肺癌瘀血舌象特征及凝血机制相关研究
|
摘要
肺癌是目前世界发达国家及我国大中城市发病率及死亡率最高的恶性肿瘤之一,并且近几十年来其发病率及死亡率在全部恶性肿瘤中上升幅度最大。血瘀证是肿瘤的基本证型、主要证型之一,瘀血舌象对肿瘤的辨证分型、指导诊治具有十分重要的意义。近年来应用中西医结合治疗肿瘤显示出其在稳定病灶、改善症状、延长生存期、改善生存质量等方面优势,因此中西医结合防治肿瘤已成为广大医学工作者的一种共识。瘀血舌象是肿瘤最常见舌象之一,在舌象研究中具有较强的代表性。本课题以导师课题组的前期瘀血舌研究成果为基础,以肺癌瘀血舌象为切入点,从文献研究、临床研究、实验研究等方面入手,拍摄有代表性的肺癌瘀血舌彩色照片,分析肺癌瘀血舌的临床分布特征,从部分凝血指标入手分析其微观机理,进一步分析其对肺癌临床诊治的指导意义。论文分为三个部分：
第一部分文献研究
本研究通过计算机检索结合手工检索的方法,系统整理了古代瘀血舌象、血瘀证、肿瘤相关文献进行系统论述；通过计算机检索的方法,系统整理了现代瘀血舌与肺癌及其它肿瘤相关研究的文献。文献研究结果显示：古代医家对瘀血舌象、血瘀证、肿瘤均有丰富的文献记载,对肿瘤与血瘀证之间的密切关系有非常深刻的认识。但纵览历代中医古文献,却未见肺癌等肿瘤瘀血舌象方面的描述,具体有待于进一步研究。近年来许多医学工作者对肺癌及其它肿瘤患者血瘀证舌象的研究发现,肿瘤患者血瘀证舌象的舌质、舌苔、舌下络脉在不同病程阶段的分布及表现皆有一定的规律性。肺癌及其它肿瘤患者存在血液高凝状态,主要表现为血液流变学异常、微循环障碍及血液凝固性升高,血小板增多等。肺癌患者血液高凝状态与肿瘤的发生、进展和转移有一定相关性,肺癌的中医辨证分型与临床TNM分期、病理类型,以及实验室指标(血液流变学、凝血四项指标等)存在一定的关系和规律性。
第二部分临床观察
目的
通过肉眼诊察肺癌患者舌象,分析其舌象分布特征,对典型、有代表性的肺癌瘀血舌象进行采集。
方法
144例肺癌患者,包括血瘀证组(肺郁痰瘀证)93例,非血瘀证组(脾虚痰湿证、阴虚痰热证、气阴两虚证)中51例,肉眼诊察舌象与数码相机彩色舌象照片相结合。
结果
在144例研究对象中,舌质颜色表现为暗红舌、淡红舌、淡暗舌、红舌、暗舌、淡舌、紫舌、瘀斑瘀点舌,其中以暗红舌、淡红舌、淡暗舌所占比例最重,分别占34.03%,20.83%,19.44%。血瘀证组和非血瘀证组进行舌质分布比较,血瘀证组的瘀血舌象明显多于非血瘀证组,两组差异有统计意义(p<0.05)。在肺癌血瘀证组中舌色表现为暗红舌>淡暗舌>淡红舌>红舌>暗舌>淡舌>紫舌>瘀斑瘀点舌；其中以暗红舌最多,占44.09%；淡暗次之,占18.28%。肺癌非血瘀证组中舌质表现为淡红舌>淡暗舌>暗红舌>红舌>紫舌>暗舌>淡舌>瘀斑瘀点舌,主要以淡红舌、淡暗舌为主,分别占31.37%、21.57%。肺癌患者的舌色随着年龄、性别、是否有远处转移病灶、早晚分期、病理类型不同,其分布特征也不相同。早期、中晚期组肺癌血瘀证患者舌色均以暗红、淡暗、淡红为主,但从中晚期组紫舌、瘀斑瘀点舌、舌下络脉曲张均呈增高趋势,考虑可能与中晚期患者病情较重,其血瘀程度也较重有关。在144例研究对象中,白苔、薄白苔、白腻苔、薄黄苔所占比例较重,特别是白苔所占比例最重。依据各种舌苔的出现频率,血瘀证组舌苔依次为白苔>薄白苔>薄黄苔>白腻苔>黄苔>白厚苔>黄腻苔>黄厚苔>少苔>黄厚腻苔>剥苔；非血瘀证组舌苔依次为白苔>白腻苔>薄白苔>少苔>薄黄苔>黄苔>剥苔>白厚苔>白厚腻苔>黄厚苔>无苔。肺癌血瘀证组与非血瘀证组舌苔分布比较,差异有统计意义。肺癌血瘀证组见舌下络脉瘀血征象者占24.73%,非血瘀证组见舌下络脉瘀血征象者占5.88%,血瘀证组明显高于非血瘀证组。
结论
淡红舌是正常舌质的表现,暗红舌、淡暗舌这两种瘀血舌象共占53.47%,提示肺癌患者多数有瘀血征象,与中医对癌瘤的认识一致,与临床辨证分型结果相符合。血瘀证组舌色以“暗”为主要特征,非血瘀证组以“淡”为主要特征,这与血瘀证组主要辨证为“肺郁痰瘀”的“瘀”证,非血瘀证组主要辨证为“脾虚痰湿、阴虚痰热、气阴两虚”的“虚”证一致。肺癌患者的年龄、性别、是否有远处转移病灶、早晚分期、病理类型不同,其舌苔分布特征也不相同。舌下络脉瘀血可能是肺癌血瘀证比较早期和敏感的指标。
第三部分实验研究
目的
从实验层面探讨肿瘤瘀血舌象形成的病理机制。
方法
144例肺癌患者,包括血瘀证组(肺郁痰瘀证)93例,非血瘀证组(脾虚痰湿证、阴虚痰热证、气阴两虚证)中51例；32例健康人。早餐前静脉采血,用Sysmex CA1500、sysmex XE2100全自动血液分析仪检测以下指标：血浆凝血酶原时间(PT)测定：散射光测试法；活化部分凝血活酶时间(APTT)测定：散射光测试法；纤维蛋白原(FIB)测定：散射光测试法；血小板计数(PLT)测定：光学法(PLT-O)。
结果
(一)凝血酶原时间(PT)比较
1.血瘀证组、非血瘀证组PT均较健康人对照组缩短,但差异无统计学意义(P>0.05)；血瘀证组PT较非血瘀证组缩短,但差异无统计学意义(P>0.05)。
2.未转移组、远处转移组PT均较健康人对照组缩短,但差异无统计学意义(P>0.05)；未转移组PT较转移组缩短,但差异无统计学意义(P>0.05)。
3.早期组、中晚期组PT均较健康人对照组缩短,但差异无统计学意义(P>0.05)；早期组PT较中晚期组缩短,但差异无统计学意义(P>0.05)。
4.不同中医证型组比较,肺郁痰瘀证组、脾虚痰湿证组、阴虚痰热证组PT值均较健康人组缩短,但差异无统计学意义(P>0.05)；气阴两虚组与健康人组比较,差异有统计学意义(P<0.01),可认为气阴两虚组PT值高于健康人组；不同中医证型组之间比较,组间差异无统计学意义(P>0.05)。
(二)活化部分凝血酶原时间(APTT)比较
1.血瘀证组、非血瘀证组、健康人对照组之间相互比较,差异无统计学意义(P>0.05)；血瘀证组、非血瘀证组之间相互比较,差异无统计学意义(P>0.05)。
2.未转移组、远处转移组、健康人对照组之间相互比较,差异无统计学意义(P>0.05)；未转移组、远处转移组之间相互比较,差异无统计学意义(P>0.05)。
3.早期组、中晚期组、健康人对照组之间相互比较,差异无统计学意义(P>0.05)；早期组、中晚期组之间相互比较,差异无统计学意义(P>0.05)。
4.不同中医证型组与健康人对照组之间相互比较,差异无统计学意义(P>0.05)；不同中医证型组之间相互比较,差异无统计学意义(P>0.05)。
(三)纤维蛋白原(FIB)比较
1.血瘀证组与健康人对照组FIB值比较,血瘀证组高于健康人对照组,差异有统计学意义(P<0.01)；非血瘀证组与健康人对照组FIB值比较,非血瘀证组FIB值高于健康人对照组,但差异无统计学意义(P>0.05)；血瘀证组与非血瘀证组FIB值比较,血瘀证组高于非血瘀证组,但差异无统计学意义(P>0.05)。
2.早期组与健康人组比较,早期组高于健康人组,差异有统计学意义(P<0.05)；中晚期组与健康人组比较,中晚期组高于健康人组,差异有统计学意义(P<0.05)；早期组、中晚期组比较,中晚期组高于早期组,但差异无统计学意义(P>0.05)。
3.未转移组与健康人组比较,未转移组高于健康人组,差异有统计学意义(P<0.05)；转移组与健康人组比较,转移组高于健康人组,差异有统计学意义(P<0.05)；转移组与未转移组比较,转移组高于未转移组,但差异无统计学意义(P>0.05)。
4.肺癌不同中医证型组FIB值与健康人组比较,肺癌不同证型组FIB值均明显高于健康人组,差异有统计学意义(P<0.05)；不同中医证型组FIB值比较,肺郁痰瘀证组>气阴两虚证组>阴虚痰热证组>脾虚痰湿证组,但组间比较差异无统计学意义(P>0.05)。
(四)血小板计数(PLT)比较
1.血瘀证组PLT明显高于健康人对照组,差异有统计学意义(P<0.01)；血瘀证组PLT高于非血瘀证组,但差异无统计学意义(P>0.05)；非血瘀证组高于健康人对照组,但差异无统计学意义(P>0.05)。
2.早期组、中晚期组、健康人对照组PLT比较,差异有统计学意义(P<0.05)；早期组与健康人对照组比较,早期组PLT高于健康人组,差异有统计学意义(P<0.05)；中晚期组高于健康人组,但差异无统计学意义(P>0.05)。
3.未转移组、转移组、健康人对照组PLT比较,差异有统计学意义(P<0.05)；未转移组PLT明显较健康人组增高,差异有统计学意义(P<0.01)；转移组PLT明显较健康人组增高,差异有统计学意义(P<0.05)；未转移组高于转移组,但差异无统计学意义(P>0.05)。
4.不同中医证型组PLT比较,肺郁痰瘀证组高于非血瘀证组(脾虚痰湿证、阴虚痰热证、气阴两虚证),但差异没有统计意义(P>0.05)；肺郁痰瘀证组与健康人对照组比较,明显高于健康人组(P<0.01)。
结论
1.PT是血瘀证重要参考指标
肿瘤患者PT缩短提示血液高凝状态,血瘀证组PT与非血瘀证组、健康人组比较,统计结果虽无统计学意义,但三组比较,体现了健康人组>非血瘀证组>血瘀证组的趋势,体现了血瘀证组比非血瘀证组,非血瘀证组比健康人组机体血液更加高凝的状态,与中医临床辨证为血瘀证(肺郁痰瘀证)、非血瘀证(脾虚痰湿证、阴虚痰热证、气阴两虚证)的认识相一致。2.APTT是血瘀证重要参考指标
APTT缩短,常提示血液高凝状态。本研究结果显示血瘀证组APTT时间并没有比非血瘀证组缩短,但也没有比非血瘀证组APTT时间延长。考虑APTT并非血瘀证的特异性实验指标,只是重要参考指标有关。3.FIB值的升高是瘀血舌象形成的重要病理基础
FIB值的升高与肺癌的发生、进展、转移相关,FIB的升高使肺癌患者的血液处于“浓、粘、凝、聚”的高凝状态,血瘀证组的FIB值高于非血瘀证组,且明显高于健康人对照组,推测FIB值的升高可能是肺癌瘀血舌象形成的重要病理基础。4.PLT值的升高是肺癌瘀血舌象形成的重要环节
PLT值的升高,机体血小板增多,血小板大量堆积,形成血小板血栓,并且血小板表面粘附的蛋白复合物激活凝血酶,使得机体血液凝固性增高,血流减慢,组织缺氧,反映于舌出现瘀血舌象。血瘀证组的PLT值高于非血瘀证组,且明显高于健康人对照组,提示PLT值的升高可能是肺癌瘀血舌象形成的重要环节。
结语
本课题的创新点：
1.本课题研究发现,肺癌患者瘀血舌象以“暗”为主要特征,主要为“暗红舌、淡暗舌”,与以往文献报道肿瘤患者瘀血舌象以“青舌、紫舌、瘀斑瘀点舌”为主的特征不同。认为“暗红舌、淡暗舌”是肺癌瘀血舌的基本舌象,而“青舌、紫舌、瘀斑瘀点舌”是肺癌瘀血舌象的典型舌象。
2.本研究首次从PT、APTT、FIB、PLT角度分析了肺癌瘀血舌象的微观机理,拓宽了肺癌瘀血舌象的研究思路。
Lung carcinoma, as one of the malignant tumors with highest occurrence and mortality rates in the developed countries and the large cities in our country, is a carcinoma with highest ccurrence and mortality rates over the world, with largest increasing occurrence and mortality rates among all the carcinomas. Blood stasis syndrome is one of the basic and main syndromes of the tumors, and the tongue manifestation of blood stasis is of significance in the syndrome differentiation, diagnosis and treatment of tumors. In recent years, more and more clinical practice of integrated traditional and western medicine has demonstrated the superiority and advantages in stabilizing the foci, improving the symptoms, prolonging the survival, enhancing the quality of life, etc, which has paid much attention in the medical field at home and abrord. The blood stasis tongue manifestation is one of the commonly seen manifestations of the tumors, which is of significance in the studies of tongue manifestaions. In the present dissertation, based on the research results of early phase of the project, taking the blood stasis tongue manifestations of lung carcinoma as the breakthrough point, with the literature research, clinical practise and experimental study, etc, the colorful pictures of blood stasis tongue manifestation with representatives were taken. By analyzing the clinical distribution characteristics of the blood stasis tongue of lung carcinoma and the correlations with the indexes of the modern medical tests, it provides the scientific basis for the clinical diagnosis and treatment of lung carcinoma. The present dissertation includes three parts.
Part 1 Literature research
In the present study, with the methods of computer-based comtbined with manual retrievals, the related ancient literatures of the blood stasis tongue, blood stasis syndrome and tumor were systematically discussed. With the methods of computer-based retrieval, the related modern literactures of blood stasis tongue and other tumor studies were systematically analyzed. The literature research indicated that there were rich records of blood stasis tongue manifestations, blood syndrome and tumors in ancient China and there was deep understanding to the close relationships among the three. However, according to these ancient literatures, there were no references of the blood stasis tongue of tumors, which needs further studies. In recent years, increasing research of the blood stasis tongue manifestation of lung carcinoma and other tumors has found that there were some certain rules of the distributions and manifestations of the tongue body, tongue coating and sublingual veins in different phases among the tumor patients. There was hypercoagulability among the patients with lung carcinoma or other tumors, which manifest as abnormal hemorheology, impediment of microcirculation, increasing coagulability of blood, increasing amounts of blood platelet, etc. There was certain relationship between the hypercoagulability of blood and the occurrence, development and metastasis of the carcinoma, and there were certain relationships and rules between the syndrome differentiation and clinical TNM, pathological categories and biolocial indexes (such as hemorheology, four items of coagulation function test, etc).
Part 2 Clinical observation
Objective:By diagnosing and observing the tongue manifestaions of lung carcinoma, the cases with representative blood stasis tongue manifestation were enrolled and the distribution characteristics of the tongue manifestation were analyzed.
Subjects:144 patients with lung carcinoma, including 93 cases in the blood stasis tongue manifestation group and 51 cases in the non-blood stasis tongue manifestation group.
Methods:Integration of observation of tongue manifestation by eye and tongue manifestation pictures taken with digital cameras.
Results and conclusions
2.1 Tongue body
2.1.1 Among the 144 cases enrolled, the colors of the tongues manifest as dull-red, pale dark red, red, dark, pale, purple and ecchymosis, with the dull-red, pale red and pale dark the lagest ratio, accounting for 34.03%, 20.83% and 19.44% respectively. The pale red tongue manifestion is normal, but the dark red and pale dark tongue manifestations account for 53.47%, indicating that there were mostly blood stasis signs among the lung carcinoma patients, which was accordance with the TCM understanding to the tumors and the clinical results of syndrome differentiation.
2.1.2 With the comparison of the tongue body distribution between the blood stasis tongue group and the non-blood stasis tongue group, there were apparently more blood stasis tongue manifestation in the former group than that in the latter group, with significant difference between the two (P<0.05). In the former group, the tongue manifestations from large to small ratio successively were dull-red, pale dark, pale red, dark, pale, purple and ecchymosis, with the dark red the largest, accounting for 44.09%; pale dark secondly, accounting for 18.28%. In the latter group, the tongue manifestations from large to small ratio successively were pale red, pale dark, dull-red, red, purple, dark, pale and ecchymosis, mainly as the pale red and pale dark, accounting for 31.37% and 21.57% respectively. In the former group, the tongue manifestations were manily characteristic as dark, which was accordance with the syndrome differentiation as blood stasis syndrome due to lung depression, phlegm and blood stasis; in the latter group, the tongue manifestations were manily characteristic as pale, which was accordance with the syndrome differentiation as deficiency syndrome due to spleen deficiency and phlegm-dampness, yin-deficiency and phlegm-heat and dual deficiency of qi and yin.
2.1.3 The tongue colors changed with the difference of ages, sexes, metastasis, phases and pathological categories. The distribution characteristics were also different. In the early and middle phases, the cases of blood stasis syndrome of lung carcinoma manifest mainly as dull-red, pale dark and pale red tongue manifestations. However, in the middle and late phases, the ratios of purple and ecchymosis tongue manifestations and sublinguial varicose veins have the tendency of increasing, which maybe was closely related with the serious situation of the patients and the serious blood stasis situation.
2.2 Tongue coating
2.2.1 Among the 144 cases enrolled, most of the manifestations of the tongue coating were white, thin-white, white-greasy and thin-yellowish, particularly the white, accounting the largest ratio.
2.2.2 According to the occurrence frequency of all kinds of the tongue coating, the tongue coating manifestations from large to small ratio in the blood stasis tongue group successively were white, thin-white, thin-yellowish, white-greasy, yellowish, white-thick, yellowish-greasy, yellowish-thick, little coating, yellowish-thick-greasy and peeling coatings. The tongue coating manifestations from large to small ratio in the non-blood stasis tongue group successively were white, white-greasy, little coatings, thin-yellowish, yellowish, peeling coatings, white-thick, white-thick-greasy, yellowish-thick and little coatings. With the statistical management, there was significant difference of the distribution of the tongue coating between the two groups.
2.2.3 The distribution characteristics of the tongue coating among the lung carcinoma patients were different with the difference of the ages, sexes, metastasis, phases and the pathological categories.
2.3 Sublinguial veins
The signs of sublinguial veins accounted for 24.73% in the blood stasis tongue group and 5.88% in the non-blood stasis tongue group, with the signs in the former group obviously higher than that in the latter group, which was accordance with the results of the TCM clinical syndrome differentiation.
Part 3 Clinical experimental research
3.1 Objective:To explore the pathological mechanism of the formation of the blood stasis tongue manifestation of tumors from the experimental aspects.
3.2 Subjects:144 lung carcinoma patients (including 93 cases in the blood stasis tongue group and 51 cases in the non-blood stasis tongue group) and 32 healthy people.
3.3 Methods:Venous blood before breakfast was collected. The following indexes such as prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), platelet count (PLT) were tested with the Sysmex CA1500 and Sysmex XE2100 Auto-blood analyzer.
3.4 Results and conclusions
3.4.1 Comparison of the prothrombin time (PT)
3.4.1.1 The PT of the blood stasis tongue group and the non-blood stasis tongue group were lower than the healthy group, with no significant difference (P>0.05); the PT of the blood stasis tongue group was lower than the non-blood stasis tongue group, with no significant difference (P>0.05).
3.4.1.2 The PT of the non-metastasis group and the metastasis group were lower than the healthy group, with no significant difference (P>0.05); the PT of the non-metastasis group was lower than the metastasis group, with no significant difference (P>0.05).
3.4.1.3 The PT of the early phase group and the middle-late phase group were lower than the healthy group, with no significant difference (P>0.05); the PT of the early phase group was lower than the middle-late phase group, with no significant difference (P>0.05).
3.4.1.4 Among different Chinese medicine syndrome group, the PT of the lung depression, phlegm and blood stasis group, the spleen deficiency, phlegm and dampness group and the Yin deficiency, phlegm and heat group were lower than the healthy group, with no significant difference (P>0.05); the PT of the Qi and Yin deficiency group was higher than the healthy group, with significant difference (P<0.01);the PT among different Chinese medicine groups were not statistically significant (P>0.05).
PT is an important reference index for blood stasis tongue syndrome. The shortening of PT of cancer patients prompted hypercoagulative state of blood. Among the comparison of the PT of the blood stasis tongue group, the non-blood stasis tongue group and the healthy group, the statistical result showed no significant difference.But the result showed as follow:the healthy group > the non-blood stasis tongue group> the blood stasis tongue group.That meaned hypercoagulative state of the blood stasis tongue group was higher than that of the non-blood stasis tongue group, and hypercoagulative state of the non-blood stasis tongue group was higher than that of the healthy group. They are coincide with the understanding of TCM clinical syndrome differentiation for blood stasis tongue syndrome (the lung depression, phlegm and blood stasis syndrome) and non-blood stasis tongue syndrome(the spleen deficiency, phlegm and dampness syndrome, the Yin deficiency, phlegm and heat syndrome and the Qi and Yin deficiency syndrome).
3.4.2 Comparision of the activated partial thromboplastin time (APTT)
3.4.2.1 The APTT among the blood stasis tongue group, the non-blood stasis tongue group and the healthy group were not statistically significant (P>0.05); The APTT between the blood stasis tongue group and the non-blood stasis tongue group was not statistically significant (P>0.05).
3.4.2.2 The APTT between the non-metastasis group, the metastasis group and the healthy group were not statistically significant (P>0.05); The APTT between the non-metastasis group and the metastasis group was not statistically significant (P>0.05).
3.4.2.3 The APTT among the early phase group, the middle-late phase group and the healthy group were not statistically significant (P>0.05); The APTT between the early phase group and the middle-late group was not statistically significant (P>0.05).
3.4.2.4 The APTT between different TCM syndrome group and the healthy group were not statistically significant(P>0.05); The APTT between different TCM syndrome group were not statistically significant (P>0.05).
APTT is an important reference index for blood stasis tongue syndrome. The shortening of APTT often prompted hypercoagulative state of blood. This research showed that the APTT of the blood stasis tongue group was the same as that of the non-blood stasis tongue group. That pointed out APTT was just an important reference index, but not a specificity experimental index.
3.4.3 Comparision of the Fibrinogen (FIB)
3.4.3.1 The FIB of the blood stasis tongue group was higher than the healthy group, with significant difference(P<0.01); the FIB of the non-blood stasis tongue group was higher than the healthy group, with no significant difference(P>0.05); The FIB of the blood stasis tongue group was higher than the non-blood stasis tongue group, with no significant difference (P>0.05).
3.4.3.2 The FIB of the early phase group was higher than the healthy group, with significant difference(P<0.05); the FIB of the middle-late phase group was higher than the healthy group, with significant difference(P<0.05); The FIB of the middle-late phase group was higher than the early phase group, with no significant difference (P>0.05).
3.4.3.3 The FIB of the non-metastasis group was higher than the healthy group, with significant difference(P<0.05); the FIB of the metastasis group was higher than the healthy group, with significant difference(P<0.05); the FIB of the metastasis group was higher than the non-metastasis group, with no significant difference(P>0.05).
3.4.3.4 The FIB of different TCM syndrome group was higher than the healthy group, with siginificant difference(P<0.05); the comparison of different TCM syndrome group on FIB showed that as follow:the lung depression, phlegm and blood stasis group>the Qi and Yin deficiency group>the Yin deficiency, phlegm and heat group>the spleen deficiency, phlegm and dampness group, with no significant difference (P>0.05).
The increasing of the FIB was the important pathologic basis of the formation of blood stasis tongue. The increasing of FIB was related to the occurrence, evolution and metastasis of lung carcinoma. It keeped the blood of lung carcinoma patient in a "thick, sticky, concretionary, congregative" hypercoagulative state. The FIB of blood stasis tongue group was higher than the non-blood stasis group, and was significantly higher than the healthy group. That pointed out the increasing of FIB was the important pathologic basis of the formation of blood stasis tongue.
3.4.4 Comparison of Platelet count (PLT)
3.4.4.1 The PLT of blood stasis tongue group was higher than the healthy group, with significant difference(P<0.01); The PLT of blood stasis tongue group was higher than the non-blood stasis tongue group, with no significant difference(P>0.05); The PLT of non-blood stasis tongue group was higher than the healthy group, with no significant difference (P>0.05).
3.4.4.2 The PLT among the early phase group, the middle-late phase group and the healthy group were statistically significant (P<0.05); the PLT of the early phase group was higher than the healthy group, with significant difference (P<0.05); the PLT of the middle-late phase group was higher than the healthy group, with no significant difference (P>0.05).
3.4.4.3 The PLT among the non-metastasis group,the metastasis group and the healthy group were statistically significant (P<0.05); the PLT of the non-metastasis group was higher than the healthy group, with significant difference (P<0.01); the PLT of the metastasis group was higher than the healthy group, with significant difference(P<0.05); the PLT of the non-metastasis group was higher than the metastasis group, with no significant difference(P>0.05).
3.4.4.4 Among different TCM syndrome group, the PLT of the lung depression, phlegm and blood stasis group was higher than the other syndrome group, with no significant difference (P>0.05); the PLT of the lung depression, phlegm and blood stasis group was higher than the healthy group, with significant difference(P<0.01).
The increasing of the PLT was an important part of the formation of lung carcinoma blood stasis tongue. The number of PLT increased, the number of PLT in body increased, lots of PLT accumulated, all of that formed the PLT thrombosis. The protein complexes which adhered on the surface of the PLT activated thrombin. That increased the blood coagulability, slowed the blood flow, and the tissue were hypoxia. All of that reflectd in the blood stasis tongue. The PLT of the blood stasis tongue group was higher than the non-blood stasis tongue group, and was significantly higher than the healthy group. That pointed out the increasing of the number of PLT maybe an important part of the formation of lung carcinoma blood stasis tongue.
Conclusion
Innovation of the present study 4.1 Taking the blood stasis tongue manifestation as the breakthrough point, in the present research, the characteristics, the rules of the clinical distribution and the mechanism of the formation of the tongue manifestation were systematically analyzed. It indicated that the blood stasis tongue manifestations of lung carcinoma were mainly characteristic with dark, mostly were dull-red, pale dark, which were different from the previous literacture reports on the blood stasis manifestations of tumors as green, purple or ecchymosis. It was thought that the dark red tongue and the dark pale tongue was the basic tongue manifestations of the blood stasis syndrome of lung carcinoma, and the blue, purple and ecchymosis petechia tongues were the typtical tongue manifestations of the blood stasis syndrome of lung carcinoma.
4.2 In the present study, it was firstly analyzed the micro-mechanism of the blood stasis tongue manifestations of lung carcinoma from the perspective of PT, APTT, FIB and PLT, which consequently broadens the study strategies for the blood stasis tongue manifestations of lung carcinoma.
第一部分文献研究
本研究通过计算机检索结合手工检索的方法,系统整理了古代瘀血舌象、血瘀证、肿瘤相关文献进行系统论述；通过计算机检索的方法,系统整理了现代瘀血舌与肺癌及其它肿瘤相关研究的文献。文献研究结果显示：古代医家对瘀血舌象、血瘀证、肿瘤均有丰富的文献记载,对肿瘤与血瘀证之间的密切关系有非常深刻的认识。但纵览历代中医古文献,却未见肺癌等肿瘤瘀血舌象方面的描述,具体有待于进一步研究。近年来许多医学工作者对肺癌及其它肿瘤患者血瘀证舌象的研究发现,肿瘤患者血瘀证舌象的舌质、舌苔、舌下络脉在不同病程阶段的分布及表现皆有一定的规律性。肺癌及其它肿瘤患者存在血液高凝状态,主要表现为血液流变学异常、微循环障碍及血液凝固性升高,血小板增多等。肺癌患者血液高凝状态与肿瘤的发生、进展和转移有一定相关性,肺癌的中医辨证分型与临床TNM分期、病理类型,以及实验室指标(血液流变学、凝血四项指标等)存在一定的关系和规律性。
第二部分临床观察
目的
通过肉眼诊察肺癌患者舌象,分析其舌象分布特征,对典型、有代表性的肺癌瘀血舌象进行采集。
方法
144例肺癌患者,包括血瘀证组(肺郁痰瘀证)93例,非血瘀证组(脾虚痰湿证、阴虚痰热证、气阴两虚证)中51例,肉眼诊察舌象与数码相机彩色舌象照片相结合。
结果
在144例研究对象中,舌质颜色表现为暗红舌、淡红舌、淡暗舌、红舌、暗舌、淡舌、紫舌、瘀斑瘀点舌,其中以暗红舌、淡红舌、淡暗舌所占比例最重,分别占34.03%,20.83%,19.44%。血瘀证组和非血瘀证组进行舌质分布比较,血瘀证组的瘀血舌象明显多于非血瘀证组,两组差异有统计意义(p<0.05)。在肺癌血瘀证组中舌色表现为暗红舌>淡暗舌>淡红舌>红舌>暗舌>淡舌>紫舌>瘀斑瘀点舌；其中以暗红舌最多,占44.09%；淡暗次之,占18.28%。肺癌非血瘀证组中舌质表现为淡红舌>淡暗舌>暗红舌>红舌>紫舌>暗舌>淡舌>瘀斑瘀点舌,主要以淡红舌、淡暗舌为主,分别占31.37%、21.57%。肺癌患者的舌色随着年龄、性别、是否有远处转移病灶、早晚分期、病理类型不同,其分布特征也不相同。早期、中晚期组肺癌血瘀证患者舌色均以暗红、淡暗、淡红为主,但从中晚期组紫舌、瘀斑瘀点舌、舌下络脉曲张均呈增高趋势,考虑可能与中晚期患者病情较重,其血瘀程度也较重有关。在144例研究对象中,白苔、薄白苔、白腻苔、薄黄苔所占比例较重,特别是白苔所占比例最重。依据各种舌苔的出现频率,血瘀证组舌苔依次为白苔>薄白苔>薄黄苔>白腻苔>黄苔>白厚苔>黄腻苔>黄厚苔>少苔>黄厚腻苔>剥苔；非血瘀证组舌苔依次为白苔>白腻苔>薄白苔>少苔>薄黄苔>黄苔>剥苔>白厚苔>白厚腻苔>黄厚苔>无苔。肺癌血瘀证组与非血瘀证组舌苔分布比较,差异有统计意义。肺癌血瘀证组见舌下络脉瘀血征象者占24.73%,非血瘀证组见舌下络脉瘀血征象者占5.88%,血瘀证组明显高于非血瘀证组。
结论
淡红舌是正常舌质的表现,暗红舌、淡暗舌这两种瘀血舌象共占53.47%,提示肺癌患者多数有瘀血征象,与中医对癌瘤的认识一致,与临床辨证分型结果相符合。血瘀证组舌色以“暗”为主要特征,非血瘀证组以“淡”为主要特征,这与血瘀证组主要辨证为“肺郁痰瘀”的“瘀”证,非血瘀证组主要辨证为“脾虚痰湿、阴虚痰热、气阴两虚”的“虚”证一致。肺癌患者的年龄、性别、是否有远处转移病灶、早晚分期、病理类型不同,其舌苔分布特征也不相同。舌下络脉瘀血可能是肺癌血瘀证比较早期和敏感的指标。
第三部分实验研究
目的
从实验层面探讨肿瘤瘀血舌象形成的病理机制。
方法
144例肺癌患者,包括血瘀证组(肺郁痰瘀证)93例,非血瘀证组(脾虚痰湿证、阴虚痰热证、气阴两虚证)中51例；32例健康人。早餐前静脉采血,用Sysmex CA1500、sysmex XE2100全自动血液分析仪检测以下指标：血浆凝血酶原时间(PT)测定：散射光测试法；活化部分凝血活酶时间(APTT)测定：散射光测试法；纤维蛋白原(FIB)测定：散射光测试法；血小板计数(PLT)测定：光学法(PLT-O)。
结果
(一)凝血酶原时间(PT)比较
1.血瘀证组、非血瘀证组PT均较健康人对照组缩短,但差异无统计学意义(P>0.05)；血瘀证组PT较非血瘀证组缩短,但差异无统计学意义(P>0.05)。
2.未转移组、远处转移组PT均较健康人对照组缩短,但差异无统计学意义(P>0.05)；未转移组PT较转移组缩短,但差异无统计学意义(P>0.05)。
3.早期组、中晚期组PT均较健康人对照组缩短,但差异无统计学意义(P>0.05)；早期组PT较中晚期组缩短,但差异无统计学意义(P>0.05)。
4.不同中医证型组比较,肺郁痰瘀证组、脾虚痰湿证组、阴虚痰热证组PT值均较健康人组缩短,但差异无统计学意义(P>0.05)；气阴两虚组与健康人组比较,差异有统计学意义(P<0.01),可认为气阴两虚组PT值高于健康人组；不同中医证型组之间比较,组间差异无统计学意义(P>0.05)。
(二)活化部分凝血酶原时间(APTT)比较
1.血瘀证组、非血瘀证组、健康人对照组之间相互比较,差异无统计学意义(P>0.05)；血瘀证组、非血瘀证组之间相互比较,差异无统计学意义(P>0.05)。
2.未转移组、远处转移组、健康人对照组之间相互比较,差异无统计学意义(P>0.05)；未转移组、远处转移组之间相互比较,差异无统计学意义(P>0.05)。
3.早期组、中晚期组、健康人对照组之间相互比较,差异无统计学意义(P>0.05)；早期组、中晚期组之间相互比较,差异无统计学意义(P>0.05)。
4.不同中医证型组与健康人对照组之间相互比较,差异无统计学意义(P>0.05)；不同中医证型组之间相互比较,差异无统计学意义(P>0.05)。
(三)纤维蛋白原(FIB)比较
1.血瘀证组与健康人对照组FIB值比较,血瘀证组高于健康人对照组,差异有统计学意义(P<0.01)；非血瘀证组与健康人对照组FIB值比较,非血瘀证组FIB值高于健康人对照组,但差异无统计学意义(P>0.05)；血瘀证组与非血瘀证组FIB值比较,血瘀证组高于非血瘀证组,但差异无统计学意义(P>0.05)。
2.早期组与健康人组比较,早期组高于健康人组,差异有统计学意义(P<0.05)；中晚期组与健康人组比较,中晚期组高于健康人组,差异有统计学意义(P<0.05)；早期组、中晚期组比较,中晚期组高于早期组,但差异无统计学意义(P>0.05)。
3.未转移组与健康人组比较,未转移组高于健康人组,差异有统计学意义(P<0.05)；转移组与健康人组比较,转移组高于健康人组,差异有统计学意义(P<0.05)；转移组与未转移组比较,转移组高于未转移组,但差异无统计学意义(P>0.05)。
4.肺癌不同中医证型组FIB值与健康人组比较,肺癌不同证型组FIB值均明显高于健康人组,差异有统计学意义(P<0.05)；不同中医证型组FIB值比较,肺郁痰瘀证组>气阴两虚证组>阴虚痰热证组>脾虚痰湿证组,但组间比较差异无统计学意义(P>0.05)。
(四)血小板计数(PLT)比较
1.血瘀证组PLT明显高于健康人对照组,差异有统计学意义(P<0.01)；血瘀证组PLT高于非血瘀证组,但差异无统计学意义(P>0.05)；非血瘀证组高于健康人对照组,但差异无统计学意义(P>0.05)。
2.早期组、中晚期组、健康人对照组PLT比较,差异有统计学意义(P<0.05)；早期组与健康人对照组比较,早期组PLT高于健康人组,差异有统计学意义(P<0.05)；中晚期组高于健康人组,但差异无统计学意义(P>0.05)。
3.未转移组、转移组、健康人对照组PLT比较,差异有统计学意义(P<0.05)；未转移组PLT明显较健康人组增高,差异有统计学意义(P<0.01)；转移组PLT明显较健康人组增高,差异有统计学意义(P<0.05)；未转移组高于转移组,但差异无统计学意义(P>0.05)。
4.不同中医证型组PLT比较,肺郁痰瘀证组高于非血瘀证组(脾虚痰湿证、阴虚痰热证、气阴两虚证),但差异没有统计意义(P>0.05)；肺郁痰瘀证组与健康人对照组比较,明显高于健康人组(P<0.01)。
结论
1.PT是血瘀证重要参考指标
肿瘤患者PT缩短提示血液高凝状态,血瘀证组PT与非血瘀证组、健康人组比较,统计结果虽无统计学意义,但三组比较,体现了健康人组>非血瘀证组>血瘀证组的趋势,体现了血瘀证组比非血瘀证组,非血瘀证组比健康人组机体血液更加高凝的状态,与中医临床辨证为血瘀证(肺郁痰瘀证)、非血瘀证(脾虚痰湿证、阴虚痰热证、气阴两虚证)的认识相一致。2.APTT是血瘀证重要参考指标
APTT缩短,常提示血液高凝状态。本研究结果显示血瘀证组APTT时间并没有比非血瘀证组缩短,但也没有比非血瘀证组APTT时间延长。考虑APTT并非血瘀证的特异性实验指标,只是重要参考指标有关。3.FIB值的升高是瘀血舌象形成的重要病理基础
FIB值的升高与肺癌的发生、进展、转移相关,FIB的升高使肺癌患者的血液处于“浓、粘、凝、聚”的高凝状态,血瘀证组的FIB值高于非血瘀证组,且明显高于健康人对照组,推测FIB值的升高可能是肺癌瘀血舌象形成的重要病理基础。4.PLT值的升高是肺癌瘀血舌象形成的重要环节
PLT值的升高,机体血小板增多,血小板大量堆积,形成血小板血栓,并且血小板表面粘附的蛋白复合物激活凝血酶,使得机体血液凝固性增高,血流减慢,组织缺氧,反映于舌出现瘀血舌象。血瘀证组的PLT值高于非血瘀证组,且明显高于健康人对照组,提示PLT值的升高可能是肺癌瘀血舌象形成的重要环节。
结语
本课题的创新点：
1.本课题研究发现,肺癌患者瘀血舌象以“暗”为主要特征,主要为“暗红舌、淡暗舌”,与以往文献报道肿瘤患者瘀血舌象以“青舌、紫舌、瘀斑瘀点舌”为主的特征不同。认为“暗红舌、淡暗舌”是肺癌瘀血舌的基本舌象,而“青舌、紫舌、瘀斑瘀点舌”是肺癌瘀血舌象的典型舌象。
2.本研究首次从PT、APTT、FIB、PLT角度分析了肺癌瘀血舌象的微观机理,拓宽了肺癌瘀血舌象的研究思路。
Lung carcinoma, as one of the malignant tumors with highest occurrence and mortality rates in the developed countries and the large cities in our country, is a carcinoma with highest ccurrence and mortality rates over the world, with largest increasing occurrence and mortality rates among all the carcinomas. Blood stasis syndrome is one of the basic and main syndromes of the tumors, and the tongue manifestation of blood stasis is of significance in the syndrome differentiation, diagnosis and treatment of tumors. In recent years, more and more clinical practice of integrated traditional and western medicine has demonstrated the superiority and advantages in stabilizing the foci, improving the symptoms, prolonging the survival, enhancing the quality of life, etc, which has paid much attention in the medical field at home and abrord. The blood stasis tongue manifestation is one of the commonly seen manifestations of the tumors, which is of significance in the studies of tongue manifestaions. In the present dissertation, based on the research results of early phase of the project, taking the blood stasis tongue manifestations of lung carcinoma as the breakthrough point, with the literature research, clinical practise and experimental study, etc, the colorful pictures of blood stasis tongue manifestation with representatives were taken. By analyzing the clinical distribution characteristics of the blood stasis tongue of lung carcinoma and the correlations with the indexes of the modern medical tests, it provides the scientific basis for the clinical diagnosis and treatment of lung carcinoma. The present dissertation includes three parts.
Part 1 Literature research
In the present study, with the methods of computer-based comtbined with manual retrievals, the related ancient literatures of the blood stasis tongue, blood stasis syndrome and tumor were systematically discussed. With the methods of computer-based retrieval, the related modern literactures of blood stasis tongue and other tumor studies were systematically analyzed. The literature research indicated that there were rich records of blood stasis tongue manifestations, blood syndrome and tumors in ancient China and there was deep understanding to the close relationships among the three. However, according to these ancient literatures, there were no references of the blood stasis tongue of tumors, which needs further studies. In recent years, increasing research of the blood stasis tongue manifestation of lung carcinoma and other tumors has found that there were some certain rules of the distributions and manifestations of the tongue body, tongue coating and sublingual veins in different phases among the tumor patients. There was hypercoagulability among the patients with lung carcinoma or other tumors, which manifest as abnormal hemorheology, impediment of microcirculation, increasing coagulability of blood, increasing amounts of blood platelet, etc. There was certain relationship between the hypercoagulability of blood and the occurrence, development and metastasis of the carcinoma, and there were certain relationships and rules between the syndrome differentiation and clinical TNM, pathological categories and biolocial indexes (such as hemorheology, four items of coagulation function test, etc).
Part 2 Clinical observation
Objective:By diagnosing and observing the tongue manifestaions of lung carcinoma, the cases with representative blood stasis tongue manifestation were enrolled and the distribution characteristics of the tongue manifestation were analyzed.
Subjects:144 patients with lung carcinoma, including 93 cases in the blood stasis tongue manifestation group and 51 cases in the non-blood stasis tongue manifestation group.
Methods:Integration of observation of tongue manifestation by eye and tongue manifestation pictures taken with digital cameras.
Results and conclusions
2.1 Tongue body
2.1.1 Among the 144 cases enrolled, the colors of the tongues manifest as dull-red, pale dark red, red, dark, pale, purple and ecchymosis, with the dull-red, pale red and pale dark the lagest ratio, accounting for 34.03%, 20.83% and 19.44% respectively. The pale red tongue manifestion is normal, but the dark red and pale dark tongue manifestations account for 53.47%, indicating that there were mostly blood stasis signs among the lung carcinoma patients, which was accordance with the TCM understanding to the tumors and the clinical results of syndrome differentiation.
2.1.2 With the comparison of the tongue body distribution between the blood stasis tongue group and the non-blood stasis tongue group, there were apparently more blood stasis tongue manifestation in the former group than that in the latter group, with significant difference between the two (P<0.05). In the former group, the tongue manifestations from large to small ratio successively were dull-red, pale dark, pale red, dark, pale, purple and ecchymosis, with the dark red the largest, accounting for 44.09%; pale dark secondly, accounting for 18.28%. In the latter group, the tongue manifestations from large to small ratio successively were pale red, pale dark, dull-red, red, purple, dark, pale and ecchymosis, mainly as the pale red and pale dark, accounting for 31.37% and 21.57% respectively. In the former group, the tongue manifestations were manily characteristic as dark, which was accordance with the syndrome differentiation as blood stasis syndrome due to lung depression, phlegm and blood stasis; in the latter group, the tongue manifestations were manily characteristic as pale, which was accordance with the syndrome differentiation as deficiency syndrome due to spleen deficiency and phlegm-dampness, yin-deficiency and phlegm-heat and dual deficiency of qi and yin.
2.1.3 The tongue colors changed with the difference of ages, sexes, metastasis, phases and pathological categories. The distribution characteristics were also different. In the early and middle phases, the cases of blood stasis syndrome of lung carcinoma manifest mainly as dull-red, pale dark and pale red tongue manifestations. However, in the middle and late phases, the ratios of purple and ecchymosis tongue manifestations and sublinguial varicose veins have the tendency of increasing, which maybe was closely related with the serious situation of the patients and the serious blood stasis situation.
2.2 Tongue coating
2.2.1 Among the 144 cases enrolled, most of the manifestations of the tongue coating were white, thin-white, white-greasy and thin-yellowish, particularly the white, accounting the largest ratio.
2.2.2 According to the occurrence frequency of all kinds of the tongue coating, the tongue coating manifestations from large to small ratio in the blood stasis tongue group successively were white, thin-white, thin-yellowish, white-greasy, yellowish, white-thick, yellowish-greasy, yellowish-thick, little coating, yellowish-thick-greasy and peeling coatings. The tongue coating manifestations from large to small ratio in the non-blood stasis tongue group successively were white, white-greasy, little coatings, thin-yellowish, yellowish, peeling coatings, white-thick, white-thick-greasy, yellowish-thick and little coatings. With the statistical management, there was significant difference of the distribution of the tongue coating between the two groups.
2.2.3 The distribution characteristics of the tongue coating among the lung carcinoma patients were different with the difference of the ages, sexes, metastasis, phases and the pathological categories.
2.3 Sublinguial veins
The signs of sublinguial veins accounted for 24.73% in the blood stasis tongue group and 5.88% in the non-blood stasis tongue group, with the signs in the former group obviously higher than that in the latter group, which was accordance with the results of the TCM clinical syndrome differentiation.
Part 3 Clinical experimental research
3.1 Objective:To explore the pathological mechanism of the formation of the blood stasis tongue manifestation of tumors from the experimental aspects.
3.2 Subjects:144 lung carcinoma patients (including 93 cases in the blood stasis tongue group and 51 cases in the non-blood stasis tongue group) and 32 healthy people.
3.3 Methods:Venous blood before breakfast was collected. The following indexes such as prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), platelet count (PLT) were tested with the Sysmex CA1500 and Sysmex XE2100 Auto-blood analyzer.
3.4 Results and conclusions
3.4.1 Comparison of the prothrombin time (PT)
3.4.1.1 The PT of the blood stasis tongue group and the non-blood stasis tongue group were lower than the healthy group, with no significant difference (P>0.05); the PT of the blood stasis tongue group was lower than the non-blood stasis tongue group, with no significant difference (P>0.05).
3.4.1.2 The PT of the non-metastasis group and the metastasis group were lower than the healthy group, with no significant difference (P>0.05); the PT of the non-metastasis group was lower than the metastasis group, with no significant difference (P>0.05).
3.4.1.3 The PT of the early phase group and the middle-late phase group were lower than the healthy group, with no significant difference (P>0.05); the PT of the early phase group was lower than the middle-late phase group, with no significant difference (P>0.05).
3.4.1.4 Among different Chinese medicine syndrome group, the PT of the lung depression, phlegm and blood stasis group, the spleen deficiency, phlegm and dampness group and the Yin deficiency, phlegm and heat group were lower than the healthy group, with no significant difference (P>0.05); the PT of the Qi and Yin deficiency group was higher than the healthy group, with significant difference (P<0.01);the PT among different Chinese medicine groups were not statistically significant (P>0.05).
PT is an important reference index for blood stasis tongue syndrome. The shortening of PT of cancer patients prompted hypercoagulative state of blood. Among the comparison of the PT of the blood stasis tongue group, the non-blood stasis tongue group and the healthy group, the statistical result showed no significant difference.But the result showed as follow:the healthy group > the non-blood stasis tongue group> the blood stasis tongue group.That meaned hypercoagulative state of the blood stasis tongue group was higher than that of the non-blood stasis tongue group, and hypercoagulative state of the non-blood stasis tongue group was higher than that of the healthy group. They are coincide with the understanding of TCM clinical syndrome differentiation for blood stasis tongue syndrome (the lung depression, phlegm and blood stasis syndrome) and non-blood stasis tongue syndrome(the spleen deficiency, phlegm and dampness syndrome, the Yin deficiency, phlegm and heat syndrome and the Qi and Yin deficiency syndrome).
3.4.2 Comparision of the activated partial thromboplastin time (APTT)
3.4.2.1 The APTT among the blood stasis tongue group, the non-blood stasis tongue group and the healthy group were not statistically significant (P>0.05); The APTT between the blood stasis tongue group and the non-blood stasis tongue group was not statistically significant (P>0.05).
3.4.2.2 The APTT between the non-metastasis group, the metastasis group and the healthy group were not statistically significant (P>0.05); The APTT between the non-metastasis group and the metastasis group was not statistically significant (P>0.05).
3.4.2.3 The APTT among the early phase group, the middle-late phase group and the healthy group were not statistically significant (P>0.05); The APTT between the early phase group and the middle-late group was not statistically significant (P>0.05).
3.4.2.4 The APTT between different TCM syndrome group and the healthy group were not statistically significant(P>0.05); The APTT between different TCM syndrome group were not statistically significant (P>0.05).
APTT is an important reference index for blood stasis tongue syndrome. The shortening of APTT often prompted hypercoagulative state of blood. This research showed that the APTT of the blood stasis tongue group was the same as that of the non-blood stasis tongue group. That pointed out APTT was just an important reference index, but not a specificity experimental index.
3.4.3 Comparision of the Fibrinogen (FIB)
3.4.3.1 The FIB of the blood stasis tongue group was higher than the healthy group, with significant difference(P<0.01); the FIB of the non-blood stasis tongue group was higher than the healthy group, with no significant difference(P>0.05); The FIB of the blood stasis tongue group was higher than the non-blood stasis tongue group, with no significant difference (P>0.05).
3.4.3.2 The FIB of the early phase group was higher than the healthy group, with significant difference(P<0.05); the FIB of the middle-late phase group was higher than the healthy group, with significant difference(P<0.05); The FIB of the middle-late phase group was higher than the early phase group, with no significant difference (P>0.05).
3.4.3.3 The FIB of the non-metastasis group was higher than the healthy group, with significant difference(P<0.05); the FIB of the metastasis group was higher than the healthy group, with significant difference(P<0.05); the FIB of the metastasis group was higher than the non-metastasis group, with no significant difference(P>0.05).
3.4.3.4 The FIB of different TCM syndrome group was higher than the healthy group, with siginificant difference(P<0.05); the comparison of different TCM syndrome group on FIB showed that as follow:the lung depression, phlegm and blood stasis group>the Qi and Yin deficiency group>the Yin deficiency, phlegm and heat group>the spleen deficiency, phlegm and dampness group, with no significant difference (P>0.05).
The increasing of the FIB was the important pathologic basis of the formation of blood stasis tongue. The increasing of FIB was related to the occurrence, evolution and metastasis of lung carcinoma. It keeped the blood of lung carcinoma patient in a "thick, sticky, concretionary, congregative" hypercoagulative state. The FIB of blood stasis tongue group was higher than the non-blood stasis group, and was significantly higher than the healthy group. That pointed out the increasing of FIB was the important pathologic basis of the formation of blood stasis tongue.
3.4.4 Comparison of Platelet count (PLT)
3.4.4.1 The PLT of blood stasis tongue group was higher than the healthy group, with significant difference(P<0.01); The PLT of blood stasis tongue group was higher than the non-blood stasis tongue group, with no significant difference(P>0.05); The PLT of non-blood stasis tongue group was higher than the healthy group, with no significant difference (P>0.05).
3.4.4.2 The PLT among the early phase group, the middle-late phase group and the healthy group were statistically significant (P<0.05); the PLT of the early phase group was higher than the healthy group, with significant difference (P<0.05); the PLT of the middle-late phase group was higher than the healthy group, with no significant difference (P>0.05).
3.4.4.3 The PLT among the non-metastasis group,the metastasis group and the healthy group were statistically significant (P<0.05); the PLT of the non-metastasis group was higher than the healthy group, with significant difference (P<0.01); the PLT of the metastasis group was higher than the healthy group, with significant difference(P<0.05); the PLT of the non-metastasis group was higher than the metastasis group, with no significant difference(P>0.05).
3.4.4.4 Among different TCM syndrome group, the PLT of the lung depression, phlegm and blood stasis group was higher than the other syndrome group, with no significant difference (P>0.05); the PLT of the lung depression, phlegm and blood stasis group was higher than the healthy group, with significant difference(P<0.01).
The increasing of the PLT was an important part of the formation of lung carcinoma blood stasis tongue. The number of PLT increased, the number of PLT in body increased, lots of PLT accumulated, all of that formed the PLT thrombosis. The protein complexes which adhered on the surface of the PLT activated thrombin. That increased the blood coagulability, slowed the blood flow, and the tissue were hypoxia. All of that reflectd in the blood stasis tongue. The PLT of the blood stasis tongue group was higher than the non-blood stasis tongue group, and was significantly higher than the healthy group. That pointed out the increasing of the number of PLT maybe an important part of the formation of lung carcinoma blood stasis tongue.
Conclusion
Innovation of the present study 4.1 Taking the blood stasis tongue manifestation as the breakthrough point, in the present research, the characteristics, the rules of the clinical distribution and the mechanism of the formation of the tongue manifestation were systematically analyzed. It indicated that the blood stasis tongue manifestations of lung carcinoma were mainly characteristic with dark, mostly were dull-red, pale dark, which were different from the previous literacture reports on the blood stasis manifestations of tumors as green, purple or ecchymosis. It was thought that the dark red tongue and the dark pale tongue was the basic tongue manifestations of the blood stasis syndrome of lung carcinoma, and the blue, purple and ecchymosis petechia tongues were the typtical tongue manifestations of the blood stasis syndrome of lung carcinoma.
4.2 In the present study, it was firstly analyzed the micro-mechanism of the blood stasis tongue manifestations of lung carcinoma from the perspective of PT, APTT, FIB and PLT, which consequently broadens the study strategies for the blood stasis tongue manifestations of lung carcinoma.
引文
[1]任廷革点校.黄帝内经灵枢经：新校版[M].北京：人民军医出版社,2006.
[2]春秋·秦越人著；柴铁劬,付漫娣校注.难经[M].北京：科学技术文献出版社,2010.
[3]晋·王叔和著.脉经[M].北京：科学技术文献出版社,1996.
[4]宋·严用和著；浙江省中医研究所文献组,湖州中医院整理.重订严氏济生方[M].北京：人民卫生出版社,1980.
[5]李任先主编；徐志伟,陈群副主编.古今舌诊研究与图谱[M].广东：广东科技出版社,1998.
[6]任廷革点校.黄帝内经素问：新校版[M].北京：人民军医出版社,2006.
[7]陈纪藩主编.金匮要略[M].北京：人民卫生出版社,2000.
[8]隋·巢元方等著.诸病源候论[M].北京：人民卫生出版社,1955.
[9]丁光迪主编.诸病源候论校注·上[M].北京：人民卫生出版社,1991.
[10]宋·王怀隐等编.太平圣惠方[M].北京：人民卫生出版社1958.
[11]宋·赵佶编.圣济总录[M].北京：人民卫生出版社,1962.
[12]宋·陈自明著；明·薛已校注；许润三等注释.《校注妇人良方》注释[M].南昌：江西人民出版社,1983.
[13]宋·齐仲甫著.女科百问[M].上海：上海古籍书店,1983.
[14]宋·王璆原著；王伊明点校.是斋百一选方[M].上海：上海中医学院出版社,1990.
[15]宋·施桂堂著.察病指南[M].上海：上海卫生出版社,1957.
[16]清·杜清碧原编；史介生重订.史氏重订敖氏伤寒金镜录[M].杭州：新医书局,1955.
[17]元·滑寿著；张彦红校.难经本义：新校版[M].北京：人民军医出版社,2006.
[18]元·戴起宗撰.脉诀刊误[M].上海：上海科学技术出版社,1958.
[19]明·王肯堂辑；倪和宪,施仲安点校.证治准绳·中册,伤寒证治准绳疡医证治准绳[M].北京：人民卫生出版社,2003.第2版.
[20]明·王肯堂辑；陆拯主编.王肯堂医学全书[M].北京：中国中医药出版社,1999.
[21]明·李中梓著述.诊家正眼[M].上海：上海科学技术出版社,1966.
[22]明·张景岳著；罗元恺点注.妇人规[M].广州：广东科技出版社,1984.
[23]明·薛己等著.薛氏医案选[M].北京：人民卫生出版社,1983.
[24]郑洪新,李敬林主编.周学海医学全书[M].北京：中国中医药出版社,1999.
[25]清·周学海撰.形色外诊简摩[M].北京：人民卫生出版社,1987.
[26]沈凤阁,王灿晖等编著.《外感温热篇》《薛生白温热病篇》阐释[M].南京：江苏科学技术出版社,1983.
[27]汪宏注.望诊遵经[M].上海：上海科学技术出版社,1959.
[28]清·吴坤安撰；清·邵仙根评.伤寒指掌[M].上海：上海卫生出版社,1957.
[29]俞根初遗著；徐荣齐重订.重订通俗伤寒论[M].上海：上海卫生出版社,1956.
[30]清·裘吉和原编；王玉润等审订,五邦傅.脉诀乳海[M].上海：上海科学技术出版社,1985.
[31]清·张登撰.伤寒舌鉴[M].上海：上海科学技术出版社,1958.
[32]清·吴谦等编.医宗金鉴[M].北京：人民卫生出版社,1963.
[33]民国·吴瑞甫编著；刘德荣,金丽点校.中西温热串解[M].福州：福建科学技术出版 社,2003.
[34]曹炳章原著；张成博,欧阳兵,唐迎雪点校.辨舌指南[M].天津：天津科学技术出版社,2004.
[35]何文彬.“瘀血”与“血瘀”辨[J].北京中医药大学学报,2000,23(6)：14-15
[36]周岱翰主编.临床中医肿瘤学[M].北京：人民卫生出版社,2003.
[37]唐·孙思邈著.备急千金要方[M].太原：山西科学技术出版社,2010.
[38]朱震亨撰.丹溪心法[M].北京：北京市中国书店,1986.
[39]明·陈实功编著；吴少祯,许建平点校.外科正宗[M].北京：中国中医药出版社,2002.
[40]明·徐春甫编集；崔仲平,王耀廷主编.古今医统大全[M].北京：人民卫生出版社,1991.
[41]清·祁坤编著.外科大成[M].上海：上海科学技术出版社,1958.
[42]清·邹五峰著.外科真诠[M].上海：上海中医书局,1955.
[43]清·王清任撰；李天德,张学文整理.医林改错[M].北京：人民卫生出版社,2005.
[44]清·唐宗海原著；欧阳兵,李文华,韩涛点校.血证论[M].天津：天津科学技术出版社,2003.
[45]清·杨云峰,刘恒瑞著.临症验舌法察舌辨症新法[M].北京：人民卫生出版社,1960.
[46]柴雅倩.基于数据挖掘技术的瘀血舌研究[D].广州,广州中医药大学,2008年
[47]苏全胜,林勇,杨继红,等.癌症患者猝死前舌脉象变化分析[J].中国中医急症,2005；14(2)：152-152.
[48]陈群,徐志伟,路艳.79例肺癌患者瘀血舌象临床观察研究[J].国医论坛,2005；20(3)：10-11.
[49]王淑英.426例蓝紫舌探析[J].浙江中医杂志,2001；36(9)：406-407.
[50]李乃民,闫子飞,林晓东,等.舌脉的临床研究[J].中华临床医学杂志,2007；8(4)：14-16.
[51]窦永起.舌下络脉与传统舌象对血瘀证诊断价值的比较[J].中国中医急症,2005；14(1)：44-45,68.
[52]靳士英,何尚宽,司兆学,等.舌下络脉显现类型及其实质的研究[J].广州中医药大学学报,1998；15(1)：1-5.
[53]季光,张海峰.从200例舌下脉看其对瘀血症的诊断意义[J].中医研究,1994；7(1)：23-24.
[54]武哲丽,刘梅,陈群,等.肝病瘀血舌象不同证型血液流变学的临床实验研究[J].辽宁中医杂志,2008；35(7)：968-970.
[55]柴雅倩,徐志伟,陈群.瘀血舌辨证分型与血液流变学指标变化的关系探讨[J].中医药通报,2006；5(4)：43-46.
[56]柴雅倩,陈群,徐志伟.瘀血舌血液流变学指标与血管超声指标的相关性[J].中医杂志,2007；48(8)：733-734,744.
[57]王东方,干祖望.慢性鼻炎舌诊和血液流变学观察与血瘀关系探讨[J].中国中西医结合耳鼻咽喉科杂志,1996；4(3)：106-108.
[58]王东方,覃都安.声带息肉的舌诊及血液流变与血瘀关系的探讨[J].辽宁中医杂志，1995；22(10)：433-434.
[59]李芝秀,李慧曼,潭自民,等.慢性结石性胆囊炎血液流变学研究[J].贵阳医学院学报,1989；14(1)：16-18.
[60]孙艳,贾彦焘.肿瘤患者瘀血舌象与凝血五项指标间的联系[J].辽宁中医杂志,2007；34(6)：718-719.
[61]路艳,陈群,刘展华.60例肺癌患者瘀血舌象、肿瘤转移与tPA、PAI-1的联系[J].中医研究,2006；19(5)：26-27.
[62]陈群,徐志伟,路艳.肺癌患者瘀血舌象与血浆TXA2／PGI2相关性研究[J].中国中西医结合杂志,2006；26(1)：71.
[63]陈群,杨爱萍,易玮.妇科疾病瘀血舌象与血浆α-颗粒膜蛋白相关性研究[J].中华现代中西医杂志,2003；1(2)：137-139.
[64]徐志伟,陈群,柴雅倩,等.瘀血舌彩色多普勒血流分析的初步探讨[J].中医杂志,2008；49(2)
[65]李乃民,张永丰,王淑英,等.血瘀证的舌象研究[J].中西医结合杂志,1991；11(1)：28-30.
[66]梁民里道.舌脉与血淤证关系的研究[J].福建中医药,1990；21(6)：15-17.
[67]武哲丽,陈群,徐志伟,等.肝病瘀血舌象患者与血瘀证各组ET/NO的临床实验研究[J].四川中医,2008；26(5)：4-5.
[68]赵京生,代启宇,李拴位,等.瘀证舌象与中分子物质[J].实用新医学,2000；2(10)：868-869.
[69]武哲丽,陈群,徐志伟,等.肝病瘀血舌象与血瘀证舌温临床研究[J].中国中医药信息杂志,2008；15(7)：22-24.
[70]唐永祥,陈群,王晓玲.慢性阻塞性肺病急性发作期瘀血舌象的相关性研究[J].广西中医药,2004；27(2)：8-9.
[71]陈群,徐志伟,杨爱萍.内分泌紊乱与子宫肌瘤慢性盆腔炎瘀血舌象形成相关性研究[J].中医药学刊,2004；22(9)：1576-1577.
[72]张延年,孙宗信,李为民等.内科急腹症舌质表现与血清微量元素锌铜含量关系的观察[J].微量元素与健康研究,1994；11(4)：36.
[73]陈连起.舌苔血清微量元素与辨证相关性的探讨[J].辽宁中医杂志,1993；20(10)：8-9.
[74]魏海峰,亚白柳,赵玲,等.急性脑缺血大鼠模型血瘀证舌象表现的评价方法及其与血液流变学的关系[J].中西医结合学报,2008；6(1)：73-76.
[75]李乐军,田金洲,尹军祥,等.不同脑缺血诱发血瘀证表征模型的研究[J].北京中医药大学学报,2007；30(12)：816-818.
[76]尹军祥,田金洲,王永炎,等.血瘀证模型大鼠舌象评价标准研究[J].北京中医药大学学报,2007；30(8)：529-531.
[77]扈新刚,张允岭,柳洪胜,等.气虚血瘀大鼠模型表征及血液流变学研究[J].天津中医药,2007；24(2)：138-141.
[78]姜智浩,王怡,范祥,等.血瘀证动物模型舌体动脉血管形态研究[J].辽宁中医杂志,2008；35(7)：1098-1099.
[79]陈群,徐志伟,莫传伟,等.运用信息融合技术建立瘀血舌象及血瘀证智能诊断推理模型的思路[J].广州中医药大学学报,2007；24(6)：506-508.
[80]徐志伟,陈群,张书河.青紫类舌色的色度量化特征研究新探[J].中医药学刊,2004；22(8)：1374-1376.
[81]许秀森,翁维良.血瘀证舌质定量诊断研究[J].中国中医药科技,1994；1(1)10-14.
[82]Yan Z, Wang K, Li N. Computerized feature quantification of sublingual veins from color sublingual images [J].Comput Methods Programs Biomed.2009; 93(2):192-205.
[83]Chiu CC, Lan CY, Chang YH. Objective assessment of blood stasis using computerized inspection of sublingual veins [J]. Comput Methods Programs Biomed. 2002;69(1):1-12.
[84]翁维良,黄世敬,洪尚杓.运用中医舌诊专家系统对血瘀证舌下络脉的观察[J].中医杂 志,2001；42(4)：233-235.
[85]Takeichi M, Sato T. Computerized color analysis of "xue yu" (blood stasis) in the sublingual vein using a new technology [J]. Am J Chin Med.1997; 25(2):213-219.
[86]张灵芝.肺癌辨证论治的探讨[J].河南中医,2006；26(；)：37-38.
[87]张霆.肺癌辨证治疗误区之我见[J].辽宁中医杂志,2007；34(2)：153-154.
[88]赵炜.李佩文治疗肺癌的经验[J].北京中医杂志,2002；21(6)：329-330.
[89]邓海滨,王中奇.徐振晔辨治肺癌经验[J].四川中医,2002；20(6)：1-2.
[90]陈延武,樊惠连.胡国良老中医临证经验总结[J].湖南中医杂志,1998；14(3)：27-28.
[91]周晓园,陶凯.顾振东治疗肿瘤的经验[J].中医杂志,1999；40(7)：395-397.
[92]孙宏新,孙君.周宜强教授诊治肺癌经验[J].中国中医药信息杂志,2000；7(4)：68-69.
[93]洪广祥.原发性支气管肺癌中医药治疗的探讨[J].江西中医药,1995；26(6)：3.
[94]李华.肺癌的中医辨治体会[J].光明中医,2002；17(99)：20-22.
[95]常青.对中医规范化辨证治疗肺癌的探讨[J].光明中医,2002；17(100)：16-18.
[96]孙钢.刘嘉湘辨治肺癌特色[J].中医杂志,2000；41(2)：75.
[97]朴炳奎.原发性支气管肺癌中西医结合诊治方案[J].中国肿瘤,1995；4(5)：4.
[98]周岱翰.肿瘤治验集要[M].广州：广东高教出版社,1997：141.
[99]陈四清.原发性支气管肺癌辨证分型探讨[J].新中医,2002；34(11)：6-8.
[100]左明焕,王芬,胡凯文等.中晚期肺癌的中医聚类分型[J].中国中医药信息杂志,2006；10,13(10)：28-29.
[101]胡小梅,张培彤,杨宗艳等.中晚期非小细胞肺癌患者中医证型分布规律研究[J].中国肿瘤,2007；16(1)：51-53.
[102]施志明.原发性肺癌中医辨证分型与西医分期及细胞类型关系[J].中国癌症杂志,1998；8(4)：317-318.
[103]顾梦飚.480例原发性肺癌中医证型与国际TNM分期相关分析[J].上海中医药杂志,1994；(4)：1.
[104]吴燕波,蔡明明,朱旭东.100例原发性肺癌中医辨证分型与临床病理分型的关系[J].江苏中医,1993；(2)：11-12.
[105]申维玺,孙燕,刘玉梅.中医虚证与肺癌生物学行为关系的研究[J].实用肿瘤杂志,2001；16(2)：126-128.
[106]周伟生.中晚期周围型肺癌临床分期病理分型与中医证型相关性研究[J].中医药学刊,2006；24(8)：1436-1437.
[107]胡小梅,张培彤,杨宗艳等.非小细胞肺癌不同病病理分类与中医证候分布规律关系探讨[J].中国中医药信息杂志,2006；12,13(12)：19-21.
[108]应丽雅.原发性肺癌与中医“痰”和“瘀”相关性临床观察[J].浙江中西医结合杂志,2001；11(7)：434-435.
[109]张有明,吕学术,彭金花,等.20例晚期肺癌病人的中医分型与血流变学改变[J].天津中医,1991；(2)：19-20.
[110]章康尔,郭勇.中晚期肺癌66例临床辨证分析[J].辽宁中医杂志,1999,26(6)：256.
[111]富琦,王笑民,杨国旺.肺癌患者化疗期间中医证型及升血汤干预作用研究[J].中国中医药信息杂志,2006；13(9)：17-19.
[112]孙韬.原发小细胞肺癌化疗前后中医证候特征研究[J].中国医药学报,2002；17(6)：378-379.
[113]黎敬波,张征,林丽珠.非小细胞肺癌手术前后证候变化的对照研究[J].新中医,2008；9,40(9)：24-25.
[114]姚嫱,徐宗佩.107例癌症患者舌象临床观察[J].天津中医学院学报,1996；14(1)：16.
[115]徐文均,吴建华.326例癌症患者舌象分析[J].福建中医药,1994；25(3)：14-15.
[116]陈健民.癌症患者舌象的临床观察及原理研究[J].中国医药学报,1990；5(1)：35-37.
[117]李晓丽,李焕荣.肿瘤转移的“毒结、血瘀、寒凝”病机探讨[J].中华中医药杂志,2006；21(7)：440-441.
[118]刘忠源.舌像在恶性肿瘤治疗前后变化的临床观察[J].中国肿瘤临床,1997；24(5)：374-376.
[119]崔立献,栗海青.232例恶性肿瘤病人舌象分析[J].山东中医杂志,1994；13(3)：106-106.
[120]王福田.癌症的舌象浅析[J].辽宁中医杂志,1991；18(9)：27-27.
[121]朴万山,马淑坤.上消化道恶性肿瘤与舌象关系[J].黑龙江中医药,1994；(6)：3-4.
[122]向荣.上消化道癌与消化系统良性疾病舌象的对比研究[J].云南中医中药杂志,2005；26(2)：38-39.
[123]李天海,李瑞英.舌诊在食管责门癌防治中的应用[J].河北中医,1997；19(1)：2-3.
[124]施边镇.125例食管、贲门癌患者的舌象与临床诊断资料分析[J].陕西中医,1990；11(8)：340-341.
[125]周阿高,黄大慰,顾伟威.胃肿瘤患者4项观察指标相关性探讨[J].浙江中西医结合杂志,2000；10(6)：327-329.
[126]范德荣,林瑞奋,林欣.胃癌患者舌象与病机分析[J].中医杂志,1991；(10)：34-35.
[127]胡丕丽,黄火文,张蓓.活血化瘀汤对鼻咽癌放射治疗患者舌象及血液流变性的影响[J].中医杂志,1996；37(2)：104-106.
[128]张蓓,陈效莲,黄伙文.鼻咽癌放疗后青紫舌患者远期疗效观察[J].中医杂志,1990；31(4)：29-30.
[129]张欣,崔雅平,钱海龙.52例肺肿瘤患者放疗前后舌象分析及病机临床研究[J].中华临床医学研究杂志,2007；13(24)：3516-3516.
[130]万晓凤.肺癌的常见临床舌象观察[J].实用中西医结合临床,2003；3(4)：32-32.
[131]黄海茵,苏晋梅,韩明权,等.肺癌与一般呼吸系统疾病舌象的对比研究[J].中医杂志,2002；43(7)：535-536.
[132]刘庆.原发性肝癌舌象“肝瘿线”探析[J].安徽中医学院学报,2002；21(6)：3-5.
[133]冯晓灵,聂玉萍,吴恒举,等.128例原发性肝癌临床分期与舌象的关系分析[J].江苏中医,1991；12(1)：41-42.
[134]王其萍,祝肇刚.青紫舌与血液流变学关系的探讨[J].中国微循环,1997；1(1)：46-47.
[135]Koh S C, Tham-K-F, Razvi Ketal, et al. hemostatic and fibrinolytiec status in patients with ovarian cancer and benign ovarian cysts:could D-dimer and antithrombinⅢlevels be included as prognostic markers for survival outcome? [J]. Clinical and Applied Thrombosis/Hemostasis,2001; 7(2):141-148.
[136]Caputo F, Musardo G, Savini P, et al. Occult colon cancer in a patient with an unexplained episode of pulmonary embolism[J]. Hepato-gastroenterology,2000; 47(31):165-167.
[137]Falanga A, Levine M N, Consonni R, et al. The effect of very-low-dose warfarin on markers of hypercoagulation in metastatic breast cancer: results from a randomized trial [J]. Thrombosis and Haemostasis,1998; 79(1):23-27.
[138]Falanga A, Toma S, Marchetti M, et al.Effect of all-trans-retinoic acid on the hypercoagulable state of patients with breast cancer [J]. American Journal of Hematology, 2002; 70(1):9-15.
[139]Gastpar H, Ambrus JL, Ambrus CM. Platelet cancer cell interaction in metastasis formation. Platelet aggregation inhibitors:a possible approach to metastasis prevention [J]. Prog Clin Biol Res,1982; 89:63-82.
[140]Honn KV, Tang DC, Chen YQ. Platelet and cancer metastasis:more than an epiphenomenon [J]. Semin Thromb Hemost.1992; 18(4):392-415.
[141]Grignani G, Pacchiarini L, Pagliarino M.The possible role of blood platelet in tumor growth and dissemination. Haematologica [J].1986; 71(3):245-255.
[142]Costantini V, Zacharski LR, Moritz TE, et al. The platelet count in carcinoma of the lung and colon[J]. Thromb Haemost,1990; 64(4):501-505.
[143]Frojmovic M M, Milton J G. Human platelet size, shape, and related functions in health and disease. physiological reviews,1982;62(1):185-261.
[144]Wu GX, Xi Xd, Li PX. Preparation of a monoclonal antibody, SZ-51, that recognizes as a granule membrane protein (GMP-140) on the surface of activated human platelets [J]. Nouv Rev Fr Hematol.1990; 32(4):231-235.
[145]Sherlock S. Diseases of the liver and biliary system (M). London:Blackwell Science Ltd,1975; 5th edition:677.
[146]De Bruin PA, Griffioen G, Verspaget HW, et al. Plasminogen activators and tumor development in the human colon:activity levels in normal mucosa, adenomatous polyps, and adenocarcinomas[J]. Cancer Res,1987; 47(17):4654-4657.
[147]Reich R, Thompson EW, Iwamoto Y, et al. Effects of Inhibitors of Plasminogen Activator, Serine Proteinases, and Collagenase Ⅳ on the Invasion of Basement Membranes by Metastatic Cells[J]. Cancer research,1988; 48(12):3307-3312.
[148]Lee JH, Ryu KW, Kim S, et al. Preoperative plasma fibrinogen levels in gastric cancer patients correlate with extent of tumor [J]. Hepatogastroenterology,2004; 51(60):1860-1863.
[149]Wang WS, Lin JK, Lin TC, et al. Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma [J]. World J Gastroenterol, 2005;11(14):2166.
[150]刘永惠,杨晓峰,周冬枝等.肿瘤转移与血瘀证的临床研究[J].中国中医基础医学杂志,2002；8(4)：50-58.
[151]刘永惠.血瘀证与肿瘤及其转移患者血浆内血小板GMP-140的研究[J].中医药学刊,2002；20(3)：364-365.
[152]周阿高,丁钰熊,陈梅芳.140例胃部恶性肿瘤患者手术前后和死亡前血瘀证研究[J].中西医结合杂志,1990；10(9)：540-541.
[153]Aitokallio-Tallberg A, Karkkainen J, Pantzar P, et al. Prostacyclin and thromboxane in breast cancer:relationship between steroid receptor status and medroxyprogesterone acetate[J]. Br J Cancer,1985; 51(5):671-674.
[154]Slotman GJ. Plasma thromboxane A2 and prostacyclin concentrations in squamous cell carcinoma of the head and neck[J]. J Surg Oncol,1988; 38(1):33-37.
[155]Mehta P. Potential role of platelets in the pathogenesis of tumor metastasis [J]. Blood, 1984; 63(1):55-63.
[156]陈群,徐志伟,路艳.肺癌患者瘀血舌象与血浆TXA2/PGI2相关性研究[J].中国中西医结合杂志,2006；26(1)：71.
[157]齐元富,钱伯文,陈伟.41例胃癌患者血瘀证研究及活血化瘀治疗作用的观察[J].陕西中医,1996；17(1)：12.
[158]陈震,刘鲁明,何以蓓.血瘀证模型大鼠血栓烷B2、6-酮-前列腺素F与肿瘤肝转移的关系[J].中西医结合学报,2003；1(3)：199-201.
[159]吴朝泰,陈群,徐勤,等.血瘀证在肿瘤不同阶段的变化特征[J].国医论坛,2000；15(2)： 23-25.
[160]李绮云,罗泽民,罗香宁.恶性肿瘤患者甲襞微循环检测临床意义研究[J].临床肿瘤学杂志,1999；4(2)：43-44.
[161]高捷,李学.甲皱微循环检查在肿瘤治疗中的应用[J].中日友好医院学报,1996；10(4)：319-322.
[162]宋丽杰,马雪平,姚桂玲,等.血小板计数临床应用研究现状[J].临床检验杂志,1999；17(4)：252-253.
[163]Nieswandt B, Hafner M, Echtenacher B, et al. Lysis of tumor cells by natural killer cells in mice is impeded by platelets [J]. Cancer Res,1999; 59(6):1295-1300.
[164]Ikeda M,Furukawa H,Imamura H,et al.Poor prognosis associated with thrombocytosis in patients with gastric cancer[J].Ann Surg Oncol,2002;9(3):287-291.
[165]Corbett G, Perry DJ. Significance of thrombocytosis [J]. Lancet, 1983;1(8314-8315):77.
[166]吕新厅,李英杰.血小板计数与胃癌分期及预后的关系[J].中国肿瘤临床,2008；35(24)：1393-1394.
[167]樊丽娟,么玲,何恒,等.血小板计数与结肠癌的临床病理分析[J].中国全科医学,2008；11(8)：1364-1365.
[168]梁致怡,张虹.卵巢上皮性癌和血小板计数增高相关性分析[J].中国肿瘤临床,2008；35(13)：729-735.
[169]张雯,王婷婷,杜鹃,等.血小板计数与非小细胞肺癌分期及预后的关系[J].现代肿瘤医学,2007；15(3)：341-342.
[170]黄建国,王勇强,贺江虹,等.恶性肿瘤患者不同病期血小板参数变化及其临床意义[J].中国误诊学杂志,2009；9(22)：5356-5357.
[171]Syrjala H, Surcel H M, Ilonen J. Low CD4/CD8 T lymphocyte ratio in acute myocardial infarction [J]. Clin Exp Immunol,1991; 83(2):326-328.
[172]陈群,杨爱萍,易玮.妇科疾病瘀血舌象与血浆a-颗粒膜蛋白相关性研究[J].中华现代中西医杂志,2003；1(2)：137-139.
[173]山东省医科所.“舌诊”物质基础的探讨[J].山东医药,1978；(8)：27.
[174]湖南中医学院.206例舌象临床观察的初步分析[J].湖南省肿瘤防治研究,1979；(1)： 52.
[175]郭英华,孟繁会,王仁本.恶性肿瘤患者与血栓症[J].中华肿瘤防治杂志,2006；13(11)：875.
[176]欧晋平,虞积仁.恶性肿瘤与血栓[J].内科急危重症杂志,2001；7(4)：214.
[177]Yoshida T, Osato H, Sakon M, et al. Locoregional injection of OK-432/fibrinogen/thrombin for unresectable metastatic liver tumors [J]. Gan To Kagaku Ryoho.1996; 23(11):1575-1577.
[178]Wang WS, Lin JK, Lin TC, et al. Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma [J]. World J Gastroenterol.2005; 11(14):2166-2170.
[179]Lee JH, Ryu KW, Kim S, et al. Preoperative plasma fibrinogen levels in gastric cancer prtients correlate with extent of tumor[J]. Hepatogas-troente rology,2004;51(60): 1860-1863.
[180]Wang WS, LinJK, Lin TC, et sl. Plasma von Willebrand factor level as a pmgnostic indicator of patients with metastatic coloreetal careinoma[J]. World J Gastroenterol, 2005;11(14):2166.
[181]Zetter BR. The cellular basis of site-specific tumor metastasis [J]. N Engl J Med. 1990;322(9):605-612.
[182]Peerschke El. Recognition of platelet-associated fibrinogen by polyclonal antibodies: correlation with platelet aggregation. Blood.1992; 79(8):2028-2033.
[183]Biggerstaff JP, Seth N, Amirkhosravi A, et, al. Soluble fibrin augments platelet/tumor cell adherence in vitro and in vivo, and enhances experimental metastasis. Clin Exp Metastasis.1999; 17(8):723-730.
[184]王玉斌,刘晓棠,陈文俊,等.恶性肿瘤患者治疗前后血浆纤维蛋白原含量分析[J].浙江临床医学,2007；9(7)：893-894.
[185]Levin J, et al.Thrombocytosis associated with malignant disease [J].Arch Inter Med, 1964; 114:479.
[186]CostantiniV, ZacharskiLR, MoritzTE, etal.The platelet count in carcinoma of the lung and colon [J]. Thromb Haemost,1990; 64(4):501-505.
[187]FerrignoD, BuccheriG. Hematologic counts and clinical correlates in 1201 newly diagnosed lung cancer patients [J].Monaldi Arch ChestDis,2003; 59(3):193-198.
[188]Pedersen LM, Milman N. Diagnostic significance of platelet count and other blood analyses in patientswith lung cancer [J]. Oncol Rep,2003; 10(1):213-216.
[189]O'Keefe S C, Marshall F F, Issa M M, et al.Thrombocytosis is associated with a significant increase in the cancer specific death rate after radical nephrectomy [J]. J Urol, 2002; 168:1378-1380.
[190]Hernandez E, Donohue K A, Anderson L L, et al. The significance of thrombocytosis in patients with locally advanced cervical carcinoma:a Gynecologic Oncology Group study [J]. Gynecol Oncol,2000; 78:137-142.
[191]JuraszP, Alonso-EscolanoD, RadomskiMW. Platelet-cancer interactions:mechanisms and pharmacology of tumor cell-induced platelet aggregation [J]. Br J Pharmaco, 2004;143(7):819-826.
[192]BOZKURT N, YUCE K, BASARAN M et al.Correlation of platelet count with second-look laparotomy results and disease progression in patients with advanced epithelial ovarian cancer [J].Obstet Gynecol,2004; 103(1):82-85.
[193]Furuhashi M,Miyabe Y,Oda H.A case of thrombopoietin producing ovarian carcinoma confirmed by immunohistochemistry[J].Gynecol Oncol,1999;74:278-281.
[194]Salgado R,Benoy I, Weytjens R, et al. Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer [J].Br J Cancer,2002; 87:1437-1444.
[195]BOZKURT N, YUCE K, BASARAN M et al.Correlation of platelet count with second-look laparotomy results and disease progression in patients with advanced epithelial ovarian cancer [J].Obstet Gynecol,2004; 103(1):82-85.
[196]MONREAL M, FERNANDEZ-LIAMAZARES J,PINOL M,et al. Platelet count and survival in patients with colorectal cancer-a preliminary study [J].Thromb Haemost,1998;79(5):916-918.
[197]DOMINGUEZ I.CRIPPA S,THAYER S P,et al. Preoperative platelet count and survival prognosis in resected pancreatic ductal adenocarcinoma [J].World J Surg,2008;32(6):1051-1056.
[198]Honn KV, Tang DG, Crissman JD. Platelets and cancer metastasis:a causal relationship? [J]. Cancer Metastasis Rev.1992; 11(3-4):325-351.
[199]Gastpar H, Ambrus JL, Ambrus CM. Platelet cancer cell interaction in metastasis formation. Platelet aggregation inhibitors:a possible approach to metastasis prevention [J]. Prog Clin Biol Res.1982; 89:63-82.
[200]Nies wandt B, HafnerM, Echtenacher B, et al.Lysis of tumor cells by natural killer cells in mice is impeded by platelets[J].Cancer Res,1999; 59 (6):1295-1300.
[2]春秋·秦越人著；柴铁劬,付漫娣校注.难经[M].北京：科学技术文献出版社,2010.
[3]晋·王叔和著.脉经[M].北京：科学技术文献出版社,1996.
[4]宋·严用和著；浙江省中医研究所文献组,湖州中医院整理.重订严氏济生方[M].北京：人民卫生出版社,1980.
[5]李任先主编；徐志伟,陈群副主编.古今舌诊研究与图谱[M].广东：广东科技出版社,1998.
[6]任廷革点校.黄帝内经素问：新校版[M].北京：人民军医出版社,2006.
[7]陈纪藩主编.金匮要略[M].北京：人民卫生出版社,2000.
[8]隋·巢元方等著.诸病源候论[M].北京：人民卫生出版社,1955.
[9]丁光迪主编.诸病源候论校注·上[M].北京：人民卫生出版社,1991.
[10]宋·王怀隐等编.太平圣惠方[M].北京：人民卫生出版社1958.
[11]宋·赵佶编.圣济总录[M].北京：人民卫生出版社,1962.
[12]宋·陈自明著；明·薛已校注；许润三等注释.《校注妇人良方》注释[M].南昌：江西人民出版社,1983.
[13]宋·齐仲甫著.女科百问[M].上海：上海古籍书店,1983.
[14]宋·王璆原著；王伊明点校.是斋百一选方[M].上海：上海中医学院出版社,1990.
[15]宋·施桂堂著.察病指南[M].上海：上海卫生出版社,1957.
[16]清·杜清碧原编；史介生重订.史氏重订敖氏伤寒金镜录[M].杭州：新医书局,1955.
[17]元·滑寿著；张彦红校.难经本义：新校版[M].北京：人民军医出版社,2006.
[18]元·戴起宗撰.脉诀刊误[M].上海：上海科学技术出版社,1958.
[19]明·王肯堂辑；倪和宪,施仲安点校.证治准绳·中册,伤寒证治准绳疡医证治准绳[M].北京：人民卫生出版社,2003.第2版.
[20]明·王肯堂辑；陆拯主编.王肯堂医学全书[M].北京：中国中医药出版社,1999.
[21]明·李中梓著述.诊家正眼[M].上海：上海科学技术出版社,1966.
[22]明·张景岳著；罗元恺点注.妇人规[M].广州：广东科技出版社,1984.
[23]明·薛己等著.薛氏医案选[M].北京：人民卫生出版社,1983.
[24]郑洪新,李敬林主编.周学海医学全书[M].北京：中国中医药出版社,1999.
[25]清·周学海撰.形色外诊简摩[M].北京：人民卫生出版社,1987.
[26]沈凤阁,王灿晖等编著.《外感温热篇》《薛生白温热病篇》阐释[M].南京：江苏科学技术出版社,1983.
[27]汪宏注.望诊遵经[M].上海：上海科学技术出版社,1959.
[28]清·吴坤安撰；清·邵仙根评.伤寒指掌[M].上海：上海卫生出版社,1957.
[29]俞根初遗著；徐荣齐重订.重订通俗伤寒论[M].上海：上海卫生出版社,1956.
[30]清·裘吉和原编；王玉润等审订,五邦傅.脉诀乳海[M].上海：上海科学技术出版社,1985.
[31]清·张登撰.伤寒舌鉴[M].上海：上海科学技术出版社,1958.
[32]清·吴谦等编.医宗金鉴[M].北京：人民卫生出版社,1963.
[33]民国·吴瑞甫编著；刘德荣,金丽点校.中西温热串解[M].福州：福建科学技术出版 社,2003.
[34]曹炳章原著；张成博,欧阳兵,唐迎雪点校.辨舌指南[M].天津：天津科学技术出版社,2004.
[35]何文彬.“瘀血”与“血瘀”辨[J].北京中医药大学学报,2000,23(6)：14-15
[36]周岱翰主编.临床中医肿瘤学[M].北京：人民卫生出版社,2003.
[37]唐·孙思邈著.备急千金要方[M].太原：山西科学技术出版社,2010.
[38]朱震亨撰.丹溪心法[M].北京：北京市中国书店,1986.
[39]明·陈实功编著；吴少祯,许建平点校.外科正宗[M].北京：中国中医药出版社,2002.
[40]明·徐春甫编集；崔仲平,王耀廷主编.古今医统大全[M].北京：人民卫生出版社,1991.
[41]清·祁坤编著.外科大成[M].上海：上海科学技术出版社,1958.
[42]清·邹五峰著.外科真诠[M].上海：上海中医书局,1955.
[43]清·王清任撰；李天德,张学文整理.医林改错[M].北京：人民卫生出版社,2005.
[44]清·唐宗海原著；欧阳兵,李文华,韩涛点校.血证论[M].天津：天津科学技术出版社,2003.
[45]清·杨云峰,刘恒瑞著.临症验舌法察舌辨症新法[M].北京：人民卫生出版社,1960.
[46]柴雅倩.基于数据挖掘技术的瘀血舌研究[D].广州,广州中医药大学,2008年
[47]苏全胜,林勇,杨继红,等.癌症患者猝死前舌脉象变化分析[J].中国中医急症,2005；14(2)：152-152.
[48]陈群,徐志伟,路艳.79例肺癌患者瘀血舌象临床观察研究[J].国医论坛,2005；20(3)：10-11.
[49]王淑英.426例蓝紫舌探析[J].浙江中医杂志,2001；36(9)：406-407.
[50]李乃民,闫子飞,林晓东,等.舌脉的临床研究[J].中华临床医学杂志,2007；8(4)：14-16.
[51]窦永起.舌下络脉与传统舌象对血瘀证诊断价值的比较[J].中国中医急症,2005；14(1)：44-45,68.
[52]靳士英,何尚宽,司兆学,等.舌下络脉显现类型及其实质的研究[J].广州中医药大学学报,1998；15(1)：1-5.
[53]季光,张海峰.从200例舌下脉看其对瘀血症的诊断意义[J].中医研究,1994；7(1)：23-24.
[54]武哲丽,刘梅,陈群,等.肝病瘀血舌象不同证型血液流变学的临床实验研究[J].辽宁中医杂志,2008；35(7)：968-970.
[55]柴雅倩,徐志伟,陈群.瘀血舌辨证分型与血液流变学指标变化的关系探讨[J].中医药通报,2006；5(4)：43-46.
[56]柴雅倩,陈群,徐志伟.瘀血舌血液流变学指标与血管超声指标的相关性[J].中医杂志,2007；48(8)：733-734,744.
[57]王东方,干祖望.慢性鼻炎舌诊和血液流变学观察与血瘀关系探讨[J].中国中西医结合耳鼻咽喉科杂志,1996；4(3)：106-108.
[58]王东方,覃都安.声带息肉的舌诊及血液流变与血瘀关系的探讨[J].辽宁中医杂志，1995；22(10)：433-434.
[59]李芝秀,李慧曼,潭自民,等.慢性结石性胆囊炎血液流变学研究[J].贵阳医学院学报,1989；14(1)：16-18.
[60]孙艳,贾彦焘.肿瘤患者瘀血舌象与凝血五项指标间的联系[J].辽宁中医杂志,2007；34(6)：718-719.
[61]路艳,陈群,刘展华.60例肺癌患者瘀血舌象、肿瘤转移与tPA、PAI-1的联系[J].中医研究,2006；19(5)：26-27.
[62]陈群,徐志伟,路艳.肺癌患者瘀血舌象与血浆TXA2／PGI2相关性研究[J].中国中西医结合杂志,2006；26(1)：71.
[63]陈群,杨爱萍,易玮.妇科疾病瘀血舌象与血浆α-颗粒膜蛋白相关性研究[J].中华现代中西医杂志,2003；1(2)：137-139.
[64]徐志伟,陈群,柴雅倩,等.瘀血舌彩色多普勒血流分析的初步探讨[J].中医杂志,2008；49(2)
[65]李乃民,张永丰,王淑英,等.血瘀证的舌象研究[J].中西医结合杂志,1991；11(1)：28-30.
[66]梁民里道.舌脉与血淤证关系的研究[J].福建中医药,1990；21(6)：15-17.
[67]武哲丽,陈群,徐志伟,等.肝病瘀血舌象患者与血瘀证各组ET/NO的临床实验研究[J].四川中医,2008；26(5)：4-5.
[68]赵京生,代启宇,李拴位,等.瘀证舌象与中分子物质[J].实用新医学,2000；2(10)：868-869.
[69]武哲丽,陈群,徐志伟,等.肝病瘀血舌象与血瘀证舌温临床研究[J].中国中医药信息杂志,2008；15(7)：22-24.
[70]唐永祥,陈群,王晓玲.慢性阻塞性肺病急性发作期瘀血舌象的相关性研究[J].广西中医药,2004；27(2)：8-9.
[71]陈群,徐志伟,杨爱萍.内分泌紊乱与子宫肌瘤慢性盆腔炎瘀血舌象形成相关性研究[J].中医药学刊,2004；22(9)：1576-1577.
[72]张延年,孙宗信,李为民等.内科急腹症舌质表现与血清微量元素锌铜含量关系的观察[J].微量元素与健康研究,1994；11(4)：36.
[73]陈连起.舌苔血清微量元素与辨证相关性的探讨[J].辽宁中医杂志,1993；20(10)：8-9.
[74]魏海峰,亚白柳,赵玲,等.急性脑缺血大鼠模型血瘀证舌象表现的评价方法及其与血液流变学的关系[J].中西医结合学报,2008；6(1)：73-76.
[75]李乐军,田金洲,尹军祥,等.不同脑缺血诱发血瘀证表征模型的研究[J].北京中医药大学学报,2007；30(12)：816-818.
[76]尹军祥,田金洲,王永炎,等.血瘀证模型大鼠舌象评价标准研究[J].北京中医药大学学报,2007；30(8)：529-531.
[77]扈新刚,张允岭,柳洪胜,等.气虚血瘀大鼠模型表征及血液流变学研究[J].天津中医药,2007；24(2)：138-141.
[78]姜智浩,王怡,范祥,等.血瘀证动物模型舌体动脉血管形态研究[J].辽宁中医杂志,2008；35(7)：1098-1099.
[79]陈群,徐志伟,莫传伟,等.运用信息融合技术建立瘀血舌象及血瘀证智能诊断推理模型的思路[J].广州中医药大学学报,2007；24(6)：506-508.
[80]徐志伟,陈群,张书河.青紫类舌色的色度量化特征研究新探[J].中医药学刊,2004；22(8)：1374-1376.
[81]许秀森,翁维良.血瘀证舌质定量诊断研究[J].中国中医药科技,1994；1(1)10-14.
[82]Yan Z, Wang K, Li N. Computerized feature quantification of sublingual veins from color sublingual images [J].Comput Methods Programs Biomed.2009; 93(2):192-205.
[83]Chiu CC, Lan CY, Chang YH. Objective assessment of blood stasis using computerized inspection of sublingual veins [J]. Comput Methods Programs Biomed. 2002;69(1):1-12.
[84]翁维良,黄世敬,洪尚杓.运用中医舌诊专家系统对血瘀证舌下络脉的观察[J].中医杂 志,2001；42(4)：233-235.
[85]Takeichi M, Sato T. Computerized color analysis of "xue yu" (blood stasis) in the sublingual vein using a new technology [J]. Am J Chin Med.1997; 25(2):213-219.
[86]张灵芝.肺癌辨证论治的探讨[J].河南中医,2006；26(；)：37-38.
[87]张霆.肺癌辨证治疗误区之我见[J].辽宁中医杂志,2007；34(2)：153-154.
[88]赵炜.李佩文治疗肺癌的经验[J].北京中医杂志,2002；21(6)：329-330.
[89]邓海滨,王中奇.徐振晔辨治肺癌经验[J].四川中医,2002；20(6)：1-2.
[90]陈延武,樊惠连.胡国良老中医临证经验总结[J].湖南中医杂志,1998；14(3)：27-28.
[91]周晓园,陶凯.顾振东治疗肿瘤的经验[J].中医杂志,1999；40(7)：395-397.
[92]孙宏新,孙君.周宜强教授诊治肺癌经验[J].中国中医药信息杂志,2000；7(4)：68-69.
[93]洪广祥.原发性支气管肺癌中医药治疗的探讨[J].江西中医药,1995；26(6)：3.
[94]李华.肺癌的中医辨治体会[J].光明中医,2002；17(99)：20-22.
[95]常青.对中医规范化辨证治疗肺癌的探讨[J].光明中医,2002；17(100)：16-18.
[96]孙钢.刘嘉湘辨治肺癌特色[J].中医杂志,2000；41(2)：75.
[97]朴炳奎.原发性支气管肺癌中西医结合诊治方案[J].中国肿瘤,1995；4(5)：4.
[98]周岱翰.肿瘤治验集要[M].广州：广东高教出版社,1997：141.
[99]陈四清.原发性支气管肺癌辨证分型探讨[J].新中医,2002；34(11)：6-8.
[100]左明焕,王芬,胡凯文等.中晚期肺癌的中医聚类分型[J].中国中医药信息杂志,2006；10,13(10)：28-29.
[101]胡小梅,张培彤,杨宗艳等.中晚期非小细胞肺癌患者中医证型分布规律研究[J].中国肿瘤,2007；16(1)：51-53.
[102]施志明.原发性肺癌中医辨证分型与西医分期及细胞类型关系[J].中国癌症杂志,1998；8(4)：317-318.
[103]顾梦飚.480例原发性肺癌中医证型与国际TNM分期相关分析[J].上海中医药杂志,1994；(4)：1.
[104]吴燕波,蔡明明,朱旭东.100例原发性肺癌中医辨证分型与临床病理分型的关系[J].江苏中医,1993；(2)：11-12.
[105]申维玺,孙燕,刘玉梅.中医虚证与肺癌生物学行为关系的研究[J].实用肿瘤杂志,2001；16(2)：126-128.
[106]周伟生.中晚期周围型肺癌临床分期病理分型与中医证型相关性研究[J].中医药学刊,2006；24(8)：1436-1437.
[107]胡小梅,张培彤,杨宗艳等.非小细胞肺癌不同病病理分类与中医证候分布规律关系探讨[J].中国中医药信息杂志,2006；12,13(12)：19-21.
[108]应丽雅.原发性肺癌与中医“痰”和“瘀”相关性临床观察[J].浙江中西医结合杂志,2001；11(7)：434-435.
[109]张有明,吕学术,彭金花,等.20例晚期肺癌病人的中医分型与血流变学改变[J].天津中医,1991；(2)：19-20.
[110]章康尔,郭勇.中晚期肺癌66例临床辨证分析[J].辽宁中医杂志,1999,26(6)：256.
[111]富琦,王笑民,杨国旺.肺癌患者化疗期间中医证型及升血汤干预作用研究[J].中国中医药信息杂志,2006；13(9)：17-19.
[112]孙韬.原发小细胞肺癌化疗前后中医证候特征研究[J].中国医药学报,2002；17(6)：378-379.
[113]黎敬波,张征,林丽珠.非小细胞肺癌手术前后证候变化的对照研究[J].新中医,2008；9,40(9)：24-25.
[114]姚嫱,徐宗佩.107例癌症患者舌象临床观察[J].天津中医学院学报,1996；14(1)：16.
[115]徐文均,吴建华.326例癌症患者舌象分析[J].福建中医药,1994；25(3)：14-15.
[116]陈健民.癌症患者舌象的临床观察及原理研究[J].中国医药学报,1990；5(1)：35-37.
[117]李晓丽,李焕荣.肿瘤转移的“毒结、血瘀、寒凝”病机探讨[J].中华中医药杂志,2006；21(7)：440-441.
[118]刘忠源.舌像在恶性肿瘤治疗前后变化的临床观察[J].中国肿瘤临床,1997；24(5)：374-376.
[119]崔立献,栗海青.232例恶性肿瘤病人舌象分析[J].山东中医杂志,1994；13(3)：106-106.
[120]王福田.癌症的舌象浅析[J].辽宁中医杂志,1991；18(9)：27-27.
[121]朴万山,马淑坤.上消化道恶性肿瘤与舌象关系[J].黑龙江中医药,1994；(6)：3-4.
[122]向荣.上消化道癌与消化系统良性疾病舌象的对比研究[J].云南中医中药杂志,2005；26(2)：38-39.
[123]李天海,李瑞英.舌诊在食管责门癌防治中的应用[J].河北中医,1997；19(1)：2-3.
[124]施边镇.125例食管、贲门癌患者的舌象与临床诊断资料分析[J].陕西中医,1990；11(8)：340-341.
[125]周阿高,黄大慰,顾伟威.胃肿瘤患者4项观察指标相关性探讨[J].浙江中西医结合杂志,2000；10(6)：327-329.
[126]范德荣,林瑞奋,林欣.胃癌患者舌象与病机分析[J].中医杂志,1991；(10)：34-35.
[127]胡丕丽,黄火文,张蓓.活血化瘀汤对鼻咽癌放射治疗患者舌象及血液流变性的影响[J].中医杂志,1996；37(2)：104-106.
[128]张蓓,陈效莲,黄伙文.鼻咽癌放疗后青紫舌患者远期疗效观察[J].中医杂志,1990；31(4)：29-30.
[129]张欣,崔雅平,钱海龙.52例肺肿瘤患者放疗前后舌象分析及病机临床研究[J].中华临床医学研究杂志,2007；13(24)：3516-3516.
[130]万晓凤.肺癌的常见临床舌象观察[J].实用中西医结合临床,2003；3(4)：32-32.
[131]黄海茵,苏晋梅,韩明权,等.肺癌与一般呼吸系统疾病舌象的对比研究[J].中医杂志,2002；43(7)：535-536.
[132]刘庆.原发性肝癌舌象“肝瘿线”探析[J].安徽中医学院学报,2002；21(6)：3-5.
[133]冯晓灵,聂玉萍,吴恒举,等.128例原发性肝癌临床分期与舌象的关系分析[J].江苏中医,1991；12(1)：41-42.
[134]王其萍,祝肇刚.青紫舌与血液流变学关系的探讨[J].中国微循环,1997；1(1)：46-47.
[135]Koh S C, Tham-K-F, Razvi Ketal, et al. hemostatic and fibrinolytiec status in patients with ovarian cancer and benign ovarian cysts:could D-dimer and antithrombinⅢlevels be included as prognostic markers for survival outcome? [J]. Clinical and Applied Thrombosis/Hemostasis,2001; 7(2):141-148.
[136]Caputo F, Musardo G, Savini P, et al. Occult colon cancer in a patient with an unexplained episode of pulmonary embolism[J]. Hepato-gastroenterology,2000; 47(31):165-167.
[137]Falanga A, Levine M N, Consonni R, et al. The effect of very-low-dose warfarin on markers of hypercoagulation in metastatic breast cancer: results from a randomized trial [J]. Thrombosis and Haemostasis,1998; 79(1):23-27.
[138]Falanga A, Toma S, Marchetti M, et al.Effect of all-trans-retinoic acid on the hypercoagulable state of patients with breast cancer [J]. American Journal of Hematology, 2002; 70(1):9-15.
[139]Gastpar H, Ambrus JL, Ambrus CM. Platelet cancer cell interaction in metastasis formation. Platelet aggregation inhibitors:a possible approach to metastasis prevention [J]. Prog Clin Biol Res,1982; 89:63-82.
[140]Honn KV, Tang DC, Chen YQ. Platelet and cancer metastasis:more than an epiphenomenon [J]. Semin Thromb Hemost.1992; 18(4):392-415.
[141]Grignani G, Pacchiarini L, Pagliarino M.The possible role of blood platelet in tumor growth and dissemination. Haematologica [J].1986; 71(3):245-255.
[142]Costantini V, Zacharski LR, Moritz TE, et al. The platelet count in carcinoma of the lung and colon[J]. Thromb Haemost,1990; 64(4):501-505.
[143]Frojmovic M M, Milton J G. Human platelet size, shape, and related functions in health and disease. physiological reviews,1982;62(1):185-261.
[144]Wu GX, Xi Xd, Li PX. Preparation of a monoclonal antibody, SZ-51, that recognizes as a granule membrane protein (GMP-140) on the surface of activated human platelets [J]. Nouv Rev Fr Hematol.1990; 32(4):231-235.
[145]Sherlock S. Diseases of the liver and biliary system (M). London:Blackwell Science Ltd,1975; 5th edition:677.
[146]De Bruin PA, Griffioen G, Verspaget HW, et al. Plasminogen activators and tumor development in the human colon:activity levels in normal mucosa, adenomatous polyps, and adenocarcinomas[J]. Cancer Res,1987; 47(17):4654-4657.
[147]Reich R, Thompson EW, Iwamoto Y, et al. Effects of Inhibitors of Plasminogen Activator, Serine Proteinases, and Collagenase Ⅳ on the Invasion of Basement Membranes by Metastatic Cells[J]. Cancer research,1988; 48(12):3307-3312.
[148]Lee JH, Ryu KW, Kim S, et al. Preoperative plasma fibrinogen levels in gastric cancer patients correlate with extent of tumor [J]. Hepatogastroenterology,2004; 51(60):1860-1863.
[149]Wang WS, Lin JK, Lin TC, et al. Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma [J]. World J Gastroenterol, 2005;11(14):2166.
[150]刘永惠,杨晓峰,周冬枝等.肿瘤转移与血瘀证的临床研究[J].中国中医基础医学杂志,2002；8(4)：50-58.
[151]刘永惠.血瘀证与肿瘤及其转移患者血浆内血小板GMP-140的研究[J].中医药学刊,2002；20(3)：364-365.
[152]周阿高,丁钰熊,陈梅芳.140例胃部恶性肿瘤患者手术前后和死亡前血瘀证研究[J].中西医结合杂志,1990；10(9)：540-541.
[153]Aitokallio-Tallberg A, Karkkainen J, Pantzar P, et al. Prostacyclin and thromboxane in breast cancer:relationship between steroid receptor status and medroxyprogesterone acetate[J]. Br J Cancer,1985; 51(5):671-674.
[154]Slotman GJ. Plasma thromboxane A2 and prostacyclin concentrations in squamous cell carcinoma of the head and neck[J]. J Surg Oncol,1988; 38(1):33-37.
[155]Mehta P. Potential role of platelets in the pathogenesis of tumor metastasis [J]. Blood, 1984; 63(1):55-63.
[156]陈群,徐志伟,路艳.肺癌患者瘀血舌象与血浆TXA2/PGI2相关性研究[J].中国中西医结合杂志,2006；26(1)：71.
[157]齐元富,钱伯文,陈伟.41例胃癌患者血瘀证研究及活血化瘀治疗作用的观察[J].陕西中医,1996；17(1)：12.
[158]陈震,刘鲁明,何以蓓.血瘀证模型大鼠血栓烷B2、6-酮-前列腺素F与肿瘤肝转移的关系[J].中西医结合学报,2003；1(3)：199-201.
[159]吴朝泰,陈群,徐勤,等.血瘀证在肿瘤不同阶段的变化特征[J].国医论坛,2000；15(2)： 23-25.
[160]李绮云,罗泽民,罗香宁.恶性肿瘤患者甲襞微循环检测临床意义研究[J].临床肿瘤学杂志,1999；4(2)：43-44.
[161]高捷,李学.甲皱微循环检查在肿瘤治疗中的应用[J].中日友好医院学报,1996；10(4)：319-322.
[162]宋丽杰,马雪平,姚桂玲,等.血小板计数临床应用研究现状[J].临床检验杂志,1999；17(4)：252-253.
[163]Nieswandt B, Hafner M, Echtenacher B, et al. Lysis of tumor cells by natural killer cells in mice is impeded by platelets [J]. Cancer Res,1999; 59(6):1295-1300.
[164]Ikeda M,Furukawa H,Imamura H,et al.Poor prognosis associated with thrombocytosis in patients with gastric cancer[J].Ann Surg Oncol,2002;9(3):287-291.
[165]Corbett G, Perry DJ. Significance of thrombocytosis [J]. Lancet, 1983;1(8314-8315):77.
[166]吕新厅,李英杰.血小板计数与胃癌分期及预后的关系[J].中国肿瘤临床,2008；35(24)：1393-1394.
[167]樊丽娟,么玲,何恒,等.血小板计数与结肠癌的临床病理分析[J].中国全科医学,2008；11(8)：1364-1365.
[168]梁致怡,张虹.卵巢上皮性癌和血小板计数增高相关性分析[J].中国肿瘤临床,2008；35(13)：729-735.
[169]张雯,王婷婷,杜鹃,等.血小板计数与非小细胞肺癌分期及预后的关系[J].现代肿瘤医学,2007；15(3)：341-342.
[170]黄建国,王勇强,贺江虹,等.恶性肿瘤患者不同病期血小板参数变化及其临床意义[J].中国误诊学杂志,2009；9(22)：5356-5357.
[171]Syrjala H, Surcel H M, Ilonen J. Low CD4/CD8 T lymphocyte ratio in acute myocardial infarction [J]. Clin Exp Immunol,1991; 83(2):326-328.
[172]陈群,杨爱萍,易玮.妇科疾病瘀血舌象与血浆a-颗粒膜蛋白相关性研究[J].中华现代中西医杂志,2003；1(2)：137-139.
[173]山东省医科所.“舌诊”物质基础的探讨[J].山东医药,1978；(8)：27.
[174]湖南中医学院.206例舌象临床观察的初步分析[J].湖南省肿瘤防治研究,1979；(1)： 52.
[175]郭英华,孟繁会,王仁本.恶性肿瘤患者与血栓症[J].中华肿瘤防治杂志,2006；13(11)：875.
[176]欧晋平,虞积仁.恶性肿瘤与血栓[J].内科急危重症杂志,2001；7(4)：214.
[177]Yoshida T, Osato H, Sakon M, et al. Locoregional injection of OK-432/fibrinogen/thrombin for unresectable metastatic liver tumors [J]. Gan To Kagaku Ryoho.1996; 23(11):1575-1577.
[178]Wang WS, Lin JK, Lin TC, et al. Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma [J]. World J Gastroenterol.2005; 11(14):2166-2170.
[179]Lee JH, Ryu KW, Kim S, et al. Preoperative plasma fibrinogen levels in gastric cancer prtients correlate with extent of tumor[J]. Hepatogas-troente rology,2004;51(60): 1860-1863.
[180]Wang WS, LinJK, Lin TC, et sl. Plasma von Willebrand factor level as a pmgnostic indicator of patients with metastatic coloreetal careinoma[J]. World J Gastroenterol, 2005;11(14):2166.
[181]Zetter BR. The cellular basis of site-specific tumor metastasis [J]. N Engl J Med. 1990;322(9):605-612.
[182]Peerschke El. Recognition of platelet-associated fibrinogen by polyclonal antibodies: correlation with platelet aggregation. Blood.1992; 79(8):2028-2033.
[183]Biggerstaff JP, Seth N, Amirkhosravi A, et, al. Soluble fibrin augments platelet/tumor cell adherence in vitro and in vivo, and enhances experimental metastasis. Clin Exp Metastasis.1999; 17(8):723-730.
[184]王玉斌,刘晓棠,陈文俊,等.恶性肿瘤患者治疗前后血浆纤维蛋白原含量分析[J].浙江临床医学,2007；9(7)：893-894.
[185]Levin J, et al.Thrombocytosis associated with malignant disease [J].Arch Inter Med, 1964; 114:479.
[186]CostantiniV, ZacharskiLR, MoritzTE, etal.The platelet count in carcinoma of the lung and colon [J]. Thromb Haemost,1990; 64(4):501-505.
[187]FerrignoD, BuccheriG. Hematologic counts and clinical correlates in 1201 newly diagnosed lung cancer patients [J].Monaldi Arch ChestDis,2003; 59(3):193-198.
[188]Pedersen LM, Milman N. Diagnostic significance of platelet count and other blood analyses in patientswith lung cancer [J]. Oncol Rep,2003; 10(1):213-216.
[189]O'Keefe S C, Marshall F F, Issa M M, et al.Thrombocytosis is associated with a significant increase in the cancer specific death rate after radical nephrectomy [J]. J Urol, 2002; 168:1378-1380.
[190]Hernandez E, Donohue K A, Anderson L L, et al. The significance of thrombocytosis in patients with locally advanced cervical carcinoma:a Gynecologic Oncology Group study [J]. Gynecol Oncol,2000; 78:137-142.
[191]JuraszP, Alonso-EscolanoD, RadomskiMW. Platelet-cancer interactions:mechanisms and pharmacology of tumor cell-induced platelet aggregation [J]. Br J Pharmaco, 2004;143(7):819-826.
[192]BOZKURT N, YUCE K, BASARAN M et al.Correlation of platelet count with second-look laparotomy results and disease progression in patients with advanced epithelial ovarian cancer [J].Obstet Gynecol,2004; 103(1):82-85.
[193]Furuhashi M,Miyabe Y,Oda H.A case of thrombopoietin producing ovarian carcinoma confirmed by immunohistochemistry[J].Gynecol Oncol,1999;74:278-281.
[194]Salgado R,Benoy I, Weytjens R, et al. Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer [J].Br J Cancer,2002; 87:1437-1444.
[195]BOZKURT N, YUCE K, BASARAN M et al.Correlation of platelet count with second-look laparotomy results and disease progression in patients with advanced epithelial ovarian cancer [J].Obstet Gynecol,2004; 103(1):82-85.
[196]MONREAL M, FERNANDEZ-LIAMAZARES J,PINOL M,et al. Platelet count and survival in patients with colorectal cancer-a preliminary study [J].Thromb Haemost,1998;79(5):916-918.
[197]DOMINGUEZ I.CRIPPA S,THAYER S P,et al. Preoperative platelet count and survival prognosis in resected pancreatic ductal adenocarcinoma [J].World J Surg,2008;32(6):1051-1056.
[198]Honn KV, Tang DG, Crissman JD. Platelets and cancer metastasis:a causal relationship? [J]. Cancer Metastasis Rev.1992; 11(3-4):325-351.
[199]Gastpar H, Ambrus JL, Ambrus CM. Platelet cancer cell interaction in metastasis formation. Platelet aggregation inhibitors:a possible approach to metastasis prevention [J]. Prog Clin Biol Res.1982; 89:63-82.
[200]Nies wandt B, HafnerM, Echtenacher B, et al.Lysis of tumor cells by natural killer cells in mice is impeded by platelets[J].Cancer Res,1999; 59 (6):1295-1300.