单中心卵巢畸胎瘤患者中合并抗N-甲基-D-天冬氨酸受体脑炎的比例调查及临床特征分析

目的 探究卵巢畸胎瘤患者中发生抗N-甲基-D-天冬氨酸受体（NMDAR）脑炎的比例,并将合并抗NMDAR脑炎的卵巢畸胎瘤患者与未合并抗NMDAR脑炎的卵巢畸胎瘤患者的临床特征进行总结对比。方法 收集卵巢畸胎瘤患者的临床资料,将其分为合并抗NMDAR脑炎组与未合并抗NMDAR脑炎组,对其临床特征进行对比分析。结果 共收集到168例卵巢畸胎瘤患者,其中14例（8.3%）合并抗NMDAR脑炎;合并抗NMDAR脑炎的卵巢畸胎瘤患者年龄低于未合并抗NMDAR脑炎的卵巢畸胎瘤患者[（23.8±5.5）岁 vs. （29.8±9.1）岁,P = 0.016]。合并抗NMDAR脑炎的卵巢畸胎瘤患者肿瘤标志物以癌抗原125及血清铁蛋白升高为主,而未合并抗NMDAR脑炎的卵巢畸胎瘤患者肿瘤标志物以糖类抗原199升高为主。合并抗NMDAR脑炎与未合并抗NMDAR脑炎的卵巢畸胎瘤患者的肿瘤组织均可含有神经组织。结论 卵巢畸胎瘤患者中发生抗NDMAR脑炎的比例不低,对于无明显症状的卵巢畸胎瘤患者,可考虑积极行手术治疗,以降低发生抗NMDAR脑炎的风险。     

Prognostic value of myocardial perfusion imaging after first-line coronary computed tomography angiography: A multi-center cohort study

PurposeFurther diagnostic testing may be required after a coronary computed tomography angiography (CTA) showing suspected coronary stenosis. Whether myocardial perfusion imaging (MPI) provides further prognostic information post-CTA remains debated. We evaluated the prognosis for patients completing CTA stratified for post-CTA diagnostic work-up using real-world data.MethodsWe identified all patients in our uptake area with angina symptoms undergoing first-time CTA over a 10-year period. Follow-up time was a median of 3.7 years [1.9–5.8]. The primary endpoint was a composite of myocardial infarction or death. The secondary endpoint was late revascularization.ResultsDuring the study period 53,351 patients underwent CTA. Of these, 24% were referred for further down-stream testing, 3,547 (7%) to MPI and 9,135 (17%) to invasive coronary angiography (ICA). The primary and secondary endpoints occurred in 2,026 (3.8%) and 954 (1.8%) patients. Patient-characteristic-adjusted hazard ratios for the primary and secondary endpoint using patients with a normal CTA as reference were 1.37 (1.21–1.55) and 2.50 (1.93–3.23) for patient treated medically, 1.68 (1.39–2.03) and 6.13 (4.58–8.21) for patients referred to MPI and 1.94 (1.69–2.23) and 9.18 (7.16–11.78) for patients referred for ICA, respectively. Adjusted analysis with stratification for disease severity at CTA showed similar hazard ratios for patients treated medically after CTA and patients referred for MPI and treated medically after the MPI.ConclusionIn patients completing coronary CTA, second-line MPI testing seems to identify patients at low risk of future events. MPI seems to have the potential to act as gatekeeper for ICA after coronary CTA.     

中西医结合治疗卵巢储备功能减退患者成功妊娠二例并文献复习

卵巢储备功能减退（diminished ovarian reserve，DOR）是卵巢因素所致不孕症的主要原因之一，西医临床治疗方法主要依赖于口服提高卵巢储备功能的药物、人工激素周期替代疗法和辅助生殖技术助孕，中医运用补肾健脾法治疗DOR具有不良反应少、疗效持久、治疗手段多样化等优势。报告2例在常规西医治疗基础上应用中医补肾健脾法综合治疗DOR患者成功妊娠的情况，强调个体化中西医结合治疗方案对于解决疑难病证的重要性，为临床应用中医药治疗DOR患者提供证据。     

CCNE1基因在卵巢高级别浆液性癌中的研究进展

细胞周期蛋白E1（Cyclin E1,CCNE1）基因扩增是卵巢高级别浆液性癌（high-grade serous ovarian carcinoma,HGSOC）最常见的拷贝数变异之一,扩增率为20%左右。CCNE1基因扩增不仅参与HGSOC的早期癌前病变,促进恶性肿瘤的发生、发展,还可引起细胞周期紊乱和染色体不稳定,从而增加HGSOC的铂类耐药性和复发率,最终导致患者的化疗效果不佳和预后较差。为改善CCNE1扩增的HGSOC患者的预后和生活质量,在暂时没有CCNE1扩增的HGSOC的靶向治疗药物的情况下,使用细胞周期蛋白依赖性激酶2（cyclin-dependent kinases 2,CDK2）小分子抑制剂或者多腺苷二磷酸核糖聚合酶[poly (ADP-ribose) polymerase,PARP]抑制剂与其他药物联合治疗,一定程度上能有效地抑制肿瘤细胞的增殖活性,促进肿瘤细胞死亡。因此,从CCNE1扩增对HGSOC的早期发病机制的影响和产生铂类耐药的角度上来说,CCNE1基因有望成为HGSOC的潜在治疗靶标和预后评价生物学指标,在改善患者的治疗和预后方面具有重要意义。     

紫杉醇脂质体与紫杉醇分别联合卡铂治疗卵巢癌疗效的Meta分析

摘 要 目的：系统评价紫杉醇脂质体与普通紫杉醇制剂分别联合卡铂治疗卵巢癌的有效性和安全性。方法: 计算机检索中国知识资源总库（CNKI）、中国生物医学文献数据库（CBM）、中文科技期刊数据库（VIP）、中国学术期刊数据库（万方数据）、PubMed、Cochrane Library、Embase 中紫杉醇脂质体联合卡铂与紫杉醇联合卡铂化疗治疗卵巢癌的临床随机对照试验,检索范围均为建库至2017年7月12日。2名研究者根据Cochrane系统评价手册5.1.0,按纳入与排除标准独立进行文献筛选、资料提取、质量评价,并使用RevMan5.3软件Meta分析。 结果:共纳入8篇随机对照试验,共计793例受试者。结果显示,在卵巢癌的治疗中,紫杉醇脂质体联合卡铂与紫杉醇联合卡铂比较,客观缓解率有统计学意义（P=0.02）。在不良反应方面,紫杉醇脂质体联合卡铂与紫杉醇联合卡铂比较：血小板减少（P=0.02）、恶心呕吐（P＜0.000 01）、肌肉关节痛（P＜0.000 01）、皮疹（P＜0.000 01）、呼吸困难（P=0.000 8）和面部潮红（P=0.001 0）,差异有统计学意义;而白细胞减少（P=0.13）、血红蛋白减少（P=0.28）、腹泻便秘（P=0.15）、脱发（P=0.62）,差异无统计学意义。结论:紫杉醇脂质体联合卡铂化疗治疗卵巢癌的疗效优于紫杉醇联合卡铂化疗,且能减轻患者不良反应,提高用药有效性和安全性。     

Microvascular heart involvement in systemic autoimmune diseases: The purinergic pathway and therapeutic insights from the biology of the diseases

Heart involvement – often asymptomatic – is largely underestimated in patients with systemic autoimmune diseases (SADs). Cardiovascular events are more frequent in patients with SADs compared to the general population, owing to the consequences of inflammation and autoimmunity and to the high prevalence of traditional risk factors. Coronary microvascular disease (CMD) is a form of cardiac involvement that is increasingly recognised yet still largely neglected. CMD, the incapacity of the coronary microvascular tree to dilate when myocardial oxygen demand increases or when there is a microvascular spasm (or subclinical myocarditis), is increasingly reported because of the widespread use of new cardiac imaging tools, even in a subclinical phase. The assessment of myocardial coronary flow reserve (CFR) emerged as the most effective clinical tool to detect microvascular damage. The potential causes of microvascular damage, molecular and cellular inflammation along with a pathological CD39-CD73 axis, need always to be considered because data show that they play a role in the occurrence of acute coronary syndromes, heart failure and arrhythmias, even in the early asymptomatic stage. Data suggest that controlling disease activity by means of methotrexate, biologic drugs, antimalarial medications, statins and aspirin, according to indication, might reduce the cardiovascular risk related to macrovascular and microvascular damage in most patients with SADs, provided that they are used early and timely to control diseases. The need of new biomarkers and a careful assessment of myocardial CFR emerged as the most effective clinical tool to detect microvascular damage.     

Controlled ovarian hyperstimulation (COH) parameters associated with euploidy rates in donor oocytes

Although oocyte donors are young and are expected to provide a high rate of euploid oocytes, significant differences of euploidy rates for donor embryos exist between different IVF centers (1). Laboratory conditions can lead to differences of euploidy (2,3,4,5,6,7); but, the role of COH has not been investigated. In this study, we investigated whether euploidy rates in the embryos created from donor oocytes are influenced by controlled ovarian hyperstimulation parameters used during assisted reproduction. Euploidy rates in egg donor cycles undergoing PGT-A (N = 423) were examined retrospectively for associations with donor age, gonadotropin doses (dose per day), the fraction of gonadotropin provided by hMG (F(hMG)), days of stimulation, estradiol per mature oocyte on day of trigger, number of mature oocytes retrieved, number of embryos biopsied, incidence of euploidy and physician of record. Differences in euploidy rates between physicians were examined using analysis of variance. The proportion of euploid embryos per donor cycle was examined for associations with COH parameters using pairwise post-hoc comparisons, adjusting for multiple testing. The set of variables from this analysis was then submitted to a principal component analysis. Linear regression analysis was used to assess the relationships between stimulation parameters and the incidence of euploidy (the dependent variable). Euploidy rates and cycle parameters varied significantly among treating physicians. Euploidy rates (expressed as a fraction of biopsied embryos) were associated (p = 0.01) only with the F(hMG) but not with the number of MII retrieved or other variables. On the other hand, the number of euploid embryos (in contrast to the euploidy rate) was associated with the number of MII produced. Donor euploidy rates are significantly associated with the fraction of total gonadotropin comprising human menopausal gonadotropin (or F(hMG)) during controlled ovarian hyperstimulation but are not associated with other cycle parameters. The study provides the first suggestion that patient stimulation parameters can affect the incidence of euploidy in embryos generated through the use of standard assisted reproductive techniques. The study is limited by its retrospective approach and because the aCGH analysis used is less sensitive than more recent NGS technology. Further, it provides a suggestion that the use of hMG is beneficial for obtaining euploid embryos.     

Effects of plane of nutrition and arginine on ovarian follicles in non-pregnant sheep: Cell proliferation,and expression of endothelial nitric oxide and its receptor

The aim of this study was to investigate the role of the nitric oxide (NO) system in ovarian function, by determining if arginine (Arg) supplementation impacts follicle number, cell proliferation, and expression of the NO system members in nutritionally compromised ewes. Ewes were randomly assigned into maintenance (C, 100% requirements), excess (O; 2xC), or restricted (U; 0.6xC) diets 8 weeks prior to Arg treatment. Ewes were individually fed twice daily with pelleted diets. Ewes from each nutritional group were randomly assigned to one of two treatments: saline or Arg, which was initiated on day 0 of the estrous cycle and administered 3 times per day. Ovaries were collected at the early-luteal, mid-luteal and late-luteal/follicular phases of the estrous cycle to determine 1) the number of surface follicles, 2) follicle cell proliferation marked by Ki67 protein expression, and 3) expression of endothelial nitric oxide (eNOS; NOS3) and soluble guanylyl cyclase beta (sGC; GUCY1B3) protein and mRNA in granulosa (G) and theca (T) layers using immunohistochemistry followed by image analysis and qPCR, respectively. During nutritional treatment, C maintained body weight, O gained 6±1.2 kg, and U lost 14±1.3 kg. Our data show that: 1) Ki67 was expressed in all ovarian compartments, eNOS protein was detected in blood vessels of T and stroma, and sGC protein was detected in T cells, and blood vessels of T layer and other ovarian compartments; 2) plane of nutrition affected the number of surface follicles, and thus folliculogenesis, cell proliferation in the T layer, eNOS and sGC protein expression in T, and NOS3 and GUCY1B3 mRNA expression in G; 3) Arg treatment affected cell proliferation in G and T, eNOS and sGC protein expression in T, mRNA expression of NOS3 in T in all groups, and GUCY1B3 in G depending on the stage of the estrous cycle; and 4) G and T cell proliferation, and expression of eNOS and sGC protein in T was affected by the stage of the estrous cycle. Our data demonstrated that plane of nutrition and Arg are involved in the regulation of follicular functions in non-pregnant sheep.     

HER2在上皮性卵巢癌中的研究进展

HER2是原癌基因HER2/neu编码的跨膜糖蛋白,可以通过IHC、FISH和分子影像等方法测定。这种癌基因在不同组织学分型和临床分期的上皮性卵巢癌中的表达对预后和治疗靶值的临床应用已被广泛研究,但是目前尚无一致意见。近期的文献中表明HER2过度表达与低分化晚期肿瘤及化疗耐药和生存期缩短有关。对于晚期卵巢癌患者,最初先行减压手术和紫杉醇、铂类药物组合的标准治疗,但后来发展为化疗耐药性疾病,因此需要更多的治疗方法来提高患者生存率。近年来针对HER2的靶向治疗成为临床研究的热点。