1.Injectable and biodegradable thermosensitive PLGA-PEG-PLGA copolymer-based hyd rogels for a controlled in vitro drug delivery
Zhikui CHEN ; Liwu LIN ; Yahfang LIN ; Ensheng XUE ; Liyun YU
Chinese Journal of Tissue Engineering Research 2008;12(49):9792-9796
BACKGROUND:Ricin possesses strong cytotoxicity but lacks of specificity.Severe adverse reactions can be caused if ricin is systemically administered.Interstitial chemotherapy with ricin coated by a sustained-release carrier can enhance local therapeutic effects of tumor,avoiding systemic-toxic occurrence.OBJECTIVE:To prepare injectable and biodegradable thermosensitive poly(D,L-lactide-co-glycolide)(PLGA)-polyethylene glycol(PEG)-PLGA copolymer-based hydrogels and to observe the in vitro drug delivery of the PLGA-PEO-PLGA copolymer hydrogel as a sustained-release carrier of ricin.DESIGN,TIME AND SETTING:A controlled observation was performed at the Center for Medical Bioengineering.Fujian Medical University between August and December 2007.MATERlALS:Ricin with a purity of 95%was purified by Fuiian Institute of Ultrasonic Medicine.DL-lactide and L-glycolide were provided by Glycolide Lactide Co.,Ltd..China.METHODS:PLGA-PEG-PLGA-copolymer was synthesized by ring-opening polymerization.MAIN OUTCOME MEASURES:Phase transition temperature was determined by test tube turnover.relativemolecular mass by high-performance gel permeation chromatography,the proportion of block copolymer by nuclear magnetic resonance spectrometry.the in vitro drug delivery of ricin coated by PLGA-PEG-PLGA copolymcr hydrogelby enzyme linked immunosorbent assay.the structural integrity of released ricin by high-performance liquid chromatography,the cytotoxicity of released ricin by methyl thiazolyl tetrazolium assay.RESULTS:The synthesized copolymer PLGA-PEG-PLGA exhibited reverse.thermosensitivity.The phase transition temperature of the copolymer was 26℃at 230 g/L.The weight-average molecular weight and number-average molecular weight of this copolymer was 8 027 and 6 643,respectively,and the multiple-dispersion toefficient was 1.17.The block ratio for PEG and PLGA was 3:2.Drug-loaded PLGA-PEG-PLGA hydrogel could release ricin in vitro for a total of 18 successive days and simultaneously well maintain cytotoxicity and the structural stability of ricin.CONCLUSION:PLGA-PEG-PLGA copolymer is an ideal carrier for sustained delivery of ricin
2.Ultrasound-guided percutaneous ethanol injection in the treatment of hepatocellular carcinoma combined with portal vein tumor thrombosis
Xiujuan ZHANG ; Liwu LIN ; Ensheng XUE ; Zhikui CHEN ; Liyun YU
Chinese Journal of Interventional Imaging and Therapy 2011;08(5):367-370
ObjectiveTo assess the clinical value of ultrasound-guided percutaneous ethanol injection (PEI) in the treatment of hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT).MethodsNinety HCC patients with different type PVTT underwent ultrasound-guided PEI once or twice a week.The follow-up lasted 12 to 60 months,and the 1-,2-,3-,4- and 5-year survival rates were calculated.ResultsThe median survival time of HCC combined with PVTT patients treated with PEI was 12 months,and the 1-,2-,3-,4- and 5-year survival rates was 52.22%,23.33%,15.56%,12.22% and 10.00%,respectively.The survival rate correlated significantly to the type of PVTT.The lower the type of PVTT was,the longer the patients lived.ConclusionUltrasound-guided PEI is a safe and effective method for the treatment of HCC combined with PVTT,and can prolong the survival time of HCC patients with low type PVTT.
3.Superficial property and drug release in vitro of poly lacticoglycolic acid-loaded cytotoxin nanoparticles
Zhikui CHEN ; Liwu LIN ; Zhiqiang ZHANG ; Ensheng XUE ; Yan WANG ; Liyun YU
Chinese Journal of Tissue Engineering Research 2009;13(3):575-578
BACKGROUND: Cytotoxin (CTX) is characterized by strong cytotoxic activity and absent specificity, of which systemic administration can cause severe toxicity and side effects; however, interstitial chemotherapy may improve therapeutic effect of local tumor and relieve general toxicity using sustained release vector. OBJECTIVE: To prepare cytotoxin/poly lacticoglycolic acid (CTX-PLGA) nanoparticles, and to study the general property and drug release in vitro. DESIGN, TIME AND SETTING: Observational study was performed at Medical Bicangineedng Center of Fujian Medical University between December 2007 and May 2008. MATERIALS: Poly lacticoglycolic acid (PLGA) and polyvinyl alcohol were purchased from Chengdu, and CTX was purchased from Guangdong. METHODS: CTX was purified by molecular sieve, ion exchange separation, and reversed-phase high performance liquid chromatography; cytotoxic activity was measured by MTT method; nanoparticles were prepared by multiple emulsion-solvent evaporation technique. MAIN OUTCOME MEASURES: Superficial morphological characteristics were observed using scanning electron microscope, while diameter was measured using laser particle sizing analyzer in order to calculate encapsulation efficiency, drug loading, and release cycle in vitro. RESULTS: Purified CTX had apparent cytotoxic activity, and the IC<,50> values of HepG2 cells were respectively 1.43 and 1.12 mg/L at 12 and 24 hours. By using multiple emulsion-solvent evaporation technique, the nanoparticles were smooth and intact, diameter 2-8 μ m. The encapsulation efficiency was (74.10±9.92)%, and the drug loading was (0.72±0.09)%. In addition, drug accumulated release was 63.3% at day 21. The released CTX still had a great biologic activity. CONCLUSION: Multiple emulsion-solvent evaporation technique is surely prepared the CTX-PLGA nanoparticles, characterizing by high encapsulation efficiency, great drug release, and entire biologic activity.
4.Study of influential factors in evaluating tissue stiffness by virtual touch tissue quantification
Liyun XUE ; Jiexian WEN ; Qing LU ; Cuiju YAN ; Beijian HUANG ; Wenping WANG
Chinese Journal of Ultrasonography 2012;21(6):526-528
ObjectiveTo investigate the influence of different depths and mediums on tissue stiffness measurement by virtual touch tissue quantification technology.Methods Four kinds of in vitro porcine tissue were recruited,three (fat,muscle and liver) were assigned as medium group and three (kidney,liver and muscle) as sample group.The shear wave velocity (Vs) of the samples was measured under different mediums and at different depths (2 cm,3 cm,4 cm and 5 cm),respectively.ResultsAccording to the depth of measurement,two groups of Vs were defined with one group at the depth of 2 cm and 3 cm while the other at 4 cm and 5 cm.The difference of Vs between the two groups was of statistical significance and with the increase of the depth Vs values decreased.Even at the same depth,the differences of Vs under different mediums were statistically significant.ConclusionsDepths and mediums have great influence on evaluating elasticity measurements by virtual touch tissue quantification technology.
5.Parametric imaging for characterizing clear cell renal cell carcinoma with contrast-enhanced ultrasound
Cuiju YAN ; Beijian HUANG ; Lijuan MAO ; Liyun XUE ; Feng MAO ; Wenping WANG
Chinese Journal of Ultrasonography 2012;21(10):872-875
Objective To investigate the features of quantitative analysis and parametric imaging of contrast-enhanced ultrasound (CEUS) in renal clear cell carcinoma (ccRCC).Methods Ninety-seven pathologically confirmed ccRCCs underwent conventional ultrasound and CEUS.Both quantitative parameters and dynamic vascular pattern (DVP) reconstructure were analyzed with Sonoliver software.Four types of DVP curves were described with type Ⅰ (Unipolar +),type Ⅱ (Bipolar + /-),type Ⅲ (Bipolar -/+) and type Ⅳ (Unipolar-),while the DVP parametric images,similarly,were divided into four types,with type Ⅰ,Ⅱ,Ⅲ and Ⅳ,respectively.Results As for the parameter of CEUS,there were statistical differences in maximum intensity (IMAX),area under the curve (AUC) and mean transit time (mTT) (P <0.05) and no statistic differences in rise time (RT) and time to peak (TTP) between ccRccs and peripheral renal parenchyma.Concerning of DVP of ccRCCs,type Ⅰ,Ⅱ,Ⅲ and Ⅳ accounted for 58.8% (57/97),11.3% (11/97),10.3% (10/97) and 19.6% (19/97) respectively.As for each type in DVP parametric images,the percentages were 58.8% (57/97),11.3% (11/97),8.2% (8/97),21.7% (21/97),respectively.Conclusions Quantitative analysis and parametric imaging can depict different features of vascularity in ccRCCs and improve the diagnosis of the tumors.
6.Evaluation of liver fibrosis in a rat model by acoustic radiation force impulse elastography
Senhao LIN ; Hong DING ; Liyun XUE ; Lijuan MAO ; Feng MAO ; Hongguang ZHU ; Wenjiao ZENG ; Wenping WANG
Chinese Journal of Ultrasonography 2012;21(2):164-166
Objective To investigate the usefulness of acoustic radiation force impulse (ARFI) elastography for noninvasive evaluation of liver fibrosis in rats.Methods A total of 70 male Wistar rats were included in the group for dimethylnitrosamine (DMN)-induced liver injury,and 10 saline-injected rats were used as normal control.Hepatic injury was induced by a single intraperitoneal injection of DMN at a dose of 50 mg/kg of body weight.Several rats in the group with DNM injected and the normal control group were randomly selected and sacrificed at each of the following post-injection time:day 5,7,10,14,21,24,and 28.And their livers were taken for pathology analysis.All the rats underwent ARFI elastography before sacrificed in order to acquire a shear wave velocity (Vs) to represent liver stiffness.Correlation between Vs and the histological finding was analysed.ResultsAmong 58 successfully modeled rats,9,13,14 and 12 rats were found to be with S1,S2,S3 and S4 of liver fibrosis pathologically,respectively.And 10 rats were found to be with severe inflammatory activity without any fibrosis.Values of Vs increased with the stage of liver fibrosis ( P <0.05).There was a significant correlation between Vs and stage of liver fibrosis ( r =0.947,P =0.000).The areas under ROC curve for the diagnosis of fibrosis S≥S1,S≥S2,S≥S3 and S=S4 were 0.983,0.995,0.999 and 0.964,respectively;for the cutoff values of Vs were 1.59 m/s,2.13 m/s,2.33 m/s and 2.51 m/s,respectively,the sensitivity was 95.8%,92.3%,100% and 84.6%,and specificity was 100%,100%,96.9% and 95.6%,respectively.The values of Vs in the group with severe inflammatory activity were significantly higher than those in the control group ( P =0.000).ConclusionsARFI has a relatively high value in the evaluation of liver fibrfosis in rats,while severe inflammatory activity may affect its accuracy.
7.Value of contrast-enhanced ultrasound in diagnosis of renal epithelioid angiomyolipoma
Cuixian LI ; Beijian HUANG ; Qing LU ; Liyun XUE ; Lixia YAN ; Jiexian WEN ; Wenping WANG
Chinese Journal of Ultrasonography 2014;23(9):786-790
Objective To investigate the value of contrast-enhanced ultrasound (CEUS) in diagnosis of renal epithelioid angiomyolipoma (eAML).Methods The CEUS features of 18 patients with 18 histopathologically proved renal eAMLs were retrospective analyzed using both of qualitative and quantitative approachs.Tumor conventional ultrasound and CEUS features were observed.The Sonoliver software was applied to perform quantitative analysis,which provided five parameters,including the maximum intensity (IMAX),rise time (RT),time to peak (TTP),mean transit time (mTT) and area under the curve (AUC).Results All of 18 lesions were pathological proved as eAML,among them,heterocyst was observed in 7 lesions,1 lesion had dissemination inter-kidney and vessel invasion,necrosis or cystic degeneration was found in 3 eAMLs.On conventional ultrasound,eAML showed hypoecho,isoecho and hyperecho were 14(77.8%),3(16.7%) and 1 (5.6%) respectively.Blood flow could be detected in 16 (88.9%) lesions.On CEUS,the characters of slow-in,synchronous-in,slow centripetal enhancement and entire enhancement were observed in 10 (55.6%),8 (44.4%),8 (44.4%) and 12 (55.6%) lesions,respectively.Most of eAMLs showed homogeneous enhancement (15/18,83.3%) and hyper-or iso-enhancement (16/18,88.8 %) at peak time.The characters of fast-out,synchronous-out and slow out were observed in 8 (44.4%),2 (11.2%) and 8 (44.4%) cases,respectively.Pseudocapsule was detected in 5 (27.8%) lesions.The parameters of RT,TP and AUC for eAMLs were higher than that for renal cortex (P < 0.05),while the parameters of IMAX and mTT had no significant statistical difference between eAMLs and renal cortex(P >0.05).Conclusions Qualitative and quantitative analysis of CEUS reflect the blood perfusion of eAMLs in different aspect,which offer some useful informations for the diagnosis of eAMLs.
8.Value of ultrasonography in diagnosis and differential diagnosis of breast sclerosing adenosis
Ying HOU ; Liwu LIN ; Ensheng XUE ; Zhikui CHEN ; Liyan HUANG ; Liyun YU ; Yimi HE
Chinese Journal of Ultrasonography 2014;23(10):889-892
Objective To investigate the value of color Doppler ultrasonography in diagnosis and differential diagnosis of breast sclerosing adenosis (SA).Methods Preoperative sonography in 32 SA,99 invasive ductal carcinoma(IDC),51 ductal carcinoma in situ(DCIS) and 64 fibroadenoma(FA) confirmed by pathology were retrospectively analyzed.Results The average age of SA group was younger than IDC and DCIS groups',but older than FA group's (P <0.05).The focal maximum diameter of SA group was the smallest among all(P <0.05).All the SA sonograms showed solid hypoechoic lesions,with spiculate margin was less than IDC group and larger than DCIS and FA groups (P <0.05).Similar ultrasonic characteristics,such as irregular shape,unclear border,acoustic halos were seen in SA and DCIS groups (P >0.05),while IDC group showed the highest rate and FA group had the least(P <0.05).SA masses' uneven internal echo,calcification,posterior acoustic attenuation was higher than FA group(P <0.05),but less than IDC and DCIS groups(P >0.05).Meanwhile,A/T ratios(≥0.7) were higher than DCIS and FA groups,but less than IDC group(P >0.05).In addition,SA group had a similar detection rate of the internal blood flow with FA group(P >0.05),but less than the IDC and DCIS groups(P <0.05).Conelusions Ultrasonography has a significant clinical value in diagnosis and differential breast sclerosing adenosis.
9.Experimental study on contrast-enhanced ultrasound to evaluate testicular microvascular injury
Wenjin LIN ; Ensheng XUE ; Liyun YU ; Yusheng LI ; Shun CHEN ; Rongxi LIANG ; Wenrong LIN ; Liping HUANG
Chinese Journal of Ultrasonography 2015;(6):535-540
Objective To explore the way of contrast-enhanced ultrasound(CEUS)and quantitative analysis technology to assess testicular microvascular ischemia-reperfusion inj ury.Methods Twenty-four healthy adult rabbits were randomly divided into the control group and the microvascular mild,moderate, serve ischemic inj ury group (group Ⅰ,including group Ⅰ1 ,Ⅰ2 ,Ⅰ3 ).The spermatic cord of the control group were threaded but not ligated.The group Ⅰ1 ,Ⅰ2 ,Ⅰ3 were reperfused 2 h after 2 h,4 h,6 h complete testicular ischemia respectively.The ultrasound contrast angiographic parameters of each group were analyzed by the quantitative analysis techniques,including peak intensity(PI),time to peak(TP),slope,mean transmit time(MTT),DT/2 and area.The levels of plasma vWF,NO and ET-1 were tested after the CEUS. The pathological changes of the ipsilateral testicular were observed by the HE and immunohistochemical staining.Statistical analysis was performed by SPSS 13.0 software.Results Preoperativeiy,each parameter of the experimental group and the control group showed no statistical significance (P > 0.05 ). Postoperatively,the PI,slope,area of the group Ⅰ1 increased significantly,while the TP,MTT were prolonged(P <0.05).Contrast time-intensity curve was significantly higher peak and retrusion.The groupⅠ2's PI,slope,area increased further,DT/2 was significantly prolonged,but TP significantly reduced (P <0.05).The contrast curve significantly increased,forward and decreased slowly.The contrast curves of the group Ⅰ3 was approximate a straight line.The vWF,NO,ET-1 levels of each experimental group were significantly higher than those in control group (P <0.05),among them,the levels of group Ⅰ2 were the highest (P <0.05 ).With the aggravation of ischemia,the testicular capillaries expansion,erythrocyte sedimentation,leakage,infiltration of inflammatory cells,MMP-9 expression in vascular basement membrane gradually increased.Conclusions The CEUS and quantitative analysis techniques can effectively evaluate testicular microvascular inj ury.
10.Comparative study of ultrasound characteristics on microinvasive breast carcinoma,ductal carcinoma in situ and ;invasive ductal carcinoma
Xiaoshuang CHEN ; Weili WEI ; Zhikui CHEN ; Liwu LIN ; Ensheng XUE ; Liyun YU ; Yimi HE
Chinese Journal of Ultrasonography 2015;(8):688-691
Objective To investigate the ultrasound characteristics of microinvasive breast carcinoma (MBC),and to improve its detection rate.Methods Sixty-five MBC,85 breast ductal carcinoma in situ (DCIS)and 99 breast invasive ductal carcinoma(IDC)confirmed by pathology were divided into mass type and ductal type according to ultrasonic manifestaions,and the ultrasound characteristics were retrospectively analyzed.Results MBC showed 89.23%(58/65)mass type with 64 lesions and 10.77%(7/65)ductal type. DCIS showed 88.24% (75/85 )mass type with 78 lesions and 1 1 .76% (10/85 )ductal type.IDC group showed all mass type with 102 lesions.In MBC,most mass type lesions were solid and hypoechoic with a mean maximum diameter,which was larger than DCIS,but similar with IDC(P >0.05).More mass type lesions with irregular shape and calcification were found in MBC than in DCIS(P < 0.05 ),while similar with IDC(P >0.05).The detection rate of spiculate margin in mass type lesions of MBC was higher than DCIS(P <0.05),but lower than IDC(P <0.05).Less mass type lesions showed unclear border,high A/T ratio and hyperechoic halos in MBC than in IDC(P <0.05),but similar with DCIS(P >0.05).More ductal type lesions displayed indistinct duct wall in MBC than DCIS(P <0.05 ).Meanwhile,MBC had a higher detection rate of internal blood flow(grade 2-3)than DCIS.Conclusions There are more lesions with large diameter,irregular shape,short spiculate margin and calcification in MBC than DCIS.Compared with IDC, MBC lesions are atypical in spiculate margin,and less lesions show hyperechoic halos and high A/T ratio. To be familiar with ultrasound characteristics of MBC is significant for improving its ultrasound detection rate.