G protein-coupled estrogen receptor in colon function, immune regulation and carcinogenesis

Estrogens play important roles in the development and progression of multiple tumor types.Accumulating evidence points to the significance of estrogen action not only in tumors of hormonally regulated tissues such as the breast,endometrium and ovary,but also in the development of colorectal cancer(CRC).The effects of estrogens in physiological and pathophysiological conditions are mediated by the nuclear estrogen receptorsαandβ,as well as the membranebound G protein-coupled estrogen receptor(GPER).The roles of GPER in CRC development and progression,however,remain poorly understood.Studies on the functions of GPER in the colon have shown that this estrogen receptor regulates colonic motility as well as immune responses in CRC-associated diseases,such as Crohn’s disease and ulcerative colitis.GPER is also involved in cell cycle regulation,endoplasmic reticulum stress,proliferation,apoptosis,vascularization,cell migration,and the regulation of fatty acid and estrogen metabolism in CRC cells.Thus,multiple lines of evidence suggest that GPER may play an important role in colorectal carcinogenesis.In this review,we present the current state of knowledge regarding the contribution of GPER to colon function and CRC.

肠黏膜雌孕激素受体表达在肠易激综合征发病机制中的作用研究

目的 探讨雌、孕激素受体在肠易激综合征 (IBS)患者肠道内的分布、变化及其临床意义 ,并对在消化道的作用靶点和可能的细胞学机制做出合理解释和推断。方法 经结肠镜钳取 2 4名正常人和 5 9例肠易激综合征患者的回肠末端、盲肠和降结肠黏膜 ,分别采用抗人雌、孕激素受体抗体标识肠黏膜上雌、孕激素受体 ,并应用免疫组化方法检测了雌、孕激素受体阳性细胞数目改变。结果 1、IBS患者回肠末端和盲肠黏膜雌激素受体阳性细胞数目增多 (P <0 .0 1) ,降结肠黏膜与正常组无显著差别 ;2、肠道黏膜未见孕激素受体表达 结论 IBS患者肠黏膜雌激素受体高表达在IBS病理过程中发挥一定作用 ,并认为肥大细胞为雌激素在消化道的重要靶点 ,其对于揭示IBS在女性中的高发病率和月经期加重的临床现象有重要意义 ;

肾虚脾弱型黄体功能不健性不孕症临床研究

目的 探讨肾虚脾弱型黄体功能不健性不孕症患者子宫内膜的雌、孕激素受体 (ER、PR)及宫腔异常的情况 ,为研究此类不孕症提供实践依据。方法 在子宫内膜增生中晚期进行宫腔镜检查和通过免疫组化法对宫内膜的雌、孕激素受体进行半定量分析 ,并与非黄体功能异常的不孕组进行了比较。结果 15例观察组不孕患者的增生中晚期宫内膜间质细胞、腺上皮细胞的PR明显低于对照组 (P <0 .0 5、P <0 .0 1) ,间质细胞的ER也明显低于对照组 (P <0 .0 5 ) ,腺上皮细胞的ER 2组虽无显著差异 ,但观察组有降低趋势。宫腔镜检发现 ,此类型不孕症患者的宫腔异常改变以宫内膜苍白、肥厚 ,局部呈息肉样增生最多见。结论 增生中晚期子宫内膜的ER、PR含量明显降低 ,宫腔存在明显异常改变 。

清化止泻方治疗脾胃湿热型腹泻型肠易激综合征的疗效及对患者血清炎症因子和TLR4/MyD88/NF-κB信号通路相关蛋白的影响

目的观察清化止泻方治疗脾胃湿热型腹泻型肠易激综合征(IBS-D)的临床疗效及对患者血清炎症因子和Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核转录因子κB(NF-κB)信号通路相关蛋白的影响。方法将120例脾胃湿热型IBS-D患者按照随机数字表法分为2组,对照组60例予匹维溴铵片治疗,治疗组60例在对照组治疗基础上加用清化止泻方治疗。2组均治疗4周。比较2组疗效;比较2组治疗前后中医证候评分变化;比较2组治疗前后焦虑自评量表(SAS)评分、抑郁自评量表(SDS)评分变化;比较2组治疗前后血清白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平变化,以及TLR4/MyD88/NF-κB信号通路相关蛋白TLR4、MyD88、NF-κB p65表达变化。结果治疗组总有效率93.3%(56/60),对照组总有效率80.0%(48/60),治疗组疗效优于对照组(P<0.05)。2组治疗后中医证候各项评分及总评分均较本组治疗前降低(P<0.05),且治疗组降低更明显(P<0.05)。2组治疗后SAS评分、SDS评分均较本组治疗前降低(P<0.05),且治疗组降低更明显(P<0.05)。2组治疗后血清IL-1β、IL-6及TNF-α水平均较本组治疗前降低(P<0.05),且治疗组降低更明显(P<0.05)。2组治疗后TLR4、MyD88、NF-κB p65表达水平均较本组治疗前降低(P<0.05),且治疗组降低更明显(P<0.05)。结论清化止泻方可能通过调控血清TLR4、MyD88、NF-κB p65表达,降低血清IL-1β、IL-6、TNF-α水平来改善脾胃湿热型IBS-D患者临床症状,缓解焦虑、抑郁状态。

雌、孕激素受体在乳腺癌及增生性病变组织中的表达及意义

目的探讨雌、孕激素受体在女性乳腺癌与各种增生性病变组织中的表达及临床意义。方法取2006年2月至2007年2月中日联谊医院乳腺甲状腺外科手术后经病理科诊断证实的病例,乳腺增生性疾病52例(40人),乳腺癌52例(49人)。其中普通型增生10例,轻度非典型增生12例,中度非典型增生9例,重度非典型增生21例,乳腺浸润性导管癌52例。用免疫组化SP法检测ER、PR的表达。结果在乳腺普通型增生、轻、中、重度非典型增生及乳腺浸润性导管癌组织中ER表达的阳性率分别为30.00%、41.67%、44.44%、61.90%和69.23%,PR表达的阳性率分别为20.00%、25.00%、44.44%、52.38%和55.77%,ER阳性和/或PR阳性率分别为30.00%、41.67%、55.56%、66.67%、69.23%,仅普通型增生与乳腺癌组织中有显著性差异。结论(1)乳腺普通型增生与乳腺癌组织无明显联系。其余三种非典型增生组织中ER、PR阳性表达率与乳腺癌组织差异不显著,且其相关性由轻、中、重度逐级递增。(2)ER、PR表达强度的逐级递增及单细胞中强阳性(+++)率的逐级增高表明这一过程与雌激素过刺激有关,因此对乳腺增生性疾病行ER、PR检测有利于早期发现乳腺癌,根据ER、PR检测结果判断病变向乳腺癌发展的风险性。(3)在ER和/或PR阳性的乳腺增生性疾病患者中可以考虑应用内分泌治疗。

雌激素受体α基因敲除对小鼠认知功能的影响机制

目的探讨ERα调节小鼠认知功能的作用及可能机制。方法将6只8～12周龄ERa基因敲除鼠和6只同周龄野生型小鼠分为2组：正常对照组和ERα基因敲除组。用水迷宫检测这2组小鼠的认知功能；ELISA法检测脑内Aβ含量；免疫组化法检测脑内Aβ沉淀情况。结果定位航行实验显示：与正常对照小鼠相比，ERα基因敲除鼠的逃避潜伏期显著延长（P〈O．01）；空间探索实验显示：ERα基因敲除鼠在目标象限的游泳距离占总的游泳距离的比例低于正常对照小鼠（P〈0．01）ELISA和免疫组化显示：与正常对照小鼠相比，ERα基因敲除鼠脑内Aβ生成增加（P〈0．01）。结论ERα基因敲除可导致认知功能下降，其机制可能与脑内Aβ生成增多有关。ERα基因敲除小鼠表现出类似阿尔芡海默病（AD）的病理以及行为学特征，提示其可以作为一种研究AD及其干预措施的新的动物模型。

Etiological characteristics and treatment of tardive dyskinesia

OBJECTIVE ： The pathogenesis of tardive dyskinesia （TD） is complicated and uncertain, Thus, there is not any effective treatment for it. The psychiatrists pay more and more attention to TD, which lasts for a long time and is difficult to treat. DATA SOURCES： A computer-based online search of Medline database was undertaken to identify articles about the feature of etiology and the progression of treatment for TD published in English by using the keywords of ＂rD, etiology, pathogenesis＂ and ＂TD, therapy, drug treatment＂. Meanwhile, Chinese articles about the feature of etiology and the progression of treatment for TD were searched in Wanfang database and China journal full-text database, and the keywords were ＂TD, etiology, pathogenesis＂ and ＂TD, therapy, drug Treatment＂ in Chinese. STUDY SELECTION： Articles met the following inclusion criteria were selected in this paper. Inclusion criteria： （1） Researches of randomized blind control design, before and after control design and retrospective. （2） Researches of the feature of etiology and the progression of treatment for TD. Exclusion criteria： the repetitive researches and individual reports. DATA EXTRACTION ： Totally 65 articles related the feature of etiology and the progression of treatment for TD of randomized blind control design, before and after control design and retrospective studies were collected, and 53 of them were accorded with the inclusion criteria. Of the 12 excluded ones, 8 were concerning with genetics, 4 were repetitive researches. DATA SYNTHESIS ： The feature of etiology for TD includes：（1） Hypothesis of dopamine receptor super-sensitivity： The dopamine receptor is persistently blocked, so it will result in functional disorder in CNS, and then TD may take place. （2）） Hypothesis of neuronal degeneration： The concentration of aminosuccinic acid and glutamic acid will increase after the antipsychotic used for a long time and this will result in neuronal degeneration through glutamic acid receptor in the postsynaptic membrane; meanwhile with free radical, the nerve cells of corpus striatum may degenerate and become necrosis. （3） Sex and age： The females and gerontal patients are liability to the TD disease. It is may related to the lower estrogen. （4） Molecule heredity： TD may association with the dopamine and 5-HT receptor gene polymorphism. （5） Other theories： Hypofunction of γ-amino-butyri acid （GABA）, hypothesis of noradrenaline 5-serotonin and nutrition metabolism can cause TD disease. Treatlent for TD： （1） Dopamine receptor agonist： The therapeutic effect is not satisfactory, especially for gerontism females. （2） Oxygen free radical scavenger： As represent of vitamin E, it can clear out free radicals and reduce the potential cytotoxic effect of free radicals. （3） Calcium channel blocker： This maybe related to block calcium ions releasing from muscle cells and inhibit muscle convulsion; therefore, it can be used for symptomatic treatment. （4） GABA receptor agonist： It is more effective for the prominent dysmyotonia than dancing slowly symptom. （5） Antipsychotic： There is some therapeutic effect with ciozapine, but the effect will reduce because of the age growing up and the symptom exacerbating. （6） Other therapies： Valproate sodium, cyproheptadine, melatonin, branched chain amino acid, ahalysantinfarctasum, electric acupuncture and injection ad acumen, traditional Chinese drug have a certain effects on TD. Prevention of TD： The serum creatine phosphokinase （CPK） combined with symptoms should be checked regularly so as to early discovery TD. CONCLUSION ： （1） Etiology of TD： The hypothesis of dopamine receptor super-sensitivity is denyed; the hypothesis of neuronal degeneration is approved in academic circles; the sex and age is a finding of generally received; but the dopamine and 5-HT receptor gene polymorphism, hypofunction of GABA, noradrenaline, 5-serotonin and nutrition metabolism cannot explain the pathogenesis of TD. （2） Treatment for TD： The therapeutic effect of dopamine receptor agonist is not satisfactory; the oxygen free radical scavenger maybe effective; calcium channel blocker maybe used for symptomatic treatment; GABA receptor agonist maybe more effective for the prominent dysmyotonia than dancing slowly symptom; the consequence of antipsychotic is discrepancy; other therapies maybe use to adjunctive therapies. （3） As far as prevention of TD is concerned, and the serum CPK combined with symptoms should be checked regularly so as to early discovery TD.

拮抗或激活促肾上腺皮质激素释放因子受体对肠易激综合征大鼠内脏敏感性及结肠动力的影响

目的探讨促肾上腺皮质激素释放因子（CRF）及其受体对肠易激综合征大鼠内脏敏感性及结肠动力的影响。方法SD大鼠60只，随机平均分入空白组（不做处理）、模型组（特殊气味条件刺激和肢体束缚直肠刺激非条件刺激轮替致敏）、干预对照组（造模前侧脑室注射0．9％NaCl）、干预一组（造模前侧脑室注射CRF-R1拮抗剂）和干预二组（造模前侧脑室注射CRF-R2激动剂）。采用腹部收缩反射（AWR）评分标准评估各组大鼠肠道敏感性，记录各组大鼠结肠快、慢波波动率、最大振幅、收缩波数及振幅指数等电生理活动改变。采用SPSS16．0统计软件分析，计量资料采用方差分析，等级资料采用秩和检验。结果以AWR=3分时所需的直肠注水量作为评价指标，模型组大鼠[（0．90士0．11）mn较空白组[（1．23士0．07）ml]内脏敏感性增高（F=82．586，P〈0．01）；结肠电生理活动增强，造模成功。干预对照组直肠注水量为（0．81±0．11）ml，与模型组[（0．90±0．u）m1]差异无统计学意义（F=3．734，P〉0．05），干预一组[（1．28±0．07）ml，F=161．878，P〈0．01]和干预二组[（1．22土0．05）ml，F=121．564，P〈0．01]较干预对照组内脏敏感性降低。干预对照组大鼠结肠快、慢波波动率、最大振幅、收缩波数及振幅指数等电生理活动与模型组无明显差异（P均〉O．05）；干预一组和干预二组大鼠结肠电生理活动均较干预对照组明显减弱（均P〈0．05）。结论CRF在IBS发病中起重要作用，抑制CRF-R1或激活CRF-R2可降低IBS大鼠内脏敏感性并抑制结肠运动。

下呼吸道细菌定植对稳定期COPD患者TLR2/NF-κB信号通路、免疫功能及气道重塑的影响

目的探讨下呼吸道细菌定植对稳定期慢性阻塞性肺疾病(COPD)患者Toll样受体2(TLR2)/核转录因子-κB(NF-κB)信号通路、免疫功能及气道重塑的影响。方法选取2018年6月-2020年6月南阳市中心医院收治的稳定期COPD患者102例,根据患者痰培养细菌定植结果分为细菌定植组和细菌未定植组,比较两组患者肺功能[用力肺活量(FVC)、第1秒用力呼气容积(FEV_(1))、FEV_(1)%预计值(FEV_(1)%)、1秒率(FEV_(1)/FVC)]、血气指标[氧分压(PaO_(2))、动脉二氧化碳分压(PaCO_(2))、氧合指数(PaO_(2)/FiO_(2))]、免疫功能[CD_(3)^(+)、CD_(4)^(+)、CD_(8)^(+)、CD_(4)^(+)/CD_(8)^(+)]和血清炎性因子[C-反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)]、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制剂(TIMP-1)水平,采用聚合酶链式反应(PCR)检测外周血单个核细胞中TLR2和NF-κB mRNA水平。结果细菌定植组FEV_(1)、FEV_(1)%、FEV_(1)/FVC、PaO_(2)、PaO_(2)/FiO_(2)、CD_(3)^(+)、CD_(4)^(+)和CD_(4)^(+)/CD_(8)^(+)均低于细菌未定植组(P<0.05),而PaCO_(2)、WBC、CRP、TNF-α、IL-6、IL-8、MMP-9、MMP-2、TIMP-1、TLR2、NF-κB mRNA相对水平均高于细菌未定植组(P<0.05)。结论稳定期COPD患者下呼吸道细菌定植会降低患者机体免疫功能,提高机体炎症反应和气道重塑,影响患者肺功能,可能与提高TLR2/NF-κB信号通路活性存在关系。

女性激素相关生物指标在乳腺癌癌前病变中的表达与乳腺癌发生的关系

目的:探讨女性激素相关生物指标雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)、雌激素诱导基因(estrogen induced gene,pS2)在乳腺非典型增生癌变过程中的意义。方法:检测正常乳腺、乳腺单纯性增生、乳腺非典型增生及原发性乳腺癌细胞中ER、PR、pS2的表达。结果:ER、PR、pS2在26例正常对照组中阳性表达率分别为11.53%,15.38%,0;在50例乳腺单纯性增生疾病中阳性率分别为22%,28%,8%;在45例非典型增生症中阳性率分别为64.44%,73.33%,31.11%;在46例原发乳腺癌中阳性率分别为67.39%,56.52%,34.78%。结论:女性激素相关生物指标ER、PR在不典型增生细胞中检测阳性时临床上应特别重视,其发生乳腺癌的可能性增大。pS2的阳性表达可能与乳腺癌的发生也有一定的关系。