1.Neurotoxicity Mechanism of Dictamni Cortex Based on Network Toxicology and Metabolomics
Xiaomin XU ; Jiameixue WO ; Suxia JIA ; Wenkai HU ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):31-39
ObjectiveThis study aims to explore the neurotoxicity mechanism of Dictamni Cortex by integrating network toxicology and metabolomics techniques. MethodsThe neurotoxicity targets induced by Dictamni Cortex were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Information Database (TCM-ID), and Comparative Toxicogenomics Database (CTD). The target predictions of the components were performed by the Swiss Target Prediction tool. Neurotoxicity-related targets were collected from the Pharmacophore Mapping and Potential Target Identification Platform (PharmMapper), GeneCards Human Gene Database (GeneCards), DisGeNET Disease Gene Network (DisGeNET), and Online Mendelian Inheritance in Man (OMIM), and the intersection targets were identified. Protein-protein interaction (PPI) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Ontology (GO) enrichment analysis were conducted. A "drug-compound-toxicity target-pathway" network was constructed via Cytoscape software to display the core regulatory network. Based on the prediction results, the neurotoxicity mechanism of Dictamni Cortex in mice was verified by using hematoxylin-eosin (HE) staining, Nissl staining, enzyme-linked immunosorbent assay (ELISA), quantitative real-time fluorescence polymerase chain reaction (Real-time PCR), and Western blot. The effects of Dictamni Cortex on the metabolic profile of mouse brain tissue were further explored by non-targeted metabolomics. ResultsNetwork toxicology screening identified 13 compounds and 175 targets in Dictamni Cortex that were related to neurotoxicity. PPI network analysis revealed that serine/threonine-protein kinase (Akt1) and tumor protein 53 (TP53) were the core targets. Additionally, GO/KEGG enrichment analysis indicated that Dictamni Cortex may regulate the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and affect oxidative stress and cell apoptosis, thereby inducing neural damage. The "Dictamni Cortex-compound-toxicity target-pathway-neural damage" network showed that dictamnine, phellodendrine, and fraxinellone may be the toxic compounds. Animal experiments showed that compared with those in the blank group, the hippocampal neurons in the brain tissue of mice treated with Dictamni Cortex were damaged. The level of superoxide dismutase (SOD) and acetylcholine (ACh) in the brain tissue was significantly reduced, while the content of malondialdehyde (MDA) was significantly increased. The level of Akt1 and p-Akt1 mRNAs and proteins in the brain tissue was significantly decreased, while the level of TP53 was significantly increased. Non-targeted metabolomics results showed that Dictamni Cortex could disrupt the level of 40 metabolites in mouse brain tissue, thereby regulating the homeostasis of 13 metabolism pathways, including phenylalanine, glycerophospholipid, and retinol. Combined analysis revealed that Akt1, p-Akt1, and TP53 were significantly correlated with phenylalanine, glycerophospholipid, and retinol metabolites. This suggested that Dictamni Cortex induced neurotoxicity in mice by regulating Akt1, p-Akt1, and TP53 and further modulating the phenylalanine, glycerophospholipid, and retinol metabolism pathways. ConclusionDictamni Cortex can induce neurotoxicity in mice, and its potential mechanism may be closely related to the activation of oxidative stress, inhibition of the PI3K/Akt signaling pathway, and regulation of phenylalanine, glycerophospholipid, and retinol metabolism pathways.
2.Effect of Dictamni Cortex on Intestinal Barrier Damage by Untargeted Metabolomics and Targeted Metabolomics for Short-chain Fatty Acids
Xiaomin XU ; Donghua YU ; Yu WANG ; Pingping CHEN ; Jiameixue WO ; Suxia JIA ; Wenkai HU ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):40-47
ObjectiveThis study aims to investigate the effect of Dictamni Cortex on intestinal barrier damage in rats and its mechanism by untargeted metabolomics and targeted metabolomics for short-chain fatty acids (SCFAs). MethodsRats were randomly divided into a control group, a high-dose group of Dictamni Cortex (8.1 g·kg-1), a medium-dose group (2.7 g·kg-1), and a low-dose group (0.9 g·kg-1). Except for the control group, the other groups were administered different doses of Dictamni Cortex by gavage for eight consecutive weeks. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in the ileal tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to detect the level of cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), in the ileal tissue of rats. Quantitative real-time fluorescence polymerase chain reaction (Real-time PCR) technology was used to detect the expression level of tight junction proteins, including zonula occludens-1 (ZO-1), Occludin, and Claudin-1 mRNAs, in the ileal tissue of rats to preliminarily explore the effects of Dictamni Cortex on intestinal damage. The dose with the most significant toxic phenotype was selected to further reveal the effects of Dictamni Cortex on the metabolic profile of ileal tissue in rats by non-targeted metabolomics combined with targeted metabolomics for SCFAs. ResultsCompared with the control group, all doses of Dictamni Cortex induced varying degrees of pathological damage in the ileum, increased TNF-α (P<0.01), IL-6 (P<0.01), and IL-1β (P<0.01) levels in the ileal tissue, and decreased the expression level of ZO-1 (P<0.05, P<0.01), Occludin (P<0.01), and Claudin-1 (P<0.05) in the ileal tissue, with the high-dose group showing the most significant toxic phenotypes. The damage mechanisms of the high-dose group of Dictamni Cortex on the ileal tissue were further explored by integrating non-targeted metabolomics and targeted metabolomics for SCFAs. The non-targeted metabolomics results showed that 21 differential metabolites were identified in the control group and the high-dose group. Compared with that in the control group, after Dictamni Cortex intervention, the level of 14 metabolites was significantly increased (P<0.05, P<0.01), and the level of seven metabolites was significantly decreased (P<0.05, P<0.01) in the ileal contents. These metabolites collectively acted on 10 related metabolic pathways, including glycerophospholipids and primary bile acid biosynthesis. The quantitative data of targeted metabolomics for SCFAs showed that Dictamni Cortex intervention disrupted the level of propionic acid, butyric acid, acetic acid, caproic acid, isobutyric acid, isovaleric acid, valeric acid, and isocaproic acid in the ileal contents of rats. Compared with those in the control group, the level of isobutyric acid, isovaleric acid, and valeric acid were significantly increased, while the level of propionic acid, butyric acid, and acetic acid were significantly decreased in the ileal contents of rats after Dictamni Cortex intervention (P<0.05, P<0.01). ConclusionDictamni Cortex can induce intestinal damage by regulating glycerophospholipid metabolism, primary bile acid biosynthesis, and metabolic pathways for SCFAs.
3.Association between unhealthy lifestyle and risk of heart disease and diabetes in the elderly in Xi'an
Ning CUI ; Jun LIU ; Rui WANG ; Nini MA ; Man ZHANG ; Aiping SUN ; Xiaomin RAN ; Aiqing PAN
Journal of Public Health and Preventive Medicine 2025;36(5):163-167
Objective To investigate the association between lifestyle and risk of heart disease and diabetes in the elderly population in Xi'an City. Methods From January 2021 to January 2024, a staged cluster sampling method was used to investigate the lifestyle and the occurrence of heart disease and diabetes in elderly population aged 60 years and above in the communities of Xi'an. Multivariate logistic regression was used to analyze the relationship between lifestyle and the risk of heart disease and diabetes. Results A total of 413 elderly people were investigated, of which 31.96% had heart disease, 27.12% had diabetes, and 10.90% had diabetes with heart disease. Multivariate logistic regression analysis revealed that age, BMI, family history, sweet food preference, smoking, and sitting and lying for a long time were risk factors for diabetes in the elderly population (P<0.05). Age, BMI, family history, history of diabetes, preference for salted products, smoking, drinking, and sitting and lying for a long time were risk factors for heart disease in the elderly population (P<0.05). Conclusion The incidence rates of heart disease and diabetes are high in the elderly population in Xi'an City. The risk of diabetes is related to unhealthy lifestyles such as sweet food preference, smoking, and sitting and lying for a long time, while heart disease is related to unhealthy lifestyles such as preference for salted products, smoking, drinking, and sitting and lying for a long time.
4.Association between unhealthy lifestyle and risk of heart disease and diabetes in the elderly in Xi'an
Ning CUI ; Jun LIU ; Rui WANG ; Nini MA ; Man ZHANG ; Aiping SUN ; Xiaomin RAN ; Aiqing PAN
Journal of Public Health and Preventive Medicine 2025;36(5):163-167
Objective To investigate the association between lifestyle and risk of heart disease and diabetes in the elderly population in Xi'an City. Methods From January 2021 to January 2024, a staged cluster sampling method was used to investigate the lifestyle and the occurrence of heart disease and diabetes in elderly population aged 60 years and above in the communities of Xi'an. Multivariate logistic regression was used to analyze the relationship between lifestyle and the risk of heart disease and diabetes. Results A total of 413 elderly people were investigated, of which 31.96% had heart disease, 27.12% had diabetes, and 10.90% had diabetes with heart disease. Multivariate logistic regression analysis revealed that age, BMI, family history, sweet food preference, smoking, and sitting and lying for a long time were risk factors for diabetes in the elderly population (P<0.05). Age, BMI, family history, history of diabetes, preference for salted products, smoking, drinking, and sitting and lying for a long time were risk factors for heart disease in the elderly population (P<0.05). Conclusion The incidence rates of heart disease and diabetes are high in the elderly population in Xi'an City. The risk of diabetes is related to unhealthy lifestyles such as sweet food preference, smoking, and sitting and lying for a long time, while heart disease is related to unhealthy lifestyles such as preference for salted products, smoking, drinking, and sitting and lying for a long time.
5.Research progress of traditional Chinese medicine in regulating Nrf2/HO-1 signaling pathway to interfere with myocardial ischemia-reperfusion injury
Suxia JIA ; Xiaomin XU ; Huicong YANG ; Shumin LIU
China Pharmacy 2024;35(1):124-128
Myocardial ischemia-reperfusion injury (MIRI) is a serious complication of revascularization in patients with myocardial infarction. The nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway plays an important role in the pathological process of MIRI. Currently,research has found that traditional Chinese medicine has a good effect on myocardial injury caused by ischemia-reperfusion. Based on the Nrf2/HO-1 signaling pathway,this article summarizes the action mechanism of traditional Chinese medicine formulas and monomers in intervening with MIRI. It is found that traditional Chinese medicine formulas (Yixin formula,Wenyang tongmai formula,Dingxin formula Ⅰ),monomers such as terpenoids (ginkgolides, astragaloside Ⅳ,ginsenosides),phenols (brazilin,hematoxylin A,resveratrol) and quinones (aloe,emodin) can alleviate MIRI by activating the Nrf2/HO-1 signaling pathway,inhibiting oxidative stress and inflammatory reactions,etc.
6.Status of health communication of medical institutions using new media platforms in Shanghai
Zongmin JIANG ; Huilin LIU ; Wei JIN ; Jingfeng ZHOU ; Quqing WANG ; Ting WANG ; Jiwei WANG ; Xiaomin WEI
Shanghai Journal of Preventive Medicine 2024;36(3):269-273
ObjectiveTo investigate the current situation of health communication carried out by medical institutions in Shanghai through new media platforms such as WeChat, Weibo, Toutiao, Douyin, Kuaishou, Bilibili and WeChat Videos, and to propose targeted measures. MethodsBased on the systematic collection of new media accounts of medical institutions in Shanghai, and through the combination of keyword screening and manual audit, health communication data of medical institutions on new media platforms were determined. ResultsData from 1 117 new media accounts of 162 medical institutions in Shanghai were collected, including 610 WeChat official accounts, 105 WeChat video accounts, 89 Weibo accounts, 18 Bilibili accounts, 198 Douyin accounts, 37 Toutiao accounts, and 60 Kuaishou accounts, totaling 111 853 posts. After keyword sorting and manual screening, a total of 66 761 health science posts were collected, with WeChat Official Accounts, Douyin, and Weibo having the top three highest number of posts. Video-based new media such as Douyin, WeChat Videos, Kuaishou, and Bilibili had a better communication impact than text and image-based new media like WeChat Official Accounts, Weibo, and Toutiao. Among them, Douyin and Toutiao were the best platforms for video and text-image-based new media, respectively. ConclusionMedical institutions in Shanghai recognize the importance of new media in health communication and have made full use of various media platforms to carry out health communication,having a certain impact on health education. In the future, medical institutions should choose appropriate platforms based on target audiences and content characteristics, fully leverage the advantages of various platforms, explore innovative communication strategies, promote the dissemination of health knowledge, and enhance the health literacy of the public.
7.Clinical efficacy and safety of camrelizumab and sintilimab in the treatment of advanced non-small cell lung cancer
Aiting YAN ; Cuizhu WANG ; Chungui LIU ; Xiaomin LU
Journal of International Oncology 2024;51(3):137-142
Objective:To compare the clinical efficacy of camrelizumab and sintilimab in the treatment of advanced non-small cell lung cancer (NSCLC) , and to explore its impact on tumor marker levels and immune function index, as well as to perform safety analysis.Methods:A total of 87 patients with advanced NSCLC who were treated in Hai'an People's Hospital of Jiangsu Province from May 2019 to May 2021 were selected as the research objects. According to the treatment scheme, the patients were divided into camrelizumab group ( n=41) and sintilimab group ( n=46) . The clinical efficacy, prognosis, tumor marker levels, immune function index and immune related adverse reactions of the two groups were compared. Results:There were no statistically significant differences in objective response rate [48.78% (20/41) vs. 39.13% (18/46) , χ2=0.82, P=0.365] or disease control rate [78.05% (32/41) vs. 71.74% (33/46) , χ2=0.46, P=0.499] in both camrelizumab and sintilimab group. The median progression-free survival (PFS) in the camrelizumab group was 9.1 months, and the median overall survival (OS) was 15.4 months. The median PFS in the sintilimab group was 9.7 months, and the median OS was 15.7 months. There were no statistically significant differences in median PFS and median OS between the two groups ( χ2=0.18, P=0.633; χ2=0.15, P=0.697) . Before treatment, there were no statistically significant differences in carcinoembryonic antigen (CEA) [ (47.68±8.12) ng/ml vs. (49.03±8.70) ng/ml, t=0.75, P=0.458], cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) [ (18.06±3.41) ng/ml vs. (17.25±3.78) ng/ml, t=1.05, P=0.299], and carbohydrate antigen 125 (CA125) [ (72.26±21.06) U/ml vs. (74.03±22.10) U/ml, t=0.38, P=0.704] levels between the camrelizumab group and sintilimab group. After treatment, there were no statistically significant differences in CEA [ (28.11±7.68) ng/ml vs. (27.63±5.71) ng/ml, t=0.33, P=0.740], CYFRA21-1 [ (9.29±1.88) ng/ml vs. (9.06±1.80) ng/ml, t=0.15, P=0.814], and CA125 [ (61.39±21.22) U/ml vs. (60.51±11.03) U/ml, t=0.25, P=0.806] levels between the two groups, but CEA, CYFRA21-1, and CA125 levels decreased after treatment compared with those before treatment in both groups (all P<0.05) . Before treatment, there were no statistically significant differences in T cells CD4 + [ (41.15±3.24) % vs. (41.17±2.90) %, t=0.03, P=0.976], CD8 + [ (68.82±3.94) % vs. (70.06±4.08) %, t=1.44, P=0.154], and CD4 +/CD8 + (1.88±0.33 vs. 1.76±0.25, t=1.92, P=0.058) between the two groups. After treatment, there were no statistically significant differences in T cells CD4 + [ (47.08±3.22) % vs. (48.53±5.07) %, t=1.57, P=0.120], CD8 + [ (61.22±1.67) % vs. (61.45±1.66) %, t=0.64, P=0.522], and CD4 +/CD8 + (2.31±0.17 vs. 2.36±0.12, t=1.60, P=0.114) between the two groups, while T cells CD8 + was lower than that before treatment, and CD4 + as well as CD4 +/CD8 + were higher than those before treatment in both groups (all P<0.05) . The overall incidence of adverse reactions in the sintilimab group [10.87% (5/46) ] was lower than that in the camrelizumab group [31.71% (13/41) ], and with a statistically significance ( χ2=5.74, P=0.016) . Conclusion:The clinical efficacy of camrelizumab and sintilimab in NSCLC patients is basically the same, the impacts of which on tumor markers and immune function are comparable, but the safety of sintilimab is better than that of camrelizumab.
8.Application of dynamic coronary roadmap in coronary artery low-dose mode
Xiaomin WU ; Zi YE ; Yaping WANG ; Yang LIU ; Yi'an YAO ; Fei CHEN ; Yiping WANG ; Yu TANG ; Yan LAI
Journal of Interventional Radiology 2024;33(3):236-239
Objective To clarify whether the use of dynamic coronary artery roadmap(DCR)technology in a low-dose mode with 7.5 frames per second during coronary intervention can further reduce the total radiation dose,fluoroscopy time,and contrast agent usage.Methods A total of 94 patients,who received coronary angiography at the Shanghai Tongji Hospital of China between July 2022 and December 2022,were enrolled in this study.The patients were randomly divided into DCR group(n=53)and control group(n=41).DCR technology was used in the DCR group to guide the performance of percutaneous coronary intervention(PCI),while low-dose mode coronary angiography was adopted in the control group.The total air kerma(AK),dose-area product(DAP),intraoperative fluoroscopy time,and contrast agent usage were compared between the two groups.Results In the DCR group AK was(597.9±222.8)mGy,which was significantly lower than(717.0±326.8)mGy in the control group(P=0.039);DAP was(33.2±13.3)Gycm2/s,which was also remarkably lower than(41.3±21.5)Gycm2/s in the control group(P=0.027).In the DCR group and the control group,the intraoperative fluoroscopy time was(9.8± 3.3)min and(12.1±4.3)min respectively(P<0.01),and the contrast agent usage was(122.3±19.0)mL and(130.5± 28.5)mL respectively(P=0.116).Conclusion In a low-dose mode during coronary intervention,the use of DCR technology can further reduce radiation dose,fluoroscopy time,and contrast agent usage.(J Intervent Radiol,2024,33:236-239)
9.Short term clinical efficacy and influencing factors of ustekinumab monoclonal antibody in the treatment of Crohn's disease
Rui WANG ; Changqin LIU ; Cui ZHANG ; Qinglu YANG ; Jiaolan YANG ; Pengyun YIN ; Xiaohui LI ; Yongshun SUN ; Zhanju LIU ; Xiaomin SUN
The Journal of Practical Medicine 2024;40(7):989-995
Objective To analyze the short-term clinical efficacy and influencing factors of ustekinumab monoclonal antibody(UST)in the treatment of Crohn′s disease(CD).Methods Retrospective cohort study was used to collect the clinical data of CD patients treated with UST in the 10th People′s Hospital affiliated to Tongji University from December 2020 to October 2022.The main analysis is the short-term clinical efficacy and influencing factors of UST treatment for CD at weeks 8 and 16,And analyze the endoscopic response rate of some patients.Results A total of 91 CD patients who first used UST were included.The 8-week clinical response rate of UST treat-ment for CD was 61.5%,and the clinical response rate was 45%;The clinical response rate at 16 weeks was 71.4%,and the clinical response rate was 54.9%.56 cases underwent endoscopic re-examination in our hospital,and the endoscopic response rate at 16 weeks was 41.1%.Univariate analysis showed that fistula(including anal fistula,personal history of anal fistula,and intestinal skin fistula)is associated with clinical remission in Crohn′s disease patients at 8/16 weeks.Further multivariate COX regression analysis showed that the presence of a history of anal fistula surgery was an independent protective factor affecting clinical remission in CD patients treated with UST at 8 weeks(HR = 0.04,95%CI:0.00~0.38;P = 0.005)and 16 weeks(HR = 0.04,95%CI:0.01~0.34;P = 0.003)compared to those without fistula;Narrow lesions are an independent risk factor for 16 week clinical remission in CD patients compared to non-narrow and non-penetrating lesions(HR = 1.75,95%CI:1.08~2.84;P = 0.023).No patients were found to have stopped medication due to serious adverse reactions.Conclusions UST can improve the clinical remission and response of CD patients at 8/16 weeks,and has good short-term clinical efficacy.CD patients with a personal history of anal fistula are recommended to use UST monoclonal antibodies,while patients with stenotic lesions should be cautious in using UST monoclonal antibodies.Whether the patient has undergone surgical treatment in the past,as well as whether UST has been used on the first or non-first line,has no significant impact on clinical remission.
10.Effect and Mechanism of Cyclocarya paliurus(Batal.)lljinskaja Polysaccharides on Type 2 Diabetic Rats by Regulating GLUT4 Translocation in Islet and Liver
Haiyun LIU ; Miaoting SHI ; Xinyi LUO ; Minyan SUN ; Chenxi XU ; Kunhan CHEN ; Xiaomin WANG ; Rengeng SHU
Herald of Medicine 2024;43(1):13-19
Objective To investigate the effect of Cyclocarya paliurus(Batal.)lljinskaja polysaccharides on insulin resistance in type 2 diabetic rats by regulating glucose transporter 4(GLUT4)translocation in islet and liver.Methods High-fat diet combined with low-dose streptozotocin(35 mg·kg-1)to induce type 2 diabetes model,all the rats were randomly divided into model control group,Cyclocarya paliurus polysaccharides groups(5,10 g·kg-1)and metformin group(0.25 g·kg-1),and treated for eight weeks(n=9 in each group).Fasting glucose and lipid were determined.Histopathology of rat islet and liver were observed by hematoxylin and eosin staining.Protein expressions of phosphorylated phosphoinositide-3-kinase(p-PI3K),phosphorylated serine-threonine kinase 1(p-Akt1),and GLUT4 in islet were measured by immunohistochemistry staining.GLUT4 translocation in the islet and liver was detected by immunofluorescence.Results Compared with the model control group,the Cyclocarya paliurus polysaccharides group and metformin group had declined fasting glucose levels and increased high-density lipoprotein(P<0.05).The structure of the islets and liver was relatively complete.The content of p-PI3K,p-Akt1 and GLUT4 in the islet increased(P<0.05).GLUT4 translocation in the liver and islet enhanced(P<0.05).Conclusions Cyclocarya paliurus polysaccharides alleviate glucose and lipid metabolism disorders.The mechanism may lay in it activating protein expressions of p-PI3K,p-Akt1,and GLUT4 in islet cells.GLUT4 translocation to the islet and liver cell membrane are increased to regulate peripheral islet resistance.


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