Synuclein-γ在直肠癌组织中表达及与直肠癌中西医临床指标关系的研究
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摘要
中医是应用型科学,需要有坚实的基础科学的支撑。西医靠强大的现代科学技术取得了飞速发展。中医也应该充分利用现代科学技术发展的成果,为进一步解释中医理论和拓展临床治疗寻求支撑。
中医临床研究中证型和证候是真实可靠的,但是因为缺乏客观评价的标准,让人感觉既难以完全相信又没法予7以否定。那么,应当怎样正确记录和评价中医的临床证型和证候?如何处理临床研究中的共性与个性的关系?
中医具备形象思维和直觉思维能力、拥有“天人合一”整体思维。但是在现代科学技术突飞猛进的今天,在人类疾病谱、基因遗传和生活环境与古代迥异的今天,还能够无视科学技术在诊治疾病中带来的好处,固守不需任何仪器设备的帮助,用“司外揣内”诊断疾病、仅仅延用古代理论和方法去治疗疾病?
中医对于直肠癌的认识起源于先秦,此后历代医家对直肠癌的病因病机进行了论述。晋、隋、唐时期进行了进一步探索和研究,宋以后逐渐完善了对直肠癌的认识。
中医古典医籍中无直肠癌病名。直肠癌的描述散在于“积聚'、“肠覃”、“锁肛痔”、“脏痈痔”、“癥瘕”等病证的论述中。已认识到直肠癌是一种全身性疾病,认为其发生的根本病因是正气亏虚,与脾胃功能密切相关。其兼挟病因为七情、饮食、外感邪气三种。现代医家认为,直肠癌根本病机是机体阴阳失调,脾虚、肾亏、正气不足为病之本,湿热、火毒、瘀滞属病之标,常是几种因素互为因果。因此对于直肠癌的中医理论探索还任重道远。
由于不同学者受疾病认识和不同的知识结构等因素的影响,给中医归纳总结不同学者的经验带来了困难。而且经验总结虽然为以后的中医临床研究提供了直肠癌证治规律的线索,但是无法用现代科学的指标和语言对其进行准确的概括和量化,使这些经验的可重复性和概括性以及今后的标准化受到了限制,也成了中医持续向前发展的瓶颈。
实践证明,中医药在直肠癌的综合治疗中效果是肯定的,但是直肠癌的中医临床研究虽有很多,也有以中医为主治疗直肠癌且取得满意疗效的报道,但多为个案报道,没有严格设计的大宗病例的研究,少数还有比较严重的统计学分析错误,导致晚期直肠癌成为目前中医治疗的主要对象。患者全身状况往往较差,经中医扶正祛邪,虽可使症状减轻,生存质量提高,但多数已无治愈可能。随着大众医疗保健意识的增强,晚期病例越来越少,并且中医治未病的优势仍然没有发挥出来,这和中医理论无法用现代科学理论解释,中医指标无法用现代科学技术标准量化是有关的。
肿瘤中医辩证分型是根据中医理论对疾病过程中某一阶段病因、病机、病性、病势要素的综合性概括,是对疾病当前本质做出的结论,是辨证施治的依据。肿瘤的西医学指标反映了病变的程度和发展趋势及肿瘤的生物学特性,因此,了解肿瘤的中医学指标与西医学指标之间的关系,有可能为中医理论提供现代科学理论依据,为中医指标用现代科学技术标准量化提供帮助。但是如何使直肠癌病因病机研究与现代医学的科研成果相结合,并利用现代医学的科研成果进一步拓展和深入中医直肠癌病因病机理论研究仍然需要探索。
中医临床以辨证论治为指导核心,“同病异治,异病同治”,处方用药随证而变。中医“证”与西医的病存在一定的分歧,而且中医的临床特点决定了符合中医医理的大多中医临床研究难以完全严格按照随机、对照、重复的标准设计和实施。另有一些研究只是临床病例报告和描述,或是治疗经验的总结,这些研究由于没有严格的科研设计和质量控制方法而缺乏可信度。
本研究希望结合现代科学技术的发展成果,为进一步理解中医基础理论和协助临床治疗提供方法和依据。
γ-syn是神经核蛋白家族成员,正常主要位于神经元的轴突内。异常表达与许多肿瘤的发生、分期、有无淋巴结转移相关。SNCG异常调节发生在转录水平,和SNCG低甲基化有关。γ-syn异常表达危害正常有丝分裂监控点,使细胞通过非整倍体持续增殖,还可抑制半胱天冬酶活性,阻断凋亡应答;可通过MAPK途径,使MMP基因表达增加,提高MMP2活性和水平,促进肿瘤转移。γ-syn是潜在肿瘤生物标志,用基因调控技术抑制肿瘤转移复发和针对γ-syn的分子靶向药物研究正在进行。
为了研究直肠癌组织中γ-syn蛋白的表达情况,我们选取2005年～2007年南京市中医院肛肠中心病理证实的直肠癌患者86例,收集手术切除的癌组织标本进行检测。同时收集患者的人口学和临床资料,包括年龄、性别、肿瘤距肛门距离、术前血清CEA水平、肿瘤分化程度、有无淋巴结转移。用免疫组织化学法检测86例直肠癌组织γ-syn蛋白的表达。我们发现86例直肠癌组织中都有γ-syn蛋白的表达(86/86)。γ-syn蛋白的表达与患者年龄、性别、直肠癌部位、术前血清CEA水平之间无相关性;与直肠癌的组织分化程度,有无淋巴结转移无关。表明直肠癌组织高表达γ-syn蛋白;γ-syn蛋白是直肠癌普遍存在表达的蛋白,可以作为直肠癌的生物标记。目前国内文献尚无γ-syn蛋白在直肠癌组织中表达的报道。
为了解γ-syn蛋白在直肠癌组织中表达调控的状况,我们选取22对新鲜直肠癌组织标本和相同直肠正常粘膜标本,用甲基化特异PCR(methylation-specific PCR,MSP)技术来检测直肠癌组织的γ-syn基因(SNCG)甲基化情况。我们发现,直肠癌组织中SNCG普遍存在甲基化的现象。提示直肠癌中SNCG表达的调控,可能与SNCG某些CpG位点是否甲基化有关,而并非是SNCG整个基因的低甲基化。
为了解直肠癌的常见证候及其分布规律与现代西医学指标之间的联系,我们选取2004年一2006年间在南京市中医院全国肛肠医疗中心进行手术治疗并经病理证实,符合纳入标准的直肠癌患者71例(n=71)。将所有入选病例编号,在术前完成中、西医指标,术后完成病理分型,同时进行相关性分析。我们发现,中医辨证分型在西医Dukes B、C期以气血瘀滞型最为常见,以薄腻苔和弦涩脉多见;体重70.4%在正常范围,25.4%体重超重。未见中医虚证患者。气血瘀滞型患者的肿瘤病变部位距肛门口的平均距离显著大于湿热毒蕴型患者,有统计学差异(P＜0.01)。我们认为,目前直肠癌患者多为气血瘀滞和湿热毒蕴型(西医Dukes B、C期),中西医指标间有相似分布,可以相互佐证。气血瘀滞型患者的肿瘤病变部位距肛门口的平均距离显著大于湿热毒蕴型,术前分型为气血瘀滞型保肛手术的几率较大。没有发现中医虚症患者,我们分析认为,这是因为直肠癌和结肠癌对身体的影响不同造成的。结肠癌早期对人体营养物质的摄取会造成影响,因此会出现虚症表现。而直肠癌患者,到了晚期才会对人体的营养状况产生影响,才会出现虚症的表现。建议今后对于结肠和直肠癌的中医诊治应该加以区分,以使中医直肠癌的诊断治疗更加具体可行。
为了解直肠癌的常见证候及其分布与西医学肿瘤生物标记之间的联系,是否在直肠癌早期西医学指标可以检测的同时,有无可能发现中医证候和症型的变化和规律,为中医治疗尚无症状的直肠癌提供依据,发挥中医治疗未病的优势?
我们选取2004年一2006年间在南京市中医院全国中医肛肠医疗中心进行手术治疗并符合纳入标准的直肠癌患者71例(17=71)。将所有入选病例编号,在术前完成中医指标,术后完成病理分型和癌组织中γ-syn表达的检测,同时进行相关性分析。我们发现气血瘀滞型与湿热毒蕴型两组患者γ-syn表达无统计学差异(P=0.54＞0.05)。超重与非超重患者γ-syn表达,两组间没有统计学差异(P=0.82＞0.05)。滑腻苔患者与薄腻苔两组患者γ-syn表达有统计学差异(P=0.03＜0.05)。弦涩脉患者与弦滑脉患者两组患者γ-syn表达有统计学差异(P=0.03＜0.05)。我们认为,直肠癌患者肿瘤组织中γ-syn表达与中医分型没有统计学相关性。薄腻苔,弦滑脉患者与滑腻苔,弦涩脉患者γ-syn表达有统计学差异,有可能和其他指标一起对直肠癌的中医诊断治疗起参考作用。但是早期直肠癌的中医学常见证候及其分布与西医学肿瘤生物标记之间是否有其他的联系和分布规律,还需要大样本的多中心随机对照研究去证明。
通过本研究,我们得出以下结论:1.γ-syn蛋白是直肠癌普遍存在表达的蛋白,可以作为直肠癌的生物标记。目前国内文献尚无γ-syn蛋白在直肠癌组织中表达的报道。2.目前直肠癌患者(西医Dukes B、C期)多为气血瘀滞和湿热毒蕴型。气血瘀滞型患者的肿瘤病变部位距肛门口的平均距离显著大于湿热毒蕴型,推测术前分型为气血瘀滞型保肛手术的几率较大。3.没有发现中医虚症患者,结肠癌和直肠癌由于对机体影响不同,其中医诊治应该加以区分,以使中医直肠癌的诊断治疗更加具体可行。4.薄腻苔,弦滑脉患者γ-syn表达呈梯度上升,滑腻苔和弦涩脉患者γ-syn表达以2+为主,有可能和其他指标一起对直肠癌的中医诊断治疗起参考作用。但是早期直肠癌的中医学指标和西医学肿瘤生物标记之间是否有其他的联系和分布规律,还需要大样本的多中心随机对照研究去证明。5.直肠癌组织中SNCG普遍存在甲基化的现象。提示直肠癌中SNCG表达的调控,可能与SNCG某些CpG位点是否甲基化有关,而并非是SNCG整个基因的低甲基化。
通过本研究,我们也提出了一个研究思路,即是否可以通过研究西医临床指标与中医证型证侯之间的关系,以及肿瘤的生物标记与中医证型证侯之间的关系,发现常见证候及其分布与现代科学技术指标之间的联系,使中医指标可以用现代科学技术标准量化,进而使中医诊治规范化。最终用现代科学技术手段去揭示古老中医理论的秘密,同时用现代技术手段去延伸和丰富中医四诊的信息,有助于古老中医理论系统和临床诊治的补充和完善。
我们认为,对直肠癌中医学指标与西医学临床指标之间关系的深入研究,对用现代科学理论解释中医理论,使中医指标可以用现代科学技术标准量化,指导中医临床治疗分析预后有重要作用。有助于了解直肠癌的常见证候及其分布与现代科学技术指标之间的联系;有助于古老中医理论的补充和完善;有助于直肠癌中医指标的量化和诊治的规范化。并对运用现代医学理论对古老中医理论进行现代科学技术语言的解释具有重要意义。
Traditional Chinese medicine is one of practical science which need basic science to prop up substantial support. Western medicine got a significant development depending on modern science and technique. Traditional Chinese medicine should make the best of achievements of modern science and technique to find out support for explaining it's theory and expanding it's clinic.
Pattern of syndrome and zheng hou in clinical research of Traditional Chinese medicine are real and dependable. Because of lacking of Standards of objective evaluation, they neither to be completely accredit nor to be deny. Hence, how can we precision record and evaluate pattern of syndrome and zheng hou of Traditional Chinese medicine? How to deal with the relationships between the commonness and individuality in clinical research?
Traditional Chinese medicine posses ability of concrete thinking and intuitive thinking, and provided with organism thinking of "unification of human and environment". Today, with the rapid progress of modern science and technique, and changes of human spectrum of disease, heredity and gene, living environment, can we ignore the benefits which science and technique bring to us in diagnosis and treatment of disease and just use the methods of "si wai chuai nei" which set up in ancient dynasty to diagnose and treat disease without any instrument?
Traditional Chinese medicine realized rectal cancer from Qin dynasty. After this, the doctor in different dynasty discussed the causes and pathogenesis about rectal cancer. The theory was forward in Jin, Sui and Tang dynasty. The system theory was set up after Song dynasty. Hence, the theory of traditional Chinese medicine in rectal cancer has long way to go.
There is no the name of rectal cancer in ancient classical documents. The delineation of rectal cancer scattered in the discussion of "ji ju", "chang xun", "suo gang zhi", "zang yong zhi", "zheng jia" et al. Ancient doctor had realized that it is a systemic disease. They considered the primary causation of disease is deficient of zhen qi, closeness relation to function of "pi wei". The other causes are emotion, diet, exogenous pathogenic factors. The modern tradition Chinese medicine doctor considers that the primary causation of rectal cancer is Yin-yang unbalance, Pi xu, Shen kui, insufficiency of zhen qi are the basic cause, and Shi re, Huo du, Pi zhi are the symptom,they are causes and effects for each other.
But, it is difficult to summary the experiences come from different scholars in traditional Chinese medicine because of the effects originated from different knowledge structure and recognition to the diseases of different scholars. Even though the experience summary provides the clue to disciplinarian of syndrome and treatment of rectal cancer to further traditional Chinese medicine clinical research, but it is impossible to accurately summary and quantify them by modern science language and index. These cause the restrain to the experience in repeatability and generality, standardization. These will be a bottleneck to continue development of traditional Chinese medicine.
It has been proved that the effectiveness of traditional Chinese medicine and Chinese herbal drugs are positive in Combined Modality Therapy of rectal cancer. Even though there are a lot of clinical researches of traditional Chinese medicine in rectal cancer, and there are positive reports about the clinical treatment of rectal cancer mainly using by traditional Chinese medicine, but they are usually individual case reports, less mass cases reports were reported by accurate design. There are some serious mistakes of statistic analysis in some reports. These lead to the fact that advanced stage patients of rectal cancer become the main population in treatment of traditional Chinese medicine. Total body condition of patients frequently are worse. Even though we can decrease the symptoms and increase life quality, but it is impossible to most of patients to be cured. With the increasing of health care consciousness of people, there are less and less advanced stage patients of rectal cancer, and the advantage of traditional Chinese medicine in following the prognosis of a disease still is not brought into full play. These are caused by the reason that the theory of traditional Chinese medicine can not be explain by modern science theory and the index of traditional Chinese medicine can not be quantified by modern science technology.
Tumor dialectical grouping of traditional Chinese medicine is a kind of comprehensiveness summary to elemental of cause of disease, pathogenesis, peculiarity of disease and tendency of disease in different disease stage according to traditional Chinese medicine theory. It is the conclusion to the essence of currently disease, it is the foundation of determining the treatment based on differentiation of symptoms and signs. The index of western medicine reflect the tendency of disease and biology characteristics of tumor. Thus, if we know the relationship between the dialectical grouping of traditional Chinese medicine and index of western medicine, it is going to be possible to provide the evidence of modern science theory to the theory of traditional Chinese medicine, and is going to be helpful to quantified index of traditional Chinese medicine by standard of modern science technology. But it is still needed to be explore how we combine the achievements of modern medicine science technology with the research about the cause and pathogenesis of traditional Chinese medicine and to further expand research and deeply comprehend the theory of the cause and pathogenesis of traditional Chinese medicine by the achievements of modern medicine science technology.
The zheng differentiation treatment of traditional Chinese medicine is the key of guide in clinical treatment. "Same disease different treatments, different diseases in same treatment", to prescribe and medication change according to the changes of symptom. The "symptom" of traditional Chinese medicine is different from the disease of western medicine, and the characteristic of traditional Chinese medicine in clinic lead to the result that most clinical research of traditional Chinese medicine which fit to the theory of traditional Chinese medicine are difficult to practice according to design of strict random, matched contral, reduplication standard. The others of researches of traditional Chinese medicine are just clinical cases report and describe or are summaries of therapy experiences. These researches of traditional Chinese medicine are short of reliability coefficient because they are lack of strict science research designed and Quality control approach.
Hence, the subject of this research is to provide the method and evidence for further and deeply comprehending the theory of basica theory of traditional Chinese medicine and Assisting clinical treatment by combining to the achievements of modern medicine science technology.
γ-syn is one of the synuclein family, mainly localizes to the axons of neurons. The abnormally expression of this protein may be linked to the process of tumorigenesis, stage-specific of tumors and lymph node invasion. The transcriptional deregulation that results in SNCG in cancer cells induce SNCG expression through demethylation. Overexpression ofγ-syn disrupt mitotic check point and allow cells to continue progression in aneuploidy. Suppressed caspase activity disrupting the apoptotic response. Expression and action of MMP2 result in overexpression of MMP gene through MAPK signaling pathways promote cancer cell metastasis.γ-syn is proving to be a potential biomarker in tumor. Studies have been carried out to explore the methods of suppressing cancer metastasis and recurrence by gene control andγ-syn targeting medicine.
To investigate the expression ofγ-syn in rectal adenocarcinomas and its correlation with rectal carcinomas. We selected 86 cases rectal cancer patients (n = 86) who had been treated in national medicine centre of colorectal disease of Nanjing municipal traditional Chinese medical hospital and had been diagnosed by pathology from 2005 to 2007. To collect and detect the cancer tissue sample which were surgical ablation. To collect the demography and clinical dates of patients at the same time, including age and gender of patients, distance between tumor edge and anus, CEA level in serum before operation, degree of tumor cell differentiation, situation of lymph nodes metastasis. Immunohistochemistry with anti-γ-syn antibody was performed in 86 cases rectal adenocarcinomas tissues. We discovered that theγ-syn expression was detected in all of rectal adenocarcinomas tissue (86/86). There is no expression difference in gender and age of patients, CEA in serum before operation, differentiation of adenocarcinomas, length from anus to rectal adenocarcinomas edge and metastasis situation of lymph nodes.γ-syn is highly expressed in rectal adenocarcinomas. Our findings suggest thatγ-syn is a ubiquity express protein and it may represent a biological marker of rectal adenocarcinomas. There is no paper to reportγ-syn expression in rectal adenocarcinomas in China.
To investigate the expression regulate ofγ-syn in rectal adenocarcinomas, we chose 22 fresh tissue samples, both of rectal adenocarcinomas and normal mucosa. Detected the SNCG methylation by methylation-specific PCR(MSP). We find that SNCG methylation is common situation in rectal adenocarcinomas. It is suggest that the regulate of SNCG associated to unique CpG island hypomethylation rather than whole gene hypomethylation.
To explore whether there are some internal regularity relationship and associativity between the common Zheng hou and distribution regularity of traditional Chinese medicine and index of Western medicine in rectal cancer. We selected 71 cases rectal cancer patients (n= 71) who had been performed operation in national medicine centre of colorectal disease of Nanjing municipal traditional Chinese medical hospital and had been diagnosed by pathology, fitting to the internalization standard from 2004 to 2006. Then numbered those patients. Complete The Chinese and Western medicine index before operation, and define pathological type after operation then proceed Associativity analysis. We discovered that according to the differentiation of symptoms and signs of classification of syndrome of traditional Chinese medicine , QI-blood stagnant existed was the most common type in Dukes B、C stage. The thinness and greasy tongue fur and unsmooth pulse are the common signs in these patients. Weight in the normal range was found in 70.4% patients, overweight was found in 25.4 % patients. There is not Asthenia syndrome patient. The average distance from edge of rectal cancer to anus was (7.2±4.9cm) in QI-blood stagnant type patient, significantly exceeded the type of Shi Re Du Yun patients (4.6±2.0cm). There is statistics difference(P < 0.01). This research discovered that most of rectal cancer patients belong to QI-blood stagnant and Shi Re Du Yun in classification of syndrome of traditional Chinese medicine (Dukes B. C stage). The distance from edge of rectal cancer to anus in QI-blood stagnant type patients was significantly exceeded the type of Shi Re Du Yun type patients. These suggest that it is more possible to process the sphincter perservation operation in the type of QI-blood stagnant type patients. There is similar distribution in index between Western medicine and Traditional Chinese medicine. They can be evidence for each other. We did not find the Asthenia syndrome patient. We think that it is caused by different effect to total body situation between rectal cancer patients and colon cancer patients. The intake of nutrient substance is decreased in early stage of colon cancer patients so that the patients have sign of Asthenia syndrome. To rectal cancer patients, The intake of nutrient substance is decreased in advanced stage, the sign of Asthenia syndrome can be found only in advanced stage. We suggest that it is necessary to classify colon cancer and rectal cancer in diagnose and treatment of traditional Chinese medicine, which would make diagnose and treatment are more accuracy.
To explore the relationship and associativity between the common Zheng hou and distribution regularity of traditional Chinese medicine and tumor biological marker of Western medicine in rectal cancer. Whether we can find out the regularity and variation of Zheng hou and Zheng xing of traditional Chinese medicine while the index of western medicine can be detected in early stage of rectal cancer? And to provide the evidence for traditional Chinese medicine in treatment of no symptom rectal cancer, so as to the advantage of following the prognosis of a disease of traditional Chinese medicine bring into full play?
We selected 71 cases rectal cancer patients (n = 71) who had been performed operation in national medicine centre of colorectal disease of Nanjing municipal traditional Chinese medical hospital and had been diagnosed by pathology, fit to the internalization standard from 2004 to 2006.Then numbered those patients. To complete The traditional Chinese medicine index before operation and to define pathological type ,detected the expression ofγ-syn after operation then proceed Associativity analysis. We discovered that the expression ofγ-syn in QI-blood stagnant group and Shi Re Du Yun group in classification of syndrome of traditional Chinese medicine are no statistics difference(P=0.54). There is not statistics difference between the overweight group and no overweight group in the expression ofγ-syn(P= 0.82 > 0.05). There is statistics difference between the smooth greasy tongue fur group and thin greasy tongue fur group in the expression ofγ-syn(P=0.03 < 0.05). There is statistics difference between the string unsmooth pulse group and string slippery pulse group in the expression ofγ-syn(P=0.03 < 0.05). we conclude that there is a tendency to smooth greasy tongue fur and thin greasy tongue fur, the string unsmooth pulse and string slippery pulse which maybe have consult effect for diagnosis and treatment of traditional Chinese medicine in rectal cancer while it combine to other index. But if there is a relationship and associativity between the common Zheng hou and distribution regularity of traditional Chinese medicine and tumor biological marker of Western medicine in rectal cancer still need larger sample, multicentre randomised control trial to prove.
We can conclude in behalf of this study: 1.γ-syn is a ubiquity express protein and it may represent a biological marker of rectal adenocarcinomas. There is no paper to reportγ-syn expression in rectal adenocarcinomas in the china. 2. Most of rectal cancer patients belong to QI-blood stagnant and Shi Re Du Yun in classification of syndrome of traditional Chinese medicine (Dukes B. C stage). The distance from edge of rectal cancer to anus in QI-blood stagnant type patients was significantly exceeded the type of Shi Re Du Yun type patients. These suggest that it is more possible to process the sphincter perservation operation in the type of QI-blood stagnant type patients.3. We did not find the Asthenia syndrome patient,it is necessary to classify colon cancer and rectal cancer in diagnose and treatment of traditional Chinese medicine, which would make diagnose and treatment are more accuracy. 4. There is statistics difference between the smooth greasy tongue fur group and thin greasy tongue fur group in the expression ofγ-syn(P=0.03 < 0.05) and statistics difference between the string unsmooth pulse group and string slippery pulse group in the expression ofγ-syn(P=0.03 < 0.05). There is a tendency to smooth greasy tongue fur and thin greasy tongue fur, the string unsmooth pulse and string slippery pulse which maybe have consult effect for diagnosis and treatment of traditional Chinese medicine in rectal cancer while it combine to other index. But if there is a relationship and associativity between the common Zheng hou and distribution regularity of traditional Chinese medicine and tumor biological marker of Western medicine in rectal cancer still need larger sample, multicentre randomised control trial to prove.5. SNCG methylation is common situation in rectal adenocarcinomas. It is suggest that the regulate of SNCG associated to unique CpG island hypomethylation rather than whole gene hypomethylation.
After finished this study, we provide a new research method that if we can find the relationship between the common Zheng hou of traditional Chinese medicine and index of modern science technique for quantificated the index of traditional Chinese medicine by index of modern science technique, then standardize the diagnosis and treatment of traditional Chinese medicine by studying the relationship between Zheng hou of traditional Chinese medicine and index of western medicine and the relation between Zheng hou of traditional Chinese medicine and tumor biological marker. The subject is to find out the secret of theory of ancient traditional Chinese medicine, and to extend and enlarge the diagnosis information of traditional Chinese medicine in order to help the supplement and consummate of theory system of ancient traditional Chinese medicine and diagnosis and treatment of traditional Chinese medicine.
In conclusion, to further studying the relationship between index of traditional Chinese medicine and index of western medicine in rectal cancer patients has important effect to explain theory system of ancient traditional Chinese medicine by theory of modern science technique, quantificating the index of traditional Chinese medicine by index of modern science technique, and guiding clinic treatment and prognosis of traditional Chinese medicine. It is helpful to get the message of the distribution of common Zheng hou of traditional Chinese medicine in rectal cancer and the relationship with the index of modern science technique. It is helpful for the supplement and consummate of theory system of ancient traditional Chinese medicine. It is helpful for quantificated the index of traditional Chinese medicine and standardize the diagnosis and treatment of traditional Chinese medicine. It is important to explain the theory of ancient traditional Chinese medicine using modern medical theory by language of modern science technique.
中医临床研究中证型和证候是真实可靠的,但是因为缺乏客观评价的标准,让人感觉既难以完全相信又没法予7以否定。那么,应当怎样正确记录和评价中医的临床证型和证候?如何处理临床研究中的共性与个性的关系?
中医具备形象思维和直觉思维能力、拥有“天人合一”整体思维。但是在现代科学技术突飞猛进的今天,在人类疾病谱、基因遗传和生活环境与古代迥异的今天,还能够无视科学技术在诊治疾病中带来的好处,固守不需任何仪器设备的帮助,用“司外揣内”诊断疾病、仅仅延用古代理论和方法去治疗疾病?
中医对于直肠癌的认识起源于先秦,此后历代医家对直肠癌的病因病机进行了论述。晋、隋、唐时期进行了进一步探索和研究,宋以后逐渐完善了对直肠癌的认识。
中医古典医籍中无直肠癌病名。直肠癌的描述散在于“积聚'、“肠覃”、“锁肛痔”、“脏痈痔”、“癥瘕”等病证的论述中。已认识到直肠癌是一种全身性疾病,认为其发生的根本病因是正气亏虚,与脾胃功能密切相关。其兼挟病因为七情、饮食、外感邪气三种。现代医家认为,直肠癌根本病机是机体阴阳失调,脾虚、肾亏、正气不足为病之本,湿热、火毒、瘀滞属病之标,常是几种因素互为因果。因此对于直肠癌的中医理论探索还任重道远。
由于不同学者受疾病认识和不同的知识结构等因素的影响,给中医归纳总结不同学者的经验带来了困难。而且经验总结虽然为以后的中医临床研究提供了直肠癌证治规律的线索,但是无法用现代科学的指标和语言对其进行准确的概括和量化,使这些经验的可重复性和概括性以及今后的标准化受到了限制,也成了中医持续向前发展的瓶颈。
实践证明,中医药在直肠癌的综合治疗中效果是肯定的,但是直肠癌的中医临床研究虽有很多,也有以中医为主治疗直肠癌且取得满意疗效的报道,但多为个案报道,没有严格设计的大宗病例的研究,少数还有比较严重的统计学分析错误,导致晚期直肠癌成为目前中医治疗的主要对象。患者全身状况往往较差,经中医扶正祛邪,虽可使症状减轻,生存质量提高,但多数已无治愈可能。随着大众医疗保健意识的增强,晚期病例越来越少,并且中医治未病的优势仍然没有发挥出来,这和中医理论无法用现代科学理论解释,中医指标无法用现代科学技术标准量化是有关的。
肿瘤中医辩证分型是根据中医理论对疾病过程中某一阶段病因、病机、病性、病势要素的综合性概括,是对疾病当前本质做出的结论,是辨证施治的依据。肿瘤的西医学指标反映了病变的程度和发展趋势及肿瘤的生物学特性,因此,了解肿瘤的中医学指标与西医学指标之间的关系,有可能为中医理论提供现代科学理论依据,为中医指标用现代科学技术标准量化提供帮助。但是如何使直肠癌病因病机研究与现代医学的科研成果相结合,并利用现代医学的科研成果进一步拓展和深入中医直肠癌病因病机理论研究仍然需要探索。
中医临床以辨证论治为指导核心,“同病异治,异病同治”,处方用药随证而变。中医“证”与西医的病存在一定的分歧,而且中医的临床特点决定了符合中医医理的大多中医临床研究难以完全严格按照随机、对照、重复的标准设计和实施。另有一些研究只是临床病例报告和描述,或是治疗经验的总结,这些研究由于没有严格的科研设计和质量控制方法而缺乏可信度。
本研究希望结合现代科学技术的发展成果,为进一步理解中医基础理论和协助临床治疗提供方法和依据。
γ-syn是神经核蛋白家族成员,正常主要位于神经元的轴突内。异常表达与许多肿瘤的发生、分期、有无淋巴结转移相关。SNCG异常调节发生在转录水平,和SNCG低甲基化有关。γ-syn异常表达危害正常有丝分裂监控点,使细胞通过非整倍体持续增殖,还可抑制半胱天冬酶活性,阻断凋亡应答;可通过MAPK途径,使MMP基因表达增加,提高MMP2活性和水平,促进肿瘤转移。γ-syn是潜在肿瘤生物标志,用基因调控技术抑制肿瘤转移复发和针对γ-syn的分子靶向药物研究正在进行。
为了研究直肠癌组织中γ-syn蛋白的表达情况,我们选取2005年～2007年南京市中医院肛肠中心病理证实的直肠癌患者86例,收集手术切除的癌组织标本进行检测。同时收集患者的人口学和临床资料,包括年龄、性别、肿瘤距肛门距离、术前血清CEA水平、肿瘤分化程度、有无淋巴结转移。用免疫组织化学法检测86例直肠癌组织γ-syn蛋白的表达。我们发现86例直肠癌组织中都有γ-syn蛋白的表达(86/86)。γ-syn蛋白的表达与患者年龄、性别、直肠癌部位、术前血清CEA水平之间无相关性;与直肠癌的组织分化程度,有无淋巴结转移无关。表明直肠癌组织高表达γ-syn蛋白;γ-syn蛋白是直肠癌普遍存在表达的蛋白,可以作为直肠癌的生物标记。目前国内文献尚无γ-syn蛋白在直肠癌组织中表达的报道。
为了解γ-syn蛋白在直肠癌组织中表达调控的状况,我们选取22对新鲜直肠癌组织标本和相同直肠正常粘膜标本,用甲基化特异PCR(methylation-specific PCR,MSP)技术来检测直肠癌组织的γ-syn基因(SNCG)甲基化情况。我们发现,直肠癌组织中SNCG普遍存在甲基化的现象。提示直肠癌中SNCG表达的调控,可能与SNCG某些CpG位点是否甲基化有关,而并非是SNCG整个基因的低甲基化。
为了解直肠癌的常见证候及其分布规律与现代西医学指标之间的联系,我们选取2004年一2006年间在南京市中医院全国肛肠医疗中心进行手术治疗并经病理证实,符合纳入标准的直肠癌患者71例(n=71)。将所有入选病例编号,在术前完成中、西医指标,术后完成病理分型,同时进行相关性分析。我们发现,中医辨证分型在西医Dukes B、C期以气血瘀滞型最为常见,以薄腻苔和弦涩脉多见;体重70.4%在正常范围,25.4%体重超重。未见中医虚证患者。气血瘀滞型患者的肿瘤病变部位距肛门口的平均距离显著大于湿热毒蕴型患者,有统计学差异(P＜0.01)。我们认为,目前直肠癌患者多为气血瘀滞和湿热毒蕴型(西医Dukes B、C期),中西医指标间有相似分布,可以相互佐证。气血瘀滞型患者的肿瘤病变部位距肛门口的平均距离显著大于湿热毒蕴型,术前分型为气血瘀滞型保肛手术的几率较大。没有发现中医虚症患者,我们分析认为,这是因为直肠癌和结肠癌对身体的影响不同造成的。结肠癌早期对人体营养物质的摄取会造成影响,因此会出现虚症表现。而直肠癌患者,到了晚期才会对人体的营养状况产生影响,才会出现虚症的表现。建议今后对于结肠和直肠癌的中医诊治应该加以区分,以使中医直肠癌的诊断治疗更加具体可行。
为了解直肠癌的常见证候及其分布与西医学肿瘤生物标记之间的联系,是否在直肠癌早期西医学指标可以检测的同时,有无可能发现中医证候和症型的变化和规律,为中医治疗尚无症状的直肠癌提供依据,发挥中医治疗未病的优势?
我们选取2004年一2006年间在南京市中医院全国中医肛肠医疗中心进行手术治疗并符合纳入标准的直肠癌患者71例(17=71)。将所有入选病例编号,在术前完成中医指标,术后完成病理分型和癌组织中γ-syn表达的检测,同时进行相关性分析。我们发现气血瘀滞型与湿热毒蕴型两组患者γ-syn表达无统计学差异(P=0.54＞0.05)。超重与非超重患者γ-syn表达,两组间没有统计学差异(P=0.82＞0.05)。滑腻苔患者与薄腻苔两组患者γ-syn表达有统计学差异(P=0.03＜0.05)。弦涩脉患者与弦滑脉患者两组患者γ-syn表达有统计学差异(P=0.03＜0.05)。我们认为,直肠癌患者肿瘤组织中γ-syn表达与中医分型没有统计学相关性。薄腻苔,弦滑脉患者与滑腻苔,弦涩脉患者γ-syn表达有统计学差异,有可能和其他指标一起对直肠癌的中医诊断治疗起参考作用。但是早期直肠癌的中医学常见证候及其分布与西医学肿瘤生物标记之间是否有其他的联系和分布规律,还需要大样本的多中心随机对照研究去证明。
通过本研究,我们得出以下结论:1.γ-syn蛋白是直肠癌普遍存在表达的蛋白,可以作为直肠癌的生物标记。目前国内文献尚无γ-syn蛋白在直肠癌组织中表达的报道。2.目前直肠癌患者(西医Dukes B、C期)多为气血瘀滞和湿热毒蕴型。气血瘀滞型患者的肿瘤病变部位距肛门口的平均距离显著大于湿热毒蕴型,推测术前分型为气血瘀滞型保肛手术的几率较大。3.没有发现中医虚症患者,结肠癌和直肠癌由于对机体影响不同,其中医诊治应该加以区分,以使中医直肠癌的诊断治疗更加具体可行。4.薄腻苔,弦滑脉患者γ-syn表达呈梯度上升,滑腻苔和弦涩脉患者γ-syn表达以2+为主,有可能和其他指标一起对直肠癌的中医诊断治疗起参考作用。但是早期直肠癌的中医学指标和西医学肿瘤生物标记之间是否有其他的联系和分布规律,还需要大样本的多中心随机对照研究去证明。5.直肠癌组织中SNCG普遍存在甲基化的现象。提示直肠癌中SNCG表达的调控,可能与SNCG某些CpG位点是否甲基化有关,而并非是SNCG整个基因的低甲基化。
通过本研究,我们也提出了一个研究思路,即是否可以通过研究西医临床指标与中医证型证侯之间的关系,以及肿瘤的生物标记与中医证型证侯之间的关系,发现常见证候及其分布与现代科学技术指标之间的联系,使中医指标可以用现代科学技术标准量化,进而使中医诊治规范化。最终用现代科学技术手段去揭示古老中医理论的秘密,同时用现代技术手段去延伸和丰富中医四诊的信息,有助于古老中医理论系统和临床诊治的补充和完善。
我们认为,对直肠癌中医学指标与西医学临床指标之间关系的深入研究,对用现代科学理论解释中医理论,使中医指标可以用现代科学技术标准量化,指导中医临床治疗分析预后有重要作用。有助于了解直肠癌的常见证候及其分布与现代科学技术指标之间的联系;有助于古老中医理论的补充和完善;有助于直肠癌中医指标的量化和诊治的规范化。并对运用现代医学理论对古老中医理论进行现代科学技术语言的解释具有重要意义。
Traditional Chinese medicine is one of practical science which need basic science to prop up substantial support. Western medicine got a significant development depending on modern science and technique. Traditional Chinese medicine should make the best of achievements of modern science and technique to find out support for explaining it's theory and expanding it's clinic.
Pattern of syndrome and zheng hou in clinical research of Traditional Chinese medicine are real and dependable. Because of lacking of Standards of objective evaluation, they neither to be completely accredit nor to be deny. Hence, how can we precision record and evaluate pattern of syndrome and zheng hou of Traditional Chinese medicine? How to deal with the relationships between the commonness and individuality in clinical research?
Traditional Chinese medicine posses ability of concrete thinking and intuitive thinking, and provided with organism thinking of "unification of human and environment". Today, with the rapid progress of modern science and technique, and changes of human spectrum of disease, heredity and gene, living environment, can we ignore the benefits which science and technique bring to us in diagnosis and treatment of disease and just use the methods of "si wai chuai nei" which set up in ancient dynasty to diagnose and treat disease without any instrument?
Traditional Chinese medicine realized rectal cancer from Qin dynasty. After this, the doctor in different dynasty discussed the causes and pathogenesis about rectal cancer. The theory was forward in Jin, Sui and Tang dynasty. The system theory was set up after Song dynasty. Hence, the theory of traditional Chinese medicine in rectal cancer has long way to go.
There is no the name of rectal cancer in ancient classical documents. The delineation of rectal cancer scattered in the discussion of "ji ju", "chang xun", "suo gang zhi", "zang yong zhi", "zheng jia" et al. Ancient doctor had realized that it is a systemic disease. They considered the primary causation of disease is deficient of zhen qi, closeness relation to function of "pi wei". The other causes are emotion, diet, exogenous pathogenic factors. The modern tradition Chinese medicine doctor considers that the primary causation of rectal cancer is Yin-yang unbalance, Pi xu, Shen kui, insufficiency of zhen qi are the basic cause, and Shi re, Huo du, Pi zhi are the symptom,they are causes and effects for each other.
But, it is difficult to summary the experiences come from different scholars in traditional Chinese medicine because of the effects originated from different knowledge structure and recognition to the diseases of different scholars. Even though the experience summary provides the clue to disciplinarian of syndrome and treatment of rectal cancer to further traditional Chinese medicine clinical research, but it is impossible to accurately summary and quantify them by modern science language and index. These cause the restrain to the experience in repeatability and generality, standardization. These will be a bottleneck to continue development of traditional Chinese medicine.
It has been proved that the effectiveness of traditional Chinese medicine and Chinese herbal drugs are positive in Combined Modality Therapy of rectal cancer. Even though there are a lot of clinical researches of traditional Chinese medicine in rectal cancer, and there are positive reports about the clinical treatment of rectal cancer mainly using by traditional Chinese medicine, but they are usually individual case reports, less mass cases reports were reported by accurate design. There are some serious mistakes of statistic analysis in some reports. These lead to the fact that advanced stage patients of rectal cancer become the main population in treatment of traditional Chinese medicine. Total body condition of patients frequently are worse. Even though we can decrease the symptoms and increase life quality, but it is impossible to most of patients to be cured. With the increasing of health care consciousness of people, there are less and less advanced stage patients of rectal cancer, and the advantage of traditional Chinese medicine in following the prognosis of a disease still is not brought into full play. These are caused by the reason that the theory of traditional Chinese medicine can not be explain by modern science theory and the index of traditional Chinese medicine can not be quantified by modern science technology.
Tumor dialectical grouping of traditional Chinese medicine is a kind of comprehensiveness summary to elemental of cause of disease, pathogenesis, peculiarity of disease and tendency of disease in different disease stage according to traditional Chinese medicine theory. It is the conclusion to the essence of currently disease, it is the foundation of determining the treatment based on differentiation of symptoms and signs. The index of western medicine reflect the tendency of disease and biology characteristics of tumor. Thus, if we know the relationship between the dialectical grouping of traditional Chinese medicine and index of western medicine, it is going to be possible to provide the evidence of modern science theory to the theory of traditional Chinese medicine, and is going to be helpful to quantified index of traditional Chinese medicine by standard of modern science technology. But it is still needed to be explore how we combine the achievements of modern medicine science technology with the research about the cause and pathogenesis of traditional Chinese medicine and to further expand research and deeply comprehend the theory of the cause and pathogenesis of traditional Chinese medicine by the achievements of modern medicine science technology.
The zheng differentiation treatment of traditional Chinese medicine is the key of guide in clinical treatment. "Same disease different treatments, different diseases in same treatment", to prescribe and medication change according to the changes of symptom. The "symptom" of traditional Chinese medicine is different from the disease of western medicine, and the characteristic of traditional Chinese medicine in clinic lead to the result that most clinical research of traditional Chinese medicine which fit to the theory of traditional Chinese medicine are difficult to practice according to design of strict random, matched contral, reduplication standard. The others of researches of traditional Chinese medicine are just clinical cases report and describe or are summaries of therapy experiences. These researches of traditional Chinese medicine are short of reliability coefficient because they are lack of strict science research designed and Quality control approach.
Hence, the subject of this research is to provide the method and evidence for further and deeply comprehending the theory of basica theory of traditional Chinese medicine and Assisting clinical treatment by combining to the achievements of modern medicine science technology.
γ-syn is one of the synuclein family, mainly localizes to the axons of neurons. The abnormally expression of this protein may be linked to the process of tumorigenesis, stage-specific of tumors and lymph node invasion. The transcriptional deregulation that results in SNCG in cancer cells induce SNCG expression through demethylation. Overexpression ofγ-syn disrupt mitotic check point and allow cells to continue progression in aneuploidy. Suppressed caspase activity disrupting the apoptotic response. Expression and action of MMP2 result in overexpression of MMP gene through MAPK signaling pathways promote cancer cell metastasis.γ-syn is proving to be a potential biomarker in tumor. Studies have been carried out to explore the methods of suppressing cancer metastasis and recurrence by gene control andγ-syn targeting medicine.
To investigate the expression ofγ-syn in rectal adenocarcinomas and its correlation with rectal carcinomas. We selected 86 cases rectal cancer patients (n = 86) who had been treated in national medicine centre of colorectal disease of Nanjing municipal traditional Chinese medical hospital and had been diagnosed by pathology from 2005 to 2007. To collect and detect the cancer tissue sample which were surgical ablation. To collect the demography and clinical dates of patients at the same time, including age and gender of patients, distance between tumor edge and anus, CEA level in serum before operation, degree of tumor cell differentiation, situation of lymph nodes metastasis. Immunohistochemistry with anti-γ-syn antibody was performed in 86 cases rectal adenocarcinomas tissues. We discovered that theγ-syn expression was detected in all of rectal adenocarcinomas tissue (86/86). There is no expression difference in gender and age of patients, CEA in serum before operation, differentiation of adenocarcinomas, length from anus to rectal adenocarcinomas edge and metastasis situation of lymph nodes.γ-syn is highly expressed in rectal adenocarcinomas. Our findings suggest thatγ-syn is a ubiquity express protein and it may represent a biological marker of rectal adenocarcinomas. There is no paper to reportγ-syn expression in rectal adenocarcinomas in China.
To investigate the expression regulate ofγ-syn in rectal adenocarcinomas, we chose 22 fresh tissue samples, both of rectal adenocarcinomas and normal mucosa. Detected the SNCG methylation by methylation-specific PCR(MSP). We find that SNCG methylation is common situation in rectal adenocarcinomas. It is suggest that the regulate of SNCG associated to unique CpG island hypomethylation rather than whole gene hypomethylation.
To explore whether there are some internal regularity relationship and associativity between the common Zheng hou and distribution regularity of traditional Chinese medicine and index of Western medicine in rectal cancer. We selected 71 cases rectal cancer patients (n= 71) who had been performed operation in national medicine centre of colorectal disease of Nanjing municipal traditional Chinese medical hospital and had been diagnosed by pathology, fitting to the internalization standard from 2004 to 2006. Then numbered those patients. Complete The Chinese and Western medicine index before operation, and define pathological type after operation then proceed Associativity analysis. We discovered that according to the differentiation of symptoms and signs of classification of syndrome of traditional Chinese medicine , QI-blood stagnant existed was the most common type in Dukes B、C stage. The thinness and greasy tongue fur and unsmooth pulse are the common signs in these patients. Weight in the normal range was found in 70.4% patients, overweight was found in 25.4 % patients. There is not Asthenia syndrome patient. The average distance from edge of rectal cancer to anus was (7.2±4.9cm) in QI-blood stagnant type patient, significantly exceeded the type of Shi Re Du Yun patients (4.6±2.0cm). There is statistics difference(P < 0.01). This research discovered that most of rectal cancer patients belong to QI-blood stagnant and Shi Re Du Yun in classification of syndrome of traditional Chinese medicine (Dukes B. C stage). The distance from edge of rectal cancer to anus in QI-blood stagnant type patients was significantly exceeded the type of Shi Re Du Yun type patients. These suggest that it is more possible to process the sphincter perservation operation in the type of QI-blood stagnant type patients. There is similar distribution in index between Western medicine and Traditional Chinese medicine. They can be evidence for each other. We did not find the Asthenia syndrome patient. We think that it is caused by different effect to total body situation between rectal cancer patients and colon cancer patients. The intake of nutrient substance is decreased in early stage of colon cancer patients so that the patients have sign of Asthenia syndrome. To rectal cancer patients, The intake of nutrient substance is decreased in advanced stage, the sign of Asthenia syndrome can be found only in advanced stage. We suggest that it is necessary to classify colon cancer and rectal cancer in diagnose and treatment of traditional Chinese medicine, which would make diagnose and treatment are more accuracy.
To explore the relationship and associativity between the common Zheng hou and distribution regularity of traditional Chinese medicine and tumor biological marker of Western medicine in rectal cancer. Whether we can find out the regularity and variation of Zheng hou and Zheng xing of traditional Chinese medicine while the index of western medicine can be detected in early stage of rectal cancer? And to provide the evidence for traditional Chinese medicine in treatment of no symptom rectal cancer, so as to the advantage of following the prognosis of a disease of traditional Chinese medicine bring into full play?
We selected 71 cases rectal cancer patients (n = 71) who had been performed operation in national medicine centre of colorectal disease of Nanjing municipal traditional Chinese medical hospital and had been diagnosed by pathology, fit to the internalization standard from 2004 to 2006.Then numbered those patients. To complete The traditional Chinese medicine index before operation and to define pathological type ,detected the expression ofγ-syn after operation then proceed Associativity analysis. We discovered that the expression ofγ-syn in QI-blood stagnant group and Shi Re Du Yun group in classification of syndrome of traditional Chinese medicine are no statistics difference(P=0.54). There is not statistics difference between the overweight group and no overweight group in the expression ofγ-syn(P= 0.82 > 0.05). There is statistics difference between the smooth greasy tongue fur group and thin greasy tongue fur group in the expression ofγ-syn(P=0.03 < 0.05). There is statistics difference between the string unsmooth pulse group and string slippery pulse group in the expression ofγ-syn(P=0.03 < 0.05). we conclude that there is a tendency to smooth greasy tongue fur and thin greasy tongue fur, the string unsmooth pulse and string slippery pulse which maybe have consult effect for diagnosis and treatment of traditional Chinese medicine in rectal cancer while it combine to other index. But if there is a relationship and associativity between the common Zheng hou and distribution regularity of traditional Chinese medicine and tumor biological marker of Western medicine in rectal cancer still need larger sample, multicentre randomised control trial to prove.
We can conclude in behalf of this study: 1.γ-syn is a ubiquity express protein and it may represent a biological marker of rectal adenocarcinomas. There is no paper to reportγ-syn expression in rectal adenocarcinomas in the china. 2. Most of rectal cancer patients belong to QI-blood stagnant and Shi Re Du Yun in classification of syndrome of traditional Chinese medicine (Dukes B. C stage). The distance from edge of rectal cancer to anus in QI-blood stagnant type patients was significantly exceeded the type of Shi Re Du Yun type patients. These suggest that it is more possible to process the sphincter perservation operation in the type of QI-blood stagnant type patients.3. We did not find the Asthenia syndrome patient,it is necessary to classify colon cancer and rectal cancer in diagnose and treatment of traditional Chinese medicine, which would make diagnose and treatment are more accuracy. 4. There is statistics difference between the smooth greasy tongue fur group and thin greasy tongue fur group in the expression ofγ-syn(P=0.03 < 0.05) and statistics difference between the string unsmooth pulse group and string slippery pulse group in the expression ofγ-syn(P=0.03 < 0.05). There is a tendency to smooth greasy tongue fur and thin greasy tongue fur, the string unsmooth pulse and string slippery pulse which maybe have consult effect for diagnosis and treatment of traditional Chinese medicine in rectal cancer while it combine to other index. But if there is a relationship and associativity between the common Zheng hou and distribution regularity of traditional Chinese medicine and tumor biological marker of Western medicine in rectal cancer still need larger sample, multicentre randomised control trial to prove.5. SNCG methylation is common situation in rectal adenocarcinomas. It is suggest that the regulate of SNCG associated to unique CpG island hypomethylation rather than whole gene hypomethylation.
After finished this study, we provide a new research method that if we can find the relationship between the common Zheng hou of traditional Chinese medicine and index of modern science technique for quantificated the index of traditional Chinese medicine by index of modern science technique, then standardize the diagnosis and treatment of traditional Chinese medicine by studying the relationship between Zheng hou of traditional Chinese medicine and index of western medicine and the relation between Zheng hou of traditional Chinese medicine and tumor biological marker. The subject is to find out the secret of theory of ancient traditional Chinese medicine, and to extend and enlarge the diagnosis information of traditional Chinese medicine in order to help the supplement and consummate of theory system of ancient traditional Chinese medicine and diagnosis and treatment of traditional Chinese medicine.
In conclusion, to further studying the relationship between index of traditional Chinese medicine and index of western medicine in rectal cancer patients has important effect to explain theory system of ancient traditional Chinese medicine by theory of modern science technique, quantificating the index of traditional Chinese medicine by index of modern science technique, and guiding clinic treatment and prognosis of traditional Chinese medicine. It is helpful to get the message of the distribution of common Zheng hou of traditional Chinese medicine in rectal cancer and the relationship with the index of modern science technique. It is helpful for the supplement and consummate of theory system of ancient traditional Chinese medicine. It is helpful for quantificated the index of traditional Chinese medicine and standardize the diagnosis and treatment of traditional Chinese medicine. It is important to explain the theory of ancient traditional Chinese medicine using modern medical theory by language of modern science technique.
引文
1.《灵枢·水胀篇》
2.《素问·腹中论》
3.许叔微,宋,《普济本事方》
4.龚信,明,《古今医鉴》
5.巢元方,隋,《诸病源候论》
6.严用和,宋,《济生方》
7.罗天益,元,《卫生宝鉴》
8.张景岳,明,《景岳全书》
9.祁坤,清,《外科大成·二十四痔》
10.陈实功,明,《外科正宗》
11.张仲景,汉,《金匮要略·疟病脉证并治第四》
12.葛洪,晋,《肘后备急方》
13.《灵枢.百病始生》
14.李中梓,明,《医宗必读》
15.《素问·生气通天论》
16.张从正,金元时期,《儒门事亲》
17.《灵枢·百病始生》
18.《素问,风论》
19.宋·徽宗,《圣济总录》
20.朱丹溪,元,《丹溪手镜》
21.孙思邈,唐,《千金要方》
22.李用粹,清,《证治汇补》
23.《内经》
24.朱丹溪,元,《丹溪心法》
25.《灵枢·五变》
26.朱丹溪,元,《丹溪摘玄》
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1.Ji H.,Liu YE,Jia T,et al.Identification of a breast cancer-specific gene,BCSG1,by direct differential cDNA sequencing.Cancer Res.1997,57(4):759-764.
2.Lavedan C,Leroy E.,Dehejia A,et al.Identification,localization and characterization of the human gammasynuclein gene.Hum Genet.1998,103(1):106-111.
3.Lavedan C,Leroy E,Torres R,et al.Genomic organization and expression of the human beta-synuclein gene(SNCB).Genomics1998,54(1):173-175.
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4.曹洋,刘展华,陈志坚.陈锐深教授治疗大肠癌的经验.中医药学刊,2005,23(10):1750-1751.
5.田劭丹,李忠.大肠癌的中西医结合诊治.中国临床医师杂志,2007,5(4):26-28.
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7.吴苏冬,周冬枝,贾宗良,等.结肠癌脾虚证p53,Bc 1-2和Bax的表达.第四军医大学学报,2003,24(12):1111
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11.范小华,吴文江,罗湛滨,梁学敏.大肠癌围手术期中医证候规律研究的临床价值,辽宁中医杂志,2005,32:857-858.
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13.郭蕾,王永炎,张志斌,张俊龙.关于证候概念研究的思考.山西中医学院学报,2006,7:54-55.
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1.李忠.临床中医肿瘤学.沈阳:辽宁科学技术出版社,2002:99.
2.杨宇飞,吴煜,许云.大肠癌中医临床研究方法学探讨.中国肿瘤,2006,15:(6),354-355.
3.王晓锋,李华山.大肠癌中医证治临床研究进展.世界华人消化杂志,007,15(29):3062-3066.
4.曹洋.刘展华,陈志坚.陈锐深教授治疗大肠癌的经验,中医药学刊,2005,23:1750-1751.
5.田劭丹,李忠.大肠癌的中西医结合诊治.中国临床医师杂志,2007:5(4),26-28.
6.刘静,张军,朱琦.中医药治疗大肠癌辨证用药分析.辽宁中医杂志,2006:33(9):1166-1167.
7.吴苏冬,周冬枝,贾宗良等.结肠癌脾虚证p53,Bc 1-2和Bax的表达.第四军医大学学报,2003,24(12):1111.
8.SABISTON Textbook of Surgery(the Biological Basis of Modern Surgical Practice),18th edition,section X,Charpter 50.
9.Ji H.,Liu YE,Jia T,et al.Identification of a breast cancer-specific gene,BCSG1,by direct differential cDNA sequencing.Cancer Res,1997,57(4):759-764.
10.Liu H,Liu W,Wu Y,et al.Loss of epigenetic control of synuclein-gamma gene as a molecular indicator of metastasis in a wide range of human cancers.Cancer Res,2005,65(17):7635-7643.
11.Wu K,Quan Z,Weng Z et al.Expression of neuronal protein synuclein gamma gene as a novel marker for breast cancer prognosis.Breast Cancer Res Treat,2006,101,259-267.
12. Singh VK, Zhou Y, Marsh JA, et al. Synuclein-gamma targeting peptide inhibitor that enhances sensitivity of breast cancer cells to antimicrotubule drugs. Cancer Res, 2007, 67(2):626-33.
13. Jianping Guo, Cheng Chao Shou, Lin Meng et al. Neuronal protein synuclein y predicts poor clinical outcome in breast cancer. International journal of cancer, 2007,121:1296-1305.
14. Liu H, Zhou Y, Boggs SE, et al. Cigarette smoke induces demethylation of prometastatic oncogene synuclein-gamma in lung cancer cells by downregulation of DNMT3B. Oncogene, 2007, 26(40):5900-5910.
15. Singh VK, Jia Z.Targeting synuclein-gamma to counteract drug resistance in cancer. Expert Opin Ther Targets, 2008,12(1):59-68.
16. Frandsen PM, Madsen LB, Bendixen C, et al.Porcine gamma-synuclein: molecular cloning, expression analysis, chromosomal localization and functional expression. Mol Biol Rep, 2008,18:461-469.
17. Yu-Mei Gua, Jian-Xin Tana,et al.BCSGl Methylation Status and BCSG1 Expression in Breast Tissues Derived from Chinese Women with Breast Cancer Oncology 2008, 74(1-2):61-68.
18. Zhao W,Liu H,Liu W, et al. Abnormal activation of the synuclein-gamma gene in hepatocellular carcinomas by epigenetic alteration. Int J Oncol, 2006,28(5), 1081-1088.
2.《素问·腹中论》
3.许叔微,宋,《普济本事方》
4.龚信,明,《古今医鉴》
5.巢元方,隋,《诸病源候论》
6.严用和,宋,《济生方》
7.罗天益,元,《卫生宝鉴》
8.张景岳,明,《景岳全书》
9.祁坤,清,《外科大成·二十四痔》
10.陈实功,明,《外科正宗》
11.张仲景,汉,《金匮要略·疟病脉证并治第四》
12.葛洪,晋,《肘后备急方》
13.《灵枢.百病始生》
14.李中梓,明,《医宗必读》
15.《素问·生气通天论》
16.张从正,金元时期,《儒门事亲》
17.《灵枢·百病始生》
18.《素问,风论》
19.宋·徽宗,《圣济总录》
20.朱丹溪,元,《丹溪手镜》
21.孙思邈,唐,《千金要方》
22.李用粹,清,《证治汇补》
23.《内经》
24.朱丹溪,元,《丹溪心法》
25.《灵枢·五变》
26.朱丹溪,元,《丹溪摘玄》
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41.李梢,从维度与阶度探讨中医证候的特征及标准化方法.北京中医药大学学报,2003,26:1-4.
42.范小华,吴文江,罗湛滨,梁学敏.大肠癌围手术期中医证候规律研究的临床价值,辽宁中医杂志2005,32:857-858.
43.郭蕾,王永炎,张志斌.关于证候概念的诠释.北京中医药大学学报,2003,26:5-8.
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