经阴道三维超声联合CA125、CA199、NLR及PLR检测对绝经后子宫内膜癌的诊断效能

摘要 目的：探讨经阴道三维超声联合糖类抗原125（CA125）、糖类抗原199（CA199）、中性粒细胞/淋巴细胞比值（NLR）及血小板/淋巴细胞比值（PLR）检测对绝经后女性子宫内膜癌（EC）的诊断效能。方法：回顾性分析本院2019年5月至2022年5月收治的因绝经后出血就诊的92例疑似子宫内膜肿瘤患者的病历资料,经手术病理证实,EC患者48例（EC组）、子宫内膜良性病变患者44例（良性组）。比较两组CA125、CA199、NLR及PLR水平,对比两组子宫内膜血管指数（VI）、血流指数（FI）、血管-血流指数（VFI）、子宫内膜容积（EV）变化及血流信号分布情况。绘制受试者工作特征（ROC）曲线分析经阴道三维超声联合CA125、CA199、NLR及PLR检测对绝经后EC的诊断效能。结果：EC组CA125、CA199、NLR及PLR水平均高于良性组（P＜0.05）。EC组三维超声参数VI、FI、VFI及EV均高于良性组（P＜0.05）。EC组血流信号Ⅱ级占比25.00%,Ⅲ级占比70.83%;良性组血流信号Ⅱ级占比88.64%,Ⅲ级占比2.27%。EC组血流信号Ⅱ级占比低于良性组,血流信号Ⅲ级占比高于良性组（P＜0.05）。两组血流信号0级、Ⅰ级比较无差异（P＞0.05）。ROC结果显示五项检查联合检测曲线下面积（AUC）值为0.944（95%Cl：0.902~0.985）,具有更优的诊断效能（敏感度为89.10%、特异度为91.80%）。结论：CA125、CA199、NLR及PLR检测联合经阴道三维超声检查诊断绝经后EC效果显著,可为临床诊断提供参考。     

IGFBP-1 inhibits EGF mitogenic activity in cultured endometrial stromal cells

The properties of the insulin-like growth factor-binding proteins (IGFBP-1 to 6) are not limited to modulation of IGF actions. IGFBP-1, which shares an Arg-Gly-Asp (RGD) motif in its C-terminal domain, modulates cell motility by binding to integrin alpha5beta1. The cross-talks between integrins and growth factor receptor signalling pathways are extensively documented, particularly in the case of the epidermal growth factor receptor (EGFR). However, whether IGFBP-1 can modulate growth factor signalling through its interaction with integrin alpha5beta1 has not yet been studied. As EGF is involved in the decidualisation of endometrial stromal cells (ESCs) and as decidualised ESCs are a source of IGFBP-1, we investigated if IGFBP-1 can modulate EGF effects on ESCs. RGD- and IGF-independent inhibition of EGF mitogenic activity and EGFR signalling by IGFBP-1 were demonstrated in ESC primary cultures, A431, cells and in mouse fibroblasts lacking IGF receptors.     

Adenovirus mediated homozygous endometrial epithelial Pten deletion results in aggressive endometrial carcinoma

Pten is the most frequently mutated gene in uterine endometriod carcinoma (UEC) and its precursor complex atypical hyperplasia (CAH). Because the mutation frequency is similar in CAH and UEC, Pten mutations are thought to occur relatively early in endometrial tumorigenesis. Previous work from our laboratory using the Pten^+/− mouse model has demonstrated somatic inactivation of the wild type allele of Pten in both CAH and UEC. In the present study, we injected adenoviruses expressing Cre into the uterine lumen of adult Pten floxed mice in an attempt to somatically delete both alleles of Pten specifically in the endometrium. Our results demonstrate that biallelic inactivation of Pten results in an increased incidence of carcinoma as compared to the Pten^+/− mouse model. In addition, the carcinomas were more aggressive with extension beyond the uterus into adjacent tissues and were associated with decreased expression of nuclear ERα as compared to associated CAH. Primary cultures of epithelial and stromal cells were prepared from uteri of Pten floxed mice and Pten was deleted in vitro using Cre expressing adenovirus. Pten deletion was evident in both the epithelial and stromal cells and the treatment of the primary cultures with estrogen had different effects on Akt activation as well as Cyclin D3 expression in the two purified components. This study demonstrates that somatic biallelic inactivation of Pten in endometrial epithelium in vivo results in an increased incidence and aggressiveness of endometrial carcinoma compared to mice carrying a germline deletion of one allele and provides an important in vivo and in vitro model system for understanding the genetic underpinnings of endometrial carcinoma.     

Aromatase and comparative response to its inhibitors in two types of endometrial cancer

Aromatase activity (AA) was evaluated totally in 80 tumors collected from primary endometrial cancer (EC) patients. All patients were divided into cases belonging to the types I or II of EC (respectively, 50 and 30 observations). Samples of malignant endometrium from type II demonstrated inclination to the higher AA in comparison with type I samples; the difference reached level of statistical significance in non-smoking patients (p = 0.02). Although no positive correlation was revealed between AA in EC tissue and percentage of cells with DNA damage in normal endometrium from the same patients, the rate of DNA damage (percent of comets, comet's tail average length, etc.) was higher in intact endometrium collected from patients with type II of the disease. In 19 tumor samples, CYP19 gene expression was evaluated by RT-PCR and level of mRNA signal demonstrated positive correlation with AA (R_s = +0.63, p = 0.05) in the whole this material. Of note, though, CYP19 mRNA expression was not revealed in six cases, and all of them belonged to the type I of disease. Finally, in 23 EC patients (15 with type I and 8 with type II of the disease) effects of 2 weeks treatment with letrozole (10 pts) and exemestane (13 pts) were evaluated in neoadjuvant setting. Although diminishing of endometrial M-echo signal and the increases in FSH and LH concentration after treatment were more pronounced in type I patients, decrease in tumor PR content (p = 0.04) was more revealing in patients with type II of EC; besides, the decreases in AA in tumor tissue by the end of treatment were noted predominantly in patients with lower body weight (BMI <27.5). Thus, although type II of EC is frequently considered as hormone-independent, increased ability of this type of the tumor to estrogen biosynthesis (at CYP19 gene and protein level) may lead to the reconsideration of such conclusion and warrants further investigation. The search of possible ethnic differences in AA and in the biologic response to aromatase inhibitors in EC can be of importance too.     

Partial silencing of fucosyltransferase 8 gene expression inhibits proliferation of Ishikawa cells,a cell line of endometrial cancer

Endometrial cancer is the most common gynecologic malignancy and is associated with increased morbidity each year, including young people. However, its mechanisms of proliferation and progression are not fully elucidated. It is well known that abnormal glycosylation is involved in oncogenesis, and fucosylation is one of the most important types of glycosylation. In particular, fucosyltransferase 8 (FUT8) is the only FUT responsible for α1, 6-linked fucosylation (core fucosylation), and it is involved in various physiological as well as pathophysiological processes, including cancer biology. Therefore, we aimed to identify the expression of FUT8 in endometrial endometrioid carcinoma and investigate the effect of the partial silencing of the FUT8 gene on the cell proliferation of Ishikawa cells, an epithelial-like endometrial cancer cell line. Quantitative real-time PCR analysis showed that FUT8 gene expression was significantly elevated in the endometrial endometrioid carcinoma, compared to the normal endometrium. The immunostaining of FUT8 and Ulex europaeus Agglutinin 1 (UEA-1), a kind of lectin family specifically binding to fucose, was detected endometrial endometrioid carcinoma. The proliferation assay showed FUT8 partial knockdown by transfection of siRNA significantly suppressed the proliferation of Ishikawa cells, concomitant with the upregulation in the gene expressions associated with the interesting pathways associated with de-ubiquitination, aspirin trigger, mesenchymal-epithelial transition (MET) et al. It was suggested that the core fucosylation brought about by FUT8 might be involved in the proliferation of endometrial endometrioid carcinoma cells.     

宫腔镜下子宫内膜电切术联合刮宫术治疗多发性子宫内膜息肉的效果探讨

目的:探讨宫腔镜下采取子宫内膜电切术联合刮宫术对于治疗多发性子宫内膜息肉(EMP)患者的临床效果。方法:选取2012年6月至2014年3月在我院确诊为EMP的患者100例,随机平均分为两组,研究组采取宫腔镜下子宫内膜电切术联合刮宫术治疗,对照组单纯采取宫腔镜下子宫内膜电切术治疗。观察两组患者术中出血量、手术时间、一年内子宫息肉的复发率及子宫异常出血的发病率。结果:两组术中出血量、手术时间及子宫息肉复发率比较差异无统计学意义(P0.05)。研究组子宫异常出血发病率低于对照组,差异有统计学意义(P0.05)。结论:宫腔镜下电切术联合刮宫术对于治疗EMP的效果更佳,可降低子宫异常出血发病率,安全有效,值得临床进一步推广。     

Mesenchymal stem cells as anti-inflammatories: Implications for treatment of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a lethal X-linked musculodegenerative condition consisting of an underlying genetic defect whose manifestation is augmented by inflammatory mechanisms. Previous treatment approaches using gene replacement, exon-skipping or allogeneic cell therapy have been relatively unsuccessful. The only intervention to mediate improvement in survival, albeit minor, is glucocorticoid treatment. Given this modality appears to function via suppression of underlying inflammation; we focus this review on the inflammatory response as a target for mesenchymal stem cell (MSC) therapy. In contrast to other cell based therapies attempted in DMD, MSC have the advantages of (a) ability to fuse with and genetically complement dystrophic muscle; (b) possess anti-inflammatory activities; and (c) produce trophic factors that may augment activity of endogenous repair cells. We conclude by describing one practical scenario of stem cell therapy for DMD.     

Prevalence, risk factors for and impact of subclinical endometritis in repeat breeder dairy cows

The aim of this study was to determine the prevalence and risk factors for subclinical endometritis (SE) and its effects on fertility in repeat breeder dairy cows. Dairy cows of parity 1 to 5 that were artificially inseminated (AI) 3 or more times (selected cows were artificially inseminated an average of 3.9 times) were examined at 190 ± 40 days in milk, and clinically normal cows (n = 77) were selected based on the absence of abnormal discharges on external inspection and the absence of abnormal findings on transrectal palpation and ultrasonographic examination. Endometrial samples were collected from the uterus by using the lavage technique in the luteal phase of the estrus cycle. Collected samples were centrifuged and a drop of sediment was streaked on to a clean microscopic slide and stained with Giemsa. The percentage of polymorphonuclear cells (neutrophils) was counted for each specimen. The analysed data showed that the average amount of neutrophils was 3.1% (0-9) in the selected cows. Abnormal calving (dystocia, twin births, and abortion), retained placenta, and postpartum uterine infections were associated with an increase in prevalence of SE. Subsequently, SE was significantly associated with a decrease in conception rate in the next AI. Conception rate in the next AI was 5% for cows (n = 38) with SE (≥ 3% neutrophil), and 47% for cows (n = 34) without SE (< 3% neutrophil) (P = 0.001). The prevalence of cytologically diagnosed SE (≥ 3% neutrophil) was 52.7% (n = 38). In conclusion, abnormal calving, retained placenta, and postpartum uterine infections may be associated with an increase in prevalence of SE and subsequently, SE may decrease reproductive performance and increase the incidence of repeat breeder syndrome.     

The dystonia gene THAP1 controls DNA double-strand break repair choice

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