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

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.

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.

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.

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.

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.

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.

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.

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.

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.