用户名: 密码: 验证码:
四种方法治疗腋臭的临床疗效分析及ApoD表达异常在腋臭发病中的作用研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
腋臭是整形美容外科的常见病,常发生于年轻人,与大汗腺分泌功能异常有关。腋臭虽然不对机体功能造成损害,但给患者带来很大的精神和心理压力,影响正常的生活和工作。目前治疗腋臭的方法很多,治疗效果多不相同。本研究在传统的腋部皮肤切除Z成形术、微小切口肿胀麻醉吸刮术的基础上,创新的设计了电针(第四军医大学唐都医院研制的具有自主知识产权的超高频皮肤整形仪)疗法及顺腋纹切口厚中厚皮原位植皮术治疗腋臭。对这4种方法的治疗效果进行深入分析,探讨临床效果好、并发症少的治疗腋臭的适宜方法。
     此外,进一步阐明腋臭发生的分子机制,在深入认识腋臭发生病理机制的同时,有望发现无创治疗腋臭的新手段,对腋臭治疗具有重要的意义。研究表明,(E)-3-甲基-2-已烯酸(E-3M2H)的分泌在腋臭发生过程中具有重要作用,而载脂蛋白D(ApoD)是调控其分泌的重要分子。然而,腋臭患者中ApoD的表达情况及其与腋臭的关系尚不清楚。深入分析腋臭患者中ApoD的表达及其机制,对于认识腋臭的发生具有重要的意义。
     目的:
     用4种方法治疗腋臭,对治疗效果进行观察,并对疗效和并发症进行对比分析,总结每种治疗方法的技术要点和优缺点。在分子机制方面,观察与E-3M2H分泌相关的载脂蛋白D(ApoD)和雄激素受体AR在腋臭患者的大汗腺的表达与正常人的差异,探讨导致腋臭患者ApoD表达异常的原因。
     方法:
     1)对2006年9月至2010年9月的109名腋臭患者分别采用电针疗法、腋部皮肤切除Z成形术、微小切口肿胀麻醉吸刮术及顺腋纹切口厚中厚皮原位植皮术4种方法进行治疗,并对4种治疗方法的效果及并发症进行观察和对比分析。
     2)收集4例正常对照和10例腋臭患者的组织样本,采用免疫组化、realtime-PCR和western-blot检测腋臭患者组织中ApoD、AR的表达水平,通过细胞培养和激素诱导,分析AR信号调控ApoD表达的可能性,并阐明JNK1信号通路在其中扮演的作用。
     3) 2008年10月~2010年12月来自第四军医大学唐都医院整形激光美容中心的腋臭患者78例。吩咐腋臭志愿者在腋臭气味强度检测前一天沐浴并禁食辛辣刺激食物,检测当天在舒适的环境下进行(室内清洁,室温28°C,关闭门窗)。志愿者充分暴露腋区,由3名医生分别距志愿者1m、3m、5m闻腋臭气味。按照能在≤1m、≤3m、≤5m距离闻及气味把志愿者分为轻、中、重3级。结果:轻、中、重3级的腋臭志愿者人数分别为12、24、42。术中取患者左右两侧腋下新鲜皮肤组织长约5-6cm(深及脂肪层),对组织标本进行多点取材。取材标本立即放入液氮速冻,随后放入-80℃冰箱保存,提取RNA,检测目的基因的表达丰度。
     结果:
     1)新设计的两种方法均能有效的治疗腋臭,四种治疗腋臭方法总有效率94%,电针疗法治愈率低,有一定的复发;腋部皮肤切除Z成形术和顺腋纹切口厚中厚皮原位植皮术治愈率高,有效率均达到100%;微小切口肿胀麻醉吸刮法治疗腋臭有效率80%,偶有臭味残留和复发,四种治疗方法均有不同程度的并发症;顺腋纹切口厚中厚皮原位植皮术是目前治疗腋臭比较理想的方法。
     2)我们的实验发现ApoD和AR在腋臭患者的大汗腺的表达与正常人有明显的差异,腋臭患者中ApoD表达几乎是正常人的2倍;而腋臭患者中AR表达也明显增加,与此同时,腋臭患者中JNK1活化增强。
     3)雄激素可以增强正常人ApoD的表达,且该过程中同样伴有JNK1活化;抑制JNK1活化,可以降低腋臭患者和雄激素诱导的ApoD的表达。
     4)按照AB 7500 Real-Time PCR系统分析软件的结果,把ApoD的相对表达量分为低(1~2)、中(2~4)、高(﹥4)三个等级。ApoD相对表达量的等级与气味强度之间有线性关系(P﹤0.05)。ApoD相对表达量的等级随着气味强度的增加而增高。
     结论:
     1)应根据患者不同的情况选择适宜的治疗腋臭方法。电针疗法具有痛苦小、操作简单容易、易被患者接受的优点,症状轻、惧怕开刀手术的患者较合适,但治愈率较低,有一定的复发;腋部皮肤切除Z成形术治愈率及有效率高,但术后并发症的发生率也较高;微小切口肿胀麻醉吸刮术有效率较高,有少数复发,并发症发生率比腋部皮肤切除Z成形术低,与顺腋纹切口厚中厚皮原位植皮术相比并发症无显著差异;顺腋纹切口厚中厚皮原位植皮术治愈率和有效率高,术后并发症低,是目前较理想的治疗腋臭方法。但这几种治疗方法都存在一定的痛苦和并发症,所以对腋臭的发病机制进行进一步的研究和探讨,有望发现腋臭发生新的机理,找到治疗和预防腋臭的新突破点,为其治疗提供新思路。
     2) ApoD表达增加是腋臭患者的重要分子特征,其表达增加与AR信号增强密切相关。
     3) JNK1的活化是腋臭患者和雄激素导致的ApoD表达增加的重要原因,抑制JNK1活化,可以抑制腋臭患者内源和雄激素诱导的ApoD的表达。
     4) ApoD的表达丰度与腋臭的强度呈正相关。
Axillary Osmidrosis (AO) is a common disease which most frequently occurs in young adults. It is generally considered that axillary osmidrosis is related to the abnormal secretions of the apocrine sweat gland and has strong genealogical links. In China, AO has a powerful negative psychological influence on patients, leading to a high demand for therapy. Currently, there are four surgical therapeutic methods in use when dealing with axillary osmidrosis in our department: electro-acupuncture therapy; axillary skin resection and Z-remodeling operation; suction and curettage with tumescent anaesthesia; intermediate-thickness skin grafting. Each procedure is replete with its own particular advantages and disadvantages. In this study, we systematically compare the efficacy of the four different therapeutic strategies. For a full understanding of the mechanism through which AO occurs, we must begin by exploring the genesis of ApoD; from its essence in E-3M2H secretion, which is so often characterized by its symptomatic unpleasant odor.
     Aim:
     To compare the efficacy of the four different therapeutic strategies used in our hospital. To compare the differences in the physical symptoms of patients with ApoD in axillary osmidrosis and normal subjects. To explore the underlying mechanism, especially the role of JNK1, in the process through which AO occurs.
     Methods:
     1) 109 axillary osmidrosis patients, recruited from 2006.9 until 2010.9, were divided into four groups. Patients from each these four groups all underwent a different type of curative procedure; electro-acupuncture therapy, axillary skin resection and Z-remodeling operation, suction and curettage with small skin incision and Local anesthesia, and inter-mediate thickness skin graft respectively. The efficacy and complications associated with each type of therapy were then systematically evaluated and compared.
     2) Biopsy specimens of the underarm area were obtained from healthy male donors (n =4) and axillary osmidrosis patients (n = 10) following local anesthesia with lidocaine hydrochloride [containing epinephrine hydrochloride at a dilution of 1:100 000]. We compared the expression of ApoD between the normal and osmidrosis subjects through; Western Blot, immunohistochemistry and qRT-PCR. The activation of JNK1 was also studied to explore the potential for involvement of JNK1 and AR signaling in ApoD regulation.
     3) Seventy-eight axillary osmidrosis patients were recruited from our department from 2008.10-2010.12 in Tangdu Hospital. Patients were classified into three groups according to the extent of the osmidrosis. Briefly, the osmidrosis patients were asked to stay in a room (with a constant temperature of 28°C and with the door closed) and to keep their arms naked and exposed. The same examiner was asked to smell the unpleasant odor from each of the different test patients sequentially: from 5, 3 and 1 meter’s distance. The extent of the osmidrosis was classified into a basic scale of; mild, middle and severe odor, and corresponded to the unpleasantness of the odor detected. Biopsy specimens of the underarm area were also obtained from axillary osmidrosis patients following local anesthesia with lidocaine hydrochloride [containing epinephrine hydrochloride at a dilution of 1:100 000]. For RNA analysis, intact skin from was rinsed with D-Hank buffer, and subcutaneous fat was removed. The skin was minced (1mm3) with sharp scissors in a culture plate. The pieces were then incubated with type II collagenase (3 mL) at 37°C in a humidified atmosphere of 5% CO2 and 95% air. On the following day, the gland coils were removed and harvested for RNA isolation. Tissue samples were rinsed twice in cold sterile PBS, and total RNA was extracted by Trizol (Invitrogen) following the manufacturer’s instructions. Total RNA was quantified and 1μg RNA was reverse transcribed by M-MLV. qPCR was performed using an AB 7500 Real-Time PCR System. Each sample was run in triplicate for both genes of interest and the housekeeping gene.
     Results:
     1) The general efficacy of the four surgeries was 94%. The therapeutic effect of electro-acupuncture therapy was much lower than the other three. This procedure also resulted in some recurrence of the symptoms. Axillary skin resection with Z-remodeling operation and inter-mediate thickness skin graft cured the disease. The success ratio of suction and curettage with tumescent anaesthesia was around 80%,with some patients having some remaining unpleasant odor or later recurrence. All four surgeries had certain complications and side effects.
     2) The relative expression levels of ApoD in axillary osmidrosis patients are nearly 2 times higher than that found in the normal control sample. Consistently, ApoD expression at protein level was also higher in osmidrosis patients than that in the normal subjects. In addition, AR expression was also found to be higher in axillary osmidrosis subjects. Accordingly, phosphorylated JNK was also higher but there was no significant difference of the absolute level between the two groups.
     3) Apocrine gland cells from the axillary osmidrosis subjects were cultured in vitro. Activation of JNK1 and high expression of ApoD continued even after 10 days of culture generation. JNK1 inhibitor SP600125 significantly blocked the activation of JNK1. Accordingly, ApoD decreased both at protein level and mRNA level. In contrast, in vitro cultured apocrine cells expressing low level of ApoD from the normal subject were stimulated with 5α-dihydrotestosterone at concentration levels of 10-7M and 10-6M. When the drug concentration was increased, ApoD expression enhanced gradually. Whilst blocking JNK activation with SP600125, increased ApoD was seen to be compromised both at protein and mRNA level.
     4) We analyzed a total of 78 individuals with axillary osmidrosis. There were 12“mild”, 24“middle”and 42“severe”patients. Of the 78 axillary osmidrosis patients, 29 were females and 49 were males. Therefore, more males were in the severe axillary osmidrosis category. Next we tested the expression of ApoD at mRNA level among these 78 patients by real-time assay. The expression of ApoD differed among these subjects. The highest level was nearly 6 times higher than that of the lowest level. It seems that expression of ApoD in severe axillary osmidrosis patients is much higher than that in mild patients.
     Conclusion:
     1) All of the four different surgeries have advantages and disadvantages. Though the therapeutic effect of electro-acupuncture therapy was the lowest, it causes less invasive lesion and the operation fee is much cheaper. Selection of the surgery should be based upon the severity of the axillary osmidrosis, the effect on the will of the patients and so on.
     2) Our study here demonstrates that the apocrine glands in axillary osmidrosis have a higher expression of ApoD (ASOB2), which is consistent with higher expression of AR and pJNK. Stimulation of cultured apocrine gland epithelial cells with 5α-DHT resulted in a concentrated dependent rise in ApoD protein as well as in mRNA, indicating regulation of ApoD on both protein and mRNA levels by androgen receptor stimulation.
     3) The increase of ApoD could be blocked by the JNK inhibitor, demonstrating an involvement of JNK in the axillary osmidrosis. Furthermore, inhibition of JNK1 in the apocrine cells from the axillary osmidrosis subjects also reduces the endogenous expression of ApoD. Further studies are needed to confirm the role of JNK inhibition in axillary osmidrosis.
     4) In the study, we demonstrated a strong association between the ApoD expression and the extent of axillary osmidrosis. Our results suggest that the increased ApoD expression is one of the important characteristics of axillary osmidrosis. This expression is also much more prevalent in severe axillary osmidrosis.
引文
1.栗颖利,陈辉.腋臭发病机制的研究进展.中国美容医学, 2010,19(7):1082-1084
    2.杜洁,曹彦,陈辉.腋臭的外科治疗现状.中国美容医学,2008,17(10): 1555-1557
    3. Tung,Tung-Chain,Endoscopic Shaver with Liposuction for Treatment of Axillary osmidrosis,Ann,Plast,Surg, 2001,46:400
    4. Akutsu T, Sekiguchi K, Ohmori T, Sakurada K. Individual comparisons of the levels of (E)-3–methyl -2-hexenoic acid, an axillary odor-related compound, in Japanese.Chem Senses,2006, 31(6):557-563
    5. Natsch A, Gfeller H, Gygax P,et al . A specific bacterial aminoacylase cleaves odorant precursors secretedin the human axilla.J Biol Chem, 2003, 278(8) :5718-5727
    6. Natsch A, Schmid J, Flachsmann F. Identification of odoriferous sulfanylalkanols in human axilla secretions and their formation through cleavage of cysteine precursors by a C-S lyase isolated from axilla bacteria. Chem Biodivers, 2004,1(7) :1058-1072.
    7. Nakane T,Gomyo H,Sasaki I,et a1.New antiaxillaryodour deodorant made with antimicrobial Ag—zeolite (silver~exchanged zeolite).Int J Cosmet Sci,2006,28(4):299-309
    8.陈玉平,金优,韦晶星.5-氟脲嘧啶加无水酒精局部注射治疗腋臭.中国美容医学,2006,15(12):1398-1399
    9. Atkins JL, Butler PE.Hyperhidrosis: A review of cur-rentmanagement. Plast. Reconstr. Surg,2002,110:222.
    10.王荫椿,韩义贞.肉毒毒素在医学美容中的应用.中国美容医学,2002, 11(1):88-91
    11. Salmanpoor R, Rahmanian MJ. Treatment of axillary hyperhidrosis with botulinum-A toxin. Int J Dermatol,2002,41(7):428-430
    12.王琳,高赫,魏丽岩,孔雀.A型肉毒毒素注射治疗腋窝多汗症或伴腋臭症.中华医学美学美容杂志,2009,15(3):173-175
    13.谢爱国,陈曦,周宏,王淑琴,谭谦.A型肉毒毒素局部注射治疗腋部臭汗症.中国美容医学,2009,18(7):911-913
    14.陈学荣,朱耀芬.脉冲管冷冻仪治疗腋臭疗效观察.临床皮肤科杂志,1999,28(5):299-300
    15. Ichikawa K,Miyasaka M,Aikawa Y.Subcutaneous laser treatment of axillary osmidrosis:a new technique.Hast Reconstr Surg, 2006,8(1):1 70-174
    16.姚春丽,王桂芝,姜萍等.Nd:YAG激光治疗腋臭的临床体会.激光杂志,2008,29(2):46
    17.吴展航,曾艺红,欧丽婵.超脉冲CO_2激光治疗腋臭55例.中国美容医学,2009,18(9):1314-1315
    18.罗文,孙林潮.半导体激光结合超脉冲CO_2激光治疗腋臭临床观.中国美容医学,2007,16(4):539-540
    19.王丽凤,宋祥红,钱英等.多功能电离子治疗机治疗48例腋臭患者的临床观察.齐齐哈尔医学院学报,2009,30(22):2794
    20.尹淑英,石现,常雄等.高频电火针治疗腋臭392例.中国针灸, 2003,23(6):366
    21.刘趁芬,刘增柱,李恒用等.微波治疗腋臭42例疗效观察.中国麻风皮肤病杂志,2007,23(3):225
    22.赵新华,陈辉,张辉,王玉静,郑大雁,陈红艳.XH-超高频整形手术的临床应用.中国美容医学,2000,9(6):421-422
    23.汪卫平.不同方法治疗腋臭的临床对比分析.中国美容医学,2007, 16(7):988-989.
    24.赵景华,罗旭松,于蓉等.局部切除连续多Z成形手术治疗腋臭.华西医学报,2000,15(1):86.
    25.陈剑名,杨怡佳.改良"S"形切口腋臭根治术.中国美容医学, 2006,15(1):39
    26.高建武,曾维慧,张美芳,等.保留真皮下血管网皮瓣法治疗腋臭103例体会.中国实用美容整形外科杂志,2008,17(5):640-641
    27.张鹏,胡永璐.中厚皮瓣法腋臭根治术108例报道.实用美容整形外科杂志,2003,14(5):247-248.
    28.刘庆阳,宋业光,郑江红等.“全厚皮”法根治腋臭.中国美容医学, 2008,17(4):479-482
    29. Tung TC,Wei FC.Excision of subcutaneous tissue for the treatment of axillary osmidrosis.Br J Plast Surg, 1997, 50:61-66.
    30.田宗华,何勇.腋窝汗腺毛囊祛除和原位植皮法治疗腋臭28例临床分析.贵州医学,2008,32(1):64
    31.杨东华,关志江.腋窝皮下组织切除和原位植皮法治疗腋臭28例临床分析.中华医学实践杂志,2006,5(3):313
    32.王朝霞,李明霞.肿胀抽吸术治疗腋臭的临床应用.现代医药卫生, 2005,21(3):311-312
    33. Yoo WM,Pae NS,Lee SJ,et al.Endoscopy-assisted ultrasonic surgical- laspiration of axillary osmidrosis: A retrospective reviewof 896 consecutive patients from 1998 to 2004 .Plast Reconstr & Aesth Surg,2006,59:978-982
    34.汪峰.自制有齿刮匙微创祛除腋臭.中华医学美学美容杂志,2007,3:321
    35.曹彦,陈辉,杜洁等.肿胀麻醉负压吸引联合修剪根治腋臭的疗效分析.中国实用整形外科杂志,2009,20(11):668-670
    36.朱正鹏,杨一梅,鲜华等.皱襞切口修剪加CO_2激光汽化大汗腺治疗腋臭.中国美容医学,2006,15(11):1268-1269
    37. Kao TH, Pao HC, SunMH, et al. Upper thoracic sympathectomy for axillary osmidrosis or bromidrosis.J Clin Neurosci, 2004,11(7):7192- 7222
    38. Bang YH, Kim JH, Paik SW,et al. Histopathology of apocrine brom hidrosis. Plast Reconstr Surg,1996,98: 288
    39.秦维郎.腋臭症の基本的事项と治療の灾際.形成外科,1995,38(增刊):213
    40. H.Chen, C.X.Li, J Du,et al.Distribution of apocrine sweat gland in Han patients with axillary osmidrosis and its surgical treatments. Scientific Research and Essays,2010,5(17):2556-2559
    41.陈辉,李承新,杜洁.汉族人腋臭大汗腺的分布及手术治疗.中国美容医学, 2008,17(9):1286-1287
    42.杨光荫,彭苏格.内蒙古伊克昭盟地区蒙古族、汉族人群腋臭发病率调查报告.人类学学报,1993,13:80-82
    43.亓发芝.腋臭.实用美容整形外科杂志,2002,13(1):55-56
    44. Gallagher M,Wysocki CJ,Leyden JJ,et al.Analyses of volatile organic compounds from human skin. British Journal of Dermatology,2008,159(4): 780-791
    45. Akutsu T, Sekiguchi K, Ohmori T,et al.Individual comparisons of the levels of (E)-3-methyl-2-hexenoic acid,an axillary odor-related compound,in Japanese. Chem Senses, 2006, 31(6): 557- 563
    46. Spielman AI, Zeng XN, Leyden JJ, et al.Proteinaceous precursors of human axillary odor:isolation of two novel odor-binding proteins. Experientia, 1995,51(1):40-47
    47. Kurata S, Itami S, Komada S, et al . Int ranuclear androgen and cytosolic receptor concent rations in the axillary skin of osmidrosis. Arch Dermatol Res,1990,282(1):33-37
    48. Beier K, Ginez I, Schaller H. Localization of steroid hormone receptors in the apocrine sweat glands of the human axilla. Histochemistry and Cell Biology,2005,123 (1):61-65
    49. Zeng XN, Leyden JJ, Brand JG, et al.An investigation of human apocrine gland secretion for axillary odor precursors. J Chem Ecol,1992,18(7):1039 -1055
    50.鲁开化,澎湃,刘斌,等.腋臭外科治疗的临床与病理观察.中国美容医学,2008,17(10):1421-1424
    51.栗颖利,陈辉,杨国栋,曹彦,杜洁,孙超峰,李晓莉.大汗腺中分泌物气味结合蛋白、雄激素受体表达水平及其与腋臭相关性研究.中国美容医学,2010,19(12):1822-1826
    52. Akutsu T, Sekiguchi K, Ohmori T, Sakurada K. Individual comparisons of the levels of (E)-3–methyl -2-hexenoic acid, an axillary odor-related compound, in Japanese. Chem Senses, 2006, 31(6):557-563
    53. Hall RE, Horsfall DJ, Stahl J, Vivekanandan S, Ricciardelli C, Stapleton AM, Scardino PT, Neufing P, Tilley WD. Apolipoprotein-D: a novel cellular marker for HGPIN and prostate cancer. Prostate,2004,58(2):103-108
    54. Kurata S, Itami S, Komada S, Takayasu S. Int ranuclear androgen and cytosolic receptor concent rations in the axillary skin of osmidrosis. Arch Dermatol Res,1990,282(1):33-37
    55. Ogawa S, Hosoi T,Shirake M,Orimo H,Emi M,Muramatsu M,Ouchi Y,Inoue S.Association of estrogen receptor beta gene polymorphism with bone mineral density. Biochem Biophys Res Commun, 2000, 269(2):537-541
    56.姚毓奇,李晓玫.JNK信号通路研究进展.细胞生物学杂志,2005,27(3): 242-246
    57.刘乐江,唐圣松.JNK信号通路研究进展.现代生物医学进展,2010,10(7): 1378-1380
    58. Verzola D, Villaggio B, Procopio V, et al. Androgen-mediated apoptosis of kidney tubule cells: role of c-Jun amino terminal kinase. Biochem Biophys Res Commun,2009,387(3): 531-536
    59. Lee S H, Heo J S, Lee M Y, et al. Effect of dihydrotestosterone on hydrogen peroxide-induced apoptosis of mouse embryonic stem cells. J Cell Physiol, 2008, 216(1): 269-275
    60. Shimada K, Nakamura M, Ishida E, et al. Requirement of c-jun for testosterone-induced sensitization to N-(4-hydroxyphenyl) retinamide- induced apoptosis. Mol Carcinog, 2003,36(3): 115-122
    61. Gao M Q, Guo S B, Chen X H, et al. Molecular mechanisms of polypeptide from Chlamys farreri protecting HaCaT cells from apoptosis induced by UVA plus UVB. Acta Pharmacol Sin, 2007, 28(7): 1007-1014
    62. Do CS, Seguin D, Milne R, et al. Modulation of apolipoprotein D and apolipoprotein E mRNA expression by growth arrest and identification of key elements in the promoter. J Biol Chem, 2002, 277(7): 5514-5523
    63. Schoenmakers E, Verrijdt G, Peeters B, et al. Differences in DNA binding characteristics of the androgen and glucocorticoid receptors can determine hormone-specific responses. J Biol Chem, 2000, 275(16): 12290-12297
    64. Foradori C D, Weiser M J, Handa R J. Non-genomic actions of androgens.Front Neuroendocrinol, 2008, 29(2): 169-181
    65. Hull-Thompson J, Muffat J, Sanchez D, et al. Control of metabolic homeostasis by stress signaling is mediated by the lipocalin NLaz. PLoS Genet, 2009, 5(4): e1000460
    66. Verzola D, Villaggio B, Procopio V, et al. Androgen-mediated apoptosis of kidney tubule cells: role of c-Jun amino terminal kinase. Biochem Biophys Res Commun, 2009, 387(3): 531-536
    67. Wang Z, Liu L, Hou J, et al. Rapid membrane effect of testosterone in LNCaP cells. Urol Int, 2008, 81(3): 353-359
    68. Lee S H, Heo J S, Lee M Y, et al. Effect of dihydrotestosterone on hydrogen peroxide-induced apoptosis of mouse embryonic stem cells. J Cell Physiol, 2008, 216(1): 269-275
    69. Shimada K, Nakamura M, Ishida E, et al. Requirement of c-jun for testosterone-induced sensitization to N-(4-hydroxyphenyl) retinamide- induced apoptosis. Mol Carcinog, 2003, 36(3): 115-122
    70. Saga K. Histochemical and immunohistochemical markers for human eccrine and apocrine sweat glands: an aid for histopathologic differentiation of sweat gland tumors. J Investig Dermatol Symp Proc, 2001, 6(1): 49-53

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700