1.DIFFERENT FACTORS AFFECTING ANTIBODY RESPONSES IN MICE IMMUNIZED BY GENE RECOMBINANT OF HCV STRUCTURE REGION
Jun DOU ; Kezhou LIU ; Zhi CHEN ; Jianer WO ; Nanxiang HE ; Yong LIU ; Mingtai ZHANG ; Xinzi WANG ; Chenghuai XU
Immunological Journal 1999;(3):151-155
To seek the optimum experiment methods of animal immunization with HCV gene and to explore the effect on antibody responses in mice immunized by pCD-HCV1 recombinant in different administration, recombinant pCD-HCV1 was constructed by technique of molecular biology and was injected into muscles of Balb/c of mice with different times, routes and dosage of inoculations as well as different treatment. The results showed that the serum antibody level reached 0.183±0.06,0.428±0.05,0.707±0.08 and 0.773±0.07(OD410 value) respectively after recombinant pCD-HCV1(100μg/mouse) were injected into mice once, twice, three times and four times. The antibody level of mice (n=12) with four times inoculation was the highest; pCD-HCV1 was perfused into stomach orally in mice or were into mice by i.p, s.c and i.m(100μg/mouse, three times) in different routes (n=6), and the antibody levels were 0.138±0.05, 0.178±0.07, 0.233±0.08 and 0.691±0.05 respectively; after the mice (n=8) were inoculated with the pCD-HCV1 of different dosage(10μg, 50μg and 100μg) the antibody levels of three groups were 0.11±0.09, 0.33±0.04, and 0.700±0.07, and the results showed a significant difference (P<0.01); Mice was injected with procaine (100μl, 0.4mg) by i.m or s.c. Then pCD-HCV1 was injected into mice and antibody levels were higher than that of mice immunized directly with recombinant pCD-HCV1 of same dosage. The results may provide a reference data deserved for screening the optimum immunization method of development HCV-DNA-based vaccine in mice model.
2.Study on the molecular mechanism of Linggui Zhugan Decoction in treating hypertension and obesity based on network pharmacology and molecular docking technology
Jixin LI ; Wenru WANG ; Yan REN ; Linjie QIU ; Xinzi SONG ; Haiyan REN ; Xiaoqing LIU ; Jin ZHANG
International Journal of Traditional Chinese Medicine 2023;45(4):456-463
Objective:To explore the material basis and mechanism of Linggui Zhugan Decoction in treating hypertension and obesity by means of network pharmacology and molecular docking technique.Methods:The TCMSP was retrieved and the main active components and action targets of Linggui Zhugan Decoction were screened. The GeneCards, OMIM, TTD, DisGeNET and DrugBank databases were used to screen disease-related targets of hypertension and obesity. The Cytoscape 3.9.0 was used to draw Chinese materia medica-composition-intersection target-disease network diagram. The STRING 11.5 database was used to draw PPI network. The cytoNCA plug-in was used to screen core active components and targets. The bioenrichment analysis of GO and KEGG was carried out in the R4.1.2, and the Chinese materia medica-intersection target-path diagram was drawn, and the core active components and core targets were docked in PyMOL and AutoDockTools 1.5.7.Results:A total of 102 potentially active components and 62 intersection targets were obtained, and 8 active components and 7 core targets were screened. Enrichment analysis showed that the key targets were mainly enriched through the signaling pathways of fluid shear stress and atherosclerosis, lipid and atherosclerosis, and AGE-RAGE, which were involved in biological processes such as the response to nutritional levels and the regulation of small molecule metabolism. Molecular docking showed that there were 37 groups with addinity < -7 kcal/mol.Conclusion:The main active components of Linggui Zhugan Decoction are quercetin, kaempferol and naringenin, which may play a role in fluid shear stress and atherosclerosis pathway, lipid and atherosclerosis pathway and AGE-RAGE signal pathway through AKT1, EGFR, IL1B and other targets.
3.The Common Somatic Symptoms of Bipolar Disorder and Their Relationships with Five-State Personality and Emotional Symptoms Based on Complex Networks and Linear Regression
Ziyan LI ; Xinzi LIU ; Dongqing YIN ; Hong ZHU ; Hongxiao JIA
Journal of Traditional Chinese Medicine 2024;65(14):1464-1468
ObjectiveTo analyze the relationship between somatic symptoms, five-state personality and emotional symptoms of bipolar disorder (BD), and to provide a reference for the clinical diagnosis and treatment of BD. MethodsThe basic information of the BD patients was collected, and the self-administered somatic symptom questionnaire was used to investigate the somatic symptoms with a frequency of >20%, which were scored as the somatic symptom scores; the 24-item Hamilton Depression Scale (HAMD) was used to evaluate the patients' depressive symptoms, the Young Mania Rating Scale (YMRS) was used to evaluate the patients' manic symptoms, the Hamilton Anxiety Scale (HAMA) was used to evaluate the patients' anxiety symptoms, and Five-State Personality Test was used to evaluate the patients' five-state personality (including taiyang personality, shaoyang personality, yin-yang balance personality, shaoyin personality, and taiyin personality). Network analysis and linear regression were used to analyse the correlation between the somatic symptom scores and the five-state personality scores, HAMD scores, YMRS scores, and HAMA scores. ResultsThere were 269 patients with BD included, and 19 somatic symptoms with a frequency of >20%, the top three being lack of strength (152 cases, 56.51%), dry mouth (137 cases, 50.93%), and preference for cold drinks (112 cases, 41.64%), and the somatic symptom scores were [7.0 (0,10.0)] points; the YMRS scores were [3.0 (0, 7.5)] points; the HAMD scores were [11.0 (5.0, 18.0)] points; and HAMA score was [6.0 (2.0, 10.0)] points. Among the five-state personalities, taiyang personality [10.0 (7.0, 13.0)] score; shaoyang personality [10.0 (7.5, 13.0)] score; yin-yang balance personality [5.0 (3.0, 7.0)] score; shaoyin personality [13.0 (10.0, 16.0)] score; and taiyin personality [14.0 (9.0, 18.0)] score. Complex network analysis showed that BD somatic symptoms were positively correlated with taiyin personality score (r = 0.23), HAMD score (r = 0.21), and YMRS score (r = 0.13); taiyin personality score was positively correlated with HAMD score (r = 0.17) and negatively correlated with YMRS score (r = -0.03). Linear regression analyses showed that somatic symptom scores were positively correlated with HAMD score (β = 0.138, P = 0.003), YMRS score (β = 0.128, P = 0.006), and taiyin personality scores (β = 0.182, P<0.001). ConclusionDepression, mania, and taiyin personality are independent risk factors for somatic symptoms in patients with BD, and taiyin personality is strongly associated with somatic symptoms in patients with BD.
4.Prediction of 1p/19q codeletion status in diffuse lower-grade glioma using multimodal MRI radiomics.
Mingjun LU ; Yaoming QU ; Andong MA ; Jianbin ZHU ; Xue ZOU ; Gengyun LIN ; Yuxin LI ; Xinzi LIU ; Zhibo WEN
Journal of Southern Medical University 2023;43(6):1023-1028
OBJECTIVE:
To develop a noninvasive method for prediction of 1p/19q codeletion in diffuse lower-grade glioma (DLGG) based on multimodal magnetic resonance imaging (MRI) radiomics.
METHODS:
We collected MRI data from 104 patients with pathologically confirmed DLGG between October, 2015 and September, 2022. A total of 535 radiomics features were extracted from T2WI, T1WI, FLAIR, CE-T1WI and DWI, including 70 morphological features, 90 first order features, and 375 texture features. We constructed logistic regression (LR), logistic regression least absolute shrinkage and selection operator (LRlasso), support vector machine (SVM) and Linear Discriminant Analysis (LDA) radiomics models and compared their predictive performance after 10-fold cross validation. The MRI images were reviewed by two radiologists independently for predicting the 1p/19q status. Receiver operating characteristic curves were used to evaluate classification performance of the radiomics models and the radiologists.
RESULTS:
The 4 radiomics models (LR, LRlasso, SVM and LDA) achieved similar area under the curve (AUC) in the validation dataset (0.833, 0.819, 0.824 and 0.819, respectively; P>0.1), and their predictive performance was all superior to that of resident physicians of radiology (AUC=0.645, P=0.011, 0.022, 0.016, 0.030, respectively) and similar to that of attending physicians of radiology (AUC=0.838, P>0.05).
CONCLUSION
Multiparametric MRI radiomics models show good performance for noninvasive prediction of 1p/19q codeletion status in patients with in diffuse lower-grade glioma.
Humans
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Magnetic Resonance Imaging
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Chromosome Aberrations
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Area Under Curve
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Glioma/genetics*
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ROC Curve
5.Traditional Chinese Medicine Syndromes in Depressive Episodes of Bipolar Disorder Based on Cluster Analysis and Bayesian Network:A Cross-sectional Study
Xinzi LIU ; Ziyan LI ; Sisi ZHENG ; Mingkang SONG ; Hong ZHU ; Dongqing YIN ; Hongxiao JIA
Journal of Traditional Chinese Medicine 2024;65(1):79-85
ObjectiveTo explore the elements, distribution and characteristics of traditional Chinese medicine (TCM) syndromes in depressive episodes of bipolar disorder (BD). MethodsBasic information, along with the four examination information, the Hamilton Depression Scale and Young Mania Rating Scale scores, were collected from 293 outpatients with BD at Beijing Anding Hospital, Capital Medical University. The four examination information with an occurrence rate greater than 12% were retained. The R language “dist” function was used to calculate the distances between samples using the Euclidean distance method. The hierarchical clustering of the four examination information was performed using the “hclust” function and the squared Euclidean distance method. A team of five researchers was formed to determine the nature and location of the essential elements of TCM syndrome in BD based on the clustering results. The PC algorithm was used to construct a Bayesian network model of the essential elements. The working group combined the essential elements of TCM syndromes in the Bayesian network according to the reference model results, and then extracted common TCM syndromes. The score of each patient based on the essential elements was matched with the common TCM syndromes to determine the syndrome type of each patient. The working group then performs conformity and revision based on this, obtaining the final distribution of TCM syndromes for the patients. ResultsThere were 77 common TCM symptoms in BD with a frequency greater than 12%. The top 15 symptoms with higher frequencies were slippery pulse, mental fatigue and lack of strength, wiry pulse, excessive rumination, preference for solitude, vexation, agitation and irritability, dry mouth, palpitations, profuse dreaming, unwarranted worries, chest oppression, thin white coating, amnesia, frequent sighing, and poor appetite. TCM syndrome elements of BD can be grouped into 11 categories. The nature of disease-related essential elements included fire, qi deficiency, blood deficiency, qi counterflow, yin deficiency, dampness, heat, fire from constraint, and phlegm. The location of disease-related essential elements included heart, liver, spleen, stomach, kidney, bladder channel, and gallbladder. By constructing a Bayesian network model and considering the opinions from the experts, six common syndromes of BD were identified, among which the highest proportion was heart-stomach heat accumulation, accounting for 27.99% (82 cases), followed by heart-spleen deficiency (55 cases, 18.77%), non-interaction between the heart and the kidney (49 cases, 16.72%), liver constraint and blood deficiency (42 cases, 14.33%), heart qi deficiency (37 cases, 12.63%), and damp-heat in the liver and gallbladder (28 cases, 9.56%). ConclusionsThe nature of disease-related elements of BD are predominantly fire and heat, while the location of disease-related essential elements are primarily associated with the heart, liver, and spleen. The most common TCM syndromes are heart-stomach heat accumulation and heart-spleen deficiency.
6.Mitochondrial uncoupler triclosan induces vasorelaxation of rat arteries.
Xiyue ZHANG ; Xinzi ZHANG ; Yanqiu ZHANG ; Mingyu LIU ; Jing JIN ; Jie YAN ; Xin SHEN ; Nan HU ; Deli DONG
Acta Pharmaceutica Sinica B 2017;7(6):623-629
Our previous studies found that mitochondrial uncouplers induced vasodilation. Triclosan, the broad spectrum antibacterial agent, is the active ingredient in soaps and toothpastes. It was reported that triclosan induced mitochondrial uncoupling, so we aim to investigate the effects of triclosan on vascular function of rat mesenteric arteries and aorta. The isometric tension of rat mesenteric artery and thoracic aorta was recorded by multi-wire myograph system. The cytosolic [Ca], mitochondrial reactive oxygen species (mitoROS), and mitochondrial membrane potential of smooth muscle cells (A10 cells) were measured using laser scanning confocal microscopy. Triclosan treatment relaxed phenylephrine (PE)- and high K(KPSS)-induced constriction, and pre-treatment with triclosan inhibited PE- and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, triclosan also relaxed PE- and KPSS-induced constriction. Triclosan induces vasorelaxation without involving Kchannel activation in smooth muscle cells of arteries. Triclosan treatment increased cytosolic [Ca], mitochondrial ROS production and depolarized mitochondrial membrane potential in A10 cells. In conclusion, triclosan induces mitochondrial uncoupling in vascular smooth muscle cells and relaxes the constricted rat mesenteric arteries and aorta of rats. The present results suggest that triclosan would indicate vasodilation effect if absorbed excessively.
7.Arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells: comparison of vasorelaxant effects of verapamil and phentolamine.
Jing JIN ; Xin SHEN ; Yu TAI ; Shanliang LI ; Mingyu LIU ; Changlin ZHEN ; Xiuchen XUAN ; Xiyue ZHANG ; Nan HU ; Xinzi ZHANG ; Deli DONG
Acta Pharmaceutica Sinica B 2017;7(3):319-325
Mitochondria are morphologically dynamic organelles which undergo fission and fusion processes. Our previous study found that arterial constriction was always accompanied by increased mitochondrial fission in smooth muscle cells, whereas inhibition of mitochondrial fission in smooth muscle cells was associated with arterial relaxation. Here, we used the typical vasorelaxants, verapamil and phentolamine, to further confirm the coupling between arterial constriction and mitochondrial fission in rat aorta. Results showed that phentolamine but not verapamil induced vasorelaxation in phenylephrine (PE)-induced rat thoracic aorta constriction. Verapamil, but not phentolamine, induced vasorelaxation in high K(KPSS)-induced rat thoracic aorta constriction. Pre-treatment with phentolamine prevented PE- but not KPSS-induced aorta constriction and pre-treatment with verapamil prevented both PE- and KPSS-induced aorta constriction. Transmission electron microscopy (TEM) results showed that verapamil but not phentolamine inhibited KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells, and verapamil prevented both PE- and KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells. Verapamil inhibited KPSS-induced excessive mitochondrial fission in cultured vascular smooth muscle cells (A10). These results further demonstrate that arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells.