围绝经期及绝经后女性性功能障碍状况及与更年期症状的关系分析

目的 调查围绝经期及绝经后女性性功能障碍状况,分析更年期症状对女性性功能障碍（female sexual dysfunction,FSD）的影响。方法 选取2019年6月至2019年10月在首都医科大学附属北京妇产医院内分泌科就诊的40岁以上女性180例进行问卷调查,根据生殖衰老分期研讨会（Stages of Reproductive Aging Workshop,STRAW+10）标准将研究对象分为4组：绝经过渡早期（A组）、绝经过渡晚期（B组）、绝经后期早期（C组）、绝经后期晚期（D组）。应用改良Kupperman评分表（Modified Kupperman Index,KMI）评价女性更年期症状;女性性功能指数（Female Sexual Function Index,FSFI）量表评价女性性功能障碍。结果 随着生殖衰老分期的提高,4组患者的年龄中位数逐渐增大,从45.5岁提高到57.0岁;与伴侣共同生活时间的年限中位数从20年增加到23.5年,性生活的间隔时间中位数从7 d增加到15 d;KMI中位数从9.5分提高到15分（P<0.05）。随着生殖衰老分期的升高,FSD和性欲障碍、性唤起障碍、阴道湿润障碍、性高潮障碍、性满意度障碍和性交痛的患病率均明显升高（P<0.05）。FSD和性欲障碍、性唤起障碍、阴道湿润障碍、性高潮障碍、性满意度障碍和性交痛的患病率随更年期症状的严重程度提高而升高（P<0.05）。结论 随着女性生殖衰老分期的提高,FSD的患病率明显升高。出现更年期症状以及其严重程度是40岁以上女性发生FSD的重要影响因素,应积极治疗更年期症状以提高女性的生活质量。     

Nuclear factor-κB binding motifs specify Toll-like receptor-induced gene repression through an inducible repressosome

Sustained Toll-like receptor (TLR) stimulation continuously activates antimicrobial genes but paradoxically represses inflammatory genes. This phenomenon, termed TLR tolerance, is essential for preventing fatal inflammatory conditions such as sepsis, but its underlying mechanisms are unclear. We report here that NF-κB binding nucleic acids of gene promoters are tolerogenic motifs, which selectively recruit an NcoR-Hdac3-deacetylated-p50 repressosome to inflammatory genes. Genome-wide analyses of TLR4-induced genes revealed that NF-κB motifs were the only regulatory elements significantly enriched in tolerizable genes. Mutating the NF-κB motifs of tolerizable genes converted them into nontolerizable ones, whereas inserting NF-κB binding motifs into nontolerizable genes conferred the tolerance. Although NF-κB p50 was essential for assembling the repressosome, genetic disruption of the NcoR-Hdac3 interaction alone was sufficient to completely abolish TLR4 tolerance and to render mice vulnerable to sepsis. Thus, the specificity of TLR tolerance is dictated by evolutionally conserved nucleic acid motifs that bound by NF-κB and the NcoR repressosome.     

Association analysis of genetic variants in microRNA networks and gastric cancer risk in a Chinese Han population

Purpose

To investigate associations between genetic variants involved in microRNA networks (microRNA biogenesis, microRNA and microRNA binding sites) and risk of gastric cancer.

Methods

We genotyped 19 SNPs of the microRNA-related genes in a case–control study of 311 gastric cancers and 425 cancer-free controls in a Chinese Han population.

Results

We found that two of the SNPs were significantly associated with gastric cancer. Inhibitory effect of minor allele T of rs2071504 SNP within the exon of POLR2A gene was significantly associated with gastric carcinogenesis (p?=?0.033, aOR?=?0.742, 95%CI?=?0.564–0.977) and the SNP rs895819 in the miR-27a gene with the minor allele C presented significantly reduced risk to gastric cancer (p?=?0.037, aOR?=?0.771, 95%CI?=?0.604–0.985). Further stratified analysis with regard to clinical pathological parameters of the patients indicated that the SNP rs2071504 was associated with lymph node metastasis (p?=?0.021, aOR?=?0.529, 95%CI?=?0.307–0.910) and TMN stage (p?=?0.021, aOR?=?0.532, 95%CI?=?0.311–0.908), respectively.

Conclusions

Our findings provided evidence that the SNP rs2071504 in the exon of POLR2A gene would not only confer a decreased risk of gastric cancer, but also influence lymph node metastasis and TMN stage of gastric cancer in the Chinese population.     

Breast cancer risk during hormone therapy: experimental versus clinical data

Evidence is increasing suggesting that adding progestogens to estrogens can increase the risk of breast cancer. However, our experimental data as a result of scientific collaboration between university of Tuebingen, Germany, and university of Beijing, China, comparing all available progestogens used in hormone therapy and hormonal contraception present high evidence that there may be differences regarding breast cancer risk. Especially of concern may be to differentiate between primary and secondary risk i.e. between the effect of on benign and malignant breast epithelial cells suggesting differences in primary risk and risk in patients after breast cancer. Of importance also is that in contrast to natural progesterone the apocrine impact of stromal growth factors and also certain cell components of breast epithelial cells can strongly increase proliferation rates of some (but not all. synthetic progestogens which can lead to clinical cancer before (in contrast to estrogen-only therapy. carcinoprotective mechanisms can work. Regarding clinical data, epidemiological studies and especially the Women's Health Initiative, so far the only prospective placebo-controlled study, demonstrate an increased risk under combined estrogen/progestogen-, but not under estrogen-only therapy. However, up to now the clinical studies cannot discriminate between the various progestogens mostly due to too small patient numbers in the subgroups, and in most studies either medroxyprogesterone acetate or norethisterone have been used. However, there is evidence that the natural progesterone and dydrogesterone, possibly also the transdermal usage of synthetic progestogens, may have less risks, but this must be proven in further clinical trials.     

An improved method for the isolation and culture of rat epidermal stem cells

The management of burns and injuries using novel treatment strategies involving epidermal stem cells (ESC) requires a better understanding of the biology of these cells, in particular, their isolation and the maintenance of their unique characteristics in culture. The purpose of this study was to describe an improved method for isolating putative ESC from fetal rat skin and to maintain them long term in culture. Single ESC suspensions were obtained from fetal rat skin by enzyme digestion containing 0.5% neutral protease. The target cells were harvested by rapid adherence on type IV collagen plates and were cultured in complex DMEM. After primary isolation, cells were continuously cultured in K-serum free medium. After reaching 70-80% confluence, the cells were digested with 0.25% trypsin at 37°C for 5-10 minutes, and passaged at a ratio of 1:2. The cultured ESC showed good growth, resulting in cell viability of over 98%. Four days later, clones containing 100-200 cells were detected, showing cobblestone-like characteristics. The rapidly adherent cells were positive for keratin 15, 19 and P63. Eighty three percent of cells expressed β1 integrin. The growth-curve showed that the rapidly adherent cells were in the exponential growth phase. The protocol described in this paper provides a simplified and effective method to isolate and maintain long-term culture of epidermal stem cells from fetal rat skin. This method should be valuable for isolating and studying ESC from various transgenic rat lines that are currently available.     

LED固化灯光照强度对光固化复合树脂聚合收缩的影响

目的采用数字图像相关法动态研究LED光固化灯不同光照强度对光固化复合树脂聚合收缩的影响。方法收集12颗大小接近的新鲜离体磨牙,随机分为3组,制备大小为2.0 mm×2.0 mm×2.0mm的邻(?)面洞形,洞面酸蚀冲洗后涂粘接剂光照10 s,充填3M Z350纳米复合树脂,邻面快速制造散斑,LED固化灯垂直(?)面光照40s,3组光照强度分别为300 mW/cm~2、500 mW/cm~2和800 mW/cm~2,数码相机同步实时采集光照过程中试件表面散斑的变化序列图像,用数字图像相关法计算获得各序列图上逐个像素点水平方向(x)和垂直方向(y)位移,统计线性收缩率,描绘各像素点的时域变化曲线,并用SPSS 12.01统计软件包进行方差分析和配对t检验。结果 3种光照强度下树脂x方向线收缩率分别为0.081%～0.486%、0.004%～0.316%和0.063%～0.560%,y方向线收缩率分别为0.088%～0.981%、0.003%～0.77%和0.157%～1.252%,3组之间差异有统计学意义(P<0.05);3组第20 s树脂游离面收缩x方向位移差异无统计学意义,y方向位移差异有统计学意义。结论 LED光固化灯500 mW/cm~2光照时引起的树脂聚合收缩最小。     

大学生口腔保健意识和饮食习惯的调查研究

目的了解在校大学生的口腔保健意识和饮食习惯,为完善口腔健康教育提供原始数据,探讨更优化的教育模式。方法采用分层抽样的方法,对四川大学1 500名大学生以问卷调查的形式对其口腔保健意识和饮食习惯进行调查。结果大学生主要为保持口气清新而刷牙,甜食食用频率主要为每周1～2次,数量集中在100～400 g,女生食用甜食的频率显著高于男生,而男生饮用饮料的频率和量更高,食用甜食后多数学生不做清洁措施,大多数学生在牙疼或变色时不会及时就诊,仅当疼痛难忍时才就医。结论大学生的口腔保健行为缺乏,食用甜食频率数量较高,就诊意识淡薄,学校等机构应该加强口腔保健知识的宣传和教育来提高大学生自我口腔保健意识。     

Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab

Pharmacological inhibition of VEGF-A has proven to be effective in inhibiting angiogenesis and vascular leak associated with cancers and various eye diseases. However, little information is currently available on the binding kinetics and relative biological activity of various VEGF inhibitors. Therefore, we have evaluated the binding kinetics of two anti-VEGF antibodies, ranibizumab and bevacizumab, and VEGF Trap (also known as aflibercept), a novel type of soluble decoy receptor, with substantially higher affinity than conventional soluble VEGF receptors. VEGF Trap bound to all isoforms of human VEGF-A tested with subpicomolar affinity. Ranibizumab and bevacizumab also bound human VEGF-A, but with markedly lower affinity. The association rate for VEGF Trap binding to VEGF-A was orders of magnitude faster than that measured for bevacizumab and ranibizumab. Similarly, in cell-based bioassays, VEGF Trap inhibited the activation of VEGFR1 and VEGFR2, as well as VEGF-A induced calcium mobilization and migration in human endothelial cells more potently than ranibizumab or bevacizumab. Only VEGF Trap bound human PlGF and VEGF-B, and inhibited VEGFR1 activation and HUVEC migration induced by PlGF. These data differentiate VEGF Trap from ranibizumab and bevacizumab in terms of its markedly higher affinity for VEGF-A, as well as its ability to bind VEGF-B and PlGF.