南京中医药大学学报

Research Ideas and Methods of Intelligent Diagnosis and Treatment of Traditional Chinese Medicine Driven by Large Language Model

YANG Tao, WANG Xin-yu, ZHU Yao, HU Kong-fa, ZHU Xue-fang

2023, 39(10): 967-971. doi: 10.14148/j.issn.1672-0482.2023.0967

[Abstract](436) [FullText HTML] (59) [PDF 2190KB](67)

Abstract:
Intelligent diagnosis and treatment of traditional Chinese medicine is an important direction for the modern development of traditional Chinese medicine. Large language model technology has promoted the development of artificial intelligence. Combining it with traditional Chinese medicine to build intelligent diagnosis and treatment methods and applications of traditional Chinese medicine driven by large language models is of great significance to the innovative development of traditional Chinese medicine. On the basis of analyzing and summarizing the challenges faced by intelligent diagnosis and treatment of traditional Chinese medicine, it is proposed to build research ideas and methods for intelligent diagnosis and treatment of traditional Chinese medicine driven by large language models based on large language models, covering corpus preparation, knowledge representation, instruction fine-tuning and reinforcement learning, in order to provide reference for intelligent research on traditional Chinese medicine diagnosis and treatment.

An Automated Completion Study of Knowledge for the Treatment of Lung Cancer by Famous TCM Experts Based on Knowledge Representation Learning

WANG Xin-yu, YANG Tao, HU Kong-fa

2023, 39(10): 972-978. doi: 10.14148/j.issn.1672-0482.2023.0972

[Abstract](133) [FullText HTML] (17) [PDF 2120KB](16)

Abstract:
OBJECTIVE To build the knowledge base of medical cases for the treatment of lung cancer by famous TCM experts, and to realize the automatic completion of the knowledge base. METHODS A method of completing the drug use of famous old Chinese medicine for the treatment of lung cancer was designed, the correlation between symptoms, diagnosis, traditional Chinese medicine, tongue image and pulse image was analyzed and divided according to the threshold, and the CrossE knowledge representation model was used in conjunction with negative sampling techniques to learn the embedded representation of each entity and relationship in the knowledge base in the vector space, and the link prediction task was carried out to mine the hidden relationships in the knowledge base. RESULTS Based on the Pearson correlation analysis conducted on entities within medical cases, the relationships predicted using the CrossE model achieved the following results for the Hit@1, Hit@3, Hit@5, and Hit@10 metrics: 16.19%, 29.12%, 35. 85%, and 47.60%, respectively. Additionally, the MeanRank metric reached 13.19. Compared to models such as TransE and TransR, there is a significant improvement. CONCLUSION The use of knowledge completion technology in conjunction with clinical practices in TCM can deeply explore the hidden knowledge of famous TCM experts in the treatment of lung cancer.

Discussion on Classical Formula Artificial Intelligence Research Path Based on Graph Theory

LIU Chang, QU Yi-qian, LI Yu, CAO Ling-yong, LIN Shu-yuan

2023, 39(10): 979-985. doi: 10.14148/j.issn.1672-0482.2023.0979

[Abstract](175) [FullText HTML] (21) [PDF 2888KB](22)

Abstract:
This article analyzes the correlation between classical formula theory and graph theory, puts forward the research path of classical formula AI based on graph theory, introduces the related contents of graph theory and classical formula AI research, analyzes the correlation between graph theory and classical formula theory and thinking from the perspective of logical reasoning and propositional logic, and proposed feasible research path. The application of graph theory can solve the problem of knowledge representation in the intelligent research of classical formula. The graph properties and their measurement methods are helpful for knowledge discovery from the perspective of TCM thinking. The matrix representation and connectivity of graph integrate the domain knowledge of classical formula into AI-assisted diagnosis and treatment model and improve the model efficiency. Graph theory can provide theoretical guidance for the research of classical formula AI, and knowledge graph based on graph theory can provide solutions for the difficult problems in the research of classical formula AI.

Exploration of the Modern Spleen-Yin Theory and Its Clinical Application

GU Ming-jia, QIU Xiao-hong, ZHU Jie-bin, YANG Jin

2023, 39(10): 986-991. doi: 10.14148/j.issn.1672-0482.2023.0986

[Abstract](263) [FullText HTML] (36) [PDF 978KB](27)

Abstract:
The origin, development, and maturation status of the spleen-yin theory in the history of Chinese medicine are discussed. The main contents of the spleen-yin theory are introduced, including its vital role in the process of spleen transport and transformation, the syndrome characteristics of spleen-yin deficiency and the key to identify it, as well as the treatment of spleen-yin deficiency by nourishing and benefiting yin with sweet-cold medicines. After Miao Xi-yong, the spleen-yin theory was further developed. The modern theoretical research on spleen-yin theory mainly includes three aspects: the study of the connotation of spleen-yin, the study of the differentiation points between spleen-yin deficiency and stomach-yin deficiency, and the study of the treatment of spleen-yin deficiency. The modern clinical application of spleen-yin theory is mainly applied to various gastrointestinal diseases.

Exploring the Mechanism of Chinese and Western Medicine for Recurrent Spontaneous Abortion and Traditional Chinese Medicine Diagnosis and Treatment Caused by Emotional Factors

RUAN Yuan-yuan, LIU Yu-nan, XUE Miao-miao, ZHAO Jia-lin, HUO Yan, GAO Shuai, XU Guang-li, ZHANG Wei-yi, CHEN Ping

2023, 39(10): 992-998. doi: 10.14148/j.issn.1672-0482.2023.0992

[Abstract](107) [FullText HTML] (14) [PDF 1051KB](12)

Abstract:
Based on the modern theory of psychological stress and emotional pathogenesis in traditional Chinese medicine, this paper analyzes the mechanism of recurrent spontaneous abortion (RSA) caused by emotional factors. Studies have found that the biological mechanism of RSA caused by emotional factors such as psychological stress includes endocrine system, central nervous system, oxidative stress, immune defense and other aspects; spleen and kidney deficiency caused by mental disturbance and liver qi stagnation are the TCM pathogenesis of RSA caused by emotional factors, and the diagnosis and treatment ideas of treating from the heart, treating from the liver and TCM emotional therapy are proposed.

Exploring the Target and Mechanism of Sanfeng Tongqiao Dropping Pills in the Treatment of Allergic Rhinitis Based on Systematic Pharmacological Methods

SUN Shu-xian, GU Xiao-qun, QIAN Pei-yao, YU Xue-rui, ZHENG Jie, ZHAO Qian, LI Jia-yu, HONG Min

2023, 39(10): 999-1005. doi: 10.14148/j.issn.1672-0482.2023.0999

[Abstract](180) [FullText HTML] (16) [PDF 3346KB](18)

Abstract:
OBJECTIVE To screen the active components of Sanfeng Tongqiao (SFTQ) by using network pharmacological method and to investigate the target and mechanism of SFTQ in the treatment of allergic rhinitis (AR). METHODS The active components and targets of SFTQ were screened by TCMSP. TCMSP and TTD database were used to screen AR-related therapeutic targets. SFTQ active components-AR target network was constructed by Cytoscape to predict potential targets. KEGG pathway enrichment analysis was performed on Davidv 6.8 database. An AR mouse model was established, and different doses of SFTQ were used for intervention during the stimulation period. The results were evaluated through behavioral indicators, pathological sections, HE staining, peripheral blood EOS and IgE levels, and the number of ILC2 in cervical lymph nodes. RESULTS 42 active components and 16 potential targets were identified. KEGG enrichment analysis revealed 18 potential signaling pathways involving T cell receptor signaling pathway, HIF-1 signaling pathway, etc. In vivo, SFTQ significantly reduced the frequency of sneezing and rubbing, the degree of mucosal thickening, peripheral blood EOS, IgE level and the amount of ILC2 in cervical lymph nodes. CONCLUSION Using systems pharmacology methods, the study revealed the multi-component, multi-target, and multi-pathway characteristics of SFTQ in treating AR, providing possible targets and active components for the mechanism study of SFTQ, and laying the foundation for a more comprehensive understanding and application of this prescription.

Effects of Buyang Huanwu Decoction on RhoA/ROCK Pathway after Cerebral Ischemia/Reperfusion Injury in Mice

XING Ye-feng, ZHAO Wu-xia, OU Zhi-jie, ZHANG Tian-ai, HU Yue

2023, 39(10): 1006-1014. doi: 10.14148/j.issn.1672-0482.2023.1006

[Abstract](88) [FullText HTML] (30) [PDF 2503KB](9)

Abstract:
OBJECTIVE To investigate the effect of Buyang Huanwu Decoction on microglial P2Y12 receptor-mediated RhoA/ROCK inflammatory signaling pathway in mice with cerebral ischemia/reperfusion (I/R) injury. METHODS The C57BL/6J mice were randomly assigned to the Sham group, MCAO group, BYHW-L (low-dose, 6.5 g·kg^-1) group, BYHW-H (high-dose, 26 g·kg^-1) group, and BYHW-H+MRS2395 group. The middle cerebral artery occlusion (MCAO) model was constructed, and the neurological impairment of the mice was evaluated by Longa biological score and TTC staining. The phenotypic polarization of microglia towards M1 or M2 was detected by immunofluorescence staining and qPCR. The protein expression levels of factors in RhoA/ROCK pathway mediated by the P2Y12 receptor were detected by Western blot. RESULTS Compared with MCAO group, Buyang Huanwu Decoction could reduce the neurological impairment (P < 0.05) and infarct volume of I/R injured mice (P < 0.05, P < 0.01), increase the polarization of M1 to M2 in microglia cells (P < 0.05, P < 0.01), inhibit the expression of P2Y12 receptor protein (P < 0.05, P < 0.01), block the P2Y12-mediated RhoA/ROCK pathway and p38 MAPK phosphorylation in the downstream pathway (P < 0.05, P < 0.01), and inhibit the inflammatory damage (P < 0.05, P < 0.01). The P2Y12 receptor inhibitor MRS2395 did not block the anti-inflammatory effect of Buyang Huanwu Decoction. CONCLUSION Buyang Huanwu Decoction may help to improve brain function after cerebral I/R injury in mice through P2Y12-mediated RhoA/ROCK inflammatory signaling pathway, it may also play an anti-inflammatory role through other pathways, but the other mechanisms need further exploration.

Studies on Differences and Mechanisms of Various Fractions Extracted from Angelicae Sinensis Radix and Wine-Processed Angelicae Sinensis Radix on Activating Blood Circulation

MAO Yu-jie, ZHANG Shao-meng, GUO Shuang-yan, SHI Yong-jie, DONG Gao-pan, YAN Hui-juan, ZHANG Lai-bin, LYU Jie-li

2023, 39(10): 1015-1033. doi: 10.14148/j.issn.1672-0482.2023.1015

[Abstract](119) [FullText HTML] (38) [PDF 6962KB](14)

Abstract:
OBJECTIVE To explore the differences and the mechanisms of various fractions extracted from Angelicae Sinensis Radix (AS) and wine-processed Angelicae Sinensis Radix (WAS) on activating blood circulation based on network pharmacology and animal experiments validation. METHODS Drug targets of AS and blood stasis (BS)-associated targets were screened from disease and drug related database, and the key targets and the core components were screened according to topological eigenvalues. Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed. The acute blood stasis model in rats induced by adrenaline hydrochloride and ice-water bath was used to explore the differences of various fractions extracted from AS and WAS. And then the screened targets based on network pharmacology were further verified. RESULTS A total of 134 potential active components, 1 062 targets of AS, 476 BS-associated targets, 145 common targets, 15 key targets and 36 core components were obtained. Enrichment analysis showed that the key targets were mainly involved in biological processes such as vascular endothelial growth factor production, positive regulation of nitric oxide biosynthetic process and cellular response to hypoxia, as well as Vascular endothelial growth factor (VEGF) signaling pathway, Phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway, and Tumor necrosis factor (TNF) signaling pathway. The results of animal experiments showed that compared with the model group, the effect of activating circulation of n-butyl alcohol-soluble fraction from WAS (WASB) was superior to those of other fractions. WASB remarkably improved the histopathological manifestations and appearance morphological characteristics of the acute blood stasis model in rats, significantly reduced organ index, evidently inhibited the release of inflammatory mediators (Nitric oxide, NO; Prostaglandin E₂, PGE₂; Tumor necrosis factor-α, TNF-α), suppressed oxidative stress, and significantly restrained the expression of VEGFA and the phosphorylation of AKT and PI3K (P<0.05, 0.01, 0.001). The effects of various fractions extracted from WAS on activating blood circulation were superior to those of the same fractions of AS. CONCLUSION The mechanisms of the enhanced effects from WAS on activating blood circulation may be related to down-regulation the expression levels of VEGFA, p-AKT and p-PI3K, inhibition of VEGF and PI3K/AKT signal pathways, decrease of pro-inflammatory mediator production (such as NO, PGE₂ and TNF-α), suppressing the production of MDA, and increasing the level of SOD to alleviate oxidative stress.

Effects of Shenmai Dihuang Decoction Combined with Valsartan on Oxidative Stress, Vascular Endothelial Function and Serum miR-133b, miR-135b in Patients with Diabetic Nephropathy

ZHAO Li-chang, YUAN Chao, YIN Na, JI Zhong-ning, XIANG Chun-bo, ZENG Jing-rong, LI Ping

2023, 39(10): 1034-1038. doi: 10.14148/j.issn.1672-0482.2023.1034

[Abstract](85) [FullText HTML] (16) [PDF 1000KB](10)

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OBJECTIVE To explore the effect of Shenmai Dihuang Decoction combined with valsartan on oxidative stress, vascular endothelial function and serum miR-133b, miR-135b in patients with diabetic nephropathy. METHODS A total of 90 patients with diabetic nephropathy who were treated in the outpatient department of Jiangyin Hospital of Traditional Chinese Medicine from January 2017 to October 2020 were selected as the research objects, and they were divided into the control group and the observation group, with 45 cases in each group according to the random number table method. The control group was treated with valsartan dispersible tablets orally, and the observation group was additionally given Shenmai Dihuang Decoction on the basis of the treatment of the control group. The course of treatment for both groups was 3 months. Before and after treatment, TCM syndrome scores were evaluated; fasting blood glucose (FPG), serum creatinine (SCr), blood urea nitrogen (BUN), urine albumin/creatinine ratio (UACR), the changes of oxidative stress indexes [superoxide dismutase (SOD) and malondialdehyde (MDA)], vascular endothelial function indicators [soluble intercellular adhesion molecule-1 (sICAM-1) and endothelin-1 (ET-1)] and miR-133b, miR-135b were assessed. RESULTS After treatment, the TCM syndrome scores, FPG, SCr, BUN, UACR, and the expression levels of MDA, sICAM-1, ET-1, miR-133b, and miR-135b were significantly decreased, and the SOD activity was significantly increased in the two groups (P<0.01). The observation group showed better therapeutic efficacy than the control group (P<0.01), with the total effective rate higher than the control group (P<0.01). CONCLUSION Shenmai Dihuang Decoction combined with valsartan can effectively improve the clinical symptoms of diabetic nephropathy, which may be related to the regulation of oxidative stress, vascular endothelial function, and serum miR-133b and miR-135b levels.

Clinical Study on the Treatment of Patients with Secretory Otitis Media after Novel Coronavirus Infection with Erlong Zhifei Decoction

QIAO Zhi, LIU Yu, CHEN Xiao-ning, ZHU Hui-lan, CHEN Chen, SHI Jun

2023, 39(10): 1039-1044. doi: 10.14148/j.issn.1672-0482.2023.1039

[Abstract](105) [FullText HTML] (9) [PDF 993KB](16)

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OBJECTIVE To observe the clinical efficacy of Erlong Zhifei Decoction combined with western medicine in the treatment of patients with secretory otitis media after novel coronavirus infection and its influence on inflammatory cytokines. METHODS A total of 100 patients with secretory otitis media after novel coronavirus infection who met the inclusion criteria were selected and randomly divided into a control group and a treatment group with 50 cases each. The control group was treated with azithromycin capsules and eucalyptus acid enteric coated soft capsules orally, and the treatment group was given TCM pieces, Erlong Zhifei Decoction, on the basis of the control group. The course of treatment for both groups was 2 weeks. TCM syndrome scores, clinical efficacy, cytokines [Interleukin-1β (IL-1β) and Interleukin-18 (IL-18)], Caspase-1 activity and safety indicators were observed before and after treatment. RESULTS After treatment, the scores of TCM syndromes in the two groups were significantly decreased (P<0.01), and the treatment group was better than the control group in terms of improving the sensation of tightness and swelling in the ear, tinnitus, nasal congestion, headache, tympanic membrane examination and total score (P<0.05); the TCM clinical curative effect of the treatment group was better than that of the control group (P<0.05); the levels of IL-1β, IL-18 and Caspase-1 activity in the two groups were significantly reduced (P<0.01), among which the reduction in the level of IL-18 and Caspase-1 activity in the treatment group was better than that in the control group (P<0.05). During the treatment, no obvious adverse reaction occurred in the two groups of patients. CONCLUSION Erlong Zhifei Decoction combined with western medicine can relieve the symptoms of patients with secretory otitis media after novel coronavirus infection, and reduce the damage of inflammatory cytokines to middle ear tissue and the swelling of eustachian tube lumen mucosa.

The Treatment of Hypertensive Heart Failure from "Wind Leads to Water Invasion" Theory

ZHAO Fu-sen, MAO Chen-han, DONG Qi-mei, SHEN Jian-ping, LIN Yan, WANG Xin-dong

2023, 39(10): 1045-1048. doi: 10.14148/j.issn.1672-0482.2023.1045

[Abstract](128) [FullText HTML] (26) [PDF 952KB](22)

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The key pathogenic factors and the basic pathogenesis of hypertension with concomitant heart failure are water evil and water evil invading the lung. In response to the cognitive difficulties of how water fluid, which tends to descend, ascends and invades the heart and lungs during the onset of heart failure, the pathogenesis theory of "fluid evil accumulates, wind evil instigates, and water fluid ascends and invades" was proposed. It is believed that the yin deficiency of liver and kidney and qi deficiency of lung, spleen and kidney are the basis of the pathogenesis of hypertensive heart failure. The qi deficiency of lung and spleen and imbalance of ying and wei lead to easy attack of external wind; the yin deficiency of liver and kidney and yin not restricting yang cause internal wind to move easily; the deficiency of the lungs, spleen, and kidneys, as well as the dysfunction of transportation and dispersion, lead to the accumulation of water fluid. Induced by wind evil, water fluid invades upwards, leading to invasion of the heart and lungs, resulting in various heart failure symptoms such as asthma, stuffiness, palpitations, swelling, sweating, and obstruction of the chest and abdominal qi. The principle of "treating wind as the main focus, regulating the hub as the foundation, and preventing occurrence as the priority" and the treatment methods of "regulating ying and wei to resist external wind, nourishing yin fluid to extinguish internal wind, regulating the liver and spleen to benefit the hub, purging lung water to help promote lung transport, supplementing heart qi to unblock blood vessels, warming kidney yang to facilitate qi movement" are proposed.

Professor Huang Chunlin's Experience in Treating IgA Nephropathy with the Theory of "Correlation between the Five Viscera"

CHEN Yi, CAI Yu-yuan, YU Hao-kai, ZOU Chuan

2023, 39(10): 1049-1053. doi: 10.14148/j.issn.1672-0482.2023.1049

[Abstract](76) [FullText HTML] (5) [PDF 973KB](10)

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The article summarizes Professor Huang Chunlin's experience in treating IgA nephropathy with the theory of "correlation between the five viscera" and proposes that although the disease location of IgA nephropathy is mainly in the kidney and bladder, it is closely related to the lungs, spleen, heart, liver and other organs. The etiology and pathogenesis can be summarized into two aspects: external infection and internal injury, among which external infection is often caused by pathogenic toxins such as wind, heat, and dampness invading the human body; internal injuries are often attributed to dysfunction of viscera. The core of the pathogenesis is that the kidney qi is not solid, the yin and yang in the kidney are out of balance, and the movement of qi is abnormally ascending and descending, which can easily lead to external and internal pathogenic factors. The excess of evil qi along the meridians can affect the kidney meridians, resulting in powerlessness in constraint, overflow of essence and blood, leading to IgA nephropathy. The treatment should start from a holistic perspective of "kidney-based and five-viscera-related", and be dialectical based on the onset, progression, refractory factors and complications that affect IgA nephropathy.

To Discuss the Mechanism and Intervention Treatment of Intestinal Microecology in the Development of Chronic Kidney Disease Based on the Theory of "Gut-Kidney Axis"

ZHU Jin-hui, WANG Ling, TAO Jin-hua, MA Zhen-xiang, DUAN Jin-ao, LIU Pei, JIANG Shu

2023, 39(10): 1054-1062. doi: 10.14148/j.issn.1672-0482.2023.1054

[Abstract](266) [FullText HTML] (28) [PDF 1550KB](30)

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Chronic kidney disease(CKD) refers to chronic renal structure and dysfunction caused by various causes, including various primary and secondary glomerulonephritis, renal tubular injury and renal vascular lesions. The complex mechanisms and the lack of specific treatment make the disease become a major problem threatening human life and health. Based on the "gut-kidney axis" theory, etiology of intestinal flora studies provide a new perspective for the study of the mechanisms. In this review, we discuss the role of intestinal microecology in the CKD, summarize the research status of treating CKD with intestinal flora as target and traditional chinese medicine or prebiotics (probiotics) as intervention approaches. These studies provide an important theoretical basis for new treatment strategies of chronic kidney disease.

2023 Vol. 39, No. 10

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