1.Metabolomics study of kidney tissue in a mouse model of oxygen-induced retinopathy
Lijun DONG ; Hui QI ; Yuhang YANG ; Xingxing MAO ; Guoming ZHANG ; Shaochong ZHANG ; Hetian LEI
Chinese Journal of Experimental Ophthalmology 2024;42(1):19-28
Objective:To explore the effects of hyperoxic environments on renal metabolites to understand the potential mechanisms that contribute to pathologic retinal vascular neovascularization and renal injury through metabolomic studies in a mouse model of oxygen-induced retinopathy (OIR) model.Methods:Sixteen C57/B6J mice pups born to day 7 (P7) were randomly and equally divided into an OIR model group and a normal control group using a randomized numerical table of mother mice.Mice were reared standardly from birth until day 7 (P7), then mice and their mother mice in the OIR group were placed in a hyperoxic (75±2)% chamber until day 12 (P12) and then reared normally.Mice in the normal control group were reared normally throughout.Mice in two groups were killed by carbon dioxide euthanasia on postnatal day 17 (P17). The mice retinal wholemount from the two groups were made and stained with isolectin B4 (IB4) to observe the morphology of retinal vessels, central non-perfusion area and pathological neovascularization.The kidney tissue of P17 mice was analyzed by liquid chromatograph mass spectrometer.After anticoagulant treatment, the whole blood of mice was centrifuged and precipitated, and the obtained plasma without cellular components was analyzed by targeted metabonomics.Mass spectral information was interpreted using metabolomics data processing software Progenesis QI v2.3.Overall differences in metabolic profiles were distinguished by unsupervised principal component analysis and orthogonal partial least squares analysis (OPLS-DA). The fold change and P values of metabolites were compared between the two groups.The variable importance of projection value>1 and P value<0.05 was used to screen out differential metabolites.Metabolic pathway enrichment analysis of differential metabolites was performed based on the KEGG database.The feeding and use of animals were strictly in accordance with the requirements of the Ethics Committee of Jinan University, and the research protocol was reviewed and approved by the Ethics Committee of Jinan University (No.20200401-54). Results:The IB4 staining of retinal wholemounts showed that the retinal blood vessels were evenly distributed in the P17 mice from control group.The peripheral retinal vessels were tortuous and disordered with a large non-perfusion area in central region in P17 mice from OIR group, and a large number of neovascularization clusters were formed at the junction of the nonperfusion area and the vascular area of the retina, showing strong fluorescent staining.The relative area of retinal nonperfusion area in OIR group was (25.16±3.50)%, which was significantly larger than (0.63±0.30)% in normal control group ( t=12.07, P<0.001). The OPLS-DA parameter R2X cum (0.578), interpretation rate R2Y cum (0.978) and prediction rate Q2 cum (0.857) values were all greater than 0.5, indicating that the OPLS-DA model had a good predictive ability.A total of 26 main differential metabolites were found, among which 17 were up-regulated and 9 were down-regulated, including glycerophospholipids (PC 20∶4(5Z, 8Z, 11Z, 14Z)/0∶0, PC 22∶6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z)/0∶0, PC 14∶1(9Z)/20∶2(11Z, 14Z), PE P-18∶0/20∶4(6E, 8Z, 11Z, 14Z)(5OH[S]), amino acid metabolites (arginine, ornithine, pipecolic acid, and hydroxylysine), purines (guanine, hypoxanthine, hydroxypurinol), and fatty acids (methyl 15-palmitate, 2, 6, 8, 12-tetramethyl-2, 4-tridecadien-1-ol), and so on.Differential metabolites were mainly enriched in ABC transporters (L-arginine, taurine, inositol, adenosine, N-acetyl-D-glucosamine, L-glutamine), aminoacyl-tRNA biosynthesis (L-isoleucine, L-proline, L-arginine, L-histidine, L-glutamine), arginine biosynthesis (L-arginine, L-ornithine, L-glutamine) metabolic pathways.The plasma targeted metabonomics showed that the differential amino acid metabolites were mainly enriched in metabolic pathways such as aminoacyl-tRNA biosynthesis, arginine biosynthesis and metabolism, and ABC transporters. Conclusions:ABC transporter, aminoacyl-tRNA biosynthesis, and arginine biosynthesis metabolic pathways in OIR mice may participate in the pathological changes of renal injury and neovascularization in retinopathy of prematurity.
2.Effects of eicosanoic acid on proliferation and migration of human retinal vascular endothelial cells by mediating increased expression of angiopoietin-like protein 4 after binding to peroxisome proliferator-activated receptor 8
Yuhang YANG ; Hui QI ; Lijun DONG ; Zixin FAN ; Xiaofeng LU ; Mingliang WANG ; Zhen YU ; Hetian LEI ; Guoming ZHANG
Recent Advances in Ophthalmology 2024;44(9):679-685
Objective To investigate the effects of eicosanoic acid(C20DC)on the proliferation and migration of human retinal endothelial cells(HRECs)and its mechanism.Methods The optimal working concentration of C20DC in human retinal pigment epithelium 19(ARPE-19)cells and HRECs was determined as 30 mg·L-1 and 25 mg·L-1,respec-tively.HRECs were divided into the C20DC treatment group(HRECs treated with C20DC)and the control group[HRECs treated with dimethyl sulfoxide(DMSO)].The effects of C20DC on the migration and proliferation of HRECs were detec-ted by cell proliferation and migration experiments.The molecular docking method was used to simulate the binding ability of C20DC to peroxisome proliferator-activated receptor δ(PPARδ).ARPE-19 cells were divided into the C20DC+ARPE-19 group(ARPE-19 cells treated with C20DC)and the DMSO+ARPE-19 group(ARPE-19 cells treated with DMSO).The ex-pression levels of PPARδ and angiopoietin-like protein 4(ANGPTL4)in ARPE-19 cells and ANGPTL4 protein in HRECs were detected using Western blot.The ANGPTL4 protein expression levels in ARPE-19 cells and HRECs were quantitatively analyzed using enzyme-linked immunosorbent assay(ELISA).Results Compared with the control group,the prolifera-tion and migration of cells in the C20DC treatment group significantly increased(both P<0.05),and C20DC could stably bind to PPAR8(binding energy:-7.20 kcal·mol-1).Western blot showed that the expression level of ANGPTL4 protein in the C20DC+ARPE-19 group was higher than that in the DMSO+ARPE-19 group,and the difference was statistically sig-nificant(P<0.05);there was no statistically significant difference in the expression level of PPARδ receptor protein be-tween the two groups(P>0.05).The expression level of ANGPTL4 protein in the C20DC treatment group was higher than that in the control group,and the difference was statistically significant(P<0.05).ELISA quantitative analysis showed that the expression level of ANGPTL4 in the C20DC+ARPE-19 group was higher than that in the DMSO+ARPE-19 group(P<0.001);the expression level of ANGPTL4 in the C20DC treatment group was higher than that in the control group,and the difference was statistically significant(P<0.05).Conclusion C20DC can promote the expression of ANGPTL4 pro-tein by binding to PPARδ and thus increase the proliferation and migration of retinal related cells(HRECs and ARPE-19 cells).Its mechanism may be related to the increased angiogenesis in retinopathy of prematurity.
3.Data mining of medical rule in Lingnan TCM masters for treating Allergic rhinitis
Caishan FANG ; Xiangjun QI ; Shuai GAO ; Haorui LIANG ; Tengyu CHEN ; Min ZHOU ; Shenjian ZHENG ; Jiahao MO ; Guoming CHEN ; Yan RUAN
International Journal of Traditional Chinese Medicine 2022;44(3):319-324
Objective:To analyze the characteristics of prescription about Lingnan Traditional Chinese Medicine (TCM) masters for Biqiu treatment based on data mining, so as to provide reference for the clinical practice and patent drug research and development of rhinorrhea in Lingnan district.Methods:By searching journal documents and medical records in CNKI, VIP, Wanfang, Chinese BioMedical Database (SinoMed) and Duxiu Data Retrieval Platform, we selected the articles and famous TCM medical records that met the criteria on the TCM medical rules of treating Biqiu. We screened database in strict accordance with inclusion and exclusion criteria and extracted prescription information from medical cases. The software Ancient and Modern Consilia Cloud Platform (V 1.5) was used for data mining analysis and medical case standardization, and SPSS Clementine 12.0 software were used to conduct frequency statistics, association analysis and cluster analysis of drugs in medical cases. Results:A total of 31 articles and 42 medical cases including 73 prescriptions were screened. The frequency results showed that there were 40 kinds of high frequency TCMs (frequency more than 5), mainly including drugs for benefiting the qi and strengthening the spleen, medicine to relieve cold and promote nasal passages, which was the same as the frequency statistics of the effects of herbal medicine. Seven drug groups were obtained by cluster analysis. The results of rule analysis showed that 16 association rules for drug pairs and 18 association rules for 3 TCMs pairs were obtained.Conclusions:While treating allergic rhinitis, Lingnan medical doctors focus on tonifying spleen qi, dispersing wind and cold, and promoting the nasal passages, which reflect the treatment theory of cultivating earth and generating gold, and attacking and tonifying. Lingnan medical doctors commonly used Guangdong medicinal herbs, which have distinct regional characteristics. The data mining methods can comprehensively summarize and explore the potential rules of Lingnan prominent practitioners' treatment of allergic rhinitis, and provide reference for guiding the treatment of congested nose and congested nose in TCM.
4.Study on Potential Mechanism of the Seed of Draba nemorosa Based on Network Pharmacology
Peiyu SHI ; Jian LIN ; Guoming CHEN ; Caishan FANG ; Xiangjun QI ; Yingyue HOU ; Dongqiang LUO ; Wanli XING ; Ruilan HUANG ; Wenting LUO
China Pharmacy 2019;30(20):2823-2828
OBJECTIVE: To investigate the potential pharmacological mechanism of the seed of Draba nemorosa, and to provide reference for further development, utilization and clinical application. METHODS: Effective components and related target proteins of D. nemorosa were screened and identified by using TCMSP and STRING database. Cytoscape 3.7.0 software was used to construct a visual network of effective components and target proteins for the seed of D. nemorosa, and the network topology analysis was performed. The targeting protein-protein interaction (PPI) network was constructed and analyzed by STRING database and Cytoscape 3.7.0 software. KEGG pathway enrichment of target proteins was analyzed by DAVID bioinformatics resource database. RESULTS: A total of 9 effective components were screened from the seed of D. nemorosa, including quercetin, kaempferol, β-sitosterol, etc. Totally 174 target proteins were obtained, mainly including PTGS2, NCOA2, PGR, etc. Among them, JUN and MAPK1 were core proteins in PPI network. KEGG enrichment pathway included PI3K/Akt signaling pathway, TNF-α signaling pathway, HIF-1 signaling pathway, Toll-like receptor signaling pathway and thyroid hormone signal pathway, etc. CONCLUSIONS: Effective components from the seed of D. nemorosa such as quercetin, kaempferol and β-sitosterol may act on PTGS2, JUN and MAPK1 target proteins through PI3K-Akt signaling pathway and TNF-α signaling pathway, thus exert the effects of purging lung, relieving asthma, promoting edema and reducing edema.
5. Neuropathologic findings in intractable epilepsy: a clinicopathologic analysis of 822 cases
Zejun DUAN ; Kun YAO ; Jian ZHOU ; Lin LI ; Feng ZHAI ; Changqing LIU ; Zhong MA ; Yu BIAN ; Guoming LUAN ; Xueling QI
Chinese Journal of Pathology 2017;46(10):673-678
Objective:
To investigate the clinicopathologic characteristics of intractable epilepsy.
Methods:
Based on the classification criteria proposed by the International League Against Epilepsy (ILAE), a retrospective analysis of the pathological characteristics was done in 822 patients who underwent epilepsy surgery in Sanbo Brain Hospital, Capital Medical University, from June 2008 to December 2012.
Results:
The mean age of epilepsy onset was 9.9 years, mean duration of epilepsy was 11.9 years. Complex partial seizures were the main presenting features. Histopathological study showed 33 cases (4.01%) with mild forms of cortical malformations, 690 cases (83.94%) with focal cortical dysplasia (FCD) and 99 cases with others (including 39 pure hippocampal sclerosis, 20 cystosclerosis, 19 Sturge-Weber syndrome, 8 tuberous sclerosis complex, 6 without significant pathological changes, 5 gyral malformations and 2 hamartoma). Among the 690 FCD cases, 106 were FCD typeⅠ, 91 were FCD typeⅡ and 493 were FCDⅢ(Ⅲa: 160, Ⅲb: 106, Ⅲc: 26 and Ⅲd: 201).
Conclusions
FCDⅢd is the most common histopathological subtype causing intractable epilepsy, mainly due to focal hypoxia/ischemia in the perinatal period, which results in scarring of local brain tissue; this is followed by other isolated forms of FCD (FCDⅠand FCDⅡ), and then FCD Ⅲa and FCD Ⅲb. The reason to distinguish isolated forms of FCD (types Ⅰ and Ⅱ) from FCD Ⅲ and to subclassify FCD Ⅲ is to allow better definition of cortical dyslamination. Therefore, the pathogenic factors of intractable epilepsy can be grouped in greater details, and facilitate the diagnosis and potential curative treatment of intractable epilepsy.
6.Research of in vitro Anti-tumor Effect of Hydroxychloroquine
Tao YANG ; Guoming LI ; Linlu XUE ; Bo HUANG ; Qi WANG ; Changsheng DENG ; Qin XU ; Jianping SONG
China Pharmacist 2016;19(3):417-419
Objective:To investigate and evaluate the anti-tumor activity of hydroxychloroquine ( HCQ) in vitro. Methods:CCK-8 assay was applied to detect the inhibitory effect of HCQ at different concentrations(4. 78, 9. 55, 19. 10, 38. 20,76. 40 μg?ml-1 ) on A549 cells, HepG2 cells, HT-29 cells, K562 cells, Hela cells and B16 cells. Absorbance was detected by a microplate reader, and then the inhibitory rate of the tumor cells and the IC50 was calculated. Results:Compared with those of the negative control group, the inhibitory rates of HCQ at different concentrations against the six tumor cells were all increased significantly in a dose-dependent manner (P<0. 01). The inhibitory rates of the tumor cells were all above 60% when the concentration reached 38. 20μg?ml-1. The IC50 was 26. 70(A549), 27. 47(HepG2), 5. 72(HT-29), 14. 03(K562), 20. 21(Hela) and 13. 62(B16) μg?ml-1, respectively. Conclusion:HCQ shows anti-tumor activity on several cancer cells in vitro. There may be a good application prospect for HCQ in the treatment of colorectal cancer, liver cancer, cervical cancer, melanoma and leukemia.
7.Diagnosis value of high frequency ultrasonography and MRI in giant cell arteritis
Guoming CUI ; Hengtao QI ; Xiandong ZHANG ; Hongsheng SUN ; Qingrui YANG ; Zhenglun PAN ; Jiamei LI
Chinese Journal of Ultrasonography 2014;23(3):218-221
Objective To study the diagnosis value of giant cell temporal arteritis with high frequency ultrasonography and magnetic resonance imaging.Methods The total of 29 cases testified as giant cell temporal arteritis clinically were assessed by high frequency ultrasonography and magnetic resonance imaging.The 29 cases were assessed by high frequency ultrasonography,the 11 cases were assessed by magnetic resonance imaging,mural thickness and lumen diameter of temporal arteries were examined,and were compared with the biopsy specimens.Meanwhile 30 healthy volunteers were randomly selected as control group,the ultrasonography of normal temporal arteries were analyzed.Results All temporal arteries were diaplayed clearly.27 cases were diagnosed for giant cell temopral arteritis by high frequency ultrasonography in 29 cases,the diagnostic accuracy was 93.1%.The 11 cases were diagnosed by magnetic resonance imaging,the diagnostic accuracy was 100%.The imaging features were mural thickness,the lumen stenosis,and partial temporal arteries occluded,the mural was contrasted by Gd-DTPA.Conclusions High frequency ultrasonography and magnetic resonance imaging are noninvasive methods for giant cell temporal arteritis diagnosis,it is important clinical value for therapy.
8.Logistic regression analysis on relationships between traditional Chinese medicine constitutional types and overweight or obesity.
Yanbo ZHU ; Qi WANG ; Chengyu WU ; Guoming PANG ; Jianxiong ZHAO ; Shilin SHEN ; Zhongyuan XIA ; Xue YAN
Journal of Integrative Medicine 2010;8(11):1023-8
To explore the relationships between traditional Chinese medicine (TCM) constitutional types and overweight or obesity so as to provide evidence for adjusting constitutional bias and preventing and treating obesity.
9.Changes of endocrine and immune function in subjects of yang deficiency constitution.
Qi WANG ; Shilin YAO ; Jing DONG ; Hongdong WU ; Chengyu WU ; Zhongyuan XIA ; Hefeng SHI ; Guoming PANG ; Qiwei DENG ; Jianxiong ZHAO ; Jing CAI ; Zhengzhi CUI
Journal of Integrative Medicine 2008;6(12):1226-32
To investigate the changes of endocrine, cyclic nucleotide and immune systems in subjects of yang deficiency constitution, and to explore the relationship among characteristics and causes of yang deficiency constitution, the physiological and biochemical parameters.
10.The Study on the Relationship between IGR and the Rule about the Somatotypes of TCM with the correlative index
Guoming PANG ; Yong YAN ; Pu ZHU ; Qi WANG ; Yanbo ZHU
China Journal of Traditional Chinese Medicine and Pharmacy 2005;0(12):-
Objective:To confirm the correlations between the soma ofthe traditional Chinese Medicine and the objective index about Homeostasis model assessment-Insulin Resistance index(HOMA-IR)and the function about beta Cell ofislet(HOMA-?)with Impaired glucose regulation(IGR),to explore the basis for the syndrome ofthe traditional Chinese Medicine and insulin function.Methods:According from the epidemiological investigation,we had a Oral Glucose Tolerance Test and insulin releasing test to the 1 500 persons who came from downtown area、county、small towns、village,in accordance with the soma ofTCM,then investigate and analysis the correlations who meet the diagnosis ofIGR.Results:①In all 322 cases,each ratio ofthe group about signal soma、twice soma、three soma is 74.8%、19.5%、8.1%,Ahead somas are mild, deficiency ofQi, deficiency ofYang, deficiency ofQi and Yang,phlegmatic hygrosis.②The BMI ofmild group is higher than the deficiency ofQi,deficiency ofYang,deficiency ofQi and Yang group(P

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