1.Experimental Study on Regulation of Nrf2/HO-1 by Linalool to Inhibit Hepatic Injury Induced by Aflatoxin B1
Meng WANG ; Chunmiao XUE ; Xin HUANG ; Wenhui LIU ; Ruoyu GAO ; Xuehui BAI ; Guodong HUA ; Baochen ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):89-96
		                        		
		                        			
		                        			ObjectiveTo investigate the effect of linalool against acute liver injury induced by aflatoxin B1(AFB1) in rats and explore its protective mechanism. MethodTwenty male SPF SD rats were randomly divided into three groups: Control (n=6), AFB1 (n=7), and linalool (n=7) groups. Linalool solution (200 mg·kg-1) was administered preventatively for 14 days, while the control and AFB1 groups intragastrically received an equivalent volume of double distilled water. After preventative administration of linalool, AFB1 solution (1 mg·kg-1, dissolved in saline) was intraperitoneally injected for two consecutive days to induce acute liver injury in rats. Samples were collected and processed 14 days after model establishment. Pathological changes in liver tissue of rats were observed using Hematoxylin-eosin(HE) staining and Masson staining. Biochemical detection was performed to measure the levels of alanine transaminase(ALT), aspartate transaminase(AST), γ-glutamyl transferase(GGT), lactate dehydrogenase(LDH), alkaline phosphatase(ALP), total bilirubin(TBil), direct bilirubin(DBil), indirect bilirubin(IBil), malondialdehyde(MDA), superoxidedismutase(SOD), catalase(CAT) , glutathione(GSH), Fe3+, and Fe2+ in the liver tissue. Western blot was adopted to assess protein expression levels of nuclear factor-erythroid 2-related factor 2(Nrf2) and heme oxygenase-1(HO-1). Molecular docking was performed to verify the binding between linalool and key proteins of the Nrf2/HO-1 signaling pathway. Molecular dynamics techniques were used to confirm the stability and affinity of linalool binding with key proteins of the Nrf2/HO-1 signaling pathway. ResultPathological results showed that compared to that in the AFB1 group, the liver structure in the linalool group tended to be normal, with a significant decrease in blue collagen fibers. The linalool group exhibited significantly reduced levels of ALT, AST, GGT, LDH, ALP, TBil, DBil, and IBil (P<0.01), Fe3+ and Fe2+ content, and oxidative stress marker MDA (P<0.01). The levels of antioxidants SOD, CAT, and GSH significantly increased (P<0.01). Molecular docking showed a molecular docking energy between linalool and Nrf2 and HO-1 targets of -5.495 6 and -5.199 4 kcal·mol-1(1 cal≈4.186 J), respectively. Molecular dynamics results indicated strong affinity in the binding of linalool with Nrf2 and HO-1. Western blot revealed a significant increase in Nrf2 protein expression (P<0.05) and a decrease in HO-1 protein expression (P<0.01) in the linalool group. ConclusionLinalool may protect against AFB1-induced acute liver injury by modulating the Nrf2/HO-1 ferroptosis signaling pathway to inhibit liver cell ferroptosis and regulate hepatic oxidative stress levels. 
		                        		
		                        		
		                        		
		                        	
2.Investigation on Preventive Effect of Total Saponins of Notoginseng Radix et Rhizoma on Aspirin-induced Small Intestine Injury Based on Serum Metabolomics
Wenhui LIU ; Guodong HUA ; Baochen ZHU ; Ruoyu GAO ; Xin HUANG ; Meng WANG ; Zheng LIU ; Jiaojiao CHENG ; Zhibin SONG ; Jingui WANG ; Chunmiao XUE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):196-203
		                        		
		                        			
		                        			ObjectiveMetabolomics was utilized to investigate the preventive effect of notoginseng total saponins(NTS) on aspirin(acetyl salicylic acid, ASA)-induced small bowel injury in rats. MethodFifty male SD rats were randomly divided into normal and model groups, NTS high-dose and low-dose groups(62.5, 31.25 mg·kg-1), and positive drug group(omeprazole 2.08 mg·kg-1+rebamipide 31.25 mg·kg-1), with 10 rats in each group. Except for the normal group, rats in other groups were given ASA enteric-coated pellets 10.41 mg·kg-1 daily to establish a small intestine injury model. On this basis, each medication group was gavaged daily with the corresponding dose of drug, and the normal group and the model group were gavaged with an equal amount of drinking water. Changes in body mass and fecal characteristics of rats were recorded and scored during the period. After 14 weeks of administration, small intestinal tissues of each group were taken for hematoxylin-eosin(HE) staining, scanning electron microscopy to observe the damage, and the apparent damage of small intestine was scored. Serum from rats in the normal group, the model group, and the NTS high-dose group was taken and analyzed for metabolomics by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS), and the data were processed by multivariate statistical analysis, the potential biomarkers were screened by variable importance in the projection(VIP) value≥1.0, fold change(FC)≥1.5 or ≤0.6 and t-test P<0.05, and pathway enrichment analysis of differential metabolites was performed in conjunction with Human Metabolome Database(HMDB) and Kyoto Encyclopedia of Genes and Genomes(KEGG). ResultAfter 14 weeks of administration, the average body mass gain of the model group was lower than that of the normal group, and the NTS high-dose group was close to that of the normal group. Compared with the normal group, the fecal character score of rats in the model group was significantly increased(P<0.05), and compared with the model group, the scores of the positive drug group and the NTS high-dose group were reduced, but the difference was not statistically significant. HE staining and scanning electron microscopy results showed that NTS could significantly improve ASA-induced small intestinal injury, compared with the normal group, the small bowel injury score of the model group was significantly increased(P<0.01), compared with the model group, the small bowel injury scores of the NTS low and high dose groups were significantly reduced(P<0.05, P<0.01). Serum metabolomics screened a total of 75 differential metabolites between the normal group and the model group, of which 55 were up-regulated and 20 were down-regulated, 76 differential metabolites between the model group and the NTS groups, of which 14 were up-regulated and 62 were down-regulated. NTS could modulate three differential metabolites(salicylic acid, 3-hydroxybenzoic acid and 4-hydroxybenzoic acid), which were involved in 3 metabolic pathways, namely, the bile secretion, the biosynthesis of folic acid, and the biosynthesis of phenylalanine, tyrosine and tryptophan. ConclusionNTS can prevent ASA-induced small bowel injury, and the underlying mechanism may be related to the regulation of bile secretion and amino acid metabolic pathways in rats. 
		                        		
		                        		
		                        		
		                        	
3.Application of dual-energy CT in differential diagnosis of lung metastases and benign nodules in breast cancer
Guihan LIN ; Weibo MAO ; Weiyue CHEN ; Chunmiao CHEN ; Xue CHENG ; Xianghua HU ; Jiansong JI
Chinese Journal of Radiology 2022;56(11):1209-1214
		                        		
		                        			
		                        			Objective:To investigate the application value of dual-energy CT in the differential diagnosis of lung metastases and benign nodules in breast cancer.Methods:The data of 96 patients with pathology-confirmed breast cancer at the Fifth Affiliated Hospital of Wenzhou Medical University from March 2017 to June 2021 were analyzed retrospectively. All patients received dual-energy chest CT scans within 2 weeks before surgery. All 96 patients were female, aged 31-84 (56±12) years. A total of 207 pulmonary nodules from 96 patients were classified into 81 lung metastases and 126 benign nodules according to pathological findings. Conventional CT features [longest diameter, boundary, location and CT value difference between arterial and venous phases (ΔCT) of nodules] and dual-energy CT parameters [standardized iodine concentration (NIC), slope of energy spectrum (λ HU) and normalized effective atomic number (nZ eff) in arterial and venous phases] were analyzed and measured. The χ 2 test, independent samples t test and Kruskal-Wallis rank-sum test were used to analyze the differences of conventional CT features and dual-energy CT parameters between lung metastases and benign nodules. First, the least shrinkage and selection operator (LASSO) regression method was used to screen conventional CT features and dual-energy CT parameters, and then logistic regression analysis was performed to screen out independent risk factors for lung metastases. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of CT parameters alone and logistic model in differentiating lung metastases from benign lung nodules. Results:There were statistically significant differences between lung metastases and benign nodules in longest diameter, ?CT, NIC, λ HU and nZ eff in arterial and venous phases (all P<0.05). LASSO regression and binary logistic regression analysis showed that the venous phase λ HU (OR=59.413, 95%CI 14.233-248.002, P<0.001) and the venous phase nZ eff (OR=4.508, 95%CI 2.787-7.290, P<0.001) were independent risk factors for predicting lung metastases. Among them, the venous phase λ HU had the highest diagnostic efficiency, with an area under curve (AUC) of 0.794 and an accuracy of 74.88%. The AUC of the logistic model constructed by combining the venous phase λ HU and the venous phase nZ eff could reach 0.958, and the accuracy was improved to 92.27%, which was significantly higher than the efficacy of the two alone ( Z=6.02, 9.54, all P<0.001). Conclusion:Dual-energy CT has great application value in the identification of lung metastases and benign nodules in patients with breast cancer, especially when combined with venous phase λ HU and venous phase nZ eff, the diagnostic efficiency is further improved.
		                        		
		                        		
		                        		
		                        	
4.Case Analysis of One Acute Hypotension Adverse Event after PCI Participated by Clinical Pharmacist
Liang YANG ; Junling CAO ; Haiyan ZHU ; Lin PAN ; Chunmiao XUE
China Pharmacist 2018;21(10):1799-1801
		                        		
		                        			
		                        			Clinical pharmacist participated in the whole process of drug therapy for one case of acute hypotension adverse event af-ter PCI. Based on the patient's preoperative and postoperative medication, the hypothesis was proposed and the causes of acute hypo-tension were positively analyzed. From the perspective of pharmacology, professional advice was given and satisfactory therapeutic effects were obtained. The experience of pharmaceutical care after PCI was summarized as well.
		                        		
		                        		
		                        		
		                        	
5.Ribociclib: new antitumor drug of cyclindependent kinase 4/6 inhibitor
mei Yan WANG ; Chunmiao XUE ; wei Xiao YU ; ling Jun CAO
Drug Evaluation Research 2017;40(10):1520-1524
		                        		
		                        			
		                        			Ribociclib is an oral small molecule cyclindependent kinase 4/6 inhibitor,which inhibits tumor progression by inhibiting the conversion of tumor cells from G1 phase to S phase.The combination ofribociclib and letrozole was approved in the United States on March 13,2017 as a treatment for HR+/HER2-advanced and metastatic breast cancer patients.Clinical results showed that the drug on advanced and metastatic tumors had a significant inhibitory effect and could extend the survival of patients without deterioration compared with using letrozole alone.The incidence of adverse drug reactions is higher,but the tolerance is better.This article focuses on pharmacodynamics,pharmacokinetic,clinical results and adverse effects of this drug.
		                        		
		                        		
		                        		
		                        	
6.The regulatory effect of IL-35 on the balance of Treg/Th17 cells in allergic rhinitis patients.
Xue YIN ; Xiumin REN ; Chunmiao LIU ; Jianxing WANG ; Jinhui DONG ; Ou XU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2016;30(3):213-216
		                        		
		                        			OBJECTIVE:
		                        			To study the regulatory effect of IL-35 on the balance of Treg/Th17 cells in AR patients.
		                        		
		                        			METHOD:
		                        			In this study, 30 cases were randomly selected from outpatients of otolaryngological department in the second hospital of Hebei Medical university who were diagnosed as AR. Another 20 healthy cases enrolled from physical examination branch of our hospital were control group. The expression level of IL-35 and IL-17 in peripheral blood were detected by using ELISA and defeced CD4+CD25+Foxp3+ T cell and CD4+IL-17+T cell expression level were identified via flow cytometry.
		                        		
		                        			RESULT:
		                        			The expression level of IL-35 in AR group was obviously lower than that in control group, and the difference was a statistically significance (t = -8.145, P < 0.01). The expression level of IL-17 in AR group was obviously higher than that in control group, and the difference was a statistically significance (t = 14.969, P < 0.01). There was a remarkable negative correlation between the IL-35 and IL-17 expression in the serum of AR group (r = -0.773, P < 0.01). The percentage of CD4+CD25+Foxp3+ T cell in CD4+ T cell was significant lower in AR group than that in control group (t = -13.678, P < 0.01). The percentage of CD4+IL-17+ T cell in CD4+ T cell was much higher in AR group than that in control group (t = 5.632, P < 0.01). There was a remarkable negative correlation between the Treg and Th17 expression in the peripheral blood of AR group (r = -0.613, P < 0.01). There was a positive correlation between the expression of CD4+ CD25+Foxp3+ T cell and IL-35. There was a negative correlation between the IL-35 and Th17 in AR group (r = 0. -594, P < 0.01).
		                        		
		                        			CONCLUSION
		                        			The lower expression of IL-35 was related to the incidence of AR, and it was an important cytokines for that. The lower expression of IL-35 may inhibit the proliferation of Treg cells, lead to hyper function of Th17 cells, increase secretion of s IL-17 and result in unbalance of Treg/Th17 cells; these may be the important mechanism of the occurrence of AR, thus regulation of IL-35 may become a new target for the immunological therapy of AR.
		                        		
		                        		
		                        		
		                        			Case-Control Studies
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		                        			Enzyme-Linked Immunosorbent Assay
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		                        			Flow Cytometry
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		                        			Humans
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		                        			Interleukin-17
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		                        			blood
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		                        			Interleukins
		                        			;
		                        		
		                        			Rhinitis, Allergic
		                        			;
		                        		
		                        			immunology
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		                        			T-Lymphocytes, Regulatory
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		                        			immunology
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		                        			Th17 Cells
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		                        			immunology
		                        			
		                        		
		                        	
7.An improved association-mining research for exploring Chinese herbal property theory: based on data of the Shennong's Classic of Materia Medica.
Rui JIN ; Zhijian LIN ; Chunmiao XUE ; Bing ZHANG
Journal of Integrative Medicine 2013;11(5):352-65
		                        		
		                        			
		                        			Knowledge Discovery in Databases is gaining attention and raising new hopes for traditional Chinese medicine (TCM) researchers. It is a useful tool in understanding and deciphering TCM theories. Aiming for a better understanding of Chinese herbal property theory (CHPT), this paper performed an improved association rule learning to analyze semistructured text in the book entitled Shennong's Classic of Materia Medica. The text was firstly annotated and transformed to well-structured multidimensional data. Subsequently, an Apriori algorithm was employed for producing association rules after the sensitivity analysis of parameters. From the confirmed 120 resulting rules that described the intrinsic relationships between herbal property (qi, flavor and their combinations) and herbal efficacy, two novel fundamental principles underlying CHPT were acquired and further elucidated: (1) the many-to-one mapping of herbal efficacy to herbal property; (2) the nonrandom overlap between the related efficacy of qi and flavor. This work provided an innovative knowledge about CHPT, which would be helpful for its modern research.
		                        		
		                        		
		                        		
		                        	
8.Establishment and practice of traditional Chinese medicine property cognitive model based on three elements.
Bing ZHANG ; Rui JIN ; Jianmei HUANG ; Xiaoqing LIU ; Chunmiao XUE ; Zhijian LIN
China Journal of Chinese Materia Medica 2012;37(15):2344-2348
		                        		
		                        			
		                        			Traditional Chinese medicine (TCM) property theory is believed to be a key and difficult point of basic theory studies of TCM. Complex concepts, components and characteristics of TCM property have long puzzled researchers and urged them to develop new angles and approaches. In the view of cognitive science, TCM property theory is a cognitive process of storing, extracting, rebuilding and summarizing the sensory information about TCMs and their effects during the medical practice struggling against diseases under the guidance of traditional Chinese philosophical thinking. The cognitive process of TCM property has particular cognitive elements and strategies. Taking into account clinical application characteristics of TCMs, this study defines the particular cognitive elements. In the combination of research methods of modern chemistry, biology and mathematics, and on the basis early-stage work for five years, we have built a TCM property cognition model based on three elements and practiced with drugs with pungent and hot properties as example, in the hope of interpreting TCM properties with modern science and providing thoughts for the nature of medical properties and instruction for rational clinical prescription.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Cognition
		                        			;
		                        		
		                        			Drug Therapy
		                        			;
		                        		
		                        			psychology
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		                        			Drugs, Chinese Herbal
		                        			;
		                        		
		                        			chemistry
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		                        			pharmacology
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Medicine, Chinese Traditional
		                        			;
		                        		
		                        			psychology
		                        			;
		                        		
		                        			Models, Theoretical
		                        			
		                        		
		                        	
9.A theoretical and experimental study on the Fuzzy evaluation model of biological performance of Chinese materia medica with an either cold or hot herbal property.
Rui JIN ; Bing ZHANG ; Xiaoqing LIU ; Chunmiao XUE ; Qian ZHANG ; Lianzhen LI ; Qian ZHAO ; Kang LI
Journal of Integrative Medicine 2012;10(10):1106-19
		                        		
		                        			
		                        			The concepts of cold and hot herbal properties in traditional Chinese medicine (TCM), reflecting the efficacy trends of medicinal herbs, have the Fuzzy characteristics. It is suited for the application of Fuzzy mathematics in research of herbal properties. For a comprehensive evaluation of herbal properties, this work constructed and made a practice of the Fuzzy discrimination model regarding the biological performance of Chinese materia medica.
		                        		
		                        		
		                        		
		                        	
10.Study of biological performance of Chinese materia medica with either a cold or hot property based on the three-element mathematical analysis model.
Rui JIN ; Bing ZHANG ; Xiaoqing LIU ; Senmao LIU ; Xin LIU ; Lianzhen LI ; Qian ZHANG ; Chunmiao XUE
Journal of Integrative Medicine 2011;9(7):715-24
		                        		
		                        			
		                        			The properties of Chinese materia medica are believed to be the summarization of the effects of biological performance on the various body states. Systemic discussion of chemical-factor elements, body-condition elements, biological-performance elements and their interrelationships is needed for research into the properties of Chinese materia medica. Following the practical characteristics of Chinese medicine, the three-element mathematical model was formed by introducing some mathematical concepts and methods and was used to study the cold or hot property of Chinese medicine, and to investigate the difference in biological performances of the two properties.
		                        		
		                        		
		                        		
		                        	
            

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