细菌介导肿瘤治疗的进展与思考

肿瘤是危害人类健康的严重疾病,探索新型肿瘤治疗方式、提高其靶向性和药物递送效率、避免肿瘤细胞免疫逃逸、降低副反应是目前肿瘤治疗研究的热点问题。细菌既可以依赖天然的特性靶向缺氧、低pH、高渗透性和免疫抑制的肿瘤微环境,又可以通过免疫调节、细菌毒素促凋亡、抑制血管新生等机制发挥抗肿瘤作用。同时,研究者可以利用基因工程技术改造细菌,使之成为靶向性更高、穿透性更好的工程菌。此外,利用细菌外膜囊泡装载化疗药物或结合纳米材料抗肿瘤以及细菌联合化疗、放疗、光热/光动疗法的出现,使得细菌治疗肿瘤方面研究进展迅速。本文综述了近年来细菌介导肿瘤治疗的最新研究进展,并展望了其未来的发展方向。     

抗苗勒管激素在预测卵泡发育与卵母细胞质量的研究进展

抗苗勒管激素(anti-Müllerian hormone,AMH)由自分泌、旁分泌产生,主要通过II型跨膜丝氨酸/苏氨酸激酶受体发挥作用,可以抑制原始卵泡募集,阻碍卵泡生长发育,并参与调节颗粒细胞类固醇生成。卵泡液AMH不仅在小窦卵泡中表达,在排卵前大窦卵泡中仍持续表达,通过直接调节各种细胞因子的表达,参与调控卵母细胞成熟的最后阶段,即AMH表达量逐渐减少是卵泡优势化的必备条件,从而影响卵母细胞的质量,在预测卵巢储备方面发挥重要作用,也是预测卵泡发育和卵母细胞质量的重要指标。而血清AMH与卵母细胞质量之间的关系仍存在争议。     

Sister-to-sister oocyte donation: couples’ experiences with regard to genetic ties

Objective: This study aimed to gain an in-depth understanding of the experiences of genetic ties in intrafamily oocyte donation families. Background: Previous research has shown that most mothers have a good and stable relationship with their donor. Little is known about the meaning of the difference in genetic ties for parents who conceived through sister-to-sister oocyte donation. Methods: An Interpretative Phenomenological Analysis was performed and focused on both individual experiences and couple experiences with regard to genetic ties. Ten participants were recruited via an infertility clinic and took part in semistructured couple interviews. Results: Our analysis revealed that the donation was seen as a way to equal genetic parenthood. Participants struggled with this prevailing ideal of genetic parenthood and questioned the legitimacy of their motherhood. Several dynamics were identified when couples tried to deal with the imbalance in genetic ties: they acknowledged each other, convinced one another, or pushed away the difference in genetic ties. Couples also managed the presence of a genetic tie with the donor by negotiating the closeness in their family relationships. Conclusion: The lack of a full genetic tie remained a meaningful absence for some mothers and the way couples dealt with this varied. We plead that the option of post-donation care should be offered to support couples with the complexities they try to deal with.     

卵泡液代谢组学最新研究进展

代谢组学是继基因组学、转录组学、蛋白质组学之后系统生物学的主要研究平台,并逐渐成为生命科学的研究热点。在辅助生殖技术(assisted reproductive technology,ART)领域,卵泡液代谢组学已取得较大进展。目前,国内外大多数回顾性研究表明卵泡液相关代谢物(糖类、脂肪酸、氨基酸、激素等)可预测卵母细胞发育潜能,但有待大样本、多中心随机对照试验进一步证实。卵泡液代谢组学的深入研究有望成为评估卵母细胞质量并改善ART治疗结局的重要方法和手段。     

自然周期IVF取卵时机的掌控

目的:寻找自然周期体外受精-胚胎移植(IVF-ET)技术取卵时机的敏感指标。方法:对206例不孕妇女实施自然周期IVF-ET治疗,分析不同获卵结局与血清激素及尿黄体生成素(LH)变化的关系。结果:206例患者,获卵率为75.2%、提前排卵率为15%、未获卵率为9.7%。雌二醇(E2)和LH水平在取卵前、后变化最明显,LH峰值日血清E2和LH水平在获卵组、提前排卵组和未获卵组组间无统计学差异(P0.05),而决定取卵时获卵组E2为119.4±21.7μg/L,LH为13.3±9.4 IU/L;孕酮(P)为1.19±0.57μg/L,与提前排卵组(E2:77.6±22.5μg/L,LH:3.0±1.6 IU/L;P:3.35±1.64μg/L)和未获卵组(E2:167.8±53.5μg/L,LH:30.8±11.3 IU/L;P:0.84±0.45μg/L)比较有统计学差异(P0.05)。应用半定量尿LH试纸变化确定取卵时机显示,自尿LH峰下降到10~25 IU/L和5~10 IU/L时获卵率最高,分别为80.6%和84.8%。结论:E2和LH水平在排卵前、后变化最明显,是预测自然周期取卵时机的敏感指标。当出现LH峰时,尿LH自峰值降至5~25 IU/L,血清E2水平降至100μg/L左右,血清LH水平在10~20 IU/L是最适宜的取卵时机。     

人卵母细胞辅助激活研究进展

卵胞质内精子注射(intracytoplasmic sperm injection,ICSI)是目前治疗男性不育最有效的方法,但在ICSI周期中仍然有1%~3%的受精失败发生。近年来逐渐发展起来的卵母细胞辅助激活(assisted oocyte activation,AOA)技术在改善ICSI后受精失败患者的妊娠结局方面取得了较为明显的效果,有望成为治疗男性不育的重要辅助手段。本文综述了卵母细胞激活机制领域的研究成果,揭示了精子中的PLCξ蛋白引起卵母细胞内Ca2+震荡进而触发激活的机制,介绍了目前对ICSI受精失败患者精子激活能力的检测与诊断方法,以及不同卵母细胞辅助激活技术如电激活,Ca2+载体和Sr Cl2等激活技术的研究现状,并总结了这些技术在安全性方面所获得的证据,在此基础上对AOA技术今后的发展方向和前景作了探讨。     

Paediatric marginal zone lymphoma and hyperplasia

Marginal zone lymphomas (MZL) are low-grade B-cell lymphomas arising from post-germinal memory B-cells occurring in adults with a slight female predilection. They are sub-categorized into nodal (NMZL), extra-nodal/mucosa-associated lymphoid tissue (MALT) and splenic (SMZL). MALT lymphomas are the most common (70%) followed by SMZL (20%) and NMZL (10%). Histologic transformation into aggressive B-cell lymphoma can rarely occur. MZL is extremely uncommon in the paediatric population and unlike in adults, is predominantly nodal. Paediatric NMZL (pNMZL) is an indolent, low-grade lymphoma with unique clinical and morphologic features. In contrast paediatric MALT lymphoma and SMZL are extremely uncommon and resemble their adult counterparts. Paediatric marginal zone lymphomas must be differentiated from paediatric-type follicular lymphoma (PFL) and marginal zone hyperplasia (MZH) of lymph nodes and mucosa-associated lymphoid tissue. This review summarizes the pathogenesis, morphology, genetic features of paediatric MZL and marginal zone hyperplasia. Recognition of these entities is important to avoid unnecessary therapy.     

Nuclear and cytoplasmic maturation of in vitro matured human oocytes after temporary nuclear arrest by phosphodiesterase 3-inhibitor

BACKGROUND: The use of hormones for controlled ovarian stimulation results in follicular heterogeneity, with oocytes at diverse stages of nuclear and cytoplasmic development. This study evaluated the impact of temporary nuclear arrest by a specific phosphodiesterase 3-inhibitor (PDE3-I), cilostamide, on nuclear and cytoplasmic maturation of cumulus-free germinal vesicle (GV) human oocytes from controlled ovarian stimulated cycles. METHODS: GV oocytes (n = 234) were cultured in: (i) medium without the inhibitor (control); (ii) medium supplemented with 1 microM cilostamide and (iii) medium supplemented with 10 microM cilostamide. Oocytes in groups (ii) and (iii) were exposed to cilostamide for 24 h. The PDE3-I was subsequently removed by transfer of oocytes to fresh in vitro maturation (IVM) medium and the reversibility of GV arrest was assessed during IVM culture for maximum 48 h. RESULTS: Cilostamide (1 and 10 microM) could maintain >80% of the oocytes at the GV stage, without affecting subsequent maturation to metaphase II. Oocytes exposed to 1 microM cilostamide were more likely to have normal bipolar spindles with aligned chromosomes than control oocytes (P < 0.05). When GV chromatin configurations before and after arrest were compared, a significantly higher proportion of oocytes had acquired a nucleolus completely surrounded by a rim of highly condensed chromatin (P < 0.05). CONCLUSIONS: Temporary nuclear arrest of human GV oocytes with PDE3-I proved to be beneficial for obtaining normal spindle and chromosome configurations after IVM. It resulted also in synchronization within the population of GV oocytes.