免疫性炎症与前列腺体积及雄激素受体表达的关系

目的:探讨免疫性炎症与前列腺体积及雄激素受体表达的关系。方法:回顾性的分析了105例手术获得的前列腺标本。使用免疫组化的方法研究前列腺组织中CD4、CD8和雄激素受体表达情况。如果CD4或CD8阳性则被定义为免疫性炎症,并进一步探讨了免疫性炎症与前列腺体积、雄激素受体表达之间的关系。结果:在前列腺增生组织中,CD4、CD8和雄激素受体表达的阳性率分别为20(19.0%),21(20.0%)和48(45.7%)。在免疫性炎症组,前列腺体积为67.0±26.3ml,而在非免疫性炎症组,为54.0±24.2ml,有显著性差别。免疫性炎症组雄激素受体表达的阳性率为65.6%,而非免疫性炎症组雄激素受体表达的阳性率为37.0%(X~2=7.35,P<0.05)。结论:免疫性炎症与前列腺体积、雄激素受体表达明显相关。免疫性炎症可能导致前列腺增生进展,因此,抗炎治疗可能是治疗前列腺增生的一个新的靶点。     

Cox-2、P504s、CK34βE12和P63在前列腺腺癌中的表达及其临床意义

目的：研究Cox-2、P504s、CK34βE12和P63在前列腺腺癌组织中的表达及其临床病理学意义。方法：用免疫组织化学法检测134例正常前列腺、良性前列腺增生和前列腺腺癌石蜡包埋组织中Cox-2、P504s、CK34βE12和P63的表达。结果：正常前列腺组织或良性前列腺增生组织未见或偶见P504s弱表达,但CK34βE12和P63均表达良好;前列腺腺癌组织中P504s表达良好,但CK34βE12和P63均表达消失,P504s表达阳性率为91．07％;与正常前列腺组和良性前列腺增生组相比,前列腺癌组的P504s阳性表达率存在显著性差异（p=0．001）。COX-2在正常的前列腺组织几乎不表达,而良性前列腺增生组织及前列腺腺癌组织均可见阳性表达,阳性率分别为4．76％和80．36％;COX．2阳性表达率在正常前列腺组或良性前列腺增生组和前列腺腺癌组间有显著性差异（p=0．0027）。COX-2与P504s表达存在相关性（r=0．377,P=0．039）;COX-2的表达与年龄、临床分期、分化程度、有无远处转移等临床病理特征间无明显相关关系。结论：联合P504s、P63、CK3413E12和COX-2免疫组化检测可提高前列腺腺癌病理诊断的准确率。     

PSA在前列腺增生和前列腺癌中的诊断价值

目的：探讨临床上检测前列腺特异性抗原（PSA）的变化情况对前列腺增生和前列腺癌等疾病的诊断价值。方法：采用回顾性分析的方法,选取2010年6月至2012年4月在我院泌尿科接受治疗的前列腺增生患者64例定义为前列腺增生组（BPH）,前列腺癌患者83例定义为前列腺癌组（PCa）,另选取同期接受体检的健康人群137例作为对照组。分别检测三组患者入院时的游离前列腺特异性抗原和总前列腺特异性抗原的水平变化情况。对比并分析三组检测结果。结果：经检测,前列腺增生患者的血清总PSA明显高于对照组健康人群的正常值,而前列腺癌患者的血清总PSA比前列腺增生患者增高的更为明显。对照组游离PSA为（2．78±0．94）ng／mL,总PSA（1．05±0．57）ng／mL,游离PSA与总PSA的比值为,（0．38±0．61）;前列腺增生患者游离PSA为（6．36＋3．24）ng／mL,总PSA为（1．64±0．76）ng／mL,游离PSA与总PSA的比值为（0．26±0．23）;前列腺癌患者游离PSA为（12．42±4．97）ng／mL,总PSA为（1．44±0．78）ng／mL,游离PSA与总PSA的比值为（0．12±0．16）。组间比较差异明显,具有统计学意义（P〈0．05）。结论：对患者的PSA进行检测,对前列腺增生和前列腺癌的诊断具有良好的辅助作用和,临床价值。     

子宫内膜癌组织中生长抑素受体、VEGF的表达及其与血管形成的关系

目的探讨生长抑素受体（somatostatin receptor,SSTR）、血管内皮生长因子（vascular endothelial growth factor,VEGF）在子宫内膜癌组织中的表达及其与肿瘤血管形成的关系。方法应用免疫组织化学方法检测60例子宫内膜癌组织中SSTR各亚型、VEGF及CD34标记的微血管密度（microvessel denisity,MVD）的表达情况,探讨其与子宫内膜癌临床病理学特征及肿瘤血管形成的关系。结果在60例子宫内膜癌组织中,SSTR各亚型（SSTR1、SSTR2、SSTR3、SSTR4及SSTR5）的阳性表达率分别为70．0％,15．0％。21．7％,23．3％及18．3％;SSTR3、SSTR4在中高分化组表达阳性率明显高于低分化组（P〈0．05）。VEGF的阳性表达率为83．3％,VEGF在低分化组表达阳性率明显高于中高分化组、深肌层浸润组表达阳性率明显高于浅肌层浸润组、FIGO分期≥II期组表达阳性率明显高于I期组（P〈0．05）。子宫内膜癌组MVD（44．85±15．78）明显高于正常子宫内膜组MVD（18．96±4．30）（P〈0．01）。SSTR5的表达与VEGF呈负相关,VEGF阳性表达组子宫内膜癌组织MVD高于VEGF阴性组。结论联合检测SSTR和VEGF对子宫内膜癌预后的评估有一定临床意义。生长抑素类似物（somatostatin analogs,SSTA）可能为子宫内膜癌的诊治提供新的靶点。     

聚乙二醇干扰素α-2a对慢性乙型肝炎患者树突状细胞B7-H1表达的影响

目的：观察聚乙二醇干扰素α-2a对慢性乙型肝炎患者外周血树突状细胞功能及B7-H1的影响,探讨慢性乙型肝炎病毒逃逸的的机制。方法：慢性乙型肝炎患者31例,给予聚乙二醇干扰素α-2a180txg抗病毒治疗52周,分别于0、12、26、52周检测肝功能、HBV-DNA;流式细胞术检测外周血mDC表面HLA-DR、CD80、CD86、CD83、CDla、B7一H1水平。根据患者HBV—DNA水平,将患者分为应答组（A组）、非应答组（B组）,10例健康志愿者作正常对照组（C组）。结果：慢性乙肝患者的树突状细胞膜表面分子HLA-DR、CD80、CD86、CD83、CDla的表达均降低。聚乙二醇干扰素α-2a治疗后应答组膜表面分子HLA-DR、CD80、CD86、CD83、cDla的表达高于非应答组65．3±6．2％VS44．2±5．5％,67．2±7．4％VS37.3±7．2％,68．4±3．6％VS42．5±7．3％,65．6±6．8％VS43．2±3．9％,49．4±9．5％VS37．5±7．9％,（P〈0．05）。应答组B7-H1表达水平较治疗前下降,非应答组B7-H1水平无明显变化12．73±3．8％VS25．24±2．92％,（P〈0．05）。结论：慢性乙型肝炎患者树突状细胞功能低下,聚乙二醇干扰素α-2a治疗可以提高树突状细胞功能,降低B7-H1表达,促进HBV-DNA的清除。树突状细胞功能低下及B7-H1高表达是乙型肝炎病毒免疫逃逸的因素之一。     

血清前列腺特异性抗原与前列腺增生的相关性研究

目的：探讨前列腺增生患者年龄,前列腺体积以及BMI与血清前列腺特异性抗原（PSA）之间的关系。方法：对224例前列腺增生患者的年龄,前列腺体积以BMI与PSA的相关性进行Spearman相关性分析。结果：224例前列腺增生患者有25％的患者PSA水平高于正常,并且年龄,前列腺体积与血清PSA存在明显的正相关：（r=0．672．P〈0．01,r=0．785．P〈0．01）,而血清PSA与BMI指数存在明显的负相关：（r=-0．873,P〈0．01）。结论：前列腺增生患者的血清PSA值随患者年龄增长和体积增大而增加,对于PSA轻度升高的前列腺增生患者,要考率到体重因素对结果的影响。     

TLR4在四氯化碳诱导的肝硬化大鼠骨髓血窦内皮细胞的表达

目的：检测Toll样受体4（TLR4）在四氯化碳诱导的肝硬化大鼠骨髓血窦内皮细胞的表达,为进一步研究肝硬化时骨髓损伤的发生机制提供实验依据。方法：选择Wistar大鼠给予腹腔注射CCl4,一周两次,建立肝硬化大鼠模型。分别于建模8周和12周检测大鼠血浆内毒素的水平,免疫组化检测大鼠骨髓血窦内皮细胞上TLR4的表达情况,RT-PCR测定骨髓组织中TLR4mRNA的表达,分析TLR4的表达与内毒素血症间的关系。结果：给予CCl4 8周和12周时,对照组大鼠血浆内毒素水平分别为（0．216±0．024）Eu／ml和（0．133±0．022）Eu／ml,模型组大鼠血浆内毒素水平分别为（0．626±0．021）Eu／ml和（0．725±0．031）Eu／ml,分别较对照组显著升高,差异均有统计学意义（P〈0．001）;骨髓血窦内皮细胞TLR4蛋白表达及骨髓组织中TLR4mRNA的表达均显著高于对照组,差异均有统计学意义（P〈0．05）。大鼠骨髓TLR4蛋白和mRNA表达与血浆内毒素水平均呈显著正相关（r=0．841,0．803,P均〈0．001）。结论：CCl4诱导的肝硬化大鼠骨髓血窦内皮细胞TLR4表达升高,并伴随大鼠内毒素血症的发生,提示肝硬化时肠源性内毒素血症可能参与了骨髓的造血功能的损害和病变。     

全反式维甲酸联合替莫唑胺对胶质瘤U251细胞增殖与凋亡的影响

目的：研究全反式维甲酸（ATRA）联合替莫唑胺（TMZ）对胶质瘤细胞株U251增殖及凋亡的影响。方法：体外培养胶质瘤细胞株U251,分为ATRA组、TMZ组、ATRA＋TMZ组和空白对照4组,应用MTT法测定U251细胞生长抑制率,流式细胞仪检测细胞周期分布和细胞凋亡率,westernblot法检测细胞维甲酸受体β（RARβ）蛋白和凋亡相关蛋白Caspase．3蛋白的表达情况。结果：对照组、ATRA组、TMZ组及ATRA＋TMZ组的细胞生长抑制率分别为（1．72±0．12）％、（9．87±0．87）％、（23．87＋1．32）％及（35．74±1．44）％,ATRA＋TMZ组的细胞生长抑制率显著高于单独应用TMZ（P〈0．01）。对照组、ATRA组、TMZ组及ATRA＋TMZ组的细胞凋亡率分别为（1．32±0．11）％、（4．16±0．35）％、（8．44±0149）％、（15．27±1．03）％,ATRA＋TMZ组的凋亡率显著高于单独应用TMZ有更高的凋亡率（P〈0．01）。对照组、ATRA组、TMZ组及ATRA＋TMZ组RARp蛋白相对表达量分别0．452±0．054、0．837±0．068、0．195±0．021、0．376±0．039,ATRA＋TMZ组RARβ蛋白相对表达量显著高于TMZ组（P〈0．01）。ATRA＋TMZ组Caspase．的3蛋白表达相对水平为（0．832±0．059）,明显高于ATRA组（0．334±0．041）及TMZ组（0．521＋0．032）,差异具有统计学意义（P〈0．01）。结论：全反式维甲酸联合替莫唑胺能更有效抑制U251细胞的增殖,增加其凋亡率,这可能与其增加RARβ和Caspase-3蛋白的表达抑制U251细胞增殖、诱导细胞凋亡有关。     

表达CD19^＋CD56^-的多发性骨髓瘤浆细胞免疫表型的鉴别

目的：研究多发性骨髓瘤患者浆细胞和对照组正常浆细胞免疫表型,有效地识别表达CD19^＋CD56^-的多发性骨髓瘤恶性浆细胞。方法：采用四色流式细胞仪（BD,FACSCalibur）检测44例MM患者浆细胞以及25例健康骨髓捐献者正常浆细胞膜上的抗原表达。采用CellQuest软件分析结果。细胞膜表面抗原表达率大于20％定义为表达阳性。阳性率为表达阳性的患者及健康对照者所占百分比。结果：44例MM患者浆细胞免疫表型表达频率为：CD^138＋;97．72％（43／44）、CD38^＋：100％（44／44）、CD56^＋：63．64％（28／44）、CD19：84．09％（37／44）、CD200^＋：77．27％（34／44）、CD28^＋：38．64％（17／44）;25例对照组正常浆细胞免疫表型表达频率为：CD138^＋：100％（25／25）、CD38^＋：100％（25／25）、CD56^＋-：100％（25／25）、CD19^＋：96％（24／25）、CD200^＋：0％（0／25）、CD28^＋：0％（0／25）。在44例MM患者中,9％（4／44）患者表达CD19^＋CD56^-,利用CD200检测4例表达CD19^＋CD56^-的患者,有3例患者伴有CD200阳性表达,可与正常浆细胞鉴别。结论：CD200有利于鉴别表达CD19＋CD56-MM恶性浆细胞与正常浆细胞。     

PDGF-D、MPO与CD15在大肠癌中的表达及临床相关性研究

目的：探讨血小板源性生长因子D（PDGF-D）、髓过氧化物酶（MPO）YL粒细胞相关抗原（CD15）在大肠癌组织中的表达及其与临床特征之间的关系。方法：采用免疫组化染色方法检测88例大肠癌组织、72例大肠腺瘤组织及50例正常大肠粘膜组织中PDGF-D、MPO及CD15的表达情况。结果：PDGF—D、MPO、CD15在大肠癌组织中的阳性表达率分别为85．23％、63．64％、61．36％。PDGF—D、MPO在正常组、大肠腺瘤组和大肠癌组三者之间的表达均有显著性差异（P〈0．05）。CD15在正常组、大肠腺瘤组中的阳性表达率与大肠癌组中的阳性表达率有显著性差异（P〈0．05）,但在正常组与大肠腺瘤组中的阳性表达率无显著性差异（P〉0．05）。PDGF—D、MPO、CD15的表达在有淋巴结转移组织中的阳性率分别为92_31％、75．00％,73．08％;在无淋巴结转移组织中的阳性率分别为75．00％、52．78％,47．22％,三者在有无淋巴结转移组织中的阳性率均有显著性差异（P〈0．05）。PDGF．D、MPO、CD15在大肠癌中的表达与性别、年龄及组织分化程度均无相关（P〉0．05）。经Spearman相关性分析,PDGF—D及MPO在大肠癌的表达具有相关性（P〈O．05）。大肠癌中CD15与PDGF—D、MPO的表达无明显相关性（P〉0．05）：结论：PDGF—D、MPO与CDl5在大肠癌中的高表达,提示均参与了大肠癌的发生发展,可作为大肠癌恶性程度和侵袭转移的分子生物学标志物。     

Increased infiltrated macrophages in benign prostatic hyperplasia (BPH): role of stromal androgen receptor in macrophage-induced prostate stromal cell proliferation

Infiltrated macrophages may play important roles in the development and progression of benign prostatic hyperplasia (BPH), but the underlying mechanisms remain largely unknown. We found increased macrophages infiltration in human and mouse BPH tissues. By establishing a co-culture transwell system, we found increased migration of macrophages and proliferation of prostate stromal cells during co-culture. Importantly, stromal androgen receptor (AR) could enhance the migration of macrophages and macrophage-mediated stromal cell proliferation. We identified CCL3 as an AR downstream player, and found CCL3 levels were notably increased in human and mouse BPH prostates. Ablation of prostate stromal AR in a mouse BPH model significantly reduced CCL3 expression levels in prostates. Consistently, targeting AR via an AR degradation enhancer, ASC-J9§, or neutralization of CCL3 with an antibody, resulted in suppression of macrophage migration and prostate stromal cell growth. Our study provides mechanistic insights on the regulation of prostate stromal cells by macrophages via stromal AR/CCL3 signaling pathways, which could potentially allow the development of therapeutic approaches for battling BPH with persistent inflammation.     

雄激素受体共调节因子与雄激素非依赖性前列腺癌

雄激素介导的雄激素受体（AR）信号途径对雄性胚胎的发育及雄激素依赖性靶组织的分化发育是必需的。异常的AR活性与前列腺癌由雄激素依赖转变为雄激素非依赖性密切相关。已证实AR共调节因子参与前列腺癌的发生和发展,并在雄激素非依赖性前列腺癌细胞的增殖中扮演着重要角色。它们的表达失衡,可导致AR转录活性的改变,促进晚期前列腺癌的进展。简要综述了AR共调节因子的类型和功能,及其与雄激素非依赖性前列腺癌的关系。     

Sex steroid receptor expression and localization in benign prostatic hyperplasia varies with tissue compartment

Androgens and estrogens, acting via their respective receptors, are important in benign prostatic hyperplasia (BPH). The goals of this study were to quantitatively characterize the tissue distribution and staining intensity of androgen receptor (AR) and estrogen receptor-alpha (ERα), and assess cells expressing both AR and ERα, in human BPH compared to normal prostate. A tissue microarray composed of normal prostate and BPH tissue was used and multiplexed immunohistochemistry was performed to detect AR and ERα. We used a multispectral imaging platform for automated scanning, tissue and cell segmentation and marker quantification. BPH specimens had an increased number of epithelial and stromal cells and increased percentage of epithelium. In both stroma and epithelium, the mean nuclear area was decreased in BPH relative to normal prostate. AR expression and staining intensity in epithelial and stromal cells was significantly increased in BPH compared to normal prostate. ERα expression was increased in BPH epithelium. However, stromal ERα expression and staining intensity was decreased in BPH compared to normal prostate. Double positive (AR and ERα) epithelial cells were more prevalent in BPH, and fewer double negative (AR and ERα) stromal and epithelial negative cells were observed in BPH. These data underscore the importance of tissue layer localization and expression of steroid hormone receptors in the prostate. Understanding the tissue-specific hormone action of androgens and estrogens will lead to a better understanding of mechanisms of pathogenesis in the prostate and may lead to better treatment for BPH.     

Transforming growth factor beta 1 and androgen receptors in prostate neoplasia

OBJECTIVE: To investigate the interplay between transforming growth factor (TGF) beta 1, androgen receptors and stromal-epithelial interactions in benign prostatic hyperplasia (BPH), prostate intraepithelial neoplasia (PIN) and prostate carcinoma areas of prostate neoplasia. STUDY DESIGN: In this immunohistochemical study we investigated staining patterns and then determined the correlation between TGF-beta 1 expression and androgen receptor status in the epithelium and stroma of 60 paraffin-embedded tissues from radical prostatectomies. RESULTS: Staining patterns differed in the epithelium and stroma of tumor and peritumor prostatic tissue. TGF-beta 1 immunostaining (H-scores) in the epithelium and stroma increased significantly from BPH to PIN and from BPH to prostate carcinoma in the epithelium (P < .05), whereas androgen receptor (AR) immunoreactivity significantly (P < .05) increased from BPH to PIN to prostatic carcinoma in epithelium and stroma. TGF-beta 1 did not correlate with histologic grade of differentiation, whereas AR proteins were more strongly expressed in Gleason score 5 and 6 than score 7 tumors (P < .05). Nonlinear regression showed a significant correlation (P < .01) between TGF-beta 1 and AR expression only in the stromal compartment of PIN. CONCLUSION: These findings argue in favor of an interaction between TGF-beta 1 and AR in the early stages of prostate carcinogenesis and suggest that TGF-beta 1 plays a central role in stromal-epithelial interactions during the early stages of malignant transformation.     

Androgen receptors in rat and human prostate

In intact adult rats almost all androgen receptor (AR) sites of the rat ventral prostate (RVP) are occupied by endogenous dihydrotestosterone, and about 80% of these sites are nuclear. Nuclear AR disappears rapidly after castration (half-life of 3 h). The amount of cytosolic AR does not change within the initial 36 h, then markedly decreases during the next 2-5 days. An early and specific action of androgen is a remarkable increase of its own receptor. RVP also contains an estradiol receptor (ER) which rapidly disappears after castration and which, contrary to AR, is predominantly localized in the cytosol of stromal elements. The published procedures for steroid receptors grossly underestimate receptors concentrations in normal (NHP) and hyperplastic (BPH) human prostate. We have recently established a reliable method for the measurement of total AR, and we have found no difference in AR concentrations between NHP and BPH. BPH also contains a progesterone receptor and an elusive ER. Finally, we have used specific immunoglobulins in sex hormone binding plasma protein (SBP) for the demonstration of SBP-like immunoreactivity by the indirect immunofluorescence technique. The specific antigenic material was exclusively localized in the cytoplasm of BPH epithelial cells.     

CD8+ T cells specific for the androgen receptor are common in patients with prostate cancer and are able to lyse prostate tumor cells

The androgen receptor (AR) is a hormone receptor that plays a critical role in prostate cancer, and depletion of its ligand has long been the cornerstone of treatment for metastatic disease. Here, we evaluate the AR ligand-binding domain (LBD) as an immunological target, seeking to identify HLA-A2-restricted epitopes recognized by T cells in prostate cancer patients. Ten AR LBD-derived, HLA-A2-binding peptides were identified and ranked with respect to HLA-A2 affinity and were used to culture peptide-specific T cells from HLA-A2+ prostate cancer patients. These T-cell cultures identified peptide-specific T cells specific for all ten peptides in at least one patient, and T cells specific for peptides AR805 and AR811 were detected in over half of patients. Peptide-specific CD8+ T-cell clones were then isolated and characterized for prostate cancer cytotoxicity and cytokine expression, identifying that AR805 and AR811 CD8+ T-cell clones could lyse prostate cancer cells in an HLA-A2-restricted fashion, but only AR811 CTL had polyfunctional cytokine expression. Epitopes were confirmed using immunization studies in HLA-A2 transgenic mice, in which the AR LBD is an autologous antigen with an identical protein sequence, which showed that mice immunized with AR811 developed peptide-specific CTL that lyse HLA-A2+ prostate cancer cells. These data show that AR805 and AR811 are HLA-A2-restricted epitopes for which CTL can be commonly detected in prostate cancer patients. Moreover, CTL responses specific for AR811 can be elicited by direct immunization of A2/DR1 mice. These findings suggest that it may be possible to elicit an anti-prostate tumor immune response by augmenting CTL populations using AR LBD-based vaccines.     

前列腺癌雄激素受体和PI3K/Akt信号通路相互作用研究进展

前列腺癌的发生、进展依赖于雄激素,因此去势手术成为治疗晚期前列腺癌的标准疗法。但是去势后大多前列腺癌最终将转化为雄激素非依赖性前列腺癌,甚至进展为激素难治性前列腺癌,使得肿瘤的进展不受低水平雄激素的影响。即使如此,大多数激素非依赖性前列腺癌,依然阳性表达雄激素受体。因而雄激素受体在前列腺癌发生发展中起着重要作用。而PI3K/Akt信号通路能够通过维持细胞生存、抑制细胞凋亡、促进细胞代谢及血管生成等促进前列腺癌进展。本综述旨在总结前人研究,阐述雄激素受体和PI3K/Akt信号通路之间相互作用关系。研究表明Akt信号通路能够正性或者负性调控AR蛋白表达、蛋白的稳定性及其转录活性,从而维持细胞的生存、代谢。而AR即可以通过基因转录途径抑制Akt活化又能通过非转录基因途径激活Akt及其下游蛋白。因此,AR和Akt信号通路相互协同促进前列腺癌的发生及其向雄激素非依赖性前列腺癌进展。     

雄激素受体共调节因子及其在前列腺癌进展中的作用

雄激素受体（AR）信号通路在前列腺癌的发生、进展和转移中发挥着重要作用,但AR介导组织对雄激素的特异应答是通过与其相互作用的AR共调节因子共同完成的,许多AR共调节因子的功能已被广泛研究。简要综述了目前发现的部分AR共调节因子在调节AR转录活性及前列腺癌发生、进展中的生物学作用。     

五味牵牛胶囊主要药效学研究

目的：观察和验证五味牵牛胶囊对治疗前列腺增生、镇痛和抗炎的药理作用;方法：采用前列腺增生、致痛、致炎动物模型（小鼠、大鼠）等方法进行实验观察。结果：①五味牵牛胶囊对小鼠、大鼠的前列腺增生有明显的治疗作用（P〈0.01）,可显著减低增生的前列腺重量,使前列腺腺体缩小,腺腔扩张降低;②五味牵牛胶囊对醋酸诱发的疼痛具有明显的镇痛作用;③五味牵牛胶囊对角叉菜胶诱发的炎症具有显著的抗炎作用;④结果表明五味牵牛胶囊对前列腺增生的治疗具有明显的量效和时效关系。结论：①拟推荐临床用药采用口服法;②根据文献相关剂量换算的方法,五味牵牛胶囊临床成人拟日用量为1519 mg/日;③拟推荐临床用药疗程为6周。