1.Application of circular dichroism to the study of interactions between small molecular compounds and DNA.
Zhenjia LIU ; Yikang SI ; Xiaoguang CHEN
Acta Pharmaceutica Sinica 2010;45(12):1478-84
Circular dichroism (CD) is an useful technique for monitoring DNA conformation changes resulting from changes in environmental conditions, such as temperature, ionic strength, and pH, and also for the study of the interaction between DNA and ligands (including small molecules and proteins). CD spectroscopy of DNA arises from the asymmetric backbone sugars and by the helical structures often adopted by nucleic acids. By the interpretation of induced circular dichroism (ICD) of ligand signals resulting from the coupling of electric transition moments of the ligand, DNA bases within the asymmetric DNA environment, ligand-DNA interactions, as well as the DNA-binding mode can be assessed. A number of important conclusions have been reported that related to the observed ICD signals resulting from the interactions between intercalators and groove binders with DNA. If short oligonucleotide sequences are used in the study, sequences-specific of binding also can be deduced. CD determination requires smaller amounts of sample, and not limited by the molecular weight or size and can be performed rapidly; though CD is of low resolution, but it's a complement to NMR and X-ray diffraction methods. This review will introduce the characters of the CD spectra of DNA, and its application to the studies of DNA with small molecules; some progress of the studies in our laboratory will also be discussed. CD is expected to be used as a screening method in seeking more DNA-targeted drugs, such as, antineoplastic, antimicrobial and antiviral drugs.
2.Analysis of complicating ascites of mini-percutaneous nephrolithotripsy
Yu LIU ; Zhenjia GUO ; Zengjun ZHU ; Wenwen SUN
Chinese Journal of Postgraduates of Medicine 2014;37(5):17-19
Objective To explore the clinical causes and preventive measures of complicating ascites of mini-percutaneous nephrolithotripsy (MPCNL).Methods Retrospective analysis of 285 patients with MPCNL for upper urinary tract calculus,which were divided into ascites group and no-ascites group.Results All the procedures were successful.Ascites group of 21 cases,no-ascites group of 264 cases.Univariate analysis showed that the diameter and number of calculus,perfusion pressure,perfusion time,pressure volume of irrigation fluid,preoperative upper urinary tract infection,history of treatment associated with complicating ascites (P< 0.05),with age,gender,body mass index no correlation (P> 0.05).Logistic regression analysis showed that perfusion pressure,perfusion time,pressure volume of irrigation fluid was independent risk factors after MPCNL concurrent ascites (P < 0.05).Conclusions MPCNL concurrent ascites are closely related to the large perfusion volume,the long operative perfusion time,the high perfusion pressure of irrigation fluid.On the premise of keeping the operative visual field clear,as far as possible to reduce the perfusion pressure,control irrigation fluid-flow rate,reduce the large peffusion volume.These could decrease the coincidence of the ascites.
3.The interaction between C5aR,C5L2 and chemotaxis inhibitory protein secreted by Staphylococcus aureus
Zhenjia LIU ; Guanhua DU ; Lili GONG ; Jinming GAO
Basic & Clinical Medicine 2010;30(5):496-499
Objective To investigate the mutual effect between G protein-coupled receptors(GPCR)including C5a receptor(C5aR),C5a like receptor 2(C5L2)and chemotaxis inhibitory protein(CHIPs)secreted by Staphylococcus aureus.Methods The purified CHIPs was incubated with HEK 293T cells overexpressing C5aR,C5L2 and C-X-C chemokine receptor type 3(CXCR3).Binding signal was detected by Western blot.Results HEK 293T cells overexpressing C5aR can efficiently bind to CHIPs.No apparent relation between CHIPs and C5L2 or CXCR3 was identified.Conclusion C5aR but not C5L2 is a membrane receptor for binding CHIPs,suggesting a difference between C5aR and C5L2 in association with binding CHIPs.
4.Three different drug interaction mathematical models used to evaluate the cytotoxicity of SAHA and arsenic trioxide in combination
Na LU ; Zhenjia LIU ; Zheng YAN ; Nan WANG
Acta Pharmaceutica Sinica 2010;45(5):601-7
To clarify the source of deviations of drug combination effects evaluated with different drug interaction mathematical models, the cytotoxicity of SAHA and arsenic trioxide and their combinations were observed in a series of human cancer cell lines and a normal cell line. The combined effects were evaluated with three drug interaction models: Loewe Additivity (LA), Bliss Independence (BI) and Chou's Median Effect Model. The evaluations with three different models were further compared with each other. We demonstrated that when dose-response curves were fitted with the same method, similar evaluated results for drug combinations would be derived with different models. The deviations of evaluated effects of drug combinations were attributed to different curve fitting methods used rather than the models themselves. The effects of drug combinations showed discrepancies on different cell lines, and at different combined drug concentrations on same cell line.
5.The Application of Multi-slice CT in the Diagnosis and Treatment of the Colonic Tumor
Ximing WANG ; Lebin WU ; Cheng LIU ; Zhenjia LI ; Zhuodong XU
Journal of Practical Radiology 1996;0(04):-
Objective To improve the applied value of Multi-slice CT (MSCT) in the diagnosis and treatment of the colonic tumours.Methods MSCT axial images reconstruction 4-D,MIP and CT virtual colonoscopy (CTVC) in 30 patients with colonic tumours proved histologically were analysed and compared these results with that of barium enema and colon endoscopy.Results The diagnostic correctly rate in this group was 100% by MSCT,while the diagnostic rate by CTVE and colon endoscopy was basicly identical.Conclusion MSCT is recommended for the diagnosis and treatment of the colonic tumour.
6.The clinical application of 64-slices spiral CT in angiography of coronary artery
Ximing WANG ; Lebin WU ; Zhenjia LI ; Cheng LIU ; Haisong CHEN
Chinese Journal of Radiology 2000;0(11):-
Objective To study the clin ic al application of 64-slices spiral CT in coronary artery. Methods Twenty-six patients were performed 64-slices spiral CT in coronary artery, 15 of the 26 patients underwent selective coronary artery angiography. Results The main branches and part of the sub-branches o f the coronary artery were clearly displayed. 38 coronary artery branches of 16 patients were found stenosis. In 15 cases with conventional angiography, all mai n branches and parts of sub-branches of coronary artery were displayed clearly. All patients demonstrated coronary artery stenosis. The diagnostic accuracy of 64-slices spiral CT was 94.12%. Conclusion As a minimall y invasive examination, 64-slices spiral CT is a valuable method to detect and diagnose the diseases of coronary artery.
7.The value of dual-source CT in the diagnosis of interrupted aortic arch
Ximing WANG ; Lebin WU ; Zhaoping CHENG ; Dawei WU ; Zhenjia LI ; Baoting CHAO ; Min WANG ; Cheng LIU ; Tao WANG
Chinese Journal of Radiology 2008;42(2):123-126
ObjectiveTo explore the value of low-dose gated dual-source CT(DSCT)in the diagnosis of interrupted aortic.arch.MethodsNine pediatric patients performed DSCT angiography and color Doppler flow imaging(CDFI)in the thoracic aorta and heart.All patients were operated.ResultsDSCT examination was finished in all patients with interrupted aortic arch.Nine patients were associated with ventricular septal defect(VSD),8 patients with patent ductus arteriosus(PDA),2 with bronchus artery dilation and 3 with abnormal origin of the coronary artery.Seven patients were diagnosed as interrupted aortic arch by CDFI,2 patients were diagnosed as truncus arteriosus and coarctation of the aorta respectively.All VSDs and PDAs were detected by CDFI.The diagnostic accuracy of DSCT and CDFI were 94.12%(32/34)and 82.35(28/34)respectively.Conclusion DSCT is a valuable imaging method for the diagnosis of pediatric interrupted aortic arch.
8.Experimental study on small molecule combinations inducing reprogramming of rat fibroblasts into functional neurons
Qunwei GAO ; Zhenjia DAI ; Xinkang YANG ; Changqing LIU ; Gaofeng LIU
Journal of Zhejiang University. Medical sciences 2024;53(4):498-508
Objective:To establish a methodological system for reprogramming rat embryonic fibroblasts(REF)into chemically induced neurons(ciNCs)via small molecule compounds to provide safe and effective donor cells for treatment of neurodegenerative diseases.Methods:Based on the method established by PEI Gang's research group to directly reprogram human fibroblasts into neurons,the induction medium and maturation medium was optimized by replacing the coating solution,mitigating oxidative stress injury,adding neurogenic protective factors,adjusting the concentration of trichothecenes,performing small-molecule removal experiments,and carrying out immunofluorescence and Western blotting on cells at different stages of induction to validate the effect of induction.Results:When the original protocol was used for induction,the cell survival rate was(34.24±2.77)%.After replacing the coating solution gelatin with matrigel,the cell survival rate increased to(45.41±4.27)%;after adding melatonin,the cell survival rate increased to(67.95±5.61)%and(23.43±1.42)%were transformed into neural-like cells;after adding the small molecule P7C3-A20,the cell survival rate was further increased to(76.27±1.41)%,and(39.72±4.75)%of the cells were transformed into neural-like cells.When the concentration of trichothecene was increased to 30 μmol/L,the proportion of neural-like cells reached(55.79±1.90)%;after the removal of SP600125,(86.96±2.15)%of the cells survived,and the rate of neural-like cell production increased to(63.43±1.60)%.With the optimized protocol,REF could be successfully induced into ciNC through the neural precursor cell stage,in which the neural precursor cells were able to highly express the neural precursor cell markers SRY-related HMG-box gene 2(Sox2)and paired box 6(Pax6)as well as neuron-specific marker tubulin 1(Tuj1),while the expression of fiber-associated protein vimentin was reduced.After two weeks of induction of neural precursor cells in a maturation medium,most cells displayed neuronal-like cell morphology.The induced ciNCs were able to highly express the mature neuronal surface markers Tuj1 and microtubule-associated protein 2(MAP2),while the expression of vimentin was reduced.Conclusion:The small molecule combinations optimized in this study can reprogram REF to ciNCs under normoxic conditions.
9.In vitro susceptibility of commonly used antibiotics on community-acquired uncomplicated urinary tract infection pathogens in Beijing
Chunxia YANG ; Shan CHEN ; Yong YANG ; Yingmei LIU ; Hui WANG ; Zhanwei WANG ; Qiwen YANG ; Binbin LI ; Fang LI ; Shanshan WANG ; Chunlei WANG ; Jiuxin QU ; Zhenjia LIU ; Ludong QIAO ; Bin CAO
Chinese Journal of Urology 2012;33(2):132-137
Objective To investigate the distribution and susceptibility patterns of common uropathogens causing community-acquired urinary tract infection (UTI) in Beijing.MethodsA total of 300non-duplicate isolates were randomly collected from 3 hospitals in Beijing between Jan,1 2010 and Mar,312011.Minimal inhibitory concentrations (MICs) were determined by the broth microdilution methods,which were performed and interpreted according to the guidelines established by the Clinical and Laboratory Standards Institute (CLSI).A panel of 8 antimicrobial agents were tested:amikacin,cefaclor,cefepime,cefoperazone/sulbactam,ciprofloxacin,levofloxacin,gentamicin and nitrofurantoin. Fosfomycin trometamol MICs were determined by the agar-dilution method in cation-adjusted MH agar supplemented with glucose 6-phosphate at a concentration of 25 mg/L as detailed in the guidelines issued by 2010 CLSI. All the Escherichia coli,Klebsiella pneumoniae and Proteus mirabilis strains were screened and confirmed by double-disk synergy test for extended-spectrum β-lactamase (ESBLs).Results Among the organisms cultured,E.coli wasthepredominantpathogen(65.0% ), followedby Enterococcus(11.7% ),Staphylococcus( 6.3% ), Klebsiella pneumoniae( 5. 3% ), Proteus mirabilis( 4. 7% ), and Pseudomonas aeruginosa (3.0%).Lower susceptibility rates to ciprofloxacin and levofloxacin (31.4% -47.4% ) were observed among all the stains.Amikacin,cefoperazone/sulbactam,nitrofurantoin and fosfomycin trometamol were the most active drugs (92.1%,92.1%,88.4% and 87.9% susceptible strains,respectively) among the Gram-negative strains.Isolates of Staphylococcus were highly sensitive to amikacin ( 100.0% ),cefoperazone/sulbactam (94.7%),nitrofurantoin ( 100.0% ).Higher susceptibility rates to nitrofurantoin (91.4%) and fosfomycin trometamol (90.0%) were observed in Enterococcus.ESBLs-producing strains accounted for 52.3% (102/195) in E.coli,43.8% (7/16) in K.pneumoniae and 14.3%(2/14) in P.mirabilis,respectively.ConclusionsResistance is most common to ciprofloxacin and levofloxacin of all the stains.Currently,the most appropriate agents for the empirical management of uncomplicated UTI seems to be amikacin,cefoperazone/sulbactam,nitrofurantoin and fosfomycin trometamol.
10.Incremental diagnostic value of neck vessel wall imaging technique with T1?weighted three?dimensional variable?flip?angle turbo spin?echo before revascularization in patients with carotid atherosclerotic disease
Zhenjia WANG ; Zhaoyang FAN ; Wen LIU ; Mi LU ; Tiejin ZHENG ; Lei KOU ; Shuo WANG ; Wei YU
Chinese Journal of Radiology 2019;53(8):691-697
Objective To determine the feasibility of neck vessel wall imaging technology with three?dimensional variable?flip?angle turbo spin?echo (3D T1w?SPACE) for the detection of carotid atherosclerotic disease before revascularization. Methods Thirty?one patients who underwent carotid endarterectomy (CEA) and fifty?three patients who underwent carotid stenting (CAS) were enrolled prospectively. Neck vessel wall imaging examination were performed in all patients whilecarotid artery DSA were performed in all CAS patients. Quantitative measurements including stenosis, lesion length, and the presence or absence of plaque ulceration obtained with 3D T1w?SPACE and DSA were independently determined. And images of the 3D T1w?SPACE were compared with corresponding histology to identify major plaque components including intraplaque hemorrhage (IPH), lipid rich necrotic core (LRNC), and calcification (CA). The consistency rate, sensitivity, specificity, positive predictive value and negative predictive value were used to assess diagnostic value. Bland?Altman plots, intraclass correlation coefficient (ICC), and Cohen Kappa were determined. Results DSA was served as the reference standard. There was an excellent correlation between 3D T1w?SPACE and DSA images in measuring stenosis (r=0.984, P<0.01) and luminal stenosis [ICC=0.98 (95% confidence interval: 0.96-0.99)]. Bland?Altman plots showed that the two examinations were in good consistency in evaluating the extent of stenosis. Sensitivity (89.5%) and specificity (95.1%) was high in 3D T1w?SPACE images compared to DSA for the detection of ulcers. The consistency rate between 3D T1w?SPACE images and histological results for IPH, LRNC and CA detection were 85.7%, 82.1% and 92.9%, respectively. Sensitivity and specificity were 90.0% and 75.0% for IPH;83.3% and 80.0% for LRNC; 91.3% and 100.0% for CA respectively. However, lesion length measurements by using 3D T1w?SPACE were longer than those measured by using DSA (P<0.01).Conclusion Neck vessel wall imaging technology with 3D T1w?SPACE is a noninvasive and accurate technique for the diagnosis of carotid artery atherosclerotic disease before revascularization.