1.Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice
Qiuyan GUO ; Jiangpeng WU ; Qixin WANG ; Yuwen HUANG ; Lin CHEN ; Jie GONG ; Maobo DU ; Guangqing CHENG ; Tianming LU ; Minghong ZHAO ; Yuan ZHAO ; Chong QIU ; Fei XIA ; Junzhe ZHANG ; Jiayun CHEN ; Feng QIU ; Jigang WANG
Journal of Pharmaceutical Analysis 2023;13(8):908-925
		                        		
		                        			
		                        			Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.
		                        		
		                        		
		                        		
		                        	
2.Correlation analysis of 3D-FLAIR MRI characteristics of the inner ear and vestibular function in the patients with vestibular neuritis.
Hui Rong JIAN ; Na HU ; Xiao Fei LI ; Ya Feng LYU ; Ya Wei LI ; Zhao Min FAN ; Hai Bo WANG ; Dao Gong ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(5):578-583
		                        		
		                        			
		                        			Objective: The characteristics of 3D-FLAIR MRI images of the inner ear of patients with vestibular neuritis were preliminarily studied to explore the possible pathogenesis of vestibular neuritis, and the correlation analysis was conducted in combination with vestibular function to provide a basis for accurate diagnosis of vestibular neuritis. Methods: A total of 36 patients with vestibular neuritis (VN) from December 2019 to October 2020 were collected from the Vertigo Department of Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University. There were 36 cases (18 females, 18 males) with unilateral acute vestibular neuritis, 17 cases of left ear and 19 cases of right ear. According to the results of 3D-FLAIR MRI in the inner ears, the patients were divided into the enhanced group and the non-enhanced group (the health side served as the normal control group). The results of vestibular function examination in the two groups were compared. SPSS19.0 software was used for statistical processing to analyze the relationship between the vestibular function and the characteristics of 3D-FLAIR imaging in the inner ears. Results: Abnormal enhancement of 3D-FLAIR was found in 31 cases (86.1%) of the 36 cases, including 14 cases of both vestibular nerve and vestibular terminal organ enhancement, eight cases of superior vestibular nerve enhancement alone, seven cases of vestibular terminal organ enhancement alone, and two cases of cochlear enhancement alone. Observation of abnormal reinforcement of vestibular nerve showed: twenty-one cases of superior vestibular nerve reinforcement, one case of superior and inferior vestibular nerve reinforcement. No abnormalities were found in 3D-FLAIR of inner ear in 5 cases. According to the analysis of vestibular function results, there were 19 cases (52.8%) with total vestibular involvement, sixteen cases (44.4%) with superior vestibular involvement alone, and one case (2.8%) with inferior vestibular involvement alone. Comparison of vestibular function between the five cases (non-enhancement group) and the 31 cases (enhanced group) in the 3D-FLAIR group of the inner ears showed that the CP values of caloric tests in the enhanced group were higher (60.81±3.49 vs 34.12±7.37), with statistically significant difference (t=-2.898, P<0.01). Conclusion: In patients with vestibular neuritis, 3D-FLAIR MRI scan of the inner ear provides visual imaging evidence for clinical practice, considering that the lesion site of vestibular neuritis is not only in the vestibular nerve, but also in the vestibular end organ. Patients with 3D-FLAIR enhanced in the inner ear may have more significant vestibular function damage.
		                        		
		                        		
		                        		
		                        			Caloric Tests
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		                        			Female
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		                        			Humans
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		                        			Imaging, Three-Dimensional/methods*
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		                        			Magnetic Resonance Imaging/methods*
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		                        			Male
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		                        			Vestibular Neuronitis/diagnosis*
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		                        			Vestibule, Labyrinth
		                        			
		                        		
		                        	
3.Frequency characteristics of horizontal semicircular canals damage and the ultrastructure analysis of crista ampullaris in patients with Meniere's disease.
Xian Feng LIU ; Dao Gong ZHANG ; Ya Feng LYU ; Xiao Fei LI ; Yong Dong SONG ; Li Gang KONG ; Bo Qin LI ; Zhao Min FAN ; Hai Bo WANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2021;56(7):698-703
		                        		
		                        			
		                        			Objective: To investigate the frequency characteristics and the pathological characteristics of the horizontal crista ampullaris in patients with Meniere's disease,and to analyse its structural basis. Methods: Between March, 2019 and November, 2019, seventy-two patients diagnosed as Meniere's disease (27 males and 45 females, aged from 13 to 74 years, with a course of disease ranging from 4 months to 32 years)in Shandong Provincial ENT Hospital were included.Caloric test, sinusoidal harmonic acceleration test (SHA), video-head impulse test (v-HIT), Gadolinium-enhanced inner-ear 3D-FLAIR MRI and pure tone audiometry were conducted in the patients. The function of the horizontal semicircular canal in these patients were analysed as well as its relationship with the degree of endolymphatic hydrops,clinical stage and duration. Light microscopy and transmission electron microscopy were used to observe the ultrastructure of horizontal semicircular canal crista ampullaris from six patients with refractory Meniere's disease who underwent labyrinthectomy. The number of type Ⅰ and type Ⅱ vestibular hair cells, the common pathophysiological changes of horizontal semicircular canal crista ampullaris were investigated in these patients. Statistical analysis was performed using SPSS 19.0. Results: With the increase of detection frequency, the abnormal rate decreased gradually. The abnormal rate of caloric test was 69.4% (50/72), SHA 51.4% (37/72), V-HIT 36.1% (26/72), comparation of the positive rate among the three tests showed statistically significant differences(P<0.05).Neither caloric test nor SHA had correlation with the degree of hydrops(P>0.05), but v-HIT(r=0.434,P<0.01).There was correlation with clinical stage to SHA and v-HIT(r=0.338,0.462,P<0.01), except caloric test(P>0.05).No significant relation was found with caloric test, SHA, v-HIT and course of disease(P>0.05).Morphological observation found abnormal monolayer epithelialization of the horizontal semicircular canal crista ampullaris significantly decreased number of type Ⅱ hair cells compared with type Ⅰhair cells. Hair cells showed perinuclear vacuolization, cytoplasmic vacuoles, mitochondrial electron density increasement and loss of stereocilia. Conclusions: The horizontal semicircular canal damage in the patients with Meniere's disease has a frequency-dependent characteristic, mainly occurres in low frequency area. With progress of the disease, the high frequency area of ampulla will be impaired gradually, and it is related to the degree of endolymphatic hydrops and hearing level. Hair cell injury would be observed,the frequency characteristics may be more associated with the disorder of type Ⅱ hair cells.
		                        		
		                        		
		                        		
		                        			Caloric Tests
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		                        			Endolymphatic Hydrops
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		                        			Female
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		                        			Humans
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		                        			Male
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		                        			Meniere Disease
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		                        			Semicircular Canals
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		                        			Semicircular Ducts
		                        			
		                        		
		                        	
4.Research Progress of Comprehensive Utilization of Ziziphi Spinosae Semen and Its By-products
Li GONG ; Jun-bo XIE ; Chang-jiang-sheng LAI ; Yan-qing ZHANG ; Xu-sheng CUI
Chinese Journal of Experimental Traditional Medical Formulae 2021;27(3):222-230
		                        		
		                        			
		                        			As a traditional Chinese medicine, Ziziphi Spinosae Semen (ZSS) has the functions of tonifying liver, tranquilizing heart, astringent sweat and producing body fluid, which is used to treat neurasthenia, insomnia, dreaminess, debility, night sweat and so on. With the rapid and constant development of ZSS resource industry and its medicinal value, a large number of by-products and waste generated in the production and processing process, resulting in serious environmental problems. In general, the utilization rate of ZSS resources was still not high. Based on this, the chemical components and potential resources of ZSS were systematically combed from the perspective of the medicinal parts and bioactive components in this paper, and the authors had summarized that the widely application of ZSS
		                        		
		                        	
5.Effect of Yuanzhisan on Learning and Memory Abilities and Food Intake of AD Rats Based on Ghrelin Level of Cerebrointestinal Peptide
Yan-wei HAO ; Bin LI ; Yi ZHANG ; Pei-jun XIE ; Jun-rong YU ; Jin-song XIANG ; Dao-yin GONG
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(21):8-14
		                        		
		                        			
		                        			Objective:Through the preparation of Alzheimer's disease (AD) rat model, the effect of Yuanzhisan on the expression of Ghrelin was observed, and the possible mechanisms in preventing and treating AD were discussed. Method:A total of 120 SD rats were randomly divided into sham-operated group, model group, donepezil group(1.02 mg·kg-1), and high, medium and low-dose Yuanzhisan groups (12,6,3 g·kg-1), with 20 rats in each group, including half male and half female. The rats in sham-operated group were injected with normal saline (NS), and the rats in other groups were injected with 
		                        		
		                        	
6.Cardioprotective Effect of Three Borneol Prevention and Administration on AMI Model Rats
Ya-mei FAN ; Li-ying WANG ; Jian WANG ; Ying-rui ZHANG ; Yin FU ; Xian-juan YANG ; Xiao-qing GUO ; Dao-yin GONG
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(6):64-72
		                        		
		                        			
		                        			Objective::The effects of three different doses of borneol on acute myocardial infarction (AMI) model rats and the effects on oxidative stress factors were compared to provide reference for elucidation of the dose-effect relationship and mechanism of anti-myocardial infarction. Method::Healthy adult male SPF SD rats were randomly divided into sham operation group, model group, solvation model group, nitroglycerin group, Borneolum high, medium and low dose(0.6, 0.3, 0.15 g·kg-1) group, l-Borneolum and Borneolum syntheticum high, medium, low dose(0.2, 0.1, 0.05 g·kg-1) group, a total of 13 groups, 20 in each group. Gavage was performed at 20 mL·kg-1 once a day for 3 days of continuous preventive administration. The sham operation group and the model group were given the same volume of distilled water, and the solvation model group was given the same volume of 5% polysorbate 80.On the third day of the pre-administration, 30 minutes after the last dose, the left anterior descending coronary artery was ligated to make a model, and the successful rats were treated for 3 days. BL-420N biological system analyzer was used to record the ST-segment amplitude and hemodynamic changes. Rat body weight and cardiac weight were weighed to calculate cardiac viscera coefficients, 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining was used to calculate the myocardial infarction rate. Hematoxylin-eosin (HE) staining was used to evaluate the degree of myocardial pathological damage. According to the kit requirements, serum levels of lactate dehydrogenase (LDH), aspartate amino-transaminase (AST), creatine kinase isoenzyme (CK-MB) and oxidative stress factors superoxide dismutase (SOD), malondialdehyde (MDA) were detected. Result::Compared with the sham operation group, the ST segment amplitude of the model group significantly increased after 5 minutes, the left ventricular diastolic blood pressure (LVDP) value increased significantly, and the measured maximum shortening velocity (Vpm) value of the left ventricular myocardial contraction component significantly decreased. The organ coefficient and myocardial infarction rate were extremely significantly increased, and the myocardial pathological tissue was severely damaged. The serum CK-MB, AST, LDH, and MDA contents were significantly increased (
		                        		
		                        	
7.Bioinformation analysis of chorismate synthase in Baphicacantus cusia and other 78 species of plants.
Jian YU ; Qi YE ; Shu-Ju NING ; Qing LI ; He-Xin TAN ; Jing-Xian FENG ; Rui-Bing CHEN ; Xiao-Li MA ; Pei-Min GONG ; Xuan-Xuan ZHAO ; Lei ZHANG ; Dao-Zhi WEI
China Journal of Chinese Materia Medica 2018;43(4):721-730
		                        		
		                        			
		                        			Chorismate synthase(CS, EC:4.2.3.5) catalyses 5-enolpyruvy-shikimate-3-phosphate to form chorismate, which is the essential enzyme for chorismate biosynthesis in organisms. The amino acid sequences of CS from 79 species of higher plants were reported in GenBank at present. 125 amino acid sequences of CS from Baphicacanthus cusia and other 78 species of plants were predicted and analyzed by using various bioinformatics software, including the composition of amino acid sequences, signal peptide, leader peptide, hydrophobic/hydrophilic, transmembrane structure, coiled-coil domain, protein secondary structure, tertiary structure and functional domains. The phylogenetic tree of CS protein family was constructed and divided into eight groups by phylogenetic analysis. The homology comparison indicated that B. cusia shared a high homology with several plants such as Sesamum indicum, Nicotiana tabacum, Solanum tuberosum and so on. The open reading frame(ORF) of all samples is about 1 300 bp, the molecular weight is about 50 kDa, the isoelectric point(pI) is 5.0-8.0 which illustrated that CS protein is slightly basic. The ORF of CS we cloned in B. cusia is 1 326 bp, the amino acid residues are 442, the molecular weight is 47 kDa and pI is 8.11. The CS in B.cusia showed obvious hydrophobicity area and hydrophilicity area, no signal peptide, and may exists transmembrane structure areas. The main secondary structures of CS protein are random coil and Alpha helix, also contain three main structural domains which are an active structural domain, a PLN02754 conserved domain and a FMN binding site. The acquired information in this study would provide certain scientific basis for further study on structure-activity relationship and structure modification of CS in plants in the future.
		                        		
		                        		
		                        		
		                        			Acanthaceae
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		                        			enzymology
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		                        			Amino Acid Sequence
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		                        			Computational Biology
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		                        			Phosphorus-Oxygen Lyases
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		                        			chemistry
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		                        			Phylogeny
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		                        			Plant Proteins
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		                        			chemistry
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		                        			Protein Structure, Secondary
		                        			
		                        		
		                        	
8.Monitoring EGFR T790M mutations by Blocker PCR in plasma of advanced non-small-cell lung cancer patients with EGFR-TKI acquired resistance
Mei-Ling ZHANG ; Chun LI ; Mao-Song YE ; Zi-Ying GONG ; Dao-Yun ZHANG ; Xin ZHANG
Fudan University Journal of Medical Sciences 2018;45(1):45-51
		                        		
		                        			
		                        			Objective To evaluate the feasibility of Blocker PCR assays in monitoring T790M mutations in plasma of non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) acquired resistance.Methods Blocker PCR assays were employed to identify mutations in plasma for 127 advanced NSCLC with acquired EGFR-TKI resistance.In addition,the paired tumor re-biopsy or PE samples were obtained to analyze EGFR mutations.Meanwhile,we evaluated the detection accuracy of Blocker PCR assays in comparison with the next generation sequencing (NGS).Results Among the 127 patients,40.15% (51/127) EGFR T790M was detected in the plasma,78.44% (40/51) coexisted with an EGFR activating mutation.Additionally,54.54 % (6/11) EGFR T790M was identified in re-biopsy tissues,while 43.75 % (14/32) were detected in the plasma.Furthermore,the concordance rate of Blocker PCR and NGS in identifying EGFR sensitizing mutations and EGFR T790M mutations was 100%.Conclusions Blocker PCR is a highly sensitive and reliable method in monitoring EGFR T790M mutations in the plasma of NSCLC patients with EGFR-TKI acquired resistance.
		                        		
		                        		
		                        		
		                        	
9.Global Longitudinal Strain at Rest for Detection of Coronary Artery Disease in Patients without Diabetes Mellitus
Hou-Juan ZUO ; Xiu-Ting YANG ; Qi-Gong LIU ; Yan ZHANG ; He-Song ZENG ; Jiang-Tao YAN ; Dao-Wen WANG ; Hong WANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2018;38(3):413-421
		                        		
		                        			
		                        			Global longitudinal strain (GLS) at rest on two-dimensional speckle tracking echocardiography (2D STE) was demonstrated to help detect coronary artery disease (CAD).However,the optimal cut-off point of GLS and its diagnostic power for detecting critical CAD in non-diabetes mellitus (DM) patients are unknown.In the present study,211 patients with suspected CAD were prospectively included,with DM patients excluded.All patients underwent echocardiography and subsequently coronary angiography within 3 days.Left ventricular (LV) GLSs were quantified by 2D STE.Territorial peak systolic longitudinal strains (TLSs) were calculated based on the perfusion territories of the 3-epicardial coronary arteries in a 17-segment LV model.Critical CAD was defined as an area stenosis ≥70% in ≥1 epicardial coronary artery (≥50% in left main coronary artery).Totally 145 patients were diagnosed as having critical CAD by coronary angiography.Significant differences were observed in all strain parameters between patients with and without critical CAD.The area under the receiver operating charcteristic (ROC) curve (AUC) for GLS in the detection of left main (LM) or threevessel CAD was 0.875 at a cut-off value of-19.05% with sensitivity of 78.1% and specificity of 72.7%,which increased to 0.926 after exclusion of apical segments (cut-off value-18.66%;sensitivity 84.4% and specificity 81.8%).The values of TLSs were significantly lower in regions supplied by stenotic arteries than in those by non-stenotic arteries.The AUC for the TLSs to identify critical stenosis of left circumflex (LCX) artery,left anterior descending (LAD) artery and right coronary artery (RCA),in order of diagnostic accuracy,was 0.818 for LCX,0.764 for LAD and 0.723 for RCA,respectively.In conclusion,in non-DM patients with suspected CAD,GLS assessed by 2D STE is an excellent predictor for LM or three-vessel CAD with high diagnostic accuracy,and a higher cut-off point than reported before should be used.Excluding apical segments in the calculation of GLS can further improve the predictive accuracy of GLS.It is unsatisfactory for TLSs to be used to identify stenotic coronary arteries.
		                        		
		                        		
		                        		
		                        	
10.Research on extraction of ginseng planting distribution information based on object-oriented classification--by case study of Fusong country in Jilin.
Ting-Ting SHI ; Xiao-Bo ZHANG ; Xiao-Bo QU ; Zhi-Dong QIU ; Qiang ZHANG ; Lan-Ping GUO ; Lu-Qi HUANG ; Qiao-Yan FU ; Zheng LV ; Ya-Li GONG
China Journal of Chinese Materia Medica 2017;42(22):4353-4357
		                        		
		                        			
		                        			Due to the particularity of ginseng cultivation, the soil fertility of cultivated ginseng is seriously depleted, so that the cultivated ginseng land can not be reused in the short term, and the land area available for cultivating ginseng becomes less and less with the growth of ginseng cultivation time. Therefore, in order to effectively manage ginseng cultivation, and achieve the sustainable use of ginseng land, it is necessary to obtain accurate information on the distribution of ginseng planting space. In this study, the object-oriented classification method based on rule set was used to extract ginseng planting area based on the ZY-3 satellite data in Fusong county, Jilin province. Firstly, multi-scale segmentation of ZY-3 remote sensing image in the study area was made, and the optimal segmentation scale was determined on the basis of multi-scale segmentation results. Secondly, a spectral curve according to the different feature type samples was generated. The similarities and differences between ginseng plot and other types of surface features were analyzed, and a rule set based on the results of spectral analysis was established to achieve the final extraction. The results show that the object-oriented classification method based on rule set can effectively extract the ginseng planting plots in the study area, and solve the problem that the extraction result is broken compared with the traditional pixel-based classification method.
		                        		
		                        		
		                        		
		                        	
            
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