latent disease relationships, and provides alternative metric to assess clinical efficacy for modern disease-drug pairs. Finally, we construct a comprehensive and integrative TCM knowledge graph, which predicts potential associations between diseases and targets, drugs, herbal compounds, and herbal therapies, providing TCM-informed opportunities for disease analysis and drug development.

Herb classification presents a critical challenge in botanical research, particularly in regions with rich biodiversity such as Nepal. This study introduces a novel deep learning approach for classifying 60 different herb species using Convolutional Neural Networks (CNNs) and transfer learning techniques. Using a manually curated dataset of 12,000 herb images, we developed a robust machine learning model that addresses existing limitations in herb recognition methodologies. Our research employed multiple model architectures, including DenseNet121, 50-layer Residual Network (ResNet50), 16-layer Visual Geometry Group Network (VGG16), InceptionV3, EfficientNetV2, and Vision Transformer (VIT), with DenseNet121 ultimately demonstrating superior performance. Data augmentation and regularization techniques were applied to mitigate overfitting and enhance the generalizability of the model. This work advances herb classification techniques, preserving traditional botanical knowledge and promoting sustainable herb utilization.

Traditional Chinese medicine (TCM) exhibits remarkable therapeutic efficacy in disease treatment and healthcare through personalized herb prescriptions. However, current herb recommendation models inadequately capture the multiscale relations between herbs and clinical symptoms, particularly neglecting latent correlations at the chemical-molecular scale. To address these limitations, we propose the Fusion of Multiscale Correlations of Herbs and Symptoms (FMCHS), an innovative framework that synergistically integrates molecular-scale chemical characteristics of herbs with clinical symptoms. The framework employs multi-relational graph transformer layers to generate enriched embeddings that preserve both structural and semantic features within herbs and symptoms. Through systematic incorporation of herb chemical profiles into node embeddings and implementation of attention-based feature fusion, FMCHS effectively utilizes multiscale correlations. Comprehensive evaluations demonstrate FMCHS's superior performance over the state-of-the-art (SOTA) baseline, achieving relative improvements of 8.85% in Precision@5, 12.30% in Recall@5, and 10.86% in F1@5 compared to the SOTA model on benchmark datasets. This work facilitates the practical application of TCM in disease treatment and healthcare.

Aligning Large Language Models (LLMs) to human preferences in content, style, and presentation is challenging, in part because preferences are varied, contextdependent, and sometimes inherently ambiguous. While successful, Reinforcement Learning from Human Feedback (RLHF) and Direct Preference Optimization (DPO) are prone to the issue of proxy reward overoptimization. Analysis of the DPO loss reveals a critical need for regularization for mislabeled or ambiguous preference pairs to avoid reward hacking. In this work, we develop a pessimistic framework for DPO by introducing preference uncertainty penalization schemes, inspired by offline reinforcement learning. The penalization serves as a correction to the loss which attenuates the loss gradient for uncertain samples. Evaluation of the methods is performed with GPT2 Medium on the Anthropic-HH dataset using a model ensemble to obtain uncertainty estimates, and shows improved overall performance compared to vanilla DPO, as well as better completions on prompts from high-uncertainty chosen/rejected responses. Aligning LLMs to human preferences in content, style, and presentation has become a central challenge in improving and deploying LLMs, leading to the advent of Reinforcement Learning with Human Feedback (RLHF), now a prominent technique to fine-tune state-of-the-art LLMs (Casper et al., 2023). The standard RLHF pipeline involves human feedback collection, reward model training, and LLM policy optimization via reinforcement learning (RL). Despite its success, each stage presents challenges, from feedback interpretation and policy generalization to challenging RL implementation (Casper et al., 2023). Direct Preference Optimisation (DPO) (Rafailov et al., 2023) effectively bypasses the reward model by fine-tuning the policy to maximize the likelihood of the preference data under the Bradley-Terry model (A. DPO is easier to implement than RL algorithms, and benefits from computational efficiency and stability by avoiding potential inaccuracies and biases of a reward model (Xu et al., 2024; Casper et al., 2023).

Objective: To explore and compare the performance of ChatGPT and other state-of-the-art LLMs on domain-specific NER tasks covering different entity types and domains in TCM against COVID-19 literature. Methods: We established a dataset of 389 articles on TCM against COVID-19, and manually annotated 48 of them with 6 types of entities belonging to 3 domains as the ground truth, against which the NER performance of LLMs can be assessed. We then performed NER tasks for the 6 entity types using ChatGPT (GPT-3.5 and GPT-4) and 4 state-of-the-art BERT-based question-answering (QA) models (RoBERTa, MiniLM, PubMedBERT and SciBERT) without prior training on the specific task. A domain fine-tuned model (GSAP-NER) was also applied for a comprehensive comparison. Results: The overall performance of LLMs varied significantly in exact match and fuzzy match. In the fuzzy match, ChatGPT surpassed BERT-based QA models in 5 out of 6 tasks, while in exact match, BERT-based QA models outperformed ChatGPT in 5 out of 6 tasks but with a smaller F-1 difference. GPT-4 showed a significant advantage over other models in fuzzy match, especially on the entity type of TCM formula and the Chinese patent drug (TFD) and ingredient (IG). Although GPT-4 outperformed BERT-based models on entity type of herb, target, and research method, none of the F-1 scores exceeded 0.5. GSAP-NER, outperformed GPT-4 in terms of F-1 by a slight margin on RM. ChatGPT achieved considerably higher recalls than precisions, particularly in the fuzzy match. Conclusions: The NER performance of LLMs is highly dependent on the entity type, and their performance varies across application scenarios. ChatGPT could be a good choice for scenarios where high recall is favored. However, for knowledge acquisition in rigorous scenarios, neither ChatGPT nor BERT-based QA models are off-the-shelf tools for professional practitioners.

Traditional Chinese medicine (TCM) relies on specific combinations of herbs in prescriptions to treat symptoms and signs, a practice that spans thousands of years. Predicting TCM prescriptions presents a fascinating technical challenge with practical implications. However, this task faces limitations due to the scarcity of high-quality clinical datasets and the intricate relationship between symptoms and herbs. To address these issues, we introduce DigestDS, a new dataset containing practical medical records from experienced experts in digestive system diseases. We also propose a method, TCM-FTP (TCM Fine-Tuning Pre-trained), to leverage pre-trained large language models (LLMs) through supervised fine-tuning on DigestDS. Additionally, we enhance computational efficiency using a low-rank adaptation technique. TCM-FTP also incorporates data augmentation by permuting herbs within prescriptions, capitalizing on their order-agnostic properties. Impressively, TCM-FTP achieves an F1-score of 0.8031, surpassing previous methods significantly. Furthermore, it demonstrates remarkable accuracy in dosage prediction, achieving a normalized mean square error of 0.0604. In contrast, LLMs without fine-tuning perform poorly. Although LLMs have shown capabilities on a wide range of tasks, this work illustrates the importance of fine-tuning for TCM prescription prediction, and we have proposed an effective way to do that.

Traditional Chinese medicine (TCM) prescription is the most critical form of TCM treatment, and uncovering the complex nonlinear relationship between symptoms and TCM is of great significance for clinical practice and assisting physicians in diagnosis and treatment. Although there have been some studies on TCM prescription generation, these studies consider a single factor and directly model the symptom-prescription generation problem mainly based on symptom descriptions, lacking guidance from TCM knowledge. To this end, we propose a RoBERTa and Knowledge Enhancement model for Prescription Generation of Traditional Chinese Medicine (RoKEPG). RoKEPG is firstly pre-trained by our constructed TCM corpus, followed by fine-tuning the pre-trained model, and the model is guided to generate TCM prescriptions by introducing four classes of knowledge of TCM through the attention mask matrix. Experimental results on the publicly available TCM prescription dataset show that RoKEPG improves the F1 metric by about 2% over the baseline model with the best results.

Traditional Chinese Medicine (TCM) has a rich history of utilizing natural herbs to treat a diversity of illnesses. In practice, TCM diagnosis and treatment are highly personalized and organically holistic, requiring comprehensive consideration of patients' states and symptoms over time. However, existing TCM recommendation approaches overlook the changes in patients' states and only explore potential patterns between symptoms and prescriptions. In this paper, we propose a novel Sequential Condition Evolved Interaction Knowledge Graph (SCEIKG), a framework that treats the model as a sequential prescription-making problem by considering the dynamics of patients' conditions across multiple diagnoses. In addition, we incorporate an interaction knowledge graph to enhance the accuracy of recommendations by considering the interactions between different herbs and patients' conditions. Experimental results on the real-world dataset demonstrate that our approach outperforms existing TCM recommendation methods, achieving state-ofthe-art performance. Traditional Chinese Medicine (TCM) is an ancient and comprehensive system that has been integral to Chinese society for millennia (Cheung, 2011). TCM differs from Western medicine in light of its unique theoretical foundation, diagnosis methods, and treatment approaches, emphasizing the harmonious functioning of the body's structures (Zhang et al., 2015). Chinese Herbal Medicine, a key component of TCM, has gained global recognition for its positive impact on various illnesses. As a result, TCM recommendation systems, which assist physicians in making informed decisions about prescribing herbs, have emerged as crucial tools.