anogenital

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  • 文章类型: Journal Article
    背景:宫颈癌和宫颈上皮内瘤变(CIN)均与不同肛门生殖器部位的人乳头瘤病毒(HPV)感染有关,但这些部位的高危(HR)HPV的感染特征及其与宫颈病变的关系尚未得到很好的表征.鉴于宫颈HPV16/18检测在筛查高级别CIN(CIN2+)患者中的局限性,需要研究非16/18HR-HPV亚型是否有可能作为改善CIN2+筛查的额外指标.
    方法:外阴15例HR-HPV感染,肛门,阴道,分析了499名中国女性的子宫颈,发现与CIN病变相关的HR-HPV亚型。
    结果:除了众所周知的宫颈癌相关HPV16、52和58之外,HPV51、53和56也被鉴定为高频率检测的亚型,并且始终存在于所研究的肛门生殖器部位。优先在多重感染模式中。HPV16、52、58、56和53是CIN2+患者的前5种流行亚型。此外,我们发现宫颈HPV33/35/52/53/56/58与HPV16/18联合检测可能会提高CIN2+筛查效果.
    结论:这项研究为基于不同亚型组合的HR-HPV筛查策略提供了新的见解,可用于临床风险分层。
    BACKGROUND: Both cervical cancer and cervical intraepithelial neoplasia (CIN) are associated with human papillomavirus (HPV) infection at different anogenital sites, but the infection features of high-risk (HR) HPVs at these sites and their association with cervical lesions have not been well characterized. Given the limitation of cervical HPV 16/18 test in screening patients with high-grade CIN (CIN 2+), studies on whether non-16/18 HR-HPV subtype(s) have potential as additional indicator(s) to improve CIN 2+ screening are needed.
    METHODS: The infection of 15 HR-HPVs in vulva, anus, vagina, and cervix of 499 Chinese women was analyzed, and CIN lesion-associated HR-HPV subtypes were revealed.
    RESULTS: In addition to the well-known cervical-cancer-associated HPV 16, 52, and 58, HPV 51, 53, and 56 were also identified as high-frequency detected subtypes prevalently and consistently present at the anogenital sites studied, preferentially in multi-infection patterns. HPV 16, 52, 58, 56, and 53 were the top five prevalent subtypes in patients with CIN 2+. In addition, we found that cervical HPV 33/35/52/53/56/58 co-testing with HPV 16/18 might improve CIN 2+ screening performance.
    CONCLUSIONS: This study provided a new insight into HR-HPV screening strategy based on different subtype combinations, which might be used in risk stratification clinically.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    背景:大鼠肛门生殖器距离(AGD)的测量可追溯到至少1912年。近几十年来,人们对内分泌干扰化学物质的兴趣增加,并将AGD用作胎儿雄激素作用的生物标志物,这增加了该终点的研究数量。文献综述揭示了不同的地标,测量方法,以及调整体重差异的方法。AGD通常被报告为百分之一毫米,因此,在所有这些方面都值得精确。本文提出了啮齿动物AGD的测量和分析建议。
    方法:综述了提到或测量啮齿动物AGD的文献和监管指导文件。使用来自三个大鼠研究的可用在线数据评估了四种调整方法,每个大鼠研究具有两代后代。
    结果:研究表格显示,物种/种群和数据收集时间,但更重要的是解剖标志和测量方法产生了各种难以比较的结果。并非所有研究都针对测试物品对体重(以及因此大小)的影响进行了调整。四种调整方法相当可比。
    结论:建议如下。应使用显微镜方法测量晚期啮齿动物胎儿和出生后早期幼崽的AGD。生殖器结节的尾部边缘和肛门的颅部边缘是清晰且可识别的标志。最简单的调整是将单个AGD除以动物体重的立方根。这些建议将有助于确保数据的一致性和准确性。并促进跨实验室和化学类的有意义的比较。
    BACKGROUND: Measurement of rat anogenital distance (AGD) dates to at least 1912. Increased interest in endocrine disrupting chemicals and the use of AGD as a biomarker for fetal androgen effects have increased the number of studies with this endpoint in recent decades. A literature review revealed different landmarks, methods of measurement, and methods to adjust for body weight differences. AGD is often reported to hundredths of millimeters and as such, deserves precision in all these aspects. This paper presents recommendations for the measurement and analysis of rodent AGD.
    METHODS: Literature and regulatory guidance documents that mentioned or measured rodent AGD were reviewed. Four adjustment methods were evaluated using available online data from three rat studies each with two generations of offspring.
    RESULTS: Tabulation of studies reveals that species/stocks and time of data collection, but more importantly anatomical landmarks and methods of measurement have produced a variety of results which are difficult to compare. Not all studies have adjusted for test article effects on body weight (and thus size). The four adjustment methods were fairly comparable.
    CONCLUSIONS: Recommendations are as follows. A microscopic method should be used to measure AGD of late rodent fetuses and early postnatal pups. The caudal edge of the genital tubercle and the cranial edge of the anus are clear and identifiable landmarks. The simplest adjustment is to divide individual AGDs by the cube root of animals\' body weight. These recommendations will help ensure data consistency and accuracy, and facilitate meaningful comparisons across laboratories and chemical classes.
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  • 文章类型: Journal Article
    生殖器牛皮癣是一种慢性炎症性皮肤病,据报道,多达63%的牛皮癣患者皮肤其他部位。它对生活质量和性功能有深远的影响,而目前的严重程度评分往往忽略了这一点。尽管它的患病率和疾病负担,生殖器银屑病在很大程度上仍未得到充分报道和治疗。历史上,这是由于标准牛皮癣治疗应用于生殖器皮肤时不切实际且疗效数据有限.然而,最近有一些进展,目前正在开发和评估生殖器银屑病的几种新药。本临床综述旨在概述有关生殖器银屑病临床特征的现有证据。评估患者生活质量的可用管理选项和工具。这篇综述的主要收获强调生殖器牛皮癣是一种慢性和衰弱的疾病,其对患者生活质量的影响是独一无二的,需要采取敏感和细心的方法来满足他们的需求。
    Genital psoriasis is a chronic inflammatory skin condition that has been reported in up to 63% of patients with psoriasis on other parts of their skin. It has a profound impact on quality of life and sexual function which is often overlooked by current severity scores. Despite its prevalence and disease burden, genital psoriasis remains largely under-reported and under-treated. Historically, this was due to the impracticality and limited efficacy data of standard psoriasis treatments when applied to genital skin. However, there have been recent advancements with several new agents currently being developed and evaluated for genital psoriasis. This clinical review aims to provide an overview of the current evidence regarding the clinical features of genital psoriasis, available management options and tools for assessing patients\' quality of life. Key takeaways from this review emphasise the recognition of genital psoriasis as a chronic and debilitating condition, unique in its impact on patients\' quality of life, necessitating sensitive and attentive approaches to address their needs.
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  • 文章类型: Journal Article
    睾酮及其代谢物促进了有性经验的动物中男性典型的社会行为。代谢物雌二醇作用于末端纹状体(BNST)床核内的雌激素受体(ER),以促进社会性行为。虽然在幼稚的男性中循环睾酮不会增加,幼稚男性的BNST中表达芳香化酶的神经元是性别识别所必需的,这表明当地的雌二醇生产可能是原因。在本研究中,我们在与新型动物相遇后24小时,检查了性幼稚雄性大鼠脑内ERα-免疫反应性(ir)细胞数量。不出所料,男性比男性更多地调查女性。此外,与遇到新的男性或非社会对照的男性相比,遇到女性的男性在前BNST和后BNST中的ER﹤-ir细胞较少。AVPV内没有变化,MPN,或MeA。后部BNST内ERα-ir细胞数量的减少仅发生在遇到发情期女性的男性中,而前BNST的减少仅发生在遇到非发情期女性的男性中。此外,肛门生殖器检查与后部BNST中的较少的ERā-ir细胞相关,而笼嗅探与前BNST中ERα-ir细胞的数量相关。在相遇45分钟或24小时后,血清睾酮没有差异,提示ER的变化是由于雌二醇水平的局部变化。我们的结果扩展了先前关于雌二醇在BNST亚区中在幼稚雄性大鼠社会性行为中的作用的研究。
    Testosterone and its metabolites facilitate male-typical social behaviors in sexually experienced animals. The metabolite estradiol acts on estrogen receptors (ERs) within the bed nucleus of the stria terminalis (BNST) to facilitate socio-sexual behaviors. While circulating testosterone does not increase in naïve males, aromatase-expressing neurons within the BNST of naïve males are necessary for sex recognition, suggesting that local estradiol production may be responsible. In the present study, we examined ERɑ-immunoreactive (ir) cell number within the brain of sexually naïve male rats 24 h after an encounter with a novel animal. As expected, males investigated females more than males. Additionally, males that encountered females had fewer ERɑ-ir cells within both anterior and posterior BNST compared to those who encountered a novel male or a non-social control. There were no changes within the AVPV, MPN, or MeA. The decrease in ERɑ-ir cell number within the posterior BNST only occurred in males that encountered estrus females whereas the decrease in the anterior BNST occurred only in males that encountered non-estrus females. Additionally, anogenital investigations were correlated with fewer ERɑ-ir cells in the posterior BNST, while cage sniffing correlated with the number ERɑ-ir cells in the anterior BNST. There were no differences in serum testosterone 45 min or 24 h after the encounter, suggesting changes in ERɑ were due to local changes in estradiol levels. Our results expand upon previous research regarding the role of estradiol within the subregions of the BNST in naïve male rat socio-sexual behavior.
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  • 文章类型: Journal Article
    背景:疣状黄色瘤(VX)并不常见,口腔粘膜良性上皮病变。虽然这个实体也可以口外呈现,包括皮肤和肛门生殖器区域,口外部位组织学特征的变化尚不明确.评估了口腔与口外VX的人口统计学和形态学特征的差异,以帮助促进该病变的准确诊断和治疗。
    方法:获得IRB批准后,从2000年至2022年的机构档案中回顾性收集了110例确诊的VX病例。患者年龄,性别,可用的病史,病变外观,并获得每个病例的持续时间。
    结果:中位年龄为55岁(13-86岁),男女比例为1.2:1。最常见的口腔部位,按降序排列,是腭(n=24,22%),颊粘膜(n=18,16%),牙龈(n=16,15%),和舌头(n=13,12%)。口外部位占所有病变的9%,包括阴囊(9),外阴(2),脸颊(1),手腕(1),臀区(1),腹壁(1)。所有病变的中值大小为6.0mm,与口腔病变相比,口外病变的大小比口腔病变大6.7mm(B±SE:6.7±2.5cm,p=0.01)。病变最常见的是粉红色或白色,通常被描述为乳头状,有花梗,疣状,和/或外生。微观上,楔形角化不全的存在,上皮/表皮上方的角蛋白突起,和相关的炎症在口腔和口外病变之间存在显着差异。在口外病变中,明显的楔形角化不全(p=0.04)和上皮/表皮上方的角蛋白突起(p<0.001)更为普遍。角蛋白突起与上皮异型性之间没有显着联系(p=0.44)。
    结论:熟悉VX的广泛形态光谱,包括楔形角化不全的存在和程度,上皮/表皮上方的角蛋白突起,和相关的潜在炎症,将有助于在不寻常的地方诊断它。
    BACKGROUND: Verruciform xanthoma (VX) is an uncommon, benign epithelial lesion of the oral mucosa. While this entity can also present extraorally, including on the skin and in anogenital areas, the variation in its histologic features in extraoral sites is not yet well defined. Differences in the demographics and morphologic features of oral versus extraoral VX were assessed to help facilitate the accurate diagnosis and management of this lesion.
    METHODS: After obtaining IRB approval, 110 cases of diagnosed VX were retrospectively collected from our institutional archives spanning from 2000 to 2022. Patient age, gender, available medical history, lesion appearance, and duration were obtained for each case.
    RESULTS: The median age was 55 years (range 13-86) with a male-to-female ratio of 1.2:1. The most common oral sites, in descending order, were the palate (n = 24, 22%), buccal mucosa (n = 18, 16%), gingiva (n = 16, 15%), and tongue (n = 13, 12%). Extraoral sites comprised 9% of all lesions, including the scrotum (9), vulva (2), cheek (1), wrist (1), gluteal region (1), and abdominal wall (1). The median size for all lesions was 6.0 mm, and extraoral lesions were associated with a 6.7 mm larger size compared to oral lesions (B ± SE: 6.7 ± 2.5 cm, p = 0.01). The lesions were most frequently pink or white in color and often described as papillary, pedunculated, verrucous, and/or exophytic. Microscopically, the presence of wedge-shaped parakeratosis, keratin projections above the epithelium/epidermis, and associated inflammation significantly differed between oral and extraoral lesions. Prominent wedge-shaped parakeratosis (p = 0.04) and keratin projections above the epithelium/epidermis (p < 0.001) were more prevalent in extraoral lesions. There was no significant link between keratin projections and epithelial atypia (p = 0.44).
    CONCLUSIONS: Familiarity with the broad morphological spectrum of VX, including the presence and degree of wedge-shaped parakeratosis, keratin projections above the epithelium/epidermis, and associated underlying inflammation, will be helpful in diagnosing it in unusual locations.
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  • 文章类型: Meta-Analysis
    背景:人乳头瘤病毒相关的肛门生殖器癌症是一个巨大的全球负担。血液中生物标志物(循环肿瘤DNA;ctDNA或循环HPVDNA;cHPVDNA)的检测称为“液体活检”,可能支持早期诊断和监测受影响的个体。
    方法:系统综述,包括文献中关于利用ctDNA和cHPVDNA作为诊断的研究的荟萃分析,预测性,按照PRISMA标准进行HPV相关肛门生殖器癌的生物标志物监测试验.
    结果:共有31项研究符合系统评价的条件;20项在宫颈癌中使用cHPVDNA;7项在宫颈癌中使用ctDNA;5项在肛门癌中使用cHPVDNA;没有关于外阴的合格研究,有阴道癌或阴茎癌。荟萃分析确定cHPVDNA的低敏感性(0.36)和高特异性(0.96)可诊断宫颈癌。相对而言,cHPVDNA对肛门癌的诊断具有较高的敏感性(0.95)和特异性(1.0)。宫颈癌中cHPVDNA和/或ctDNA是与不良临床结局相关的预后标志物。此外,在肛门癌中,cHPVDNA的治疗后检测对于预测治疗反应或无进展生存期具有重要意义.
    结论:ctDNA和cHPVDNA是检测肛门生殖器疾病的有希望的诊断和预后生物标志物。分子工具的进化和完善可能会进一步提高性能。此外,在外阴的研究比较缺乏,阴道和阴茎背景值得进一步探索和研究。
    Human papillomavirus associated anogenital cancers are a significant global burden. The detection of biomarkers (circulating tumour DNA; ctDNA or circulating HPV DNA; cHPV DNA) in blood referred to as \"liquid biopsy\" may support the early diagnosis and monitoring of affected individuals.
    A systematic review, including meta-analysis of studies available in the literature on the utilization of ctDNA and cHPV DNA as diagnostic, predictive, and monitoring biomarker tests of HPV associated anogenital cancers was performed following the criteria of PRISMA.
    A total of 31 studies were eligible for systematic review; 20 used cHPV DNA in cervical cancers; 7 used ctDNA in cervical cancer; 5 used cHPV DNA in anal cancer; no eligible studies on vulva, vaginal or penile cancer were available. The meta-analysis identified low sensitivity (0.36) and high specificity (0.96) of cHPV DNA as diagnostic for cervical cancer. Comparatively, there was high sensitivity (0.95) and specificity (1.0) of cHPV DNA for the diagnosis of anal cancer. cHPV DNA and/or ctDNA in cervical cancer were prognostic markers associated with poor clinical outcomes. Additionally, in anal cancer the post treatment detection of cHPV DNA was informative in the prediction of treatment response or progression-free survival.
    ctDNA and cHPV DNA are promising diagnostic and prognostic biomarkers for the detection of anogenital disease. Evolution and refinement of molecular tools is likely to improve performance further. Additionally the comparative absence of studies in the vulval, vaginal and penile context warrants further exploration and research.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    背景:患有持续低度炎症的疾病与抑郁和焦虑并存,并与社交退缩有关。基底外侧杏仁核(BLA)对于情感和社会行为至关重要,并且对炎性挑战敏感。大全身剂量的脂多糖(LPS)引发外周炎症,增加BLA神经元活动,扰乱啮齿动物的社会和情感措施。然而,行为研究中常用的LPS剂量足以引起疾病综合征,这可以混淆杏仁核相关行为的解释。
    目的:本研究的目的是在成年雄性大鼠中找到能引发轻度外周炎症但未观察到疾病综合征的LPS剂量。测试持续轻度炎症对BLA和社会行为的影响。要做到这一点,我们给予单剂量的LPS(0-100μg/kg,腹膜内)和测量的开放场行为,或重复的LPS(5μg/kg,连续3天),测量BLA神经元放电,社交互动,和高架加上迷宫行为。
    结果:反复低剂量LPS降低了BLA神经元的放电率,但增加了活跃的BLA神经元的总数。反复的低剂量LPS还导致社交发作期间的早期脱离接触和较少的肛门生殖器调查,以及在社交过程中与社交熟悉度降低相关的增强社交谨慎的整体模式。
    结论:这些结果为长期轻度炎症引起的社交互动和杏仁核活动的平行变化提供了证据。炎症的这种作用可能导致与共病抑郁症和慢性炎症相关的社会症状。
    BACKGROUND: Conditions with sustained low-grade inflammation have high comorbidity with depression and anxiety and are associated with social withdrawal. The basolateral amygdala (BLA) is critical for affective and social behaviors and is sensitive to inflammatory challenges. Large systemic doses of lipopolysaccharide (LPS) initiate peripheral inflammation, increase BLA neuronal activity, and disrupt social and affective measures in rodents. However, LPS doses commonly used in behavioral studies are high enough to evoke sickness syndrome, which can confound interpretation of amygdala-associated behaviors.
    OBJECTIVE: The objectives of this study were to find a LPS dose that triggers mild peripheral inflammation but not observable sickness syndrome in adult male rats, to test the effects of sustained mild inflammation on BLA and social behaviors. To accomplish this, we administered single doses of LPS (0-100 μg/kg, intraperitoneally) and measured open field behavior, or repeated LPS (5 μg/kg, 3 consecutive days), and measured BLA neuronal firing, social interaction, and elevated plus maze behavior.
    RESULTS: Repeated low-dose LPS decreased BLA neuron firing rate but increased the total number of active BLA neurons. Repeated low-dose LPS also caused early disengagement during social bouts and less anogenital investigation and an overall pattern of heightened social caution associated with reduced gain of social familiarity over the course of a social session.
    CONCLUSIONS: These results provide evidence for parallel shifts in social interaction and amygdala activity caused by prolonged mild inflammation. This effect of inflammation may contribute to social symptoms associated with comorbid depression and chronic inflammatory conditions.
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