宫腔镜结合C—erbB-2、nm23及ER表达对子宫内膜癌早期诊断意义

目的 探讨宫腔镜结合C—erbB-2、nm23及ER表达在子宫内膜癌中的诊断意义。方法 宫腔镜检查2400例患者，对筛查出的35例子宫内膜癌、10例内膜不典型增生及10例正常内膜，用免疫组化SP法检测C—erbB-2、nm23和ER表达。结果C—erbB-2、nm23、ER阳性表达率依次为74．29％、51．43％、54．29％；50％、30％、60％；30％、10％、90％。三者nm23、ER阳性表达率明显升高，差异有显著性（P〈0．05）；C—erbB-2阳性表达率明显降低，差异有显著性（P〈0．05）。宫腔镜定位活检确诊子宫内膜癌35例（35／2400），占1．46％。结论 宫腔镜直观病灶，结合c—erbB-2、nm23及ER表达对内膜癌早期诊断有意义。     

环氧化酶-2在结直肠癌组织中的表达及其临床意义

目的：探讨环氧化酶-2（COx-2）在结直肠癌组织中的表达及其临床意义。方法：采用链霉素抗生物素卵白素-过氧化物酶（SP）法进行免疫组化染色，观察43例结直肠癌组织和14例正常大肠组织中COX-2的表达情况。结果：COX-2在83．72％的结直肠癌组织中表达，仅在14．29％的正常大肠组织中表达（P〈0．005）。COX-2表达水平与肿瘤Duke’s分期、大小、淋巴结转移呈正相关（P〈0．05），而与肿瘤分化程度、位置、浸润深度及患者性别无明显相关性（P〉0．05）。结论：COX-2在结直肠癌组织中过表达，可能在结直肠癌的发生发展中起重要作用。     

NF—KBp65、VEGF-C及受体VEGFR-3在乳腺癌组织中的表达

目的检测乳腺癌组织内NF．KBp65、VEGF—C及受体VEGFR-3的表达水平,并观察它们与临床病理特征的关系,为乳腺癌的早期诊断、治疗提供依据。方法采用免疫组化染色法检测50例乳腺癌组织及10癌旁组织内NF。KBp65、VEGF—C及受体VEGFR-3的表达,并分析与临床病理因素的关系。结果乳腺癌组织内NF．KBp65蛋白表达的阳性率为76．0％,明显高于癌旁对照组织30．0％,二者相比差异显著（尸〈0．05）;乳腺癌组织内VEGF—C蛋白表达的阳性率为84．0％,明显高于癌旁对照组织20．0％,二者相比差异显著（P〈0．05）;乳腺癌组织内VEGFR-3蛋白表达的阳性率为88．0％,明显高于癌旁对照组VEGFR-3阳性表达率20．0％,两者相比差异显著（P〈O．05）;乳腺癌组织内NF—KBp65、VEGF—C及受体VEGFR-3三者的表达存在显著相关性（P〈O．05）,均与肿瘤淋巴转移密切相关（P〈0．05）,而与病人年龄、肿瘤大小无关（Jp〉0．05）。结论乳腺癌中NF—KBp65的表达可能上调VEGF—C的表达,进而导致肿瘤周围淋巴管增生、扩张,促进肿瘤细胞向区域淋巴结转移。     

ER、PR、P53、P16和CerbB-2在乳腺癌中的表达及与临床、病理的关系

目的联合检测抑癌基因P53、P16和癌基因CerbB-2在乳腺癌中的表达情况,结合ER、PR探讨与乳腺癌发生发展及临床、病理因素之间的联系.方法采用免疫组化S-P法分别检测145例乳腺癌和10例正常乳腺组织ER、PR、P53、P16和CerbB-2蛋白的表达.结果145例乳腺癌中ER、PR、P53、P16和CerbB-2的阳性表达率分别为43.4%、40.6%、45.5%、27.5%和84.8%.与正常乳腺组织比较,P53、P16和CerbB-2的阳性表达有差异（p＜0.05）.乳腺癌各病理类型之间表达没有差异（p＞0.05）.ER与年龄、PR、CerbB-2、肿瘤直径、月经状态、癌周浸润相关（p＜0.05）;PR与ER、肿块直径、癌周浸润相关;P53与淋巴结转移个数,癌周浸润相关;P16与初潮年龄、癌周浸润相关（＜0.05）;CerbB-2与ER、肿瘤直径、转移淋巴结个数、月经状态、癌周浸润相关（p＜0.05）.结论ER、PR是对激素治疗有价值的指标,并与P53、P16、CerbB-2等可作为评价乳腺癌的生物学行为、病理特征和预后的指标.     

子宫腺肌症雌激素受体、孕激素受体与bcl-2的表达

目的 探讨雌激素受体（ER）、孕激素受体（PR）和bcl-2在子宫腺肌症中异位和在位内膜的表达及意义。方法 用免疫组化EnVision法检测40例子宫腺肌症在位子宫内膜和肌间异位内膜ER、PR和bcl-2的表达情况。结果 在位和异位子宫内膜组织中均有ER、PR和bcl-2的阳性表达。其中腺上皮阳性表达率高于间质（P〈0．05）,且异位内膜的腺上皮bcl-2阳性表达率高于在位组织（P〈0．05）;ER和PR的表达两者差异无显著性（P〉0．05）。异位内膜腺体ER、PR与bcl-2表达具有相关性（P〈0．01）。结论 子宫腺肌症异位和在位子宫内膜组织中均有ER、PR和bcl-2的阳性表达,可能与子宫腺肌症的发生、发展有关。     

非小细胞肺癌survivin、p53和COX-2蛋白的表达

目的探讨非小细胞肺癌组织中survivin、p53和环氧合酶-2（COX-2）蛋白表达及其在肺癌发生、分化程度、淋巴结转移以及预后评估中的意义。方法采用SP法免疫组化技术检测70例非小细胞肺癌组织中的survivin、p53和COX-2表达情况。结果survivin和COX-2阳性表达与肺非小细胞癌组织的分化程度、有无淋巴结转移及临床TNM分期有关（P〈0．01）;p53阳性表达与非小细胞肺癌组织的分化程度有关（P〈0．01）。同时发现,survivin、p53和COX-2（＋＋＋～＋＋＋＋）阳性表达率明显高于（＋～＋＋）,差异有显著性（P〈0．01）。这3种抗体中在非小细胞肺癌中的阳性表达占76％。结论survivin、p53和COX-2的表达在非小细胞肺癌组织的浸润、转移和发展中具有重要意义,有助于对非小细胞肺癌的诊断及预后的评价。     

COX-2与P73在胃癌中的表达及相关性探讨

目的：探讨COX-2和P73在胃癌组织中的表达及临床意义。方法：应用免疫组化Envision法检测COX-2和P73在62例胃癌组织中的表达情况。结果：全组COX-2阳性率为64.5%（40/62），P73阳性率为69.4%（43/62）。COX-2的表达与组织分化程度、浸润深度、淋巴结转移和临床TNM分期相关（P〈0.05）；P73的表达与浸润深度、淋巴结转移和临床TNM分期相关（P〈0.05）。COX-2和P73同时表达、单独表达及不表达时，胃癌的组织分化程度、病变浸润深度（T分期）、淋巴结转移（N分期）和临床分期组间差异有统计学意义（P〈0.05）。COX-2和P73在胃癌组织中的表达具有相关性（r=0.384，P〈0.05）。结论：胃癌组织中存在COX-2和P73基因的过度表达，COX-2和P73基因的过度表达与胃癌发生发展有关。     

乳腺浸润性导管癌中ER、PR、Her-2、Ki-67表达与病理特征及预后的相关性

目的 探究Ki-67、ER、PR、Her-2等基因在乳腺浸润性导管癌（IDC）组织中的表达,分析其与患者临床病理特征及预后的相关性。方法 收集2013年1月~2014年12月广东医科大学附属医院病理科乳腺包埋石蜡块IDC组织74例。采用免疫组织化学法检测ER、PR、Her-2、Ki-67在IDC组织中的表达,分析其与患者年龄、组织学分级、TNM分期、淋巴结转移及预后的相关性。结果 ①不同年龄、组织学分级、淋巴结转移及TNM分期的IDC患者ER、PR表达情况比较,差异均无统计学意义（P＞0.05）;未发生淋巴结转移的IDC患者Her-2表达低于转移患者,差异有统计学意义（P＜0.05）;不同年龄、组织学分级、TNM分期的IDC患者Her-2表达比较,差异无统计学意义（P＞0.05）;不同TNM分期的IDC患者Ki-67表达情况比较,差异有统计学意义（P＜0.05）,不同年龄、组织学分级、淋巴结转移的IDC患者Ki-67表达比较,差异均无统计学意义（P＞0.05）。 ②Spearman相关性分析显示,ER与PR正相关,ER与Her-2、PR与Her-2负相关,ER、Ki-67和PR、Ki-67负相关,Her-2与Ki-67正相关。③Ki-67阳性表达的IDC患者病死率高于Ki-67阴性表达的患者,差异有统计学意义（P＜0.05）;不同ER、PR、Her-2表达情况的IDC患者病死率比较,差异无统计学意义（P＞0.05）;Ki-67阴性表达患者的总生存时间（OS）高于阳性表达患者,COX多因素分析显示,Ki-67阳性表达是影响IDC患者OS的独立因素（95%CI:0.212~0.865,P=0.018）。结论 Ki-67可作为乳腺浸润性导管癌危险评估的分子标志物,其阳性表达可影响乳腺癌患者的预后。ER、PR、Her-2的表达对乳腺浸润性导管癌患者的预后没有明显影响。     

乳腺癌中环氧化酶-2的表达及其与VEGF、MVD、MMP-9、 TIMP-1的关系

目的研究乳腺癌组织中环氧化酶-2（COX-2）的表达及其与VEGF、MVD、MMP-9和TIMP-1的相互关系,探讨其在乳腺癌发生和浸润中的生物学意义。方法应用S-P法检测65例浸润性乳腺癌组织中COX-2、VEGF、MMP-9、TIMP-1及血管内皮标记物CD34的表达情况,并观察7例导管原位癌（DCIS）、45例癌旁乳腺组织中COX-2的表达。结果65例浸润性乳腺癌、7例DCIS均表达COX-2,其中浸润性乳腺癌中COX-2高表达率为66．2％（43／65）,而45例癌旁组织中21例有COX-2弱表达,两者之间差异有显著性（P〈0．01）。COX-2与乳腺癌患者的年龄、肿瘤大小、组织学分级、TNM分期、腋窝淋巴结转移均无相关性,但COX-2在浸润性乳腺癌中的表达与VEGF、MMP-9、TIIMP-1及MVD均呈正相关（P〈0．05）。结论COX-2可能与乳腺癌组织中微血管形成和细胞外基质代谢有关。     

uPA与ER在乳腺癌组织中的表达及相关性分析

目的研究雌激素受体（ER）与尿激酶型纤溶酶原激活物（urokinasc-type plasminogen activator,uPA）在乳腺癌组织中的表达及其临床意义。方法免疫组织化学染色采用PV-6000二步法,对40例乳腺癌蜡块中ER、uPA表达进行研究。结果乳腺腺瘤、腺病和乳腺癌中ER阳性率分别为85.O％、82.5％和60.6％,三者差异有统计学意义（P〈O.05）;ER表达阳性患者淋巴结转移率（33.33％）低于ER表达阴性者（81.25％）,差异有统计学意义（P〈O.01）。uPA在乳腺纤维腺瘤、腺病均呈阴性表达,在乳腺癌中的阳性率为60.00％,三者差异有统计学意义（P〈0.05）;uPA表达阳性患者淋巴结转移率（88.5％）显著高于阴性者（50.O％）,两者的表达差异有统计学意义（P〈O.05）。结论uPA的高表达和ER的缺失表达与乳腺癌的浸润转移密切相关,检测ER和uPA对临床选择治疗方法有指导意义。     

HER-2、P53、Ki-67、Nm23、ER、PR蛋白在乳腺癌中的表达及临床意义

探讨HER-2、P53、Ki-67、Nm23、ER、PR蛋白在乳腺癌组织中表达的特性,同时分析它们之间的相关性和临床意义.应用SP免疫组织化学法检测73例乳腺癌标本中HER-2、P53、Ki-67、Nm23、ER、PR蛋白的表达,并结合其临床和病理资料进行回顾性分析.HER-2、P53、Ki-67、Nm23、ER、PR...     

COX-2 expression in invasive breast cancer: correlation with prognostic parameters and outcome.

Lipoxygenases (LOX) and cyclooxygenases (COX) are key mediators of arachidonic acid metabolism. Recently, studies have reported that human breast carcinomas aberrantly express LOX and cyclooxygenase-2 (COX-2), and that decreased levels of 15-lipoxygenase (15-LOX) and raised levels of COX-2 and 12-LOX have prognostic value in patients with breast cancer. 15-LOX was significantly reduced with increasing stage, and in patients who developed metastatic disease, local recurrence, and/or died. With high COX-2, patients developed local recurrence, died from breast cancer and had reduced disease-free and disease-related overall survival in estrogen receptor (ER)-negative but not ER-positive disease. COX-2 expression is also associated with increased angiogenesis, lymph node metastasis, and Her2-neu overexpression. The purpose of this study is to evaluate COX-2 expression in breast cancer and to determine its correlation with prognostic parameters and outcome. Five tissue microarrays were constructed from 43 breast carcinomas and 5 normal breast tissues, represented by 1 mm cores in triplicate from each of 3 foci. Tissue microarray cores were immunostained with monoclonal COX-2. Expression was assessed as intensity and scored as percentage of cells positive. Prognostic parameters and follow-up information were obtained from the hospital records of Mexican Oncology Hospital, Mexico, where the carcinomas were diagnosed. Ninety-five percent (41/43) of the breast carcinomas showed cytoplasmic COX-2 expression. COX-2 intensity and percentage of cells positive correlated significantly with size of carcinoma (P=0.0271; P=0.0539, respectively). COX-2 intensity correlated significantly with histologic grade (P=0.0182). COX-2 did not correlate with outcome (disease-free and overall survival). There was no significant correlation between COX-2 and ER. In conclusion, COX-2 correlates with poor prognostic markers in breast cancer (large tumor size and high tumor grade), but not with outcome. The therapeutic value of COX-2 inhibitors in COX-2 positive breast cancer patients requires further investigation.     

The Differences in CXCR4 Protein Expression Are Significant for the Five Molecular Subtypes of Breast Cancer

The aim was to investigate the expression of the CXCR4 protein in five molecular subtypes of breast cancer. The authors randomly selected the breast cancer paraffin-embedded specimens of the Affiliated Third Hospital of Harbin Medical University between 2007 and 2009. Details are as follows: basal-like subtype—ER (–), PR (–), C-erbB-2 (–), CK5/6 (+), n = 36; normal breast subtype—ER (–), PR (–), C-erbB-2 (–), CK5/6(–), n = 40; luminal A subtype—ER/PR (+), C-erbB-2 (–), n = 38; luminal B subtype—ER/PR (+), C-erbB-2 (+), n = 60; C-erbB-2 (+) subtype—ER (–), PR (–), C-erbB-2 (+), n = 58. Using the immunohistochemistry method, the authors detected the expression of the CXCR4 protein in the five subtypes. The CXCR4 protein expression in the basal-like subtype was the highest, and that in the luminal A subtype was the lowest. In terms of five molecular subtypes of breast cancer, the differences in CXCR4 protein expression were significant (p < .001). In terms of C-erbB-2 expression, tumor stage, and lymph node metastasis of breast cancer, the differences in CXCR4 protein expression were significant (p < .01).     

乳腺癌的钼靶X线征象与免疫组化标记物表达的关系

目的 分析乳腺癌的主要X线征象,肿块、局限性致密浸润影与病理检测常用的免疫组化标记物ER,PR,C-erbB-2,nm23之间的关系。方法 收集云南省第一人民医院2016年1月~2019年1月经病理证实107例乳腺癌患者作为研究对象,病灶共108例,所有患者均行钼靶X线摄影。根据X线征象将所有病灶分为肿块组73例及局限性致密影组35例。使用免疫组化技术测定乳腺癌ER,PR,C-erbB-2,nm23的表达水平,比较两组癌灶中基因表达水平。结果 乳腺癌钼靶X线征象表现为局限性致密浸润影组（80.00%）C-erbB-2的表达高于肿块组（56.16%）,差异有统计学意义（P＜0.05）;局限性致密浸润影组（40.00%）nm23高表达者低于肿块组（64.38%）,差异有统计学意义（P＜0.05）;局限性致密浸润影组腋窝淋巴结转移多于肿块组（P＜0.05）;肿块和局限性致密浸润影其ER,PR阳性表达比较,差异均无统计学意义（P＞0.05）。结论 乳腺癌主要X线征象的差异可反映肿瘤细胞基因表达C-erbB-2与nm23水平,针对乳腺癌具体征象分析对于其早期诊断及其预后的初步判断有一定意义。     

Overexpression of cyclooxygenase-2 is associated with a favorable prognostic phenotype in breast carcinoma.

OBJECTIVES: Cyclooxygenase (COX) is the rate-limiting enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. The purpose of the present study was to investigate the involvement of COX-2 protein in breast cancer biological behavior through its correlation with the well-known clinicopathological parameters and the expression of p53, c-erbB-2, topoisomerase IIalpha (topoIIalpha) and peroxisome proliferator-activated receptor (PPARgamma) proteins, as well as its effect on patients' survival. METHODS: We performed immunohistochemistry to detect COX-2, estrogen receptor (ER), progesterone receptor (PR), p53, c-erbB-2, topoIIalpha and PPARgamma proteins in 175 cases of invasive breast carcinomas. The results were elaborated by statistic analysis. RESULTS: Cytoplasmic expression of COX-2 was detected in 66.9% of breast carcinoma samples and was inversely correlated with both nuclear and histological grade (p < 0.0001 and p = 0.039, respectively), whereas its association with PR was found to be positive (p = 0.016). COX-2 expression was inversely correlated with topoIIalpha and p53 (p = 0.033 and p = 0.002, respectively), whereas its association with PPARgamma was parallel (p < 0.0001). In addition, c-erbB-2 of tumor cells was inversely correlated with COX-2 in stromal cells of the tumor (p = 0.011). Neither univariate nor multivariate analysis demonstrated any association between COX-2 expression and patient overall or disease-free survival. CONCLUSIONS: The current data suggest that increased expression of COX-2 may be related to breast carcinomas with less aggressive phenotype. This suggestion is further supported by the positive correlation between COX-2 and PPARgamma, since the latter is considered to be indicative of a less malignant phenotype of tumor cells.     

Lack of expression of androgen receptor may play a critical role in transformation from in situ to invasive basal subtype of high-grade ductal carcinoma of the breast

Androgen receptor has been implicated in the pathogenesis of breast carcinoma. In this study, we explored the potential role of androgen receptor in breast cancer by analyzing its expression using immunohistochemistry and its relationship with tumor progress (ductal carcinoma in situ [DCIS] versus invasive ductal carcinoma [IDC]); nuclear grades (high grade [HG] versus non-high grade); expression of estrogen receptor (ER), progesterone receptor (PR), HER-2; and 3 molecular classifications: cytokeratin classification, triple (ER/PR/HER-2) negative classification, and ER/HER-2 classification in 184 breast carcinomas. We found that (1) lack of androgen receptor expression was associated with HG-IDC and with basal subtypes of HG-IDC, suggesting androgen receptor may play an important role in preventing the invasive transformation in this subgroup of breast carcinoma. (2) HG-IDC and HG-DCIS more frequently expressed androgen receptor than ER (55%-93% for androgen receptor and 18%-30% for ER) and were frequently androgen receptor+/ER- (63% for HG-DCIS and 39% for HG-IDC), which made androgen receptor a possible therapeutic target. (3) One third of HG-IDC was negative for androgen receptor, ER, PR, and HER-2, suggesting that further studies are needed to identify other key molecules for targeted therapy. We purpose that androgen receptor should be routinely measured for breast cancer.     

Assessment of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status in the fine needle aspirates of metastatic breast carcinomas

The assessment of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2) status in the fine needle aspirates of metastatic breast carcinomas has prognostic and therapeutic implications. In this study, expression of ER, PR, and HER2 was assessed by immunohistochemical study in 70 cases of metastatic breast carcinomas and HER2 gene amplification was further evaluated by fluorescence in situ hybridization (FISH) in 38 (54%) cases. Positive expression of ER and PR was seen in 42 (60%) and 16 (23%) cases of metastatic breast carcinomas, respectively. HER2 immunoreactivity was scored as 0/1+ in 39 (56%), 2+ in 10 (14%), and 3+ in 21 (30%) cases. HER2 gene amplification was seen in 20% of HER2 2+ and 64% of HER2 3+ cases. ER, PR, and HER2 status in primary breast cancers were available to comparison in 31 cases (44%). The concordance rates between metastatic and primary breast carcinomas were 81% for ER, 65% for PR and 71% for HER2. Our study demonstrates that ER, PR, and HER2 status can be assessed in the fine needle aspirates of metastatic breast carcinomas and ER has a higher concordance rate between metastatic and primary breast carcinomas than PR and HER2. The addition of HER2 gene amplification FISH test helps in accurate assessment of HER2 status in metastatic breast carcinomas.     

乳腺Paget病细胞角蛋白-8、c-erbB-2、雌激素受体和孕激素受体的表达及意义

目的探讨乳腺Paget病中细胞角蛋白-8(CK-8)、c-erbB-2、雌激素受体(ER)和孕激素受体(PR)的表达及意义。方法对12例乳腺paget病组织进行免疫组织化学染色,检测CK-8、c-erbB-2、ER、PR在Paget细胞与同一例深部癌组织中表达的异同。结果Paget细胞CK-8表达阳性率为100%、c-erbB-2表达阳性率为91.67%,而ER、PR表达阳性率为16.67%。CK-8、c-erbB-2、ER及PR中每一标记物在Paget细胞和同一病例深部癌组织中阳性表达一致。结论乳腺Paget病内Paget细胞来源于乳腺深部存在的导管内癌或浸润性导管癌,是深部癌细胞在表皮内的扩散。     

Pathobiologic findings in DCIS of the breast: morphologic features, angiogenesis, HER-2/neu and hormone receptors.

With the increasing incidence of ductal carcinoma in situ (DCIS) of the breast and its relationship to invasive breast carcinoma, it is important to understand the biology of this entity. We report on a hospital-based survey of 219 case subjects with DCIS of the breast without associated invasive carcinoma diagnosed between 1982 and 1994. The cases of DCIS were analyzed for architectural type, size, nuclear grade, necrosis, calcification, periductal fibrosis, neovascularization, estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu expression. Periductal neovascularization was associated with tumor size, microcalcifications, periductal fibrosis, and HER-2/neu overexpression. Expression of ER and PR was observed in 60 and 62% of the cases, respectively, and HER-2/neu overexpression in 28% of the cases. ER and PR expression were both inversely associated with comedo histology and nuclear grade. HER-2/neu overexpression was positively associated with comedo histology, high nuclear grade, and periductal neovascularization and was inversely correlated with both ER and PR expression. High nuclear grade was positively associated with comedocarcinoma, necrosis, microcalcification, and periductal fibrosis. The role of these molecular/pathologic markers in the biology of DCIS and their potential clinical implications are discussed.     

雄激素受体在乳腺癌中的表达及其与雌、孕激素受体和HER2的关系

目的 研究雄激素受体(AR)在乳腺浸润性导管癌中的表达及其与雌激素受体(ER)、孕激素受体(PR)和HER2状态的关系,探讨其作为乳腺癌治疗靶点的可行性.方法 采用免疫组织化学EnVision法检测AR、ER、PR、HER2在175例乳腺浸润性导管癌中的表达,依据结果分为腺腔A型、腺腔B型、HER2过表达型和三阴性型(ER-/PR-/HER2-)组.结果 175例中AR阳性88例(50.3%),AR表达与ER、PR、HER2均呈正相关(P＜0.01).腺腔A型53例(30.3%),腺腔B型33例(18.9%),HER2过表达型23例(13.1%),三阴性型66例(37.7%),AR阳性率分别为56.6%(30/53),75.8%(25/33)、47.8%(11/23)和33.3%(22/66),组间AR阳性率差异显著(x2=17.054,P=0.001).三阴性型组AR阳性者核分裂象较少(x2=5.140,P=0.023),腺腔A型组AR阳性者多为年轻患者(x2=4.567,P=0.033),差异有统计学意义.其他组内AR表达与否和临床病理学特征比较无统计学意义.结论 AR在乳腺癌中有较高的阳性率,可作为乳腺癌,特别是三阴性型乳腺癌的治疗靶点.