Lactobacillus plantarum AR113 attenuates liver injury in D-galactose-induced aging mice via the inhibition of oxidative stress and endoplasmic reticulum stress

Probiotics could effectively eliminate excess reactive oxygen species(ROS)generated during aging or lipid metabolism disorders,but their mechanism is unclear.The major purpose of this study was to investigate the mechanism of Lactiplantibacillus plantarun AR113 alleviating oxidative stress injury in the D-galactose induced aging mice.The result showed that pretreatment with L.plantarun AR113 significantly relieving H_(2)O_(2)induced cytotoxicity in HepG2 cells by maintain cell membrane integrity and increasing antioxidant enzyme activities.In D-galactose induced aging mice,L.plantarun AR113 could significantly attenuate liver damage and inflammatory infiltration by promoting endogenous glutathione(GSH)synthesis and activating the Nrf2/Keap1 signaling pathway in mice,and increasing the expression of regulated phaseⅡdetoxification enzymes and antioxidant enzymes.Further analysis shown that gavage of L.plantarun AR113 could significantly reduce the expression of G protein-coupled receptor 78(GPR78)and C/EBP homologous protein(CHOP)proteins,and promote the restoration of endoplasmic reticulum(ER)homeostasis,thereby activating cell anti-apoptotic pathways.These results were also confirmed in H_(2)O_(2)-treated HepG2 experiments.It indicated that L.plantarun AR113 could inhibit D-galactose-induced liver injury through dual inhibition of ER stress and oxidative stress.L.plantarun AR113 have good application potential in anti-aging and alleviating metabolic disorders.

Exercise-induced modulation of miR-149-5p and MMP9 in LPS-triggered diabetic myoblast ER stress: licorice glycoside E as a potential therapeutic target

Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.

NDRG2调控IRE1α-XBP1介导内质网应激逆转ER+乳腺癌他莫昔芬耐药

他莫昔芬(tamoxifen,TAM)作为雌激素受体阳性(estrogen receptor,ER+)乳腺癌的一线化疗药物使大多数患者受益,但原发性和继发性耐药问题严重影响临床治疗效果。深入研究ER+乳腺癌TAM耐药机制,改善治疗效果是当前亟待解决的问题。抑癌因子NDRG2(N-myc downstream regulated gene 2,NDRG2)在肿瘤发生发展中发挥重要作用,但是否参与ER+乳腺癌TAM耐药尚不清楚。本研究旨在探明NDRG2在ER+乳腺癌TAM耐药中发挥的作用和机制。通过RT-PCR与免疫印迹分析对比TAM敏感型和耐药型ER+乳腺癌细胞发现,NDRG 2的mRNA转录水平和蛋白质翻译水平在TAM耐药细胞中表达显著下调,且与耐药能力负相关(P<0.001);CCK-8细胞毒性实验和软琼脂克隆形成实验证实,在耐药细胞中过表达NDRG2可显著降低TAM药物半抑制浓度IC 50和软琼脂克隆形成率(P<0.001),逆转耐药表型。分子机制上,X-box结合蛋白1(X-box binding protein 1,XBP1)mRNA剪切实验与内质网相关降解(endoplasmic-reticulum associated degradation,ERAD)报告蛋白的结果显示,过表达NDRG2可增强耐药细胞中剪切型XBP1s mRNA转录与ERAD报告蛋白CD3ε-YFP表达(P<0.001),引发耐药细胞内质网强应激反应;免疫印迹检测结果显示,过表达NDRG2可显著提高耐药细胞中内质网应激感受器肌醇需要激酶1α(inositol requiring enzyme 1,IRE1α)的磷酸化水平及其下游因子,例如内质网EIP辅助因子(endoplasmic reticulum-localized DnaJ 4,ERdj4)、PKR蛋白激酶的细胞抑制剂(cellular Inhibitor of the PKR protein kinase,P58 IPK)、α甘露糖苷酶样应激蛋白(er degradation enhancingαmannosidase likeprotein,EDEM)和蛋白质二硫键异构酶家族A成员5(protein disulfide isomerase family a member 5,PDIA5)的表达水平(P<0.001)。小鼠异种移植瘤研究进一步证实,在耐药细胞中过表达NDRG2可增强TAM治疗效果,显著抑制耐药移植瘤生长(P<0.001)。以上研究结果表明,通过提高耐药细胞中NDRG2表达,增强TAM治疗引发的内质网强烈应激,可逆转ER+乳腺癌细胞耐药性,改善TAM治疗效果。研究结果为解决ER+乳腺癌TAM耐药问题提供了新的思路和有价值的潜在药物靶点。

Job Stress, Gene Polymorphism of β_2-AR, and Prevalence of Hypertension

Objective To study the interactive effect of job stress and genetic susceptibility （or gene polymorphism） on hypertension. Methods A cross-sectional epidemiological study was conducted in 452 workers from a thermal power plant in China. Extrinsic effort, occupational reward, and over-commitment were measured. Hypertensive patients were defined by three phases of screening, reexamination, and final diagnosis. β2-AR genotypes and allele frequencies at amino acid positions 16 （β2-AR-16： Arg→Gly） and 27 （β2-AR-27： Gln→Glu） were identified by PCR-RFLE Results Job stress was related with the prevalence of hypertension in males （P〈0.05）, whereas no significant relationship was found in females （P〉0.05）. Differences in genotypes and allele frequencies of the β2-AR-16 were statistically significant between the hypertension and control groups （P〈0.05）, whereas those of β2-AR-27 were not （P〉0.05）. The prevalence of hypertension was higher in individuals carrying Gly16 allele than in those carrying Arg16 allele of the high job stress group （P〈0.01 or 0.05）. Conclusion High job stress and polymorphism of β2-AR-16 have an interactive effect on the prevalence of hypertension in male workers.

Physiological and molecular mechanisms of cytokinin involvement in nitrate-mediated adventitious root formation in apples

Potassium nitrate(KNO_(3))promotes adventitious root(AR)formation in apple stem cuttings.However,evidence for the possible involvement of cytokinin(CK)in KNO_(3)-mediated AR formation in apples is still lacking.In this study,we cultured GL-3 apple microshoots in different treatment combinations.While the T1(KNO_(3)9.4 mmol L^(-1)+6-benzyl adenine(6-BA)2.22μmol L^(-1))and T3(6-BA 2.22μmol L^(-1))treatments completely inhibited AR formation,the control,T2(KNO_(3)9.4 mmol L^(-1)),and T4(KNO_(3)9.4 mmol L^(-1)+lovastatin(Lov)1.24μmol L^(-1))treatments developed ARs.However,T4-treated microshoots developed fewer and shorter ARs,indicating that optimum CK synthesis is needed for normal AR growth.This also suggests that these fewer and shorter ARs developed because of the presence of KNO_(3) in the same medium.The anatomy of the stem basal part indicated that the inhibition of CK biosynthesis delayed AR primordia formation.The endogenous levels of indole-3-acetic acid(IAA)and zeatin riboside(ZR)were higher in T2-treated microshoots,while the abscisic acid(ABA),gibberellic acid 3(GA_(3)),and brassinosteroid(BR)levels were higher in T4-treated microshoots.The expression levels of MdNRT1.1and MdNRT2.1 were higher in T2-treated microshoots at 3 and 8 days,while MdRR2 and MdCKX5 were higher at 8 and 16 days,respectively.Furthermore,higher IAA levels increased MdWOX11 expression,which in turn increased MdLBD16 and MdLBD29 expression in response to T2.The combined expression of these genes stimulated adventitious rooting by upregulating cell cycle-related genes(MdCYCD1;1 and MdCYCD3;1)in response to T2 treatment.This study shows that specific genes and hormonal pathways contribute to KNO_(3)-CK-mediated adventitious rooting in apples.

过量甲状腺激素T3对β2-AR基因敲除小鼠骨代谢的影响

目的研究过量甲状腺激素T3对β2-AR基因敲除小鼠(β2-AR-/-)骨代谢的影响。方法取18只正常C57BL/6J小鼠,分为野生型组、野生型+10倍T3组(35μg/kg)和野生型+20倍T3组(70μg/kg),每组6只。另取18只β2-AR-/-小鼠,分为纯合子组、纯合子+10倍T3组(35μg/kg)和纯合子+20倍T3组(70μg/kg),每组6只。腹腔注射12周,野生型组与纯合子组腹腔注射等量生理盐水。免疫酶联实验(Elisa)检测血清中三碘甲状腺原氨酸(TT3)、四碘甲状腺原氨酸(TT4)、碱性磷酸酶(ALP)、骨桥蛋白(BGP)、骨吸收标志物(CTX)、酒石酸酸性磷酸酶5b(TRAP-5b)、超氧化物歧化酶(SOD)和丙二醛(MDA)含量。显微计算机断层扫描(micro-CT)分析小鼠股骨远端,计算骨小梁模式因子(Tb.Pf)、骨小梁数量(Tb.N)、骨小梁分离度(Tb.sp)、骨厚度(Tb.th)、骨链接密度(Conn.Dn)和骨密度(BMD)。结果与T3处理前相比,野生型和纯合子小鼠血清中TT3、TT4、CTX、TRAP-5b、MDA含量均显著性升高,SOD、BGP和ALP含量显著下降,野生型小鼠组织中Tb.Sp升高,Tb.N、Conn.Dn和BMD降低,纯合子+10倍T3小鼠组织中Tb.Pf升高,Tb.Th、Tb.N、Conn.Dn和BMD降低,纯合子+20倍T3小鼠组织中Tb.Th、Tb.Sp升高,Tb.N和Conn.Dn降低(P<0.05);与野生型+10倍T3组相比,20倍浓度T3野生型小鼠血清中TT3、TT4、CTX、TRAP-5b、MDA含量均显著升高,SOD、BGP和ALP含量显著下降,组织中Tb.Pf升高,Tb.Th降低,(P<0.05);与纯合子+10倍T3组相比,纯合子+20倍T3小鼠组织中Tb.Th升高(P<0.05);与野生型+20倍T3组相比,纯合子+20倍T3组小鼠血清中TT3、TT4、BGP、SOD和ALP含量均显著升高,血清中CTX、TRAP-5b、MDA含量均显著性降低,组织中Tb.Th、Tb.N和BMD升高,Tb.Pf和Tb.Sp降低(P<0.05)。结论β2-AR缺乏可能避免小鼠因过量T3作用产生骨代谢异常,减少体内氧化应激损伤,保护骨组织形态。

大豆异黄酮对去卵巢大鼠小脑ERα、NGF、IL-2、AR mRNA表达的影响

建立去卵巢SD大鼠模型,运用原位组织杂交方法,通过补充不同剂量大豆异黄酮观察其对ERα、NGF、IL-2、AR mRNA在小脑中的表达和分布影响,探讨大豆异黄酮对小脑的作用机制和意义及其剂量关系。结果显示:ERα、NGF、IL-2、AR mRNA杂交信号主要分布于小脑皮质的蒲肯野氏细胞层和小脑室顶核、间位核和齿状核中,小脑皮质的分子层和颗粒层也有少量弱杂交信号表达;杂交信号主要定位于胞核,也存在于胞浆、胞膜和突起中,4种杂交信号变化的总趋势为去卵巢大鼠小脑皮质及小脑核中ERα、NGF、IL-2、AR mRNA的表达强度和阳性数目显著降低;而补充不同剂量大豆异黄酮后,4种物质的阳性杂交信号强度和数目均有不同程度回升,其中高剂量组基本恢复到假手术组水平,低剂量组仅有少许回升或无变化,中剂量组介于两者之间。从以上结果得出:大豆异黄酮可在基因水平上促进ERα、NGF、IL-2、AR在小脑中的表达,且存在剂量依赖性;这4种物质表达变化的相似性提示四者在大豆异黄酮对小脑的作用中是相互调节和影响的。

免疫组化法测定小儿隐睾睾丸周围组织AR,ER的意义

目的 探讨隐睾患儿睾丸周围组织中雄激素受体 (AR)和雌激素受体 (ER)的分布及临床意义。方法 隐睾组患儿共 3 9例 ,其中单侧隐睾 2 6例 ,双侧 13例 ,取隐睾睾丸周围组织 (鞘状突、提睾肌、睾丸引带、阴囊皮肤 ) ,对照组共 2 9例 ,取同期手术的小儿斜疝及鞘膜积液的上述相应部位组织 (阴囊皮肤除外 ) ,包埋石蜡切片 ,免疫组化法 (SP)测定AR、ER阳性率。结果 隐睾组患儿鞘膜及睾丸引带AR阳性率低于对照组 (P <0 .0 5 ) ,单侧隐睾组患儿鞘膜及睾丸引带AR和ER阳性率高于双侧组 (P <0 .0 5 )。隐睾组患儿鞘膜ER阳性率低于对照组 (P <0 .0 5 ) ,阴囊皮肤中AR阳性率在四种组织中最高 ,不同年龄阶段的阴囊皮肤中AR阳性率存在差别 (P <0 .0 5 ) ,以 3～ 6岁年龄段阳性率居高。结论 隐睾组患儿在睾丸周围组织鞘膜及睾丸引带中AR表达率低于正常儿 ,而ER在鞘突中的阳性表达率高于正常儿 ,这表明隐睾患儿睾丸周围组织中AR的低下为隐睾的特点 ,可考虑为其病因之一 ,而ER的异常尚不能考虑构成为隐睾的病因。双侧隐睾鞘膜和引带中AR和ER阳性表达低于单侧隐睾 ,可能是双侧隐睾患儿雄性化程度较差的因素。阴囊皮肤中的AR的表达明显高于其它三种睾丸周围组织 ,在 3～ 6岁年龄段易于表达。

ER、PR、AR受体和C-erbB-2、p16、p53基因蛋白在乳腺癌中的表达

为了评价雌激素受体（Ｅｓｔｒｏｇｅｎ Ｒｅｃｅｐｔｏｒ，ＥＲ）、孕激素受体（ＰｒｏｇｅｓｔｅｒｏｎｅＲｅｃｅｐｔｏｒ ＰＲ）、雄激素受体（Ａｎｄｒｏｇｅｎ Ｒｅｃｅｐｔｏｒ，ＡＲ）和癌基因（Ｏｎｃｏｇｅｎｅ）Ｃ－ｅｒｂＢ－２Ｏｎｃｏｐｒｏｔｅｉｎ（Ｃ－ｅｒｂＢ－２），抑癌基因（Ｔｕｍ ｏｒ Ｓｕｐｐｒｅｓｓｏｒ Ｇｅｎｅｓ） ｐ５３ 蛋白（ｐ５３）和ｐ１６蛋白（ｐ１６）在乳腺癌发生发展中的作用，以及上述蛋白检测对诊断与治疗的意义。用免疫组化Ｓ－ Ｐ法检测６ 种蛋白在６２ 例乳腺癌和１０ 例乳腺良性病变中的表达。结果ＥＲ、ＰＲ、ＡＲ、Ｃ－ｅｒｂＢ－２、ｐ１６、ｐ５３ 在乳腺癌中的表达率分别为 ８５．５％ 、７４．２％ 、２２．６％ 、７４．２％ 、９０．３％ 、４８．４％ 与良性病变表达率相比差异显著（Ｐ＜ ０．００１），乳腺癌不同组织类型之间无显著差异（Ｐ＞ ０．０５）。核异型性与ＲＰ，ｐ１６ 明显相关（Ｐ＜ ０．０５）；ＥＲ与ｐ１６、肿瘤腺管评分、组织学分级；ＲＰ与ｐ１６；ＡＲ与ｐ５３、患者年龄；ｐ５３ 与核异型性、核分裂相、组织学分级；肿瘤大小与淋巴结转移率分别明显相关。结果表明：ＥＲ、ＰＲ、ＡＲ对患者激素治疗是有价值的指标。

前列腺癌中ER、AR及VEGF表达的临床意义

目的 探讨 ER、AR及 VEGF在前列腺癌中的表达情况。方法 采用免疫组织化学染色 (SP)法 ,对 10例前列腺癌和 30例前列腺增生病理切片组织检测 ER、AR和 VEGF。结果 10例前列腺癌中 ER全部阴性 :AR阳性 9例 ,占 90 % (9/ 10 ) ;VEGF 4例阳性 ,占 40 % (4 / 10 ) ,其中 + 2例 , 1例 , 1例。 30例 BPH中 ER阳性 15例 ,占 5 0 %(15 / 30 ) ,VEGF 12例阳性 ,占 40 % (12 / 30 )。结论 PCa与 BPH中 VEGF含量比例相同 ,阻止 VEGF的生成作用达到治疗只能对部分患者有效。 ER、AR、VEGF可作为检测前列腺癌的临床指标。

VEGF、ER、PR及AR在颈鼓室副神经节瘤的表达

目的观察血管内皮生长因子(vascular endothelial growth factor,VEGF)及雌激素受体(estrogen receptor,ER)、孕激受体(progestogen receptor,PR)、雄激素受体(androgen receptor,AR)在颈鼓室副神经节瘤的表达,分析其与肿瘤生物学行为的关系。方法回顾性分析17例颈鼓室副神经节瘤的临床资料,对其存档的手术标本行Envision法免疫组织化学检查,并运用SPSS 10.0 for Windows对资料进行Spearman等级相关分析。结果在17例标本中,11例表达VEGF,且表达强度与Fisch分级相关,r=0.529,P<0.05;无1例表达ER、PR及AR。结论 VEGF可能对颈鼓室副神经节瘤的生长有促进作用;颈鼓室副神经节瘤的性别偏向似乎与性激素异常无关。

原发性肺癌的性激素受体ER、PR、AR检测及其意义

近年来，对人体肿瘤的性激素受体研究成果的报导很多，尤其是对乳腺等靶器官肿瘤的性激素受体研究取得了很大进展。雌、孕激素受体与肺癌关系的研究在国内外已有报导。但肺癌与雄激素受体(AR)关系的研究，笔者还未见到国内外报导。本文对47例原发性肺癌进行ER，PR和AR的对比检测，旨在探讨肺癌性激素受体的表达规律及其对内分泌治疗的可行性和预测预后的价值。

miR-29a up-regulation in AR42J cells contributes to apoptosis via targeting TNFRSF1A gene

AIM: To investigate the expression of mi R-29 a in rat acute pancreatitis and its functional role in AR42 J cell apoptosis.METHODS: Twelve SD rats were divided into a control group and an acute edematous pancreatitis(AEP) group randomly. AEP was induced by intraperitoneal injection of L-arginine(150 mg/kg) in the AEP group and equal volume of 0.9% Na Cl was injected in the control group. The apoptosis of acinar cells in pancreatic tissue was determined by TUNEL assay. mi RNA chip assay was performed to examine the expression of mi RNAs in two groups. Besides, to further explore the role of mi R-29 a in apoptosis in vitro, recombinant rat TNF-α(50 ng/m L) was administered to treat the rat pancreatic acinar cell line AR42 J for inducing AR42 J cell apoptosis. Quantitative real-time PCR(q RT-PCR) was adopted to measure mi R-29 a expression. Then, mi RNA mimic, mi RNA antisense oligonucleotide(AMO) and control vector were used to transfect AR42 J cells. The expression of mi R-29 a was confirmed by q RT-PCR andthe apoptosis rate of AR42 J cells was detected by flow cytometry analysis. Western blot was used to detect the expression of activated caspase3. Moreover, we used bioinformatics software and luciferase assay to test whether TNFRSF1 A was the target gene of mi R-29 a. After transfection, q RT-PCR and Western blot was used to detect the expression of TNFRSF1 A in AR42 J cells after transfection.RESULTS: The expression of mi R-29 a was much higher in the AEP group compared with the control group as displayed by the mi RNA chip assay. After inducing apoptosis of AR42 J cells in vitro, the expression of mi R-29 a was significantly increased by 1.49 ± 0.04 times in comparison with the control group. As revealed by q RT-PCR assay, the expression of mi R-29 a was 2.68 ± 0.56 times higher in the mi R-29 a mimic group relative to the control vector group, accompanied with an obviously increased acinar cell apoptosis rate(42.83 ± 1.25 vs 24.97 ± 0.15, P < 0.05). Moreover, the expression of mi R-29 a in the mi RNA AMO group was 0.46 ± 0.05 times lower than the control vector group, and the cell apoptosis rate was much lower accordingly(17.27 ± 1.36 vs 24.97 ± 0.15, P < 0.05). The results of bioinformatics software and luciferase assay showed that TNFRSF1 A might be a target gene of mi R-29 a. TNFRSF1 A expression was up-regulated in the mi R-29 a mimic group, while the mi R-29 a AMO group showed the reverse trend.CONCLUSION: mi R-29 a might promote the apoptosis of AR42 J cells via up-regulating the expression of its target gene TNFRSF1 A.

Profile and removal of endocrine disrupting chemicals by using an ER/AR competitive ligand binding assay and chemical analyses

An estrogen receptor （ER）/androgen receptor （AR） ligand competitive binding assay （ER/AR-binding assay） and chemical analyses were used to evaluate the endocrine disrupting chemicals （EDCs） behavior of two municipal wastewater treatment plants （WWTPs） （K and S）. In the influents, estrone （E 1）, androsterone （A）, androstenedione （AD）, BPA （bisphenol A）, NP （nonylphenol） and daidzein （DZ） were detected in high amounts with subsequent 24 h-average concentrations of 350, 1000, 29, 1300, 3900, and 5700 ng/L in K-WWTP and of 310, 620, 59, 1600, 2600, and 8400 ng/L in S-WWTP. The estrogenic （androgenic） activity as 17β-estradiol （E2） equivalents （EEQ） or testosterone （Te） equivalents （TEQ） was consequently 620 ng E2/L （570 ng Te/L） and 580 ng E2/L （800 ng Te/L） for the two WWTPs. The removal efficiencies of the above mentioned sole target chemicals were 51%-100% for K-WWTP and 55.6%-100% for S-WWTP. The removal efficiencies of EEQ were about 73% for both WWTPs, while the removal efficiencies of TEQ were 62.1% for K-WWTP and 98.4% for S-WWTP. In addition, chemical-derived EEQ were about 1.2%-52.4% of those by ER-binding assay for K-WWTP and the corresponding ratios were 1.3%-83.3% for S-WWTP, while chemical derived TEQ were less than 3% of values measured by the AR-binding assay for both WWTPs.

Studies of the Expression of Estrogen Receptor Gene in the Rat Uterus during the Estrous Cycle and Periimplantational Period

The correlation or serum estradiol concentrstion and uterine estrogen receptor (ER) gene expression (ERn and ERc quantitated by Dextrsn Coat Charcoal assay and ER mRNA by Northern blotting) was studied during the rat estrous cycle and early Pregnant stage (dl-d10). The ER gone expression was up - regulated by estrogen and the levels of ER mRNA synchronized with the changes of ER protein, suggesting that estrogen influenced the trsnscriPtional step of the ER gene. Post-coitum ER expression increased with the serum estrsdiol progressively, reached a peak on d4-ds (Just before implantation), but drastically dropped to the nadir on d6-d7 (during implantation) and then recovered. It was of interest to discover that ER mRNA level in the nonimplantstion sites (NIS) of uterus was much higher than that in the implantstion sites (IS).

AR在乳腺导管原位癌中的表达及其与ER、PR表达的关系

目的:研究导管原位癌中雄激素受体(androgen receptor,AR)的表达情况,探讨AR表达与组织分级及与雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)表达的关系。方法:用免疫组织化学方法研究51例不同级别导管原位癌(breast ductal carcinoma in situ,DCIS)中AR的表达及与ER、PR表达状态的相关性。结果:AR阳性表达于18例DCIS中,33例DCIS中没有表达。13例低级别导管内癌中有3例AR阳性表达,15例中级导管内癌中有7例AR阳性表达,23例高级导管内癌中有8例AR阳性表达(P=0.4270)。导管内癌的分化程度与ER(P=0.0036)及PR(P=0.0398)的表达密切相关。在导管内癌的不同组织学亚型间AR的表达差异有统计学意义(P=0.0156),但ER(P=0.0695)与PR(P=0.4672)的表达无差异。绝经前与绝经后患者导管内癌的AR表达无差异(P=0.6510),但ER(P=0.0074)与PR(P=0.0259)的表达有差异。结论:有一部分乳腺导管内癌表达AR,导管内癌的AR表达与组织分化程度无关,与DCIS中ER、PR表达也没有相关性。

关于名词性后缀-er,-or和-ar的选用

在现代英语中,名词性后缀-er 使用频率很高,它可以附在动词、名词、形容词以及由动词词组构成的复合词后,构成名词。附在动词后,-er 可以理解为发出该动词所表示的行为的人或具备某种特性的物。但有些动词是通过加后缀-or,甚至-ar 来构成表达上述意义的名词形式。面对三种名词性后缀,英语初学者不免感到困惑、茫然。本文选用部分常用例词,根据单词的读音和拼写形式,总结出正确选用-er,-or 和-ar 三种名词性后缀的一般规律。

4例46,XY性发育障碍患者遗传学分析

目的:探讨4例46,XY性发育障碍发生的分子机制。方法:收集患者临床病历资料,采集其肝素抗凝外周血进行淋巴细胞培养,染色体G显带技术制备并分析染色体核型,提取外周血DNA行SRY基因检测和测序,SRY基因检测结果阴性者外送标本行性发育相关基因靶向测序,生物信息学方法分析测序结果。结果:查体显示4例患者社会性别均为女性,而外周血淋巴细胞核型分析结果提示核型均为男性(46,XY),社会性别与生物学性别不一致;性别决定基因SRY均为阳性,测序结果提示病例1为SRY基因编码区第5位碱基缺失(c.del5A),病例2为SRY基因编码区第5位碱基发生错义突变(c.5A>T),病例3为SRY基因编码区第6位碱基缺失(c.del6A),病例4的SRY基因检测范围内未见突变位点,靶向测序结果提示雄激素受体基因(AR)编码区发生错义突变(c.2117 A>G);生物信息学软件Mutation taster提示c.del5A、c.del6A和c.2117 A>G等3种突变可能导致疾病发生,c.5A>T突变可能为人群多态现象;Raptor X蛋白质三维结构预测软件分析结果显示SRY基因c.5A>T突变对SRY蛋白的三维构象没有影响,而AR基因c.2117 A>G突变可导致AR蛋白的三维结构明显变化,并增加两个氢键;PolyPhen-2显示SRY基因c.5A>T和AR基因c.2117A>G突变为可能致病;ClinvAR软件分析结果提示4种突变均未见临床病例报道。结论:基因突变可能是导致患者性器官发育异常的原因,基因检测有助于明确诊断以及家庭再生育咨询。

浸润性乳腺癌中AR的表达及其预后意义

目的探讨乳腺癌中AR表达与临床病理特征的关系及预后意义。方法采用免疫组化EnVision法检测584例浸润性乳腺癌中AR、ER、PR、HER^-2及Ki-67的表达,对比分析AR表达与临床病理特征及预后的相关性。结果单因素分析显示,584例乳腺癌中AR阳性率为86.5%,AR表达与患者年龄、肿块大小、WHO分级、ER、PR、Ki-67、HER^-2、分子分型有关(P<0.05)。多因素Logistics回归分析显示,AR表达与患者年龄、WHO分级、ER、HER^-2有关(P<0.05)。生存分析表明,ER^+/AR^+组患者无复发生存(relapse free survival,RFS)、总生存(overall survival,OS)、无远处转移生存(distant metastasis-free survival,DMFS)明显高于ER^+/AR-组(P<0.05);ER^-/AR^+组患者的RFS、OS、DMFS则明显低于ER^-/AR-组(P<0.05)。结论AR在浸润性乳腺癌中有较高的阳性率,AR在ER^-和ER^+这两类乳腺癌发生、发展中的生物学功能有明显差异,ER^+/AR^+乳腺癌患者与ER^-/AR^+者相比,有更好的预后。