超声造影定量与动态增强MRI定量在宫颈癌诊断中的应用价值

摘要 目的：探究超声造影定量与动态增强MRI定量在宫颈癌诊断中的应用价值。方法：选择2016年1月至2019年1月于我院接受治疗的86例疑似宫颈癌患者为实验组,另选取同期于我院接受治疗的50例宫颈良性病变患者为对照组,分别对两组患者实施超声造影定量检测及动态增强MRI检查,对比两组患者各参数组间差异性,同时以病理学检测结果为金标准,分析两种检查手段对宫颈癌的筛查效果并实施组间比较。结果：（1）比较显示实验组患者的峰值强度（peak intensity,PI）及时间-曲线下面积（area under curve,AUC）均高于对照组,达峰时间（time to peak,TTP）及平均渡越时间（mean transit time,MTT）均低于对照组（P<0.05）;（2）比较显示实验组患者的容积转移常数（volume transfer constant,K ^trans ）、速率常数（rate constant,k _ep ）以及血管外细胞外容积分数（extravascular extracellular volume fraction,V _e ）均高于对照组,表观扩散系数（apparent diffusion coefficient,ADC）低于对照组（P<0.05）;（3）以病理学检测结果为金标准,超声造影定量检测对宫颈癌检测一致性为93.02 %,灵敏度为94.44 %,特异度为85.71 %,增强MRI对宫颈癌检测一致性为96.51%,灵敏度为98.61%,特异度为85.71%。结论：宫颈癌患者实施超声造影定量与增强MRI检测时检测参数与正常宫颈组织相比会出现明显的差异性,可将上述两种检测方式用于宫颈癌患者的筛查诊断中。     

超声造影检查对早期甲状腺单发结节良恶性的鉴别诊断价值

目的:建立以甲状腺单发结节超声诊断为变量的回归模型,分析比较超声造影与常规超声检查对甲状腺单发结节良恶性的鉴别诊断价值。方法:选择来我院就诊的甲状腺单发结节患者274例,让所有患者均接受常规超声检查和超声造影检查,并手术后进行病理诊断,建立相应回归模型,评价超声造影对甲状腺单发性良恶性结节的鉴别诊断价值,为临床检查及治疗提供参考。结果:超声造影检查的良恶性检出率均优于常规超声检查。超声造影检查良性结节检出率为65.69%,恶性检出率为34.31%,敏感度96.70%,特异度95.65%,准确率96.35%,均优于常规超声检查。Logistic回归分析显示,钙化、达峰时间、增强程度及最大灌注强度以上四项特征出现的越多,待测的甲状腺结节越有可能是恶性结节。结论:超声造影对良、恶性甲状腺单发结节的鉴别具有重要的临床诊断意义。     

Unsupervised clustering of fMRI and MRI time series

Unsupervised clustering represents a powerful technique for self-organized segmentation of biomedical image time series data describing groups of pixels exhibiting similar properties of local signal dynamics. The theoretical background is presented in the beginning, followed by several medical applications demonstrating the flexibility and conceptual power of these techniques. These applications range from functional MRI data analysis to dynamic contrast-enhanced perfusion MRI and breast MRI. For fMRI, these methods can be employed to identify and separate time courses of interest, along with their associated spatial patterns. When applied to dynamic perfusion MRI, they identify groups of voxels associated with time courses that are clinically informative and straightforward to interpret. In breast MRI, a segmentation of the lesion is achieved and in addition a subclassification is obtained within the lesion with regard to regions characterized by different MRI signal time courses. In the present paper, we conclude that unsupervised clustering techniques provide a robust method for blind analysis of time series image data in the important and current field of functional and dynamic MRI.     

Assessment of Early Tumor Response to Cytotoxic Chemotherapy with Dynamic Contrast-Enhanced Ultrasound in Human Breast Cancer Xenografts

There is a strong need to assess early tumor response to chemotherapy in order to avoid adverse effects from unnecessary chemotherapy and allow early transition to second-line therapy. This study was to quantify tumor perfusion changes with dynamic contrast-enhanced ultrasound (CEUS) in the evaluation of early tumor response to cytotoxic chemotherapy. Sixty nude mice bearing with MCF-7 breast cancer were administrated with either adriamycin or sterile saline. CEUS was performed on days 0, 2, 4 and 6 of the treatment, in which time-signal intensity (SI) curves were obtained from the intratumoral and depth-matched liver parenchyma. Four perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WiAUC), wash-in rate (WiR) and wash-in perfusion index (WiPI) were calculated from perfusion curves and normalized with respect to perfusion of adjacent liver parenchyma. Histopathological analysis was conducted to evaluate tumor perfusion, tumor cell density, microvascular density (MVD) and proliferating cell density. Significant decreases of tumor normalized perfusion parameters (i.e., nPE, nWiAUC, nWiR and nWiPI) were noticed between adriamycin-treated and control groups (P<0.01) 2 days after therapy. There were significant differences of tumor volumes between control and treated groups on day 6 (P<0.001) while there were no significant differences in tumor volume on days 0, 2 and 4 (P>0.05). Significant decreases of tumor perfusion, tumor cell density, MVD and proliferating cell density were seen in adrianycin-treated group 2 days after therapy when compared to control group (P<0.001). Dynamic CEUS for quantification of tumor perfusion could be used for early detection of cancer response to cytotoxic chemotherapy prior to notable tumor shrinkage.     

A new method to study changes in microvascular blood volume in muscle and adipose tissue: real-time imaging in humans and rat

We employed and evaluated a new application of contrast-enhanced ultrasound for real-time imaging of changes in microvascular blood volume (MBV) in tissues in females, males, and rat. Continuous real-time imaging was performed using contrast-enhanced ultrasound to quantify infused gas-filled microbubbles in the microcirculation. It was necessary to infuse microbubbles for a minimum of 5-7 min to obtain steady-state bubble concentration, a prerequisite for making comparisons between different physiological states. Insulin clamped at a submaximal concentration (～75 μU/ml) increased MBV by 27 and 39% in females and males, respectively, and by 30% in female subcutaneous adipose tissue. There was no difference in the ability of insulin to increase muscle MBV in females and males, and microvascular perfusion rate was not increased significantly by insulin. However, perfusion rate of the microvascular space was higher in females compared with males. In rats, insulin clamped at a maximal concentration increased muscle MBV by 60%. Large increases in microvascular volume and perfusion rate were detected during electrical stimulation of muscle in rats and immediately after exercise in humans. We have demonstrated that real-time imaging of changes in MBV is possible in human and rat muscle and in subcutaneous adipose tissue and that the method is sensitive enough to pick up relatively small changes in MBV when performed with due consideration of steady-state microbubble concentration. Because of real-time imaging, the method has wide applications for determining MBV in different organs during various physiological or pathophysiological conditions.     

The central performance drop in texture segmentation: a simulation based on a spatial filter model

 This article presents a computational model of early visual information processing that attempts to account for the central performance drop (CPD) in texture segmentation. CPD is the finding that detection performance on short stimulus displays of line textures using orientation differences to set off the target is not maximal at the foveal center but in parafoveal areas. A comparison between a simulation and psychophysical experimental data supported the assumption that the CPD may be explained by properties of spatial frequency channels whose band-pass filter characteristics are not constant over the retina but differ with eccentricity in a defined manner. The model provided satisfactory predictions of experimental data based on densely or widely spaced line elements in texture fields. It is concluded that preattentive texture analysis might be performed by a relatively small number of simple spatial filters. Received: 14 November 1996 / Accepted in revised form: 3 June 1997     

Optical and acoustical dynamics of microbubble contrast agents inside neutrophils

Acoustically active microbubbles are used for contrast-enhanced ultrasound assessment of organ perfusion. In regions of inflammation, contrast agents are captured and phagocytosed by activated neutrophils adherent to the venular wall. Using direct optical observation with a high-speed camera and acoustical interrogation of individual bubbles and cells, we assessed the physical and acoustical responses of both phagocytosed and free microbubbles. Optical analysis of bubble radial oscillations during insonation demonstrated that phagocytosed microbubbles experience viscous damping within the cytoplasm and yet remain acoustically active and capable of large volumetric oscillations during an acoustic pulse. Fitting a modified version of the Rayleigh-Plesset equation that describes mechanical properties of thin shells to optical radius-time data of oscillating bubbles provided estimates of the apparent viscosity of the intracellular medium. Phagocytosed microbubbles experienced a viscous damping approximately sevenfold greater than free microbubbles. Acoustical comparison between free and phagocytosed microbubbles indicated that phagocytosed microbubbles produce an echo with a higher mean frequency than free microbubbles in response to a rarefaction-first single-cycle pulse. Moreover, this frequency increase is predicted using the modified Rayleigh-Plesset equation. We conclude that contrast-enhanced ultrasound can detect distinct acoustic signals from microbubbles inside of neutrophils and may provide a unique tool to identify activated neutrophils at sites of inflammation.     

Validation of Perfusion Quantification with 3D Gradient Echo Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using a Blood Pool Contrast Agent in Skeletal Swine Muscle

The purpose of our study was to validate perfusion quantification in a low-perfused tissue by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with shared k-space sampling using a blood pool contrast agent. Perfusion measurements were performed in a total of seven female pigs. An ultrasonic Doppler probe was attached to the right femoral artery to determine total flow in the hind leg musculature. The femoral artery was catheterized for continuous local administration of adenosine to increase blood flow up to four times the baseline level. Three different stable perfusion levels were induced. The MR protocol included a 3D gradient-echo sequence with a temporal resolution of approximately 1.5 seconds. Before each dynamic sequence, static MR images were acquired with flip angles of 5°, 10°, 20°, and 30°. Both static and dynamic images were used to generate relaxation rate and baseline magnetization maps with a flip angle method. 0.1 mL/kg body weight of blood pool contrast medium was injected via a central venous catheter at a flow rate of 5 mL/s. The right hind leg was segmented in 3D into medial, cranial, lateral, and pelvic thigh muscles, lower leg, bones, skin, and fat. The arterial input function (AIF) was measured in the aorta. Perfusion of the different anatomic regions was calculated using a one- and a two-compartment model with delay- and dispersion-corrected AIFs. The F-test for model comparison was used to decide whether to use the results of the one- or two-compartment model fit. Total flow was calculated by integrating volume-weighted perfusion values over the whole measured region. The resulting values of delay, dispersion, blood volume, mean transit time, and flow were all in physiologically and physically reasonable ranges. In 107 of 160 ROIs, the blood signal was separated, using a two-compartment model, into a capillary and an arteriolar signal contribution, decided by the F-test. Overall flow in hind leg muscles, as measured by the ultrasound probe, highly correlated with total flow determined by MRI, R = 0.89 and P = 10⁻⁷. Linear regression yielded a slope of 1.2 and a y-axis intercept of 259 mL/min. The mean total volume of the investigated muscle tissue corresponds to an offset perfusion of 4.7mL/(min ⋅ 100cm³). The DCE-MRI technique presented here uses a blood pool contrast medium in combination with a two-compartment tracer kinetic model and allows absolute quantification of low-perfused non-cerebral organs such as muscles.     

A study of non-invasive Patlak quantification for whole-body dynamic FDG-PET studies of mice

Physiological changes in dynamic PET images can be quantitatively estimated by kinetic modeling technique. The process of PET quantification usually requires an input function in the form of a plasma-time activity curve (PTAC), which is generally obtained by invasive arterial blood sampling. However, invasive arterial blood sampling poses many challenges especially for small animal studies, due to the subjects' limited blood volume and small blood vessels. A simple non-invasive quantification method based on Patlak graphical analysis (PGA) has been recently proposed to use a reference region to derive the relative influx rate for a target region without invasive blood sampling, and evaluated by using the simulation data of human brain FDG-PET studies. In this study, the non-invasive Patlak (nPGA) method was extended to whole-body dynamic small animal FDG-PET studies. The performance of nPGA was systematically investigated by using experimental mouse studies and computer simulations. The mouse studies showed high linearity of relative influx rates between the nPGA and PGA for most pairs of reference and target regions, when an appropriate underlying kinetic model was used. The simulation results demonstrated that the accuracy of the nPGA method was comparable to that of the PGA method, with a higher reliability for most pairs of reference and target regions. The results proved that the nPGA method could provide a non-invasive and indirect way for quantifying the FDG kinetics of tumor in small animal studies.     

超声造影和超声弹性成像在甲状腺良恶性结节鉴别诊断中的临床价值

目的:探讨超声造影与超声弹性成像鉴别诊断甲状腺良恶性结节的临床价值。方法:回顾性分析2011年1月-2013年6月我院经病理证实的128例甲状腺占位性病变患者(160个结节)的超声影像学资料,其中恶性结节68个,良性占位92个,评估实时超声造影与超声弹性成像诊断甲状腺良性与恶性结节的敏感性、特异性、准确率、阳性预测值及阴性预测值。结果:甲状腺良性结节超声造影检查以快进慢出、高增强为主;恶性结节以慢进快出、低增强为主。超声造影诊断甲状腺良、恶性结节的灵敏度、特异度与阳性预测值、阴性预测值及其诊断符合率分别为91.18%、92.39%、91.18%、93.41%、91.88%;超声弹性成像分别为89.71%、90.22%、87.14%、92.22%、90.00%,联合检查分别为94.12%、95.65%、94.12%、95.65%、95.00%,均高于常规超声的57.35%、72.83%、60.94%、69.79%、65.63%,比较差异有统计学意义(P0.05);联合检查灵敏度、符合率明显高于超声造影与超声弹性成像单一检查,比较差异有统计学意义(P0.05)。结论:超声造影与超声弹性成像在鉴别诊断甲状腺良恶性结节中均具有较高的应用价值,两种方法联合检查灵敏度及准确性更高。     

超声造影在肝癌分级应用中的前瞻性研究

目的：利用超声造影研究高分化和低分化肝癌患者的肿瘤血流灌注情况,探讨超声造影在肝癌分级的诊断价值。方法：选择我院原发性肝癌（HCC）患者65例并根据活检肝细胞癌病变和肿瘤分级不同分为A组37例（高分化组）和B组28例（低分化组）,对两组患者行超声造影检查,分析超声造影的血流灌注状态。结果：A组与B组病灶的到达时间（AT）、峰值时间（TTP）和峰值强度（PI）均存在显著的差异性（tAT=7．266,PAT=0．000;tTTP=5．966,PTTP=0．000;tPI=8．219,PPI=0．000）。A组与B组间的病灶增强时间（1）、增强斜率（2）、清除时间（3）、清除斜率（4）具有差异,并且差异具有统计学意义（t1=7．266,PI=0．000;t2=317,P2=0．000;t3=8．880,P3=0．000;t4=6．178,P4=0．000）。结论：超声造影可作为一种新型的肝癌分级方法,对于早期诊断肝癌和获得肿瘤分级具有很大的临床价值。     

Functional and structural characteristics of tumor angiogenesis in lung cancers overexpressing different VEGF isoforms assessed by DCE- and SSCE-MRI

The expressions of different vascular endothelial growth factor (VEGF) isoforms are associated with the degree of tumor invasiveness and the patient's prognosis in human cancers. We hypothesized that different VEGF isoforms can exert different effects on the functional and structural characteristics of tumor angiogenesis. We used dynamic contrast-enhanced MRI (DCE-MRI) and steady-state contrast-enhanced MRI (SSCE-MRI) to evaluate in vivo vascular functions (e.g., perfusion and permeability) and structural characteristics (e.g., vascular size and vessel density) of the tumor angiogenesis induced by different VEGF isoforms (VEGF121, VEGF165, and VEGF189) in a murine xenograft model of human lung cancer. Tumors overexpressing VEGF189 were larger than those overexpressing the other two VEGF isoforms. The K(trans) map obtained from DCE-MRI revealed that the perfusion and permeability functions of tumor microvessels was highest in both the rim and core regions of VEGF189-overexpressing tumors (p<0.001 for both tumor rim and core). The relative vessel density and relative vessel size indexes derived from SSCE-MRI revealed that VEGF189-overexpressing tumors had the smallest (p<0.05) and the most-dense (p<0.01) microvessels, which penetrated deeply from the tumor rim into the core, followed by the VEGF165-overepxressing tumor, whose microvessels were located mainly in the tumor rim. The lowest-density microvessels were found in the VEGF121-overexpressing tumor; these microvessels had a relatively large lumen and were found mainly in the tumor rim. We conclude that among the three VEGF isoforms evaluated, VEGF189 induces the most densely sprouting and smallest tumor microvessels with the highest in vivo perfusion and permeability functions. These characteristics of tumor microvessels may contribute to the reported adverse effects of VEGF189 overexpression on tumor progression, metastasis, and patient survival in several human cancers, including non-small cell lung cancer, and suggest that applying aggressive therapy may be necessary in human cancers in which VEGF189 is overexpressed.     

超声造影在甲状腺结节鉴别诊断及良性结节微波消融治疗中的应用价值

摘要 目的：研究超声造影在甲状腺结节鉴别诊断及良性结节微波消融治疗中的应用价值。方法：选取2015年1月～2018年2月我院收治的甲状腺结节患者100例作为研究对象,所有纳入对象均进行超声造影检查,分析甲状腺结节的超声造影特征,并与病理诊断结果进行对照。此外,将甲状腺良性结节患者以随机抽签法分成超声造影组31例和常规超声组30例。超声造影组微波消融治疗前后均予以超声造影配合,常规超声组微波消融治疗前后均予以常规超声配合。比较两组治疗前后甲状腺结节造影情况以及术后1年结节复发情况。结果：甲状腺恶性结节增强强度为低增强、增强模式为不均匀、无环绕增强占比均高于良性结节（均P＜0.05）。以病理诊断为金标准,超声造影诊断恶性甲状腺结节的灵敏度为92.31%、特异度为78.69%、准确度为84.00%。治疗后超声造影组甲状腺结节最长径、体积均低于常规超声组（均P＜0.05）。超声造影组术后1年结节复发率为0.00%,低于常规超声组的16.67%（P＜0.05）。结论：超声造影应用于甲状腺结节鉴别诊断的价值较高,且结合微波消融治疗良性结节的效果明显,预后理想,值得临床推广应用。     

Lung perfusion impairments in pulmonary embolic and airway obstruction with noncontrast MR imaging.

A noncontrast electrocardiography (ECG)-gated, fast-spin-echo magnetic resonance imaging was applied to noninvasively define perfusion impairments in pulmonary embolic and airway obstruction dog models. Two-phase ECG-gated lung images of the minimal lung signal intensity during systole and maximal signal intensity during diastole were acquired by using optimized R-wave triggering delay times in seven dogs anesthetized with pentobarbital sodium before, soon after, and 2 mo after embolization with enbucrilate and in another eight dogs before and after bronchial occlusion with balloon catheters, in combination with a gadolinium diethylenetriaminepentaacetic acid-enhanced dynamic study. An ECG-gated subtraction image between the two-phase lung images provided a uniform but gravity-dependent perfusion map in normal lungs. Furthermore, it defined all 13 variable-size perfusion deficits associated with pulmonary embolism and the dynamically decreased perfusion with time after bronchial occlusion in all the airway obstruction models. These results were consistent with contrast-enhanced pulmonary arterial perfusion phase images. This noncontrast imaging could be equivalent to a contrast-enhanced dynamic study in the definition of regionally impaired pulmonary arterial perfusion in pulmonary embolism and airway obstruction.     

超声造影在肝癌射频消融治疗前后的临床价值研究

目的:探讨实时超声造影(contrast-enhanced ultrasonography,CEUS)在原发性肝癌射频消融(radiofrequency ablation,RFA)微创介入前后治疗临床应用价值的研究。方法:通过分析139例肝癌患者175个病灶在超声引导下射频消融(RFA)治疗,对病灶数量、大小、边界、内部回声、造影剂灌注情况进行对比分析,及治疗后与增强CT结果进行对照。结果:射频消融前,超声造影显示82个病灶表现为动脉早期抱球状、弥漫或轻度增强;治疗1-3个月后超声造影判定89.1%(156/175)的病灶达到完全消融,10.9%(19/175)的病灶消融不完全;增强CT判定84.6%(148/175)的病灶达到完全消融,15.4%(27/175)的病灶消融不完全,治疗后超声造影检查结果与CT增强检查结果一致,两者在病灶残留复发的敏感性、特异性、准确性等方面比较无显著性差异,P>0.01。结论:实时超声造影(CEUS)能准确判断RFA对肿瘤消融的范围及程度,是一种指导治疗,判定治疗后疗效的新方法,在原发性肝癌(RFA)微创介入治疗中具有很高的临床应用价值。     

Statistical quantification of methylation levels by next-generation sequencing

Background/Aims

Recently, next-generation sequencing-based technologies have enabled DNA methylation profiling at high resolution and low cost. Methyl-Seq and Reduced Representation Bisulfite Sequencing (RRBS) are two such technologies that interrogate methylation levels at CpG sites throughout the entire human genome. With rapid reduction of sequencing costs, these technologies will enable epigenotyping of large cohorts for phenotypic association studies. Existing quantification methods for sequencing-based methylation profiling are simplistic and do not deal with the noise due to the random sampling nature of sequencing and various experimental artifacts. Therefore, there is a need to investigate the statistical issues related to the quantification of methylation levels for these emerging technologies, with the goal of developing an accurate quantification method.

Methods

In this paper, we propose two methods for Methyl-Seq quantification. The first method, the Maximum Likelihood estimate, is both conceptually intuitive and computationally simple. However, this estimate is biased at extreme methylation levels and does not provide variance estimation. The second method, based on Bayesian hierarchical model, allows variance estimation of methylation levels, and provides a flexible framework to adjust technical bias in the sequencing process.

Results

We compare the previously proposed binary method, the Maximum Likelihood (ML) method, and the Bayesian method. In both simulation and real data analysis of Methyl-Seq data, the Bayesian method offers the most accurate quantification. The ML method is slightly less accurate than the Bayesian method. But both our proposed methods outperform the original binary method in Methyl-Seq. In addition, we applied these quantification methods to simulation data and show that, with sequencing depth above 40–300 (which varies with different tissue samples) per cleavage site, Methyl-Seq offers a comparable quantification consistency as microarrays.     

超声造影联合HE4、CA125、CA153在子宫内膜癌诊断中的价值研究

摘要 目的：为提高对子宫内膜癌的早期诊断,本研究对超声造影联合肿瘤标志物人附睾蛋白4（human epididymis protein-4,HE4）血清糖类抗原125（carbohydrate antigen 125,CA125）及153（CA153）在子宫内膜癌中的诊断价值进行研究。方法：以80例疑似子宫内膜癌患者为研究组,另以80例于本院体检的健康女性为对照组。对患者进行超声造影检查,比较两组血清HE4、CA125以及CA153水平,考察超声造影联合HE4、CA125及CA153对子宫内膜癌的诊断作用。结果：本研究中80例疑似患者中,子宫内膜癌患者有49例,子宫内膜良性病变患者31例,而超声造影检查显示子宫内膜癌患者有41例,良性病变39例,与金标准检查结果有一定的差异,单纯的超声造影检查对子宫内膜癌的诊断有局限性。子宫内膜癌和良性病变患者的病变区灌注的时间、增强强度以及增强均度都有显著差异（P<0.05）。对照组血清HE4、CA125及CA153水平分别为82.31±15.45 pmol/mL、22.31±6.21 U/mL、16.45±4.91 U/mL,研究组血清HE4、CA125及CA153水平分别为159.28±24.01 pmol/mL、42.88±5.73 U/mL、28.30±3.76 U/mL,经统计,研究组各项指标均显著高于对照组（P<0.05）。超声造影的灵敏度为79.3 %、特异度为67.34 %、阳性似然比为2.54、阴性似然比为0.25、阳性预测值为84.63 %、阴性预测值为60.51 %及符合率为72.19 %;联合检测的灵敏度为86.58 %、特异度为78.92 %、阳性似然比为3.11、阴性似然比为0.23、阳性预测值为93.19 %、阴性预测值为67.42 %及符合率为77.90 %。结论：超声造影联合HE4、CA125及CA153检测对子宫内膜癌诊断价值更高,HE4、CA125及CA153能辅助提高超声造影的诊断效果。     

超声造影定量参数联合血清TSH、Tg、外周血NLR在甲状腺结节良恶性诊断中的应用价值

摘要 目的：探讨超声造影定量参数联合血清促甲状腺激素（TSH）、甲状腺球蛋白（Tg）、外周血中性粒细胞与淋巴细胞比值（NLR）在甲状腺结节良恶性诊断中的应用价值。方法：选取2020年7月到2022年5月我院收治的80例甲状腺结节患者,根据病理学检查结果将其分为良性组(53例）和恶性组（27例）。所有甲状腺结节患者均行甲状腺超声造影并记录定量参数,检测血清TSH、Tg水平,计算NLR。以术后病理结果为准,采用受试者工作特征（ROC）曲线分析超声造影定量参数、血清TSH、Tg及NLR鉴别诊断甲状腺良恶性结节的价值。结果：经组织病理学确诊恶性甲状腺结节27例,良性甲状腺结节53例。恶性组超声造影定量参数平均渡越时间(mTT)、曲线下面积（AUCceus）低于良性组（P＜0.05）,血清TSH、Tg水平及NLR均高于良性组（P＜0.05）。超声造影定量参数mTT、AUCceus联合血清TSH、Tg及NLR鉴别诊断良恶性甲状腺结节的曲线下面积高于以上五项指标单独诊断。结论：恶性甲状腺结节患者超声造影定量参数mTT、AUCceus降低,且血清TSH、Tg水平及NLR增高,超声造影定量参数mTT、AUCceus联合血清TSH、Tg及NLR可提高鉴别诊断良恶性甲状腺结节的效能。     

An integrative and practical evolutionary optimization for a complex, dynamic model of biological networks

Computer simulation is an important technique to capture the dynamics of biochemical networks. Numerical optimization is the key to estimate the values of kinetic parameters so that the dynamic model reproduces the behaviors of the existing experimental data. It is required to develop general strategies for the optimization of complex biochemical networks with a huge space of search parameters, under the condition that kinetic and quantitative data are hardly available. We propose an integrative and practical strategy for optimizing a complex dynamic model by using qualitative and incomplete experimental data. The key technologies are the divide and conquer method for reducing the search space, handling of multiple objective functions representing different types of biological behaviors, and design of rule-based objective functions that are suitable for qualitative and error-prone experimental data. This strategy is applied to optimizing a dynamic model of the yeast cell cycle to demonstrate the feasibility of it.     

Computational fluid dynamics modeling of mass-transfer behavior in a bioreactor for hairy root culture. II. Analysis of ultrasound-intensified process

Recently, cichoric acid production from hairy roots of Echinacea purpurea was significantly improved by ultrasound stimulation in an airlift bioreactor. In this article, the possible mechanism on ultrasound-intensified hairy root culture of E. purpurea in the bioreactor was elucidated with the help of computational fluid dynamics (CFD) simulation, membrane permeability detection, dissolved oxygen concentration detection, confocal laser-scanning microscopy (LSM) observation, and phenylalanine ammonium lyase (PAL) activity analysis. The CFD model developed in Part I was used to simulate the hydrodynamics and oxygen mass transfer in hairy root bioreactor culture stimulated by ultrasound. A dynamic mesh model combined with a changing Schmidt number method was used for the simulation of the ultrasound field. Simulation results and experimental data illustrated that ultrasound intensified oxygen mass transfer in the hairy root clump, which subsequently stimulated root growth and cichoric acid biosynthesis. Ultrasound increased the hairy root membrane permeability, and a high root membrane permeability of 0.359 h(-1) was observed at the bottom region in the bioreactor. LSM observation showed that the change in the membrane permeability recovered to normal in the further culture after ultrasound stimulation. PAL activity in the hairy roots was stimulated by ultrasound increase and was correlated well to cichoric acid accumulation in the hairy roots of E. purpurea.