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Biomedicine
High-intensity focused ultrasound with large scale spherical phased array for the ablation of deep tumors
Xiang JI, Jing-feng BAI, Guo-feng SHEN, Ya-zhu CHEN
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2009, 10(9): 639-647.   https://doi.org/10.1631/jzus.B0920130
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Under some circumstances surgical resection is feasible in a low percentage for the treatment of deep tumors. Nevertheless, high-intensity focused ultrasound (HIFU) is beginning to offer a potential noninvasive alternative to conventional therapies for the treatment of deep tumors. In our previous study, a large scale spherical HIFU-phased array was developed to ablate deep tumors. In the current study, taking into account the required focal depth and maximum acoustic power output, 90 identical circular PZT-8 elements (diameter=1.4 cm and frequency=1 MHz) were mounted on a spherical shell with a radius of curvature of 18 cm and a diameter of 21 cm. With the developed array, computer simulations and ex vivo experiments were carried out. The simulation results theoretically demonstrate the ability of the array to focus and steer in the specified volume (a 2 cm×2 cm×3 cm volume) at the focal depth of 15 to 18 cm. Ex vivo experiment results also verify the capability of the developed array to ablate deep target tissue by either moving single focal point or generating multiple foci simultaneously.
A fast automatic recognition and location algorithm for fetal genital organs in ultrasound images
Sheng TANG, Si-ping CHEN
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2009, 10(9): 648-658.   https://doi.org/10.1631/jzus.B0930162
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Severe sex ratio imbalance at birth is now becoming an important issue in several Asian countries. Its leading immediate cause is prenatal sex-selective abortion following illegal sex identification by ultrasound scanning. In this paper, a fast automatic recognition and location algorithm for fetal genital organs is proposed as an effective method to help prevent ultrasound technicians from unethically and illegally identifying the sex of the fetus. This automatic recognition algorithm can be divided into two stages. In the ‘rough’ stage, a few pixels in the image, which are likely to represent the genital organs, are automatically chosen as points of interest (POIs) according to certain salient characteristics of fetal genital organs. In the ‘fine’ stage, a specifically supervised learning framework, which fuses an effective feature data preprocessing mechanism into the multiple classifier architecture, is applied to every POI. The basic classifiers in the framework are selected from three widely used classifiers: radial basis function network, backpropagation network, and support vector machine. The classification results of all the POIs are then synthesized to determine whether the fetal genital organ is present in the image, and to locate the genital organ within the positive image. Experiments were designed and carried out based on an image dataset comprising 658 positive images (images with fetal genital organs) and 500 negative images (images without fetal genital organs). The experimental results showed true positive (TP) and true negative (TN) results from 80.5% (265 from 329) and 83.0% (415 from 500) of samples, respectively. The average computation time was 453 ms per image.
Hydraulic pressure inducing renal tubular epithelial-myofibroblast transdifferentiation in vitro
Fei-yan LI, Xi-sheng XIE, Jun-ming FAN, Zi LI, Jiang WU, Rong ZHENG
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2009, 10(9): 659-667.   https://doi.org/10.1631/jzus.B0920110
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Objective: The effects of hydraulic pressure on renal tubular epithelial-myofibroblast transdifferentiation (TEMT) were investigated. Methods: We applied hydraulic pressure (50 cmH2O) to normal rat kidney tubular epithelial cells (NRK52E) for different durations. Furthermore, different pressure magnitudes were applied to cells. The morphology, cytoskeleton, and expression of myofibroblastic marker protein and transforming growth factor-β1 (TGF-β1) of NRK52E cells were examined. Results: Disorganized actin filaments and formation of curling clusters in actin were seen in the cytoplasm of pressurized cells. We verified that de novo expression of α-smooth muscle actin induced by pressure, which indicated TEMT, was dependent on both the magnitude and duration of pressure. TGF-β1 expression was significantly upregulated under certain conditions, which implies that the induction of TEMT by hydraulic pressure is related with TGF-β1. Conclusion: We illustrate for the first time that hydraulic pressure can induce TEMT in a pressure magnitude- and duration-dependent manner, and that this TEMT is accompanied by TGF-β1 secretion.
Ursolic acid inhibits proliferation and induces apoptosis of HT-29 colon cancer cells by inhibiting the EGFR/MAPK pathway
Jian-zhen SHAN, Yan-yan XUAN, Shu ZHENG, Qi DONG, Su-zhan ZHANG
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2009, 10(9): 668-674.   https://doi.org/10.1631/jzus.B0920149
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Objective: To investigate the effects of ursolic acid on the proliferation and apoptosis of human HT-29 colon cancer cells. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays were performed to evaluate the effects of ursolic acid on the growth and apoptosis of HT-29 cells. Western blot analysis was applied to investigate the inhibitory effects of ursolic acid on the phosphorylation of the epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK), and the activity of B cell leukemia-2 (Bcl-2), B cell leukemia-xL (Bcl-xL), caspase-3, and caspase-9. Results: Ursolic acid inhibited the growth of HT-29 cells in dose- and time-dependent manners. The median inhibition concentration (IC50) values for 24, 48, and 72 h treatment were 26, 20, and 18 μmol/L, respectively. The apoptotic rates of 10, 20, and 40 μmol/L ursolic acid treatments for 24 h were 5.74%, 14.49%, and 33.05%, and for 48 h were 9%, 21.39%, and 40.49%, respectively. Ursolic acid suppressed the phosphorylation of EGFR, ERK1/2, p38 MAPK, and JNK, which is well correlated with its growth inhibitory effect. 10, 20, and 40 μmol/L ursolic acid significantly inhibited the proliferation of EGF-stimulated HT-29 cells (P<0.05). Cell proliferation was most significantly inhibited when treated with 10 and 20 μmol/L ursolic acid combined with 200 nmol/L AG 1478 or 10 μmol/L U0126 (P<0.01). Besides, it also down-regulated the expression of Bcl-2 and Bcl-xL and activated caspase-3 and caspase-9. Conclusion: Ursolic acid induces apoptosis in HT-29 cells by suppressing the EGFR/MAPK pathway, suggesting that it may be a potent agent for the treatment of colorectal cancer.
DcR3 and survivin are highly expressed in colorectal carcinoma and closely correlated to its clinicopathologic parameters
Qi-lian LIANG, Bi-rong WANG, Guo-hong LI
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2009, 10(9): 675-682.   https://doi.org/10.1631/jzus.B0920077
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Objective: To investigate the expression of death decoy receptor 3 (DcR3) and survivin in colorectal carcinoma. Methods: Tumor and normal tissues were taken from a total of 100 colorectal carcinoma patients during surgery, and the expression of DcR3 and survivin was examined by immunohistochemistry, Western blotting, and reverse transcription-polymerase chain reaction (RT-PCR) analyses. Results: RT-PCR showed that the expression levels of DcR3 mRNA (0.846±0.242, P<0.01) and survivin mRNA (0.7835±0.2392, P<0.01) in colorectal cancer tissues were significantly higher than those in adjacent normal tissues. Western blotting showed that the expression levels of DcR3 protein (0.795±0.261, P<0.01) and survivin protein (0.6765±0.1351, P<0.01) in tumor tissues were significantly higher than those in non-cancer tissues. The immunohistochemical streptavidin-peroxidase (SP) method showed that the positive expression rates of DcR3 and survivin were 67.0% and 58.0% in colorectal cancer tissues, and 18.0% and 3.0% in non-cancerous colorectal tissues (P<0.05), respectively. The positive correlations of DcR3 (P<0.01) and survivin (P<0.01) to the differentiation of colorectal carcinoma cells, lymph node metastasis, and pathological stage were observed. The expression of DcR3 and survivin was found to be positively correlated to clinicopathologic parameters of colorectal carcinoma. Conclusion: The overexpressed DcR3 and survivin in colorectal cancer may contribute to the development of the cancer. The monitoring of these two proteins may be useful for the diagnosis, differentiation, metastasis, and determination of stages of colorectal carcinoma.
Evaluation of pelvic lymph node coverage of conventional radiotherapy fields based on bony landmarks in Chinese cervical cancer patients using CT simulation
Xiang ZHANG, Hua YU
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2009, 10(9): 683-688.   https://doi.org/10.1631/jzus.B0920114
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Objective: To evaluate the pelvic lymph node coverage of conventional pelvic fields based on bony landmarks in Chinese patients with cervical cancer by using computed tomography (CT) simulation images to contour pelvic vessels as substitutes for lymph nodes location. Methods: A retrospective review of CT simulation images and conventional pelvic radiation planning data sets was performed in 100 patients with cervical cancer at the International Federation of Gynecology and Obstetrics (FIGO) Stage IIB to IIIB in our hospital. Pelvic arteries were contoured on CT simulation images, and the outlines of conventional pelvic fields were drawn as defined by the gynecologic oncology group (GOG) after hiding the contours. The distances between the following vessel contours and field borders were measured: D1, the superior border of the anterior/posterior (AP) field and the bifurcation of abdominal aorta; D2, the ipsilateral border of the AP field and the distal end of external iliac artery; and D3, the anterior border of the lateral (LAT) field and the distal end of the external iliac artery. The distances were recorded as positive values if the measuring point was within the conventional pelvic fields, or they were recorded as negative values. Lymph nodes coverage was considered adequate when D1(0 mm, D2(17 mm or D3(7 mm. Results: All patients had at least 1 inadequate margin, 97 patients (97.0%) had 2, and 22 patients (22.0%) had all the 3. On the AP field, 95 patients (95%) had the measuring point, the bifurcation of the abdominal aorta, out of the field (D1<0 mm), and all the patients had a distance less than 17.0 mm between the distal end of the external iliac artery and ipsilateral border (D2<17.0 mm). On the LAT field, 24 patients (24%) had a distance less than 7.0 mm between the distal end of the external iliac artery and anterior border (D3<7.0 mm). Conclusion: We observed that conventional pelvic fields based on bony landmarks provided inadequate coverage of pelvic lymph nodes in our patients with cervical cancer. CT simulation may be a feasible technique for planning pelvic fields optimally and individually.
Modified biplanar open-wedge high tibial osteotomy with rigid locking plate to treat varus knee
Hai-ning ZHANG, Jie ZHANG, Cheng-yu LV, Ping LENG, Ying-zhen WANG, Xiang-da WANG, Chang-yao WANG
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2009, 10(9): 689-695.   https://doi.org/10.1631/jzus.B0920095
Abstract   PDF (0KB)
Objective: To introduce and characterize the modified biplanar opening high tibial osteotomy with rigid fixation to treat varus knee in young and active patients. Methods: Between June 2001 to July 2008, 18 patients with monocompartmental degeneration of the knee combined with a varus malalignment of the leg had the modified biplanar opening high tibial osteotomy and the osteotomy was fixed with the locking plates (Locking Compression Plate System). The mean varus deformity before operation was 11.5° (5°~19°) and no degenerative changes were found in other departments. Stability of the knee was normal in 15 patients, but ruptures in anterior cruciate ligaments or lateral collateral ligament were presented in the remaining 3 patients. Preoperative symptom was mainly limited in the pain of medial compartment. The preoperative and follow-up data for the range of motion and Lysholm score were determined. Subjective satisfactory examination was also applied to the patients for the operation they selected. Results: All of the patients were followed up with an average of 32.5 months (12~82 months). There was no ununion or delayed union in this group during the follow-up period. No complications like broken plate, nerve injury, or blood vessel injury occurred. The postoperative average corrected degree was 9.5° (5.5°~18°). No degenerations developed in the three departments of the knee. The Lysholm scores before and after surgery were 42.5 and 77.5, respectively (P<0.01). The overall fineness rate was 83.3%. The subjective satisfactory survey demonstrated that about 83.3% patients showed satisfactory on the operation. There was no obvious difference in the range of motion before and after operation, but significant changes were found in the Lysholm score and varus degree from preoperative to follow-up. Conclusion: Proximal opening high tibial osteotomy performed in conjunction with the special rigid locking plate yielded good results for symptomatic genu varum. This new classic technique can be effectively applied to the medial compartment degeneration of the knee in active young patients.
Hybrid decompression technique and two-level corpectomy are effective treatments for three-level cervical spondylotic myelopathy
Yong LIU, Ke-yi YU, Jian-hua HU
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2009, 10(9): 696-701.   https://doi.org/10.1631/jzus.B0960001
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The optimal surgical strategy for multilevel cervical spondylotic myelopathy (CSM) has not been defined, and few comparative researches between hybrid decompression and multilevel corpectomy have been conducted. Here, we reported 28 patients of three-level CSM, of whom 12 underwent hybrid decompression and 16 two-level corpectomy, with each type of procedure chosen according to radiologic characteristics of those patients. Clinical and radiologic parameters of both groups showed various degrees of improvement. However, no statistically significant differences in Japanese Orthopedic Association (JOA) score improvement rate, graft fusion rate, post-operative neck disability index (NDI) or segmental lordosis between the two groups were found. We conclude that both hybrid decompression and two-level corpectomy could obtain satisfying clinical efficacy in the management of three-level CSM for appropriate patients.
PI-3 kinase pathway can mediate the effect of TGF-β1 in inducing the expression of SHARP-2 in LLC-PK1 cells
Zhang-fei SHOU, Qin ZHOU, Jie-ru CAI, Jiang-hua CHEN, Kazuya YAMADA, Kaoru MIYAMOTO
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2009, 10(9): 702-706.   https://doi.org/10.1631/jzus.B0920066
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We aim to investigate the effect of transforming growth factor (TGF)-β1 on the expression of enhancer of split- and hairy-related protein-2 (SHARP-2) messenger RNA (mRNA) and its signaling pathway. In this study, several cell lines including LLC-PK1 (a porcine kidney tubular epithelial cell line), MDCK (Madin-Darby canine kidney) and CTLL-2 (cytotoxic T-lymphocyte line) were treated with recombinant human TGF-β1, and a series of experiments were carried out, involving Northern blot analysis of total RNA from these cells. Further, several specific chemical inhibitors were applied before TGF-β1 treatment to probe the signaling pathway. The results showed that TGF-β1 can significantly up-regulate SHARP-2 mRNA expression in the LLC-PK1 cell line. The peak level of induction was found 2 h after TGF-β1 stimulation. While one phosphoinositide 3-kinases (PI-3) kinase inhibitor, LY294002, completely blocked the effect of TGF-β1 on SHARP-2 mRNA expression in LLC-PK1 cells at a low concentration, other inhibitors, including PD98059, staurosporine, AG490, wortmannin, okadaic acid and rapamycin, had no effect. The effect of LY294002 was dose-dependent. We conclude that, in LLC-PK1 cells at least, TGF-β1 can effectively induce the SHARP-2 mRNA expression and that the PI-3 kinase pathway can mediate this effect.
Subglottic adenoid cystic carcinoma mistaken for asthma
Hua-lin WANG, Lin XU, Fu-jun LI
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2009, 10(9): 707-710.   https://doi.org/10.1631/jzus.B0920071
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Adenoid cystic carcinoma rarely occurs within the subglottic larynx. In this study, a case of subglottic adenoid cystic carcinoma was reported. A 54 year-old Chinese woman developed a sudden onset of chest distress and cough worsening after physical exertion, and was diagnosed with, and treated as, bronchial asthma. Regular anti-asthmatic therapy did not improve the symptoms. Until a sudden dyspnea, a cervicothoracic computerized tomography (CT) revealed that her upper airway was obstructed by a laryngeal tumor. The patient was diagnosed with a subglottic adenoid cystic carcinoma and treated with complete surgical excision and adjuvant radiation therapy. Follow-up endoscopy and laryngeal magnetic resonance imaging (MRI) at six months showed no recurrence of the tumor. The diagnosis of subglottic adenoid cystic carcinoma should be considered in patients who are characterized by dyspnea, cough, and stridor, but do not respond to regular anti-asthmatic therapy.
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