1.Research progress on the mechanism of atherosclerosis caused by triglyceride-rich lipoprotein and its residues
Meiyi LIU ; Mingyan SHAO ; Yuanyuan GUAN ; Fangli LI ; Lingru LI
Chinese Journal of Arteriosclerosis 2025;33(4):355-362
Triglyceride(TG)is transported in the blood as specific triglyceride-rich lipoprotein(TRL).When TRL is overproduced or the catabolism is not timely,cholesterol ester-rich residues is formed.Both TRL and its residues contribute to the development of atherosclerosis(As)through various direct and indirect mechanisms.Currently,the combination of lifestyle interventions and Western medicines is considered the preferred treatment strategy for As.Howev-er,lipid-lowering therapy alone cannot fully eliminate the residual risk of As.In contrast,traditional Chinese medicine emphasizes the holistic regulation of bodily functions to prevent and treat As.This paper will begin by examining the met-abolic mechanisms of TRL,elucidate the role of TRL and its residues in the risk of As occurrence,and summarize current strategies targeting the TRL metabolic pathway to reduce the incidence of As.
2.Research progress on the mechanism of atherosclerosis caused by triglyceride-rich lipoprotein and its residues
Meiyi LIU ; Mingyan SHAO ; Yuanyuan GUAN ; Fangli LI ; Lingru LI
Chinese Journal of Arteriosclerosis 2025;33(4):355-362
Triglyceride(TG)is transported in the blood as specific triglyceride-rich lipoprotein(TRL).When TRL is overproduced or the catabolism is not timely,cholesterol ester-rich residues is formed.Both TRL and its residues contribute to the development of atherosclerosis(As)through various direct and indirect mechanisms.Currently,the combination of lifestyle interventions and Western medicines is considered the preferred treatment strategy for As.Howev-er,lipid-lowering therapy alone cannot fully eliminate the residual risk of As.In contrast,traditional Chinese medicine emphasizes the holistic regulation of bodily functions to prevent and treat As.This paper will begin by examining the met-abolic mechanisms of TRL,elucidate the role of TRL and its residues in the risk of As occurrence,and summarize current strategies targeting the TRL metabolic pathway to reduce the incidence of As.
3.Huatan Qushi formula alleviates non-alcoholic fatty liver disease via PI3K/Akt signaling and gut microbiota modulation
Xiuping Zhang ; Linghui Zhu ; Jinchen Ma ; Yi Zheng ; Xuejing Yang ; Lingling Yang ; Yang Dong ; Yan Zhang ; Baoxing Liu ; Lingru Li
Journal of Traditional Chinese Medical Sciences 2024;11(4):443-455
Objective:
To provide the mechanism-based pharmacotherapy of the Huatan Qushi formula (HTQS formula), for the health management and treatment of non-alcoholic fatty liver disease (NAFLD).
Methods:
A rat model of NAFLD was employed to examine the efficacy and safety of the HTQS formula. In vivo active components and potential mechanisms of the HTQS formula were identified using UPLC‒MS/MS combined with network pharmacology. The influence of the HTQS formula on the dominating proteins in PI3K/Akt pathway was validated in vivo using western blot. Finally, 16S rRNA sequencing of the gut microbiome was conducted followed by targeted metabolomics detecting fecal short-chain fatty acids (SCFAs) and bile acids to determine the impact of the HTQS formula on gut microbiota.
Results:
The HTQS formula reduced weight gain and hepatic steatosis in NAFLD rats and decreased serum total cholesterol (TC), triglycerides, blood glucose, and insulin resistance (IR) without causing liver or kidney injury. We detected 28 components using UPLC‒MS/MS and identified 439 shared targets between NAFLD and the HTQS formula. Primarily, we focused on the PI3K/Akt signaling pathway based on protein‒protein interaction network analysis. We validated that the HTQS formula inhibited liver steatosis and inflammation by increasing the phosphorylation levels of PI3K, AKT, P27, GSK3β in the PI3K/Akt signaling pathway. 16S rRNA sequencing revealed that the HTQS formula reduced the abundance of the genus Family_XIII_AD3011_group, which was positively correlated with IR and taurodeoxycholic acid. In addition, Lachnospiraceae_UCG_010 inversely correlated with TC and five bile acids, which could be essential to the therapeutic effect of the HTQS formula against NAFLD.
Conclusions
The HTQS formula proved to be an effective pharmacotherapy for NAFLD without causing liver or kidney injury. Multiple potent components of the HTQS formula could alleviate liver steatosis and lipid metabolism disorder by modulating the PI3K/Akt signaling pathway and restoring gut microbiota composition.
4.Mode of Interdisciplinary Research of Traditional Chinese Medicine: Learn from the Study of Biological Characteristics and Mathematical Representation of the Transformation from Phlegm-Dampness Constitution to Dyslipidemia
Huaiyu WANG ; Tong ZHAO ; Ji WANG ; Lingru LI ; Yingshuai LI ; Suixiang GAO ; Qi WANG
Journal of Traditional Chinese Medicine 2024;65(6):553-556
The current interdisciplinary research on traditional Chinese medicine (TCM) often comes from the simple combination of TCM application needs and mature engineering technology. Actually, higher goal of cross-disciplinary research should be the win-win development of TCM and interdisciplinary majors. In detail, to enhance the innovative development of original thinking mode of TCM, meanwhile, to stimulate the innovation of interdisciplinary majors with medical tasks. Previously, we successfully performed the research on the objective representation of pre-disease and disease state of dyslipidemia in population with phlegm-dampness constitution. Taking this project as an example, this paper discusses the methodology on scientific issue positioning, key medical tasks selection, interdisciplinary theory, and technology exploration, to expounds the research design and ideas which could be generalized in other cross-disciplinary research of TCM.
5.Clinical characteristics and prognoses of severe autoimmune glial fibrillary acidic protein astrocytopathy
Mengqiu PAN ; Lingru XI ; Zuying KUANG ; Sifen XIE ; Lihua ZHOU ; Yangyang DAI ; JingLong YE ; Bo LI ; Zhanhang WANG
Chinese Journal of Neuromedicine 2024;23(5):478-483
Objective:To explore the clinical characteristics and prognoses of severe autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).Methods:A retrospective analysis was performed. The clinical data of 12 patients with severe GFAP-A admitted to Department of Neurology, Guangdong 999 Brain Hospital from January 2018 to June 2023 were collected, including demography, clinical manifestations, MRI features, laboratory examination results (such as antibodies), treatments and prognoses.Results:Among the 12 patients, 9 were male and 3 were female, with an average onset age of (46.58±17.53) years. Primary symptoms included headache, limb weakness, limb numbness, mental disorder, epileptic seizure, and urinary and defecation disorder; 9 patients had fever before onset. With aggravated severe GFAP-A, 12 patients had impaired consciousness, 12 had respiratory failure, 6 had unstable blood pressure and heart rate, and 2 had status epilepticus. Cranial MRI indicated abnormal lesions in all 12 patients, including 10 with brainstem involvement (7 had involved medulla oblongata); 10 showed soft meningeal enhancement. In 8 patients received MRI of the whole spinal cord, 7 had abnormal spinal cord lesions; point-like enhancement of the whole spinal meninges was observed in 6 of the 7 patients. All 12 patients had positive cerebrospinal fluid GFAP-IgG, and 3 patients also had positive serum GFAP-IgG. All patients accepted glucocorticoids and immunoglobulin immunotherapy, and 1 patient was supplemented with mycophenolate mofetil; 8 patients had good prognosis, and 4 patients died. Pulmonary infection, hyponatremia, hypoproteinemia, and deep vein thrombosis were the common complications.Conclusion:Patients with severe GFAP-A mainly manifest as meningoencephalitis and meningoencephalomyelitis, and are likely involved medulla oblongata, enjoying rapid clinical progression; even with early immunotherapy, high mortality rate is still noted.
6.Research on the mechanism of Atractylodes-Pinellia-Poria in the treatment of pancreatic cancer based on network pharmacology and molecular docking
Jirong WANG ; Xiaofei SHI ; Yuhui CHONG ; Lingru JIA ; Xueying WAN ; Ruimin LI
Journal of Pharmaceutical Practice 2023;41(10):616-624
Objective To predict the target of Atractylodes-Panxia-Poria in the treatment of pancreatic cancer, and to explore its potential molecular mechanism by using network pharmacology and molecular docking. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PharmMapper, OMIM, GeneCards, STRING, DAVID and Cytoscape software were used to construct a series of network diagrams. The core targets and conduct GO analysis and KEGG pathway enrichment analyses of the target genes were selected. Finally, molecular docking verification of key active ingredients and potential targets were conducted by AutoDock software. Results A total of 35 active ingredients, 190 related targets, 1566 targets of pancreatic cancer and 76 intersection targets were screened for the treatment of pancreatic cancer with Atractylodes-Panxia-Poria. These intersection targets were mainly involved in several biological processes, including positive regulation of gene expression, cytokine-mediated signaling pathway and regulation of apoptotic process, etc, which were also related to pathways in cancer, hepatitis B, colorectal cancer, chemical carcinogenesis-receptor activation, pancreatic cancer, and MAPK signaling pathway, etc. Molecular docking results showed that the main active components of Atractylodes-Panxia-Poria had certain affinity with the potential targets of pancreatic cancer. Conclusion Atractylodes-Panxia-Poria mainly exerts a therapeutic effect on pancreatic cancer through multi-component, multi-target and multi-pathway, which provides a certain theoretical basis for the clinical application of Atractylodes -Panxia-Poria in the treatment of pancreatic cancer.
7.Exploration of Syndromes and Prescriptions Related to Qi-Depression Constitution
Xueke WANG ; Tianxing LI ; Yini FANG ; Lingru LI ; Qi WANG
Journal of Traditional Chinese Medicine 2023;64(20):2057-2062
Based on qi-depression constitution, we systematically sorted out and summarized the manifestations of specific symptoms and prescriptions of qi-depression constitution. It is believed that a series of syndromes can be developed due to the imbalance in patients with qi-depression constitution. The four most common syndromes inclinic were summarized as liver depression, deficient depression, phlegm-heat depression, and stagnation. “Liver depression” resulted from liver failing to free flow of qi, then qi stagnated, so Xiaoyao Powder (逍遥散) was recommended as treatment for liver qi depression, spleen deficiency and blood insufficiency; Danzhi Xiaoyao Powder (丹栀逍遥散) for liver depression and spleen deficiency, depression transforming into fire; Bentun Decoction (奔豚汤) for liver depression transforming into fire, upward rushing of qi counterflow. “Deficient depression” resulted from long-term mental disorder and will consume qi and blood potentially to qi and blood deficiency, so Ganmai Dazao Decoction (甘麦大枣汤) was recommended as treatment for deficiency of both heart and spleen, and heart and spleen failing to tonify; Baihe Dihuang Decocotion (百合地黄汤) for heart and lung with yin deficiency, spirit and soul failing to guard. “Phlegm-heat depression” resulted from disturbance of qi movement, affecting the transportation of essence, blood and body fluids, gathering dampness and forming phlegm into heat. Banxia Houpo Decoction (半夏厚朴汤) was recommended as treatment for liver depression and failing to transportation, phlegm coagulation and qi stagnation; Chaihu (or Chaiqin) Wendan Decoction (柴胡(芩)温胆汤) for liver depression and phlegm-heat harassing internally, and disharmony of gallbladder and stomach; self-made Shugan Jieyu Decoction (舒肝解郁汤) for liver-qi stagnation and phlegm-fire harassing internally. “Stagnation” resulted from stagnation of Qi and blood, accumulation of turbid phlegm, and forming stasis over time, so Yueju Pill (越鞠丸) was recommended as treatment for liver depression and failing to transportation, phlegm-fire with damp diet and blood depression; self-made Rupi Sanjie Decoction (乳癖散结汤) for liver depression, stagnation of Qi and blood.
8.Comparative study on the medication law in prescriptions of Ye Tianshi and Wu Jutong for spleen and stomach diseases based on data mining
Xing LIU ; Qi WANG ; Mingyue MA ; Lingru LI ; Kanghua MO ; Zheng YANG
International Journal of Traditional Chinese Medicine 2023;45(10):1319-1323
Objective:To analyze the medication characteristics and prescription law of Ye Tianshi and Wu Jutong in the treatment of spleen and stomach diseases based on data mining method; To provide reference for clinical treatment of spleen and stomach diseases.Methods:Records related to spleen and stomach diseases in the Lin Zheng Zhi Nan Yi An and Wu Ju Tong Yi An were collected. SPSS Statistics 26.0, SPSS Modeler 18.0 and other software were used to conduct statistical analysis on the frequency, properties and efficacy of Chinese materia medica. The association analysis and clustering analysis were carried out on high-frequency drugs. Results:A total of 423 medical records, 231 kinds of Chinese materia medica (2 752 times) were included in the Lin Zheng Zhi Nan Yi An. A total of 83 medical records, 115 kinds of Chinese materia medica (753 times) were included in Wu Ju Tong Yi An. The Chinese materia medica used by Ye Tianshi and Wu Jutong to treat spleen and stomach diseases was mainly warm, mild and cold, with pungent, sweet and bitter as the main tastes; they mainly belonged to the spleen, lung and stomach meridians, and their main functions included clearing heat, diverting water and dampness, regulating qi, resolving phlegm, relieving cough, and tonifying deficiency. 6 second-order association rule combinations and 5 effective clusters were obtained for Ye Tianshi's treatment of spleen and stomach diseases, and 15 second-order association rule combinations and 6 effective clusters for Wu Jutong's treatment. Conclusions:Ye Tianshi and Wu Jutong's medication attributes in the treatment of spleen and stomach diseases are basically similar. They often use the method of bitter catharsis to regulate the qi movement of spleen and stomach, and the products of sweet and mild infiltration are used to eliminate dampness and heat. Compared with Ye Tianshi, Wu Jutong used few tonic, heat-clearing, phlegm-resolving, cough-relieving and asthma-relieving drugs, and more diuretics and qi-regulating drugs.
9.Potential mechanism of Huatan Qushi decoction on improving phlegm-dampness constitution using microRNA array and RT-qPCR targeting on hsa-miR-1237-3p
Zhang XIUPING ; Wang JI ; Liu BAOXING ; Yao HAIQIANG ; Chen YU ; Yin YUQING ; Yang XUEJING ; Li LINGRU
Journal of Traditional Chinese Medical Sciences 2021;8(1):43-51
Background: Metabolic diseases pose considerable burden on the healthcare system worldwide, indi-cating the significance of prevention and treatment. In constitution theory of traditional Chinese med-icine, phlegm-dampness constitution (PDC) is the common basis of metabolic diseases. In clinical practice, Huatan Qushi (HTQS) decoction targeting on PDC can effectively improve metabolic indicators. However, its underlying biochemical mechanism still remains unclear.Methods: Eight PDC participants received HTQS decoction for three months. Their blood was collected at baseline and 1 and 3 months after intervention started. Related biomedical indicators were detected. High-throughput sequencing and RT-qPCR were used for validation. Due to the missing data, repeated measures with missing values in mixed models were used. Results: After 3-month treatment, HDL-C level increased (P<.001) and FBG, FINS, and HbA1c all showed decreasing trend at different time points (all P < .05). After miRNA high-throughput sequencing, compared with the baseline, differential miRNAs at 1 and 3 months were screened, and target gene prediction and KEGG pathway enrichment analysis were performed. The results displayed that metabolic disease-related pathways mainly included pathways in cancer, PI3K-Akt signaling pathway, etc. Further, RT-qPCR showed that hsa-miR-1237-3p differed statistically (P =.008). Then we validated the target genes of hsa-miR-1237-3p in the"Pathways in Cancer"pathway including SDF1, AC, CRK, and HGF, also known as upstream target genes of PI3K/AKT pathway. The results showed that two indicators of CRK and HGF were in statistical significance (P=.045 and P=.036, respectively). Conclusion: PDC serves as a common basis for various metabolic diseases. Through adjusting PDC, HTQS decoction can improve biomedical indicators including blood glucose, HbA1c, insulin, and HDL-C. The target pathway is"Pathways in cancer". Specifically, HTQS decoction acts on targets of CRK and HGF by regulating hsa-miR-1237-3p, and probably exerts effects on their downstream PI3K/AKT pathway.
10.Proteomic analysis of overweight/obesity and related abnormal glucose and lipid metabolism caused by phlegm-dampness retention
Ma JIAYI ; Sun SHUXIAN ; Ni CHENG ; Li LINGRU ; Xia JING ; Li HOUQIN ; Song HUIRONG ; Heng XUJUN ; Hu DANDAN ; Li YUANYUAN
Journal of Traditional Chinese Medical Sciences 2021;8(3):224-237
Objective: To investigate the proteomic characteristics of overweight/obesity and related abnormal glucose and lipid metabolism caused by phlegm-dampness retention to identify related biomarkers. Methods: Seventy-one subjects were enrolled in the study. We assessed blood glucose, blood lipids, body mass index (BMI), and phlegm-dampness pattern, which was confirmed by a traditional Chinese med-icine clinician. Of the participants, we included healthy participants with normal weight (NW, n =23), overweight/obese participants with normal metabolism (ONM, n = 19), overweight/obese participants with pre-diabetes (OPD, n = 12), and overweight/obese participants with marginally-elevated blood lipids (OML, n = 17). Among them, the ONM, OPD, and OML groups were diagnosed with phlegm-dampness pattern. The data-independent acquisition (DIA) method was first used to analyze the plasma protein expression of each group, and the relevant differential proteins of each group were screened. The co-expressed proteins were evaluated by Venn analysis. The pathway analyses of the differential proteins were analyzed using Ingenuity Pathway Analysis (IPA) software. Parallel reaction monitoring (PRM) was used to verify the differential and common proteins in each group. Results: After comparing ONM, OPD, and OML groups with NW group, we identified the differentially expressed proteins (DEPs). Next, we determined the DEPs among OPD, OML, and ONM groups. Using Venn analysis of the DEPs in each group, 24 co-expressed proteins were screened. Two co-expressed proteins were verified by PRM. IPA analysis showed that pathways including LXR/RXR activation, acute phase response signaling, and FXR/RXR activation were common to all three groups of phlegm-damp overweight/obesity participants. However, the activation or inhibition of these pathways was different among the three groups. Conclusion: Participants with overweight/obesity have similar proteomic characteristics, though each type shows specific proteomic characteristics. Two co-expressed proteins, VTN and ORM1, are potential biomarkers for glucose and lipid metabolism diseases with overweight/obesity caused by phlegm-dampness retention.


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