Revolutionizing pharmacological research of traditional Chinese medicine with single-cell omics technologies.

As one of the most advanced technologies, single-cell omics technology develops rapidly in recent years. Based on different technical strategies, it enables unbiased and high-throughput access to multiple omics information at single-cell resolution. So far, single-cell omics technology, by virtue of its great powder in resolving tissue heterogeneity, has become a revolutionary tool to deeply understand the functional structure of tissues, reveal complex disease processes, and elucidate drug mechanisms of action. In view of the technical challenges in deconstructing the complexity of Chinese medicine and clarifying the modern scientific connotation of traditional Chinese medicine(TCM) theory, single-cell omics technology has huge application potential in the discovery of pharmacodynamic substances, construction of action networks, and elucidation of integrated regulatory mechanisms, which brings new opportunities for modern research in TCM. The present study briefly introduced three representative single-cell omics technologies, i.e., single-cell transcriptome sequencing, spatial transcriptomics, and single-cell multimodal omics, and their main application patterns. On this basis, an outlook was proposed on the strategies and applications for modern research in TCM using single-cell omics technology.

The success rate of drug development today remains low, with long development cycles and high costs, especially in areas such as oncology, neurology, immunology, and infectious diseases. Single-cell omics, encompassing transcriptomics, genomics, epigenomics, proteomics, and metabolomics enable the analysis of gene expression profiles and cellular heterogeneity from the perspective of individual cells, offering a high-resolution view of their functional diversity. These technologies can help reveal disease mechanisms, drug target identification and validation, selection of preclinical models and candidate drugs, and clinical decision-making based on disease response to drugs, all at the single-cell level. The development of deep learning technology has provided a powerful tool for research in drug discovery based on single-cell techniques, which has evolved with the advent of large-scale public databases to predict drug responses and targets. In addition, traditional Chinese medicine (TCMs) research has also entered the era of single-cell technology. Single-cell omics technologies offer an alternative way in deciphering the mechanisms of TCMs in disease treatment, revealing drug targets, screening new drugs, and designing combinations of TCMs. This review aims to explore the application of single-cell omics technologies in drug screening and development comprehensively, highlighting how they accelerate the drug development process and facilitate personalized medicine by precisely identifying therapeutic targets, predicting drug responsiveness, deciphering mechanisms of action. It is also concluded that drug development process and therapeutic efficacy of drugs can be improved by combining single-cell omics and artificial intelligence techniques.

Single-cell omics reveal the mechanisms of traditional Chinese medicines.

Traditional Chinese medicine-based herbal medicines have gained increasing acceptance worldwide in recent years and are being pursued by pharmaceutical companies as rich resources for drug discovery. For many years, traditional Chinese medicines (TCM) have been applied for the treatment of cancers in China and beyond. Herbal medicines are generally low in cost, plentiful, and show very little toxicity or side effects in clinical practice. However, despite the vast interest and ever-increasing demand, the absence of strong evidence-based research and the lack of standardization of the herbal products are the main obstacles toward the globalization of TCM. In recent years, TCM research has greatly accelerated with the advancement of analytical technologies and methodologies. This review of TCM specifically used in the treatment of cancer is divided into two parts. Part one provides an overview of the philosophy, approaches and progress in TCM-based cancer therapy. Part two summarizes the current understanding of how TCM-derived compounds function as anticancer drugs.

Half of the 2015 Nobel Prize in Physiology or Medicine was awarded to Chinese scientist Youyou Tu in recognition of her pioneering work on the antimalarial artemisinin, extracted from Artemisia annua, a traditional Chinese herbal remedy used to treat fever. This is clearly a great encouragement for scientists who engage traditional medicine research. As Youyou Tu stated in her Nobel Prize awarding lecture, artemisinin is a gift from traditional Chinese medicine (TCM) to the world, this definitely will generate great interest in not only TCM but also other traditional medicine systems from other parts of the world, including Europe, Africa, India, Americas, etc. Though the Nobel Prize selection committee did not confess that the prize is to award traditional Chinese medicine, rather a new drug discovery inspired from TCM, this is indeed the exciting and encouraging event for Chinese TCM scientists. In my opinion, it is meaningless to dispute if artemisinin is still belonging to TCMor westernmedicine. Any contribution or new discovery derived from TCM to benefit for the human health should be recognized and respected. TCM needs to be developed and modernized. Any standpoint that developed or modernized TCM does not belong to TCM may drastically hinder the TCM modernization and integration with modern medicine process, or even deepen the gap between TCM and modern medicine. Evidence-based medicine is the future of TCM by means of modern biomedicine advances and novel approaches. In the past 20 years, TCM has undergone rapid development period evidenced by a number of achievements including the geometric growth of TCM research papers, booming TCM industry, TCM new drug research and development, etc. However, TCM is still facing grand challenges in the future development. Shortage of modern scientific evidence for safety, effectiveness, quality and mode of action should be emphasized and dealt with solutions. TCM experienced-based feature should be turned into evidence-based and science-based one. Following several aspects are suggested for the future modern TCM research: a) TCM-based new drug discovery. TCM is still a non-fully explored treasure house for new drug discovery and development. According to TCM resource survey, there are over 12000 TCM species, among which majority are herbs. Apart from artemisinin and its derivatives, a number of single chemical entity drugs have been developed and successfully marketed, such as arsenic trioxide, ginsenoside Rg3, bifendate, β-elemene, indirubin, etc. It is anticipated that more new drugs could be discovered from this vast TCM resource with modern drug discovery technology and methodology. b) Research on the holistic TCM quality control. The current quality control approach is more focused on a single marker or a few marker determinations, which follows the western drug quality control model and hence, could not really monitor the quality of TCM products. Systemic and comprehensive quality control method should be developed for the TCM crude drugs, prepared slices and finished products, especially for those multiple-ingredient herbal products. c) Research on TCM processing. All TCM crude drugs should be processed in different extent before they can be used either for decoction or for herbal production. TCM processing method is mainly based on the traditional knowledge or experience. Mechanism of processing either for the purpose of enhancing efficacy or eliminating toxicity should be thoroughly investigated and clarified. d) TCM efficacy and safety research. During the development of TCM, greater attention needs to be paid to the integrated evaluation of the effectiveness and safety based on TCM theory and modern scientific research. New evaluation methodology fit for TCM complex feature should be developed with international collaborations. Globally recognized evaluation criteria should be constructed. Other TCM research focuses include pharmacokinetics, geo-authenticity, active principles and giant data library. It is firmly believed that TCM will contribute more than ever to the human health along with the rapid advances of biomedicine science and eventually developed into an evidence-based medicine system.

<p indent="0mm">With the development of biomedicine, and significant success achieved by targeted therapy in the treatment of complex and refractory diseases such as cancers, clinical treatment and drug discovery based on molecular targets become the main direction of modern medical research. Guided by holistic concept, traditional Chinese medicine (TCM) has a unique advantage with regards to the prevention and treatment of complex diseases through its comprehensive effect. However, at present, TCM research is insufficient and problems such as inaccurate clinical findings, lack of dominant diseases, unclear evaluation of efficacy, and unclear mechanisms, cannot be solved easily. Therefore, the authors believe that the development of TCM should adopt an innovative approach that integrates the advantages of TCM and western medicine, and positively influences the development of TCM and even future medicine. This article proposes Target-combined Holistic Treatment (THT), a new concept based on the integration of TCM and western medicine. While being guided by the holistic and systematic perspective of TCM, THT also factors in the latest advances in both TCM and modern biomedical research, and uses macro-micro combination, target-syndrome combination, and internal and external co-division, as the primary strategies to establish a clinical diagnosis model that combines disease differentiation, syndrome differentiation, and target differentiation. It also uses drug ingredients/components to enable comprehensive interventions against multiple targets linked to a disease, and establishes target medication and research strategy of TCM, so as to improve its pertinence, efficacy, and safety, and ensure precise and effective medication. The theories and methods of THT fully integrate the advantages of TCM and western medicine, factoring in both macro-control and micro intervention, and also systematic confrontation, precision treatment, and embracing TCM theory and modern technology. This can guide the further development of TCM, western medicine, as well as the combination of TCM and western medicine. It will therefore help promote the integration and innovation of both TCM and western medicine, and the in-depth development of TCM. The theories and methods of THT can be used to guide not only the whole process of clinical diagnosis but also the development of innovative drugs. THT has been used to guide the formulation of TCM diagnosis and treatment for COVID-19 and has shown remarkable results. We have developed a Chinese herbal prescription “Keguan-1”, to prevent and treat COVID-19 based on the theory and method of THT, and use the doctrine of “resist foreign aggression and pacify the interior” of TCM against COVID-19. Using the findings of research in modern medicine, THT can innovate and develop TCM based treatments, and thus aid in the treatment of various diseases, and also help promote the integration and development of TCM and western medicine.

Traditional Chinese medicine (TCM) has over 3000 years of history to treat diseases in China and has played an essential role in the Chinese healthy system. More and more western scientists are now interested in TCM research and hope to learn about the basics of TCM in China. Hence, the following aspects related to TCM will be briefly overviewed in the lecture, including TCM theory, TCM resources, related research institutions and education systems, Chinese Pharmacopoeia on TCM volume, TCM new drug registration regulations by SFDA, TCM-based drug discovery, government funding sectors, TCM hospitals, recent research progress made on TCM research, which may help the audience to understand the basic current situation of TCM in China. In addition, the current research on the quality standard construction of traditional Chinese medicines will also be introduced with some concrete examples. The future directions on TCM modernization will also be insighted as a personal viewpoint.

General expert consensus on the application of network pharmacology in the research and development of new traditional Chinese medicine drugs.

The research on traditional Chinese medicine (TCM) has experienced the transition from qualitative research to quantitative study. The application of mathematical modeling for data processing and analysis offers a more efficient and precise approach compared to conventional methods, enabling the timely acquisition of key efficacy indicators for preliminary evaluation. Therefore, the concept of mathematical modeling has been proposed to form a systematic theoretical system of TCM and diseases. The article reviews the application of mathematical models in the research of traditional Chinese medicine in terms of compounding, extraction, optimization, quality evaluation, production, new drug development, pharmacokinetics, pharmacodynamics, and clinical symptom analysis. Relevant Chinese and English literature was obtained from PubMed, Cochrane Library, China Science and Technology Journal Database (VIP), Wanfang Data, CNKI and China Biomedical Literature Database (CBM). We have found that integrating the concept of mathematical modeling with TCM theory has shortened the cycle of extracting active ingredients in traditional Chinese medicine and the development of new drugs, while also accelerating the realization of maximum clinical efficacy. However, the comprehensiveness and precision of existing databases remain areas for improvement. In the future, further integration of multi-disciplinary technologies will be essential to advance the convergence of traditional medicine and modern science. This review explores the application of mathematical models in the study of traditional Chinese medicine. It is evident that mathematical modeling has played a pivotal role in promoting fundamental research and the modernization of TCM.

Several clinical cases and experiments have demonstrated the effectiveness of traditional Chinese medicine (TCM) formulas in treating and preventing diseases. These formulas contain critical information about their ingredients, efficacy, and indications. Classifying TCM formulas based on this information can effectively standardize TCM formulas management, support clinical and research applications, and promote the modernization and scientific use of TCM. To further advance this task, TCM formulas can be classified using various approaches, including manual classification, machine learning, and deep learning. Additionally, large language models (LLMs) are gaining prominence in the biomedical field. Integrating LLMs into TCM research could significantly enhance and accelerate the discovery of TCM knowledge by leveraging their advanced linguistic understanding and contextual reasoning capabilities. The objective of this study is to evaluate the performance of different LLMs in the TCM formula classification task. Additionally, by employing ensemble learning with multiple fine-tuned LLMs, this study aims to enhance classification accuracy. The data for the TCM formula were manually refined and cleaned. We selected 10 LLMs that support Chinese for fine-tuning. We then employed an ensemble learning approach that combined the predictions of multiple models using both hard and weighted voting, with weights determined by the average accuracy of each model. Finally, we selected the top 5 most effective models from each series of LLMs for weighted voting (top 5) and the top 3 most accurate models of 10 for weighted voting (top 3). A total of 2441 TCM formulas were curated manually from multiple sources, including the Coding Rules for Chinese Medicinal Formulas and Their Codes, the Chinese National Medical Insurance Catalog for proprietary Chinese medicines, textbooks of TCM formulas, and TCM literature. The dataset was divided into a training set of 1999 TCM formulas and test set of 442 TCM formulas. The testing results showed that Qwen-14B achieved the highest accuracy of 75.32% among the single models. The accuracy rates for hard voting, weighted voting, weighted voting (top 5), and weighted voting (top 3) were 75.79%, 76.47%, 75.57%, and 77.15%, respectively. This study aims to explore the effectiveness of LLMs in the TCM formula classification task. To this end, we propose an ensemble learning method that integrates multiple fine-tuned LLMs through a voting mechanism. This method not only improves classification accuracy but also enhances the existing classification system for classifying the efficacy of TCM formula.

Single-cell omics technologies have revolutionized molecular profiling by providing high-resolution insights into cellular heterogeneity and complexity. Traditional bulk omics approaches average signals from heterogeneous cell populations, thereby obscuring important cellular nuances. Single-cell omics studies enable the analysis of individual cells and reveal diverse cell types, dynamic cellular states, and rare cell populations. These techniques offer unprecedented resolution and sensitivity, enabling researchers to unravel the molecular landscape of individual cells. Furthermore, the integration of multimodal omics data within a single cell provides a comprehensive and holistic view of cellular processes. By combining multiple omics dimensions, multimodal omics approaches can facilitate the elucidation of complex cellular interactions, regulatory networks, and molecular mechanisms. This integrative approach enhances our understanding of cellular systems, from development to disease. This review provides an overview of the recent advances in single-cell and multimodal omics for high-resolution molecular profiling. We discuss the principles and methodologies for representatives of each omics method, highlighting the strengths and limitations of the different techniques. In addition, we present case studies demonstrating the applications of single-cell and multimodal omics in various fields, including developmental biology, neurobiology, cancer research, immunology, and precision medicine.

In the recent years, a wide range of metabonomic analytical techniques are widely used in the modern research of traditional Chinese medicine (TCM). At the same time, the international community has attached increasing importance to TCM toxicity problems. Thus, many studies have been implemented to investigate the toxicity mechanisms of TCM. Among these studies, many metabonomic-based methods have been implemented to facilitate TCM toxicity investigation. At present, the most prevailing methods for TCM toxicity research are mainly single analysis techniques using only one analytical means. These techniques include nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS), etc.; with these techniques, some favourable outcomes have been gained in the toxic reaction studies of TCM, such as the action target organs assay, the establishment of action pattern, the elucidation of action mechanism and the exploration of action material foundation. However, every analytical technique has its advantages and drawbacks, no existing analytical technique can be versatile. Multi-analysed techniques can partially overcome the shortcomings of single-analysed techniques. Combination of GC-MS and LC-MS metabolic profiling approaches has unravelled the pathological outcomes of aristolochic acid-induced nephrotoxicity, which can not be achieved by single-analysed techniques. It is believed that with the further development of metabonomic analytical techniques, especially multi-analysed techniques, metabonomics will greatly promote TCM toxicity research and be beneficial to the modernization of TCM in terms of extending the application of modern means in the TCM safety assessment, assisting the formulation of TCM safety norms and establishing the international standards indicators.

Single-cell Omics Assessment of Mitochondrial Function: Current Status and Future Perspectives.

In 2021, Acupuncture and Herbal Medicine (AHM) in English is officially published by Tianjin University of Traditional Chinese Medicine and China Association of Chinese Medicine. AHM is a peer-reviewed, diamond open-access international journal dedicated to publishing high quality research in the field of acupuncture and herbal medicine. The types of publication considered are editorial, review article, original article, guidelines and standards, commentary, short communications, case report, methodology, and letter to the editor. Featured by evidence-based medicine researches, AHM publishes innovative studies on acupuncture and herbal medicine, promotes academic exchanges, and drives the transformation of research achievements to serve the international development of traditional Chinese medicine (TCM) and establish the frontrunner journal for international communication of traditional medicine. Since the late 2000s, changes in the disease spectrum have led to significant transformation in medical models and the goals of medicine worldwide. World Health Organization has advocated for universal access to essential medical services for global health benefits and starts the great journey of building a healthy world. Mainly based on acupuncture and herbal medicine, TCM has a long history and has played an important role in ensuring the prosperity of the nation and safeguarding the health of the Chinese people. Although it is ancient, its concepts are not outdated, such as the concepts of harmony between human beings and the nature, the dynamic balance between yin and yang, the individualized treatment through syndrome differentiation, and the active preventive medical thought of health maintenance. All of these theories converge with the frontier directions of modern life science, and exhibit the value of TCM in modern society. The extensive practice has proven that solutions to life sciences and medical problems are entrenched in TCM, emphasizing the worth of its vigorous inheritance and development. The modernization of TCM has been more than 20 years and has made great progress. A meaningful experience is to maintain the inheritance and promote the innovation, through following the theoretical basis of TCM, introducing and learning from advanced scientific and technological methods which is making the past serve the present. “Stones from other mountains can serve to polish our jade.” The synergistic effect can be realized through complementary advantages. Since 2020, a sudden COVID-19 epidemic has wreaked havoc around the world, with China bearing the brunt. Chinese people have united in struggling against COVID-19 with the fearless heroism, and forged the great anti-epidemic spirit of “the supremacy of life, the unity of the whole country, the sacrifice of life and death, respect for science, and the sharing of destiny.” In less than three months, we have won a phased victory in the fight against the epidemic. TCM has participated in the prevention and control of COVID-19 epidemic and played a critical role in all of the stages[1]. Strict isolation and widespread use of TCM effectively blocked the spread of COVID-19 epidemic, reduced the development from mild to severe, increased the cure rate and reduced the mortality rate. In response to the different outcomes in clinical evaluation studies, the world's first Core Outcome Set (COS) was developed by Tianjin University of Traditional Chinese Medicine for clinical trials on COVID-19 (COS-COVID), which determined the “rate of mild to severe” as a critical clinical evaluation outcome[2]. This outcome was recognized and widely used in evaluating the results of clinical trials for TCM, clinical drugs and vaccines. In addition, China has also actively shared its anti-epidemic experience of integrated traditional Chinese and Western medicine with the world, which has been widely concerned and positively commented by the international community. The combination of the TCM and Western medicine is not only one of the characteristics of China's COVID-19 response[3], but also a vivid practice of inheriting the essence of TCM, maintaining the integrity and promoting the innovation. The pandemic has not only changed the world, but also change the world's attitude towards TCM. Mainly based on acupuncture and herbal medicine, TCM has been popularized and applied in more than 100 countries around the world and legalized in health insurance by dozens of countries and regions. A number of high-level papers have been published and high-level education and personnel training have been sustainably performing. AHM will hold to evidence-based medicine research and adhere to the directions of “inheriting the essence, maintaining the integrity, and promoting the innovation”, report innovative theories and excellent academic achievements in the field of acupuncture and herbal medicine, and move forward to the international leading journal. We will strive to build a bridge between traditional medicine and modern medicine, promote global communication and cooperation, and contribute to the health and well-being of all mankind! Conflict of interest statement Boli Zhang is the Editor-in-Chief of this journal. Funding This article was supported by the Action Plan for Excellence of Chinese Science and Technology Journals(Excellence Plan-D-028).

Traditional Chinese Medicine (TCM) is one of the oldest forms of medicine in the world. There has been a growing interest in TCM in Canada in terms of consumers and also among the research community. To cater for this interest, the Canadian Institute of Chinese Medicinal Research (CICMR) was established in 2004. Since its formation, CICMR has been organizing annual meetings. In 2008, the CICMR meeting, jointly organized with the Ontario Ginseng Innovation Research Centre, was held from October 16th to 19th, in London, Ontario, Canada. The meeting saw a number of participants and speakers from many countries who discussed TCM in a Canadian perspective. The talks and presentations focused on TCM practices in Asia and Canada; analytical techniques for unravelling the science behind TCM; basic and clinical research findings in the areas of cancer and cardiovascular diseases; safety and quality control issues; the regulatory and educational framework of TCM in Canada; and the latest findings in agricultural, chemical, and pharmacological research on ginseng from all over the world. The meeting successfully provided a platform for constructive discussions on TCM practices and research and education in Canada and the world.