1.Mechanism of Huangqi Chifengtang in Treating Atherosclerosis Based on 16S rRNA Sequencing and Metabolomics
Yuqin LIANG ; Jiaqi FU ; Yunhe SHI ; Fang LU ; Donghua YU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):94-103
ObjectiveTo investigate the mechanism of action of Huangqi Chifengtang (HQCFT) on rats with atherosclerosis (AS) by regulating the gut microbiota and their metabolites. MethodsA rat model of AS was induced through high-fat diet feeding and vitamin D3 injection, and the modeling lasted for 12 weeks. Fifty eight-week-old male SD rats were randomly divided into five groups: A blank group, a model group, a group receiving a low dose of HQCFT at 1.53 g·kg-1 (HQCFT-L group), a group receiving a high dose of HQCFT at 3.06 g·kg-1 (HQCFT-H group), and a group receiving atorvastatin calcium tablets at 1.8 mg·kg-1 (Ato group), with 10 rats in each group. Oral gavage administration started on the day after model establishment, once daily for four weeks. The efficacy of HQCFT was verified using aortic hematoxylin-eosin (HE) staining and determination of lipid levels and hemorrheology. The real-time polymerase chain reaction (Real-time PCR) was used for detecting inflammatory factor levels in the aorta, high-throughput sequencing for analyzing the gut microbiota composition in intestinal contents, targeted metabolomics for detecting short-chain fatty acid (SCFA) levels, and non-targeted metabolomics for identifying metabolomic profiles of intestinal contents. ResultsCompared with that in the blank group, the aortic tissue of rats in the model group showed significant AS lesions, including endothelial damage, inflammatory infiltration, and formation of fibrous plaques and calcified foci. Moreover, serum triacylglycerol (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated (P<0.05), while high-density lipoprotein cholesterol (HDL-C) levels were significantly reduced (P<0.05). Significant increases were observed in whole blood viscosity, plasma viscosity, and the mRNA expression levels of NOD-like receptor pyrin domain containing 3 (NLRP3), Caspase-1, interleukin (IL)-β, IL-6, and tumor necrosis factor-α (TNF-α) in aortic tissue (P<0.05). Additionally, gut microbiota composition, SCFA levels, and metabolomic profiles were significantly altered. Compared with those in the model group, serum TC, TG, and LDL-C levels, as well as the whole blood viscosity and plasma viscosity, were significantly reduced in all groups treated with HQCFT (P<0.05). Significant decreases were observed in NLRP3 mRNA expression levels in all groups treated with HQCFT, Caspase-1, IL-β, and IL-6 mRNA expression levels in the HQCFT-H group, and TNF-α mRNA expression levels in the HQCFT-L group (P<0.05). HQCFT reversed the increase in the F/B ratio and dialled back the decrease in the relative abundance of Blautia and the increase in that of Desulfovibrio. HQCFT promoted the production of acetic acid, valeric acid, and propionic acid. Non-targeted metabolomics identified 39 differential metabolites, which were mainly enriched in metabolic pathways such as arachidonic acid metabolism and primary bile acid biosynthesis. ConclusionThe mechanism by which HQCFT ameliorates AS injury may be related to the improvement of dyslipidemia and body inflammatory responses by altering gut microbiota composition, promoting SCFA production, and regulating the levels of metabolites in intestinal contents.
2.Mechanism of Huangqi Chifengtang in Treating Atherosclerosis Based on 16S rRNA Sequencing and Metabolomics
Yuqin LIANG ; Jiaqi FU ; Yunhe SHI ; Fang LU ; Donghua YU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):94-103
ObjectiveTo investigate the mechanism of action of Huangqi Chifengtang (HQCFT) on rats with atherosclerosis (AS) by regulating the gut microbiota and their metabolites. MethodsA rat model of AS was induced through high-fat diet feeding and vitamin D3 injection, and the modeling lasted for 12 weeks. Fifty eight-week-old male SD rats were randomly divided into five groups: A blank group, a model group, a group receiving a low dose of HQCFT at 1.53 g·kg-1 (HQCFT-L group), a group receiving a high dose of HQCFT at 3.06 g·kg-1 (HQCFT-H group), and a group receiving atorvastatin calcium tablets at 1.8 mg·kg-1 (Ato group), with 10 rats in each group. Oral gavage administration started on the day after model establishment, once daily for four weeks. The efficacy of HQCFT was verified using aortic hematoxylin-eosin (HE) staining and determination of lipid levels and hemorrheology. The real-time polymerase chain reaction (Real-time PCR) was used for detecting inflammatory factor levels in the aorta, high-throughput sequencing for analyzing the gut microbiota composition in intestinal contents, targeted metabolomics for detecting short-chain fatty acid (SCFA) levels, and non-targeted metabolomics for identifying metabolomic profiles of intestinal contents. ResultsCompared with that in the blank group, the aortic tissue of rats in the model group showed significant AS lesions, including endothelial damage, inflammatory infiltration, and formation of fibrous plaques and calcified foci. Moreover, serum triacylglycerol (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated (P<0.05), while high-density lipoprotein cholesterol (HDL-C) levels were significantly reduced (P<0.05). Significant increases were observed in whole blood viscosity, plasma viscosity, and the mRNA expression levels of NOD-like receptor pyrin domain containing 3 (NLRP3), Caspase-1, interleukin (IL)-β, IL-6, and tumor necrosis factor-α (TNF-α) in aortic tissue (P<0.05). Additionally, gut microbiota composition, SCFA levels, and metabolomic profiles were significantly altered. Compared with those in the model group, serum TC, TG, and LDL-C levels, as well as the whole blood viscosity and plasma viscosity, were significantly reduced in all groups treated with HQCFT (P<0.05). Significant decreases were observed in NLRP3 mRNA expression levels in all groups treated with HQCFT, Caspase-1, IL-β, and IL-6 mRNA expression levels in the HQCFT-H group, and TNF-α mRNA expression levels in the HQCFT-L group (P<0.05). HQCFT reversed the increase in the F/B ratio and dialled back the decrease in the relative abundance of Blautia and the increase in that of Desulfovibrio. HQCFT promoted the production of acetic acid, valeric acid, and propionic acid. Non-targeted metabolomics identified 39 differential metabolites, which were mainly enriched in metabolic pathways such as arachidonic acid metabolism and primary bile acid biosynthesis. ConclusionThe mechanism by which HQCFT ameliorates AS injury may be related to the improvement of dyslipidemia and body inflammatory responses by altering gut microbiota composition, promoting SCFA production, and regulating the levels of metabolites in intestinal contents.
3.Assessment of annual effective dose for the public caused by the discharge of uranium-containing wastewater into river
Chang LIU ; Hailong CHEN ; Dong LIANG ; Linfeng SHI ; Hongwei CHAI
Chinese Journal of Radiological Health 2025;34(2):259-263
Objective To predict the radiation impact of discharging wastewater containing uranium within the specified limit generated during the normal operation of a new production line at a nuclear fuel plant on the receiving water body and its downstream, and to provide a reference for the management of radioactive liquid effluent discharge from nuclear facilities. Methods Based on the technical guidelines for environmental impact assessment, literature on radiation environmental impact assessment, and data collected from on-site investigations, appropriate hydrological parameters and prediction models were selected to analyze and predict the variation pattern of radioactive nuclide uranium along the receiving water body and the radiation exposure of nearby residents. Results The maximum increase in uranium concentration in the receiving water body and its downstream caused by the discharge of uranium-containing wastewater was 1.14 μg/L. The maximum predicted concentration was 2.75 μg/L after adding the background data of the water body. The resulting maximum individual annual effective dose for the public was 1.49 × 10−4 mSv/a. Conclusion The maximum predicted uranium concentration in the receiving water body and its downstream is lower than the uranium concentration limit of 30 μg/L specified in the Standards for Drinking Water Quality (GB 5749-2022). The maximum individual annual effective dose for the public is much lower than the control value of 0.2 mSv/a specified in the Radiation Protection Regulations for Uranium Processing and Fuel and Fuel Manufacturing Facilities (EJ 1056-2018). The radiation impact is acceptable.
4.Expression and Clinical Significance of Nucleoporin 93 in Patients with Neuroblastoma
Minting LIANG ; Yang YANG ; Xiaojun LIU ; Huiya LIANG ; Hanyi ZHANG ; Yihan SUN ; Xiuyu SHI ; Xia YANG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):420-430
ObjectiveTo screen key genes associated with neuroblastoma (NB) diagnosis and prognosis using the Gene Expression Omnibus (GEO) database, and to investigate the expression and clinical significance of nucleoporin 93 (NUP93) in NB tissues. MethodsNB gene chip data (GSE73517, GSE49710, GSE19274) were retrieved from the GEO database. Differentially expressed genes (DEGs) commonly upregulated in high-risk groups were screened. The R2 database was then used to assess the prognostic value of DEGs that were commonly upregulated in the MYCN amplification group. Finally, NUP93 expression levels in the tissues from 60 NB, 25 ganglioneuroblastoma (GNB), and 26 ganglioneuroma (GN) cases were measured by immunohistochemistry . ResultsTwenty-five DEGs were identified as commonly upregulated in high-risk groups. Among these, 10 genes (SIVA1, NUP93, STIP1, LSM4, RAI14, MYOZ3, KNTC1, TNFRSF10B, TACC3 and CEP152) showed significantly higher expression in MYCN-amplified subgroups (P<0.05). Survival analysis revealed that high NUP93 expression was associated with shorter overall survival (HR = 4.0, 95% CI: 3.0,5.3, P = 1.80 × 10⁻³⁴). Immunohistochemistry results revealed that NUP93 expression in NB tissues was significantly higher than in GNB and GN tissues (P<0.001). NUP93 expression was positively correlated with high mitosis-karyorrhexis index (MKI; P=0.040), poor differentiation (P<0.001), and MYCN expression (rs = 0.793, P <0.001). ConclusionsHigh expression of NUP93 is associated with high MKI and poor differentiation, and predicts unfavorable prognosis in patients with NB, suggesting it may promote tumor progression by regulating MYCN. NUP93 has the potential to be a novel diagnostic biomarker and therapeutic target for NB.
5.Key Information Research and Ancient and Modern Application Analysis of Classic Prescription Houpo Sanwutang
Wenli SHI ; Qing TANG ; Huimin CHEN ; Jialei CAO ; Bingqi WEI ; Lan LIU ; Keke LIU ; Yun ZHANG ; Yujie CHANG ; Yihan LI ; Jingwen LI ; Bingxiang MA ; Lvyuan LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):214-221
Houpo Sanwutang, included in the Catalogue of Ancient Classical Prescriptions (Second Batch), was first recorded in the Synopsis of Golden Chamber written by ZHANG Zhongjing from the Eastern Han dynasty and was modified by successive generations of medical experts. A total of 37 pieces of effective data involving 37 ancient Chinese medical books were retrieved from different databases. Through literature mining, statistical analysis, and data processing, combined with modern articles, this study employed bibliometrics to investigate the historical origin, composition, decoction methods, clinical application, and other key information. The results showed that the medicinal origin of Houpo Sanwutang was clearly documented in classic books. Based on the conversion of the measurements from the Han Dynasty, it is recommended that 110.4 g Magnolia Officinalis Cortex, 55.2 g Rhei Radix et Rhizoma, and 72 g Aurantii Fructus Immaturus should be taken. Magnolia Officinalis Cortex and Aurantii Fructus Immaturus should be decocted with 2 400 mL water first, and 1 000 mL should be taken from the decocted liquid. Following this, Rhei Radix et Rhizoma should be added for further decoction, and then 600 mL should be taken from the decocted liquid. A single dose of administration is 200 mL, and the medication can be stopped when patients restore smooth bowel movement. Houpo Sanwutang has the effect of moving Qi, relieving stuffiness and fullness, removing food stagnation, and regulating bowels. It can be used in treating abdominal distending pain, guarding, constipation, and other diseases with the pathogenesis of stagnated heat and stagnated Qi in the stomach. The above results provide reference for the future development and research of Houpo Sanwutang.
6.Mechanism Exploration of TG Regulating PI3K/Akt to Improve Insulin Resistance in Liver of T2DM Rats Based on Transcriptomics
Qin LI ; Yonglin LIANG ; Xiaowei SHI ; Xuan LIU ; Xiangdong ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):99-109
ObjectiveTo investigate the effect of Tangzhi pills on the improvement of insulin resistance (IR) in the liver with type 2 diabetes (T2DM) by regulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway based on differential genes and its possible molecular mechanism. MethodT2DM rat models were prepared by high fat (HFD) diet combined with streptozotocin (STZ) intraperitoneal injection. The experiment was divided into blank group, model group, metformin hydrochloride group (0.18 g·kg-1), Tangzhi pills high (1.08 g·kg-1), medium (0.54 g·kg-1) and low (0.27 g·kg-1) dose groups. Rat serum, liver, and pancreatic tissue were collected, and the pathological tissue of the liver and pancreas was observed using hematoxylin-eosin (HE) staining. The fasting blood glucose level (FBG) was detected, and oral glucose tolerance (OGTT) tests were conducted. Enzyme-linked immunosorbent assay (ELISA) was used to detect fasting serum insulin (FINS) and glycated hemoglobin (GHb) levels in rats. IR homeostasis model index (HOMA-IR), β cellular homeostasis index (HOMA-β), and insulin sensitivity index (ISI) were calculated. Biochemical methods were used to determine the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) in rat serum. Transcriptomics obtained differentially expressed mRNA from liver tissue and enriched differentially expressed pathways. Real-time reverse transcriptase polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of cyclic adenylate responsive element binding protein 3-like protein 2 antibody (CREB3l2), B-lymphocyte tumor 2 (Bcl-2), Toll-like receptor 2 (TLR2), cyclin-dependent kinase inhibitor 1A (CDNK1A), and DNA damage induced transcription factor 4-like protein (DDIT4) in liver tissue. Western blot was used to detect the protein expression of phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-Akt), glucose transporter 4 (GLUT4), insulin receptor (INSR), and insulin receptor substrate 2 (IRS2). ResultThe pharmacodynamic experiment results showed that compared with model group, Tangzhi pills groups repaired liver and pancreatic tissue to varying degrees, reduced blood sugar (P<0.01), and promoted a decrease in serum FINS, GHb, and HOMA-IR (P<0.05, P<0.01). In addition, HOMA-β and ISI increased (P<0.05, P<0.01). The levels of TC, TG, and LDL-C decreased (P<0.05, P<0.01), while the levels of HDL-C increased (P<0.05, P<0.01). The transcriptomics experimental results confirmed that the PI3K/Akt signaling pathway was significantly expressed in both the blank group and model group, as well as in the high-dose Tangzhi pills group and model group. CDNK1A, DDIT4, CREB3l2, Bcl-2, and TLR2 were significantly differentially expressed mRNA during TG intervention in T2DM. Compared with the model group, the protein expression of p-PI3K, p-Akt, GLUT4, INSR, and IRS2 increased in all Tangzhi pills groups (P<0.01). The mRNA expression of CREB3l2, Bcl-2, and TLR2 increased (P<0.01), while that of CDNK1A and DDIT4 decreased (P<0.01). ConclusionTangzhi pills may regulate the PI3K/Akt signaling pathway based on the differential mRNA expression of CREB3l2, Bcl-2, TLR2, CDNK1A, and DDIT4, thereby improving IR in the liver with T2DM.
7.Methodology for the Development of Clinical Practice Guideline for Chinese Patent Medicine(Part 1): Development Status and Characteristics
Ning LIANG ; Lijiao YAN ; Yujing ZHANG ; Fuqiang ZHANG ; Ziteng HU ; Yaxin CHEN ; Huizhen LI ; Haili ZHANG ; Zhao CHEN ; Yin JIANG ; Bin LIU ; Nannan SHI ; Yanping WANG
Journal of Traditional Chinese Medicine 2024;65(1):44-49
The irrational use of Chinese patent medicines (CPM) is becoming more and more prominent, which makes the demand for clinical practice guidelines of CPM gradually increase. In order to make domestic scholars understand the latest developments and existing problems of the CPM guidelines, and promote its development, this paper introduced the concept of CPM guidelines, summarized the characteristics of the two development modes, namely “taking CPM as the key” and “taking disease/syndrome as the key”, and analyzed the current methodological status of developing and reporting CPM guidelines. Based on the existed problems, three suggestions have been put forward to optimize the quality of CPM guidelines, which were clarifying the target users and scope of CPM guidelines, establishing an open and transparent mechanism of the personnel involvement and process steps, and formulating implementable and operable recommendations for the use of CPM.
8.Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine(Part 5): Retrieval and Synthesis of Key Information on Rational Drug Use
Ziteng HU ; Ning LIANG ; Lijiao YAN ; Yujing ZHANG ; Fuqiang ZHANG ; Yaxin CHEN ; Bin LIU ; Qianzi CHE ; Yixiang LI ; Jing GUO ; Nannan SHI ; Yanping WANG
Journal of Traditional Chinese Medicine 2024;65(2):167-171
Recommendations for Chinese patent medicine (CPM) based on key information on rational drug use are one of the important conditions for enhancing guideline enforceability as well as facilitating guideline implementation. In this study, we discussed in detail of the key information on the rational use of CPM in five aspects, which are dosage, drug discontinuation, drug-drug and drug-food interactions, safety and economy. Following the process of multi-source search, synthesis and prioritization, it is suggested to collect key information on the rational use of CPM from a multi-source search of drug instructions, policy documents, literature, and clinical experts' experiences. Then the searched information should be summarized and prioritized with the principle that taking drug instructions as the basis and other-sources information for check and supplementation. Finally, methodological recommendations for the retrieval and synthesis of key information on rational drug use in guideline recommendations has been formed.
9.Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine (Part 6): Formation and Presentation of Recommendations
Yujing ZHANG ; Ning LIANG ; Lijiao YAN ; Ziteng HU ; Yaxin CHEN ; Fuqiang ZHANG ; Qianzi CHE ; Zhao CHEN ; Yuqi LIU ; Dingyi WANG ; Nannan SHI ; Yanping WANG
Journal of Traditional Chinese Medicine 2024;65(2):172-177
Recommendation formation is a key component of clinical practice guidelines for Chinese patent medicine (CPM), and should encompass the determination of the strength and direction of the recommendation, the rationale for the recommendation, and the methodology for implementing the recommendation. Recommendations can be formed through formal consensus and informal consensus. The strength and direction of recommendations for CPM guidelines should be determined by considering the quality of evidence for CPMs, the priority of the clinical questions, the pros and cons of efficacy and adverse effects, patient acceptance, the feasibility of the recommendation and the availability of resources, social fairness, economic benefits, and other influencing factors. In order to better guide guideline developers to consider these factors more rationally, this article provideed a detailed explanation of each factor in the context of the characteristics of TCM.
10.Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine (Part 8): Quality Evaluation with AGREE Ⅱ and RIGHT
Fuqiang ZHANG ; Ziteng HU ; Yujing ZHANG ; Lijiao YAN ; Juyi WANG ; Cehan ZHANG ; Jiaqi CHEN ; Mengyi WANG ; Shuoming LIU ; Xinyi XIE ; Ning LIANG ; Nannan SHI ; Yanping WANG
Journal of Traditional Chinese Medicine 2024;65(2):185-191
ObjectiveTo evaluate the methodological and reporting quality of clinical practice guidelines for Chinese patent medicine (CPM) with internationally recognized tools the appraisal of guidelines for research and evaluation (AGEREE) Ⅱ and reporting items for practice guidelines in healthcare (RIGHT), thereby providing refe-rence for the clinical application and future development of CPM guidelines. MethodsDatabases including CNKI, VIP, Wanfang and Sinomed were searched for CPM guidelines, as well as medlive.cn, websites of China Association of Chinese Medicine and Chinese Medical Association, and reference lists of the included papers. The quality of the guidelines was evaluated using the AGREE Ⅱand RIGHT tools, and consistency tests were performed using Interclass Correlation Coefficient, and descriptive analysis and chi-square test were used to analyze the reporting rate for each domain and the average score for each item. ResultsFinally, 140 CPM guidelines were included, of which 51 were disease-oriented and 89 were drug-oriented, all of which were issued by China. For 51 disease-oriented CPM guidelines, the highest average score of all six AGREE Ⅱ domains was 73.32% for clarity, and the lowest was 26.80% for application; for 89 drug-oriented CPM guidelines, the highest average score was 55.62% for scope and purpose, and the lowest was 31.32% for rigour of development. In terms of the seven domains of the RIGHT checklist, the highest reporting rate was 68.26% for background, and lowest was 27.45% for other areas regarding the disease-oriented CPM guidelines; the highest reporting rate was 61.31% for background, and the lowest was 4.49% for other areas regarding drug-oriented CPM guidelines. The average reporting rate was higher for disease-oriented than drug-oriented CPM guidelines in three domains of AGREE Ⅱ (rigour of development, clarity of presentation, editorial independence), as well as four domains of RIGHT checklist (basic information, evidence, funding and declaration and management of interests, and other areas). ConclusionThe overall methodology and reporting quality of the current CPM guidelines still need to be improved. It is recommended that future guideline development teams should strictly refer to the AGREE Ⅱ and RIGHT checklist, and take into account of the characteristics of CPM guidelines and relevant methodo-logical suggestions in the development and reporting of CPM guidelines, thereby guiding the clinical use of CPM in a better way.

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