原因不明性不孕患者子宫内膜基质金属蛋白酶-9 mRNA的表达及其性激素调节

目的　检测基质金属蛋白酶 9(MMP 9)及其抑制物 1 (TIMP 1 )mRNA在原因不明性不孕患者黄体中期子宫内膜中的表达 ,及与性激素的相关性。方法　采用原位杂交、逆转录聚合酶链反应(RT PCR)技术 ,对 38例原因不明不孕患者 (研究组 )和 2 0例正常生育期妇女志愿者或男方因素不孕患者 (对组照 )的黄体中期子宫内膜行MMP 9、TIMP 1mRNA检测 ,同期放射免疫法测定雌二醇 (E2 )、孕酮 (P)水平。结果　子宫内膜腺上皮、间质细胞胞浆、胞核均有MMP 9、TIMP 1mRNA的表达 ,研究组较对照组表达少 ,研究组黄体中期子宫内膜MMP 9mRNA表达水平为 0 .42± 0 .1 9,显著低于对照组的 0 .57± 0 .1 9(P <0 .0 5) ;研究组TIMP 1mRNA表达水平为 0 .59± 0 .1 9,显著低于对照组的 0 81± 0 .2 0 (P <0 .0 1 )。研究组黄体中期血清P水平为 (34± 1 5)nmol/L ,显著低于对照组的 (53± 1 7)nmol/L(P<0 .0 1 ) ,而血清E2 水平与对照组比较 ,差异无显著性 (P >0 .0 5)。对照组P水平与MMP 9mRNA表达呈正相关 (r=0 .72 2 ,P <0 .0 1 ) ,而研究组无相关性 (P >0 .0 5) ;两组P水平与TIMP 1mRNA ,E2 与MMP 9、TIMP 1mRNA均无相关性 (P >0 .0 5)。结论　原因不明不孕患者黄体中期P水平影响MMP 9、TIMP 1mRNA的表达并致活性下降 ,可能与不孕     

Expression of cyclooxygenase-2 in association with clinicopathological prognostic factors and molecular markers in epithelial ovarian cancer

OBJECTIVES: This study examines whether expression of COX-2 is associated with clinicopathological features and other molecular markers of ovarian cancer. METHODS: Sixty-four paraffin-embedded tissue specimens were obtained from patients with ovarian cancer who received cytoreductive surgery and combination chemotherapy. Tissue specimens were subjected to immunohistochemical analysis using antibodies to COX-2, p53, and VEGF. RESULTS: Increased COX-2 expression significantly correlated with histologic type (mucinous 5.6% vs. non-mucinous 65.2%, P<0.001). COX-2 expression was also significantly associated with stage, tumor grade, residual disease status, and presence of ascites. COX-2 expression correlated positively with expression of p53 (P=0.006) and VEGF (P=0.025). Although survival was lower in patients with high COX-2 expression than in those without high COX-2 expression (P<0.001), only tumor grade and stage were independent prognostic indicators. In patients with non-mucinous cancer, COX-2 expression correlated with stage (P<0.001) and presence of ascites (P=0.033). CONCLUSIONS: Our results suggest that expression of COX-2 in ovarian cancers is specific to histologic type of tumor and is associated with poor clinicopathologic prognostic factors. Expression of COX-2 also correlates well with expression of p53 and VEGF.     

Acute and chronic presentation of ectopic pregnancy may be two clinical entities

OBJECTIVE: The diagnosis of ectopic pregnancy (EP) is often confirmed at presentation (acute), but often requires serial beta-hCG levels to confirm the diagnosis (chronic). The purpose of this study is to analyze whether these clinical presentations represent a spectrum of disease. DESIGN: The retrospective cohort study of 452 patients diagnosed with EP at the University of Pennsylvania in the years 1990-1999. SETTING: University of Pennsylvania, Philadelphia, Pennsylvania. PATIENT(S): Four hundred fifty-two patients diagnosed with EP. Patients diagnosed with EP were divided into two groups according to the time of diagnosis. MAIN OUTCOME MEASURE(S): A total of 37 parameters were examined including historic and demographic factors, findings at presentation, and treatment and outcome variables. RESULT(S): The two groups were similar in terms of historic EP risk factors. Multivariable analysis demonstrates that women with a chronic presentation were less likely to have received fertility medications (odds ratio [OR] 0.23; 95% confidence interval [CI] 0.06-0.84), less likely to present with pain (OR 0.29; 95% CI 0.12-0.71), have a lower beta-hCG level at presentation (9,849 mIU/mL +/- 16,726 vs. 1,787 mIU/mL +/- 4,717), lower chance of rupture (OR 0.19; 95% CI 0.05-0.73), and less frequently have blood type 0. CONCLUSION(S): Women diagnosed with ectopic pregnancy can be categorized into two groups, those with an acute presentation and those with a chronic presentation. Differences in risk factors, presentation, and outcome may reflect differences in trophoblast viability or invasive potential.     

Hepatitis D: advances and challenges

Hepatitis D virus (HDV) infection causes the most severe form of viral hepatitis with rapid progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Although discovered > 40 years ago, little attention has been paid to this pathogen from both scientific and public communities. However, effectively combating hepatitis D requires advanced scientific knowledge and joint efforts from multi-stakeholders. In this review, we emphasized the recent advances in HDV virology, epid...     

Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential

Long considered merely a trophic and mechanical support to neurons, astrocytes have progressively taken the center stage as their ability to react to acute and chronic neurodegenerative situations became increasingly clear. Reactive astrogliosis starts when trigger molecules produced at the injury site drive astrocytes to leave their quiescent state and become activated. Distinctive morphological and biochemical features characterize this process (cell hypertrophy, upregulation of intermediate filaments, and increased cell proliferation). Moreover, reactive astrocytes migrate towards the injured area to constitute the glial scar, and release factors mediating the tissue inflammatory response and remodeling after lesion. A novel view of astrogliosis derives from the finding that subsets of reactive astrocytes can recapitulate stem cell/progenitor features after damage, fostering the concept of astroglia as a promising target for reparative therapies. But which biochemical/signaling pathways modulate astrogliosis with respect to both the time after injury and the type of damage? Are reactive astrocytes overall beneficial or detrimental for neuroprotection and tissue regeneration? This debate has been animating this research field for several years now, and an integrated view on the results obtained and the possible future perspectives is needed. With this Commentary article we have attempted to answer the above-mentioned questions by reviewing the current knowledge on the molecular mechanisms controlling and sustaining the reaction of astroglia to injury and its stem cell-like properties. Moreover, the cellular/molecular mechanisms supporting the detrimental or beneficial features of astrogliosis have been scrutinized to gain insights on possible pharmacological approaches to enhance astrocyte neuroprotective activities.     

高选择性环氧化酶—2抑制剂的进展与评价

目的 :介绍高选择性环氧化酶 - 2抑制剂———昔布类药物进展 ,并评价其临床疗效 ,以供临床参考。方法 :查阅国内、外近期相关文献进行分析、评价。结果与结论 :昔布类高选择性环氧化酶 - 2抑制剂进展十分迅速 ,对环氧化酶 - 2的选择性高 ,在治疗骨关节炎和类风湿性关节炎、关节痛、术后疼痛和肿瘤上展现了良好的治疗前景     

左旋千金藤立定对溴隐亭诱导的哺乳期大鼠促乳素水平低下的拮抗作用

目的:研究左旋千金藤立定(SPD)对溴隐亭(Bro)诱导的促乳素(PRL)水平低下的对抗作用。方法:哺乳期母鼠sc Bro 0.5mg·kg~(-1)·d~(-1),PRL显著降低,乳腺组织发育不良,而且仔鼠体重增长缓慢。用放免法测定母鼠PRL,检查乳腺发育状况,评价SPD的对抗作用。结果:SPD30及100mg·kg~(-1)·d~(-1)ip,能够显著对抗Bro诱导的母鼠PRL降低,分娩后d15PRL为11±4及23±6μg·L~(-1)(生理盐水为7±2),而且乳腺组织发育正常,仔鼠在出生后d11—15内迅速生长发育。结论:SPD能阻断大鼠脑垂体前叶的D_2受体,是一个D_2受体的拮抗剂。     

B超在孕早期的临床诊断价值分析

目的探讨分析B超在孕早期的临床诊断价值。方法回顾性分析近年来649例临床诊断为早孕的妇女行腹部B超检查,必要者给予经阴道超声检查,对B超在孕早期的诊断价值进行分析。结果正常妊娠593例(91.4%),异常妊娠61例(9.4%),其中流血47例(7.2%),异位妊娠4例(0.6%),胚胎停育10例(1.5%)。未孕2例(0.3%),B超诊断的符合率为99.1%(643/649)。结论早孕期B超检查对于早期观察胚胎的结构有着不可替代的诊断价值,B超监控对早期发现胚胎问题,异常妊娠、有着极高的诊断价值,对提高出生人口素质及减少产妇不必要的经济、精神负担都有着重要意义。     

巨噬细胞在心肌梗死治疗中的研究现状

巨噬细胞在心肌梗死损伤中发挥了“双刃”作用。近年来研究表明,心肌细胞浸润的巨噬细胞在不同因子刺激下极化成功能不同的亚群,即M1和M2。M1型巨噬细胞主要发挥促炎作用,加重心肌损伤,而M2型巨噬细胞则主要抑制受损组织炎症发生,同时能促进新生血管的生成。因此M2型巨噬细胞在心肌损伤中发挥的正面作用越来越受到关注。本文对近年来国内外关于M2型巨噬细胞在心肌组织中发挥的作用,及其重要调控机制等进行了综述,并对M2型极化在促心肌微血管治疗中的研究现状及其物质基础进行了概述。     

Dual leucine zipper kinase (MAP3K12) modulators: a patent review (2010–2015)

Introduction: The dual leucine zipper kinase (DLK, MAP3K12) is essential for neuronal development and has been shown to mediate axon regeneration. On the other hand, DLK is involved in the pathogenesis of neurodegenerative disease and diabetes mellitus. Several patents have been published claiming to modulate or inhibit DLK by various approaches including ATP competitive inhibitors. In addition, two publications describe SAR of highly selective DLK inhibitors with efficacy in distinct mouse models of neurodegeneration.

Areas covered: This review summarized patents claiming to modulate DLK activity published between 2010 and 2015. Peer-reviewed publications related to the patents and additional peer-reviewed publications are included. This article describes 18 patents from three pharmaceutical companies and three academic research groups.

Expert opinion: Several methods are proposed to modulate DLK activity, some of them very experimental and not suitable for easy application in patients. ATP competitive kinase inhibitors exert high affinity, but for the majority, no information about their selectivity is available. To date, two inhibitors have been tested in mice. Given the controversial findings that DLK is required for neurodegeneration and for axon regeneration, more research is needed to further elucidate the regulation and the function of this kinase in diverse organs/tissues and under physiological and pathological conditions.