当前位置:主页 > 医学论文 > 生物医学论文 >

HIFU致焦域处回声增强和损伤形态改变的原因初探:空化和沸腾

发布时间:2018-07-21 09:10
【摘要】:研究背景 高强度聚焦超声(High Intensity Focused Ultrasound, HIFU)作为一种新兴的非侵入性治疗手段,已经应用于临床多种疾病的治疗,诸如子宫肌瘤、肝癌、肾癌、骨肿瘤、乳腺癌等实体肿瘤和过敏性鼻炎、关节炎、宫颈炎等非肿瘤性疾病中,并取得了良好的治疗效果。HIFU治疗的原理是将体外低能量的超声束聚焦到体内病灶处并形成高能量的焦点,利用超声对生物组织的热效应、空化效应和机械效应等使焦点处的温度瞬间升至56℃以上,导致该处组织形成不可逆的凝固性坏死,但不影响周围的正常组织,从而达到治疗的目的。 作为非侵入性治疗方式,必须要有可靠而准确的监控方式。目前所用的监控方式有B超和磁共振(Magnetic Resonance Imaging, MRI)。其中,B超监控具有实时性好、价格低廉、与HIFU设备兼容性好等优点,且B超监控的HIFU设备己大量应用于临床中。B超监控的原理是以HIFU辐照后即刻B超声像图中强回声的出现作为一个单元治疗完成的标志。但是,对于该强回声出现的原因,目前尚不甚明了有部分学者指出,出现强回声主要是HIFU致靶区空化行为产生的空化泡所致;也有学者指出是靶区温度上升产生的沸腾泡所致。 HIFU辐照后组织中所形成的凝固性坏死应为椭球形,但在某些情况下,坏死形态会发生变化,呈水滴状甚至三角形。关于该形态变化的原因,争论也集中在辐照中对HIFU束遮挡的空化泡和沸腾泡之间。 目前HIFU治疗所用的主要机制是热机制,但是其另一机制——空化机制发生时,可以在局部产生高温、高压、高速射流等极端物理现象,从而对组织造成损伤。且有研究者指出,HIFU辐照中强回声的出现意味着过度治疗,即能量的过度沉积而致靶区的温度过高,会影响到治疗的安全性。另有研究者指出,脉冲HIFU (pulsed High Intensity Focused Ultrasound, pHIFU)的应用可以避免靶区的明显温升,从而利用其非热效应。 基于上述背景,本研究基于一台商业HIFU肿瘤治疗系统,选择不同的辐照参数,辐照离体牛肝组织,以在焦域处产生空化泡和/或沸腾泡,在辐照后即刻采集B超声像图,与辐照前同一位置的声像图进行比较,并解剖牛肝组织,初步研究HIFU辐照中空化泡和沸腾泡对焦域处回声增强和凝固性坏死形态改变的影响。此外,本研究还利用pHIFU辐照离体牛肝组织,利用其非热效应,特别是空化效应对组织造成损伤,并对其损伤机制和B超监控进行了初步研究。 目的 1.初步研究HIFU辐照后即刻B超声像图中强回声出现的原因; 2.初步研究HIFU辐照所致凝固性坏死形态发生改变的原因; 3.利用pHIFU辐照离体组织,研究其造成非热损伤的可行性; 4.初步研究pHIFU辐照所致非热损伤的机制及B超监控的可行性。 方法 1.HIFU辐照离体组织中的空化和沸腾对B超强回声及凝固性坏死形态的影响 1.1实验材料:屠宰后6小时内的新鲜离体牛肝组织,取血管和结缔组织较少处切成约100mm×100mm×60mm大小的方块,置于生理盐水中脱气30min待用; 1.2实验仪器与设备:JC200型HIFU肿瘤治疗系统(凹球面聚焦,B超监控,频率0.94MHz);被动空化检测(Passive Cavitation Detection, PCD)系统:平面压电换能器(中心频率0.5MHz和5MHz),LabVIEW开发平台,水浸数据线等;温度采集系统:E型热电偶,温度巡检仪,数据采集程序和计算机等。 1.3实验方法: (1)校正HIFU声输出; (2)使用HIFU定点辐照脱气后的离体牛肝组织,深度为20mm,辐照参数为:50W×10s、50W×80s、100W×10s、150W×5s、200W×2s和200W×5s; (3)HIFU辐照过程中使用PCD系统采集焦域处的声发射信号(acoustic emissions,主要为空化信号)后对该信号进行快速傅立叶变换(Fast Fourier Trans form at ion, FFT)后记录次谐波和四次谐波的幅值随辐照时间的变化情况。另对该信号进行带通滤波(3~7MHz)和带阻滤波(滤除通带内的高次谐波)后计算其均方根(Root Mean Square,RMS),并得到RMS随辐照时间的变化曲线; (4)HIFU辐照中使用温度采集系统记录焦域处的温度,并绘制其随辐照时间变化的曲线;重复6次实验,对焦域处的最高温度进行统计学分析; (5)HIFU辐照后即刻采集B超声像图,并与辐照前同一位置的B超声像图进行比较,重复20次实验,对结果进行分析; (6)HIFU辐照结束后,将牛肝组织切成1~2mm厚的薄片,找到凝固性坏死最大面积所在层面,观察坏死的形态。2.脉冲HIFU辐照离体组织所致非热损伤的初步实验研究 2.1实验材料:同上; 2.2实验仪器与设备:同上; 2.3实验方法: (1)校正HIFU声输出,并调整HIFU输出为脉冲模式; (2)使用pHIFU定点辐照脱气后的离体牛肝组织,辐照参数见后表; (3)辐照中使用PCD系统采集焦域处的空化信号,并进行FFT变换,焦域处的温度由温度采集系统获取后绘制其随辐照时间的变化曲线,并得到6次辐照中焦域处的最高温度; (4)辐照后即刻,采集B超声像图,并与辐照前同一位置的B超声像图进行比较,计算靶区灰度的变化值; (5)辐照结束后,将牛肝组织切成厚为1~2mm的薄片,找到损伤最大面积所在层面,观察损伤形态,选取标本进行hematoxylin-eosin (HE)染色,并在光镜下观察。 声功率(W)占空比脉冲重复频率(Hz)辐照时间(s)深度(mm)1%602%305004203%204%15结果 1.所有参数的HIFU辐照中均可见次谐波出现;声功率为50W和100W的HIFU辐照中宽带噪声的RMS未见增大;声功率为150W的HIFU辐照中RMS开始较小,后增大;声功率为200W的HIFU辐照开始RMS即较大,在5s的辐照中有减弱趋势; 2.参数为50W×10s、50W×80s、100W×10s、150W×5s、200W×2s、200W×5s和的HIFU辐照中焦域处的最高温度分别为62.40±6.50℃、93.61±2.46℃、67.29±2.56℃、77.84±6.96℃、75.69±5.18℃和88.10±4.06℃; 3.参数为50W×10s、100W×10s、150W×5s和200W×2s的HIFU辐照后即刻B超声像图中未见强回声(强回声出现率分别为0、15%、10%和5%),凝固性坏死形态较规则;另2个参数的HIFU辐照后即刻B超声像图中观察到强回声出现(强回声出现率均为95%),辐照后坏死形态发生改变; 4.参数为50W×80s和200W×5s的HIFU辐照中四次谐波可见增加,且200W声功率的HIFU辐照中四次谐波增加后宽带噪声的RMS减小;5. pHIFU辐照后所致非热损伤为洞状,无固态内容物; 6.500W声功率下,1%~4%占空比的pHIFU辐照中焦域处的最高温度分别为41.19±1.42℃,45.73±1.92℃,53.07±2.09℃和64.13±2.56℃,且辐照中均可见明显的宽带噪声; 7. pHIFU辐照后即刻B超声像图中靶区灰度减小,回声变弱。 结论 1. HIFU辐照中焦域处的空化泡和沸腾泡对辐照结果的影响不同; 2. HIFU辐照后即刻B超声像图中强回声的出现和凝固性坏死形态的改变主要来自于辐照中焦域处由于温度升高所致沸腾泡对回声的散射和对HIFU束的遮挡; 3.PCD系统所采信号的频谱中四次谐波的增大可能与焦域处的沸腾泡有关,若上述关系成立,则当焦域处的温度约为80℃时,出现沸腾泡; 4. pHIFU辐照中焦域处的温升受占空比的影响,高声功率、低占空比的pHIFU辐照可以由非热效应在组织内产生非热损伤,且空化效应可能是该损伤产生的主要机制; 5.B超可用于pHIFU辐照所致非热损伤的监控,但其监控的算法、有效性、准确性等需要进一步研究。
[Abstract]:Research background
High Intensity Focused Ultrasound (HIFU), as a new noninvasive treatment, has been used in the treatment of various clinical diseases, such as uterine myoma, liver cancer, kidney cancer, bone tumor, breast cancer, allergic rhinitis, arthritis, cervicitis and other non tumor diseases, and has achieved good results. The therapeutic effect of.HIFU is based on the principle of focusing the low energy ultrasound beam in vitro to the focus of the body and forming a high energy focus. The thermal effect, the cavitation effect and the mechanical effect of ultrasound on the biological tissue increase to more than 56 degrees centigrade, leading to the formation of irreversible solidification necrosis of the tissue, but it does not affect the tissue. The normal tissue around it, so as to achieve the purpose of treatment.
As a non invasive treatment, it is necessary to have reliable and accurate monitoring methods. The monitoring methods currently used are B-ultrasound and Magnetic Resonance Imaging (MRI). The B-ultrasonic monitoring system has the advantages of good real-time, low price, and good compatibility with HIFU equipment, and the HIFU equipment monitored by B-ultrasound has been widely used in clinic. The principle of controlling the emergence of strong echoes in the immediate B-ultrasound image after HIFU irradiation is a symbol for the completion of a unit treatment. However, for the reason of the emergence of the strong echo, some scholars have pointed out that the emergence of strong echoes is mainly caused by cavitation bubbles produced by the cavitation behavior in the target area of the HIFU; and some scholars point out that the target area is the target area. The boiling bubble produced by the rise of temperature.
The solidified necrosis formed in the tissue after HIFU irradiation should be ellipsoid, but in some cases the morphology of the necrosis will change, in the form of water droplets and even triangles. The reason for the change of the morphology is also concentrated on the vacuoles and boiling bubbles that are shielded by the irradiation of the HIFU beam.
At present, the main mechanism used for HIFU therapy is the thermal mechanism, but the other mechanism, cavitation mechanism, can produce extreme physical phenomena such as high temperature, high pressure, high speed jet and so on, which can cause damage to tissue. And some researchers point out that the emergence of strong echo in HIFU irradiation means overtreatment, that is, excessive deposition of energy. The high temperature of the target area affects the safety of the treatment. Other researchers point out that the application of pulse HIFU (pulsed High Intensity Focused Ultrasound, pHIFU) can avoid the obvious temperature rise in the target area, thus using its non thermal effect.
Based on the above background, this study, based on a commercial HIFU tumor treatment system, selects different irradiation parameters and irradiate isolated bovine liver tissues to produce cavitation bubbles and / or boiling bubbles at the focal region. The ultrasound images are collected immediately after irradiation, compared with the image of the same position before irradiation, and the bovine liver tissue is dissected and the HIFU spoke is preliminarily studied. The effects of hollowing and boiling bubbles on the morphological changes of echo enhancement and coagulation necrosis at the focal region. In addition, this study also uses pHIFU to irradiate bovine liver tissue in vitro, using its non thermal effect, especially the cavitation effect to tissue damage, and the damage mechanism and B ultrasonic monitoring of its damage mechanism are preliminarily studied.
objective
1. preliminary study of the causes of strong echoes in B-mode ultrasound after HIFU irradiation.
2. the causes of morphologic changes of coagulative necrosis induced by HIFU irradiation were preliminarily studied.
3. irradiating tissues in vitro with pHIFU, and studying the feasibility of non thermal damage.
4. preliminary study on the mechanism of pHIFU radiation induced non thermal injury and the feasibility of B-mode monitoring.
Method
Effects of cavitation and boiling on the morphology of hyperechoic and coagulative necrosis of B-ultrasound in vitro irradiated by 1.HIFU
1.1 experimental materials: fresh isolated bovine liver tissues in 6 hours after slaughtering were cut into about 100mm x 100mm x 60mm size in less blood vessels and connective tissues and degassed in physiological saline for 30min.
1.2 experimental instruments and equipment: JC200 HIFU tumor treatment system (concave spherical focus, B ultrasonic monitoring, frequency 0.94MHz); passive cavitation detection (Passive Cavitation Detection, PCD) system: planar piezoelectric transducer (central frequency 0.5MHz and 5MHz), LabVIEW development platform, water immersion data line and so on; temperature acquisition system: E type thermocouple, temperature patrol A test instrument, a data acquisition program and a computer, etc.
1.3 the method of experiment:
(1) correction of HIFU sound output;
(2) the isolated bovine liver tissue after HIFU degassing was irradiated with 20mm at a depth of 20mm, and the irradiation parameters were: 50W * 10s, 50W x 80s, 100W * 10s, 150W x 5S, 200W * x and X * x;
(3) in the process of HIFU irradiation, the PCD system is used to collect the acoustic emission signals at the focal region (acoustic emissions, mainly as a cavitation signal), and then the amplitude of the second harmonic and the four harmonic is changed with the radiating time of the fast Fu Liye transform (Fast Fourier Trans form at ion, FFT). The signal is also filtered by band pass filter (3 Root Mean Square (RMS) was calculated after the band elimination filter (filtered the high order harmonics in the passband), and the RMS curve with the irradiation time was obtained; 7MHz Mean was used.
(4) the temperature of the focal region was recorded by the temperature collection system in HIFU irradiation, and the curves of the change with the irradiation time were plotted, and the 6 experiments were repeated to analyze the highest temperature at the focal region.
(5) after the irradiation of HIFU, the B-mode ultrasound images were collected and compared with the B-ultrasound images at the same location before the irradiation, and the results were repeated 20 times.
(6) after HIFU irradiation, the bovine liver tissue was cut into 1 ~ 2mm thick slices, and the maximum area of the coagulation necrosis was found. The preliminary experimental study on the non thermal damage caused by the necrotic morphologic.2. pulse HIFU irradiation in vitro tissue was observed.
2.1 experimental materials: the same;
2.2 experimental instruments and equipment: the same;
2.3 the method of experiment:
(1) correct the HIFU output and adjust the HIFU output to pulse mode.
(2) the irradiated parameters of bovine liver tissue after degassing were irradiated by pHIFU.
(3) the PCD system is used to collect the cavitation signal at the focal region and FFT transform. The temperature of the focal region is obtained by the temperature acquisition system, and the change curve with the irradiation time is drawn, and the highest temperature in the focal region at the 6 irradiation is obtained.
(4) after the irradiation, the B-mode ultrasound images were collected and compared with the b-sonograms at the same location before the irradiation, and the change of the gray level of the target area was calculated.
(5) after irradiation, the bovine liver tissue was cut into thin slices of 1 ~ 2mm. The maximum area of the injury was found and the damage morphology was observed. The specimens were stained with hematoxylin-eosin (HE) and observed under light microscope.
Acoustic power (W) duty cycle pulse repetition frequency (Hz) time of irradiation (s) depth (mm) 1%602%305004203%204%15 result
1. all the secondary harmonics in all the HIFU irradiated parameters are visible, and the RMS of broadband noise in the HIFU irradiation with the sound power of 50W and 100W does not increase; RMS begins to be smaller and then increases in the HIFU irradiation of the sound power of 150W, and the HIFU irradiation with the sound power of 200W is larger than that of the RMS, and it has a weakening trend in the irradiation of the 5S.
The 2. parameters are 50W x 10s, 50W x 80s, 100W x 10s, 150W x 5S, 200W x 2S, 200W * 5S and the focal regions of the focal region are 62.40 + 6.50 C, 93.61 + 2.46, 67.29 + 2.56, 77.84 + 6.96, 75.69 + 5.18 and 88.10 + 4.06.
The 3. parameters were 50W * 10s, 100W x 10s, 150W * 5S and 200W x 2S. There was no strong echo (the occurrence rate of strong echo was 0,15%, 10% and 5%). The morphology of coagulation necrosis was more regular. The other 2 parameters were observed in the immediate B-ultrasound image after HIFU irradiation (the occurrence rate of strong echo was 95%), and necrosis after irradiation. Morphological changes;
The four harmonics in the 4. parameters of 50W * 80s and 200W x 5S increase in the HIFU irradiation, and the RMS of the wideband noise decreases after the increase of the four harmonic waves in the HIFU irradiation of the 200W sound power; the non thermal damage is a hole like and no solid content after 5. pHIFU irradiation.
Under 6.500W sound power, the highest temperature in the focal region of pHIFU irradiated from 1% to 4% occupying space ratio is 41.19 + 1.42 C, 45.73 + 1.92, 53.07 + 2.09 and 64.13 + 2.56, and there are obvious wide-band noise in the radiation.
7. after pHIFU irradiation, the intensity of the target area decreases and the echo weakens.
conclusion
1. the effects of cavitation bubbles and boiling bubbles on focal radiation in HIFU irradiation are different.
2. HIFU after irradiation, the appearance of strong echo and the change of the morphology of coagulation necrosis mainly come from the scattering of the ebulliate to the ebulliate and the occlusion of the HIFU beam in the irradiated focal region due to the increase of temperature.
The increase of the four harmonic in the frequency spectrum of the signal produced by the 3.PCD system may be related to the boiling bubble in the focal region. If the above relationship is established, the boiling bubble appears when the temperature of the focal region is about 80 C.
In 4. pHIFU radiation, the temperature rise in the focal region is affected by the duty ratio. The pHIFU irradiation with high sound power and low duty ratio can produce non thermal damage in the tissue by the non thermal effect, and the cavitation effect may be the main mechanism of the damage.
5. B ultrasound can be used to monitor the non thermal damage caused by pHIFU radiation. However, the algorithm, validity and accuracy of its monitoring should be further studied.
【学位授予单位】:重庆医科大学
【学位级别】:硕士
【学位授予年份】:2012
【分类号】:R318.0

【相似文献】

相关期刊论文 前10条

1 张园园;;84例子宫肌瘤B超声像图分析[J];咸宁学院学报(医学版);2011年04期

2 夏利,郭建德;螺丝钉滞留回盲部声像图1例[J];中国超声诊断杂志;2000年01期

3 鄢秀菊,邹建中,吴成富,谢昭鹏,彭剑萍;白内障术前超声检查的临床意义[J];临床超声医学杂志;2002年01期

4 姬军;潘美玲;张春霞;;超声图像的质量评价[J];医疗卫生装备;2010年12期

5 陈良,方惠民,申亚伟,王志梅;B型超声在上颌窦疾病诊断中的应用[J];天津医药;1995年04期

6 张丽萍,朱晓兰,陈松,赫双赤,张红,李卫;小肠平滑肌肉瘤的声像图表现[J];中国肿瘤临床与康复;1997年02期

7 王琼,高芹;对子宫肌腺病声像图征象的再认识[J];中国医学影像技术;1998年06期

8 虞梅,刘康永,王骊,钦晨,何海萍,钱武凌,王慧,曹亮,李顺钧,施利华;彩色多普勒超声检测肝豆状核变性的肝脏改变[J];上海医学影像;2004年03期

9 赵凤英;5例肠套叠的声像图特征[J];中国超声医学杂志;1996年04期

10 宋丽萍,赵芳,王柳松,马维田;彩色多普勒超声在大肠癌诊断中的应用价值[J];实用肿瘤学杂志;2000年02期

相关会议论文 前10条

1 黄大斌;;彩色多谱勒高频超声对浅表软组织肿物的诊断方法和价值[A];第十次全国中西医结合影像学术研讨会暨全国中西医结合影像学研究与诊断学习班资料汇编[C];2009年

2 程文;黄巍;;乳腺癌声像图征象与分子生物学之间的相关性研究[A];中华医学会第十次全国超声医学学术会议论文汇编[C];2009年

3 阎红焱;;超声诊断肾血管平滑肌脂肪瘤[A];中国医学影像技术学术研讨会论文集(下)[C];2004年

4 陆正生;;药线点灸疗法治疗一例[A];2005全国首届壮医药学术会议暨全国民族医药经验交流会论文汇编[C];2005年

5 蒋洁;;声像图陷阱:肾脏假肿瘤[A];中华医学会超声医学新进展学术会议论文汇编[C];2004年

6 袁静义;;超声对黄色肉芽肿性肾盂肾炎声像图的体会[A];2006年浙江省超声医学学术年会论文汇编[C];2006年

7 张云飞;王学梅;;成簇点状强回声在前列腺癌诊断中的应用[A];庆祝中国超声诊断50年暨第十届全国超声医学学术会议论文汇编[C];2008年

8 熊惠军;;超声成像技术在宠物临床上的应用[A];中国畜牧兽医学会小动物医学分会第四次学术研讨会、中国畜牧兽医学会兽医外科学分会第十六次学术研讨会论文集(1)[C];2009年

9 张云姣;赵博文;潘美;杨园;杨倩;徐海珊;王蓓;;超声心动图对胎儿心脏强回声结构的检测及其心功能评价[A];第十届全国超声心动图学术会议论文[C];2010年

10 赵玉华;陈宁宁;江泉;姚炜;;乳腺导管扩张与乳汁淤积症声像图的多种表现[A];第九届全国超声医学学术会议论文汇编[C];2006年

相关重要报纸文章 前10条

1 胡泽华;六类胆结石诊断诀窍[N];农村医药报(汉);2008年

2 解放军第546医院超声科主任 胡泽华;六类胆结石诊断诀窍[N];健康报;2008年

3 赖才魁 高营光;镜头笔头见证创业足迹 声像图文传播龙岩形象[N];闽西日报;2011年

4 佚名;基层有实用疗法[N];农村医药报(汉);2008年

5 白文佩;异常出血祸起内膜息肉[N];健康报;2006年

6 北京大学第一医院妇产科 白文佩;异常出血警惕内膜息肉[N];健康报;2007年

7 牡丹江医学院第二附属医院教授 米丰年;多科合作 诊治不难[N];健康报;2009年

8 ;解读肝胆B超报告单[N];上海中医药报;2006年

9 郝晨阳;头颅B超为新生儿脑损伤护航[N];健康报;2006年

10 健康时报特约记者 时仲省;滥服“性药”易致子宫内膜癌[N];健康时报;2008年

相关博士学位论文 前10条

1 李海东;瘢痕的超高频超声影像学研究[D];中国协和医科大学;2008年

2 邓立新;羊胚胎移植过程中的B超动态监测研究及图谱创建[D];中国农业大学;2005年

3 孙咏梅;甲状腺癌的超声显像与骨桥蛋白表达及微血管密度测定的相关研究[D];山东大学;2009年

4 侯俊剑;基于声像模式识别的故障诊断机理研究[D];上海交通大学;2011年

5 鲁文波;基于声场空间分布特征的机械故障诊断方法及其应用研究[D];上海交通大学;2012年

6 李成志;超声治疗外阴白色病变的临床研究(附:慢性宫颈炎超声治疗的临床研究)[D];重庆医科大学;2003年

7 娄丽;肝静脉和肝内门静脉的断层影像解剖及三维重建[D];山东大学;2007年

8 李文秀;超声造影引导脾脏创伤的止血治疗研究[D];中国人民解放军军医进修学院;2008年

9 朱庆莉;超声对乳腺病变的诊断及病理学对照研究[D];中国协和医科大学;2004年

10 张惠琴;超声造影在肝外伤诊断及局部注射治疗中的应用研究[D];中国人民解放军军医进修学院;2008年

相关硕士学位论文 前10条

1 艾慧坚;HIFU致焦域处回声增强和损伤形态改变的原因初探:空化和沸腾[D];重庆医科大学;2012年

2 易华容;HIFU辐照过程中温升、空化与强回声的相关性研究[D];重庆医科大学;2011年

3 陈功义;兽用B超在现代养猪生产中的综合应用技术研究[D];河南农业大学;2007年

4 王章斌;兽用B超在奶牛生产过程中的应用研究[D];河南农业大学;2009年

5 田超;兽用B超在猪繁育中的应用研究[D];河南农业大学;2009年

6 程怿;高频超声在肘管综合征诊断中的应用[D];复旦大学;2008年

7 张冬;彩色多普勒超声在乳腺癌新辅助化疗中的应用价值[D];中南大学;2008年

8 孙圣礼;高强度聚焦超声应用于兔脑的可行性研究[D];南华大学;2006年

9 刘永军;高强度聚焦超声脾脏消融治疗脾功能亢进的动物实验研究[D];重庆医科大学;2005年

10 姚庆荣;高频超声在通风性关节炎的临床应用研究[D];昆明医科大学;2012年



本文编号:2135040

资料下载
论文发表

本文链接:https://www.wllwen.com/yixuelunwen/swyx/2135040.html


Copyright(c)文论论文网All Rights Reserved | 网站地图 |

版权申明:资料由用户4d5af***提供,本站仅收录摘要或目录,作者需要删除请E-mail邮箱bigeng88@qq.com