1.Mechanism of Xuefu Zhuyutang in Intervening in Ferroptosis in Rats with Coronary Heart Disease with Blood Stasis Syndrome Based on ACSL4 Signalling Pathway
Yi LIU ; Yang YANG ; Chang SU ; Peng TIAN ; Mingyun WANG ; Ruqian ZHONG ; Xuejiao XIE ; Qing YAN ; Qinghua PENG ; Qiuyan ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):27-38
ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 (ACSL4) signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group, sham-operation group, model group, trimetazidine group (5.4 mg·kg-1), low-, medium-, and high-dose group (3.51, 7.02,14.04 g·kg-1) of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome, and continuous treatment for 7 d was conducted, while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed, and indicators such as electrocardiogram, echocardiography, and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin (HE) staining, and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe2+, lipid peroxidation (LPO), glutathione (GSH), and T-GSH/glutathione disulfide (GSSG) in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species (ROS). Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), ACSL4, and ly-sophosphatidylcholine acyltransferase3 (LPCAT3) in myocardial tissue. ResultsCompared with those in the normal group, the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage, bow-back elevation of the ST segments, elevated T waves, J-point elevation, and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01). Blood rheology showed that the viscosity of the whole blood (low, medium, and high rate of shear) was significantly increased (P<0.01). HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken, and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles, and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased (P<0.01). The content of Fe2+, LPO, and ROS in myocardial tissue was significantly increased (P<0.01). The content of GSH was significantly decreased (P<0.01), and T-GSH/GSSG was decreased (P<0.01). The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased (P<0.05, P<0.01), while those of ACSL4 and LPCAT3 increased significantly (P<0.01). Compared with the model group, the general macroscopic symptoms and electrocardiogram results of rats in low-, medium- and high-dose groups of Xuefu Zhuyutang were alleviated, and the differences in LVEF/LVFS ratios were all significantly increased (P<0.05, P<0.01). The differences in whole-blood viscosity (low, medium, and high rate of shear) were all significantly decreased (P<0.01). The results of HE staining and transmission electron microscopy showed that the morphology, structure, and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-, medium-, and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01). The content of Fe2+, LPO, and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01), and the content of GSH and T-GSH/GSSG was significantly increased (P<0.05, P<0.01). The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01), and ACSL4 and LPCAT3 were decreased to different degrees in the low-, medium-, and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01). ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway, thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.
3.Analysis of changes in visual function before and after small incision lenticule extraction in patients with different degrees of myopia
Meiluo ZHANG ; Chunyu TIAN ; Liexi JIA ; Qinghua YANG ; Hongtao ZHANG ; Hui CUI ; Mengyu PENG ; Ruihua WEI
International Eye Science 2025;25(6):980-985
AIM: To analyze the changes in binocular visual function before and after small incision lenticule extraction(SMILE)in patients with different degrees of myopia.METHODS:A prospective non-randomized controlled study was conducted. A total of 94 patients(188 eyes)who visited the refractive outpatient department of the ophthalmology department of the General Hospital of the PLA from June 2022 to June 2023 and voluntarily chose SMILE were consecutively included. They were grouped according to the degree of myopia, including 24 cases(48 eyes)in the low myopia group(-3.00 D
4.Research progress of cAMP/PKA signaling pathway in glaucoma optic neuropathy
Hongda CUI ; Yu HUANG ; Xin XIA ; Jiangwei LI ; Qinghua PENG
International Eye Science 2025;25(10):1598-1603
Glaucoma is a multifactorial degenerative optic neuropathy, and its irreversible and blinding pathological characteristics mainly come from the damage to the optic nerve, namely glaucomatous optic neuropathy(GON). The difficulty in the treatment of GON lies in the early intervention, and currently there is no optic neuroprotective drug for the treatment of all types of GON. The death of retinal ganglion cells(RGCs)is the core pathological change caused by various pathogenic mechanisms of GON. Recent studies have found that the widespread second messenger cyclic adenosine 3', 5' -monophosphate(cAMP)and its downstream effector protein kinase A(PKA)signal cascade play an important role in the pathogenesis of GON. It can also inhibit the apoptosis of RGCs and play a protective and therapeutic role in glaucoma. Therefore, this article reviews the role of cAMP/PKA pathway in the pathophysiological development of GON, focusing on its effects on glaucoma intraocular pressure regulation, oxidative stress, neuroinflammation and optic nerve degeneration, in order to find a common central regulatory target for the optic nerve damage caused by different pathological mechanisms of GON and promote the further understanding and clinical treatment of this disease.
5.Advances and prospects of the integration of multi-omics and artificial intelligence in traditional Chinese medicine research
Guicheng Liu ; Xi Long ; Qinghua PENG ; Sainan Tian ; Shujuan Hu
Digital Chinese Medicine 2025;8(3):300-312
Objective:
To map the research hotspots, developmental trends, and existing challenges in the integration of artificial intelligence (AI) with multi-omics in traditional Chinese medicine (TCM) through comprehensive bibliometric analysis.
Methods:
China National Knowledge Infrastructure (CNKI), Wanfang Data, China Science and Technology Journal Database (VIP), Chaoxing Journal Database, PubMed, and Web of Science were searched to collect literature on the theme of AI in TCM multi-omics research from the inception of each database to December 31, 2024. Eligible records were required to simultaneously address AI, TCM, and multi-omics. Quantitative and visual analyses of publication growth, core authorship networks, institutional collaboration patterns, and keyword co-occurrence were performed using Microsoft Excel 2021, NoteExpress v4.0.0, and Cite Space 6.3.R1. AI application modes in TCM multi-omics research were also categorized and summarized.
Results:
A total of 1 106 articles were enrolled (932 Chinese and 174 English). Publication output has increased continuously since 2010 and accelerated after 2016. Region-specific collaboration clusters were identified, dominated by Beijing University of Chinese Medicine, China Academy of Chinese Medical Sciences, Shanghai University of Traditional Chinese Medicine, and Nanjing University of Chinese Medicine. Keyword co-occurrence analysis revealed that current AI applications predominantly centered on metabolomics and algorithms such as cluster analysis and data mining. Research foci mainly ranked as follows: single herbs, herbal formulae, and disease-syndrome differentiation.
Conclusion
Machine learning methods are the predominant integrative modality of AI in the realm of TCM multi-omics research at present, utilized for processing omics data and uncovering latent patterns therein. The domain of TCM, in addition to investigating omics information procured through high-throughput technologies, also integrates data on traditional Chinese medicinal substances and clinical phenotypes, progressing towards joint analysis of multi-omics, high-dimensionality of data, and multi-modality of information. Deep learning approaches represent an emerging trend in the field.
6.Phenomics of traditional Chinese medicine 2.0: the integration with digital medicine
Min Xu ; Xinyi Shao ; Donggeng Guo ; Xiaojing Yan ; Lei Wang ; Tao Yang ; Hao LIANG ; Qinghua PENG ; Lingyu Linda Ye ; Haibo Cheng ; Dayue Darrel Duan
Digital Chinese Medicine 2025;8(3):282-299
Abstract
Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.
7.Treatment of vitreous opacity based on "turbid pathogen harming the clarity"
Yi LYU ; Yu HUANG ; Yuan ZHONG ; Qinghua PENG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):547-551
The theory of "turbid pathogen harming the clarity" was proposed by YE Tianshi in his book Wenre Lun, which can be applied to clear orifices diseases such as ear, eye, nose, and mouth. Based on the location and characteristics of vitreous opacity, as well as its understanding by medical professionals throughout history, this article points out that the core pathogenesis of vitreous opacity is "turbid pathogen harming the clarity" and the obstruction of the spirit light, and the basic pathogenesis is: unfavorable liver and gallbladder conditions, damp heat accumulation and turbidity; imbalance of middle jiao, qi deficiency leading to turbidity; kidney failure with yang deficiency, stagnant water and fluids; and stagnation entering the collaterals for an extended time, causing blockage and turbidity. And based on the pathogenesis of "turbid pathogen harming the clarity" , corresponding treatment principles are proposed: soothing liver and promoting bile flow, clearing heat and eliminating turbidity; cultivating soil to produce gold, enhancing clarity and reducing turbidity; tonifying kidney and promoting yang, warming and dispelling turbid pathogens; and removing blood stasis and activating collaterals, dispelling turbidity and unblocking the orifices. Based on the theory of "turbid pathogen harming the clarity" , this article summarizes the pathogenesis and treatment of vitreous opacity, in order to provide new ideas for traditional Chinese medicine treatment of this disease.
8.Analysis of Dry Eye Animal Models Based on Clinical Disease and Syndrome Characteristics in Traditional Chinese and Western Medicine
Guicheng LIU ; Yao CHEN ; Binan WANG ; Pei LIU ; Jun PENG ; Sainan TIAN ; Qinghua PENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):200-208
ObjectiveAccording to the etiology, pathogenesis, and clinical characteristics of dry eye (DE), this paper aims to analyze existing DE animal models to provide recommendations for building more clinically relevant DE models that integrate traditional Chinese and Western medicine. MethodsBy the retrieval and analysis of relevant literature on DE animal experiments, combined with expert consensus, an evaluation scale was created to assess relevance from the perspectives of pathogenesis, diagnostic criteria, and traditional Chinese medicine (TCM) differentiation. On the basis of data provided by the literature, the clinical relevance was evaluated for the animal models constructed in the literature. ResultsAmong the existing methods for establishing a DE animal model, benzalkonium chloride eye-drop induction showed the highest clinical relevance, demonstrating 98% alignment with Western medicine. However, current models generally showed higher relevance to Western medicine than to TCM, and there was a lack of models integrating disease with syndrome. ConclusionAs DE involves diverse causes and pathogenesis, single-factor models cannot fully simulate the complex pathology of DE. Future research should focus on building multi-mechanism DE models, exploring new etiological directions, standardizing model evaluation systems, and promoting integration of traditional Chinese and Western medicine. This will help precisely simulate the pathophysiological process of human DE and provide more valuable guidance for clinical diagnosis and treatment, ultimately enhancing patient outcomes and satisfaction.
9.Ziyin Mingmu Formula improve retinitis pigmentosa through the GRP78/IRE1/ATF6 pathway in vitro study
Chen OU ; Houpan SONG ; Wei XIE ; Jun PENG ; Meiyan ZENG ; Qinghua PENG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(6):773-781
Objective We aimed to explore the mechanism of Ziyin Mingmu Formula in improving retinitis pigmentosa.Methods Twenty SD rats were randomly divided into the blank serum group and the Ziyin Mingmu Formula containing serum group using a random number table method,with 10 rats in each group.The rats in the Ziyin Mingmu Formula containing serum group were given Ziyin Mingmu Formula(46.875 g/kg),while the rats in the blank serum group were given distilled water.The Ziyin Mingmu Formula containing serum and blank serum were prepared.Analysis of chemical components in Ziyin Mingmu Formula containing serum using liquid chromatography-mass spectrometry technology.Adult retinal pigment epithelial cell line-19(ARPE-19)cells were treated with tunicamycin to induce endoplasmic reticulum stress injury model.The optimal volume fraction of Ziyin Mingmu Formula containing serum was screened by CCK-8.ARPE-19 cells were divided into the blank group,the model group,the blank serum group,the Ziyin Mingmu Formula containing serum group and the tauroursodeoxycholic acid group,each group is intervened separately.After 24 hours of intervention,the morphological observation of cells was performed using a multi-time dynamic cell function analysis system,cell survival rate was detected by CCK-8,cell apoptosis rate was detected by Annexin V-FITC/PI,and protein and mRNA expressions of 78 kDa glucose regulated protein(GRP78),inositol-requiring enzyme 1(IRE1)and activating transcription factor 6(ATF6)were detected by Western blotting and ddPCR.Results The main chemical components in Ziyin Mingmu Formula containing serum were obtained by liquid chromatography-mass spectrometry analysis,such as arbutin,salicylic acid,luteolin,Salvianolic acid A,erysovine,taurine,quercetin,maltol,baicalin,and danshensu.Compared with the model group,the number of cells in Ziyin Mingmu Formula containing serum group increased,the growth was more uniform,and the floating dead ARPE-19 cells and fragments decreased.The cell survival rate of Ziyin Mingmu Formula containing serum group and taursodeoxycholic acid group increased,and the cell apoptosis rate decreased(P<0.05).The protein expressions of GRP78,IRE1,and ATF6 in Ziyin Mingmu Formula containing serum group were decreased,and IRE1 and ATF6 in taursodeoxycholic acid group were decreased(P<0.05).The mRNA expressions of GRP78,IRE1,and ATF6 in Ziyin Mingmu Formula containing serum group and tauroursodeoxycholic acid group were decreased(P<0.05).Conclusion Ziyin Mingmu Formula can reduce the cell apoptosis of ARPE-19 cells induced by endoplasmic reticulum stress,and its molecular mechanism is related to down-regulating the expression of GRP78,IRE1,ATF6 and inhibiting the endoplasmic reticulum stress response.
10.Role of endoplasmic reticulum stress in retinitis pigmentosa
Chen OU ; Wei XIE ; Qinghua PENG
International Eye Science 2024;24(12):1912-1916
Retinitis pigmentosa(RP)is a degenerative blinding disease characterized by the loss of the function of photoreceptor and retinal pigment epithelium. The activation of endoplasmic reticulum stress is a cellular defense regulatory mechanism, aimed at restoring the stability of endoplasmic reticulum function by self-regulation through a series of molecular signaling pathways. Rhodopsin mutation is a common cause of RP. Misfolding and retention of rhodopsin in endoplasmic reticulum and apoptosis of photoreceptor cells and retinal pigment epithelial cells induced by endoplasmic reticulum stress can lead to the occurrence and development of RP. This paper discusses endoplasmic reticulum stress and its role in the pathogenesis of RP and the role of endoplasmic reticulum stress inhibitors, traditional Chinese medicine and chemical drugs in regulating endoplasmic reticulum stress in RP treatment was summarized, in order to provide theoretical basis for endoplasmic reticulum stress in the clinical application of RP and provide new ideas for the research, prevention and treatment of RP.


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