摘要:ObjectiveThis study aims to construct a lightweight prompting project based on the chain of thought of syndrome element differentiation of coronary heart disease. To address high data dependence, low interpretability, and poor adaptation at the primary level of traditional differentiation methods, it also intends to develop a large language model for syndrome element differentiation and diagnosis of coronary heart disease (CHD-SEDD LLM) with both clinical interpretation and prediction accuracy.MethodsThe fine-tuning DeepSeek-r1:32b was used as the basis of the large language model for syndrome differentiation. According to Diagnostic Criteria of Angina Pectoris Syndrome Elements of Coronary Heart Disease, a three-level chain reasoning framework of ''symptom analysis-syndrome element scoring-syndrome combination'' was designed, and the differentiation rules were encoded as a structured Prompt template. A total of 6 541 cases of coronary heart disease were selected to verify the validity of CHD-SEDD LLM, and a comparison with the model without Prompts was conducted. The Macro average F1 score (Macro-F1) of syndrome classification, the accuracy of syndrome elements, and the reasoning time for a single case were used as the evaluation indicators.ResultsCHD-SEDD LLM demonstrated clear hierarchical reasoning ability in typical case validation. It accurately extracted core syndrome elements such as Qi deficiency and blood stasis and combined them into target syndromes like ''Qi deficiency and blood stasis syndrome'' and ''Yang deficiency and cold coagulation syndrome'', with reasoning processes consistent with traditional Chinese medicine (TCM) differentiation logic. Controlled experiments showed that the Macro-F1 score of the model reached 85.0%, 23.8 percentage points higher than that of the non-Prompt baseline. The accuracy of syndrome element identification was 84.8%, significantly higher than the baseline (68.7%). The logical conflict rate decreased from 37% to 4%, and the single-case reasoning time was only 4.1 seconds without significant delay caused by the reasoning chain.ConclusionsCHD-SEDD LLM achieves high accuracy and interpretability of syndrome differentiation for angina pectoris of coronary heart disease in a low-resource environment through a lightweight architecture driven by the chain thinking framework and syndrome diagnosis criteria. At the same time, the feasibility of the ''general model + chain of thought prompting for a domain'' paradigm is verified. With strong popularization, this paradigm can be applied to multi-disease syndrome differentiation and promote the standardization of intelligent TCM diagnosis and treatment.
关键词:coronary heart disease;syndrome element;large language model;chain thinking;intelligent syndrome differentiation
摘要:The simultaneous treatment of the heart and lungs is a unique theory in traditional Chinese medicine (TCM) based on the holistic concept of the interconnectedness of the five Zang organs. In TCM, the heart and lungs are closely related in terms of anatomical position, physiological functions, and pathological transmission, forming the theoretical foundation for the simultaneous treatment of the heart and lungs. This paper systematically reviewed the historical origins of the simultaneous treatment of the heart and lungs, proposed the study of the core theory of this approach through the correlation of ancestral Qi, nutritive-defense Qi, and collaterals, and applied the theory to explore the pathogenesis and treatment of representative major cardiopulmonary diseases such as chronic obstructive pulmonary disease (COPD), coronary heart disease, and atrial fibrillation. The aim is to lay the groundwork for further innovative development of the simultaneous treatment theory and its broader application in major cardiopulmonary diseases.
关键词:heart-lung correlation;simultaneous treatment of the heart and lungs;ancestral Qi;nutritive-defense Qi;collaterals
摘要:Cough variant asthma (CVA) is a special type of asthma characterized by cough as the sole or primary symptom, accompanied by airway hyperresponsiveness and cough hypersensitivity. CVA is the most common cause of chronic cough, with a high incidence and a protracted course, and some patients may progress to typical asthma. Modern medicine recommends inhaled glucocorticoids combined with bronchodilators, leukotriene receptor antagonists, and other agents as the mainstay of treatment for CVA. However, these therapies are often associated with multiple side effects, poor patient compliance, and frequent relapse after drug withdrawal. Traditional Chinese medicine (TCM) has a long history and unique advantages in the treatment of CVA, but there is still a lack of evidence-based medical support for TCM syndrome differentiation and treatment of this condition. To promote the standardized diagnosis and treatment of CVA in TCM, it is therefore particularly necessary to develop a disease-and-syndrome-based guideline in line with the principles of evidence-based medicine. The Guideline Project Team, drawing on the best available evidence and fully integrating clinical experience from experts, developed this guideline through extensive discussion and a systematic process, including expert interviews, clinical research, evidence retrieval and screening, evidence appraisal, formation of recommendations, drafting, self-assessment, solicitation of opinions, and review by the Association. Targeting CVA patients and grounded in clinical practice, the guideline provides guidance and recommendations on the TCM etiology and pathogenesis, diagnostic criteria and evaluation methods, differential diagnosis, syndrome differentiation and treatment, efficacy evaluation, and prevention and nursing of CVA. It is intended for respiratory specialists, internists, TCM practitioners (including integrative medicine physicians), general practitioners, as well as relevant nursing staff and pharmacists. This guideline aims to standardize TCM syndrome diagnosis and treatment for CVA, provide clinicians with strategies and methods for standardized TCM management, fully leverage the advantages of TCM in treating CVA, and help improve the clinical diagnosis, treatment, and research standards for this condition.
关键词:cough variant asthma;traditional Chinese medicine (TCM);integrated traditional Chinese and western medicine;diagnosis and treatment guidelin
摘要:Non-clinical pharmacology of traditional Chinese medicine (TCM) formulae plays a crucial role in elucidating their therapeutic mechanisms. With the integration of cutting-edge disciplines such as system biology, big data, and artificial intelligence, the research depth and breadth in this field continue to expand. However, technical standards for non-clinical pharmacology research on TCM formulae have not yet been established. To standardize non-clinical pharmacology research on TCM formulae, enhance the research quality, and facilitate the transformation between clinical and basic research, Technical Guidelines for Non-Clinical Pharmacology Research on Traditional Chinese Medicine Formulae were established. Guided by the integrative pharmacology of TCM and driven by clinical value, the guidelines employed multi-dimensional qualitative "pharmacokinetics (PK)-pharmacodynamics (PD)" studies and quantitative "PK-PD" studies of key components. From panoramic description to precise mechanistic research, the guidelines established a complete evidence chain system for the effectiveness of TCM formulae, demonstrating the holistic characteristics of mechanisms with "multi-component, multi-pathway, and multi-target". Meanwhile, the guidelines emphasized three requirements, including repeatability for animal models, quantifiability for pharmacodynamic evaluation, and interpretability for mechanisms of action, providing technical guidance that could be feasible and verifiable for basic research and new TCM development. The guidelines were developed by leveraging the research strengths of the drafting team, harnessing the findings from the literature review, achieving the consensus through extensive discussions among multidisciplinary experts, and collecting broad expert opinions from universities, research institutes, and enterprises engaged in new drug development, thus ensuring the guidelines are scientific, standardized, practical, and feasible.
关键词:traditional Chinese medicine formulae;non-clinical pharmacology;integrative pharmacology of traditional Chinese medicine;new traditional Chinese medicine;animal model of traditional Chinese medicine;pharmacodynamic evaluation;molecular regulation
摘要:Wilson disease is a rare copper metabolism disorder that affects multiple organs, with the kidneys being the third most commonly involved organ. Renal damage can occur at any stage of the disease, yet its manifestations are often overlooked during the disease course. Some patients present with no obvious symptoms in the early stages, resulting in delayed treatment until significant symptoms appear, often too late for optimal intervention. Due to the rarity of Wilson disease and the nonspecific nature of renal symptoms, it is difficult to conduct large-sample, multicenter controlled clinical trials. Existing diagnostic and treatment guidelines primarily focus on hepatic and neurological manifestations, with relatively little attention given to renal involvement, hindering further clinical diagnosis, treatment, and efficacy evaluation. Therefore, the timely and appropriate identification and treatment of renal damage in Wilson disease are critical to improving therapeutic outcomes and patient quality of life. This consensus was jointly developed by Chinese experts in encephalopathy (neurology), hepatology, and nephrology, encompassing both traditional Chinese medicine (TCM) and Western medicine. It integrates theoretical foundations of TCM with frontline clinical experience of TCM experts. The drafting process involved systematic collection, analysis, integration, and summarization of clinical patterns. The initial draft, prepared by the primary authors, underwent cross-disciplinary peer review and revision by expert reviewers. This consensus provides integrated TCM and Western medicine recommendations for the diagnosis, treatment, and management of Wilson disease-associated renal damage, aiming to optimize therapeutic regimens, support scientific daily management, improve disease outcomes, and enhance patients' quality of life. Furthermore, it promotes standardization, specialization, and consistency in clinical pathways for the diagnosis and management of renal involvement in Wilson disease, contributing to scientific, precise, and optimized care for this rare condition. The consensus will be continually validated in clinical practice and regularly updated to incorporate emerging medical evidence.
关键词:Wilson disease;renal damage;traditional Chinese and Western medicine;expert consensus
摘要:Dieda Huoxue capsules are derived from Dieda Huoxue powder, as recorded in the Pharmacopoeia of the People's Republic of China. Developed exclusively by Jiangxi Yuanchao Medical Technology Co., Ltd., they are classified as a Class B Chinese patent medicine covered by medical insurance. The capsules possess the effects of soothing the tendons and promoting blood circulation, dispersing blood stasis, and relieving pain. Clinically, they are used for the treatment of traumatic injuries, pain due to blood stasis, acute lumbar sprains, and chest qi stagnation. Given the current lack of sufficient clinical evidence regarding the traditional Chinese medicine (TCM) syndromes, efficacy, and safety of this product, and in the absence of corresponding expert consensus, this study was conducted in accordance with the principles of evidence-based medicine. A panel of 33 national experts in evidence-based medicine, orthopedics and traumatology, and pharmacy was organized. Using methods such as the nominal group technique and questionnaire surveys, and based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, the Expert Consensus on the Clinical Application of Dieda Huoxue capsules (hereinafter referred to as the "Consensus") was developed. The Consensus clearly defines the standardized clinical application of Dieda Huoxue capsules, including disease staging, syndrome characteristics, treatment duration, dosage, combination therapy, usage recommendations, contraindications, and precautions. It is intended for relevant personnel in medical and health institutions. Based on 19 clinical questions, the Consensus proposes 3 graded recommendations and 16 consensus-based suggestions, covering the following aspects. ① Indications and syndromes: In TCM, it is mainly used for traumatic injuries, corresponding to soft tissue contusions, acute lumbar sprains, etc., in Western medicine. The primary TCM syndrome is blood stasis. ② Administration and dosage: For oral administration, the recommended dosage is 6 capsules per dose, twice daily. For external application (limited to closed injuries), the capsule contents may be mixed with yellow rice wine or vinegar (1∶2 ratio) and applied as a topical paste. The treatment course is 2-4 weeks for mild cases and 4-6 weeks for severe cases. In elderly patients, drug holidays between treatment cycles are recommended. ③ Combination therapy: For moderate to severe cases, Dieda Huoxue capsules can be combined with non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, etc., with monitoring for adverse reactions. ④ Safety: Common adverse reactions include rash and gastrointestinal discomfort. The capsules are contraindicated in pregnant women, individuals with severe gastric ulcers, and patients with open wounds. Concurrent use with anticoagulants should be avoided. Modern research has shown that this medicine can alleviate pain from osteoporotic fractures in elderly patients with Qi stagnation and blood stasis syndromes, promote fracture healing, and improve bone metabolism. They have also demonstrated good efficacy in relieving swelling and pain associated with post-fracture conditions and osteoarthritis. This consensus provides a scientific foundation for promoting the rational clinical use of Dieda Huoxue capsules, improving therapeutic outcomes, and reducing medication-related risks. It will be dynamically revised in accordance with future research advancements.
关键词:expert consensus;Dieda Huoxue Capsules;clinical application;orthopedics and traumatology department
摘要:Traditional Chinese medicine (TCM) compound prescriptions are characterized by diverse chemical components, multi-directional pharmacological effects, and multi-dimensional mechanisms of action. With complex in vivo metabolic processes, they reflect the holistic therapeutic philosophy of TCM. Current pharmacological evaluation models and technologies for TCM compound prescriptions lack sufficient clinical relevance, making it difficult to accurately and comprehensively assess their efficacy. There is an urgent need to develop novel pharmacological evaluation models for TCM compound prescriptions. The field of drug evaluation is undergoing a technological revolution, evolving from organ-on-chip to organoids-on-chip and from single-organoids-on-chip to multi-organoids-on-chip systems and integrating advancements in robotics and artificial intelligence (AI). To harness the advantages of these emerging technologies and address the demands of TCM pharmacological research, this paper proposed the development of an organoids-on-a-chip "human-simulator" device. This device will integrate cutting-edge technologies such as organoids-on-chips, AI, and robotics to evaluate physiological, pathological, and pharmacological patterns of TCM compound prescriptions across bionic, holistic, and spatiotemporal dimensions. It aims to provide a novel tool for holistic efficacy assessment, active ingredient identification, and mechanistic exploration of TCM compound prescriptions. Furthermore, a technical standard system and a data-sharing platform for the application of the device in TCM compound prescriptions will create a standardized, open-access environment and a scientific paradigm to advance the study of TCM compound prescriptions.
摘要:Clinical Chinese materia medica centers on investigating the theory of traditional Chinese medicine (TCM) properties and their application rules. As a pivotal constituent of the TCM theoretical system, the theory of TCM properties demands multi-dimensional scientific characterization to decipher its biological essence and facilitate translation into precision medication using modern scientific theories and technical methods, with substantial progress achieved in recent years. This paper systematically summarizes advances in modern research, including bioenergetic characterization and chemical biological decoding of the four natures and five flavors, targeted localization of the meridian tropism theory, and analysis of toxicity. It introduces China's first intelligent platform focusing on TCM properties developed by our team—the Intelligent Analysis Platform of Traditional Chinese Medicine Properties (TCM-AIPP). Additionally, it sorts out the modern clinical translation pathways of TCM properties and intelligent decision-making for rational drug use enabled by advanced technologies such as artificial intelligence, systems biology, and knowledge graphs. Finally, it prospects the application of cutting-edge technologies like spatiotemporal omics, organoid models, and quantum computing in deciphering the scientific connotation of drug properties. This work aims to provide a reference for establishing a scientific modern theoretical system of TCM properties and holds great significance for the accurate clinical application of the theory of TCM properties.
关键词:clinical materia medica;theory of traditional Chinese medicine properties;modernization research;scientific characterization;precise drug application
摘要:Intelligent manufacturing technology revolutionizes traditional manufacturing industries by enhancing the automation, informatization, and intelligence of production processes, thereby creating new opportunities for the innovative advancement of the intelligent manufacturing industry of Chinese materia medica(CMM). Based on the current state of intelligent manufacturing industry of CMM, this paper summarizes technological innovations and their applications in critical stages of CMM production, such as extraction, separation, purification, and concentration, and also analyzes the shortcomings of existing technologies. In view of the low efficiency, high energy consumption, low intelligence level of unit equipment, strategies for the whole process optimization scheme of intelligent manufacturing of CMM and the intelligent management and control strategy of unit equipment are proposed. These strategies encompass multiple aspects, including data collection and processing, model construction, CMM production process simulation, intelligent optimization algorithm development, system integration and collaborative mechanisms, real-time monitoring and early-warning systems, and intelligent decision-making and precise control. The aim of the present work is to provide technical guidance and strategic suggestions for intelligent manufacturing of CMM, promoting its development towards a green and intelligent direction.
关键词:intelligent manufacturing of Chinese materia medica;intelligent unit equipment;digital twin;whole-process optimization;intelligent management and control
摘要:Chronic lung disease (CLD) is a complex and progressive group of pulmonary disorders and encompasses various disease types, mainly including chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), lung carcinoma, etc. The occurrence of CLD induces the infiltration of inflammatory cells and scar repair in lung tissue, resulting in lung tissue damage and lung function decline, which severely affects the life and health of patients. Traditional drug-delivery methods have been widely used in the clinical treatment of CLD for a long time. However, for lung tissue, the drug targeting is poor, which can induce relatively strong side effects and patient suffering, increase the cost of medication, and lead to a decrease in patient compliance. Inhalation therapy allows drugs to directly reach the lungs through inhalation, enabling direct action on lung tissue. It has higher safety, stronger targeting, and better effectiveness. The potential application value of inhalation therapy in the treatment of CLD is quite remarkable, and it has a significant curative effect on various CLDs. Due to differences in the pathogenesis of CLD and inhalation treatment approaches, this paper reviewed the modern research and clinical application characteristics of Chinese and Western medicine inhalation therapy. The aim is to provide a reference for clinical practice, optimize inhalation treatment plans, and provide new research ideas for the current drug inhalation treatment of CLD.
摘要:The core pathophysiological mechanism of coronary atherosclerotic heart disease(CHD) lies in myocardial ischemia caused by coronary artery stenosis or occlusion, with key pathways including vascular endothelial injury, lipid plaque deposition and rupture. Traditional Chinese medicine(TCM) classifies this disease under the categories of chest discomfort and heartache, viewing its nature as deficiency in origin and excess in superficiality and intermingled deficiency and excess, with the core pathogenesis involving disharmony among Qi, vessels and blood. Based on long-term theoretical and experimental research as well as clinical practice, our team proposed the theory of Qi-blood interacting in vessels, which posited that "Qi leads blood through the vessels, and blood carries Qi through the vessels", and that the vessels served as the hub for the circulation of Qi and blood. Therefore, according to the theory, combined with the clinical progression of CHD, its course is divided into three stages, and corresponding stage-specific intervention strategies are formulated accordingly:In the early stage of onset, characterized by Qi deficiency and blood stasis, and tightening of collaterals and meridians, the focus is on tonifying Qi, promoting blood circulation, softening collaterals and harmonizing meridians, emphasizing "preventing disease before it occurs". During the disease progression stage, characterized by blood obstruction and weak Qi, and swelling of the veins, the primary treatment focuses on promoting blood circulation, alleviating swelling, removing blood stasis, and clearing turbidity, aiming to achieve the goal of "preventing the progression of the disease". During the critical phase of the disease, characterized by syndrome of blockade of veins, and deficiency of both Qi and blood, the focus should be on urgently unblocking the veins, restoring Qi, and promoting blood circulation to achieve "restoring function and preventing complications". Based on TCM pathogenesis theory, this paper combined modern medical research on the pathogenesis of CHD to construct a collaborative model of TCM syndrome differentiation and modern pathology, in order to propose TCM intervention strategies for CHD patients at different stages from the perspectives of overall regulation and multi-target intervention, with the hope of providing theoretical innovation and practical guidance for the prevention and treatment of CHD by TCM.
关键词:theory of traditional Chinese medicine;Qi-blood interacting in vessels;vessel damage;coronary heart disease;pathogenesis evolution;staged intervention
摘要:ObjectiveTo investigate the effect of Xianlian Jiedu prescription in modulating antitumor immune response of intestinal flora-mediated CD8+ T cells in colorectal cancer (CRC).MethodsThirty male BALB/c mice were divided into a normal group, a model group, an oxaliplatin group [8×10-3 g·kg-1·(3 d)-1], a high-dose Xianlian Jiedu prescription (XLJD-H) group (12.9 g·kg-1·d-1), and a low-dose Xianlian Jiedu prescription (XLJD-L) group (6.45 g·kg-1·d-1). A CRC xenograft model was established through subcutaneous injection of CT-26 cells, followed by respective interventions. Additionally, ten male BALB/c mice were divided into a Xianlian Jiedu prescription-fecal microbiota transplantation (XFMT) group and a model-fecal microbiota transplantation (MFMT) group. The intestinal colonized bacteria were eradicated with a quadruple antibiotic solution, and then a pseudo-germ-free CRC xenograft mouse model was established through subcutaneous injection of CT-26 cells. Fecal samples from the model group and XLJD-H group were collected to prepare fecal microbiota solutions. The XFMT group was gavaged with the fecal microbiota solution from CRC mice treated with XLJD-H, and the MFMT group received the fecal microbiota solution from CRC mice in the model group. Tumor volume changes were monitored. Hematoxylin and eosin (HE) staining was used to assess pathological and morphological changes of the tumor. PacBio full-length diversity sequencing was used to analyze intestinal flora changes. Flow cytometry and immunofluorescence staining were employed to evaluate changes in T cell infiltration in tumor tissue. Enzyme-linked immunosorbent assay (ELISA) was performed to measure differences in IFN-γ levels in tumor tissue.ResultsCompared to those in the model group, the tumor volumes in the oxaliplatin group, XLJD-H group, and XLJD-L group were significantly reduced (P<0.01). HE staining revealed that compared to the model group, the oxaliplatin and XLJD-H groups exhibited an increased necrotic area within the tumor tissue, with a sparser cellular arrangement and reduced nuclear division figures. Intestinal flora sequencing analysis indicated that although the Chao1, ACE, Shannon, and Simpson indices in the XLJD-H group were reduced compared to the model group, the differences were not statistically significant. Principal co-ordinates analysis (PCoA) demonstrated a distinct difference in the intestinal flora structure between the normal group and model group. Moreover, the intestinal flora structure of CRC mice in the XLJD-H group was significantly more similar to that of the normal group (P<0.01). Compared to that in the control group, the abundance of Akkermansia muciniphila, Muribaculum intestinale, Parabacteroides goldsteinii, Bacteroides thetaiotaomicron, and Parabacteroides gordonii significantly decreased in the model group was significantly dropped (P<0.05, P<0.01), while the abundance of Duncaniella muris, Prevotellamassilia sp 002933955, Prevotella sp 002933775, and Kineothrix alysoides was significantly increased (P<0.05, P<0.01). Furthermore, compared to that in the model group, the abundance of Akkermansia muciniphila significantly increased in the XLJD-H group (P<0.05), whereas the abundance of Kineothrix alysoides significantly decreased (P<0.01). Linear discriminant analysis (LDA>4.0) revealed an enrichment of Alistipes, Helicobacteraceae, Helicobacter, Helicobacter pylori BU, Bacteroides acidifaciens, Campylobacterales, Kineothrix, Kineothrix alysoides, Acetatifactor sp 900066365, Faecalimonas, Faecalimonas umbilicata, Acetatifactor, Lachnospiraceae, Clostridia, Eubacteriales, and Firmicutes in the model group, whereas Verrucomicrobia, Verrucomicrobiales, Akkermansiaceae, Akkermansia, Akkermansia muciniphila, Bacteroidales, Bacteroidia, Bacteroidetes, Parabacteroides, Tannerellaceae, Muribaculum, and Parabacteroides gordonii were enriched in the XLJD-H group. Additionally, compared to the model group, the XLJD-H group exhibited a significant increase in the proportion of CD8+ T cells and a higher level of IFN-γ in tumor tissue (P<0.01), while the proportion of CD4+ T cells in the tumor tissue of the XLJD-H group was significantly reduced (P<0.05). Moreover, compared to the MFMT group, the XFMT group exhibited a significant reduction in xenograft tumor volume (P<0.05). HE staining indicated an increase in necrotic areas within the tumor tissue of the XFMT group, along with a sparser arrangement of cells and a reduction in nuclear division. Compared to the MFMT group, the XFMT group showed a significant decrease in both Shannon and Simpson indices (P<0.05, P<0.01). PCoA suggested a distinct difference in the intestinal flora structure between the MFMT and XFMT groups (P<0.01). At the species level, compared to the MFMT group, the abundance of Akkermansia muciniphila and Phocaeicola sartorii significantly increased in the XFMT group (P<0.01). Linear discriminant analysis (LDA>4.0) results indicated enrichment of Muribaculum sp 002492595, Acetatifactbr sp 900066365, Kineothrix, Duncaniella freteri, Oscillospiraceae, Acetatifactor, Faecalimonas umbilicata, Faecalimonas, Bacteroidia, Bacteroidales, Lachnospiraceae, Clostridia, Eubacteriales, and Firmicutes in the MFMT group, whereas Verrucomicrobia, Verrucomicrobiae, Verrucomicrobiales, Akkermansiaceae, Akkermansia, Akkermansia muciniphila, Phocaeicola sartorii, and Phocaeicola were enriched in the XFMT group. Compared to the MFMT group, the XFMT group exhibited a significant increase in the proportion of CD8+ T cells and a higher level of IFN-γ in tumor tissue (P<0.01).ConclusionThe Xianlian Jiedu prescription may ameliorate dysbiosis in the intestines of CRC mice and enhance the antitumor immune response mediated by CD8+ T cells, thereby exerting an anticancer effect against CRC.
关键词:intestinal flora;tumor immunity;colorectal cancer;Xianlian Jiedu prescription;traditional Chinese medicine
摘要:ObjectiveTo construct and evaluate a metastatic animal model of colorectal cancer (CRC) with spleen Qi deficiency and damp-heat stasis toxin syndrome, and to analyze the biological characteristics of the model.MethodsThe 30 BALB/c mice were randomly divided into the sham surgery group, the model group, and the spleen Qi deficiency with damp-heat stasis toxin syndrome (PXSRYD) group. Mice in the sham surgery group underwent laparotomy without injection. Mice in the model group received orthotopic injection of 1×106 CT26 cells into the cecum. In the PXSRYD group, based on orthotopic CT26 cell injection, syndrome modeling was induced using a combination of ''irregular diet + overwork + high-sugar and high-fat diet + high temperature and humidity''. A macroscopic syndrome scoring scale was developed to evaluate the general condition of the mice. The presence of orthotopic tumors and liver metastases was assessed. Hematoxylin-eosin (HE) staining was used to observe pathological features of primary tumors and liver metastases. Immunohistochemistry (IHC) was used to detect tumor invasion-related indicators, including the average optical density (AOD) of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). The phloroglucinol method was used to measure D-xylose content, and a microplate method was used to determine blood lipid levels. Tumor-associated macrophage (TAM) infiltration was assessed by flow cytometry (FCM) and immunofluorescence (IF). Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression of CD86, iNOS, CD163, and CD206. Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of IL-10, IL-17, and CXCL4, to comprehensively analyze the biological characteristics of the model.ResultsIn terms of macroscopic syndrome scoring, compared with the Sham surgery group, the Model group showed an increased syndrome score (P<0.01), while the PXSRYD group exhibited a significantly higher score than the Model group (P<0.01). In terms of biological characteristics, compared with the Sham surgery group, the Model group showed increased tumor volume and tumor weight (P<0.01), as well as a higher number and area ratio of liver metastases (P<0.05).The orthotopic tumor tissues showed tightly arranged cells with enlarged, deeply stained, irregular nuclei, nuclear mitotic figures, and nuclear atypia. The positive area rate of the proliferation marker Ki67 was increased (P<0.01), and the AOD values of VEGF, MMP-2, and MMP-9 were elevated (P<0.05, P<0.01). There was no statistically significant difference in D-xylose levels. Serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were increased, while high-density lipoprotein cholesterol (HDL-C) levels were decreased (P<0.01). In peritoneal lavage fluid and orthotopic tumor tissues, the proportion of CD86⁺ TAMs decreased, while CD206+ TAMs increased (P<0.05, P<0.01). The mRNA expression levels of CD86 and iNOS were decreased, while CD206 mRNA expression was increased (P<0.01), CD163 mRNA expression showed no statistically significant change. Levels of IL-10 and IL-17 were significantly elevated (P<0.01), whereas CXCL4 levels showed no significant difference. Compared with the model group, the PXSRYD group showed no significant differences in tumor volume or tumor weight, but exhibited a significantly higher number and area ratio of liver metastases (P<0.01). Tumor cells in orthotopic tissues were more densely packed, with more pronounced nuclear enlargement, hyperchromasia, irregular shapes, mitotic figures, and nuclear atypia. The Ki67-positive rate was significantly increased (P<0.01), along with AOD values of VEGF, MMP-2, and MMP-9 (P<0.01). D-xylose content was markedly decreased (P<0.01). TC, TG, and LDL-C levels were elevated, while HDL-C levels were reduced (P<0.01). The proportion of CD86+ TAMs in peritoneal lavage fluid and tumor tissue was significantly reduced, while CD206+ TAMs were significantly increased (P<0.01). CD86 and iNOS mRNA expression levels were markedly downregulated, while CD163 and CD206 mRNA expression levels were significantly upregulated (P<0.01). Levels of IL-10, IL-17, and CXCL4 were significantly elevated (P<0.01).ConclusionThe metastatic colorectal cancer animal model established by orthotopic cecal injection combined with irregular diet, overexertion, high-sugar and high-fat intake, and high temperature and humidity conditions exhibits the characteristic features of spleen Qi deficiency and damp-heat stasis toxin syndrome. Significant changes in biological characteristics such as histopathological features, metastasis and invasion markers, serological indicators, and TAM infiltration suggest that this model can serve as a biological evaluation standard.
关键词:colorectal cancer;metastasis;spleen Qi deficiency with damp-heat stasis toxin;biological characteristics
摘要:ObjectiveTo investigate the mechanism by which Xianlian Jiedu prescription (XLJD) suppresses colorectal cancer metastasis based on the regulation of epithelial-mesenchymal transition (EMT) by C-C motif chemokine ligand 5 (CCL5) secreted from M2-polarized tumor-associated macrophages (TAMs).MethodsHuman monocytic leukemia THP-1 cells were induced to differentiate into M2-type TAMs, identified by morphology and reverse transcription quantitative polymerase chain reaction (Real-time PCR), and co-cultured with human colorectal cancer HCT116 cells. Experimental groups included blank control (HCT116 cells), CCL5 intervention (20, 40, 60 μg·L-1), co-culture control (HCT116 + TAMs), XLJD low/medium/high dose (co-culture + 1, 2, 3 g·L-1 XLJD), and CCL5 antibody (2 mg·L-1). CCL5 levels in cell culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA). The effects of CCL5 on HCT116 proliferation were evaluated by CCK-8 and colony formation assays. Wound-healing and Transwell migration assays were used to assess cell migration. Western blot was performed to detect E-cadherin, N-cadherin, Vimentin, β-catenin, signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3) expression.ResultsReal-time PCR results showed that, compared with the M0 group, M2-type TAMs had significantly higher Arginase-1 and CCL22 expression (P<0.01). ELISA revealed that, compared with the blank control, CCL5 levels were elevated in the M0 macrophage group (not statistically significant) and significantly increased in the M2 macrophage and co-culture groups (P<0.01). Compared with the co-culture control, XLJD at low, medium, and high doses significantly reduced CCL5 levels (P<0.05, P<0.01). CCK-8 results showed no significant differences in HCT116 viability at 24, 48, or 72 h under CCL5 treatment (2.5-100 μg·L-1). Colony formation assays showed no significant differences in clonogenic rates between CCL5-treated (20, 40, 60 μg·L-1) and blank groups. Wound-healing and Transwell assays demonstrated that, compared with the blank control, CCL5-treated (20, 40, 60 μg·L-1) and co-culture groups had significantly enhanced migration (P<0.01), while the CCL5 antibody group and XLJD groups (1, 2, 3 g·L-1) had significantly reduced migration compared with the co-culture control (P<0.01). Western blot results showed that, compared with the blank control, CCL5-treated and co-culture groups exhibited significantly decreased E-cadherin expression (P<0.01) and increased N-cadherin, Vimentin, β-catenin, STAT3, p-STAT3 expression, and p-STAT3/STAT3 ratio (P<0.05, P<0.01). Compared with the co-culture control, XLJD and CCL5 antibody groups significantly decreased N-cadherin, Vimentin, β-catenin, STAT3, p-STAT3 expression, and p-STAT3/STAT3 ratio (P<0.05, P<0.01), while significantly increasing E-cadherin expression (P<0.01).ConclusionXLJD significantly inhibits the migration of HCT116 cells in a TAM-HCT116 co-culture model. Its mechanism may involve targeting TAM-derived CCL5 and suppressing STAT3 phosphorylation-mediated β-catenin activation, thereby reversing EMT marker dysregulation.
摘要:Colorectal cancer (CRC) is a common malignant tumor of the digestive tract, with incidence and mortality rates rising year by year. The pathogenesis of CRC is complex, and the tumor microenvironment (TME) together with lymphocytes influences its occurrence and development. Lymphocytes can be classified into thymus-dependent lymphocytes (T cells), natural killer (NK) cells, and bone marrow-dependent lymphocytes (B cells). By affecting tumor cell proliferation and apoptosis, invasion and metastasis, and immune regulation, they exert both tumor-promoting and tumor-suppressing effects within the TME. In recent years, traditional Chinese medicine (TCM) has shown remarkable efficacy in the comprehensive treatment of CRC, with its unique advantages of multi-target action, low toxicity, and holistic regulation becoming increasingly prominent. Studies have shown that TCM monomers such as atractylenolide Ⅰ, cycloastragenol, and curcumin, as well as single herbs like Ginseng Radix et Rhizoma Rubra, Marsdeniae Tenacissimae Caulis, and Sanguisorbae Radix, and formulas like Si Junzitang, Sinitang, and Xianlian Jiedu decoction, can increase the proportion and activity of lymphocytes such as CD4+ T cells, CD8+ T cells, and NK cells, while decreasing the proportion and activity of regulatory T cells (Tregs). They modulate the balance between type 1 helper T cells (Th1) and type 2 helper T cells (Th2), upregulate the expression of immune-activating factors such as interleukin (IL)-2, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α), and downregulate the expression of immune-suppressive factors such as IL-10, transforming growth factor-beta (TGF-β), and forkhead box P3 (FoxP3). Through activation of immune-related signaling pathways, they enhance tumor immune surveillance and cytotoxicity, remodel the tumor immune microenvironment (TIME), and thereby exert preventive and therapeutic effects against CRC. This paper reviews recent literature on the regulation of lymphocytes by TCM in the anti-CRC response, summarizing its effective components, molecular targets, and mechanisms of action, and discussing existing problems in current research, with the aim of providing new perspectives and ideas for CRC prevention and treatment using TCM.
关键词:traditional Chinese medicine;colorectal cancer (CRC);lymphocytes;mechanism research
摘要:ObjectiveThis study aims to explore the effect and mechanism of Hei Xiaoyaosan in preventing Alzheimer's disease (AD) by regulating the PTEN-induced kinase 1 (PINK1)/Parkin signaling pathway and intervening in mitophagy.MethodsFifty 4-month-old male APP/PS1 mice were randomly divided into a model group, the donepezil hydrochloride group (0.65 mg·kg-1), and the high-, medium-, and low-dose Hei Xiaoyaosan groups (22.10, 11.05, and 5.53 g·kg-1). Ten additional male C57BL/6J mice of the same age served as the blank control group. Following a 90-day treatment period, learning and memory functions were evaluated using the Y-maze test. Additionally, hippocampal morphology was examined through hematoxylin-eosin (HE) staining. Fluoro-Jade B (FJB) staining was employed to examine neuronal damage and the number of damaged cells. Transmission electron microscopy (TEM) was utilized to observe mitochondrial damage. Immunofluorescence staining was employed to assess the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3) and selective autophagy adaptor protein 1 (p62) in the hippocampus. Western blot analysis was performed to quantify the protein expression of PINK1, Parkin, phosphorylated Parkin (p-Parkin), LC3, and p62. Real-time quantitative polymerase chain reaction (Real-time PCR) was utilized to evaluate the mRNA expression levels of PINK1 and Parkin.ResultsCompared with the blank group, the model group exhibited a decreased alternation rate in the Y-maze test (P<0.01), disordered hippocampal cell arrangement, enlarged intercellular space, and severe nuclear pyknosis. There was increased neuronal damage and number of damaged cells (P<0.01), severe mitochondrial swelling and rupture, reduced protein and mRNA expression levels of PINK1 and p-Parkin (P<0.01), increased immunofluorescence intensity of p62 (P<0.01), and decreased fluorescence signal intensity of LC3 (P<0.01). Compared with the model group, the donepezil hydrochloride group and the high- and medium-dose Hei Xiaoyaosan groups showed an increased alternation rate (P<0.05, P<0.01), alleviated hippocampal neuronal damage, and reduced numbers of damaged cells (P<0.01). There was a narrowed intercellular arrangement, improved nuclear morphology, and alleviated mitochondrial injury. The donepezil hydrochloride group and the high-dose Hei Xiaoyaosan group exhibited reduced p62 fluorescence intensity (P<0.05, P<0.01), increased LC3 fluorescence intensity (P<0.05, P<0.01), elevated protein expression of PINK1 and p-Parkin (P<0.05, P<0.01), increased LC3 expression (P<0.05, P<0.01), and decreased p62 expression (P<0.05, P<0.01). The donepezil hydrochloride group and the high- and medium-dose Hei Xiaoyaosan groups showed increased mRNA expression levels of PINK1 (P<0.05, P<0.01), and the donepezil hydrochloride group and the high-dose Hei Xiaoyaosan group exhibited elevated mRNA levels of Parkin (P<0.05).ConclusionHei Xiaoyaosan can improve learning and memory abilities and ameliorate pathological damage in APP/PS1 mice. The mechanism may be related to the regulation of the PINK1/Parkin signaling pathway, enhancement of mitophagy, and repair of damaged neurons to prevent and treat AD.
摘要:ObjectiveThis study explores the intervention effect of Hei Xiaoyaosan on neuroinflammation in mice by regulating the trimethylamine (TMA)/Flavin containing monooxygenase 3 (FMO3)/trimethylamine N-oxide (TMAO) metabolic pathway.MethodsSixty 4-month-old SPF grade APP/PS1 male mice were randomly divided into the model group, the Bifidobacterium Tetravaccine Tablets group, donepezil hydrochloride group, and high, medium, and low dose groups of Hei Xiaoyaosan using a random number table. The mice were orally administered continuously for 90 days. Ten male wild-type C57BL/6J mice of the same age and lineage were used as the blank control group. The open field experiment was used to detect the autonomous activity of mice, the Morris water maze test was used to test the learning and memory ability of mice, Nissl staining was used to observe the morphology of hippocampal neurons in each group of mice, enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of interleukin (IL)-1β, IL-18 in mouse hippocampal tissue and tau, phosphorylation (p)-tau(Thr181), p-tau(Thr231), p-tau(Ser262), p-tau(Ser396) in mouse serum, Liquid Chromatography-Mass Spectrometry (LC-MS) analysis was used to detect the level of TMAO in mouse serum, and Western blot was used to detect the expression of FMO3 in mouse liver and NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), Caspase-1 proteins in hippocampus.ResultsCompared with the blank group, the model group mice showed a decrease in total distance, number of times they entered the central area, and central area activity distance in the open field experiment (P<0.01). On the 3rd and 4th days of navigation experiments, the escape latency time was prolonged (P<0.01). The number of platform crossings decreased (P<0.01). Abnormal cellular structure of hippocampal neurons and blurred Nissl bodies. The hepatic cord structure is irregular, liver cells are arranged irregularly, some have nuclear dissolution, and there is a large amount of congestion in the central vein and portal area of the liver. The levels of IL-1β, IL-18 in hippocampal tissue and tau, p-tau(Thr181), p-tau(Thr231), p-tau(Ser262), p-tau(Ser396), and TMAO in serum increased (P<0.05, P<0.01). The expression of FMO3 protein increased in liver tissue (P<0.01), while the expression of NLRP3, ASC, and Caspase-1 proteins increased in hippocampus tissue (P<0.01). Compared with the model group, in the Bifidobacterium Tetravaccine Tablets group, donepezil hydrochloride group, and high-dose Hei Xiaoyaosan group, the total distance of movement, the distance of movement in the central area, and the escape latency on the 3rd and 4th days of the mice decreased (P<0.05, P<0.01), while the number of entries into the central area and the number of platform crossings increased (P<0.05, P<0.01). In each drug administration group, the damage to hippocampal neurons was improved. The expression of FMO3 protein in liver tissue and Caspase-1 protein in hippocampal tissue decreased, and the levels of IL-1β, IL-18 in mouse hippocampal tissue and tau, p-tau(Thr181), p-tau(Thr231), p-tau(Ser262), p-tau(Ser396) in mouse serum decreased (P<0.05, P<0.01). In the Bifidobacterium Tetravaccine Tablets group, donepezil hydrochloride group, and medium- and high-dose Hei Xiaoyaosan groups, the content of TMAO in mouse serum and the expression of NLRP3 and ASC proteins in hippocampal tissue decreased (P<0.05, P<0.01).ConclusionHei Xiaoyaosan can improve cognitive impairment in APP/PS1 mice, and its mechanism of action may be related to regulating the TMA/FMO3/TMAO metabolic pathway to inhibit neuroinflammation.
摘要:ObjectiveTo explore the mechanism of action of Hei Xiaoyaosan in regulating the intestinal barrier and improving the learning and memory abilities of Alzheimer's disease (AD) model mice.MethodsSixty four-month-old male amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice were randomly divided into a model group, low, medium, and high dose groups of Hei Xiaoyaosan (5.53, 11.05, and 22.10 g·kg-1), a group treated with bifidobacterium tetravaccine tablets (0.585 g·kg-1), and a group treated with donepezil hydrochloride (6.5 mg·kg-1), with 10 mice in each group. Additionally, 10 male C57BL/6J mice of the same age were used as a blank control group. The treatment was administered continuously for 90 days. The Morris water maze test was performed for behavioral detection. Hematoxylin-eosin (HE) staining was employed to analyze the morphological changes of the colon in mice. Transmission electron microscopy (TEM) was utilized to observe the ultrastructural changes of the colonic mucosal barrier. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect the content of short-chain fatty acids (SCFAs) in the feces of mice. Western blot was carried out to detect the expression of related proteins, including tau, phosphorylation (p)-tau (Thr231), p-tau (Ser262), p-tau (Ser396), and p-tau (Thr181) in the hippocampal tissue, as well as Claudin-1, Occludin, and zonula occludens-1 (ZO-1) in the colonic tissue.ResultsCompared with those of the blank group, in the model group, the escape latency of mice was significantly prolonged (P<0.01), and the percentage of residence time in the target quadrant was significantly shortened (P<0.01). The expression of p-tau (Thr231), p-tau (Ser262), p-tau (Ser396), and p-tau (Thr181) proteins was significantly increased (P<0.01). In the intestine, the glands in the mucosal layer shrank, and the number of glands decreased severely. The number of goblet cells decreased. The lamina propria was severely edematous, and inflammatory cells infiltrated. The blood vessels dilated, and epithelial cells showed hydropic degeneration. The microvilli were arranged sparsely, and there was severe dissolution and breakage. A small amount of cellular contents exuded into the intestinal lumen, and there were a large number of highly vacuolated structures in the cytoplasm. The membranes between the tight junctions and the junction proteins dissolved, and the tonofilaments on both sides of the desmosome junctions decreased. The content of propionic acid, acetic acid, butyric acid, and isovaleric acid was significantly decreased (P<0.05, P<0.01), and the expression of Claudin-1, Occludin, and ZO-1 proteins was significantly reduced (P<0.01). Compared with those of the model group, in the high-dose group of Hei Xiaoyaosan, the escape latency was significantly shortened (P<0.01), and the percentage of residence time in the target quadrant was significantly prolonged (P<0.01). The expression of p-tau (Thr231), p-tau (Ser262), p-tau (Ser396), and p-tau (Thr181) proteins decreased significantly (P<0.01). In the intestinal tissue, the edema of the lamina propria gradually alleviated, and the number and morphology of the glands were restored. The number of goblet cells gradually increased, and the number of microvilli was acceptable. The damage to the tight junctions and desmosome junctions between cells was relatively mild. The content of propionic acid, acetic acid, butyric acid, and isobutyric acid was significantly increased (P<0.05, P<0.01). The content of valeric acid and isovaleric acid was increased, but there was no statistical significance. The expression of Claudin-1, Occludin, and ZO-1 proteins was significantly increased (P<0.01).ConclusionHei Xiaoyaosan can improve the learning and cognitive abilities of AD mice, possibly through reducing intestinal barrier permeability and increasing the content of SCFAs, thereby reducing the excessive phosphorylation of tau proteins.
关键词:Hei Xiaoyaosan;Alzheimer's disease;intestinal barrier;short-chain fatty acid;tau protein
摘要:ObjectiveTo observe the effect of Hei Xiaoyaosan on improving the learning and memory abilities of Alzheimer's disease (AD) model mice and explore the anti-AD mechanism of Hei Xiaoyaosan by regulating gut microbiota.MethodsTen four-month-old male C57BL/6J mice were selected as a blank group, and 60 male amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice of the same age were randomly divided into a model group, low-dose, medium-dose, and high-dose groups of Hei Xiaoyaosan (5.53, 11.05, 22.10 g·kg-1), a group of Bifidobacterium bifidum tetrapartum tablets (0.585 g·kg-1), and a group of donepezil hydrochloride (6.5 mg·kg-1), with 10 mice in each group. The continuous drug intervention was performed for 90 d. New object recognition experiments were performed to observe the learning and memory abilities of each group. Morphological pathological changes in the Cornu Ammonis 1 (CA1) area of the hippocampus were analysed by hematoxylin-eosin (HE) staining, and the changes in gut microbiota in the feces of the mice were detected by 16S rRNA sequencing. Ultrastructural changes in the blood-brain barrier were observed by electron transmission endomicroscopy (TEM), and Western blot was employed to detect the expression of related proteins such as Claudin-1, Occludin, and zonula occludens-1 (ZO-1).ResultsCompared with that in the blank group, the new object recognition index was significantly decreased in the model group (P<0.01). The number of neuronal cells was reduced, and the arrangement was disordered. The cell nuclei were pyknosed. The cell structures were damaged to varying degrees. The vascular endothelial cell membranes were extensively dissolved. The tight junction gaps were enlarged, with the membranes dissolved, and the junction proteins were reduced. A small part of the vascular basement membrane was dissolved and discontinuous. The astrocytic endfeet matrix and mitochondria were edematous. The expression of Claudin-1, Occludin, and ZO-1 was significantly decreased (P<0.01). Compared with that in the model group, after the intervention with Hei Xiaoyaosan, the new object recognition index was significantly increased (P<0.05, P<0.01). The number of neuronal cells increased. The arrangement was neater. The pyknosis of cell nuclei was reduced. The cell bodies were clear, and the structures were relatively complete. The endothelial cell membranes were partially dissolved. The tight junction gaps were slightly enlarged. The junction proteins were relatively abundant. The dissolution of the vascular basement membranes was alleviated, and the swelling of the astrocytic endfeet and mitochondria was reduced. The expression of Claudin-1, Occludin, and ZO-1 was significantly increased (P<0.05, P<0.01). The results of the gut microbiota analysis showed that Hei Xiaoyaosan could regulate the structure and composition of the gut microbiota in APP/PS1 mice. Compared with the blank control group, the model group showed a significant decrease in the abundance of Firmicutes, Lactobacillus, and Bifidobacterium (P<0.05, P<0.01) and a significant increase in the abundance of Bacteroidetes and unidentified_S24-7 (P<0.01). Compared with the model group, the Hei Xiaoyaosan groups showed a significant increase in the abundance of Firmicutes, Actinobacteriota, Lactobacillus, and Bifidobacterium (P<0.05, P<0.01) and a significant decrease in the abundance of Bacteroidetes and unidentified_S24-7 (P<0.05, P<0.01).ConclusionHei Xiaoyaosan can improve cognitive dysfunction and pathological damage in AD mice. Its mechanism may be related to adjusting the abundance and structure of the gut microbiota, reducing the permeability of the blood-brain barrier, and thus improving hippocampal neuronal damage.
摘要:ObjectiveTo investigate the hepatotoxic effects of Dictamni Cortex and its potential metabolic mechanisms in Sprague Dawley (SD) rats through serum metabolomics analysis with a dynamic dose-time approach.MethodsSD rats were randomly divided into a control group and high-dose, medium-dose, and low-dose groups of Dictamni Cortex. The administration was performed by gavage once daily for four, eight, and 12 weeks, followed by a one-month recovery period. Body weight, liver index, biochemical indicators in serum, and histopathological changes in liver tissue were assessed. Serum metabolomics analysis was performed by liquid chromatography-mass spectrometry (LC-MS), and differential metabolites (DEMs) were identified. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database was utilized for metabolic pathway enrichment analysis.ResultsThe high-dose Dictamni Cortex significantly inhibited weight gain in rats (P<0.05, P<0.01). The liver index was elevated in female rats of the medium-dose and high-dose groups at the 4th and 8th weeks (P<0.01). The liver index was significantly increased in male rats from all dose groups at the 8th week, and it was elevated in both male and female rats at the 12th week (P<0.05, P<0.01). During the recovery period, the liver index decreased in the high-dose group (P<0.05). Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were elevated in the low-dose, medium-dose, and high-dose groups at the 8th and 12th weeks (P<0.05, P<0.01). Notably, the high-dose group maintained elevated ALT and AST levels during the recovery period (P<0.05). The varying degrees of degeneration, necrosis, and inflammatory cell infiltration in hepatocytes were observed in the high-dose and medium-dose groups at the 4th week and in the high-dose, medium-dose, and low-dose groups at the 8th and 12th weeks. During the recovery period, only slight inflammatory cell infiltration was observed in the high-dose group. After four weeks of treatment, A total of 43, 22, and 19 DEMs were identified in the control group and the high-dose, medium-dose, and low-dose groups, enriched in pathways including arachidonic acid metabolism, retinol metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis, respectively. After eight weeks, 27, 25, and 29 DEMs were identified in the control group and the high-dose, medium-dose, and low-dose groups, all enriched in arachidonic acid metabolism. After 12 weeks, 33, 29, and 22 DEMs were identified in the control group and the high-dose, medium-dose, and low-dose groups, enriched in glutathione metabolism. In the recovery period (16 weeks), 12, 10, and 15 DEMs were identified, with significant enrichment in the biosynthesis of unsaturated fatty acids in the high-dose and medium-dose groups and significant enrichment in ascorbate and aldarate metabolism in the medium-dose group.ConclusionThe administration of Dictamni Cortex at high and medium doses of 8.1 g·kg-1 and 2.7 g·kg-1 for four weeks and a low dose of 0.9 g·kg-1 for eight weeks produces hepatotoxicity, which exhibits significant dose and time dependence. The dynamic changes in the hepatotoxicity of Dictamni Cortex are associated with CYP450 metabolism, inflammatory response, and oxidative stress, while the reversibility of its toxicity is linked to fatty acid metabolism.
关键词:Dictamni Cortex;dose, time, and toxicity relationship;hepatotoxicity;serum metabolomics;glutathione metabolism;arachidonic acid metabolism
摘要:ObjectiveTo explore the mechanism of dictamnine, the main component in Dictamni Cortex, in causing liver injury through gut microbiota and bile acid metabolism.MethodsMice were randomized into a normal group and a dictamnine (15 mg·kg-1 once a day) group. After 28 days of treatment, samples were taken and the body weight and liver weight were recorded. Enzyme-linked immunosorbent assay was employed to measure the levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) in the serum and superoxide dismutase (SOD) and malondialdehyde (MDA) in the liver. The pathological changes in the liver and colon tissue samples were observed by hematoxylin-eosin staining. Real-time PCR was employed to determine the mRNA levels of farnesoid X receptor (FXR), small heterodimer partner (SHP), cholesterol 7α-hydroxylase (CYP7A1), and bile salt export pump (BSEP) in the mouse liver. The 16S rRNA gene sequencing was performed to detect the composition of gut microbiota in each group, and ultra-high performance liquid chromatography-tandem mass spectrometry was employed to analyze the content of bile acids in the liver.ResultsCompared with the normal group, the dictamnine group showed raised levels of AST (P<0.01), ALT (P<0.01), interleukin (IL)-6 (P<0.01), IL-1β (P<0.01), and ALP (P<0.05) in the serum as well as decreased SOD activity (P<0.05) and increased MDA (P<0.05) in the liver. In addition, the dictamnine group showed down-regulated mRNA levels of FXR, SHP, and BSEP (P<0.05, P<0.01) and up-regulated mRNA level of CYP7A1 (P<0.01). At the phylum level, the dictamnine group showed lower relative abundance of Firmicutes and Verrucomicrobia (P<0.05, P<0.01) and higher relative abundance of Bacteroidetes, Desulfobacterota, and Cyanophyta (P<0.05, P<0.01) than the normal group, with a downward adjustment of Firmicutes/Bacteroidetes ratio (P<0.05). At the genus level, the dictamnine group had higher relative abundance of Staphylococcus, Corynebacterium, Desulfovibrio, and Turicibacter (P<0.05, P<0.01) and lower relative abundance of Lactobacillus and Akkermansia (P<0.05, P<0.01) than the normal group. The results of bile acid analysis showed that compared with the normal group, the dictamnine group showcased lowered levels of ursodeoxycholic acid (UDCA), taurodeoxycholic acid (TUDCA), and 3β-ursodeoxycholic acid (3β-UDCA) (P<0.01) and elevated levels of β-muricholic acid (β-MCA) and tauro-β-muricholic acid (T-β-MCA) (P<0.01).ConclusionDictamnine can cause liver injury through the gut microbiota–bile acid axis, leading to gut microbiota imbalance and bile acid dyshomeostasis.
摘要:ObjectiveTo investigate the mechanism by which the aqueous extract of Dictamni Cortex induces hepatotoxicity by regulating the expression of cytochrome P450 (CYP) 1A2 through the aryl hydrocarbon receptor (AHR) signaling pathway.MethodsThe 80 male Sprague Dawley (SD) rats were randomly divided into a blank group, high-dose (8.1g·kg-1), medium-dose (2.7 g·kg-1), and low-dose groups (0.9 g·kg-1) of aqueous extract of Dictamni Cortex. The aqueous extract of Dictamni Cortex was intragastrically administered for three months, and a recovery period of one month was set. The level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in rat serum was detected. The organ index of liver tissue was calculated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in liver tissue. Real-time quantitative reverse transcription-polymerase chain reaction (Real-time PCR) was employed to screen for key metabolic enzymes in the liver tissue of rats during the drug administration period. Subsequently, the mRNA and protein expression levels of the screened key metabolic enzyme CYP1A2 and its related pathway molecules [AHR, aryl hydrocarbon receptor nuclear translocator (ARNT), heat shock protein 90 (HSP90), p23 molecular chaperone protein (p23), and AHR-interacting protein (AIP)] were detected by Real-time PCR, Western blot, and immunohistochemistry (IHC) techniques.ResultsCompared with the blank group, the ALT and AST levels were significantly increased in the high-dose, medium-dose, and low-dose groups during the administration period (P<0.05, P<0.01) and were still significantly increased in the high-dose group during the recovery period (P<0.05). The organ index was significantly increased in the high-dose, medium-dose, and low-dose groups during the administration period (P<0.05, P<0.01) and was significantly decreased in the high-dose group during the recovery period (P<0.05). Histopathological observations revealed that during the administration period, the high-dose, medium-dose, and low-dose groups exhibited varying degrees of hepatocyte necrosis and inflammatory cell infiltration. During the recovery period, only a small number of inflammatory cells were observed in the high-dose group. During the administration period, the mRNA and protein expression level of CYP1A2 in the high-dose and medium-dose groups and AHR, ARNT, HSP90, and p23 in the low-dose, high-dose, and medium-dose groups was significantly increased (P<0.01), while the expression of AIP was significantly decreased (P<0.01). During the recovery period, the mRNA and protein expression level of CYP1A2, AHR, ARNT, HSP90, and p23 remained significantly elevated in the high-dose group (P<0.05, P<0.01), and the expression of AIP was still significantly decreased (P<0.01). Immunohistochemical results showed that the positive expression rate of CYP1A2 was significantly increased in the high-dose and medium-dose groups during the administration period (P<0.01) and remained significantly elevated in the high-dose group during the recovery period (P<0.01).ConclusionCYP1A2 is a key metabolic enzyme for hepatotoxicity during the administration period and reversibility during the recovery period of aqueous extract of Dictamni Cortex, and its mechanism is related to the AHR signaling pathway.
摘要:Dictamni Cortex is derived from the dried root bark of Dictamnus dasycarpus Turcz. It has the properties of clearing heat and drying moisture, detoxification, wind dispelling, insect killing, and itching relief. In traditional Chinese medicine (TCM), Dictamni Cortex is frequently used to treat damp-heat jaundice, damp-heat arthralgia, eczema, and scabies. Modern pharmacological studies have shown that Dictamni Cortex contains active ingredients such as dictamine, obacunone, limonin, and fraxinellone. Dictamni Cortex has multiple hepatoprotective effects on anti-hepatic fibrosis, regulation of liver lipid metabolism, and anti-liver cancer, demonstrating potential in the prevention and treatment of acute and chronic hepatitis, hepatic fibrosis, non-alcoholic fatty liver, and liver cancer. However, recent clinical reports have indicated that acute drug-induced liver damage (DILI) was induced by taking Dictamni Cortex powder or formulations containing it, such as Zengshengping tablets, Keyin pills, and Zhixue capsules, and even fatal cases were found. Toxicological studies for animals related to Dictamni Cortex have shown that it and its components significantly elevated the level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), leading to hepatocyte damage and necrosis, which indicated pronounced hepatotoxicity. Consequently, the liver toxicity risks associated with Dictamni Cortex have severely hindered its clinical application and development. By reviewing Dictamni Cortex-related literature, this paper discussed the hepatoprotective effect, the hepatotoxic effect, and the relationship between the efficacy and toxicity of Dictamni Cortex to provide important insights and a basis for related research and clinical application.
摘要:ObjectiveTo investigate the mechanism by which Yitangkang prescription ameliorates skeletal muscle insulin resistance via regulating branched chain amino acid (BCAA) metabolism.Methodsdb/m mice were set as the normal group, and db/db mice were set as the model group, low-, medium-, and high-dose groups of Yitangkang (14.46, 28.925, and 57.85 g·kg-1), and the western medicine group (semaglutide of 0.045 mg·kg-1). Medication intervention was administered to each group of mice as required. The skeletal muscle insulin resistance model and drug efficacy were evaluated using intraperitoneal glucose tolerance test (IPGTT), intraperitoneal insulin tolerance test (IPITT), and hematoxylin-eosin (HE) staining. Blood lipid levels of mice in each group were detected by a fully automated biochemical analyzer. Based on previous research, non-targeted metabolomics technology and amino acid-targeted metabolomics technology were used to screen metabolites in the skeletal muscle of mice and to determine the relative contents of 42 amino acids, respectively. Real-time polymerase chain reaction (Real-time PCR) and Wes fully automated protein expression analysis system were used to detect the mRNA and protein expression levels of branched-chain amino acid transaminase 1 (BCAT1), branched-chain α-keto acid dehydrogenase complex (BCKDH), ribosomal protein S6 kinase (S6K), mammalian target of rapamycin complex 1 (mTORC1), and insulin receptor substrate-1 (IRS-1) to verify the regulatory effect of Yitangkang on BCAA metabolism.ResultsYitangkang significantly improved the metabolic levels of mice in each group. Compared with the metabolic abnormalities in the model group, the high- and medium-dose groups of Yitangkang showed a significant decrease in FBG, TG, TC, and LDL-C (P<0.01) and a significant increase in HDL-C (P<0.01). Yitangkang significantly improved insulin resistance in mice. Compared with the model group, IPGTT results showed that blood glucose in all groups increased and then decreased, while IPITT results showed that blood glucose in the high- and medium-dose groups of Yitangkang decreased significantly (P<0.01). HE staining results indicated that Yitangkang enhanced the sensitivity of skeletal muscle to insulin and restored the normal morphology of skeletal muscle. Non-targeted metabolomics technology screened a large number of metabolites in skeletal muscle altered by different interventions, mainly involving the tricarboxylic acid cycle, oxidative phosphorylation, and protein degradation and absorption. Targeted metabolomics analysis found that Yitangkang intervention altered the contents of 35 amino acids in skeletal muscle tissue, with significant changes in BCAA levels. Further verification revealed that, compared with the model group, the mRNA and protein expression levels of BCAT1, BCKDH, and IRS-1 in the skeletal muscle tissues of mice in each dose group of Yitangkang were significantly increased (P<0.01), while those of mTORC1 and S6K were significantly decreased (P<0.01). Yitangkang could regulate the metabolic remodeling of BCAAs to exert therapeutic effects, and the efficacy in the high- and medium-dose groups of Yitangkang was comparable to that of semaglutide.ConclusionYitangkang prescription may regulate BCAA metabolism through the mTORC1/S6K signaling pathway, thereby restoring the physiological function of skeletal muscle and ameliorating skeletal muscle insulin resistance.
摘要:ObjectiveTo investigate the possible mechanism of Yitangkang (YTK) in the treatment of diabetes kidney disease (DKD) by observing the effect of YTK on promoting autophagy through regulating N6 methyladenine (m6A) methylation modification.MethodsForty five SPF grade db/db mice (DKD model) at 16 weeks of age were selected as the experimental group,and nine db/m mice were selected as the blank group. The mice in the experimental group were divided into a model group, low-, medium-, and high-dose YTK groups (14.463, 28.925, and 57.850 g·kg-1·d-1), and a finerenone group of 2.6 mg·kg-1·d-1 with the random number table method. YTK water extract and finerenone were administered orally for 8 weeks. Enzyme-linked immunosorbent assay (ELISA) was applied to detect serum and urine neutrophil gelatinase-associated lipid transport protein (NGAL). A fully automated biochemical analyzer was used to detect blood urea nitrogen (UREA), creatinine in serum(Cre-s), blood uric acid (UA), and urine albumin to creatinine ratio (UACR) to evaluate renal damage. Kidney tissues of mice were isolated and subjected to hematoxylin-eosin staining (HE) to observe the morphological changes of mouse kidney tissues. Apoptosis of mouse kidney tissues was observed by in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Immunohistochemistry (IHC) was performed to detect the average optical density values of methyltransferase-like protein 3 (METTL3), methyltransferase-like protein 14 (METTL14), lysosome-associated membrane protein type 2A (LAMP2A), microtubule-associated protein light chain 3 Ⅱ (LC3 Ⅱ), and Nod-like receptor protein 3 (NLRP3) in mouse kidney tissues. Real-time quantitative polymerase chain reaction (Real-time PCR) and the Wes fully automated protein expression analysis system were used to detect the protein expression levels of METTL3, METTL14, LAMP2A, LC3 Ⅱ, chelator 1(p62), YTHN6-methyl-adenosine RNA-binding protein 3 (YTHDF3), heat shock protein 70 (HSP70), and heat shock protein 90 alpha (HSP90AA1) in the kidney tissues of mice in each group.ResultsAfter 8 weeks of drug intervention, compared with the blank group, the model group exhibited significantly higher expression levels of serum NGAL, UREA, Cre-s, and UA (P<0.01), significantly higher expression levels of urinary UACR and NGAL (P<0.01), disordered renal tissue cells, incomplete structure, and unclear edges of cells, with obvious inflammatory hemorrhagic spots and inflammatory cell infiltration shown. Additionally, the model group had significantly increased number of positive apoptotic cells in the kidney (P<0.01), increased positive expression of METTL3, METTL14, and NLRP3, and decreased positive expression of LAMP2A and LC3 Ⅱ (P<0.01). In the model group, the mRNA and protein expression of METTL3, METTL14, p62, and HSP70 increased, and the mRNA and protein expression of YTHDF3, LAMP2A, LC3 Ⅱ, and HSP90AA1 decreased (P<0.01). Compared with the model group, the dosing groups showed significantly reduced expression levels of serum NGAL, UREA, Cre-s, and UA (P<0.01) and significantly lowered levels of urinary UACR, and NGAL (P<0.01). The renal tissues of mice were characterized by a more regular arrangement of cells, and inflammatory hemorrhagic spots and inflammatory cells were reduced to different degrees. The number of positive apoptotic cells in the kidney was significantly decreased (P<0.01). The positive expression of METTL3, METTL14, and NLRP3 was reduced, and the positive expression of LAMP2A and LC3 Ⅱ was increased (P<0.01). The mRNA and protein expression of METTL3, METTL14, p62, and HSP70 was reduced, and the mRNA and protein expression of YTHDF3, LAMP2A, LC3 Ⅱ, and HSP90AA1 increased (P<0.01).ConclusionYTK, a Chinese herbal compound, can promote autophagy in the treatment of DKD by regulating m6A modification, giving play to the unique advantages of traditional Chinese medicine.
摘要:ObjectiveTo explore the mechanism of Yitangkang prescription (YTK) in treating type 2 diabetes mellitus (T2DM) by observing the modulatory effects of YTK on the silent information regulator 6 (SIRT6)/peroxisome proliferator-activated receptor α (PPARα) signaling pathway to recover the glucose and lipid metabolism as well as the morphology of adipose tissue in the rat model of T2DM.MethodsNinety-six 8-week-old SPF-grade healthy male Wistar rats were selected and assigned by the random number table method into blank, model, high-dose (40 g·kg-1) YTK, medium-dose (20 g·kg-1) YTK, low-dose (10 g·kg-1) YTK, and western medicine (liraglutide, 0.108 mg·kg-1) groups. The rat model of T2DM was established by feeding of a high-fat diet and intraperitoneal injection of streptozotocin (STZ). After the model was successfully established, the rats were treated with corresponding agents by gavage for 8 consecutive weeks. The levels of fasting blood glucose (FBG), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured. Hematoxylin-eosin staining was performed to observe the pathological changes in the adipose tissue. Immunohistochemical staining and Western blot were employed to determine the protein levels of nuclear receptor coactivator (NCOA2), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), peroxisome proliferator-activated receptor γ coactivator-1β (PGC-1β), PPARα, PR domain Zinc finger protein 16 (PRDM16), and SIRT6 in the adipose tissue in each group of rats.ResultsCompared with the blank group, the model group showed elevations in FBG, TG, and LDL-C levels and a decrease in HDL-C level (P<0.01), with the adipose tissue cells showing increased diameters, deformed shapes, and unclear edges. In addition, the adipose tissue in the model group showed increased positive expression of NCOA2 and reduced positive expression of PGC-1α, PGC-1β, PPARα, PRDM16, and SIRT6 (P<0.01). Compared with the model group, all the treatment groups reduced the levels of FBG, TG, and LDL-C and raised the level of HDL-C (P<0.01), with the adipose tissue cells presenting reduced diameters, an increased number, and regular morphology. Moreover, the treatment groups showcased reduced positive expression of NCOA2 and increased positive expression of PGC-1α, PGC-1β, PPARα, PRDM16, and SIRT6 (P<0.01).ConclusionYTK has good therapeutic effects on STZ-induced T2DM in rats by activating the SIRT6/PPARα pathway and promoting white fat browning.
摘要:ObjectiveTo observe the therapeutic effect of Yitangkang prescription (YTK) on diabetic kidney disease (DKD) and decipher the treatment mechanism.MethodsForty-five 16-week-old male SPF-grade db/db mice were randomly allocated into five groups: model, high-, medium-, and low-dose (57.850, 28.925, and 14.463 g·kg-1·d-1, respectively) YTK, and finerenone (0.002 6 g·kg-1·d-1). Nine db/m mice were taken as the blank group. Each treatment group was administrated with the corresponding agent by gavage, and the samples were collected after 8 weeks of continuous administration. The urine and serum indicators and the pathological changes of the spleen, pancreas, and kidney tissues were used for evaluation of DKD modeling results and YTK efficacy. Tandem mass tag (TMT)-labeled quantitative proteomics was employed to decipher the possible treatment mechanism. The immunofluorescence assay was employed to measure the expression of lysosome-associated membrane protein 2A (LAMP2A), microtubule-associated protein light chain 3B (LC3 Ⅱ), and NOD-like receptor hot protein domain protein 3 (NLRP3), thus verifying the results of TMT-labeled quantitative proteomics.ResultsCompared with the blank group, the model group showed significantly elevated levels of urine albumin-to-creatinine ratio (UACR), neutrophil gelatinase-associated lipocalin (NGAL), serum NGAL, creatinine in serum (Cre-s), uric acid (UA), and urea(P<0.01), obvious pathological changes in the kidney tissue similar to those of DKD, which indicated that the DKD model was successfully established. After YTK intervention, the above indexes and pathological changes were significantly alleviated. Screening by TMT-labeled quantitative proteomics suggested that YTK played a role by regulating autophagy, aminoacyl-tRNA biosynthesis, cysteine and methionine metabolism and other pathways. The immunofluorescence assay of autophagy-related proteins showed that compared with the blank group, the model group presented significantly down-regulated expression of LAMP2A and LC3 Ⅱ and significantly up-regulated expression of NLRP3(P<0.01). After intervention with YTK, the expression of LAMP2A protein in each dose treatment group was significantly increased, YTK high and medium dose group the expression of LC3 Ⅱ protein was significantly increased, and the expression of NLRP3 protein was significantly decreased (P<0.01).ConclusionYTK can effectively recover blood glucose indicators, reduce proteinuria, and delay the progression of DKD. Its effect is related to the regulation of autophagy, while the specific mechanism remains to be explored.
关键词:Yitangkang prescription;diabetic kidney disease;tandem mass tag (TMT)-labeled quantitative proteomics;autophagy
摘要:ObjectiveTo investigate the mechanism by which the Chinese herbal compound Yitangkang prescription(YTK) ameliorates diabetic kidney disease (DKD) through regulating mast cell (MC) degranulation.MethodsSixteen-week-old db/db mice (DKD model, n=45) served as the experimental group, while db/m mice (n=9) served as the blank control group. The experimental group was divided into model, low-dose YTK (14.463 g·kg-1·d-1), medium-dose YTK (28.925 g·kg-1·d-1), high-dose YTK (57.850 g·kg-1·d-1), and finerenone (2.6 mg·kg-1·d-1) groups with the random number table method. After 8 weeks of intragastric administration, the following assessments were performed. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was utilized to identify key active components of YTK. Hematoxylin-eosin (HE) staining was used to observe morphological changes in spleen and kidney tissues. Enzyme linked immunosorbent assay(ELISA) was applied to detect serum inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and tissue levels of 5-hydroxytryptamine (5-HT) and histamine (HIS). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was adopted to assess renal cell apoptosis. Immunohistochemistry (IHC) was used to analyze the average optical densities of nephrin, podocin, Caveolin-1, and Nod-like receptor protein 3 (NLRP3) in kidney tissue. Non-targeted metabolomics was employed to analyze changes in renal tissue metabolites. Toluidine blue (TB) staining was performed to evaluate MC infiltration and degranulation in myocardium, skeletal muscle, liver, small intestine, and kidney tissues.ResultsLC-MS/MS identified 15 key active components in YTK. HE staining confirmed that YTK improved spleen and kidney tissue structure and alleviated inflammation. TB staining demonstrated that YTK significantly reduced MC infiltration and degranulation in all examined tissues. YTK significantly decreased serum IL-1β, IL-6, and TNF-α levels and tissue 5-HT and HIS levels (P<0.01), improving inflammation and MC degranulation. TUNEL staining showed YTK reduced renal cell apoptosis. IHC indicated YTK upregulated nephrin and podocin expression while downregulating Caveolin-1 and NLRP3 expression (P<0.01). Non-targeted metabolomics identified significantly altered metabolites, with key mechanisms involving tryptophan metabolism, histidine metabolism, arachidonic acid metabolism, and neuroactive ligand-receptor interaction pathways.ConclusionYTK ameliorates metabolic-inflammatory imbalance in DKD and alleviates glomerular microvascular barrier injury through cross-organ regulation of the MC network, thereby exerting therapeutic effects against DKD.
YANG Zhaoshuo, MO Mei, DONG Qiang, CAI Dingfang, ZHANG Jianjun, LIU Xu, WU Jianguo, ZHANG Xuemei, ZHONG Ping, SHI Min, LI Kaichun, GONG Yabin, DENG Wanli, CUI Huashun, CHEN Jingxian, LIU Ningning, LU Zhengyu, YU Xiaofei, GUO Jihua, FANG Fang, XIANG Jun, FAN Yue, ZHANG Xiaoxiao
摘要:Chemotherapy-induced peripheral neuropathy (CIPN) refers to peripheral neuropathy characterized by sensory abnormalities in the extremities following the use of chemotherapeutic drugs. Current diagnosis and treatment protocols fail to satisfy clinical needs. Comprehensive traditional Chinese medicine (TCM) therapies have demonstrated certain efficacy and safety in CIPN management. To clarify research status and clinical advantages of TCM/integrated Chinese and Western medicine in this field, the China Association of Chinese Medicine organized over 20 experts from oncology, neurology, acupuncture, and pain management specialties to discuss the clinical diagnosis/treatment status of CIPN and therapeutic strengths of TCM and Western medicine. Consensus recommendations were formulated in key issues, including current CIPN treatment status, pathogenesis, TCM disease mechanisms and syndrome differentiation, risk factors, and integrated treatment directions. Current clinical challenges include difficulties in quantitative diagnosis, limited pharmacological interventions, and suboptimal benefits from TCM and interventional therapies. To address these issues, this paper recommended establishing multidisciplinary collaboration among oncology, neurology, pain management, and acupuncture specialties. It emphasized patient feedback during treatment, proactive implementation of diversified interventions, and full utilization of TCM's holistic approach to play active roles in prevention, diagnosis, treatment, and rehabilitation. Additionally, it advocated synergistic integration of Chinese and Western medicine and multidisciplinary cooperation, aiming to develop CIPN diagnosis and treatment protocols with Chinese characteristics that combine TCM and modern medicine.
关键词:chemotherapy-induced peripheral neuropathy;dominant disease;traditional Chinese medicine therapy;multidisciplinary diagnosis and treatment
摘要:By consulting the ancient and modern literature, this paper intends to systematically sort out and analyze the name, origin, medicinal parts, quality, processing and others of Cicadae Periostracum(CP), and provide basis for the development and utilization of the related famous classical formulas. After research, it can be seen that there are different species and names of cicadas, and most of the books on herbal medicine use "Zhachan" or "Chantui" as the proper name. In Qin and Han dynasties, the whole adult cicada was used as medicine, after that, the adult cicada and sloughed exoskeleton left behind after the nymph of cicada both were used in medicine. Since the Song dynasty, slough was mainly used as medicine. According to the color, body shape, phonation time and other characteristics of habitual records, the main origin was Cryptotympana pustulata. The quality evaluation of CP in ancient books is roughly determined by the species of cicadas, and only the big and black ones are used in medicine. In modern times, the ones with full shape, bright yellow color, no breakage and no sediment are the best. Since ancient times, CP has been produced in most areas of the country, which now the genuine producing area was considered to be Zhejiang. CP resources mainly rely on the wild, and in recent years, the work of artificial domestication has been gradually carried out. In ancient and modern times, the soil should be removed after harvesting. The wings and feet should be removed, and dried after steaming or boiling to prevent worm-eaten in ancient times. In the early modern periods, it must be crushed and screened, in the later periods, CP just should be cleaned and dried. In medicinal properties, CP was thought to have a cold nature, a salty and sweet taste, and into the lung, spleen, and liver meridians in ancient times, while in modern times, it was thought to have a cold nature, a sweet taste, and into the lung and liver meridians. The main effects in ancient and modern times are to evacuate wind-heat, penetrate rashes, remove nebula, relieve spasms and so on. Based on the research results, it was suggested that the standard scientific name of CP protozoa should adopt C. atrata, and advanced techniques should be applied to identify the origin, the processing method should be selected according to the requirements of the formulas, and if the requirements are not specified, it is recommended to use the raw and dried products without impurities into medicine.
关键词:Cicadae Periostracum;herbal textual research;name;origin;medicinal parts;quality evaluation;harvesting and processing