Efficacy, Efficiency, and Safety of Magnetic Resonance-Guided High-Intensity Focused Ultrasound for Ablation of Uterine Fibroids: Comparison with Ultrasound-Guided Method

OBJECTIVE: The purpose of this study was to compare efficacy, sonication energy efficiency, treatment time and safety of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) and those of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for ablation of uterine fibroids. MATERIALS AND METHODS: This study included 43 patients with 44 symptomatic uterine fibroids treated with MRgHIFU and 51 patients with 68 symptomatic uterine fibroids treated with USgHIFU. After therapy, contrast-enhanced MRI was conducted and complete ablation was defined as 100% non-perfused volume (NPV) of fibroids. Patients with completely ablated fibroids were selected for the comparison of the treatment data and sonication parameters between MRgHIFU and USgHIFU treated groups. RESULTS: Thirteen completely ablated fibroids in 10 patients (23.3%, 10/43) were achieved with MRgHIFU and 28 completely ablated fibroids in 22 patients (43.1%, 22/51) were achieved with USgHIFU. In completely ablated fibroids, the energy-efficiency factor (EEF) was 5.1 ± 3.0 J/mm3 and 4.7 ± 2.5 J/mm3 in the MRgHIFU and USgHIFU, respectively (p = 0.165). There was a negative linear correlation between EEF and the NPV of fibroids for MRgHIFU (p = 0.016) and USgHIFU (p = 0.001). The mean treatment time was 174.5 ± 42.2 minutes and 114.4 ± 39.2 minutes in the MRgHIFU and USgHIFU procedures, respectively (p = 0.021). There were no severe adverse events and major complications after treatment. CONCLUSION: MRgHIFU and USgHIFU are safe and effective with the equivalent energy efficiency for complete ablation of fibroids. USgHIFU has shorter treatment time than MRgHIFU.

Construction and preliminary applications of a Saccharomyces cerevisiae detection plasmid using for screening promoter elements / 药学学报

Synthetic biology of natural products is the design and construction of new biological systems by transferring a metabolic pathway of interest products into a chassis. Large-scale production of natural products is achieved by coordinate expression of multiple genes involved in genetic pathway of desired products. Promoters are cis-elements and play important roles in the balance of the metabolic pathways controlled by multiple genes by regulating gene expression. A detection plasmid of Saccharomyces cerevisiae was constructed based on DsRed-Monomer gene encoding for a red fluorescent protein. This plasmid was used for screening the efficient promoters applying for multiple gene-controlled pathways. First of all, eight pairs of primers specific to DsRed-Monomer gene were synthesized. The rapid cloning of DsRed-Monomer gene was performed based on step-by-step extension of a short region of the gene through a series of PCR reactions. All cloned sequences were confirmed by DNA sequencing. A vector named pEASYDs-M containing full-length DsRed-Monomer gene was constructed and was used as the template for the construction of S. cerevisiae expression vector named for pYeDP60-Ds-M. pYeDP60-Ds-M was then transformed into S. cerevisiae for heterologous expression of DsRed-Monomer gene. SDS-PAGE, Western blot and fluorescence microscopy results showed that the recombinant DsRed-Monomer protein was expressed successfully in S. cerevisiae. The well-characterized DsRed-Monomer gene was then cloned into a yeast expression vector pGBT9 to obtain a promoter detection plasmid pGBT9Red. For determination efficacy of pGBT9Red, six promoters (including four inducible promoters and two constitutive promoters) were cloned by PCR from the S. cerevisiae genome, and cloned into pGBT9Red by placing upstream of DsRed-Monomer gene, separately. The fluorescence microscopy results indicated that the six promoters (GAL1, GAL2, GAL7, GAL10, TEF2 and PGK1) can regulate the expression of DsRed-Monomer gene. The successful construction of pGBT9Red lays the foundation for further analysis of promoter activity and screening of promoter element libraries.

Low intensity pulsed ultrasound combined with guided tissue regeneration for promoting the repair of defect at canines periodontal fenestration in Beagle dogs / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the effects of low intensity pulsed ultrasound (LIPUS) combined with guided tissue regeneration (GTR) for the repair of the periodontal fenestration defect at the canines in Beagle dogs.</p><p><b>METHODS</b>Four Beagle dogs were used for establishing the periodontal fenestration defect. Sixteen canines of four Beagle dogs were simple randomly assigned into experimental group 1 [LIPUS (60 mW/cm(2), 20 min/d) irradiation + GTR + the periodontal fenestration defect], experimental group 2 [LIPUS (60 mW/cm(2), 20 min/d) irradiation + the periodontal fenestration defect], experimental group 3 (GTR + the periodontal fenestration defect) and control group (the periodontal fenestration defect). Experiments conducted 28 d. The temperature of the gingive's surface of each group was tested every 14 days (analyzed by Wilcoxon rank sum test with SPSS 13.0). The demineralized bone tissue slices of the periodontal fenestration were obtained for histologic staining after 4 weeks treatment.</p><p><b>RESULTS</b>Clinically all the treatment groups healed well. The change of gingive's surface temperature [M(Q)] before and after LIPUS irradiating were: 0.225 (0.463)°C (experimental group 1), 0.265 (0.133)°C (experimental group 2), 0.090 (0.115)°C (experimental group 3); -0.175 (0.370)°C (control group). The P value of experimental group 1 and 2 with pre-and post-treatment each time were both 0.027. Histology of the demineralized bone tissue revealed that in experimental group 1, the bone defect was filled with fresh bone-like tissues, proliferatively active osteoblasts and newly formed cementum-like tissues along the defect surface. In experimental group 3, there were more new cementum- and bone-like tissues than in experimental group 2 and control group. In experimental group 2, the new bone collagen was more mature than in experimental group 3 and control group. In control group, there was less growth of new cementum along the notch, and the new bone collagen was immature.</p><p><b>CONCLUSIONS</b>LIPUS combined with GTR may have the potential of promoting the repair of periodontal fenestration defect.</p>

Repairing effects of low-intensity pulsed ultrasound on alveolar bone defects in Beagle dogs / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the potential repairing effects of low-intensity pulsed ultrasound (LIPUS) irradiation on acute horizontal alveolar bone defects at the mandibular pre-molar areas in Beagle dogs.</p><p><b>METHODS</b>Horizontal alveolar bone defect models were established under enamelo-cemental junction 6 mm at the mandibular third and forth pre-molar buccal regions on both sides in 4 beagle dogs, and bilateral sides of each dog were randomly divided into two groups: Experimental groups with LIPUS irradiation (I(SATA) 30 mW X cm(-2), 20 min x d(-1)) and control groups without opening power source of LIPUS radiation. Dual energy X-ray bone densitometer was used to detect the bony density after an 8 weeks' irradiation. Meanwhile, decalcified bone tissue sections were used to assess the histological effects of new alveolar bone.</p><p><b>RESULTS</b>The results of new bony density detection in experimental group and control group were (0.6053 +/- 0.0566) g x cm(-2), (0.6047 +/- 0.0552) g x cm(-2), respectively, and there was no statistical significance between the differences of the two groups (P = 0.9839). Hematoxylin-eosin staining of decalcified bone tissue sections demonstrated that there were more osteoblasts lining at the edge of new alveolar bone in the experimental groups than that scattered in the control groups, and Masson staining revealed that collagens in new alveolar bone stained bright red indicating higher maturity in the experimental groups, while in the control groups mainly stained blue with some virescent areas indicating lower maturity.</p><p><b>CONCLUSION</b>LIPUS irradiation on acute horizontal alveolar bone defects has potential repairing effects.</p>

Effects of low-intensity pulsed ultrasound in repairing injured articular cartilage / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the effects of low-intensity pulsed ultrasound in repairing injured articular cartilage.</p><p><b>METHODS</b>Ten adult New Zealand rabbits with bilateral full-thickness osteochondral defects on the cartilage surface of intercondylar fossas were used in this study. The wounds in the left knees were treated with low-intensity pulsed ultrasound as the experimental group. The right knees received no treatment as the control group. All the animals were killed at 8 weeks after injury and the tissues in the wounds were collected for gross appearance grading, histological grading and proteoglycan quantity.</p><p><b>RESULTS</b>The scores of the gross appearance grades, histological grades and the optical density of toluidine blue of the tissues in the experimental group were significantly higher than those of the controls at 8 weeks after injury (P < 0.05).</p><p><b>CONCLUSIONS</b>Low-intensity pulsed ultrasound can accelerate the repair of injured articular cartilage.</p>

Establishment of human hepatocellular carcinoma multidrug-resistance cell line (HepG2/Adm) and study apoptosis induced by low-frequency pulse ultrasound exposure / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To establish human hepatocellular carcinoma multidrug-resistance cell line (HepG2/ADM) and to determine the effect of low-frequency pulse ultrasound (US) on MDR cells and investigate its mechanism.</p><p><b>METHODS</b>Using gradual increase of adriamycin (ADM) concentrations in culture, an adriamycin-resistant human hepatocellular carcinoma cell sub line (HepG2/ADM) was established in vitro. HepG2/ADM cells were cultured in vitro and randomly divided into 4 groups: the control group (HepG2/ADM only), the group ADM by 1.0 mug/ml adriamycin for 1 h, the group US by low-frequency pulse ultrasound for 10 min, and the group US by low-frequency pulse ultrasound and treated with adriamycin simultaneously at same time. A sonication at a frequency of 0.8 MHz, was delivered with an intensity level of 0.5W/cm2, with continuous exposure of 10 min was applied. The ability of US to induce the apoptosis of MDR was evaluated by analyses of fluorescence microscopy, DNA fragmentation assay and flow cytometry assay.</p><p><b>RESULTS</b>HepG2/Adm was resistant to many anti-tumor agents, and its IC50 of ADM was 26 times higher than that of parent cell line HepG2. Significant over expressions of P-gp, MRP, LRP and GSTs were detected. HepG2/ADM cells radiated by US had the typical characteristics of apoptosis. Compared with the control group (HepG2/ADM, 3.47%); the apoptosis rates were higher in US (12.23%). The therapeutic alliance of US with ADM for MDR cells, have a significant change in the ratio of apoptosis (18.81%, t=1.46 to 5.36, P<0.01).</p><p><b>CONCLUSION</b>HepG2/ADM could have the biological characteristics of human multidrug-resistance cell line. The US sonication of 0.8 MHz could induce apoptosis of HepG2/ADM cell in vitro, and could act synergistically with Adriamycin.</p>

High intensity focused ultrasound therapy combined with transcatheter arterial chemoembolization for advanced hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study high intensity focused ultrasound (HIFU) therapy combined with transcatheter arterial chemoembolization (TACE) in the treatment of patients with advanced hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Fifty patients with unresectable HCC (TNM stage IV) were randomized into a TACE (T) group and a TACE plus HIFU (T + H) group. Twenty-six patients underwent TACE alone, and 24 HIFU ablation 2 - 3 weeks after TACE. The mean follow-up time for all patients was 8.16 +/- 2.79 months (range 3 to 24 months). The median survival, 6-month-, 1-year survival rates and average survival of patients who died were calculated by Kaplan-Meier method and Fisher exact test.</p><p><b>RESULTS</b>The median survival time, 6-month and 1-year survival rates were 11.3 months, 80.4 - 85.4% and 42.9% in T + H group, in contrast to 4 months, 13.2% and 0% in T group with significant differences (P < 0.01). The average survival time of patients who died was 10.21 +/- 4.12 months in T + H group, as compared with 4.35 +/- 2.39 months in T group also with significant differences (P < 0.01).</p><p><b>CONCLUSION</b>High intensity focused ultrasound therapy (HIFU) combined with transcatheter arterial chemoembolization (TACE), being better than TACE alone, may become one of the most effective treatments for patients with unresectable HCC.</p>

Ultrasound-induced uterine smooth muscle contraction / 中华物理医学与康复杂志

Objective To study the influence and dose effect of ultrasound on the contraction of uterine smooth muscle in rats.Methods Estradiol benzoate was injected into rats three days before conducting an in-vitro experiment.Their uteri were resected and irradiated with ultrasound(0.8 MHz,3 W/cm~2,0-40 rain).The contrac- tion frequency and amplitude were recorded using an MS-302 biological experiment system.Results It could be seen that the contraction frequency and amplitude,and general contractile activity were significantly increased during ultrasonic irradiation(P＜0.01).The increased contraction frequency and amplitude lasted for ten minutes,and then the normal contraction pattern resumed.The contraction frequency as well as the percentage change in eontraction fre- quency were highest during the first 15 minutes of ultrasonic irradiation;the contraction amplitude as well as the per- centage change in amplitude were highest during 40 minutes of ultrasonic irradiation.Contraction activity was at its highest for 30 minutes,but the percentage change in activity was highest for 20 minutes.Conclusions Ultrasound can induce uterine smooth muscle contraction in rats.This biological effect is related to the irradiation time.

The effect of high intensity ultrasound on micro-vessels in a tumor in a rabbit liver / 中华物理医学与康复杂志

Objective To evaluate the damage caused by high intensity ultrasound(HIU)on tumor micro- vessels.Methods Rabbit models of the VX_2 tumor were set up.The target hepatic carcinomas were treated with HIU,and the results were observed using hematoxylin-eosin(HE)staining,vascular endothelial cell biotinylated-ulex europaeus agglutininiⅠ(UEAI)immunohistochemical staining,tumor micro-vessel counts,and electron microscopy. Results Histological examination through HE staining indicated that HIU induced carcinoma vascularities with whole tumor tissue coagulative necrosis.The UEAI immunohistochemical staining of the target lesions treated by HIU was ne- gative,and complete tumor micro-vessel uhrastructure damage was observed under the electron microscope.Conclu- sion HIU can damage tumor micro-vessels thoroughly,in such way that it may inhibit tumor growth and metastasis.

Changes of VEGF protein and mRNA in the vulva of rabbits after ultrasound irradiation / 中华物理医学与康复杂志

Objective To investigate ultrasound as a therapy for white lesions of the vulva.Methods Immunohistochemistry and hybridization in situ were used to study changes in VEGF protein and mRNA in the vulva skin of rabbits after ultrasound irradiation.Results After irradiation,VEGF protein and mRNA had increased markedly after 4 and 7 days,but their levels recovered by day 14.Conclusion Ultrasound irradiation causes local edema and hypoxia which enhance production of VEGF.VEGF promotes growth of local microvessels and increases the permeability of the endothelial cells of blood vessels.These changes improve nutrition of the mierovessels and nerve endings and ameliorate the microenvironment for tissue growth.One could speculate that ultrasound irradiation helps rehabilitation and regeneration of pathologic vulva skin.

Treatment of nonneoplastic epithelial disorders of skin and mucosa of vulva with focused ultrasound / 中华妇产科杂志

Objective To explore the clinical efficacy of focused ultrasound for patients with white lesions of the vulva,as well as its safety and feasibility.Methods Clinical data of 941 patients with white lesions of the vulva treated with focused ultrasound from June 2003 to December 2005 were retrospectively reviewed.The mean age of the patients was 40.8 years(18-70 years)and the median course of the disease was 6.2 years(3 months-45 years).Meanwhile,pathological diagnosis was performed in all the patients before treatment,in which 498 cases were squamous hyperplasia,342 cases were lichen sclerosus and 101 cases were lichen sclerosus with squamous hyperplasia.Patients were followed up and therapeutic effects of focused ultrasound was evaluated at 6 and 12 months after the treatment,respectively.The symptoms of pruritus in the vulva and the changes in the color and elasticity of the vulvar lesions were observed.Results Of all the patients,900 were followed up after the treatment,and the ratio of effectiveness was 94.9%.Only 46 patients(5.1%)had no response to the therapy.Of the effective patients,434 cases were completely cured(48.2%),and 420 cases were improved(46.7%).Pruritus of vulva recurred in 101 patients (11.2%)one year after treatment;however,these patients still had a response to the second or third treatment.Conclusions Focused ultrasound therapy is a highly effective instrument in treatment of white lesions of the vulva.It can not only relieve the symptoms of itching,but is also helpful in recovering the color and elasticity of the vulva.