喉癌前病变中医证候与iNOS和VEGF表达关系及金喉片治疗的研究
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摘要
喉癌前病变(Laryngeal Precancerosis)乃喉上皮增生性病变(epithelial
hyperplastic lesions of the larynx,EHLL)中的一种特殊类型,是一类比正常粘膜更易发生癌变的病理学变化。主要包括有慢性肥厚性喉炎(hyperplastic
laryngitis);喉角化症(keratosis of the larynx),包括喉黏膜白斑病(leukoplakia)和喉厚皮病(pachydermia);成人的喉乳头状瘤(papilloma of the larynx)。临床上并非所有的喉癌前病变都最终发展为喉癌,一些可部分或完全消退,部分保持原有形态,仅少数在内源性和外源性有害因素作用下继续恶化或演变成癌。因此,及早识别和控制这些病变,研究其临床表现、病理组织学特点及其与恶变之间关系,对防止癌变的发生发展在理论上和实践上都有重要意义。
中医古籍中并无“喉癌前病变”这一名称,但根据其反复不愈的声嘶特点,把其归属于“慢喉喑”“喉瘤”的范畴。喉癌前病变的喉局部表现为粘膜充血暗红肥厚、增生隆起,与中医学的血瘀证相一致,微循环障碍为其最基本的病理改变。中医证候本质是反映人体生理、病理的改变,应与蛋白质的变化有密切关系,蛋白质的动态性、可调节性、可加工、可修饰性更符合中医证候的可变性、多样性,因此,研究蛋白质与中医证候的相关性有重要意义。
本课题以与喉癌前病变密切相关的诱导型一氧化氮合酶(inducible nitric
oxide synthase,iNOS)和血管内皮生长因子(vascular endothelial growth factor,VEGF)为切入点,采用免疫组织化学技术,从细胞、分子水平上探讨喉癌前病变与中医血瘀证密切相关的微观指标,以及微循环障碍在癌前病变到发生癌变这一量变到质变的过程中所起的影响,找寻一种有助于判断喉癌前病变发展趋势的量化微观指标,确定其基本中医证型,同时观察具有活血化瘀散结作用的金喉片对本病的干预作用,应用中医药阻断和逆转喉癌前病变,为中医药进行防癌、抗癌治疗提供理论和临床依据。
一、文献研究
本文先推本溯源,复习了中医学古文献中有关喉癌前病变病名、病因、病机及治疗等方面文献,并且对近十年来关于中医治疗喉癌前病变研究进展作了一综述。然后概述了西医学对喉癌前病变的概念、病因、分类、诊断及治疗,诱导型一氧化氮合酶和血管内皮生长因子与喉癌的关系以及嗓音的客观检测等相关研究进展。
二、临床研究
目的:探索金喉片对血瘀型喉癌前病变的干预作用。
方法:选取符合纳入标准的血瘀型喉癌前病变患者30例,采用金喉片口服治疗,每次4片,每日3次,以14天为一疗程,连续用药2个疗程,在治疗第14天、第28
Laryngeal precancerosis is a particular type of EHLL. It is a kind of pathologic change which is more inclined to be cancerated than the normal mucous membrane. It mainly includes hyperplastic laryngitis, keratosis of the larynx (including leukoplakia and pachydermia) and adults' papilloma of the larynx. In clinic, not all the precancerosis of laryngeal cancer finally lead to laryngeal cancer. Some of them can partly or even completely disappear. Some of them remain its precancerous condition. Only minority of them will deteriorate into laryngeal cancers owing to endogenous or exogenous harmful factors. So, it plays a significant role in preventing the cancerization of laryngeal cancers both in theory and practice by diagnosing and controlling the pathological changes betimes, studying it's clinical manifestation, histological features and the relationship between their histological features and canceration.Laryngeal precancreosis was never mentioned in TCM ancient books. However, it was classified into the chronic hoarseness in light of its characteristic of repeated hoarseness. The local symptom in patient' s throat manifests itself as congestive, purple mucous membrane with hypertrophy hyperplasia and swelling, which is consistent with the blood stasis TCM theory. Circulation disorder is the basic pathological changes of the disease. The essence of TCM symptom reflects the physiologic and pathologic changes in human body which was considered to have close relationship with protein changes. Furthermore,the instability and adjustability of protein are more consistent with thevariability and variety of symptom in TCM. So, the study on the correlation between protein and TCM symptom is significant.
INOS and VEGF were taken as the breakthrough point, which all have close relation with laryngeal precancerosis, with the immunohistoche-mical technique, We tried to find some micro-indexes that can indicate the correlation between laryngeal precancerosis and the blood stasis syndrome in TCM from cellar and molecular level, studying how micro-circulation disorder effects human body in the process from a precancerous condition to cancer, looking for some objective microindexes which are helpful to estimate the developing trend of Laryngeal precancerosis, identifying what type of syndrome a certain case is, observing the effects of the JinHou tablet which has been proved to be able to activate blood and dissipate stagnation as well. It can provide a lot of evidences of preventing and treating cancers with Chinese medicine by the research of blocking and reversing laryngeal precancerosis with Chinese medicine.1 Literature studyAt the beginning we made a review about the names, causes, pathomechanism and treatments of laryngeal precancreosis in ancient books. We also gave a general summarization about the recent progress in treating laryngeal precancerosis with Chinese medicine in recent 10 years. Then the research progress of the definition, causes, classification, diagnosis and therapy of Laryngeal precancerosis in western medicine theory, the relationship study on between the carcinoma of larynx and the INOS and the VEGF, the voice objective detection as well were all summarized.2 Clinical studyObjective:To investigate the efficacy of intervention of the JinHou tablet on the treatment of laryngeal precancerosis with blood stasis syndrome.Methods:30 cases with proved laryngeal precancerosis identified as blood stasis syndrome were chosen. The patients in the trial group were treated with JinHou tablets per os, with a dose of four tablets every time, three times a day. A course consists of 14 days. All the treatment lasted for two courses. A symptom and physical sign examination and computing analysis of voice were conducted respectively at the 14th, 28th day and two months later. The safety were checked once pre-treatment and post-treatment respectively. Self PA comparision statistical method were implemented to the analysis of the
curative effects.Results:A course later, the dominant healing rate was 43.30%. 83.30% for the end of the treatment, 73. 30% for the two -month - later-follow-up survey. There was significant difference between pre-treatment and post-treatment in the symptoms, physical signs and parameters of voice (includes SHIMMER JITTER NNE MPT) (P< 0. 01). No reverse effects was observed among 20 patients in the trial group. The safety of all cases is grade one.Conclusions:The JinHou tablet has the function of activating blood circulation, removing blood stagnation and dissipating stasis. The clinical study proved that the JinHou tablet can remarkably improved laryngeal precancerosis patient' s symptoms, physical signs as well as the voice quality. So, the tablet has a definite effect to treat laryngeal precancerosis by blocking up the development of canceration of laryngeal precancerosis without any harmful or side effect. Therefore, it deserves to be popularized and used in clinicin treating such disease. 3 Laboratory study Objective:To investigate the correlation between the essence of TCM syndrome of laryngeal precancerosis and the expression of INOS and VEGF in the level of genetic protein expression.Methods:10 paraffin embedded samples of laryngeal precancerosis identified as blood stasis syndrome were chosen as the trial group and 10 paraffin embedded tissue sections of laryngeal precancerosis with phlegm-dampness syndromes were chosen as the control grouop. 10 paraffin-embedded materials of laryngeal cancer stored in the department of pathology in Guangdong provincial TCM hospital were chosen as the laryngeal cancer grouop. Respectively, measuring their expression of INOS/VEGF and protein with the immunohistochemical technique.Results:? In the laryngeal cancer group, the positive expression rate of the JNOS and VEGF is 100.00% and 90.00% respectively. While in the trial groui/\he/~~
rate is 80. 00% and 60. 00% respectively. In the control group, the rate is 30. 00% and 30. 00% respectively. There was siginificant difference between any two groups in the positive rate of the INOS and VEGF among three groups.(2) There was a significant close correlation between the expression of the INOS and VEGF and the hermorheobgy (P<0. 01) .(3) There was a positive correlation between the expression of the INOS and the expression of the VEGF (/>< 0. 05) .Conclusions:(D The experimental study showed that VEGF and iNOS of all samples in three groups expressed positively at different degrees. There was a significant difference in the expression of IONS and VEGF between any two groups among three groups. There was a significant close correlation between the expression of the INOS and VEGF and the hermorheobgy. Base on the results mentioned above, we considered that blood stasis syndrome in TCM is the basic TCM type of laryngeal precancerosis.(2) There was a positive correlation between the expression of INOS and VEGF. So, we considered that in the process of blood vessel generating of laryngeal precancerosis or laryngeal cancer, INOS and VEGF may interact to accelerate the generation of new blood vessel, which play an important role in the onset and development of laryngeal cancer. 4 ConclusionsThe JinHou tablet has a definite effect to treat laryngeal precancerosis. It can remarkably improve the patient' s voice quality, blocking up the development of canceration of laryngeal precancerosis. The expression of INOS and VEFG can be an index for evaluating the disease condition of laryngeal precancerous and forecasting the risk of canceration. The blood stasis syndrome is a basic TCM type of laryngeal precancerosis.
hyperplastic lesions of the larynx,EHLL)中的一种特殊类型,是一类比正常粘膜更易发生癌变的病理学变化。主要包括有慢性肥厚性喉炎(hyperplastic
laryngitis);喉角化症(keratosis of the larynx),包括喉黏膜白斑病(leukoplakia)和喉厚皮病(pachydermia);成人的喉乳头状瘤(papilloma of the larynx)。临床上并非所有的喉癌前病变都最终发展为喉癌,一些可部分或完全消退,部分保持原有形态,仅少数在内源性和外源性有害因素作用下继续恶化或演变成癌。因此,及早识别和控制这些病变,研究其临床表现、病理组织学特点及其与恶变之间关系,对防止癌变的发生发展在理论上和实践上都有重要意义。
中医古籍中并无“喉癌前病变”这一名称,但根据其反复不愈的声嘶特点,把其归属于“慢喉喑”“喉瘤”的范畴。喉癌前病变的喉局部表现为粘膜充血暗红肥厚、增生隆起,与中医学的血瘀证相一致,微循环障碍为其最基本的病理改变。中医证候本质是反映人体生理、病理的改变,应与蛋白质的变化有密切关系,蛋白质的动态性、可调节性、可加工、可修饰性更符合中医证候的可变性、多样性,因此,研究蛋白质与中医证候的相关性有重要意义。
本课题以与喉癌前病变密切相关的诱导型一氧化氮合酶(inducible nitric
oxide synthase,iNOS)和血管内皮生长因子(vascular endothelial growth factor,VEGF)为切入点,采用免疫组织化学技术,从细胞、分子水平上探讨喉癌前病变与中医血瘀证密切相关的微观指标,以及微循环障碍在癌前病变到发生癌变这一量变到质变的过程中所起的影响,找寻一种有助于判断喉癌前病变发展趋势的量化微观指标,确定其基本中医证型,同时观察具有活血化瘀散结作用的金喉片对本病的干预作用,应用中医药阻断和逆转喉癌前病变,为中医药进行防癌、抗癌治疗提供理论和临床依据。
一、文献研究
本文先推本溯源,复习了中医学古文献中有关喉癌前病变病名、病因、病机及治疗等方面文献,并且对近十年来关于中医治疗喉癌前病变研究进展作了一综述。然后概述了西医学对喉癌前病变的概念、病因、分类、诊断及治疗,诱导型一氧化氮合酶和血管内皮生长因子与喉癌的关系以及嗓音的客观检测等相关研究进展。
二、临床研究
目的:探索金喉片对血瘀型喉癌前病变的干预作用。
方法:选取符合纳入标准的血瘀型喉癌前病变患者30例,采用金喉片口服治疗,每次4片,每日3次,以14天为一疗程,连续用药2个疗程,在治疗第14天、第28
Laryngeal precancerosis is a particular type of EHLL. It is a kind of pathologic change which is more inclined to be cancerated than the normal mucous membrane. It mainly includes hyperplastic laryngitis, keratosis of the larynx (including leukoplakia and pachydermia) and adults' papilloma of the larynx. In clinic, not all the precancerosis of laryngeal cancer finally lead to laryngeal cancer. Some of them can partly or even completely disappear. Some of them remain its precancerous condition. Only minority of them will deteriorate into laryngeal cancers owing to endogenous or exogenous harmful factors. So, it plays a significant role in preventing the cancerization of laryngeal cancers both in theory and practice by diagnosing and controlling the pathological changes betimes, studying it's clinical manifestation, histological features and the relationship between their histological features and canceration.Laryngeal precancreosis was never mentioned in TCM ancient books. However, it was classified into the chronic hoarseness in light of its characteristic of repeated hoarseness. The local symptom in patient' s throat manifests itself as congestive, purple mucous membrane with hypertrophy hyperplasia and swelling, which is consistent with the blood stasis TCM theory. Circulation disorder is the basic pathological changes of the disease. The essence of TCM symptom reflects the physiologic and pathologic changes in human body which was considered to have close relationship with protein changes. Furthermore,the instability and adjustability of protein are more consistent with thevariability and variety of symptom in TCM. So, the study on the correlation between protein and TCM symptom is significant.
INOS and VEGF were taken as the breakthrough point, which all have close relation with laryngeal precancerosis, with the immunohistoche-mical technique, We tried to find some micro-indexes that can indicate the correlation between laryngeal precancerosis and the blood stasis syndrome in TCM from cellar and molecular level, studying how micro-circulation disorder effects human body in the process from a precancerous condition to cancer, looking for some objective microindexes which are helpful to estimate the developing trend of Laryngeal precancerosis, identifying what type of syndrome a certain case is, observing the effects of the JinHou tablet which has been proved to be able to activate blood and dissipate stagnation as well. It can provide a lot of evidences of preventing and treating cancers with Chinese medicine by the research of blocking and reversing laryngeal precancerosis with Chinese medicine.1 Literature studyAt the beginning we made a review about the names, causes, pathomechanism and treatments of laryngeal precancreosis in ancient books. We also gave a general summarization about the recent progress in treating laryngeal precancerosis with Chinese medicine in recent 10 years. Then the research progress of the definition, causes, classification, diagnosis and therapy of Laryngeal precancerosis in western medicine theory, the relationship study on between the carcinoma of larynx and the INOS and the VEGF, the voice objective detection as well were all summarized.2 Clinical studyObjective:To investigate the efficacy of intervention of the JinHou tablet on the treatment of laryngeal precancerosis with blood stasis syndrome.Methods:30 cases with proved laryngeal precancerosis identified as blood stasis syndrome were chosen. The patients in the trial group were treated with JinHou tablets per os, with a dose of four tablets every time, three times a day. A course consists of 14 days. All the treatment lasted for two courses. A symptom and physical sign examination and computing analysis of voice were conducted respectively at the 14th, 28th day and two months later. The safety were checked once pre-treatment and post-treatment respectively. Self PA comparision statistical method were implemented to the analysis of the
curative effects.Results:A course later, the dominant healing rate was 43.30%. 83.30% for the end of the treatment, 73. 30% for the two -month - later-follow-up survey. There was significant difference between pre-treatment and post-treatment in the symptoms, physical signs and parameters of voice (includes SHIMMER JITTER NNE MPT) (P< 0. 01). No reverse effects was observed among 20 patients in the trial group. The safety of all cases is grade one.Conclusions:The JinHou tablet has the function of activating blood circulation, removing blood stagnation and dissipating stasis. The clinical study proved that the JinHou tablet can remarkably improved laryngeal precancerosis patient' s symptoms, physical signs as well as the voice quality. So, the tablet has a definite effect to treat laryngeal precancerosis by blocking up the development of canceration of laryngeal precancerosis without any harmful or side effect. Therefore, it deserves to be popularized and used in clinicin treating such disease. 3 Laboratory study Objective:To investigate the correlation between the essence of TCM syndrome of laryngeal precancerosis and the expression of INOS and VEGF in the level of genetic protein expression.Methods:10 paraffin embedded samples of laryngeal precancerosis identified as blood stasis syndrome were chosen as the trial group and 10 paraffin embedded tissue sections of laryngeal precancerosis with phlegm-dampness syndromes were chosen as the control grouop. 10 paraffin-embedded materials of laryngeal cancer stored in the department of pathology in Guangdong provincial TCM hospital were chosen as the laryngeal cancer grouop. Respectively, measuring their expression of INOS/VEGF and protein with the immunohistochemical technique.Results:? In the laryngeal cancer group, the positive expression rate of the JNOS and VEGF is 100.00% and 90.00% respectively. While in the trial groui/\he/~~
rate is 80. 00% and 60. 00% respectively. In the control group, the rate is 30. 00% and 30. 00% respectively. There was siginificant difference between any two groups in the positive rate of the INOS and VEGF among three groups.(2) There was a significant close correlation between the expression of the INOS and VEGF and the hermorheobgy (P<0. 01) .(3) There was a positive correlation between the expression of the INOS and the expression of the VEGF (/>< 0. 05) .Conclusions:(D The experimental study showed that VEGF and iNOS of all samples in three groups expressed positively at different degrees. There was a significant difference in the expression of IONS and VEGF between any two groups among three groups. There was a significant close correlation between the expression of the INOS and VEGF and the hermorheobgy. Base on the results mentioned above, we considered that blood stasis syndrome in TCM is the basic TCM type of laryngeal precancerosis.(2) There was a positive correlation between the expression of INOS and VEGF. So, we considered that in the process of blood vessel generating of laryngeal precancerosis or laryngeal cancer, INOS and VEGF may interact to accelerate the generation of new blood vessel, which play an important role in the onset and development of laryngeal cancer. 4 ConclusionsThe JinHou tablet has a definite effect to treat laryngeal precancerosis. It can remarkably improve the patient' s voice quality, blocking up the development of canceration of laryngeal precancerosis. The expression of INOS and VEFG can be an index for evaluating the disease condition of laryngeal precancerous and forecasting the risk of canceration. The blood stasis syndrome is a basic TCM type of laryngeal precancerosis.
引文
[1] 蔡福养,王永钦,主编.嗓音病的中医论治,北京:人民卫生出版社,1988,第一版:65～66.
[2] 王德鉴.中医耳鼻咽喉口腔科学,北京:人民卫生出版社,1994,第一版:466～467.
[3] 干祖望,著.干氏耳鼻咽喉口腔科学,南京:江苏科学技术出版社,1999,第一版:230.
[4] 王永钦.中医药学高级丛书·中医耳鼻咽喉口腔科学,北京:人民卫生出版社,2001,第一版:745.
[5] 蔡福养,王永钦,主编.嗓音病的中医论治,北京:人民卫生出版社,1988,第一版:156.
[6] 余养居,张守杰,胡素琴,主编.中西医结合嗓音病学,上海:知识出版社,1996,第一版:444.
[7] 余养居,张守杰,胡素琴,主编.中西医结合嗓音病学,上海:知识出版社,1996,第一版:453.
[8] 程爵棠.中医喉科精义,北京:学苑出版社,1993,第一版:201.
[9] 曹建国,朱敏君,金杰,等.喉癌前期病变的中西医结合治疗分析.上海医药,2004;25(3):126～127.
[10] 陆兴,吴筱莉,苏虹,等.会厌逐瘀汤加味治疗慢性喉炎的临床观察.上海中医药杂志,2003:37(6):41～42.
[11] 蔡纪堂,柴峰.慢性肥厚性喉炎辨治体会.中国中医药信息杂志,2003:10(9):66.
[12] 匡奕蘅,蔡金波,魏小明.中医嗓音学研究近况.江西中医药,1989;(3):55～57.
[13] 白桦,刘瑞娟.慢性喉炎从痰诊治体会.中国农村医学,1994:22(4):54.
[14] 徐泳,俞军.化痰活血汤治疗慢性肥厚性喉炎临床研究.辽宁中医杂志,2000;27(9):401～402.
[15] 郑昌雄.中医药治疗喉白斑1例.中国中西医结合杂志,1996;16(6):329.
[16] 郭毅.温肾活血法治喉痦.四川中医,1994;(2):50～51.
[17] 姚松苗,丁志红.自拟益气清音汤治疗慢性喉炎46例疗效浅析.中国中西医结合耳鼻咽喉科杂志,1998;6(4):208.
[18] 万爱珍.二阴煎加减治疗慢性喉炎20例.实用中西医结合临床,2002:2(6):26～27.
[19] 徐静.干祖望教授对嗓音疾病的辨治.辽宁中医杂志,1987;(7):5～7.
[20] 陈正芳,陈肖琼.上焦宣痹汤治疗慢性结节型喉炎30例.实用中西医结合杂 志,1997;10(3):236.
[21] 周来兴,辜宝珠.养阴开音汤治疗慢喉喑210例.福建中医药,2002;33(3):32～33.
[22] 于洁.桔梗甘草汤加味治疗慢喉喑57例疗效观察.甘肃中医,2003;16(6):15.
[23] 王济生,赵春霞,乔自军.活血开音汤治疗肥厚性喉炎42例.四川中医,1999;17(5):47.
[24] 郑昌雄,忻耀杰,李春芳.中医中药治疗喉白斑.上海中医药杂志,2003;37(1):41～42.
[25] 严道南,徐静,陈小宁.润喉开音片的临床和血液流变学观察.江苏中医,1996;17(6):38～39.
[26] 严道南,张蕾,卞慧明,等.开音片对微循环影响的临床和实验研究.实用中西医结合杂志,1998;11(12):1066～1067.
[27] 孙志强.喉炎清治疗慢性喉炎162例.山西中医,2003;19(6):17.
[28] 金嫣莉.针刺治疗喉痦50例临床总结.中国针灸,1994;14(5):25～26.
[29] 姜荣华.针刺治疗喉喑30例.上海针灸杂志,1996;15(3):8.
[30] 陈国琴.针刺治疗喉喑32例疗效分析.针灸临床杂志,2003;19(11):31～32.
[31] 邵素霞.针灸治疗喉痦38例.河南中医,2003;23(9):69.
[32] 崔允孟.耳针治疗声嘶症150例疗效观察.中级医刊,1993;18(10):52～53.
[33] 曹华,曹景忠.耳针治疗声音嘶哑症68例.中国针灸,1996;(5):18.
[34] 张安福.消炎止痛膏治疗慢性喉炎效佳.四川中医,1989;(1):封3.
[35] 宋南昌.耳压配合中药治疗喉痦30例.江西中医药,1997;28(3):40.
[36] 金平林.鱼际隔蒜泥敷贴为主治疗喉喑26例.中国针灸,2001;21(10):592.
[37] 马玉杰,白力学,纪建芹.中药透入治疗慢性咽喉炎35例.中国民间疗法,1998;6(5):7.
[38] 彭向东.0.5%利多卡因加vitB12穴位注射治疗慢性喉炎25例报告.广东医学,1995;16(5):350～351.
[39] 宁齐放.当归注射液治疗急慢性喉炎161例.中国乡村医学,1994;(8):45.
[40] 杨华,仲彦.推拿法治疗慢性喉炎18例.中国民间疗法,1997;(5):33.
[41] 李云英,陈海,邓时贵,等.“金喉雾化剂”治疗慢性喉炎的疗效评价及计算机声图谱分析.中国中西医结合耳鼻咽喉科杂志,1999;7(3):114～117.
[42] 郭志正,孙月梅.中药超声雾化吸入治疗慢性喉炎50例.中国中西医结合耳鼻咽喉科杂志,2000;8(4):192.
[43] 乔宗海,徐洁洁,程雷,主编.现代喉部疾病诊断与治疗.南京:东南大学出版社,1999,第一版:178～183.
[44] Ferlito A, Carbone A, DeSanto LW." Early" cancer of the larynx: the concept as defined by clinicians, pathologists and biologists. Ann Otol Rhinol Laryngol, 1996;106:245～250.
[45] Henry RC, Batsakis JC, Chinn EK, et al. Acinic cell carcinoma: A clinicopath ological study of thirty-five cases. J Laryngol Otol, 1979;93:447～450.
[46] 王军,韩德民,叶京英,等.应用CO_2激光治疗可疑喉癌前病变.耳鼻咽喉-头颈外科,2001;8(4):217～219.
[47] 李惠萍,崔秀娟,关超,等.喉癌前病变100例分析.中华耳鼻咽喉科杂志,1995;30(5):302～304.
[48] Judd R, Zaki SR, Coffied LM, et al. Human papillomavirus type 6 detected by the polymerase chain reaction in invasive sionasal papillary squamous cell carcinomas. Arch Pathol Labmed, 1991;115:1150～1153.
[49] 李晓明,卜国弦,郭晓峰.喉癌的病因学研究进展.国外医学耳鼻咽喉科分册,1998;12(1):16.
[50] Quick CA, Wra M, Foucar E, et al. Ferquency and significance of epitheliae atypia in laryngeal papillomatosis. Laryngosope, 1979;89:550.
[51] Axidano MA, Singleton GT. Adjuvant drug strategies in the treatment of recur rent respiratory papillomatosis. Otolaryngol Head Neck Surg, 1995;112:197～202.
[52] 张小伯,刘丹丹,杨大章,等.早期喉癌与声带癌前病变的诊断和微创治疗.中华耳鼻咽喉科杂志,1999;34(6):337～339.
[53] Shaw H. Tumor of the larynx. Ballantyne J, Groves J. Scoth Brown' s diseases of the ear, nose and throat. London: Butterworth, 1979:109～122.
[54] 黄选兆,汪吉宝,主编.实用耳鼻咽喉科学.北京:人民卫生出版社,1998,第一版:501～502.
[55] Plch J, Par J, Navratilova J, et al. Long term follow-up study of laryngeal precancer. Auris Nasus Larynx, 1998;25:407～412.
[56] 王正敏,陆书昌,主编.现代耳鼻咽喉科学.北京:人民军事出版社,2001,第一版:952.
[57] 孙广滨,周水淼,王昶,等.Diomed-25半导体激光在治疗喉癌前病变中的应用.山东大学基础医学院学报,2003;17(3):158～159.
[58] Maran A. Head and neck surgery: An ercyciopaedia of ignorance. J Laryngol Otol,1990;104:529.
[59] 周剑勇,梁素霞.喉癌前病变DNA含量测定及细胞周期分析的意义.广东医学,2001;22(3):201～202.
[60] Merkel DE. Flow cytometry, cellular DNA contents and prognosis in human mall gnancy. J Clini Oncol, 1987;5(10):1690.
[61] Zariwala M, Schmlu S, Pialoz M, et al. P53 gene mutations in oropharyngeal carcinomas: A comparison of solitary and mutiple primary tumours and lymph node metastases. Int J Cancer, 1994;56(6):807.
[62] Hall PA, Ray A, Lemoine NR, et al. P53 immunostaining as a marker of mall gnant disease in diagnostic cytopathology. Lancet, 1991;338:513.
[63] 周光耀,林代诚,梁传余,等.P53蛋白在喉上皮癌前病变及癌组织中的表达及其意义.华西医大学报,1999;30(3):265～267.
[64] 肖健云,罗均利,陶正德,等.P53蛋白在喉癌及癌旁病变组织中的表达.中国耳鼻咽喉颅底外科杂志,1995;1(1):47～49.
[65] Bosatra A (ed): Acta Otolaryngol, 1997:Suppl:344.
[66] Henry RC: J Laryngol Otol, 1979;93:447.
[67] Carte RL: Precancerous State pl, Oxford University Press, 1984.
[68] 邓志宏,黄维国,邱建华等.血管生成及细胞凋亡与喉黏膜上皮癌变的关系.第四军医大学学报,1999;20(1):17～20.
[69] 孙德义,李学佩,孙晓东,等.一氧化氮合酶(NOS)在喉鳞癌中的表达及意义.耳鼻咽喉一头颈外科,2000;7(3):167～170.
[70] Mozota Ortiz JR. Cancer of the vocal cord, early diagnosis by stroboscopy. Acta Otorhinolaryngol Esp, 1998;28:91～104.
[71] 宋发全,张芩娜,王建亭,等.声带癌前病变及癌变动态喉镜追踪观察.中华耳鼻咽喉科杂志,2000;35(2):144～146.
[72] Guillermo J Tearney, Mark E Brezinski, Brett E Bouma, et al. In vivo endoscopic optical biopsy with optical coherence tomogyaphy. Science, 1997;276(27):2037～2039.
[73] Ralph S Dacosta, Brian C Wilson, Norman E Marcon. New optical technologies for earlier endoscopic diagnosis of premalignant gastrointestinal lesions. Journ al of Gastroenterology and Hepatology, 2002;17(suppl):S85～S104.
[74] Kulapadituarom Bet al. Ann Otol Rhinol Laryngol, 2001;110:45～52.
[75] 顾建森,李秋珍,张艳萍.喉癌前病变早期干预治疗.南京铁道医学院学 报,2000;19(2):129～130.
[76] Benjamin BN et al. Ann Otol Rhinol Lanyngol, 1988;97:376～380
[77] Healy GB et al. N Eng J Med, 1988;319:401～407.
[78] Leventhal GB et al. N Eng J Med, 1991;325:613～617.
[79] Mc cabe BF et al. Ann Otol Rhinol Lanyngol, 1987;96:158～162.
[80] Deunas LV et al. J Lanyngol Otol, 1997;111:134～140.
[81] Lagares GJA, Moore RA, Collier B, et al. Nitric oxide synthase as a marker in colorectal careinomal. Am Surg, 2001;67(7):709～713.
[82] Shochina M, Fellig Y, Sughayer M. et al. Nitric oxide synthase immunoreactivity in human bladder carcinoma. Molpathol, 2001;54(4):248～252.
[83] Gallo O, Masini E, Morbidelli L, et al. Role of nitric oxide in angiogenesis and tumor progression head and neck cancer. J Natl Cancer Insl, 1998;90(8):587～596.
[84] Kagoura M, Matsui C, Toyoda M, et al. Immunohistochemical study of inducible nitric oxide synthase in skin cancers. J Cutan Pathol, 2001;28(9):476～481.
[85] Rousseau S, Houle F, Huot J, et al. Integrating the VEGF signals leading to actin-based motility in vascular endothelial ceils. Trends Cardiovasc Med, 2000;10(8):321～327.
[86] Dvorak HF, Brown LF, Detmar M, et al. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Path, 1995;146(5):1029～1039.
[87] 李兰,郭晓峰,李浩川.VEGF与喉癌转移的免疫荧光定量研究及意义.中国肿瘤临床与康复,2002;9(4):61～62.
[88] 邓志宏,黄维国,邱建华,等.喉粘膜癌前病变和癌变中VEGF、bFGF和KGF的表达分析.肿瘤,1999;19(6):338～340.
[89] 邓志宏,黄维国,金岩,等.血管内皮生长因子在喉粘膜上皮良性及恶性变中的表达及定量.第四军医大学学报,1997;18(6):573.
[90] 王广义,王旭.胃癌组织NOS和VEGF表达与癌细胞增殖相关性的研究.外科理论与实践,2003;8(1):44～46.
[91] 黄昭明.嗓音和言语-言语病理学的基础和临床应用.见:王正敏主编.耳鼻喉科学新理论与新技术.上海:上海科技教育出版社,1997,第一版:151～162.
[92] 王正敏,主编.耳鼻喉科学新理论与新技术.上海:上海科技教育出版社,1997,第 一版:155～173.
[93] McGlone R, Hollien H. Vocal pitch characteristics of aged women. J Speech Hear Res, 1963;6:164～170.
[94] Murry, T. Speaking fundamental frequency characteristics associated with voice pathologies. J Speech Hear Res, 1978;21:374～379.
[95] 王正敏,编.耳鼻喉科学新理论与新技术.上海:上海科技教育出版社.1997,第一版:154～161.
[96] Yumoto E, Gould WJ, Baer T. Harmonic-to-noise ratio as an index of the degree of hoarseness. J. Acoust Soc Am, 1982;(71):1544～1550.
[97] De Korm G. A cepstrum-based technique for determining a harmonics-to-noise ratio in speech signals. J Spee Hear Res, 1993;(36):244～246.
[98] Kasuya H, Ogawa S, Mashima K. Normalized noise energy as an acoustic measure to evaluate pathologic voice. J Acoust Soc Am, 1986;(80):1329～1334
[99] Guus de Krom, A cepstrum-based technique for determining a harmonics-to-noise ratio in speech singals. J Spee Hear Res, 1993;(36):254～266.
[100] 韩仲明.喉发音功能的检测及其临床意义.中华耳鼻咽喉科杂志,1998;33(6):380～381.
[101] Kitajima K. Quatitative evaluation of the noise level in the pathologic voice. Folia Phoniatr, 1981;(33):115～124.
[102] Kikuchi, Y, Kasaya, H, Zue, W, &Hirano. M. (1993).An integrated acoustic voice evaluation system, Paper presented at ASHA convention, November. Anaheim.
[103] Arends N, Povel DJ, Van Os E. Prdeicting voice quality of deaf speakers on the basis of glottal characteristics. J Spee Hear Res. 1990;33:116～122.
[104] Bielamowicz S, Kreiman J, Gerratt BR. Comparison of voice analysis sytems for perturbation measurement. J Spee Hear Res, 1996;39:126～134.
[105] 杨式麟.喉发声功能检查(继7).听力学及言语疾病杂志,2001;9(2):124.
[106] 杨式麟著.嗓音医学基础与临床.沈阳:辽宁科学技术出版社,2001,第一版:185～247.
[107] 魏春生,张毅.电声门图和嗓音声学的同步化测试.听力学及言语疾病杂志,2001;9(2):78.
[108] Huang, Z. Minifie. F, &Lin, X(1995). Dr. Speech Science for Windows. Singular Publishing Group, Inc. San Diego, California, USA. (1996,1998,1999 by Tiger DRS, Inc.).
[109] Huang, Z. Voice lab in clinical practice. IALP, 1998:104.
[110] 杨式麟.频闪喉镜的原理和利用.中华耳鼻咽喉科杂志,1996;31(2):123.
[111] Karnetl Mp. Synchronized videostrobscopy and electroglottography. Jvoice, 1989;(3):68.
[112] 平野实.人类音声的客观评价.临床方面.国外医学耳鼻咽喉科学分册,1990;14(5):274.
[113] 中国中西医结合研究会中国抗癌协会中医诊断协作组.12448例癌症患者舌象临床观察.癌症,1987;7(3):129～130.
[114] 吴水生,郑东海,林求成.胃癌转移状态血液流变学变化与中医证型的关系的临床研究.中国中西医结合杂志,2000;20(8):583～585.
[115] 陈燕云,陈健民.芎龙汤对癌症患者血液高粘滞状态的影响.中成药研究,1987;(10):21～23.
[116] 甘长青,吴凯南.血管生成抑制剂.中国癌症临床,1998;25(11):845～847.
[117] 李晓林.血小板与癌症转移及活血化瘀中药的抗转移作用.中国中西医结合杂志,1989;9(10):637～639.
[118] 秦叔逵,钱军,杨爱珍.榄香烯乳抗肺癌细胞的实验研究.癌症防治研究,1996;23(4):251～255.
[119] 郁仁存.中医癌症学.上册.北京:科学出版社,1987,第一版:132.
[120] 陈婷梅,祝彼得.抗白血病中药及天然药物的研究现状.中国中西医结合杂志,1995;15(5):317～320.
[121] 黄韧敏,袁淑兰,宋毅.丹参酮ⅡA诱导HL-60细胞凋亡.癌症,1998;17(3):164～166.
[122] 马晓华,沃兴德,梁海漫.姜黄素抗癌症作用与诱导癌症细胞凋亡的研究概况.国外医学肿瘤学分册,1999;26(1):21～23.
[123] 李蒙,于建勋.单味中药诱导癌症细胞凋亡的实验研究现状及展望.中国中西医结合杂志,2001,21(1):74～76.
[124] 韩俊庆,陈延条,满运艳,等.复春片合并放射治疗鼻咽癌临床研究.中国中西医结合杂志,1995;15(12):710～712.
[125] 郁仁存,姜廷良,于尔辛.癌症研究.上海:上海科学技术出版社,1991:106.
[126] 张凤瑞.膈下逐瘀汤现代研究概述.中成药,1995;17(5):44～45.
[127] 程剑华.中医药治疗癌症疗效测评客观化研究的思路方法探讨.中国中西医结合 杂志,2000;20(8):625～627.
[128] 颜大海,朱树林,付宝忠.鸡胚法筛选具有血管生成抑制作用中药.黑龙江医药,1998;11(2):94.
[129] 孙茂峰,王茵萍,范刚启,等.关于活血化瘀对慢性萎缩性胃炎胃壁屏障作用的探讨.中国中西医结合杂志,2000;20(7):554～556.
[130] 血瘀证综合研究国际会议暨第四届全国活血化瘀研究学术会议纪要.中国中西医结合杂志,1995;15(12):755～757.
[131] 刘明章,黄贻穗,肖伟琪.丹参酮ⅡA磺酸钠对Lewis癌无促进生长与转移的作用.中国药理学报,1991;12(6):534～537.
[132] 彭康,莫孔炼,郑有顺.血府逐瘀汤加减方对CTX所致小鼠免疫功能低下的防治作用.中国药理与临床,1996;12(1):6～8.
[133] 李云英,薛宗义,莫莉莉,等.“金喉片”治疗声带小节的临床及药理实验研究.广州中医药大学学报,1995;02:10～13.
[134] 李云英,薛宗义,莫莉莉.声带小节患者甲皱微循环改变及中药金喉片对其影响.中国中西医结合耳鼻咽喉科杂志,1996;4(4):170～172.
[135] 区勇全,莫莉莉.金喉片的药理实验研究.河北中医,1995;17(2):38.
[136] Bloom ED, Pauloski BR, Hamaker RC. Functional outcome after surgery for prevention of pharyngospasms in tracheoesophageal speakers, part 1;speech characteristics. J Laryngoscope, 1995;105:1093.
[137] 杨式麟.嗓音的声学检测.听力学及言语疾病杂志,2001;9(4):255
[138] Giovanni A. Contribution a L'elaboration d'un protocole multiparametrique devaluation objective des dysphonies. These en Science, Universite de laMediterrannee, 1998.
[139] Schoentgen J. Presentation of problem:performance of jitter in discriminating between normal and dysphonic speakers, Appl Stoch Mod Data Anal, 1988;4:127～135.
[140] Karnell M. Laryngeal Perturbation Analysis:Minimum Length of Analysis Window. J Speech Hear Res, 1991;34:544～548.
[141] Bielamowicz S, Kreiman J, Gerrat BR, Dauer MS, Berke GS. Comparison of voice analysis systems for perturbation measurement. J Speech Hear Res, 1996;39:126～134.
[142] Deem J, Manning W, Knack J, Matesich J. The automatic extraction of pitch perturbation using microcomputers:some methodological considerations. J Speech Hear Res, 1989;32:689～697.
[143] Karnell M, Hall K, Landahl K. Comparison of fundamental frequency and perturbation measurements among three analysis systems. J Yoice, 1995;9:383～393.
[144] 许良中,主编.实用肿瘤病理方法学.上海:上海人民出版社,1997,第一版:223～224.
[145] Rosbe KW, Prazma J, Petrusz P, et al, Immunohistochemic alchar acterization of nitric oxide synthase activity in squamous cell carcinoma of the head and neck. Otolaryngol Head and Neck Surg, 1995;113(5):541～549.
[146] Thomsen LL, Miles DW, Happerfield L, et al. Nitric oxidesynthase activity in human breast cancer. Br J Cancer, 1995;72(1):41～44.
[147] Goldstein SR, Yang GY, Chen X, et al. Studies of iron deposits, inducible nitric oxidesynthase and nitrotyrosine in a rat model for esophageal adenocarcinoma. Carcinogenesis, 1998;19(8):1445～1449.
[148] 罗玉琴,吴开春,孙安华,等.浅表性胃炎、胃黏膜不典型增生及胃癌组织中COX-1、COX-2、iNOS表达的意义.中华消化杂志,2000;20(4):223～226.
[149] Jenkins DC, Charles IG, Thomsen LL. Roles of nitric oxide in tumor growth proc. Natl Acad Sci USA, 1995;92(10):4392～4396.
[150] 许传杰,王贵全,沙春蕊,等.喉癌组织中诱导型一氧化氮合酶的表达与微血管密度的关系及其临床意义.中国老年学杂志,2004;24(2):110～111.
[151] Dvorak HF, Brown LF, Detmar M, et al. Vascular permeability factor/vascular endothelial grouth factor, microvascular hyper permeability, and angiogenesis, Am J Pathol, 1995;146(5):1029～1039.
[152] Zondo S, Asano M, Matsuo K, et al. Vascular endothelial growth factor/vascularperm lability factoris detectable in the sera of tumor bearing mice and cancer patients. Biochim BiophysActa, 1994;1221:211～214.
[153] 薛倩,周光耀,邹剑,等.血管内皮生长因子在喉癌组织中的表达及其意义.华西医学,2004;19(3):366～367.
[154] 李正江,唐平章,张志超,等.喉癌组织血管内皮生长因子的表达与喉癌临床病理关系.临床耳鼻咽喉科杂志,2002;16(3):111～113.
[155] Kimura H, Weisz A, Kurashima Y, et al. Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxia-inducible factor-1 activity by nitric oxide. Blood, 2000;95(1):189～197.
[156] Hood JD, Meininger CJ, Ziche M, et al. VEGF upregulates eCNOS message, protein, and NO production in human endothelial cells. Am J Physol, 1998;274(3pt2):H1054～H1058.
[157] 姜淑梅.原发性肺癌30例的血液流变学观察.哈尔滨医药,1998;(2):24.
[158] 胡庆福,邓瑶函.血瘀型恶性肿瘤病人红细胞膜流动性及血液流变性的研究.肿瘤,1990;(7):10.
[2] 王德鉴.中医耳鼻咽喉口腔科学,北京:人民卫生出版社,1994,第一版:466～467.
[3] 干祖望,著.干氏耳鼻咽喉口腔科学,南京:江苏科学技术出版社,1999,第一版:230.
[4] 王永钦.中医药学高级丛书·中医耳鼻咽喉口腔科学,北京:人民卫生出版社,2001,第一版:745.
[5] 蔡福养,王永钦,主编.嗓音病的中医论治,北京:人民卫生出版社,1988,第一版:156.
[6] 余养居,张守杰,胡素琴,主编.中西医结合嗓音病学,上海:知识出版社,1996,第一版:444.
[7] 余养居,张守杰,胡素琴,主编.中西医结合嗓音病学,上海:知识出版社,1996,第一版:453.
[8] 程爵棠.中医喉科精义,北京:学苑出版社,1993,第一版:201.
[9] 曹建国,朱敏君,金杰,等.喉癌前期病变的中西医结合治疗分析.上海医药,2004;25(3):126～127.
[10] 陆兴,吴筱莉,苏虹,等.会厌逐瘀汤加味治疗慢性喉炎的临床观察.上海中医药杂志,2003:37(6):41～42.
[11] 蔡纪堂,柴峰.慢性肥厚性喉炎辨治体会.中国中医药信息杂志,2003:10(9):66.
[12] 匡奕蘅,蔡金波,魏小明.中医嗓音学研究近况.江西中医药,1989;(3):55～57.
[13] 白桦,刘瑞娟.慢性喉炎从痰诊治体会.中国农村医学,1994:22(4):54.
[14] 徐泳,俞军.化痰活血汤治疗慢性肥厚性喉炎临床研究.辽宁中医杂志,2000;27(9):401～402.
[15] 郑昌雄.中医药治疗喉白斑1例.中国中西医结合杂志,1996;16(6):329.
[16] 郭毅.温肾活血法治喉痦.四川中医,1994;(2):50～51.
[17] 姚松苗,丁志红.自拟益气清音汤治疗慢性喉炎46例疗效浅析.中国中西医结合耳鼻咽喉科杂志,1998;6(4):208.
[18] 万爱珍.二阴煎加减治疗慢性喉炎20例.实用中西医结合临床,2002:2(6):26～27.
[19] 徐静.干祖望教授对嗓音疾病的辨治.辽宁中医杂志,1987;(7):5～7.
[20] 陈正芳,陈肖琼.上焦宣痹汤治疗慢性结节型喉炎30例.实用中西医结合杂 志,1997;10(3):236.
[21] 周来兴,辜宝珠.养阴开音汤治疗慢喉喑210例.福建中医药,2002;33(3):32～33.
[22] 于洁.桔梗甘草汤加味治疗慢喉喑57例疗效观察.甘肃中医,2003;16(6):15.
[23] 王济生,赵春霞,乔自军.活血开音汤治疗肥厚性喉炎42例.四川中医,1999;17(5):47.
[24] 郑昌雄,忻耀杰,李春芳.中医中药治疗喉白斑.上海中医药杂志,2003;37(1):41～42.
[25] 严道南,徐静,陈小宁.润喉开音片的临床和血液流变学观察.江苏中医,1996;17(6):38～39.
[26] 严道南,张蕾,卞慧明,等.开音片对微循环影响的临床和实验研究.实用中西医结合杂志,1998;11(12):1066～1067.
[27] 孙志强.喉炎清治疗慢性喉炎162例.山西中医,2003;19(6):17.
[28] 金嫣莉.针刺治疗喉痦50例临床总结.中国针灸,1994;14(5):25～26.
[29] 姜荣华.针刺治疗喉喑30例.上海针灸杂志,1996;15(3):8.
[30] 陈国琴.针刺治疗喉喑32例疗效分析.针灸临床杂志,2003;19(11):31～32.
[31] 邵素霞.针灸治疗喉痦38例.河南中医,2003;23(9):69.
[32] 崔允孟.耳针治疗声嘶症150例疗效观察.中级医刊,1993;18(10):52～53.
[33] 曹华,曹景忠.耳针治疗声音嘶哑症68例.中国针灸,1996;(5):18.
[34] 张安福.消炎止痛膏治疗慢性喉炎效佳.四川中医,1989;(1):封3.
[35] 宋南昌.耳压配合中药治疗喉痦30例.江西中医药,1997;28(3):40.
[36] 金平林.鱼际隔蒜泥敷贴为主治疗喉喑26例.中国针灸,2001;21(10):592.
[37] 马玉杰,白力学,纪建芹.中药透入治疗慢性咽喉炎35例.中国民间疗法,1998;6(5):7.
[38] 彭向东.0.5%利多卡因加vitB12穴位注射治疗慢性喉炎25例报告.广东医学,1995;16(5):350～351.
[39] 宁齐放.当归注射液治疗急慢性喉炎161例.中国乡村医学,1994;(8):45.
[40] 杨华,仲彦.推拿法治疗慢性喉炎18例.中国民间疗法,1997;(5):33.
[41] 李云英,陈海,邓时贵,等.“金喉雾化剂”治疗慢性喉炎的疗效评价及计算机声图谱分析.中国中西医结合耳鼻咽喉科杂志,1999;7(3):114～117.
[42] 郭志正,孙月梅.中药超声雾化吸入治疗慢性喉炎50例.中国中西医结合耳鼻咽喉科杂志,2000;8(4):192.
[43] 乔宗海,徐洁洁,程雷,主编.现代喉部疾病诊断与治疗.南京:东南大学出版社,1999,第一版:178～183.
[44] Ferlito A, Carbone A, DeSanto LW." Early" cancer of the larynx: the concept as defined by clinicians, pathologists and biologists. Ann Otol Rhinol Laryngol, 1996;106:245～250.
[45] Henry RC, Batsakis JC, Chinn EK, et al. Acinic cell carcinoma: A clinicopath ological study of thirty-five cases. J Laryngol Otol, 1979;93:447～450.
[46] 王军,韩德民,叶京英,等.应用CO_2激光治疗可疑喉癌前病变.耳鼻咽喉-头颈外科,2001;8(4):217～219.
[47] 李惠萍,崔秀娟,关超,等.喉癌前病变100例分析.中华耳鼻咽喉科杂志,1995;30(5):302～304.
[48] Judd R, Zaki SR, Coffied LM, et al. Human papillomavirus type 6 detected by the polymerase chain reaction in invasive sionasal papillary squamous cell carcinomas. Arch Pathol Labmed, 1991;115:1150～1153.
[49] 李晓明,卜国弦,郭晓峰.喉癌的病因学研究进展.国外医学耳鼻咽喉科分册,1998;12(1):16.
[50] Quick CA, Wra M, Foucar E, et al. Ferquency and significance of epitheliae atypia in laryngeal papillomatosis. Laryngosope, 1979;89:550.
[51] Axidano MA, Singleton GT. Adjuvant drug strategies in the treatment of recur rent respiratory papillomatosis. Otolaryngol Head Neck Surg, 1995;112:197～202.
[52] 张小伯,刘丹丹,杨大章,等.早期喉癌与声带癌前病变的诊断和微创治疗.中华耳鼻咽喉科杂志,1999;34(6):337～339.
[53] Shaw H. Tumor of the larynx. Ballantyne J, Groves J. Scoth Brown' s diseases of the ear, nose and throat. London: Butterworth, 1979:109～122.
[54] 黄选兆,汪吉宝,主编.实用耳鼻咽喉科学.北京:人民卫生出版社,1998,第一版:501～502.
[55] Plch J, Par J, Navratilova J, et al. Long term follow-up study of laryngeal precancer. Auris Nasus Larynx, 1998;25:407～412.
[56] 王正敏,陆书昌,主编.现代耳鼻咽喉科学.北京:人民军事出版社,2001,第一版:952.
[57] 孙广滨,周水淼,王昶,等.Diomed-25半导体激光在治疗喉癌前病变中的应用.山东大学基础医学院学报,2003;17(3):158～159.
[58] Maran A. Head and neck surgery: An ercyciopaedia of ignorance. J Laryngol Otol,1990;104:529.
[59] 周剑勇,梁素霞.喉癌前病变DNA含量测定及细胞周期分析的意义.广东医学,2001;22(3):201～202.
[60] Merkel DE. Flow cytometry, cellular DNA contents and prognosis in human mall gnancy. J Clini Oncol, 1987;5(10):1690.
[61] Zariwala M, Schmlu S, Pialoz M, et al. P53 gene mutations in oropharyngeal carcinomas: A comparison of solitary and mutiple primary tumours and lymph node metastases. Int J Cancer, 1994;56(6):807.
[62] Hall PA, Ray A, Lemoine NR, et al. P53 immunostaining as a marker of mall gnant disease in diagnostic cytopathology. Lancet, 1991;338:513.
[63] 周光耀,林代诚,梁传余,等.P53蛋白在喉上皮癌前病变及癌组织中的表达及其意义.华西医大学报,1999;30(3):265～267.
[64] 肖健云,罗均利,陶正德,等.P53蛋白在喉癌及癌旁病变组织中的表达.中国耳鼻咽喉颅底外科杂志,1995;1(1):47～49.
[65] Bosatra A (ed): Acta Otolaryngol, 1997:Suppl:344.
[66] Henry RC: J Laryngol Otol, 1979;93:447.
[67] Carte RL: Precancerous State pl, Oxford University Press, 1984.
[68] 邓志宏,黄维国,邱建华等.血管生成及细胞凋亡与喉黏膜上皮癌变的关系.第四军医大学学报,1999;20(1):17～20.
[69] 孙德义,李学佩,孙晓东,等.一氧化氮合酶(NOS)在喉鳞癌中的表达及意义.耳鼻咽喉一头颈外科,2000;7(3):167～170.
[70] Mozota Ortiz JR. Cancer of the vocal cord, early diagnosis by stroboscopy. Acta Otorhinolaryngol Esp, 1998;28:91～104.
[71] 宋发全,张芩娜,王建亭,等.声带癌前病变及癌变动态喉镜追踪观察.中华耳鼻咽喉科杂志,2000;35(2):144～146.
[72] Guillermo J Tearney, Mark E Brezinski, Brett E Bouma, et al. In vivo endoscopic optical biopsy with optical coherence tomogyaphy. Science, 1997;276(27):2037～2039.
[73] Ralph S Dacosta, Brian C Wilson, Norman E Marcon. New optical technologies for earlier endoscopic diagnosis of premalignant gastrointestinal lesions. Journ al of Gastroenterology and Hepatology, 2002;17(suppl):S85～S104.
[74] Kulapadituarom Bet al. Ann Otol Rhinol Laryngol, 2001;110:45～52.
[75] 顾建森,李秋珍,张艳萍.喉癌前病变早期干预治疗.南京铁道医学院学 报,2000;19(2):129～130.
[76] Benjamin BN et al. Ann Otol Rhinol Lanyngol, 1988;97:376～380
[77] Healy GB et al. N Eng J Med, 1988;319:401～407.
[78] Leventhal GB et al. N Eng J Med, 1991;325:613～617.
[79] Mc cabe BF et al. Ann Otol Rhinol Lanyngol, 1987;96:158～162.
[80] Deunas LV et al. J Lanyngol Otol, 1997;111:134～140.
[81] Lagares GJA, Moore RA, Collier B, et al. Nitric oxide synthase as a marker in colorectal careinomal. Am Surg, 2001;67(7):709～713.
[82] Shochina M, Fellig Y, Sughayer M. et al. Nitric oxide synthase immunoreactivity in human bladder carcinoma. Molpathol, 2001;54(4):248～252.
[83] Gallo O, Masini E, Morbidelli L, et al. Role of nitric oxide in angiogenesis and tumor progression head and neck cancer. J Natl Cancer Insl, 1998;90(8):587～596.
[84] Kagoura M, Matsui C, Toyoda M, et al. Immunohistochemical study of inducible nitric oxide synthase in skin cancers. J Cutan Pathol, 2001;28(9):476～481.
[85] Rousseau S, Houle F, Huot J, et al. Integrating the VEGF signals leading to actin-based motility in vascular endothelial ceils. Trends Cardiovasc Med, 2000;10(8):321～327.
[86] Dvorak HF, Brown LF, Detmar M, et al. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Path, 1995;146(5):1029～1039.
[87] 李兰,郭晓峰,李浩川.VEGF与喉癌转移的免疫荧光定量研究及意义.中国肿瘤临床与康复,2002;9(4):61～62.
[88] 邓志宏,黄维国,邱建华,等.喉粘膜癌前病变和癌变中VEGF、bFGF和KGF的表达分析.肿瘤,1999;19(6):338～340.
[89] 邓志宏,黄维国,金岩,等.血管内皮生长因子在喉粘膜上皮良性及恶性变中的表达及定量.第四军医大学学报,1997;18(6):573.
[90] 王广义,王旭.胃癌组织NOS和VEGF表达与癌细胞增殖相关性的研究.外科理论与实践,2003;8(1):44～46.
[91] 黄昭明.嗓音和言语-言语病理学的基础和临床应用.见:王正敏主编.耳鼻喉科学新理论与新技术.上海:上海科技教育出版社,1997,第一版:151～162.
[92] 王正敏,主编.耳鼻喉科学新理论与新技术.上海:上海科技教育出版社,1997,第 一版:155～173.
[93] McGlone R, Hollien H. Vocal pitch characteristics of aged women. J Speech Hear Res, 1963;6:164～170.
[94] Murry, T. Speaking fundamental frequency characteristics associated with voice pathologies. J Speech Hear Res, 1978;21:374～379.
[95] 王正敏,编.耳鼻喉科学新理论与新技术.上海:上海科技教育出版社.1997,第一版:154～161.
[96] Yumoto E, Gould WJ, Baer T. Harmonic-to-noise ratio as an index of the degree of hoarseness. J. Acoust Soc Am, 1982;(71):1544～1550.
[97] De Korm G. A cepstrum-based technique for determining a harmonics-to-noise ratio in speech signals. J Spee Hear Res, 1993;(36):244～246.
[98] Kasuya H, Ogawa S, Mashima K. Normalized noise energy as an acoustic measure to evaluate pathologic voice. J Acoust Soc Am, 1986;(80):1329～1334
[99] Guus de Krom, A cepstrum-based technique for determining a harmonics-to-noise ratio in speech singals. J Spee Hear Res, 1993;(36):254～266.
[100] 韩仲明.喉发音功能的检测及其临床意义.中华耳鼻咽喉科杂志,1998;33(6):380～381.
[101] Kitajima K. Quatitative evaluation of the noise level in the pathologic voice. Folia Phoniatr, 1981;(33):115～124.
[102] Kikuchi, Y, Kasaya, H, Zue, W, &Hirano. M. (1993).An integrated acoustic voice evaluation system, Paper presented at ASHA convention, November. Anaheim.
[103] Arends N, Povel DJ, Van Os E. Prdeicting voice quality of deaf speakers on the basis of glottal characteristics. J Spee Hear Res. 1990;33:116～122.
[104] Bielamowicz S, Kreiman J, Gerratt BR. Comparison of voice analysis sytems for perturbation measurement. J Spee Hear Res, 1996;39:126～134.
[105] 杨式麟.喉发声功能检查(继7).听力学及言语疾病杂志,2001;9(2):124.
[106] 杨式麟著.嗓音医学基础与临床.沈阳:辽宁科学技术出版社,2001,第一版:185～247.
[107] 魏春生,张毅.电声门图和嗓音声学的同步化测试.听力学及言语疾病杂志,2001;9(2):78.
[108] Huang, Z. Minifie. F, &Lin, X(1995). Dr. Speech Science for Windows. Singular Publishing Group, Inc. San Diego, California, USA. (1996,1998,1999 by Tiger DRS, Inc.).
[109] Huang, Z. Voice lab in clinical practice. IALP, 1998:104.
[110] 杨式麟.频闪喉镜的原理和利用.中华耳鼻咽喉科杂志,1996;31(2):123.
[111] Karnetl Mp. Synchronized videostrobscopy and electroglottography. Jvoice, 1989;(3):68.
[112] 平野实.人类音声的客观评价.临床方面.国外医学耳鼻咽喉科学分册,1990;14(5):274.
[113] 中国中西医结合研究会中国抗癌协会中医诊断协作组.12448例癌症患者舌象临床观察.癌症,1987;7(3):129～130.
[114] 吴水生,郑东海,林求成.胃癌转移状态血液流变学变化与中医证型的关系的临床研究.中国中西医结合杂志,2000;20(8):583～585.
[115] 陈燕云,陈健民.芎龙汤对癌症患者血液高粘滞状态的影响.中成药研究,1987;(10):21～23.
[116] 甘长青,吴凯南.血管生成抑制剂.中国癌症临床,1998;25(11):845～847.
[117] 李晓林.血小板与癌症转移及活血化瘀中药的抗转移作用.中国中西医结合杂志,1989;9(10):637～639.
[118] 秦叔逵,钱军,杨爱珍.榄香烯乳抗肺癌细胞的实验研究.癌症防治研究,1996;23(4):251～255.
[119] 郁仁存.中医癌症学.上册.北京:科学出版社,1987,第一版:132.
[120] 陈婷梅,祝彼得.抗白血病中药及天然药物的研究现状.中国中西医结合杂志,1995;15(5):317～320.
[121] 黄韧敏,袁淑兰,宋毅.丹参酮ⅡA诱导HL-60细胞凋亡.癌症,1998;17(3):164～166.
[122] 马晓华,沃兴德,梁海漫.姜黄素抗癌症作用与诱导癌症细胞凋亡的研究概况.国外医学肿瘤学分册,1999;26(1):21～23.
[123] 李蒙,于建勋.单味中药诱导癌症细胞凋亡的实验研究现状及展望.中国中西医结合杂志,2001,21(1):74～76.
[124] 韩俊庆,陈延条,满运艳,等.复春片合并放射治疗鼻咽癌临床研究.中国中西医结合杂志,1995;15(12):710～712.
[125] 郁仁存,姜廷良,于尔辛.癌症研究.上海:上海科学技术出版社,1991:106.
[126] 张凤瑞.膈下逐瘀汤现代研究概述.中成药,1995;17(5):44～45.
[127] 程剑华.中医药治疗癌症疗效测评客观化研究的思路方法探讨.中国中西医结合 杂志,2000;20(8):625～627.
[128] 颜大海,朱树林,付宝忠.鸡胚法筛选具有血管生成抑制作用中药.黑龙江医药,1998;11(2):94.
[129] 孙茂峰,王茵萍,范刚启,等.关于活血化瘀对慢性萎缩性胃炎胃壁屏障作用的探讨.中国中西医结合杂志,2000;20(7):554～556.
[130] 血瘀证综合研究国际会议暨第四届全国活血化瘀研究学术会议纪要.中国中西医结合杂志,1995;15(12):755～757.
[131] 刘明章,黄贻穗,肖伟琪.丹参酮ⅡA磺酸钠对Lewis癌无促进生长与转移的作用.中国药理学报,1991;12(6):534～537.
[132] 彭康,莫孔炼,郑有顺.血府逐瘀汤加减方对CTX所致小鼠免疫功能低下的防治作用.中国药理与临床,1996;12(1):6～8.
[133] 李云英,薛宗义,莫莉莉,等.“金喉片”治疗声带小节的临床及药理实验研究.广州中医药大学学报,1995;02:10～13.
[134] 李云英,薛宗义,莫莉莉.声带小节患者甲皱微循环改变及中药金喉片对其影响.中国中西医结合耳鼻咽喉科杂志,1996;4(4):170～172.
[135] 区勇全,莫莉莉.金喉片的药理实验研究.河北中医,1995;17(2):38.
[136] Bloom ED, Pauloski BR, Hamaker RC. Functional outcome after surgery for prevention of pharyngospasms in tracheoesophageal speakers, part 1;speech characteristics. J Laryngoscope, 1995;105:1093.
[137] 杨式麟.嗓音的声学检测.听力学及言语疾病杂志,2001;9(4):255
[138] Giovanni A. Contribution a L'elaboration d'un protocole multiparametrique devaluation objective des dysphonies. These en Science, Universite de laMediterrannee, 1998.
[139] Schoentgen J. Presentation of problem:performance of jitter in discriminating between normal and dysphonic speakers, Appl Stoch Mod Data Anal, 1988;4:127～135.
[140] Karnell M. Laryngeal Perturbation Analysis:Minimum Length of Analysis Window. J Speech Hear Res, 1991;34:544～548.
[141] Bielamowicz S, Kreiman J, Gerrat BR, Dauer MS, Berke GS. Comparison of voice analysis systems for perturbation measurement. J Speech Hear Res, 1996;39:126～134.
[142] Deem J, Manning W, Knack J, Matesich J. The automatic extraction of pitch perturbation using microcomputers:some methodological considerations. J Speech Hear Res, 1989;32:689～697.
[143] Karnell M, Hall K, Landahl K. Comparison of fundamental frequency and perturbation measurements among three analysis systems. J Yoice, 1995;9:383～393.
[144] 许良中,主编.实用肿瘤病理方法学.上海:上海人民出版社,1997,第一版:223～224.
[145] Rosbe KW, Prazma J, Petrusz P, et al, Immunohistochemic alchar acterization of nitric oxide synthase activity in squamous cell carcinoma of the head and neck. Otolaryngol Head and Neck Surg, 1995;113(5):541～549.
[146] Thomsen LL, Miles DW, Happerfield L, et al. Nitric oxidesynthase activity in human breast cancer. Br J Cancer, 1995;72(1):41～44.
[147] Goldstein SR, Yang GY, Chen X, et al. Studies of iron deposits, inducible nitric oxidesynthase and nitrotyrosine in a rat model for esophageal adenocarcinoma. Carcinogenesis, 1998;19(8):1445～1449.
[148] 罗玉琴,吴开春,孙安华,等.浅表性胃炎、胃黏膜不典型增生及胃癌组织中COX-1、COX-2、iNOS表达的意义.中华消化杂志,2000;20(4):223～226.
[149] Jenkins DC, Charles IG, Thomsen LL. Roles of nitric oxide in tumor growth proc. Natl Acad Sci USA, 1995;92(10):4392～4396.
[150] 许传杰,王贵全,沙春蕊,等.喉癌组织中诱导型一氧化氮合酶的表达与微血管密度的关系及其临床意义.中国老年学杂志,2004;24(2):110～111.
[151] Dvorak HF, Brown LF, Detmar M, et al. Vascular permeability factor/vascular endothelial grouth factor, microvascular hyper permeability, and angiogenesis, Am J Pathol, 1995;146(5):1029～1039.
[152] Zondo S, Asano M, Matsuo K, et al. Vascular endothelial growth factor/vascularperm lability factoris detectable in the sera of tumor bearing mice and cancer patients. Biochim BiophysActa, 1994;1221:211～214.
[153] 薛倩,周光耀,邹剑,等.血管内皮生长因子在喉癌组织中的表达及其意义.华西医学,2004;19(3):366～367.
[154] 李正江,唐平章,张志超,等.喉癌组织血管内皮生长因子的表达与喉癌临床病理关系.临床耳鼻咽喉科杂志,2002;16(3):111～113.
[155] Kimura H, Weisz A, Kurashima Y, et al. Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxia-inducible factor-1 activity by nitric oxide. Blood, 2000;95(1):189～197.
[156] Hood JD, Meininger CJ, Ziche M, et al. VEGF upregulates eCNOS message, protein, and NO production in human endothelial cells. Am J Physol, 1998;274(3pt2):H1054～H1058.
[157] 姜淑梅.原发性肺癌30例的血液流变学观察.哈尔滨医药,1998;(2):24.
[158] 胡庆福,邓瑶函.血瘀型恶性肿瘤病人红细胞膜流动性及血液流变性的研究.肿瘤,1990;(7):10.