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.Animal experiment of the echo tracking technique in evaluating artery elasticity
Xuejun DUAN ; Liwu LIN ; Ensheng XUE ; Yimi HE ; Shangda GAO ; Liyun YU
Chinese Journal of Ultrasonography 2009;18(3):257-260
Objective To assess the value of echo tracking(ET) technique on atherosclerosis in the rabbit models, and to probe the pathological foundation of its indexes changes and the usefulness in evaluating arterial elasticity. Methods Thirty New Zealand rabbits were divided into 3 groups randomly: group A was the control group;group B,C were fed with high lipid feedstuffs for 8 weeks and 12 weeks, respectively. The ET examination of abdominal aorta was performed in group A and group B at the end of 8 weeks,it was performed in group A and group C at the end of 12 weeks. The parameters of elasticity were measured including pressure-strain elastic modulus (Ep), stiffness parameters(β), pulse wave velocity (PWVβ), augmentation index (AI), arterial compliance (AC), etc. Two dimensional ultrasound and pathological examination of abdominal aorta were performed at the same time. Results No obvious plaque and arterial wall thickness were seen in the abdominal aorta. Ep,β,PWVβ of group C were higher than that of group A and B, while AC of group C was lower than that of group A and B, and the difference had statistical significance (P<0.05). AI had no significant difference in all groups (P>0.05). Pathological examinations indicated that foam cell formation was seen in the abdominal aorta intima, the elastic fiber layer and smooth muscle layer were kept well in B group. Lots of cholesterol crystal formation was seen in the abdominal aorta intima and the two layer were obvious destroyed in group C. Conclusions ET can detect the atherosclerosis earlier than two-dimensional ultrasound. ET can detect the elasticity changes only when the elastic fiber layer and smooth muscle layer were destroyed . So it can be concluded that the destroy of elastic fiber layer and smooth muscle layer may be the pathological foundation of ET elasticity parameters changes.
5.Comparative analysis on ultrasonic and mammographic characteristics of breast chronic inlfammation
Min, LIN ; Weili, WEI ; Zhikui, CHEN ; Liwu, LIN ; Ensheng, XUE ; Yimi, HE ; Liyun, YU
Chinese Journal of Medical Ultrasound (Electronic Edition) 2014;(3):50-53
Objective To compare the ultrasonic and mammographic appearances of breast chronic inflammation (BCI). Methods The ultrasonic and mammographic features of 20 pathologically conifrmed BCI cases were analyzed retrospectively. All cases were of single lesion. Fisher deifnite probability method was used to compare the differences between ultrasonic and mammographic appearances as well as the diagnostic coincidence rate. Results Under ultrasonography, the mean longitudinal diameter/transverse diameter (L/T) ratio of 20 lessions was calcultated as 0.47±0.15, 17 lesions were of irregular shape, unclear boundary and inhomogeneous hypoecho, 13 lesions were of posterior echo enhancement, the blood lfow of 10 lesions belonged to 0-Ⅰ, and the other 10 belonged toⅡ-Ⅲ. The lesion shape, boundary and homogeneity detected by mammography were coincident to those by ultrasonography (P=1.00, 1.00, 0.61, respectively). In 5 lesions, dotted high-echoes were detected by ultrasonography, however no calciifcation was found by mammography. Meanwhile, 1 lesion with sporadic calciifcation detected by mammography was missed by ultrasonography. Ultrasonography detected 5 cases with axillary lymphadenopathy, in which only 1 case was found by mammography. The diagnostic coincidence rate of ultrasonography was 40%(8/20), which was obviously higher than 6% (1/16) by mammography (P=0.03). Conclusion BCI possesses certain ultrasonographic characteristics, and ultrasonography combined with mammography will be helpful for the differential diagnosis of malignant and benign diseases.
6.Experimental study on ultrasound-guided injection of paclitaxel-loaded thermosensitive hydrogel in treatment of breast cancer in rats
Jiajia YANG ; Zhikui CHEN ; Liwu LIN ; Ensheng XUE ; Yimi HE ; Liyun YU
Chinese Journal of Ultrasonography 2010;19(8):711-714
Objective To prepare a sustained-delivery of paclitaxel-loaded thermosensitive hydrogel for the treatment of breast cancer by ultrasound-guided intratumoral injection,and probe the antitumor effect and mechanism of the new method. Methods Paclitaxel-loaded thermosensitive hydrogel was prepared. A total of 40 rats bearing subcutaneous breast tumor were randomized into 4 groups. Each group of rats were administered ultrasound-guided intratumoral injection of different agents as follows: salin, thermosensitive hydrogel, paclitaxel injection and paclitaxel-loaded thermosensitive hydrogel. The tumor nodules were scanned by high frequence ultrasound. The rats were sacrificed on the 14th day,and then the tumors were stripped to calculate the growth inhibitory rate. Histological examinations were undergone and RT-PCR was performed for the detection of bcl-2 and bax expression. Results Greater decrease in average tumor weight was found in paclitaxel-gel group [(16. 04 ± 2. 82)g], compared with that in paclitaxel group [(27.45 ±5.13)g, P <0. 05],and tumor growth inhibitory rate in the group was 62.77 %. In this group, blood flow signals reduction was detected on ultrasound and extensive necrosis was found in histological examination. In addition,down-regulation in bcl-2 mRNA expression and up-regulation in bax were found. Conclusions Ultrasound-guided percutaneous intratumoral injection of paclitaxel-loaded thermosensitive hydrogel may provide an effective method for breast tumor ablation therapy. The mechanism may be related to the inhibition of proliferation and induction of apoptosis.
7.Influence of aoustic contrast agent with diagnostic ultrasound on rabbits' spermatogenic cell
Weiqin HUANG ; Ensheng XUE ; Liwu LIN ; Liyun YU ; Ying LIN ; Rongxi LIANG
Chinese Journal of Ultrasonography 2010;19(6):527-531
Objective To study the impact of ultrasound contrast agent with different doses or imaging modes on rabbit spermatogenic cell in the diagnosis of radiation dose.Methods Thirty-three New Zealand white rabbits were randomly divided into 3 groups.In group Ⅰ ,three minutes gray scale ultrasound radiation was performed for three rabbits.In group Ⅱ, SonoVue was bolus injected from ear vein for eighteen rabbits.The rabbits in this group were divided into 6 sub-group according to different doses and different sampling times, the single injections of SonoVue with dosage of 0.1 ml/kg(A1, A2) or 1 ml/kg (C1 ,C2) and repeated injections with dosage of 0.1 ml/kg interval 15 min (B1 ,B2) were taken.In group Ⅲ ,twelve rabbits were bolus injected with SonoVue and then the agent bubbles were blasted when the SonoVue suffused the whole testis.The rabbits in this group were divided into 4 sub-groups according to different doses and different sampling times, and the dosages of SonoVue were 0.1 ml/kg(D1, D2) and 1 ml/kg(E1,E2).Testis were drew immediately or 24 hours later for the observation under light microscope and transmission electron microscope.Results Apoptotic cells in group Ⅲ were more than those in group Ⅰ and Ⅱ ( P <0.05) ,while no significant difference of the total number of apoptotic cells between group Ⅰ and Ⅱ ( P >0.05).The appearances of focal ultra-structural damage were observed by transmission electron microscope in group C1, such as intercellular space widening and mitochondria swelling, and no distinct damage were observed in the other groups.The appearances of intercellular space widening, mitochondria swelling and cellular edema were observed by transmission electron microscope in group Ⅲ, and spotty necrosisetc was also observed in group D1 and E1.Conclusions Large dose of contrast agent could cause germ cells slight instantaneous effects, while conventional dose had no effect.Contrast agent blasting may cause germ cells unrecoverable damage.
8.Prediction of testicular viability after unilateral testicular torsion by ultrasonography
Lijun XIE ; Ensheng XUE ; Liwu LIN ; Shun CHEN ; Rongxi LIANG ; Liyun YU ; Yu ZHANG
Chinese Journal of Ultrasonography 2010;19(5):419-422
Objective To investigate the value of predicting testicular viability following unilateral testicular torsion by color-Doppler ultrasound (CDU). Methods The clinical manifestations, intraoperative findings and scrotol CDU appearances before and after operation of 42 cases with testicular torsion were compared. According to a bleeding test intraoperatively, testicular viability was divided into A-D level. Testis of level A-C would be saved .while the level D removed. Testicular viability assessed by follow-up CDU was then classed into Ⅰ-Ⅲ level. In Ⅰ-Ⅱ level, the salvaged testis were recovery ultimatelybut atrophy in level Ⅲ. Results Seventeen cases of the 42 underwent orchidopexy and the remaining 25 cases underwent orchidectomy. As followed up, however, testis in only 7 cases were recovered, including 2 cases in level A,3 cases in level B and 2 cases in level C. respectively. The preoperative scrotal CDU appearances of the recovered testis were mainly as follows: ① Homogeneous parenchyma with decreased or disappeared blood perfusion. ②Sheet or radial hypoechoic in the local testis but with preserved blood perfusion in most area else. Testis in the remaining 10 patients, including 8 cases in level C and 2 cases in level D, respectively, were atrophy finally. And large radial hypoechoic or diffuse inhomogeneous echo with none or a small amount of blood supply on the edge parenchyma were found during their preoperative CDU (similar CDU performance was present in the orchidectomy group. The CDU appearances of contralateral testes both in orchidopexy and orchidectomy group were not obviously abnormal during follow-up. Conclusions The scrotal CDU examination is competent to predict testicular viability after detorsion. In addition, timely operation would be a key to CDU evaluation.
9.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.
10.Application value of color Doppler ultrasound in metaplastic breast carcinoma
Xiaoshuang CHEN ; Xiujuan ZHANG ; Liwu LIN ; Ensheng XUE ; Liyun YU ; Yimi HE
Chinese Journal of Ultrasonography 2016;25(3):223-227
Objective To investigate the value of color Doppler ultrasonography in metaplastic breast carcinoma(MBC).Methods The ultrasonic characteristics of 23 MBC and 1 1 8 invasive ductal carcinoma (IDC) confirmed by pathology were analyzed retrospectively.And the ultrasound characteristics of different types of MBC was analyzed according to pathology.Results Mean maximum diameter of(3.73±1 .74)cm in MBC was larger than that in IDC[(2.57 ± 1 .19)cm,P = 0.005].Most MBC lesions showed larger diameter(>3 cm),clear border(56.5%),irregular shape(65.2%),lack of hyperechoic halos(65.2%), posterior enhancement(60.9%),no calcification(60.9%) and grade 2 - 3 of blood flow (56.5%).The detection rate of unclear border,unsmooth edge and hyperechoic halos of MBC was lower than those of IDC (P <0.05).But MBC had a higher detection rate in the masses with larger than 3 cm in diameter and posterior enhancement than IDC.Five (45.5%) lesions of 1 1 squamous cell carcinoma showed cystic constituent.The mean maximum diameter of 5 MBC with mecenchymal tissue lesions was larger than spindle cell carcinoma,but smaller than squamous cell carcinoma.And 4 lesions of the 5 MBC with mecenchymal tissue showed calcification,which occupied the highest proportion among different pathological types of MBC. The ultrasonic coincidence rate for MBC was 86.96%.Conclusions The ultrasonic appearances of MBC have a certain characteristics,and different pathological types of MBC also have corresponding characteristics.It shows important value of ultrasonography in preoperative diagnosis for MBC.