温州医科大学学报
 
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2014 Vol. 44, No. 6
Published: 2014-06-25
 
 
391 Mfn-1 RNAi activates the mitochondrial unfolded protein response via the ATFS-1 mediated pathway in C. elegans
YAO Xiuping, CHEN Sixi, REN Yaguang, ZHOU Huaibin, LV Jianxin.
Objective: To research the effect of mfn-1 RNAi on mitochondrial unfolded protein response and its mechanism. Methods: Worm strains SJ4058 and SJ4100(mitochondrial unfolded protein response reporter), TJ375 (cytosolic unfolded protein response reporter), and SJ4005 (endoplasmic reticulum unfolded protein response reporter) were treated by mfn-1 RNAi, and to observe whether the corresponding chaperones were activated or not; crossing strain SJ4058 into haf-1 gene loss of function strain RB867 and atfs-1 gene loss of function strain VC3201 respectively, the obtained homozygous animals were treated by mfn-1 RNAi, and their progenies were observed for fluorescence to explore whether the activation of chaperones was relied on HAF-1 or ATFS-1. Results: Mfn-1 RNAi specifically activated the mitochondria specific chaperones HSP-6 and HSP-60, but not cytosol specific chaperon HSP-16.2 and endoplasmic reticulum specific chaperon HSP-4; We obtained the hsp-60::gfp/atfs-1(gk3094) V and hsp-60::gfp/haf-1(ok705)IV strains by crossing and their genotypes were confirmed by PCR. The two strains were treated by mfn-1 RNAi, and further studies showed that the activation of chaperon HSP-60 was relied on ATFS-1 rather than HAF-1. Conclusion: Mfn-1 RNAi treatment specifically activated mitochondrial rather than cytosolic and endoplasmic reticulum unfolded protein response, suggesting the mitochondria proteostasis is affected, but that of cytosol and endoplasmic reticulum are not; the activation of mitochondrial unfolded protein response by mfn-1 RNAi is dependent on the transcription factor ATFS-1, not the mitochondria membrane protein HAF-1.
2014 Vol. 44 (6): 391-394 [Abstract] ( 863 ) HTML (1 KB)  PDF  (0 KB)  ( 535 )
395 Prediction and identification of linear B-cell epitopes within Tarp of Chlamydia trachomatis
FENG Yan, ZHU Shanli, LIN Xiaoyun, XUE Xiangyang, LI Wenshu, ZHANG Lifang.
Objective: To predict and identify the B-cell epitope of Chlamydia trachomatis Tarp. Methods: The amino acid sequence of Tarp was analyzed using computer-assisted techniques to scan B-cell epitopes, and 6 possible linear B-cell epitopes peptides (aa80-95, aa107-123, aa152-170, aa171-186, aa239-253 and aa497-513) with high predicted antigenicity and high conservation were investigated. After coupling to KLH, the synthetic peptides were emulsifield with Freund’s adjuvant. Then, BALB/c mice were randomly assigned to receive (subcutaneous injection) peptides-KLH, KLH or PBS (n=3, 100 μg/time/mouse), respectively, and the same immunization schedule was repeated third times at a 2-week interval. ELISA was used to detect the IgG and subtypes IgG1, IgG2a in the serum as well as the sIgA in the vaginal secretions. Furthermore, the specific binding of anti-sera produced by epitopes immunization to natural Tarp antigen was detected with indirect immunofluorescence assay (IFA), immunoprecipitated and Western blot analysis, respectively. Results: The epitope peptide F4 (aa171-186) was able to induce significant Tarp specific antibody IgG in serum and sIgA in vaginal wash as compared with KLH or PBS (1:100) (P<0.05), and the major IgG antibody subtype was IgG1. Western blot and IFA results confirmed that specific antibodies were induced by epitope aa171-186 recognized natural Tarp antigen. Conclusion: Our results demonstrated that the predictive epitopes (aa171-186) are immunodominant B-cell epitope of Tarp, and if proven protective and safe, in conjunction with others well-documented epitopes, they may be included into a candidate epitope-based vaccine.
2014 Vol. 44 (6): 395-400 [Abstract] ( 665 ) HTML (1 KB)  PDF  (0 KB)  ( 557 )
401 Evaluation of mitochondrial tRNASer(UCN) G7444A mutation associated with non-syndromic hearing loss in eleven Han Chinese pedigrees 
TANG Xiaowen1,2, YANG Yaling1, GAO Yinglong1, XIAO Hongli1, HE Zheyun1, ZHENG Jing1,3, ZHENG Binjiao1, Lv Jianxin1, JIN Longjin1, GUAN Minxin1,
Objective: To report the clinical, genetic and molecular characteristics of 11 Han Chinese pedigrees with mitochondrial tRNASer(UCN) G7444A mutation and explore the role of mitochondrial tRNASer(UCN) G7444A mutation in the development of maternally inherited non-syndromic deafness. Methods: PCR amplification of mitochondrial 12S rRNA, mitochondrial tRNASer(UCN) and GJB2 gene of 2 650 Chinese Han non-syndromic deafness subjects. The proband and family members of 11 Chinese Han pedigrees with mitochondrial tRNASer(UCN) G7444A mutation underwent audiological testing, deafness associated mutational hot spots screening and pedigree assessment. Results: Among the 2 650 Han Chinese non-syndromic deafness subjects, 22 patients belonging to 11 pedigrees carried mitochondrial tRNASer(UCN) G7444A mutation, account for 0.7%. Number of pedigree carry both mitochondrial tRNASer(UCN) G7444A mutation and mitochondrial 12S rRNA A1555G, mitochondrial 12S rRNA C1494T or GJB2 c.235delC mutation were 3, 1, 2 respectively. Clinical data showed that there were huge difference in the severity of hearing loss, age of onset and penetrance among these 11 Chinese Han non-syndromic deafness pedigrees. The average penetrance of these pedigrees carrying mitochondrial tRNASer(UCN) G7444A mutation and mitochondrial 12S rRNA A1555G, C1494T or GJB2 c.235delC mutation were 29.4%, 42.9% and 19.0% respectively. The average penetrance of 4 pedigrees carrying the mitochondrial tRNASer(UCN) G7444A mutation and mitochondrial 12S rRNA A1555G or C1494T mutation is significantly higher than that of carry mitochondrial tRNASer(UCN) G7444A mutation, it was 14.0%. Conclusion: Mitochondrial tRNASer(UCN) G7444A mutation and mitochondrial 12S rRNA A1555G or C1494T mutations may co-modulate the variable penetrance and expressivity of deafness among these Han Chinese non-syndromic pedigrees.
2014 Vol. 44 (6): 401-406 [Abstract] ( 751 ) HTML (1 KB)  PDF  (0 KB)  ( 423 )
407 Value of real-time myocardial contrast echocardiography in the detection of the myocardial perfusion abnormalities in early diabetic rats model
ZHENG Lei1, ZHANG Ming2, LIANG Tianlin1, RU Ao1, LIU Min1, ZHAO Yingzheng2, TIAN Xinqiao1.
Objective: To explore the value of real-time myocardial controast echocardiography to detect myocardial perfusion abnormalities in early diabetic rats. Methods: Among twenty-four male SD rats, twelve rats were randomly selected as DM group which were induced with streptozotocin, the remain twelve rats as normal control group which were induced with buffer solution. Eight weeks after diabetic model established, all rats underwent MCE examination at the resting state. The plateau intensity (A), initial slope of the curve (β) and myocardial blood flow (A×β) of left ventricular anterior wall at the papillary muscle level were measured in left ventricular short-axis view by MCE. At last, myocardial tissue of the rats were stained with CD31 immunohistochemistry to detect myocardial microvascular density (MVD). The correlation between A and MVD at DM group was analyzed. Results: Compared with the control group, A and A×β in DM group were obviously lower (P<0.01), β in DM group was also lower, but without statistical difference. The MVD in the DM group was significantly decreased compared with the control group (P<0.01). There were significant positive correlations between A and MVD at DM group (r=0.903, P<0.01). Conclusion: MCE can be used to detect the left ventricular myocardial perfusion abnormalities in early diabetic rats and has important application value in diagnosis of the diabetic cardiomyopathy.
2014 Vol. 44 (6): 407- [Abstract] ( 705 ) HTML (1 KB)  PDF  (0 KB)  ( 417 )
411 Research on accelerated healing of skin wounds of diabetic ulceration by curcumol ointment
ZHOU Jie, ZHU Yanlin, DONG Jianyong, FU Hongxing, QIU Guanguan, FANG Lianglian, LIN Weiwei.
Objective: To study the effect of topical administration of curcumol ointment on the wound healing process in diabetic rats. Methods: The study was conducted using male Sprague Dawley rats which were separated into three groups: diabetic rats receiving control cream, diabetic rats receiving 5% curcumol ointment, and diabetic rats receiving 10% curcumol ointment. Two 1.8 cm diameter cutaneous wounds were then created at the dorsal regions of each rats. Wound healing was assessed by rate of wound closure estimation, and histological studies on the 3, 7, 14 and 21 d after wounding. Results: Curcumol ointment treatment enhanced the wound healing process by increasing rate of wound closure significantly compared to the control group (P<0.05). Histological observation also showed the 10% curcumol ointment treated groups significantly promoted the number of capillaries, improved the collagen synthesis, and increased the positive expressions of CD31 and TGF-β1. Conclusion: Curcumol ointment administrations can improve the speed and quality of skin wound healing.which could provide theoretical foundation for clinical treatment of diabetic ulcer.
2014 Vol. 44 (6): 411- [Abstract] ( 641 ) HTML (1 KB)  PDF  (0 KB)  ( 431 )
417 Analysis of epidemic characteristics of metabolic syndrome in acute coronary syndrome patients
LIU Wenmin, ZHANG Juhong, JIAN Ying, ZHANG Xingwei, ZHANG Linan, YANG Deye.
Objective: To explore the prevalence of metabolic syndrome and the combination of its components in a cohort of patients with acute coronary syndrome. Methods: Clinical histories of 387 inpatients with acute coronary syndrome were selected. They were categorized according to the specific criteria stated in the latest joint statement for the global definition of MS. Results: The metabolic syndrome presented in 58.9%. The most prevalent component was low HDL-c (87.1%) and impaired fasting glucose (81.2%). The most frequent combination of components was elevated triglycerides+lower HDL-c+impaired fasting glucose (54.7%) and elevated triglycerides+lower HDL-c+abdominal visceral obesity+hypertension. Conclusion: The metabolic syndrome has a high prevalence in patients with acute coronary syndrome. No matter with or without diabetes, the most frequent components is low HDL-c levels.
2014 Vol. 44 (6): 417- [Abstract] ( 616 ) HTML (1 KB)  PDF  (0 KB)  ( 393 )
421 The relative research on menopausal years with lumbar intervertebral disc degeneration in postmenopausal women
LOU Chao1, CHEN Hongliang1, FENG Xiaozhen2, TIAN Naifeng1, XIANG Guangheng1, ZHU Sipin1, XU Huazi1.
Objective: To investigate, in a population of healthy postmenopausal women, the relationship of years since menopause (YSM) with lumbar intervertebral disc degeneration between the 1st lumbar and 1st sacral vertebrae, with magnetic resonance imaging (MRI). Methods: Selected 589 healthy postmenopausal women in accordance with the inclusion criteria, recording their age, height, weight, age at menopause and YSM. Disc degeneration was assessed using a modified Pfirrmann grading system on 1.5T MRI. Results: All postmenopausal women’s lumbar intervertebral disc were degeneration. After removing age, height and weight effect, when YSM≤15 years, a positive trend was observed between YSM and severity of disc degeneration, respectively that L1/L2 (r=0.235), L2/L3 (r=0.161), L3/L4 (r=0.173), L4/L5 (r=0.146), L5/S1 (r=0.137) and all lumbar disc (r=0.259) (P<0.05 or 0.01). According to YSM, the subjects were divided into 3 groups separately, namely, 1～5 YSM, 6～10 YSM and 11～15 YSM. There was significant difference between each other (P<0.01). When YSM>15 years, there was no significant correlation between YSM and severity of disc degeneration (P>0.05). Goups of 16～20 YSM, 21～25 YSM and 26～30 YSM had no significant difference between each other (P>0.05). Multiple stepwise regression analysis showed that the effect of YSM on each disc degeneration mutation was respectively L1/L2 (40.3%), L2/L3 (29.1%), L3/L4 (27.6%), L4/L5(18.2%), L5/S1 (16.3%) and total (42.9%). Conclusion: There is a correlation between YSM and lumbar intervertebral disc degeneration. After menopause, lumbar intervertebral disc degeneration shows a progressive aggravation that almost entirely occurs in the first 15 years since menopause, showing that the estrogen decrease in postmenopausal women may accelerate the degeneration of lumbar intervertebral disc in a certain period of time.
2014 Vol. 44 (6): 421- [Abstract] ( 597 ) HTML (1 KB)  PDF  (0 KB)  ( 378 )
426 Exploration of the relationship between LTF gene expression and its DNA promotor region methylation in human gastric cancer cell lines BGC823
ZHUGE Xiaoju1, CHEN Renpin1, HUANG Xielin2, CHEN Chao1, LU Deyi1, HUANG Zhiming1, WU Jinming1, WU Jiansheng1.
Objective: To detect the methylation status and mRNA expression of LTF (lactotransferrin) gene in BGC823 gastric cancer cell lines, to explore the relationship between the abnormal methylation of LTF gene’s promoter region and its expression in gastric cancer. Methods: Bisulfite genomic sequencing PCR (BSP) was adopted to detect the promotor methylation status of LTF. Real-time PCR and Western blot were respectively used to evaluate LTF expression in mRNA and protein level. Meanwhile, 5-aza-CdR was used to reverse the LTF genes’ methylation status, and after the treatment, methylation and mRNA expression status was recorded. Results: The promotor methylation rates of LTF in BGC823 was 53.6%. Compared to the control group, methylation status and mRNA expression of LTF in drug treatment groups (the 5-aza-CdR concentration was 2 μmol/L and 10 μmol/L) were reversed by 5-aza-CdR, which showed statistical differences (P<0.05). But no diffenrence had shown between different treatment groups (P>0.05). Conclusion: The LTF methylation in promoter region is high in BGC823 which is related with the low expression of mRNA level. Demethylation agents can reverse the methylation status and re-express its mRNA.
2014 Vol. 44 (6): 426- [Abstract] ( 611 ) HTML (1 KB)  PDF  (0 KB)  ( 413 )
431 Ultrasound and clinical assessment on the treatment of rheumatoid arthritis
CHEN Dan, LI Yongji, WANG Xiaobing, ZHU Xiaochun.
Objective: To estimate the value of ultrasound (US) and clinical assessment on the treatment of rheumatoid arthritis (RA) patients in different stages. Method: Fourty-five RA patients, including early RA patients (group A) and non-early RA patients (group B) took traditional disease modifying anti-rheumatic drugs and etanercept for three months. Main evaluation indicators included the gray-scale US (GSUS) and the power Doppler US （PDUS） of the joints before treatment, during and after treatment, secondary evaluation indicators were clinical features, laboratory results, DAS28. Results: Compared to group B, the improvement of PDUS was greater in group A than group B after treatment for 6 weeks (2.07±0.41 vs 3.93±0.40, p<0.01) and 12 weeks (0.51±0.27 vs 1.47±0.26, p<0.05). The group A showed lower morning stiffness (0.00±0.04 vs 0.16±0.04, p<0.05), erythrocyte sedimentation rate (23.66±3.04 vs 36.84±2.97, p<0.01), c-reactive protein (6.29±1.79 vs 11.37±1.75, p<0.05), health assessment questionnaire (7.43±1.07 vs 12.73±0.97, p<0.01) than group B after treatment of 6 weeks, as well as the erythrocyte sedimentation rate (15.34±1.91 vs 23.11±1.87, p<0.01), health assessment questionnaire (2.71±0.98 vs 7.37±0.89, p<0.01) and disease activity score-28 (2.50±0.21 vs 3.20±0.20, p<0.05) after treatment of 12 weeks. And ultrasound alleviation was not showed in all clinical and laboratory remission. Conclusion: Ultrasound can accurately reflect the condition of RA involved joints, so it should be recommended in the follow-up of RA patients. Joint therapy with traditional DMARDs and etanercept helps for early and non-early RA patients, and the former is benefit more. Clinical and laboratory remission may not exclude joint inflammation in ultrasound.
2014 Vol. 44 (6): 431-434 [Abstract] ( 577 ) HTML (1 KB)  PDF  (0 KB)  ( 381 )
435 HLA-G expression and its clinical significance by HBV
ZHOU Linjie, ZHENG Zhencang, WANG Xin, CHEN Peng
Objective: To investigate HLA-G expression and its clinical significance by HBV. Methods: Real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA) were used to explore the serum HBV DNA load and plasma sHLA-G concentrations. HBV and THP-1 were cocultured for 1~6 d. RT-PCR and Western blot were used to analyse the expression of HLA-G in THP-1. Results: Plasma sHLA-G levels were dramatically increased in the peripheral blood of patients with HBV when compared with that in normal controls (P<0.01). After in vitro infection by a highly pathogenic strain of HBV, HLA-G mRNA was dramatically increased and the protein expression of HLA-G was induced. Datas showed that HLA-G transcription and protein expression were induced in 1 day and reached highest on 4 day and then decreased in a manner of time-dependent. Conclusion:  Given its immunotolerant property, an increase in HLA-G of patients with HBV may play an important role in regulation of the inflammatory response process in vivo.
2014 Vol. 44 (6): 435- [Abstract] ( 601 ) HTML (1 KB)  PDF  (0 KB)  ( 422 )
441 Effect of vinorelbine combined with xeloda on treating the patients with advanced breast cancer
XU Zhengyang, YUAN Zuguo, ZHOU Taoqi, YANG Hui, YUAN Guangbo, REN Ruiping.
Objective: To explore the clinical efficacy and tolerability of vinorelbine with xeloda for patients with advanced breast cancer. Methods: Forty-six patients with advanced breast cancer were enrolled in the study. All patients were given 25 mg/m2 of vinorelbine on days 1 and 8, combined with 2.0 g/m2 of xeloda daily from day 1 to 14. The combined chemotherapy was repeated every 21 days as one cycle. Patients received a maximum chemotherapy of 8 cycles or until disease progression. Results: All the 46 patients completed 225 chemotherapy cycles with a 5-cycle median. Adverse events and clinical efficacy were evaluated on all 46 patients. Complete remission (CR) in 2 patients, partial remission (PR) in 17 patients, stable disease (SD) in 17 patients, and progression of disease (PD) in 10 patients. The overall response rate (CR+PR) was 41.3%, and the disease control rates (DCR) was 78.3%. The median time to progression (TTP) was 8.3 months, 1 year and three-year survival rates were 70.6% and 27.6%.The most commonly observed adverse events were hematologic toxicity and hand-foot syndrome and angeitis. No mortality occurred during the treatment. Conclusion: Vinorelbine combined with xeloda is an effective and safe chemotherapeutic regimen for advanced breast cancer, and the adverse reactions are well tolerated.
2014 Vol. 44 (6): 441-444 [Abstract] ( 874 ) HTML (1 KB)  PDF  (0 KB)  ( 360 )
445  CT and MRI features of aggressive fibromatosis
SHI Shaohua1, GAO Yuantong2, XU Chongyong3, CHEN
Objective: To explore CT and MRI features of aggressive fibromatosis. Methods: The CT and MRI findings of aggressive fibromatosis confirmed by surgical pathology in 23 cases were retrospectively analyzed. Results: CT examination: the abdominal wall outside type of 7 cases: 4 mass clear boundaries and 3 unclear; 5 mass with homogeneous density and 2 uneven; 3 even density, 2 equal low density, 2 low density. The abdominal wall type of 16 cases: 15 mass clear boundaries and 1 unclear; 13 mass with homogeneous density and 3 uneven; 9 even density, 4 slight low density, 3 equal low density. The enhancement of 12 cases: 4 moderate enhancement and 8 slight enhancement in the arterial phase, mild persistent enhancement in the venous phase and delayed phase. MRI examination: 1 mass signals even and 3 uneven; 2 slightly high signal and 1 high with low signal and 1 high with low or on T2WI; 1 low or even signal and 3 low signal on T1WI; 2 low signal and 2 high signal on T2WI fat suppression. 4 bone invasion damaged, 1 compression, 1 uterine, sigmoid compression. Conclusion: The CT and MRI manifestations of aggressive fibromatosis have certain characteristics features, CT and MRI examination is of great value in the diagnosis of the disease.
2014 Vol. 44 (6): 445- [Abstract] ( 765 ) HTML (1 KB)  PDF  (0 KB)  ( 544 )
449 The value of color doppler flow imaging in evaluating the drug therapeutic response of arterial erectile dysfunction
GUAN Jingyi1, HU Yuanping1, WU Zhigang2, LI Chengdi2
Objective: To explore the application value of color doppler flow imaging in evaluating the drug therapeutic response of arterial erectile dysfunction (ED). Methods: Twenty patients with arterial ED were requested to take Phosphodiesterase type-5 (PDE5) inhibitor quarter grain every day before sleeping for six weeks. All the patients were Pre- and post - treatmenlyt scored on international index of erectile function (IIEF-5) and received intracaverous injection of vasoactive agent, followed by measurement of peak systolic velocity (PSV) of cavernosal artery by color doppler ultrasound. Results: The IIEF-5 score (20.80 ± 2.70), left PSV (35.50 ± 9.12) m/s and right PSV (33.45 ± 9.19) m/s of post-treatment group were significantly higher than the IIEF-5 score (10.20 ± 2.35), left PSV (18.35 ± 3.54) m/s and right PSV (16.35 ± 3.94) m/s of pretherapy group (P<0.05). Conclusion: Color doppler flow imaging is one of the effective method of evaluating the therapeutic response of arterial ED.
2014 Vol. 44 (6): 449- [Abstract] ( 653 ) HTML (1 KB)  PDF  (0 KB)  ( 409 )
452 Clinical value of the combined detection of three indicators for early diagnosis of diabetic nephropathy
ZHOU Yuping
Objective: To explore the clinical value of the combined detection of retinol binding protein 4 (RBP4), cystatin C (CysC) and homocysteine (Hcy) for early diagnosis of diabetic nephropathy (DN). Methods: 98 diagnosed patients with type 2 diabetes were divided into 3 groups according to the excretion rate of urine albumin: normal albumin group (group A), trace albumin group (group B) and mass albumin group (group C), at the same time, 30 healthy subjects were taken as the nephropathy control group (NC group). The levels of serum RBP4, CysC, Hcy, blood urea nitrogen (BUN) and creatinine (Cr) were detected, and the results were statistically processed. Results: The serum RBP4, CysC and Hcy in group A, B and C were higher than those of NC group, and those of the group B and C were higher than those of group A, with statistically significant differences. There was no statistically significant difference of serum BUN and Cr level between group A, group B and NC group. ROC-AUC of combined detection in group B was 0.952, showing a higher accuracy. AUCs of RBP4, Hcy and CysC were 0.850, 0.824 and 0.817, while AUCs of BUN and Cr were 0.643 and 0.633. Conclusion: The serum RBP4, Hcy and CysC are sensitive indicators for early diagnosis of DN. And the combined detection can improve the accuracy in early diagnosis of DN.
2014 Vol. 44 (6): 452- [Abstract] ( 595 ) HTML (1 KB)  PDF  (0 KB)  ( 341 )
455 Observation on the therapeutie effect of HAA regimen as induction chemotherapy for newly diagnosed acute myelogenous leukemia in the elderly
SONG Yanping1, LE Jing1, WAN Bin1, DAI Hui1, CHEN Dengbin1, TONG Yin2, XU Weilai2, JIN Jie2

Objective: To analyse the treatment outcome of 20 newly diagnosed acute myeloid leukemia (AML) in the elderly patients, and explore the efficacy and safety of HAA regimen, which consisting of homoharringtonine (HHT), cytarabine (Ara-C) and aclarubicin (Acla). Methods: All of the patients enrolled were treated with HAA regimen. The complete remission (CR) rate was observed. Results: Out of the 20 patients, 14 (70%) attained CR and the first single course of this induction regimen resulted in a CR rate of 60%. The main side effects included myelosuppression, infections and gastrointestinal disorders. These side effects improved by support and anti-infection therapy and generally did not affect the treatment. Conclusion: HAA regimen is a safe regimen and it is efficacious, well-tolerable induction therapy for newly diagnosed AML in the elderly. A high CR rate can be achieved with only one or two courses of this regimen.
2014 Vol. 44 (6): 455- [Abstract] ( 790 ) HTML (1 KB)  PDF  (0 KB)  ( 419 )
471 Effect of vinorelbine combined with xeloda on treating the patients with advanced breast cancer
XU Zhengyang, YUAN Zuguo, ZHOU Taoqi, YANG Hui, YUAN Guangbo, REN Ruiping
2014 Vol. 44 (6): 471- [Abstract] ( 629 ) HTML (1 KB)  PDF  (0 KB)  ( 374 )
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