ABSTRACT
:To explore the value of quantitative perfusion histogram parameters of dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI） in pathological classification of uterine leiomyoma and its correlation with Ki-67 protein expression. Thirty five patients with uterine leiomyoma confirmed by operation and pathology at Shaoxing People's Hospital from October 2015 to September 2017 were analyzed retrospectively，including 15 cases of ordinary type，8 cases of cellular type and 12 cases of degenerative type. All patients were examined by pelvic DCE-MRI before operation，and the histogram parameters （median，mean，skewness，kurtosis，energy，entropy） of various quantitative perfusion parameters，including volume transport constant （K），rate constant （K），extravascular extracellular space distribute volume per unit tissue volume （V），blood plasma volume per unit volume of tissue （V） were calculated，and the efficacy of different parameters in pathological classification of uterine leiomyoma was evaluated by ROC curve. The expression of Ki-67 protein in uterine leiomyoma was detected by immunohistochemical method，and the correlation between histogram parameters and Ki-67 protein expression was analyzed by Pearson and Spearman correlation analysis. The median and mean values of K，K，V and V in the cellular group were higher than those in the degenerative group and the ordinary group（<0.05 or <0.01），while the skewness of V，the skewness and kurtosis of K in the cellular group were lower than those in the ordinary group （all <0.05）. The entropy of K in the cellular group was higher than that in the degenerative group and the ordinary group （all < 0.05）. The entropy of V in the cellular group was higher than that in the ordinary group （<0.01）. The median，mean，skewness of K，median and mean of K，median and mean of V，median，mean，energy and entropy of V were correlated with Ki-67 expression（all <0.05）. The results of ROC curve analysis showed that the median threshold of K was 0.994/min，the sensitivity and specificity for the diagnosis of cellular uterine leiomyoma were 100.0% and 77.8% respectively，and the area under the ROC curve was 0.949. When the mean threshold of K was 1.170/min，the sensitivity and specificity for diagnosing cellular uterine leiomyoma were 100.0% and 77.8% respectively，and the area under the ROC curve was 0.958. The area under the ROC curve of K （entropy），K （median，mean），V （median，mean，entropy） in the diagnosis of cellular uterine leiomyoma were 0.755-0.907. :DCE-MRI quantitative perfusion histogram parameters have high diagnostic value in differentiating pathological types of uterine leiomyoma，especially for cellular uterine leiomyoma.
Subject(s)
Humans , Contrast Media , Leiomyoma/diagnostic imaging , Magnetic Resonance Imaging , Perfusion , Retrospective StudiesABSTRACT
Objective ToanalyzethevalueoftheDCE-MRIparametersofReferenceRegionandExtendedToftsmodleinthedifferential diagnosisofhyper-cellularuterineleiomyoma.Methods 59patientswithuterineleiomyomaconfirmedbysurgeryandpathologywere enrolledinthestudyfromSeptember2015toSeptember2016,including28casesofclassicalleiomyoma,12casesofcellularleiomyoma and19casesofdegenerativeleiomyoma.AllpatientsunderwentDCE-MRIbeforesurgery.Thequantitativeperfusionparameters (transferconstant(Ktrans),extravascularextracellularspacevolumeratio(Ve),effluxrateconstant(Kep),andbloodplasmavolume ratio(Vp)weremeasuredviaReferenceRegionmodel(RR model)andExtendedToftsmodel(ET model)respectively.ROCcurve wasusedtoevaluatetheefficiencyofthequantitativeperfusionparametersindifferentialdiagnosisofhyper-cellularuterineleiomyoma. Pearsoncorrelationanalysiswasalsoappliedtoobservethecorrelationsamongallequivalentparameters.Results KtransandKepinRR modelandKtrans,Kep,VeandVpinET modelshowedstatisticalsignificancesamongthreetypesofuterineleiomyoma (P＜0.05), meanwhile,theAUCsofKtrans,KepandVpderivedfrom RR modelandKtrans,Kep,VeandVpcalculatedbyET modelindiagnosisof cellularuterineleiomyomawere0.835,0.752,0.706,0.956,0.871,0.656and0.754.TheKtransintheRR modelwascorrelatedwith KtransintheET model(r＝0.600,P＜0.001),KepintheET modelwaspositivecorrelatedwithKepandVpinRR model(r＝0.275, P＝0.035;r＝0.376,P＝0.003).Conclusion Thevalueof Ktrans ,Kep and Vp in RR and Ktrans ,Kep ,Ve and Vp in ET modelcan be useful inthedifferentiationofhyper-cellularleiomyoma,especiallythevaluesofKtransandKepinET modelhavehigherdiagnosticefficacy thanthoseinRR model.
ABSTRACT
<p><b>OBJECTIVE</b>To assess the application of the dynamic-contrast enhanced magnetic resonance imaging(DCE-MRI)pharmacokinetics models in differential diagnosis of cellular uterine leiomyoma.</p><p><b>METHODS</b>Sixty four patients with uterine leiomyoma confirmed by surgery and pathology were enrolled in the study between September 2015 and September 2016, including 30 cases of classical leiomyoma, 13 cases of cellular leiomyoma and 21 cases of degenerative leiomyoma. All patients underwent DCE-MRI before surgery. Reference region (RR) model, extended tofts (ET) model and exchange (EC) model were used to quantitatively analyze DCE-MRI data, and their differences among different pathological types of uterine leiomyoma were observed. Receiver operating characteristic (ROC) curve was used to evaluate the efficiency of the quantitative perfusion parameters in differential diagnosis of cellular uterine leiomyoma.</p><p><b>RESULTS</b>The values of K(transfer constant), K(efflux rate constant) in RR model, K, K, V(blood plasma volume ratio) in ET model and V(plasma volume ratio), F(plasma flow)in EC model of cellular uterine leiomyoma were higher than those of classical type(<0.05 or<0.01). The values of K, Kin RR model,K,K, V,Vin ET model and V,V,Fin EC model of cellular uterine leiomyoma were higher than those of degenerative uterine leiomyoma(<0.05 or<0.01). There were no significant differences in other quantitative perfusion parameters among three types of uterine leiomyoma (all>0.05). ROC curves revealed that the Kof the ET model was more effective in diagnosing cellular uterine leiomyoma, the area under the curve (AUC) was 0.929, and the sensitivity and specificity were 92.3% and 83.7%, respectively; meanwhile, the AUCs of Fof the EC model, Kof the RR model and Kof the ET model in diagnosis of cellular uterine leiomyoma were 0.867, 0.849 and 0.837, the sensitivities were 91.7%, 84.6% and 92.3%, and the specificities were 78.0%, 76.0% and 73.5%, respectively.</p><p><b>CONCLUSIONS</b>Three pharmacokinetics models can be used in the differentiation of cellular uterine leiomyoma from other types of uterine leiomyoma. Kof the ET model has higher sensitivity and specificity in differential diagnosis of cellular uterine leiomyoma.</p>
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Aim To evaluate the vasorelaxant effect of two new chemical entities, J35242 and J35243, on iso-lated rat thoracic aorta rings as Rho-kinase inhibitors, and further to explore the underlying mechanisms of these two compounds. Methods Isolated rat thoracic aorta rings pre-contracted by KCl or norepinephrine ( NE) were used to evaluate the vasodilatory effect of J35242 and J35243 . Through the interventions of sev-eral tool drugs, the mechanisms of compounds concern-ing endothelium, K+ channels and Ca2+ were studied. Results J35242 and J35243 showed potent relaxant effect on both KCl and NE pre-contracted vessels, and exhibited partial endothelium dependency. L-NAME and Methylene Blue( MB) could influence the relaxant effect of these compounds. Meanwhile, the compounds could inhibit intracellular Ca2+ release and extracellu-lar Ca2+ influx, which indicated that the compounds might block the calcium channels to relax the vessels. In addition, the two compounds probably did not dilate the aorta rings through opening potassium channels. Conclusions J35242 and J35243 have vasorelaxant effects on vessels in vitro and the potency of J35242 is stronger than that of J35243 . The underlying mecha-nisms might be endothelium-dependent. Also the com-pounds might block Ca2+ channels, lowering intracel-lular Ca2+ concentration to relax the vessels.
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Aim To investigate the in vitro vasorelax-ant effect of DL0805-0, a Rho kinase inhibitor, on iso-lated rat thoracic aorta and explore its underlying mechanism. Methods Tension was measured to eval-uate the vasorelaxant effect of DL0805-0 on rat endo-thelium-intact and endothelium-denuded thoracic aorta rings. Rho kinase inhibitor fasudil, nitric oxide syn-thase inhibitor Nω-nitro-L-arginine methyl ester ( L-NAME), guanylate cyclase inhibitor methylene blue, cyclooxygenase inhibitor indomethacin, calcium-activa-ted potassium channel blocker tetraethyl ammonium ( TEA ) , ATP-sensitive potassium channel blocker glibenclamide and voltage-dependent potassium chan-nel blocker 4-aminopyridine ( 4-AP ) were used to il-lustrate the mechanisms of vasorelaxant effect of DL0805-0 . Results DL0805-0 exerted vasorelaxation in a dose-dependent manner in KCl (60 mmol·L-1 ) or NE ( 0. 1 μmol · L-1 ) -induced contraction. DL0805-0-induced vasorelaxation was significantly re-duced by L-NAME. However, methylene blue and in-domethacin did not significantly affect vasorelaxation of DL0805-0. In endothelium-denuded rings, TEA re-markably attenuated the vasorelaxant effect of DL0805-0 , while glibenclamide and 4-AP did not affect vasore laxation of DL0805-0 significantly. DL0805-0 also re-duced NE-induced transient contraction and inhibited contraction induced by increasing extracellular calci-um. Conclusion These results suggest that DL0805-0 induces vasorelaxation through an endothelium-depend-ent pathway. The opening of calcium-activated K+channels and blocking of Ca2+ channels in vascular smooth muscle cells may be one of the mechanisms of DL0805-0-induced vasorelaxation.
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Aim ToestablishthemethodofHighper-formance liquid chromatography ( HPLC ) for detecting plasma concentration of indazole compound DL0805-1 , a Rho kinase inhibitor, and to investigate its pharma-cokinetics in rats with intravenous injection. Methods ThedetectingsystemwasAgilent1200-DAD;chro-matographic column was Agilent TC-C18 ( 4. 6 mm × 250 mm, 5 μm); the ultraviolet detection wavelength was 235 nm; the column temperature was 35 ℃; the flow rate was 1 ml·min-1;the mobile phase was ace-tonitrile-0. 05% H3 PO4 gradient elute. Rat blood sam-ples were collected at different intervals after intrave-nous injection of a single dose of DL0805-1 , and the concentration of DL0805-1 in rat plasma were deter-mined by HPLC method for estimating pharmacokinetic parameters.Results Afterintravenousinjectionof DL0805-1 in rats, prototype and its metabolite were detected in plasma. T1/2 of DL0805-1=(2. 34 ± 1. 42) h, Cmax=(3. 51 ± 0. 44) mg·L-1, T1/2 of metabolite of DL0805-1 = ( 1. 27 ± 0. 45 ) h, Cmax = ( 3. 55 ± 0.22)mg·L-1.Conclusion Theseresultssuggest that DL0805-1 may be metabolized into another sub-stance in vivo and play biological functions. The meth-od is sensitive, simple, and accurate, and can be used for the determination of DL0805-1 in rat plasma and pharmacokinetic studies.
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Salvianolic acid A is a water-soluble component from Danshen, which is frequently used in traditional Chinese medicine. High performance liquid chromatography was often used to analyze content of salvianolic acid A. The yield of salvianolic acid A increased by the technological improvement of extraction and separation. Salvianolic acid A possessed multiple pharmacological activities, including antioxidants, myocardial ischemic protection, antithrombatic, neuroprotection, anti fibrosis, prevention of diabetes and complications. Recently, preliminary pharmacokinetics characteristics of salvianolic acid A were clarified. Based on the research literature and study work from author's laboratory, this review will focus on recent developments concerning the chemistry, pharmacology and pharmacokinetic of salvianolic acid A, and prospect further research.