腹腔灌注联合静脉化疗治疗晚期卵巢癌疗效观察

目的:探讨顺铂腹腔灌注联合多西他赛静脉化疗治疗晚期卵巢癌患者的疗效和不良反应。方法:选取晚期卵巢癌患者(Ⅲ-Ⅳ期)70例为研究对象,将患者随机分为顺铂联合多西他赛静脉化疗36例(对照组),以及顺铂腹腔灌注联合多西他赛静脉化疗34例(观察组)。对比分析两组化疗效果以及化疗不良反应。结果:观察组患者总有效率为76.47%,对照组总有效率为50.00%,两组比较差异有统计学意义(P<0.05)。观察组不良反应率为47.06%,毒副反应级别主要为Ⅰ-Ⅱ级。观察组与对照组相比,差异有统计学意义(P<0.05)。各组患者5年生存率无统计学意义(P>0.05);而观察组患者3年生存率为55.88%,显著高于对照组,差异有统计学意义(P<0.05)。观察组平均中位生存时间显著优于对照组,差异有统计学意义(P<0.05)。结论:顺铂腹腔灌注联合多西他赛静脉化疗治疗晚期卵巢癌,较顺铂联合多西他赛静脉化疗疗效好,化疗毒副反应小。     

海藻糖在生育力保存中的应用

肿瘤诊疗技术的进步显著提高了患者的生存率,但放化疗可能造成人类生育力的下降乃至丧失。如何有效保存生育力已成为近年来研究的热点。海藻糖属于非渗透性冷冻保护剂,是一种具有特殊生物学性能的双糖,能够在干燥、脱水、冷冻等恶劣条件下有效保护蛋白质等大分子不变性失活。随着研究的逐步深入,海藻糖已被广泛应用于生育力保存等医学领域中,有学者将其用于保存精子、精原干细胞、卵母细胞、胚胎、卵巢组织和睾丸组织并取得了显著成果。综述海藻糖的生物学性质、作用机制假说以及在生育力保存中的应用研究现状和最新进展。     

In utero exposure to the endocrine disruptor di(2-ethylhexyl) phthalate targets ovarian theca cells and steroidogenesis in the adult female rat

Di-2-ethylhexyl phthalate (DEHP) is an endocrine disruptor used in industry as an additive to polyvinyl chloride-based products. Pregnant dams were gavaged with oil, 1, 20, 50, or 300 mg of DEHP/kg/day from gestational day 14 until birth in order to characterize the effects of DEHP in the adult female offspring. In utero exposure to DEHP resulted in reduced estrogen levels at proestrus. Theca cell layer thickness was decreased starting at 50 mg DEHP/kg/day dose. Follicle-stimulating hormone levels were significantly increased at proestrus and estrus. F1 reproduction using a known breeder was not affected. F3 generation showed a decreased pregnancy rate and weight, and increased litter size in the animals exposed to 20 mg DEHP/kg/day. The data presented herein suggest that in utero exposure to DEHP targets the theca cell layer and decreases the estrus cycle steroid surge, but despite these effects, does not cause infertility.     

断乳至性成熟期暴露纳米二氧化硅对小鼠卵巢发育的影响

目的探讨断乳至性成熟期经口持续摄入纳米二氧化硅对小鼠卵巢发育的影响。方法将40只21日龄清洁级ICR雌性小鼠随机分为4组,即对照组和0.25、0.50、1.00 g/kg纳米二氧化硅染毒组,每组10只。采用经口灌胃方式进行染毒,每日1次,持续染毒5周。实验结束后记录小鼠体重增长情况、观察阴门开放时间和动情周期,病理切片计数各级卵泡数量及计算各级卵泡的构成比,并测定卵巢中丙二醛(MDA)含量和超氧化歧化酶(SOD)、谷胱苷肽过氧化物酶(GSH-Px)活力。结果与对照组比较,1.00 g/kg纳米二氧化硅染毒组小鼠卵巢重量和脏器系数下降、阴门开放时间推迟、卵巢黄体构成比下降、闭锁卵泡构成比升高,差异有统计学意义(P0.05);而各剂量纳米二氧化硅染毒组小鼠体重增长和动情周期均无明显改变。与对照组比较,1.00 g/kg纳米二氧化硅染毒组小鼠卵巢组织中MDA含量明显上升,SOD活力均明显下降,而0.50、1.00 g/kg纳米二氧化硅染毒组小鼠卵巢组织中GSH-Px活力均升高,差异具有统计学意义(P0.05)。结论经口摄入纳米二氧化硅可影响小鼠卵巢发育,其机制可能与氧化损伤有关。     

Transfer pathways between the ovaries and the uterus in the cebus monkeys (Cebus apella)

The aim of this work was to study, in the Cebus apella monkey, the developmental changes in the microanatomy of the utero-ovarian ligament (UOL) and whether their vascular and neural elements might be involved in the transfer of signals between the ovaries and uterus. Sections including uterus, UOL, and ovary obtained from two foetuses, two prepubertal, and four cycling monkeys, two of them treated with a neuron-axonal tracer, diamidino yellow (DY) into the corpus luteum (CL) and the remaining two into the endometrium, were analyzed for the expression of neurofilament protein (NFP) and tracer distribution. Eight regularly cycling females were used to investigate the transfer to the CL of pulses of prostaglandin F(2alpha) (PGF(2alpha)) (n=4) or its vehicle (n=4) given intra-uterus. A convoluted artery, in conjunction with various vein channels, passed over the UOL allowing for a direct communication between uterus and ovaries. The artery acquired prominence during adulthood, in a manner well suited with the ovarian status. Immunohistochemical analysis revealed that NFP expression by the oocyte and by the endometrial epithelial cells was a highly conserved feature during development, whereas the appearance of NFP fibers in the ovaries, UOL, and uterus was a late event in the ontogenesis, likely regulated by the hormonal environment. Neurons, as an obvious source for these NFP fibers, were not recognized at any developmental stage, although some neuron-like cells were observed within the CL. The pattern displayed by the tracer DY, further suggested a reciprocal axonal transport among endometrial cells and follicular and luteal cells of both ovaries and between the ovaries themselves. The functionality of the utero-ovarian connection was assessed after injecting PGF(2alpha) intra-uterus. A short exposition to PGF(2alpha) pulses was required for lowering ovarian and peripheral progesterone concentrations causing luteolysis, indicating that transport mechanism operating between uterus and ovary must be very efficient. The results suggest that the vessels and axons contained in the UOL of the Capuchin monkeys might be two combined key pathways underlying the reciprocal transfer of signals controlling utero-ovarian homeostasis.     

Gonadotropin-releasing hormone activates mitogen-activated protein kinase in human ovarian and placental cells

Considering that the action of gonadotropin-releasing hormone (GnRH) may be mediated via different signaling pathways in extrapituitary tissues, in the present study we investigated the role of the human GnRH receptor (GnRHR) in activating mitogen-activated protein kinases (MAPKs), which regulate cell growth, division, and differentiation. The phosphorylation state of p44 and p42 MAPKs was examined using antibodies that distinguish phospho-p44/42 MAPK (P-MAPK, Thr²⁰²/Tyr²⁰⁴) from total p44/42 MAPK (T-MAPK, activated plus inactivated) in human ovarian and placental cells. Cell cultures were treated with various concentrations of a GnRH agonist, (D-Ala⁶)-GnRH, for 5 min. (D-Ala⁶)-GnRH stimulated a rapid activation of P-MAPK in human granulosa-luteal cells (hGLCs) and immortalized extravillous trophoblast (IEVT) cells. Interestingly, (D-Ala⁶)-GnRH treatment of ovarian cancer (OVCAR-3) and placental carcinoma (JEG-3) cells induced a biphasic regulatory pattern in P-MAPK activity. In contrast, no change of T-MAPK levels was observed following addition of the GnRH agonist in the ovarian and placental cells examined. The physiological implication of MAPK activation by GnRH in the ovarian and placental cells was also investigated. Human GLCs were treated with (D-Ala⁶)-GnRH for 24 h, and progesterone secretion was measured by an established RIA. (D-Ala⁶)-GnRH induced a significant decrease in progesterone secretion with maximum inhibition (a 45% decrease over basal level) at 10⁻⁷ M. This inhibitory effect was completely reversed by pretreatment with MAPK/ERK kinase 1 (MEK1) inhibitor (PD98059), suggesting the involvement of the MAPK pathway in hGLCs. Placental JEG-3 cells were treated with (D-Ala⁶)-GnRH for 24 h, and βhCG mRNA level was measured using Northern blot analysis. (D-Ala⁶)-GnRH stimulated the expression of βhCG mRNA to 160% of control value in JEG-3 cells. In contrast to the ovarian cells, pretreatment of JEG-3 cells with PD98059 failed to block the stimulatory effect of GnRH on βhCG mRNA level, suggesting that other signaling pathway(s) may play a more dominant role in GnRH-induced βhCG mRNA expression. To our knowledge, this is the first demonstration that (1) GnRH induces activation of the MAPK signaling pathway in normal and carcinoma cells of the human ovary and placenta, and (2) MAPK mediates the direct action of GnRH on progesterone production in hGLCs.     

儿童卵巢幼年颗粒细胞瘤超声表现及病理对照研究

目的探讨儿童卵巢幼年颗粒细胞瘤（JGCTs）超声表现及病理特征。 方法回顾性分析2005年1月至2020年12月经重庆医科大学附属儿童医院手术病理证实为JGCTs的14例患儿的临床资料。依据国际卵巢肿瘤分析组织（IOTA）标准对瘤体超声图像进行模式分型,并与术后组织病理结果进行对照分析。 结果14例患儿肿瘤最大径线范围37~286 mm,最大径线平均值（105±56）mm。超声声像图表现为：实性6例（42.9%）、多房囊实性4例（28.6%）、单房囊实性1例（14.3%）、多房囊性2例（14.3%）以及单房囊性1例（7.1%）。病理结果显示,实性包块由大量颗粒细胞弥漫增生形成,其间伴有散在大小不等滤泡、坏死出血及纤维条索组织。多房囊实性、单房囊实性、多房囊性及单房囊性肿瘤内均可见数量不一的大滤泡,滤泡内大多数为颗粒细胞分泌的嗜碱性、嗜酸性液体。临床表现为乳房增大5例（35.7%）,阴道出血及分泌物5例（35.7%）;超声提示子宫增大10例（71.4%）。所有患儿术前血清雌二醇水平均升高,均值（534.0±839.5）pmol/L。 结论JGCTs超声表现多样,实性和多房囊实混合性更常见,其病理特征为大量颗粒细胞弥漫增生伴散在大小不等滤泡,超声表现结合内分泌临床表现及血清雌二醇的升高有助于临床诊断。